132
7/23/2019 Contract Pharma http://slidepdf.com/reader/full/contract-pharma 1/132
| Date post: | 17-Feb-2018 |
| Category: |
Documents |
| Upload: | sameh-ibrahim-qanadilo |
| View: | 242 times |
| Download: | 0 times |
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 1/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 2/132
1
• One partner for collaborative drug substance
and drug product development
•
Single point program management forclear and direct communications
• Simple and flexible contracts to match
business needs and rapid project starts
• Parallel processing and activities for time
savings of 8-12 weeks or more
•
Experienced and responsive experts to ensure project success
• Reliability and trust with Right First Time
and On-Time-Delivery proven with an
industry leading quality track record
Patheon OneSource™
The end-to-end development solution.
Simple and Fast + Expertise and Experience =Increased Value
Patheon OneSource™– delivering a simplified development solution with expertise in
drug substance and drug product development – getting you to market faster.
Visit www.patheon.com
The end-to-end development solution.
Patheon OneSource™ offers you the simplification and expertise to meet your unique
scientific and business requirements getting you to market faster with increased value.
a business unit of DPx Published 3/15 PATH0518R3
Visit us at
Booth #3613
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 3/132
Building Partnerships For Life.
We can support you at any point on the journey.
From Concept to Commercialization.
Cutting-edge Pharmaceutical Development and Commercial
Manufacturing services to get you where you need to go.
I
RV I C E S
C L I N I C A L
T R I A L S
M A T E R I A L
P R E - F O
R M U LA
T I O N
& F O R
M U LA T
I O N
A C T I V
I T I E S
A
V A R I E T Y
O F D
O S A G E
F O R M S
M U L T I
P L E
P R O C E S S E S
C O M M
E R C IA L
MA N U
FA C T U R
I N G
PA C KA G
I N G
HALO
PHARMA
S C A L E U P &
T E C H T R A N S F E R
R MA C E U T I
CA L
E L O P M E
N T
A NA L Y
T I CA L
S E R V I C
E S
www.halopharma.com
30 North Jefferson Road
Whippany, NJ 07981
17800 rue Lapointe
Mirabel, QC J7J 1P3
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 4/132
4 Contract Pharma contractpharma.com June 2015
T A B L E O F C O N T E N T S
JUNE 2015 | VOLUME 17 | NUMBER 5
FEATURE ARTICLES
40 16TH ANNUAL $ALARY $URVEYThis year’s results are derived from more than
500 respondents from our readership about
employment attitudes, responsibilities, education,
and their 2014 salaries
54 BIOPHARMACEUTICAL CONTRACT
MANUFACTURING CAPACITY EXPANSIONS
Biopharma contract manufacturing market continues toexpand, expected to grow 8% over the next five years
By William Downey
58 CHALLENGES IN GLOBAL BIOSIMILAR DEVELOPMENT:
A REGULATORY PERSPECTIVEMore than $60 billion worth of patents on biological products are expiring before 2020,
representing a major opportunity for the pharmaceutical industry
By Joan Boren, Costantino Congiatu and Patricia Hurley
62 A CASE FOR ONE ASSAY ANALYSIS OF PK AND
IMMUNOGENICITY IN BIOSIMILAR RESEARCH Moving forward clinical studies will have to include a
comparative assessment of pharmacokinetics and
immunogenicity to the original reference biologic drug
By Stephanie Mowery, Sherri Rinker, Franklin Spriggs and Bo Kowalcyk
64 SINGLE-USE CLARIFICATION SYSTEM FOR
HIGH-DENSITY CELL CULTURES Continuous improvements in growth media and cell line viability
have resulted in increased biomass concentrations in
biopharmaceutical production processes, making the downstream
purification step more challenging. Body feed filtration has proven
to be a successful method of solving similar issues in other
industries. This robust technology is now available as a harvesting
solution for biotechnology applications
By Tjebbe van der Meer
40
64
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 5/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 6/132
6 Contract Pharma contractpharma.com June 2015
T A B L E O F C O N T E N T S
JUNE 2015 | VOLUME 17 | NUMBER 5
FEATURE ARTICLES
68 GROWTH PROSPECTS FOR PHARMACEUTICAL CONTRACT PACKAGINGSpurred by several trends including the patent cliff, new product launches and changes in
healthcare, the contract packaging market is looking at sustained growth in the years ahead
By Walt Berghahn
74 CONSIDERATIONS, NUANCES AND CHALLENGES OF CONTINUOUS
PROCESS IN PHARMACEUTICAL MANUFACTURING A review of the business and process considerations for continuous processing in pharma
manufacturingBy Girish Malhotra
80 APPLYING RISK-BASED MONITORING
IN THE REAL WORLDImplementing an acceptable clinical monitoring plan
requires a thorough understanding of the new rules
under which we’re operating
By Lynn King
82 MOORE’S LAW FOR MORE HEALTHThis year marks the semi-centennial anniversary of a
prediction about exponential growth and productivity
By Patrick Jordan
84 COMBATING ‘SUPER-AGILITY’ OF COUNTERFEITERS
IN THE PHARMA SUPPLY CHAINLeveraging industry best practices to protect consumer safety
By Chip Meyers and Robin Hooker
88 HOW STERILIZATION OF PRIMARY PACKAGING
INFLUENCES THE RESULTS OF E&L STUDIES As the demands that are being placed on the quality and
stability of medications continue to increase, the interactions
that take place between the primary packaging container and
filled drug product are becoming increasingly important
By Thorsten Sögding, Daniel Canton, Daniel Haines, Uwe Rothhaar
Cover image courtesy of Sartorius Stedim BiotechCover design by Jessica Carlin
84
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 7/132
ABOUT
THE NEXTPROJECT
UPGRADE YOUR EFFICIENCY
Federal Equipment has been a trusted source of
pharmaceutical processing equipment for more than
50 years. Our pharmaceutical team has extensive
market knowledge, so we consistently exceed clients’needs with our extensive inventory, stored in climate-
controlled, pharma-dedicated warehouses, as well as
fast, accurately-appraised liquidations.
WE SELL and deliver high quality machinery
WE BUY and remove surplus equipment
Visit us at Interphex, New York, Booth #1742
When you
think equipment,
think Federal
Equipment
WWW.FEDEQUIP.COM
+1 877 536 1538
For more information, email us at [email protected]
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 8/132
8 Contract Pharma contractpharma.com June 2015
T A B L E O F C O N T E N T S
Contract Pharma (ISSN #1544-3469) is published monthly except February, August, and December by Contract Pharma, LLC, 70 Hilltop Rd, Ramsey, NJ 07446. Phone: (201) 825-2552, Fax: (201) 825-0553.Periodical Postage Paid at Ramsey, NJ 07446 and additional mailing offices. Publications Mail Agreement No 40028970: Return Undeliverable Canadian Addresses to P.O. Box 1051, Fort Erie, ON L2A 6C7,or Circulation Dept., [email protected].
POSTMASTER: Send address changes to Contract Pharma, 70 Hilltop Rd., Ramsey, NJ 07446-0555 USA. Printed in USA. Free subscriptions to Contract Pharma are available toqualified individuals. Others are as follows: US one year subscription $95.00, Mexico/Canada one year subscription $120.00 (5% GST required on Canadian orders. GST #134451756).Foreign Airmail one year subscription $195.00. Payment must be made in US dollars via US bank or by Visa or Mastercard. Single issues available for $12 each. The publisher reservesthe right to determine qualification of free subscriptions. Missing Issues: claims for missing issues must be made within three months of the date of the issue. Authorization to photocopyitems in Contract Pharma for internal or personal use, or internal or personal use of specific clients, is granted by Contract Pharma, LLC, provided a base fee of U.S. $1 per page is paiddirectly to: Copyright Clearance Center, 27 Salem St., Salem, MA 01970 USA.
Contract Pharma’s circulation is audited by BPA International.
JUNE 2015 | VOLUME 17 | NUMBER 5
COLUMNS
14 FROM THE EDITOR
18 THE PHARMA BEATThe Last Chance Saloon?
20 MANAGING YOUR CAREERBridging the Cultural Divide Between Employers
22 CLINICALLY SPEAKINGBiosimilars and Their Future in Medicine
24 ANALYZE TH IS!
Build It and He Will Come
28 THE LOWE DOWNSigning Off!
30 THE BIOPHARM INSIDERCMOs Facing Significant Capacity Constraints
36 INDIA REPORTEmerging Hotbed Of Surveillance Data?
38 DATAWATCH1Q R&D for Pharma & Biopharma
72 NEWSMAKERS: PCIKeeping Ahead of Growth
130 BACK PAGEDrug Development Costs Continue to Rise
DEPARTMENTS
16 TOP OF THE NEWSEndo Acquires Par Pharmaceutical In $8B Deal
100 INDUSTRY NEWSJanssen Expands Continuous Mfg. Initiative withRutgers
104 CRO NEWSQuintiles Expands Bioanalytical Capabilities
106 COLLABORATIONS & ALLIANCESJanssen, Achillion in HCV Development Pact
110 PROMOTIONS & MOVESPfizer Appoints Worldwide R&D Leaders
112 FINANCIAL REPORTSQuarterly Reports
115 ASSOCIATIONS & EVENT S2015 BIO Convention Heads to Philly
116 ASSOCIATIONS & EVENT SNews Highlights and Photos from INTERHEX 2015
118 READER SHOWCASESartorius Launches BIOSTAT D-DCU
120 INDUSTRY CALENDAR
121 COMPANY SHOWCASE
127 CLASSIFIED LISTINGS
129 ADVERTISER INDEX
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 9/132
[email protected] | 1 800 441 4225 | emergentcontractmanufacturing.com
AsepticFill/Finish
Pre-ClinicalDevelopment
BDSManufacture
Clinical& Commerical
Lyo CycleDevelopment
Emergent BioSolutions has a proven
track record as a world-class provider
of contract manufacturing services for both
bulk drug substances and sterile injectable
drug products. Our team has successfully
launched 20 commercial products and
developed/manufactured over 200
clinical candidates for our clients.
Emerging Capability
State-of-the art flexible single-use facility
enables turnkey upstream and downstream
solutions for clinical and commercial scale
biopharmaceutical drug development.
Emergent Contract Manufacturing:
Enhancing Life in Every Single Dose
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 10/132
10 Contract Pharma contractpharma.com June 2015
S T A F F
, LLC
EditorTim Wright ( [email protected] )
Editorial DirectorTom Branna ( [email protected])
Associate EditorKristin Brooks ( [email protected] )
Contributing Editors
Managing Your Career: David Jensen
The Lowe Down: Derek B. Lowe
Clinically Speaking: Ben Locwin
The Pharma Beat: Adele Graham-King
Analyze This: Emil W. Ciurczak
India Report: S. Harachand
The BioPharm Insider: Eric S. Langer
Backpage: Edward S. Price
PresidentRodman J. Zilenziger, Jr. ( [email protected] )
Executive Vice PresidentMatthew Montgomery ( [email protected])
Publisher
Gary Durr ( [email protected])
Associate PublisherDamaris Kope ( [email protected])
European RepresentativeVerena Loewenthal ( [email protected])
Production ManagerLisa St. Charles ( [email protected])
Audience Development Manager Joe DiMaulo ( [email protected] )
Circulation ManagerRich DeVoto ( [email protected])
Art DepartmentMichael Del Purgatorio ( [email protected] )
Jessica Carlin ([email protected])
Online DirectorPaul Simansky ( [email protected] )
Marketing AssistantEd Schiro ( [email protected] )
Contract PharmaPublishing Headquarters:
70 Hilltop Rd., Ste. 3000, Ramsey, NJ 07446 USA
Tel: (201) 825-2552 / Fax: (201) 825-0553
www.contractpharma.comFor reprints contact: (201) 825-2552
EDITORIAL AND SUBMISSIONS
For editorial guidelines on articlesand news items, contact:
Tim WrightEditor
CONTRACT PHARMA
70 Hilltop Rd., Ste. 3000Ramsey, NJ 07446
Tel: (201) 880-2237 | Fax: (201) 825-0553
COMING NEXT ISSUE!
TOP COMPANIES REPORT
Contract Pharma’s
Annual Report on the Top 25
Pharma and Biopharma
firms!!
Only in theJuly/August issue of
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 11/132
email: [email protected] • (608) 845-5002 • Coating Place, Inc., Box 930310, Verona, Wisconsin 53593 U.S.A. • coatingplace.com
Does your current CDMOleave you with blurred vision?
[email protected] • (608) 845-5002
Some Contract Development Manufacturing Organizations (CDMO) get youin the door then seem to go in multiple directions. There is no clear direction;
and the invoices are piling up.
At Coating Place our experienced staff believes the best results come with a
clear understanding of your ideas and goals. Trust the knowledge, quality and
insight Coating Place provides to get your vision into focus - and delivered.
a n d so much more^
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 12/132
12 Contract Pharma contractpharma.com June 2015
E D I T O R I A L A D V I S O R Y B O A R D
If you have questions for our Editorial Advisory Board, would like to contact individual
board members or have suggestions of potential members to add to the board,
please contact Tim Wright at [email protected]
Dr. Ali Afnán
President
STEP CHANGE PHARMA, INC.
Shaukat Ali, Ph.D.Technical Sales Manager
BASF CORPORATION PHARMA
INGREDIENTS & SERVICES
Dr. Jack Aurora
Chief Scientific Officer, Generic Drugs
HISUN PHARMA (H ANG ZHOU ) CO. LTD.
James L. Botkin
Senior Vice President, Operations
ALKERMES PLC
Elise Brownell, Ph.D.
Founding partner
ZEPHYRBIOTECH
Dr. Suggy S. Chrai
President
CHRAI ASSOCIATES
Joseph Colleluori
Senior Vice President of
Corporate Development
LONZA GROUP LTD.
Paul D’Angio, RP
Senior Vice President –
Global Technical Operations
CELGENE CORPORATION
Dr. Tony DeStefano
Consultant
YOURENCORE
William Downey
President
HIGHTECH BUSINESS DECISIONS
Thomas Handel
Senior Vice President –
Commercial Pharmaceuticals
MERIDIAN MEDICAL TECHNOLOGIES, A PFIZER COMPANY
Wayne HeminwayBusiness Development Executive
COOK PHARMICA LLC
Mico Holguin, Jr.
Pharma Partner Executive
B AXTER BIOPHARMA SOLUTIONS
B AXTER HEALTHCARE CORP.
Ajaz Hussain
Principal,
AJAZ S. HUSSAIN | INSIGHT, ADVICE & SOLUTIONS, LLC
Paul JosephsVice President, Sales and Marketing
DPT L ABORATORIES
Balaji V. Kadri
Director of Formulation Development &
CTM manufacturing
QS PHARMA (A WIL RESEARCH COMPANY )
Bobby A. Kanuga
Vice President, External Manufacturing
MERCK & CO., INC.
Dr. Faiz Kermani
Senior Communications Manager SFL Regulatory Affairs &
SCIENTIFIC COMMUNICATION LTD.
Richard Korsmeyer
Head of Business Development
Pharmaceutical Sciences
PFIZER WORLDWIDE R&D
Michael J. Kosko
President
PFIZER CENTRESOURCE
Steve F. Massah
Senior Manager,Strategic Drug Product Outsourcing
GILEAD SCIENCES
Dr. Jeffrey Millard
Director of Pharmaceutical Development
ONCOTHYREON, INC.
Richard V. Myer
Vice President, Business Development
ARGENTA LIMITED
Sudha Nair, Ph.D.
Director, Global Business Development
APOTEX FERMENTATION, INC.
Dilip M. Parikh
President
DPHARMA GROUP, INC.
Dr. Enrico T. Polastro
Vice President
ARTHUR D.LITTLE BENELUX SA/NV
Jack Regan
Vice President, Contract Manufacturing
BIOM ARIN PHARMACEUTICAL
Sam Ricchezza
Senior Vice President,
Business Development
WELLSPRING PHARMACEUTICAL
Gil Roth
Executive Director
PHARMA & BIOPHARMA OUTSOURCING ASSOCIATION
Fred Schulze
Vice President, Sales & Marketing
COATING PLACE, INC.
James R. Scull, Ph.D.
General Manager
NSF PHARMALYTICA
Daniel Stehn
Director of Biotechnology Packaging
SHARP P ACKAGING SERVICES
Dr. Martin Steinman
Consultant
K URARAY AMERICA
Paul TitleyManaging Director –
Formulation Development
AESICA LTD.
Phillip G. Trager
Director, Analytical Services
CONSUMER PRODUCT TESTING CO.
Michael J. Valazza
Vice President, Global Business
Development – Oral Solids and
Controlled Release TechnologiesC ATALENT PHARMA SOLUTIONS
Falguni Vaidya
Director of External
Manufacturing Procurement
BRISTOL-M YERS SQUIBB
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 13/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 14/132
14 Contract Pharma contractpharma.com June 2015
F R O M T H E E D I T O R
T
he biopharmaceutical market continues to grow and moreand more biopharma firms are calling upon the servicesof contract manufacturing organizations (CMOs), which
as we all know offer various advantages for sponsors. Technicalexpertise, operational efficiency, regulatory support, the ability toallow sponsor companies to focus on their core competencies.How many times have we heard this drum being banged? How-ever, the most valuable service CMOs probably offer is in servingas a cost-cutting tool, because let’s face it, at the end of the daybusiness is all about boosting the bottom line. Right?
So CMOs have grown to be ubiquitous across the pharma andbiopharma landscape. Are there even any pharma or biopharma firmsleft out there that don’t view outsourcing as a strategic imperative?
The biopharmaceutical contract manufacturing market has witnessed considerable growth in the past few years. There areestimated to be more than 160 biopharma CMOs operating in
today’s market whose services range from cell line developmentand API manufacturing to fill/finish of the product.Beginning on page 54 , William Downey from High Tech Busi-
ness Decisions takes a look at the trends in the current market, which he says is poised to reach $3 billion this year. Because ofthe greater demand for outsource services CMOs on the biophar-ma front are investing in new plant and equipment or acquiringcapacity to meet future industry needs.
The strong growth in the biologics market is one of the majordrivers pushing the biopharmaceutical contract manufacturingmarket forward in the coming years. By 2020 there is an estimat-ed $67 billion worth of patents on biological products expiring. Atthe same time governments are under more and more pressure to
reduce rising health care costs and biosimilars represent a majoropportunity for the pharmaceutical industry.
However, understanding biosimilars from just about anyperspective is not easy. Delving into the subject to try and sortthrough some of the confusion are PPD’s Joan Boren, Costantino
Congiatu and Patricia Hurley. Beginning on page 58 the authorsoffer their perspective on the growing interest in biosimilars,
which they say is evident by the approximately eightfold increasein the number of biosimilar clinical trials between 2007 and 2014.They also say the market growth of biosimilars is going to be sig-nificant and be worth approximately $2 billion by 2018.
Over the past ten years, regulatory authorities worldwide havebeen focusing on developing guidelines for biosimilars and thisarticle addresses current regulations and challenges impactingthe development of biosimilars.
Also on the bio front, Eric Langer from Bioplan Associates andour resident BioPharm Insider (page 30 ), talks about the capac-ity constraints CMOs are facing, while in “Biosimilars and Their
Future in Medicine”(page 22 ) , our Clinically Speaking columnistBen Locwin takes us through the first, simplest, but most impor-tant steps with biosimilars and that is understanding what theyactually are! Hope you enjoy.
Tim Wright, [email protected]
Banging the CMO DrumSponsors are calling upon the services of CMOs more and more for their “expertise”
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 15/132
Your source for success
WellSpring is a unique pharmaceutical contract manufacturer offering complete clinical and commercial
manufacturing, packaging and analytical services from a single FDA inspected and Health Canada
licensed facility. Our culture flourishes with the energy of innovation, integrity, teamwork, entrepreneurial
spirit and creative problem solving. Need fast, flexible service? We provide it. Want attention to detail at
every stage? We deliver it. Demand expertise? We guarantee it.
Find out why WellSpring is the supplier of choice for our clients
and nd out what we can do for you today.
©2014 WellSpring Pharma Services. All rights reserved.
844-879-7427 I [email protected] I WellSpringCMO.com I 400 Iroquois Shore Road, Oakville, ON L6H 1M5
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 16/132
16 Contract Pharma contractpharma.com June 2015
T O P O F T H E N E W S
Endo International and Par Pharma-
ceutical have entered into a definitiveagreement under which Endo will acquire
Par for $8.1 billion. The combination willcreate a leading specialty pharma compa-ny with a generics business that is one ofthe industry’s fastest growing and amongthe top five as measured by U.S. sales.
“Our generics business, Qualitest,continues to be an extremely attractiveand effective growth driver for Endo. Thistransaction builds on our generics growth,adding a strong portfolio of high barrier-to-entry and attractive products while alsotransforming Endo, creating a powerfulcorporate platform for future growth,”said
Rajiv De Silva, president and chief execu-tive officer, Endo. “We believe the acquisi-tion underscores the continued executionof Endo’s value-driven M&A strategy andhelps deliver on our goal of achieving rev-enue growth over the long-term.”
“This is an exciting time of growth andopportunity in the generics and specialtypharmaceutical arenas. Par is committed tosignificantly expanding our scope, capac-ity and capabilities to realize the maximum
value of our diversified product portfolioand pipeline. We believe our combination
with Endo best positions us to do so,”saidPaul Campanelli, chief executive officer, ParPharmaceutical. “We share Endo’s goal ofdeveloping generic drugs in areas of great-est revenue potential, complex formula-tions and longer life cycles.”
After the deal is completed, Mr. Cam-panelli will join Endo, where he will leadthe generics business and serve as a mem-ber of Endo’s executive leadership team.
Goodwin To Support Phase IPanacea Trials
Goodwin Biotechnology, a CDMO thatspecializes in bioprocess development
and GMP manufacture of biopharma-ceuticals utilizing mammalian cell culture
expression systems and bioconjugationtechnologies, was selected by PanaceaPharmaceuticals to complete a fill/finishproject, as well as quality control releaseand stability testing for a nanoparticlecancer vaccine to support Phase I trials inpatients with various solid tumor cancers.
“Over the last year, we partnered withGoodwin on a bioconjugation project andhave found them to be extremely respon-sive and flexible. They had an innovativeapproach to address some rather signifi-cant challenges in an effort to move our
project forward,” said Steven Fuller, chiefoperating officer, Panacea. “When we
identified the need to select a companyfor our fill/finish project that involves a
unique injector cartridge filling procedure, we evaluated Goodwin’s capabilities and we were pleased with their approach toniche fill/finish projects.”
“We are pleased to have Panacea work with us on their two lead compounds,”said SooYoung Lee, chief operating of-ficer, Goodwin Biotechnology. “Based onthe many years of successful track recordsand our commitment to bring advancesto bioconjugation and cell culture-basedprojects, it’s rewarding to know that ourinvestment to build the comprehensive
infrastructure required has been helpfulfor Panacea.”CP
ASTRAZENECA TO BUILD $285M BIOLOGICS FACILITY IN SWEDEN
AstraZeneca plans to invest approximately $285 mill ion in a new, high-techbiologics manufacturing facility in Södertälje, Sweden. The new plant will be focused
on filling and packaging of protein therapeutics. It’s anticipated that the new facility will
supply medicines for clinical trial programs of AstraZeneca and MedImmune, the com-
pany’s global biologics R&D arm, by the end of 2018, and will deliver finished products
for commercial use once fully operational by 2019.
Södertälje is currently home to AstraZeneca’s largest global tablets and capsules
manufacturing facility and is also a launch platform site for the company, with specialist
capabilities on-site that allow large-scale production of new medicines, working closely
with the R&D organization.
The planned investment will create between 150 and 250 new roles at AstraZeneca by 2019.
“This is a strategically important investment for AstraZeneca to support the accel-
erating development of biotech medicines, which now make up around half of our
pipeline,” said Pascal Soriot, chief executive officer, AstraZeneca. “We expect to bring asignificantly increased number of new specialty care medicines to patients in the com-
ing years, driven in large part by biologics. This new plant will give us greater capacity
and flexibility to handle clinical trials, and will also play an important role in our future
commercial production.”
The new manufacturing facility in Sweden will support the progression of drug candi-
dates across the main therapy areas and will be aligned with investments being made
in the current biologics manufacturing centers, such as the expansion in Frederick, MD,
announced in November.
Endo Acquires Par Pharmaceutical
In $8 Billion Deal AstraZeneca to build $285 million biologics facility in Sweden
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 17/132
REEDiscover commitment
You either have it or you don’t.
The dedication
to push yourself further.
The commitment
to do whatever it takes.
It can define your legacy for decades.
It can inspire those around you to do the impossible.
We get it.
We’re Reed-Lane.
Wayne, NJ • 877.290.1090 • www.reedlane.com
Blistering • Bottling • Pouching • Convenience Vials
PHARMACEUTICAL PACKAGING SERVICES
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 18/132
18 Contract Pharma contractpharma.com June 2015
T H E P H A R M A B E A T
Adele Graham-King
Contributing Editor
Adele is a design consultant who works in prod-
uct development for medical and healthcare ap-
plications. Her background is in pharma, and shehas a degree in applied physiology.
T
he ever increasing issue of worldobesity is constantly in the newsand with the statistics illustrating
a frightening upwards trend it is nowa critical illness it terms of cost to thehealth services worldwide. In fact in 2012it was calculated that more than a third of
Americans—34.9% or 78 million—wereobese. In 2008 the cost on U.S. healthcaredue to treatment of obesity was $147 bil-lion. More recent data suggests that if thecurrent trend continues the prevalence ofobesity will rise to 43% in adults by 2018
with the cost of treatment destined to top$344 billion.
Although the population in general ac-
cepts that a regimen of exercise and healthyeating should allow us to control and in-deed lose weight, the harsh reality of thesituation is that a large percentage of obeseand morbidly obese people either ignorethis advice, or for various reason feel thatthey are either unable or incapable of con-trolling their weight without either phar-maceutical or surgical intervention.
The pharma industry has been tryingto find the miracle weight-loss pill for de-cades. Indeed pharmaceutics have beenused for over a century to assist in shed-
ding pounds. In terms of history, the drugThyroxin (or Thyroid Extract) has beenused since before 1900 and is still usedtoday, unregulated in the U.S. by bodybuilders even though it is known to cause
potentially serious side effects. DNP (2,4Dinitrophenol), an industrial chemicalused in wood preservatives and pesti-cides, was used for weight loss through-
out the 1930s. It was indeed banned butis still used illegally to assist in fat losseven though it has been associated withover 50 deaths of U.S. body builders.
Phentermine (Adipex-P, Suprenza andLonamin) is a psychostimulant, pharma-cologically similar to amphetamine, andis available in the U.S. for short-term
weight management. Although thesedrugs are not illegal in the UK and Eu-rope, they are not prescribed on the NHS.Phentermine should only be prescribedfor short-term use alongside a managed
diet regime and exercise, however due tothe potential habit-forming effect of thedrug it shouldn’t be used long-term. Thesame goes for Diethylpropion, anotherpotentially addictive medication availablein the U.S. There has been much contro-
versy in the UK with regards to these twomedications with a legal battle aimingto ban them 10 years ago, which failed
when in 1995 the Medicines Control Agency argued that there was insufficientevidence to do so.
But the quest for the miracle cure for
obesity has continued through the 90s,00s and into the second decade of the 21st
Century. Many of the previously used anddiscontinued drugs have targeted appe-tite in order suppress the urge to binge.
A newer generation of drugs have beenresearched and trialed focusing more onregulating metabolism or interfering withprocesses of selective absorption in theGI tract.
Sibutramine (Meridia, Reductil andSibutrex) is a neurotransmitter re-uptakeinhibitor, which acts as an appetite sup-pressant. It was launched onto the mar-ket in 1997 but was withdrawn in the U.S.and Europe in 2010 due to cardiovascularrisk factors. Closely following the releaseof Sibutramine, Orlistat (Xenical and
Alli) was launched in 1999. Alli is a lowerdose formulation of Orlistat availableOTC. Orlistat works differently to previ-ously marketed anti-obesity medications
whereby it targets intestinal fat absorp-tion via inhibition of pancreatic lipase.Sounding simplistic in terms of how it
works, Orlistat has a tendency to causefatty diarrhoea (steatorrhea) as well asflatulence and other gastric problems.Regardless, following the non-launch ofRimonabant (Acomplia and Zimulti), acannabinoid (CB1) receptor antagonist
in 2007 due to potential psychiatric is-sues, Orlistat remains the only long-termpharmacological agent licensed to treatgross obesity in the UK and U.S.
And so the journey goes on, and may-be another chapter is yet to open? Theanti-diabetic medications have become anewer area of interest. It is well acknowl-edged that patients who take metforminfor Type II Diabetes may be able to lose
weight—this is thought to be relatedto the fact that its action decreases theamount of glucose excreted by the liver
while increasing absorption of the samesubstance by muscles.
The Last Chance Saloon?
Looking at the pharmaceutical ‘diet’ of anti-obesity drugs
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 19/132
June 2015 Twitter : @ContractPharma Contract Pharma 19
T H E P H A R M A B E A T
Another anti-diabetic drug is Exenatide(Byetta), which is a glucagon-like pep-tide-1 analogue (GLP-1). It is known to
delay gastric-emptying, promote and pro-long satiety and some patients taking themedication have been observed to show alarge degree of weight loss. Currently, Ex-enatide is only indicated for Type II Diabe-tes and is a subcutaneous injection, whichcan be associated with severe nausea;however this group of drugs is certainlyof interest in weight management as re-search suggests that some obese peopleare deficient in the hormone.
The world of anti-obesity drugs does just seem to be all boom and bust. Ev-
ery time a new hopeful appears on thestage the question gets asked, “Could thisbe the one?”But the figures suggest thatthe Holy Grail has yet to be found. Andthis seems to have had an effect on R&Dtime and spend in that therapeutic area.
After almost a decade it looks likely thattwo new drugs will be licensed for use inEurope. A combination therapy of nor-adrenaline reuptake inhibitor BupropionHCl and the selective opioid antagonistNaltrexone HCl will be marketed asMysimbia, and the second is an inject-
able human GLP-1 analogue Liraglutide,to be marketed as Saxenda. Liragultide isalready licensed under the name Victozafor the treatment of Type II Diabetes atmuch lower doses. Both of these drugsrely on modified calorific intake and in-creased exercise.
The question remains though: Is it thedrug, or is it the illness? Regardless of thepharmacological action of the drugs, suc-cessful weight loss must be accompaniedby a lifetime of changes in both diet andexercise. Whichever way we look at it,
obesity occurs due to over indulgence andno matter how clinically effective a drugis, consuming thousands of calories on adaily basis will render any drug therapyobsolete regardless of how pharmaco-logically efficacious it is. Accompanied bythe fact that many of these drugs are as-sociated most commonly with addictive-ness, cardiovascular risk and psychiatriceffects, it seems many of these APIs aredoomed to failure simply because of thepatient group and lack of predictability.
Furthermore all the licensed prod-
ucts have a limited period of usage ifadequate weight loss is not achieved;
therefore a stage-gated, weight focusedsystem can mean treatment is discontin-ued even if the patient is heading in the
right direction.It will be interesting to see how the
future pans out for anti-obesity medica-tion. Could we finally have newer drugsthat can combat the slippery slope into
morbid obesity, or will it be another failedstart out of the blocks? Only time will tell,but if the outcomes are not seen as being
strongly positive then pharma may welldecide to call it a day and walk away assome have already done. It could well bethe last chance saloon for anti-obesitydrugs. CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 20/132
20 Contract Pharma contractpharma.com June 2015
David G. Jensen
Contributing Editor
David G. Jensen is an executive
recruiter working in the life sci-
ences with more than three decades of biotech-
nology experience. He can be reached at (928)
274-2266 or via [email protected]
M A N A G I N G Y O U R C A R E E R
T
here are subtle but important dif-ferences in the way that work pro-ceeds in one company versus an-
other. While two work cultures may sharecommon elements, primarily centered onthe science itself, or perhaps on the prod-uct development category, there will stillbe a number of differences between oneemployer and another. These differencesin “how things work”can come as a rudeshock—particularly if you’ve made themove and discover them after the fact!
As you transition from one companyto another, you’ll likely experience somebumps—most people do. Remember
when you moved into a company for the
first time out of school? You had to learn what it’s like to be a part of a companyproject, for example, or, how to participateeffectively in daily or weekly team meet-ings. But those were small things. Some-times, the differences between companiesand managers can be substantial, thecause behind untold amounts of stress.
These cultural differences have the po-tential to trip you up and keep you fromhaving the opportunity to prove yourself inthe new environment. Or, they can hold youback from landing the job offer in the first
place. In this month’s article, my examples will show you how seemingly small differ-ences in the pace of work and information
flow can become important, even during theinitial stages of discussion.
PhilPhil had prepared well for this interview,his first outside of the company he’d been
with for more than three years. He hadstudied the agenda and the backgrounds ofthe people he’d be meeting, and knew a lotabout the company from their website. Be-cause it felt like he had really aced his twomorning sessions, he was feeling good. Nextup, though, was a noon meeting with FosterGreen, R&D head and his prospective boss.
As Phil approached the conferenceroom, his HR escort mentioned that the
meeting with Green had to be kept to45 minutes. That wasn’t a good sign, Philthought; originally this “working lunch”hadbeen scheduled for an hour; already he hadless time with the boss than he expected.Then, the head of research walked in and satdown, still talking on his cell phone. Theyexchanged smiles, but these small detailsconspired to undermine Phil’s confidenceand replaced it with a case of the interview
jitters. Green motioned for Phil to take a seat while he finished his conversation.
Phil took a moment to center himself
and recalled his thorough preparation. Hehad spent a lot of time thinking about his work experiences and how they had posi-tioned him as a scientist. He was preparedto speak eloquently and at length aboutany of his experiences over the last few
years, or even stretch back to his postdoc inthe Watson lab at State.
After a brief introduction, Green askedthe first question. “Phil, please give us asnapshot of yourself and your science.Take a few minutes and tell me whatmakes you a good fit for my team.”
Wow, this wasn’t the kind of questionthat Phil was expecting. He’d come in pre-
pared to talk in great detail about himselfand his experiences. Instead, Green wasasking him to sum his work up briefly and
connect it with the company’s needs.Phil started talking. Despite his extensive
preparation, he wasn’t prepared for this. Hefloundered. He felt self-conscious. He wasgoing on too long, and he knew it, and hedidn’t like the silences that filled the room
when he stopped talking. His most impor-tant meeting of the day was headed off inthe wrong direction. He could feel it, but hedidn’t know how to fix it.
KyraKyra put a thank you note in the mail to
Dr. Watson, who had been her Ph.D. ad- visor four years ago at Big State Univer-sity. It was nice to know that Dr. Watsonhad thought of her when making recom-mendations to her former labmate, FosterGreen, now at ABC Biotech.
Reflecting later on her interview that day,Kyra thought about what she had done welland what she could have done better. At thebeginning of the meeting, Green had askedfor a summary of her background and expe-rience—he called it a “snapshot”—and howit might relate to her work for ABC biotech.
He was asking her to convince him that she was a good fit for the company and the job. As the conversation developed, Green
asked for more and more detail—a sur-prising amount of detail about her col-laborators and what each person’s role
was—and what she had learned aboutcommunicating with other scientists,some of whom are from other disciplines.It didn’t take her long to realize that Green
wasn’t after Kyra’s Greatest Hits. Instead,he wanted to understand the breakdownof the work among the team she was
working with—not, what she achieved but what the team achieved, what her contri-
Bridging the Cultural Divide
Between Employers A few examples of how cultural differences can make or break a job offer
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 21/132
June 2015 Twitter : @ContractPharma Contract Pharma 21
M A N A G I N G Y O U R C A R E E R
bution was, and how her work benefittedfrom the contributions of others.
Once she knew what he was after, she felt
comfortable. She laid out each of her careerexperiences in detail, and he seemed satisfied
with her answers. The interview might notlead to a job, Kyra decided, but even if it didn’tit was a valuable learning experience.
Green’s perspectiveDr. Green reviewed his notes on his lasttwo interviews for the opening. His old col-league, Susan Watson, had recommendedthem, and Green had found that she had agood eye for talent. Both of them had comeout of her lab a few years earlier.
Green had asked both candidates hisusual kick-off question and found, as he hadfound before, that some candidates don’thandle it well. He asked himself, why doeshe keep asking it? But he knew the answer:It’s an effective test of how readily peoplecan adapt, intuitively and on the fly, to hisand his team’s communication style. Greenis used to accomplishing a lot each day, re-lying on his people to match his pace andprovide the succinct summaries he needs tomake sound decisions. He relies on them to
work together with each other and commu-
nicate to get things done. As he reviewed his notes, Green con-
cluded that Phil was having trouble shak-ing off his academic roots. His kick-offresponse had been long, unfocused, self-centered, and driven by examples that
weren’t relevant to the company’s activi-ties or plans. Phil obviously had spent a lotof time preparing, but he had not demon-strated that he could adapt to the team’sneeds. Was it an unfair test? Maybe. Itcertainly is possible that Phil would havecaught on quickly and become a good em-
ployee. He just didn’t seem like a safe betas it was clear the company he was withhas a completely different way of working.
Susan’s other recommendation, though—Kyra—was a different story. His conversation
with her had gone much better. She evenhandled his opening “snapshot”request pret-ty well. In contrast to Phil, Kyra had managedto give Green the information he wantedin the form he wanted it in. She intuitivelypicked up on how he communicated andthe pace he worked at. She, too, had doneher homework; she knew what was going on
in his lab. But her interview success reflectedmore than just good preparation. Kyra knows
how to adapt. She has a sense for people andtheir needs.
Kyra’s potential for a totally multidisci-
plinary team environment was also clearin her descriptions of her work. She hasthe communication skills a person needsto work effectively on a team at ABC Bio-tech. She shared credit with her collabora-
tors and spoke freely about what she hadlearned from them. Kyra seems to knowhow to get work done through others.
Green pulled out her CV and scribbleda note to HR about Kyra at the top. Theyhad found a winner, and he wanted tomake sure they didn’t waste time in mak-ing her an offer. CP
Global Reach with 16 packaging facilities
in North America and Europe
Clinical Trial Services
Manufacturing Services
Commercial Services
Laboratory Services
© Copyright 2014 Packaging Coordinators, Inc. All Rights Reserved.
www.pciservices.com
One Expert TeamTwo Industry Leaders Have Joined Forces.
We’ve combined two exceptional
and proven industry leaders into
One Expert Team, One Partner
for all your development needs.
Introducing the newPackaging Coordinators, Inc.
PCI has joined forces with Penn Pharma to form a global leader in healthcare
manufacturing and packaging services. With over 50 years of experience,
an exemplary regulatory profile, and an expert staff dedicated to delivering
unparalleled service and quality, PCI leads the market in supporting clients’
needs for innovative pharmaceutical outsourcing solutions.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 22/132
22 Contract Pharma contractpharma.com June 2015
Ben Locwin
Healthcare Science Advisors
Ben Locwin, PhD, MBA, MS writes the Clinically
Speaking column for Contract Pharma and is an
author of a wide variety of scientific articles for
books and magazines, as well as an acclaimed
speaker. He also provides advisement to many
organizations and boards for a range of health-care, clinical, and patient concerns.
C L I N I C A L L Y S P E A K I N G
S
ome great products and serviceshave been done a disservice by beingnamed something that either didn’t
conjure a sufficiently-vivid mental picture of what they were or did, or they had mostlyaccurate lexical names that didn’t have asticky quality to them, and the market didn’trespond. Unfortunately, the moniker ‘bio-similar’ is somewhere along the spectrum
where those in the industry have a conceptof what it means, but in practice it has verylittle meaning to the general public.
With direct-to-consumer marketing ofprescription drugs worth billions of dol-lars per year in the U.S., most people un-derstand that ‘generic’ refers to a cheaper
version of ‘expensive’ drugs; the two namesare almost synonymous. When I asked asample of 12 people—who passed a quali-fying test of correctly answering what a ge-neric drug meant—what a biosimilar was,0 respondents (0%) had a correct under-standing, and 3 respondents (25%) hedgeda guess that it was something that had asimilar effect in different people. This is,from a public health perspective, an inter-esting take; though biosimilar refers to thesimilarity of the resultant molecule com-pared with the original product, this should
give a similar effect in vivo. This howeveris a non sequitur logical fallacy: From Latin
“it does not follow”that a similar molecule will necessarily have similar function or ef-ficacy, with similarity (i.e., non-identicality)
becoming more possible with larger andmore complex molecules. A common ex-ample of this is ethyl alcohol that we drinkcompared with ethylene glycol, which is
very toxic. Without knowing much aboutthe molecular conformations, these twomolecules look very similar.
This has become the difficult philosophi-cal regulatory question: therapeutic mol-ecules are produced similarly, how similar isenough? It was once conventional wisdomthat biosimilars couldn’t even be produced.It was thought the molecular complexity was
just too high that it wasn’t a viable option topursue. But production and analytical tech-nologies have advanced dramatically in justthe past two decades. Interestingly though,
while generic drugs have to be chemicallyidentical and show bioequivalence, biosimi-lars need to have a high degree of similarityto the innovator product and are consideredto be biologically and clinically comparable.This leaves many large sources of error vari-ance in our ability to do like-for-like com-parisons within the market.
How Will We Measure?In order to bring less-expensive thera-pies to those in need, the ethical responseshould include biosimilars in its toolkit; itdoesn’t solve every problem, but it shouldcertainly not be eliminated from consid-eration. However, if we look at side effectprofiles between the innovator productand its biosimilar, what do we do when(not if) we detect differences? What if,over hundreds or thousands of patient-
years of exposure, the number-needed-to-treat (NNT) or number-needed-to-harm
(NNH) are different between the platformtherapy and its biosimilar? These data will
manifest soon, and being able to respondintelligently to the questions is simply pru-dent, smart business, and good pragmatic
science. How different does different haveto be before we send alert signals?
Regulatory Track Record:It Has to Start Somewhere
We have just entered a disruptive era in med-icines regulation—the first FDA-approvedbiosimilar, Zarxio (Novartis), received clear-ance on March 5. This is a biosimilar of Am-gen’s Neupogen. Much of the industry is
waiting for this regulatory track record to bebuilt-up so that further approvals can comemore quickly. This is the same sort of regu-
latory paradigm as that facing plant-basedantibody production, where therapeutic an-tibodies are produced within plant cells. Thefirst plant-based recombinant therapeuticprotein, Elelyso, was approved in 2012. Thelack of a prior regulatory track record, in amarket dominated by a long line of suc-cesses in mammalian cells, has kept fundingcapital and prospective therapies from plantcells relatively modest.
Biosimilars are currently an average ofabout one-third less expensive than theirplatform biologics where they are already
available. Similar with the pricing structureof generics relative to brand-name drugs,this ratio could become something morelike 90%+ less expensive in coming years.
So as it is with biosimilars being, well,“similar”, the strategic posture will needto be one of deciding how much signal isdifferent enough to do something aboutor leave alone. Additionally, there’s a greatdeal of value in revisiting the ethical grayspace of monitoring safety and adverseevents, but doing it in the context of be-ing able to reach a broader population of
patients potentially in need of lower-costtherapies. CP
Biosimilars and Their Future
in MedicineThe first step is understanding what biosimilars actually are
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 23/132
Balance your assay variability with
our single to multiplex protein
analysis solutions.
Measuring protein biomarkers? EMD Millipore’s
GyroMark™ HT assays for the Gyrolab® platform,
ELISAs, and multiplex assays are unique. Unlike
other kits that leave you on your own to establish
reproducibility, our kits provide:
• Standards validated to match reference lots
• Serum matrix for generating standard curves
that accurately simulate conditions of native
analyte conditions in serum or plasma
• In-assay controls
• Detection antibody cocktails
Your reproducible data will drivebetter research decisions.
Learn about our technologies and validation criteria:
www.emdmillipore.com/gyromark
Trend chart shows consistent MFI values for each analyte’s standard curveacross 29 lots. (±10% of reference lot)
Bring your biomarkers to lifewith steadfast assay consistency.
10,000
1,000
100
0
Lot
I L - 5 M F I
GyroMark is a trademark and EMD Millipore and the M logo are registered trademarks of Merck KGaA, Darmstadt, Germany.BS-GEN-15-11318 © 2015 EMD Millipore Corporation, Billerica, MA USA. All rights reserved.
EMD Millipore Corp. is a subsidiary of Merck KGaA, Darmstadt, Germany
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 24/132
24 Contract Pharma contractpharma.com June 2015
A N A L Y Z E T H I S !
Y
es, I enjoy quoting movie lines butthis is especially cogent. Last col-umn, I suggested that updating labs
and lab personnel would go a long way to- wards increasing business. This time, I willspeak directly to the process facilities man-agement: “You will not win a NASCAR race
with a Ford Falcon.”By that, I mean, you arenot going to bring in 21st century business
with 20th century equipment.There is a saying that generals tend to
prepare for the last war. This is, sadly truefor CROs and CMOs as well. Having thebest batch-wise equipment is preparingfor 1970s products, I fear, not the newergeneration. The categories I address are
research, development, and production of APIs and final dosage forms. So, I wouldsay that covers just about every aspect ofthe industry, no?
To make your facility receptive to per-forming research you may well need up-dated hardware to match the lab facilitiesof which I spoke. If you are doing APIresearch, you will need to be facile andable to both perform many trials/tests/experiments and keep costs down, si-
multaneously. Familiarity with design ofexperiment (DoE) software is essential.Gone are the days of “hunt and peck”for
bulk materials. The days of aspirin andacetaminophen are long gone; the cost ofmany new APIs is sky-high and often aresmall-dose, highly active materials. Thesehigh potency materials will need smallertrials and fewer scale-up studies to main-tain budgets.
For API trials, smaller, continuous de- vices have been used by commodity chemi-cal producers for decades. The advantagesfor APIs? Since both starting materials andfinished products are not inexpensive, trialsfor percentage yield, purity and morphol-
ogy can be run with more variables in lesstime than full-sized batches. Also, when adrug substance is still in the IND (Inves-tigational New Drug application) stages,there is always a choice of co-ions (e.g.,maleate, chloride, sulfate, etc. for positivelycharged drugs; sodium, calcium, etc. fornegatively charged drugs) and often onlya few or one is made for time and moneyconstraints. Most often, the choice is basedon highest yield, not downstream behavior.
One downside to that choice is that, while a calcium salt may have the highest
yield of say 99%, it is always possible thatthe disodium analog with maybe only 97% yield, may process better in a solid dos-age form. Maybe the maleate has a longershelf life than the sulfate form. Since weare likely working with larger equipment,the cost of producing these salts and vari-ous crystal forms is prohibitive and time-consuming. The patent clock is ticking,after all, so a full design of experiment,followed by some formulation and stabil-ity studies, is truncated, based on past ex-periences and intuition. Clearly, modern,
small-batch systems could enable morecombinations to be investigated. Coupled
with the newer lab equipment that youbought last month at my suggestion, suchas NIR or Raman, large numbers of well-
designed multivariate preformulation/sta-bility studies would go a long way in giv-ing your formulations people/clients thebest excipients to use for the clinical andfinal dosage forms.
OK, now that I opened the door, let’speek into the room. Having the ability toperform continuous manufacturing is notreserved for final production only. Indeedthe selfsame equipment is perfect for for-mulation studies. The formulation of soliddosage forms—capsules and tablets—hasbeen around for well over a half century.
There are books, courses, mentors, and, yes,experience to allow formulators to makeeducated guesses. Did I say guesses? Well,to be fair, I did use educated. The formula-tor will use his/her best judgement, basedon what similar APIs in the past did with
which excipients. I say similar, because re-search is being performed on an API thatis assumed new, not just a simple homologof something already on the market. So,
while we can make good guesses, most ofthe time, there can easily be surprises.
Using a metabolic analogy, an NSAID
(no-steroidal anti-inflammatory drug) isan NSAID is an NSAID, right? Althoughsimilar to aspirin (stomach bleeding), acet-aminophen causes liver damage, naproxencauses (reversible) kidney damage, ibupro-fen causes stomach issues and needs to betaken with food, Meloxicam seems to do atap-dance along the entire GI tract, and soit goes. How about other similar drugs andtheir formulation properties?
I had an interesting experience a few years back with a morphine derivative. It was similar to others for which we pro-
duced final products, but there was a tinydifference. This particular molecule could
Emil W. Ciurczak
DoraMaxx Consulting
Emil W. Ciurczak has worked in
the pharmaceutical industry since
1970 for companies that include Ciba-Geigy,
Sandoz, Berlex, Merck, and Purdue Pharma,
where he specialized in performing method de-
velopment on most types of analytical equip-
ment. In 1983, he introduced NIR spectroscopy
to pharmaceutical applications, and is generally
credited as one of the first to use process ana-
lytical technologies (PAT) in drug manufacturingand development.
Build It and He Will Come
Updated labs and personnel help build business
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 25/132
BIOTECHMANUFACTURING
SOLUTIONSEXPERIENCE QUALITY RELIABILITY PRODUCTIVITY4 YOUR SUCCESS
For further information please contact:SANDOZ Biopharmaceuticals, Biotech Cooperations6250 Kundl, Austria, Phone +43 (0)5338 200 [email protected], www.sandoz.com
w a o . d e
a Novartis company
Customized solutions forcGMP manufacture of recombinant Peptides,Proteins and Monoclonal Antibodies in
FDA/EMEA/PMDA approved facilities
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 26/132
26 Contract Pharma contractpharma.com June 2015
A N A L Y Z E T H I S !
form either the monohydrate or hemihy-drate in the drying stage of granulation.Since the QC test was a Karl Fisher mois-
ture with a 1% limit, it wasn’t noticed for years. When it was discerned, it was seen, with careful data mining, checking inlethumidity, etc. of former runs, that oneform had six months less stability thanthe other. So, simply controlling a factor
we didn’t know was critical (CPP’s andCQA’s… remember?), gave better expirydates. You can’t always extrapolate fromsimilar APIs.
So, let us assume that your companyinvested in a suite of continuous manu-facturing equipment, replete with all the
necessary monitoring instruments— weighing controls, NIR, Raman, etc.—andnecessary software. Where do you go fromthere? Well, there are several major careerpaths that may be followed:1. The most obvious is to simply transfer
the method(s) developed at larger,innovator companies, using theirformulation(s), speeds, compres-sion pressures, etc. Perform a quick
validation for method transfer andbegin producing product. Since eventhe biggest pharma companies have
just so much capital, they would loveto minimize the number of produc-tion suites added to their locationsby farming out their state-of-the-artformulations to similar equipment ata CMO. Then they can move on tonew product formulation on the sameequipment, without tying it up withmere production.
One great advantage of CM is thatthere is no normal or standard batch size.Using the equipment, it is just as easy to
produce 10,000 or 5,000,000 dosage forms,all with the same process signature. Pro-cess signature, simply put, is the physicalshape—hardness density, size, etc.—of atablet made on a particular instrument.
With more and more emphasis beingplace on counterfeit product, the resultanttablets from the CM suite will always beidentical, no matter the batch size.2. Since change comes more slowly to
larger companies, having the ability tobe the location of their method devel-opment and production facility. The
attractiveness of a one-stop shoppinglocation will help secure more busi-
ness, both before and after a formula-tion is nailed down. Another benefitof performing both functions is that,
by the time the production scheduleis set, your production staff is alreadyfamiliar with the formulation andprocess parameters. Performing thefirst function almost guarantees beingcontracted for the second. The cost ofthe equipment is rapidly recovered(ROI on steroids) and, when businessexpands, the suite is easily duplicatedat far less cost that classical equipmentand space.
You have avoided two major time-
consumers: product/process transfer andbatch scale-up. The first is variable, butthe second often takes between 12 and18 months. That is equivalent to adding a
year to one and a half years to the activepatent life.3. Orphan drugs are often overlooked
as sources of profit because the batchsizes seldom justify developmentcosts. Or, at least, that’s how it usedto be. With the massive time and costsavings associated with a CM set-up,the cost of developing orphan drug
dosage forms can be kept at a levelthat makes it worth the effort. Sincethere may not be large reservoirs ofthe active available, these smallerbatches are also quite practical. Thematerials can be formulated in smalllots, tested in small lots, then as muchas needed can be produced on com-mand.
4. As mentioned earlier, high activity, lowsolubility APIs are a royal pain to for-mulate and produce. Moving the bulkmaterials from blender to granulator
to tableting station to coating stationto packaging is certainly exacerbatingpotential hazards, if only the discom-fort of gowning and the breathingapparatus required for handling. TheCM system is closed and the materialsmove from one function to another
without exposure to the surroundings.This saves time and reduces hazards.This applies to controlled substances,as well.
An added benefit is the constant moni-
toring of the in-process materials and finaldosage forms. Since low-dose, high-activ-
ity materials are often low solubility, as well, the API is almost needed to be in anamorphous form. The acts of mixing, gran-
ulating, drying, tableting and even spray-ing can add energy, causing morphologychanges. In a normal process chain, thesechanges could neither be spotted nor aprocess stopped in a timely fashion. A CMunit is almost always controlled by NIRand/or Raman units; both are excellentmonitors of polymorph changes. Sinceonly small amounts of material are beingprocessed at any time, even if a polymorphchange cannot be corrected, you will stillonly lose a small portion of a batch ratherthan an entire batch and will be able to
modify process conditions to correct theproblem on the rest of the batch.
It is apparent that having modern pro-cess equipment will make any companymore than merely competitive, but, bymaking itself more versatile without mul-tiple production lines, the business shouldgrow quite nicely. Keeping in mind thatall pharma companies, both innovatorand generic, are under growing pressureto reduce costs of finished products. Sincethere will not be a major drop in API or ex-cipient costs in the near future, that leaves
two ways to lower COGS (cost of goodssold): lower labor costs or lower produc-tion costs.
With the quality of life and salariesincreasing in developing countries, it isbecoming harder to simply move to findcheaper labor. In itself, that isn’t the onlycost; there is the cost of relocation, train-ing, logistics and transportation. Not tomention that, as more factories move to acountry, labor costs rise with competition.So that becomes a case of diminishing re-turns and doesn’t solve the problem over
the long haul.The other approach is to lower produc-tion costs by speeding up the process andreducing the footprint of your company.
A CM needs far less warehousing space,fewer lab tests, less power—HVAC, lights,and production equipment—and mostimportantly, the time to market. Speed-ing completion of a batch of productfrom weeks to hours/days is one aspect.The other is never producing an OOS lot,avoiding recalls and bare shelves at phar-macies. I’m open to rebuttals, if you can
find a better way to make products, I’ll beright here. CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 27/132
SUITE SCIENCE
Preformulation Development Analytical Services Formulation Development
GMP Manufacturing Clinical Supplies Packaging & Distribution
C on t a c t u s : w w w . x c e l i e n c e . c o m + 1 . 8 1 3 . 2 8 6 . 0 4 0 4
Xcelience® offers a suite of services enabling clients to partner with
a single CDMO for all of their clinical outsourcing needs.
Xcelience takes pride in delivering the highest standards in science
and service with an emphasis on quality, cost and speed.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 28/132
28 Contract Pharma contractpharma.com June 2015
T H E L O W E D O W N
Signing Off! After 15 years, the Lowe Down column has come to a close
A
fter a multiyear run, I’m sorry toannounce that this will be my lastcolumn for Contract Pharma. I
would probably be unnerved to see theentire stack of them that I’ve written overthe years, and for all I know, I’d be un-nerved to have to read them all as well(!) But it’s been fun. I’ve enjoyed having aplatform to vent my opinions, of which Iseem to have no shortage, bring up ques-tions (ditto), and every so often spend anentire column on nothing more than in-side jokes about the industry.
We don’t have a shortage of those,either. I think that any field that’s asintrinsically hard as drug discovery and
development is going to pick up a lotof dark humor; it’s a bit like how jokesseemed to flourish in the old SovietUnion. “Under capitalism, man exploitshis fellow man. Under communism, it’sthe exact opposite!”You need that sortof thing as an outlet, and to try to keep
your perspective.So, do I have any different perspec-
tive now than when I started writingthis column? Looking back, I think that Ican see a few trends. From a med-chemstandpoint I used to be a bit more hard-
headed about drug structures. Funny-looking things got crossed right off thelist, if I had my way about it, but since
then I’ve come to wonder about thecriteria I’ve used for “funny-looking”.
Any ten medicinal chemists, it has be-
come clear, will have very different ideasabout what’s worth keeping and whatisn’t, and it’s harder than you’d think—or harder than I thought—to say whichof them are right. I’m a lot more willingto let the numbers speak for themselvesthese days.
That said, my thinking has alsoevolved about those few compoundsthat all ten random medicinal chemistsmight agree on as troublesome. Mostof the time, they’re right. If you can getthat many ornery chemists to agree on
anything, there’s probably something toit. There really are bad compounds outthere, you know—some things just can’tbe drugs. The list is shorter than I wouldhave made it ten or fifteen years ago, butthat doesn’t mean that there’s no list atall. Some classes of compounds havesuch a high probability of wasting yourtime and effort that you’re better off noteven starting with them. Overall, I thinkthat I’ve gotten rid of my middle groundin this area: most everything gets achance to prove itself, but a shorter list
must be thrown away immediately be-fore anyone has a chance to get excited
about it. A few thoughts about other areas: I
liked phenotypic screening years ago,
and I still do, although I’ve come to real-ize that a bad phenotypic screen is (1) alot easier to set up than a good one and(2) truly the worst of both worlds. Theonly problem, then, is recognizing when
you’re in the middle of a bad phenotypicscreening campaign. Formulations, itseems to me, is an area that looks to bein no danger of running out of new ideas,
which is a good thing, because some ofthe compounds we’re turning out aregoing to need all the help we can get.
About toxicology, my opinions have not
changed much—it scared me then, andit scares me now, because we’re not a lotcloser to being able to predict anything.Data rule in this business, and nowheremore than tox testing. If you droppedevery drug candidate that might havea toxicity problem, you’d have to dropthem all. The only thing to do is spendthe time and money and go out and runthe tests.
What about the whole direction ofthe industry? My pundit binocularsaren’t any better than they were—no
one’s are. I’ve complained about everybig pharma merger over the last twenty
Derek B. Lowe
Contributing Editor
Derek B. Lowe has been employed
since 1989 in pharmaceutical drug
discovery in several therapeutic areas. His blog,
In the Pipeline, is located at www.corante.com/
pipeline and is an awfully good read. He can bereached at [email protected].
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 29/132
June 2015 Twitter : @ContractPharma Contract Pharma 29
T H E L O W E D O W N
years, because none of them made verymuch sense to me, and I’ll continue to
complain when Pfizer buys someoneelse. Or two other big companies com-bine into one really big mediocre one
with more problems than ever. The onlything that I’m pretty sure of is that thecurrent model can’t go on forever. Toomuch of the industry’s profitability hasbeen coming from the ability to raiseprices every year, and I am absolutelysure that this is not a viable long-termstrategy. Meanwhile, the cost to find anddevelop drugs is rising merrily along as
well. These two lines are heading across
each other’s paths like misdirectedtrains. But what comes next, that’s whatI don’t know. I’m fond of quoting Her-bert Stein, Nixon’s old economic advi-sor, who used to say, “If something can’tgo on, then it won’t.”I think that’s what
we’re looking at here.But at the same time, I can find a lot
of things to be excited about. I doubt myown career encompasses any five-yearperiod like the most recent one whenit comes to completely new treatmentmechanisms showing promise. For all
of our problems, we can still discoverthings in this industry, and still amazeourselves and others with how wellnew ideas can work. There are some ex-traordinary things going on right now,
and more look to be coming, and that’s worth keeping in mind when gloomy
thoughts intrude. There really are a lotof great things out there waiting to befound, and we never really know wherethe next ones are coming from.
And that, in the end, is what researchhas done for me, and done to me. I’mtotally unfit by now for any kind of job
where I would know what’s going tohappen next. Being the first to try some-thing, the first to find something out,even if it’s just a minor thing like a newNMR spectrum or another salt form,has become second nature. Everything
else, by comparison, seems like work-ing at the sawmill. If you like this sort ofthing, and I do, then nothing else reallycompares. For all the craziness, all thedead ends and projects that didn’t panout, I still feel like I’m getting away withsomething and getting paid for doing it.
For that matter, I also feel as if I’mgetting away with something when I getpaid to throw out my own opinions andprejudices on paper. I really have enjoyeddoing that here at Contract Pharma. It’sa good thing that I have other outlets
for opinion-spouting, because that’s be-come second nature over the years, too.I’d like to thank the editors here, and thereaders out there, for letting me do it! CP
˝ 2015 Catalent Pharma Solutions. All rights reserved.
Discover more.
us + 1 888 SOLUTION
eu 00800 8855 6178
catalent.com/drugdelivery
l l i . ll i .
besttechnologies.broadestexpertise.fasterdevelopment.
l l i . ll i .
l l i . ll i .
Discover more.
US + 1 888 SOLUTION (765 8846)
EU 00800 8855 [email protected]
catalent.com/drugdelivery
l
l
i
.
l l i
.
l l i . ll i .
technology
spotlight
zydis® fast-dissolve
technologies
World’s best orallydissolvable tablet– about 3 seconds.Uniquely delivers smallor large molecules.20 Rx and OTC productsin 50 markets. NEWtaste-masking andhigher dose options.
l l i . ll i .
rp scherer softgel technologies
controlled release technologies
optimelt™ hme technology
osdrc® optidose™ technology
l l i . ll i .
l
l
i
.
l l i
.
“There are some extraordinary things going on right
now, and more look to be coming, and that’s worthkeeping in mind when gloomy thoughts intrude. There
really are a lot of great things out there waiting to be
found, and we never really know where the next ones
are coming from.”
LOOKING FOR TRAINING:
CGMP/HPB/FDA COMPLIANCE?
Our Contract Services Directory
has you covered!
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 30/132
30 Contract Pharma contractpharma.com June 2015
T H E B I O P H A R M I N S I D E R
CMOs Facing Significant
Capacity ConstraintsDownstream purification creating chronic problems
O
utsourcing of biomanufacturing hasbeen on the rise in recent years; onemeasure of success among con-
tract manufacturing organizations (CMOs)is their ability to ensure their facilities keepup with demand. CMO constraints are notnecessarily an unhealthy indicator, but mustbe balanced against clients’ need for ac-cess to flexible scheduling, and capacity. Infact, results from BioPlan Associates’newly-released 12th Annual Report and Survey ofBiopharmaceutical Manufacturing Capacityand Production1 show that CMOs are facingcapacity constraints to a more significant de-gree than in recent years, all while operatingat high levels of capacity. And while percep-
tions of future capacity constraints are moreoptimistic, CMOs clearly believe that, amonga broad swath of improvements they will beimplementing, improving their downstreampurification technologies will be paramountto overcoming bottleneck challenges.
What the Data ShowIn our annual global study of 237 biophar-maceutical manufacturers and CMOs, a sur-prisingly high 36% of CMOs believe theirfacility is experiencing at least “significant”
production capacity constraints today. And if we include those experiencing at least“mod-erate”constraints, roughly half of CMOs to-
day are experiencing real capacity problems.The data show some interesting trends
when compared with last year’s results. Al-though last year about the same percent-age of CMOs surveyed were experiencingat least “moderate”constraints, far more arefinding constraints are worsening. This yearalmost twice as many report significantconstraints (32.7% vs. 17.4% in 2014).
Unhealthy Capacity UtilizationCapacity constraints aren’t always a nega-tive for CMOs, as many presume future
growth is based on increasing demand.Further, when properly managed, con-straints can be an indicator of efficiency,but must be balanced against clients’need for access to flexible capacity.
On the other hand, this year’s survey re-sults show CMOs may be hitting limits of
what would be considered a healthy level ofexcess (flex) capacity. This is particularly thecase for mammalian cell culture—the domi-nant paradigm—for which CMO respon-dents this year estimated currently operat-ing at an average 82% of operating capacity.
This is a hefty increase from last year’s aver-age of 58% capacity utilization. The last time we saw levels in this range were 10 yearsago during what was often referred to as anindustry-wide capacity crunch.
Likewise, CMOs this year estimateoperating at around 68% of microbialfermentation capacity, up from last year’s54%. With CMOs operating at significant-ly higher levels of capacity this year thanlast, it’s easy to see why perceptions ofcapacity constraints are also trending up.
Future Capacity ConstraintsEven so, it’s encouraging to see that CMO
respondents to this year’s study are less like-ly to perceive significant capacity constraintsin the medium-term than they are to be
experiencing them today. Compared to the36% experiencing significant or severe con-straints today, only 1 in 5 are expecting thatlevel of bottlenecks in 2020—essentially,CMOs are confident of their ability to man-age capacity problems in the future.
Overall, our data indicates that about8 in 10 CMOs expect to face some level ofcapacity constraint at their facility within 5
years’ time, down from roughly 9 in 10 last year. Along with that, fewer respondentsthis year expect severe or significant con-straints in 5 years than did last year.
CMOs Spending on Expanding Facilities Although CMOs this year are concernedabout their current situation, they are morepositive about their ability to handle futurecapacity constraint problems. This may bea reflection of anticipated spending on newfacility construction: About 7 in 10 CMOsplan to increase their spending on new facil-ities this year, and the overall level of budgetincreases outpace expected spending hikesin many other areas, including staff hiring,process development, and new technologies
for upstream and downstream production.Moreover, CMOs this year estimate ex-panding their mammalian cell culture ca-pacity by a substantial 77% over the next 5
years, double the overall amount of expan-sion (39%) they had forecast last year. Clear-ly, these organizations seeing that they areoperating at high levels of mammalian pro-duction capacity today forecast expansionsin the future that will ease their constraints.
CMOs may also be considering thecurrent climate, in which, in contrast tothe blockbuster approvals of the early
2000s, most of the current and upcomingdrug approvals are for niche products with
Eric S. Langer
BioPlan Associates
Eric S. Langer is president and
managing partner at BioPlan Associates, Inc.,
a biotechnology and life sciences marketing re-
search and publishing firm established in Rockville,
MD in 1989. He is editor of numerous studies,
including “Biopharmaceutical Technology in Chi-
na,” “Advances in Large-scale Biopharmaceutical
Manufacturing”, and many other industry reports.
[email protected] 301-921-5979. www.bioplanassociates.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 31/132
© COOK 2013 PH- BADV-CPAPR-EN-20 1303
Simplify your contract manufacturing with process development, cell-culture manufacturing,
formulation development, vial and syringe filling and secondary packaging all in onelocation. Accelerate the delivery of your life-enhancing products to patients, and workwith one point of contact and one set of business practices.
To see our capabilities videos, visit www.youtube.com/user/cookpharmica or contact our Business Development team at [email protected].
SIMPLIFY YO U R C O N T R AC T M A N U FAC T U R I N G
DEVELOPMENT • CLINICAL • COMMERCIAL • DRUG SUBSTANCE • DRUG PRODUCT
SM
www.cookpharmica.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 32/132
32 Contract Pharma contractpharma.com June 2015
T H E B I O P H A R M I N S I D E R
inherent smaller markets, additional in-dications of therapy on existing products,new countries, for sub-$1b markets, or forbiosimilars/biogenerics production.
While the onset of biosimilars and bio-generics production is likely to favor CMOs,many of the new products in the pipeline
can be absorbed into biomanufacturers’existing facilities, as the manufacturing vol-umes are smaller. For biomanufacturers,
whose expected future constraints are moremoderate in nature than CMOs, there is lessalarm, as there are now more options forretrofitting existing facilities to add incre-mental facility in a relatively short amountof time. And the option for outsourcing willof course continue to be attractive, too.
Avoiding Constraints As part of our ongoing trend analysis of
the causes—and potential alleviators—ofcapacity constraints, we asked CMOs to
evaluate the factors likely to create produc-tion capacity constraints at their facility overthe next 5 years.
CMOs were most likely to report facilityconstraints (68%, up from 56% in 2014) asthe source of capacity constraints, with thisfactor consistently atop the rankings over
the past several years. In an interesting diver-gence from last year’s results, however, thephysical capacity of downstream purificationequipment was the factor second-most likelyto be fingered as a culprit by CMOs. This fac-tor was cited by a majority (53%) of respon-dents this year, up from 37% last year. That’san important indicator, given improvementsin purification technology that suppliers areinvesting in to move the industry away fromsuch problems, including:• Moving bed technologies;• Fast-ow resins;
• Greater binding capacity resins;• Membrane separation technologies;
• Better UF-membranes; and• More single-use equipment for puri-
fication.
With CMOs often at the forefront of newtechnology adoption, it’s a telling indicatorthat a large proportion would see physicalequipment constraints being a source of ca-pacity bottlenecks in 5 years’time. It may bethat CMOs are pessimistic about the poten-tial for truly novel DSP solutions to arrive that
will dramatically improve their downstreamprocessing. Although there are promisingnew technologies that could allow continu-ous or semi-continuous modes of operation,that could, in turn allowing for a large jump
in the titers processed by downstream opera-tions, the timeline for adoption may be lon-ger than 5 years. On the other hand, it’s pos-sible that respondents are reecting more ontheir current situation, in which downstreamequipment has failed to match upstream im-provements in recent years. Indeed, almosttwo-thirds (64%) of CMOs say that down-stream processing is impacting capacity andoverall production either by producing some(36%) or serious (27%) bottlenecks today.
Beyond facility and downstream equip-ment constraints, CMOs also see staffing
problems as contributing to future capac-ity constraints, with many pointing to an:• Inability to retain experienced techni-
cal and production staff (42%);• Inability to hire new, experienced tech-
nical and production staff (37%); and an• Inability to hire new, experienced
scientific staff (32%).
One of the primary reasons these hiringproblems are expanding, and why staffing isso important, is that much of the knowledgein the biotech community is institutional in
nature, and experienced operators help miti-gate very costly problems, like contamina-tion risks, because they provide a depth ofproduction experience that reduces costs andcycle times. Part of this trend is simply theon-going 14% growth rate in the biophar-ma industry. In addition, the move by largercompanies to expand into overseas marketsis drawing skilled workers as ‘expats’in thesefacilities. Although many still consider bio-tech to be an emerging industry, today, older
workers who have ridden the wave of successof in biotech, and are retiring early, or work-
ing as experienced consultants.Unlike many other industries, biophar-
I believe our facility is experiencing production capacity
constraints today“Biomanufacturer vs. CMO”
Severe
constraintsBiotherapeutic Developers CMOs
3.2%
3.6%
10.3%
32.7%
32.7%
29.0%
29.6%
27.9%
18.2%
12.7%
Significant
constraints
Moderate
constraints
Minor
constraints
Noconstraints
FIGURE 1: Capacity Constraints, Biotherapeutic Developers vs. CMOs
Source: 12th Annual Report and Survey of Biopharmaceutical Manufacturing, April 2015,www.bioplanassociates.com/12th
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 33/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 34/132
34 Contract Pharma contractpharma.com June 2015
T H E B I O P H A R M I N S I D E R
maceutical manufacturing requires industry-specific experience around regulatory aspects,process variability, and high service level re-quirements. This makes it difficult to employ
workers directly from related industries likechemical processing, food & beverage, etc.
without significant additional (re)training.Over the next 3-5 years, we expect to see
experienced staff—especially those involvedin operations and late-stage process devel-opment—become more sought after as theindustry shifts to lower-cost manufacturingof biosimilars and other products in whichflexibility and speed are especially important.Competition that will come about with theadvent of biosimilars may cause biomanu-facturers and CMOs to be less open aboutsharing best practices, leading them to placemore importance on retaining key technicalstaff to at least prevent loss of knowledge tocompetitors.
From our study, the inability to hire andretain experienced staff appears to be moreof a concern for CMOs than for biomanu-facturers. Not surprisingly, then, CMOs arealso more likely to emphasize training andeducation as important areas to addressin order to avoid significant capacity con-straints. Compared to biomanufacturers,CMOs are more likely to see a pressing needto increase training and education in pro-duction, technical and regulatory areas, al-though there is less of a gap in the perceivedneed for training in scientific areas.
Even so, in the near-term, CMOs aremost likely to push for the development of
better downstream purification technolo-gies to avoid future constraints. That’s tobe expected, given that physical equip-ment constraints are a leading reason theyexpect those future bottlenecks. Single-use products are in high regard, with asignificant portion of CMOs seeing thedevelopment of most cost-effective and/
or better-performing single-use productsas helping them avoid future constraints.
For the most part, CMOs and biomanu-facturers are in agreement about the impor-tant areas to address in order to avoid futureconstraints, although in some instances thereare some notable gaps between the twogroups. According to our data, for example:• CMOs are more likely to see the
value in establishing manufacturingstandards and industry benchmarks,as well as the aforementioned trainingand education efforts; while
• Biomanufacturers are more apt to feelthe industry should develop more “mod-ularized”production systems and fundmore research to maximize productionefficiencies.
In general, the areas in which biomanu-facturers felt more strongly were relatedmore to platforms and investments, focus-ing on reducing scale-up costs and improv-ing yields to lower costs and time to manu-facture. By contrast, CMOs displayed moreof a staffing and education focus, presum-
ably as a result of a tighter focus on opera-tions within existing facilities.
Conclusion
Our data indicates that a significant portion ofCMOs, compared to biopharma companies,are experiencing capacity constraints today,perhaps as mammalian cell culture produc-tion capacity utilization rates trend higher. Al-though CMOs are increasing their new facilitybudgets, and data indicates that their mam-
malian cell culture capacity continues to grow year after year, one of the key culprits remainslimitations with downstream purification, for
which CMOs continue to seek improvements.Newer and more efficient single-use
products could help; this is in keeping withthe general shift from blockbuster manufac-ture to manufacture of multiple niche prod-ucts, but also is more generally suited to theCMO model, which involves juggling mul-tiple products, platforms and processes. Infact, when we separately asked the industryto identify which new product development
areas are of interest to them, the leading areafor CMOs was disposable purification prod-ucts, cited by almost half. Not far behind,chromatography products also rated highly,reflecting CMOs’ desire for more efficientdownstream purification technologies.
Finally, while it’s easy to get caughtup in talk of innovation, CMOs are also
wary about staffing issues contributing toconstraints in the medium-term. Trainingand educating key technical and opera-tions staff will become more important toCMOs, as will retaining existing staff. After
all, sophisticated process equipment needssophisticated operators. CP
Which factors are likely to create biopharmaceutical production capacity contraints at
your facility in 5 years?Comparing Biotherapeutic Manufacturers vs. CMOs
Biomanufacturers
Facility constraints
Analytical testing and drug product release
Physical capacity of downstream purification equipment
Inability to hire new, experienced scientific staff
Inability to hire new, experienced technical and production staff
Inability to retain experienced technical and production staff
CMOs 58.9%
68.4%
38.0%
47.4%
32.6%
52.6%
27.9%
27.1%
27.1%
42.1%
31.6%
36.5%
FIGURE 2: Selected Factors Creating Future Capacity Constraints; Biotherapeutic Developers vs. CMOs
Source: 12th Annual Report and Survey of Biopharmaceutical Manufacturing, April 2015,www.bioplanassociates.com/12th
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 35/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 36/132
I N D I A R E P O R T
36 Contract Pharma contractpharma.com June 2015
Q
uickening interest among the do-mestic companies managing drugsafety data was Parexel Interna-
tional’s announcement to buy QuantumSolutions India in March.
The Boston-based CRO said the com-pany would integrate the Indian phar-macovigilance services firm into its post-approval services, expecting to close thebuy-out the following month.
Located in Chandigarh, in the north-ern part of India, the privately-owned QSIoffers services including individual casesafety report processing, brand physicianactivities, affiliate support, aggregate report
writing, literature reviews and signal detec-
tion for clientele across pharmaceutical,medical device and consumer products.The acquisition of QSI would enable
Parexel to provide a more comprehen-sive, efficient and economical solution toclients around the world, the companieschief executive stated in a news release.
Though Parexel did not reveal the finan-cial details of the deal, the news of the acqui-sition infused a shot of enthusiam into thepharmacovigilance services arena, which hasseldom grabbed headlines over the years.
Spurred by increasing requirements
for drug surveillance data by regulators,the drug safety data outsourcing marketis gaining pace world over. Currently esti-mated around $2 billion, the nascent sec-tor is forecast to double its size over the
next five years, according to TransparencyMarket Research.
Roadmap In WorksIn India, companies providing drug safetymonitoring have witnessed impressivegrowth over the last several years. Lead-ing players in the field such as Accenture,Cognizant Technology Solutions and TataConsultancy Services are managing ex-tensive pharmacovigilance operations inthe country. More than 14,000 people arepresently working in this sector, whichmarks a huge leap from a few hundred7-8 years ago.
Quite a few drug makers, including
members from Big Pharma, are offshor-ing drug safety data to these Indian firms,making use of the cost advantage factor.India’s genetically diverse population basecould also be an enabler to facilitate fasterassessment of drugs’ adverse impacts.
In sync with the tightly regulated mar-kets, India has already started workingon a roadmap for bolstering the country’spharmacovigilance regulatory system.
The existing law requires that manufac-turers submit periodic safety update reportsto the regulator for the first four years after
a new drug is introduced into the market.The companies should list out adversereactions, drug-related injuries and fatali-ties post-marketing in Indian patients ev-ery six months in the first two years. Forthe remaining two years companies needto report once a year. Companies don’thave to submit any more reports to theCentral Drugs Standard Control Organi-zation—the top drug regulator’s office—after this four-year period. The drug will,thereafter, be monitored under nationalsurveillance registry known as Pharmaco-
vigilance Programme of India (PvPI). A large number of manufacturers,
however, were not eager to fulfill this re-quirement of updating CDSCO with peri-odic safety reports, despite being listed as
mandatory in the rule book.The Drug Control General of India
(DCGI) recently, initiating the efforts tostreamline the drug safety monitoringmechanism, made the decision to link theperiodic safety updates submitted by thecompanies to PvPI.
Started in 2010, PvPI collects sponta-neous adverse drug reports (ADRs) fromthe ADR monitoring centers across thecountry. After collating and analyzing theadverse events data, it computes the risk-benefit ratio and recommends regulatory
interventions, if required.The regulator hopes such a linking wouldenable better and more efficient monitoringof the drugs from the beginning by enhanc-ing PvPI as a central point to integrate andstore all the data on the possible adversedrug reports. The process for intimatingdrug makers to send their periodic safetyupdates to PVPI has started, reports state.
At the same time, the authority is movingto make drug surveillance cells compulsoryfor pharma companies. Even though firmsare required to submit post-marketing drug
safety updates on newly introduced drugs,the specific clause in the regulation has notbeen insisting to have their own drug safetymonitoring system in place.
India’s Drug Technical Advisory Board,a high-power experts committee whichadvises DCGI on technical matters, recom-mended that firms should start the practiceof reporting adverse events of marketeddrugs to the regulator by establishing vigi-lance cells under the supervision of a medi-cal officer or a pharmacist trained in thisdiscipline. The facility would collect data,
process them and forward the adverse re-action reports to the regulator. CP
S. Harachand
Contributing Editor
S. Harachand is a pharmaceutical journal-
ist based in Mumbai. He can be reached [email protected].
Emerging Hotbed Of
Surveillance Data?Offshoring moves to Indian shores as regulations evolve
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 37/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 38/132
38 Contract Pharma contractpharma.com June 2015
D A T A W A T C H
R&D spend
1Q2015
%
change
% of
sales
R&D spend
1Q2014
% of
sales
Novartis $2,067 -15% 9% $2,432 17%
Johnson & Johnson $1,899 4% 11% $1,831 10%
Pfizer $1,877 16% 17% $1,623 14%
Merck & Co. $1,737 10% 18% $1,574 15%
Sanofi-Aventis $1,457 -7% 14% $1,566 15%
AstraZeneca $1,356 13% 22% $1,200 19%
GlaxoSmithKline $1,318 1% 15% $1,304 14%
Eli Lilly & Co. $1,039 -6% 22% $1,109 24%
Bristol-Myers Squibb $1,016 7% 25% $946 25%
Amgen $856 -17% 17% $1,027 23%
Abbvie $811 5% 16% $772 17%
Gilead Sciences $696 19% 12% $595 12%
Novo Nordisk $600 4% 13% $578 15%
Biogen $461 -13% 18% $529 25%
Actavis $431 23% 25% $349 22%
Teva $332 -6% 7% $353 7%
Baxter $300 -4% 8% $313 8%
Alexion Pharma $221 15% 37% $192 34%
Mylan $170 44% 9% $118 7%
*All dollar amounts are in millions.
1Q R&D for Pharma & Biopharma A by-the-numbers look at the industry
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 39/132
Answers that work
www.vetter-pharma.com
Complex packaging?
Vetter is the simple choice.Today’s demand for injectables that meet both patient convenience and market
requirements can make secondary packaging complex. But your choice of a packaging
partner should be simple: Vetter.
Our packaging development experts support you from early packaging concepts
through to market launch. The team is ready to help with:
n Flexibility to meet custom packaging and serialization needs
n Expertise in specialized packaging, including complex pen/autoinjector
assembly and kit packaging
n Broad spectrum of packaging options, from blister packaging
to toploader cartoning
For packaging solutions tailored to meet your product and
patient needs, there’s a simple choice. Choose Vetter.
Learn more at BIO International Convention 2015 in Philadelphia at Booth # 3727.
For US inquiries, please contact [email protected] ■ For Asia Pacific inquiries, please contact info [email protected] ■
For EU and other international inquiries, please contact [email protected]
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 40/132
40 Contract Pharma contractpharma.com June 2015
QUICK HITS
Respondent Gender: 64% male, 36% female
Respondent Sector: 71% pharma/biopharma;
22% contract research; 7% lab services
Avg. 2014 base salary (all respondents): $119,546
Avg. 2014 bonus (all): $18,175
Avg. 2014 stock opt ions (all): $31,581
Avg. 2014 benefits (all): $22,580
Avg. 2014 base salary for men: $123,159
Avg. 2014 base salary for women: $112,491
Charts and graphics by Jessica Carlin
$ ALARY $URVEY
16TH ANNUAL
Welcome to Contract Pharma’s Sixteenth Annual Salary Survey! This year’s results are derived from more than 500 respondents from our readership aboutemployment attitudes, responsibilities, education, and their 2014 salaries.
In addition to the charts on the following pages, check out the online version at www.contractpharma.com where you’ll find more information.
—TW
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 41/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 42/132
16TH ANNUAL $ALARY $URVEY
42 Contract Pharma contractpharma.com June 2015
1 4 9 2 7 5 3 t14%
13%
13%
4%
3%
7%
5%
3%
3%
12%
2%
1%
9%
11%
R&D
QA/QC/VALIDATION
BUSINESS DEVELOPMENT
CONTRACT MANAGER
PROJECT MANAGER
CORPORATE MANAGEMENT
REGULATORY AFFAIRS
ENGINEERING
PURCHASING
CLINICAL RESEARCH
PROD./MFG./PKG.
CONSUMER PRODUCT OUTSOURCING MANAGER
MARKETING/SALES
LAB MANAGER/TECH SERVICE
FINANCIAL
LEGAL
OTHER
SALARY
BONUS
OPTIONS
BENEFITS
TOTAL COMPENSATION BY JOB CATEGORY
JOB FUNCTION
$295,837CORPORATE MANAGEMENT
QA/QC
PROJECT MANAGER
R&D
BUSINESS DEVELOPMENT
PURCHASING
PRODUCTION/MFG./PACKAGING
ENGINEERING
CLINICAL RESEARCH
REGULATORY AFFAIRS
CONTRACT MANAGER
OTHER
LAB MANAGER/TECH SERVICE
$284,073
$183,806
$182,224
$175,055
$165,097
$160,654
$152,789
$147,015
$146,813
$142,409
$142,271
$124,093
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 43/132
Relieves (Development) Headaches.
Trying to keep your drug moving forward through
development can be a painful experience. Thatʼs why
Mikart is the Contract Development and Manufactu-
ring Organization (CDMO) that gives you the
services you need, plus the speed and responsive-
ness you want.
Donʼt put up with inflexible procedures
and unreturned calls. At Mikart, weʼre
quick to respond with customized solu-tions that get your projects completed
faster and to your individual specifications.
In addition to Formulation Development,
Mikart also provides Clinical Trial Supplies,
Regulatory Filing Support, plus Manufactu-
ring and Packaging solutions.
Youʼll find Mikart has everything youʼre
looking for in a pharma partner: innovativetechnology and equipment, highly skilled
people and 38 years of solid CDMO experi-
ence.
To experience just how responsive we can be,
contact us at 1-888-4MIKART or send us an
email to [email protected]
Ready. Responsive. Right for You.
Mikart, Inc. | 1750 Chattahoochee Avenue | Atlanta GA 30318www.mikart.com | 1-888-4MIKART
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 44/132
16TH ANNUAL $ALARY $URVEY
44 Contract Pharma contractpharma.com June 2015
1 3 4 9 6 5 t13%
13%
15%
12%
5%5%
3%
3%3%
4%
9%
9%
6%
NY/NJ
NORTH CAROLINA
SOUTHWEST
NEW ENGLAND
NORTHERN CALIFORNIA
SOUTHERN CALIFORNIA
MIDWEST
OTHER MID-ATLANTIC
OTHER EAST COAST
OTHER WEST COAST
EUROPE
ASIA
OTHER
SALARY
BONUS
OPTIONS
BENEFITS
TOTAL COMPENSATION BY GEOGRAPHIC REGION
GEOGRAPHIC REGION
OTHER MID-ATLANTIC
NEW ENGLAND
NY/NJ
OTHER EAST COAST
OTHER
SOUTHERN CALIFORNIA
MIDWEST
NORTHERN CALIFORNIA
OTHER WEST COAST
EUROPE
SOUTHWEST
NORTH CAROLINA
ASIA
$237,128
$200,437
$190,580
$188,767
$188,309
$186,245
$180,834
$175,007
$157,862
$156,123
$146,903
$144,184
$144,020
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 45/132
We work for some of the most trusted healthand wellness brands in the world. Brands thatmake promises to millions of customers everyday. These promises hold weight becausethey are built on trust. Trust that travelsfrom the customer to the brand to us. That’swhy our customer relationships average overten years. From contract manufacturing andpackaging to complete technology transfers,
we are here to keep the trust. Find out moreat www.pharma-tech.com or call us at
706.246.3555.
We make products that fulfill promises
Powders Effervescent & Solid Dose Capsules Plastic Molding Swabs & Applicators
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 46/132
16TH ANNUAL $ALARY $URVEY
46 Contract Pharma contractpharma.com June 2015
1 t17%
83%
YES
NO
5 2 8 4 t50%
25%
11%
8%
2% 4%
1-4
5-10
11-20
21-50
51-100
100+
HAVE YOU HAD TO LAY OFF ANY OF YOUR STAFF IN THE PAST YEAR?
IF YOU SERVE IN A MANAGEMENT POSITION, HOW MANY PEOPLE DO YOU OVERSEE?
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 47/132
platinumpress.com • 469-733-1506
With the opening of our new 60,000 square foot facility in New Jersey,Platinum Press now has two locations to provide you with today’s finesthealthcare packaging solutions. This new plant will offer the exact samedigital, flexographic and lithographic printing capabilities as our Texas facility,combined with an expert team of industry professionals to meet your most
pressing needs.
Searching for reduced shipping costs, improved turnaround time and enhanced production?
Our doors are always open.
Platinum Press... your license to succeed.
Folding Cartons • Specialty Cartons • Inserts/Outserts • Labels • Specialty Labels • Blister Packaging • Medication Guides
We just did it, with full-servicefacilities in Texas and New Jersey.
Who says youcan’t be in two places
at the same time?
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 48/132
16TH ANNUAL $ALARY $URVEY
48 Contract Pharma contractpharma.com June 2015
7 2 t 9 6 t
35%
BUSINESS DEVELOPMENT
CLINICAL RESEARCH
CONSUMER PRODUCT
OUTSOURCING MANAGER
CONTRACT MANAGER
CORPORATE MANAGEMENT
(INCL. CEO, CFO, VP OPS/MFG.)
ENGINEERING
LAB MANAGER/TECH SERVICE
PROD./MFG./PKG.
PROJECT MANAGER
PURCHASING
QA/QC
R&D
REGULATORY AFFAIRS
OTHER
TOTAL COMPENSATION BY EDUCATION LEVEL
3 t35%24%
6%
BACHELORS
MASTER’S
DOCTORATE
OTHER
EDUCATIONAL (HIGHEST DEGREE ATTAINED) JOBS FOR BACHELOR DEGREE
JOBS FOR DOCTORATE DEGREE
1 5 8 4 tJOBS FOR MASTER DEGREE
SALARY BONUS OPTIONS BENEFITS
BACHELOR’S DEGREE
MASTER’S DEGREE
DOCTORATE DEGREE
$181,518
$203,337
$169,751
13%14%
8%
8%
3%
7%
5%
9%
16% 10%
11%
4%
4%
4%
5%
5%
8%
7%
6%
6%
7%
9%4%
34%
13%
13%
10%
14%
1%
1% 2%
2%
2%
2%
20%
2%
2%
3%3%
3%35%
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 49/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 50/132
16TH ANNUAL $ALARY $URVEY
50 Contract Pharma contractpharma.com June 2015
MEN
SALARY
BONUS
OPTIONS
BENEFITS
WOMEN
SALARY
BONUS
OPTIONS
BENEFITS
TOTAL COMPENSATION BY JOB CATEGORY & GENDER
R&D
CORP MANAGEMENT
BUSINESS DEVELOPMENT
CLINICAL RESEARCH
QA/QC
PROJECT MANAGER
$198,456
$135,684
$317,282
$165,191
$180,307
$146,818
$126,394
$176,187
$205,687
$145,933
$157,595
$140,007
1 8 3 6 tBUSINESS DEVELOPMENT
CLINICAL RESEARCH
CONSUMER PRODUCT OUTSOURCING MANAGER
CONTRACT MANAGER
CORPORATE MANAGEMENT (INCL. CEO, CFO, VP OPS/MFG.)
ENGINEERING
LAB MANAGER/TECH SERVICE
PROD./MFG./PKG.
PROJECT MANAGER
PURCHASING
QA/QC
R&D
REGULATORY AFFAIRS
OTHER
5 2 tJOB FUNCTIONS BY GENDER
MEN WOMEN
14%
12%
16%
10%
14%
5%
5%
5%8%
3%
11%
10%
10%
17%
15%
8%
3%
3%
5%
5%
6%
6%
1%
3%
1%
2%
2%
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 51/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 52/132
16TH ANNUAL $ALARY $URVEY
52 Contract Pharma contractpharma.com June 2015
1 t16%
84%
YES
NO
2 3 8 t21%
35%
34%
8%2%
VERY SATISFIED
HAPPY
SOMEWHAT SATISFIED
UNHAPPY
EXTREMELY DISSATISIFIED
HAVE YOU CHANGED COMPANIES IN THE PAST YEAR?
HOW WOULD YOU DESCRIBE YOUR FEELINGS ABOUT YOUR CURRENT POSITION?
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 53/132
16TH ANNUAL $ALARY $URVEY
June 2015 Twitter: @ContractPharma Contract Pharma 53
5%
1 3 7 2 5 t16%
13%
21%
31%
7%
5%2%
LACK OF ADVANCEMENT
INTERNAL POLITICS
MERGER & ACQUISITION/LAYOFF FEARS
INADEQUATE COMPENSATION
INADEQUATE PROJECT FUNDING/RESOURCES
WALL STREET/SHAREHOLDER EXPECTATIONS
REGULATORY PROCESS
EXPLAINING PHARMA/BIOPHARMA TO OUTSIDERS
WHAT’S THE MOST FRUSTRATING ASPECT OF YOUR JOB?
JOB SECURITY?
28% of our respondents said they were “likely or very likely”
to leave their current company in the next two years, up from
27% when we last reported.
55% of all respondents answered they were “secure / very se-
cure” in their present job, flat with last survey’s results.
71% of respondents said they’d received a raise in the previous
year, down slightly from 73%, while 7% said they’d received a
pay cut, which was up from 6%. The average reported size of
a raise was roughly 6%, up from 4.5%.
5% of respondents were laid off in the past year, while 16%
had to lay off at least one staff member. Those numbers are
flat with last year’s results. 16% of respondents changed com-
panies last year.
GO ONLINE FOR MORE!
There’s plenty more of the
2015 Salary Survey online!
Find out about Raise Trends, Company
Cost-Cutting Measures, and more
including our latest responses to
the Wheel of Frustrations!
Find out more at
www.contractpharma.com
5%
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 54/132
54 Contract Pharma contractpharma.com June 2015
The biopharmaceutical contract manu-facturing industry continues to show
year-over-year growth as market condi-tions for outsourced services improve. Basedon HighTech Business Decisions’ latest re-
search, we expect the market for biophar-maceutical contract manufacturing servicesto reach $3 billion this year. The growth indemand for contract manufacturing servicesresults in part from new drug commercializa-tion, higher funding rates of biotechnologycompanies, and expanding service offeringsby biopharmaceutical contract manufacturingorganizations (CMOs). The CMO executivesinterviewed for this article are seeing greaterdemand and interest in outsourced services.Furthermore, these CMOs are either invest-ing in new plant and equipment or acquiring
capacity to meet future industry needs.
BACKGROUND
The information presented in this article drawsfrom recent interviews with six executives at biopharmaceuticalcontract manufacturing organizations, and from HighTech Busi-ness Decisions’ latest report, Biopharmaceutical Contract Manu-facturing 2015: Improving Markets, Services, and Technologies.This report is based on primary research from senior-level execu-tives and scientists at pharmaceutical and biotechnology compa-nies, and contract manufacturing organizations. For purposes ofour article, HighTech Business Decisions defines biopharmaceu-ticals as complex molecular structures created through the genetic
manipulation of living cells or organisms used for therapeutics,diagnostics, or vaccines. The biopharmaceutical contract manufac-turing market consists of services offered by contract manufactur-ing organizations producing biopharmaceutical drug substancesusing mammalian cell culture or microbial fermentation produc-tion technologies.
CURRENT DEMAND
All CMOs interviewed for this article are experiencing a higher lev-el of interest for their production services. The CMOs are receivingmore request-for-proposals (RFPs) this year compared to last year,
with one CMO respondent noting a year-over-year increase great-er than 10%. The CMO respondents noted several reasons for the
increase in the rate of request-for-proposals. One CMO respon-dent sees more RFP’s because of the industry trend to engage with
a good commercial partner in earlier project phases. This avoidsfuture technical transfer delays to a second/new commercial CMOpartner; thereby, improving the clients’ time to market. While otherCMO respondents note that they are getting more inquiries forpreclinical and process development projects, especially for mAb-related projects. Another reason for the increasing number of RFPs
was noted by another CMO who sees a trend towards their clientssending out RFPs for limited-scope projects instead of large inte-grated projects. Lastly, there also continues to be strong demand
for projects involving biosimilar development.
CAPACITY INVESTMENTS
With the increase demand for biopharmaceutical contract manu-facturing services, many CMOs are now adding or plan to addcapacity. Over the past several years, the industry has been cau-tious about adding new capacity, given the lower capacity utili-zation rates experienced earlier in this decade. From our study,HighTech Business Decisions expects the industry to increase itscapacity by 14% for mammalian cell culture production and 16%for microbial fermentation production over this year and next
year (Figure A). While much of the capacity increases have beenthrough internal capacity expansions, we are also seeing CMOs
adding to their capacity through acquisitions.For example, Patheon Biologics is adding capacity at two of
Biopharmaceutical Contract Manufacturing
Capacity ExpansionsBiopharma contract manufacturing market continues to expand, expected to grow 8%
over the next five years
William DowneyHighTech Business Decisions
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 55/132
Mark Your Calendar for the Meeting
that Extends Your Boundaries:
• Widen Your Personal Network with
Scientists from all Fields Related
to Pharmaceutical Scientists;
• Explore Programming Covering
Both Large and Small Pharma;
• Find the Latest Advances with
over 2,500 Contributed Papers;
• Find Your Supplier Solutions
in Orlando
aaps.org/annualmeeting
2015AAPS Annual Meeting
and ExpositionOctober 25–29, 2015
Orange County Convention Center
Orlando, Fla.
YOUR CALENDARS
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 56/132
BIOPHARMACEUTICAL CONTRACT MANUFACTURING CAPACITY EXPANSIONS
56 Contract Pharma contractpharma.com June 2015
its sites. “We have started expansions for enlarged USP and DSPcapacity around our 2000 L suite in St Louis. We have started ex-pansion by an extra USP suite for 1000 L and 2000 L in Groningenin the Netherlands,”said Marc Geomans, vice president, businessdevelopment, Patheon Biologics. Patheon Biologics, through itsparent DPx Holdings, B.V. acquired Gallus BioPharmaceuticalslast year. Previously, Gallus BioPharmaceuticals had acquiredLaureate BioPharmaceuticals in 2013, and acquired Johnson &
Johnson’s Centocor division in 2011. Also adding biopharmaceutical capacity in both Asia and
North America, AbbVie, Inc. is building new capacity in both Sin-
gapore and Puerto Rico. “AbbVie has announced two biologicscapacity expansion projects that are under construction in Sin-gapore and Puerto Rico. These expansions will help to serve both
AbbVie’s pipeline and CMO client needs,”said Michelle Calhoun,director-CMO sales and marketing for AbbVie. The investmentin Singapore establishes Abbvie’s first manufacturing presence in
Asia. The Singapore site will manufacture both small-molecule API and biopharmaceuticals. AbbVie’s estimated investment inSingapore is $320 million. Earlier this year, AbbVie announcedthat it will expand its Barceloneta, Puerto Rico site. AbbVie willspend $30 million for this expansion.
Another example of capacity expansion through both acqui-sition and new investment is KBI Biopharma, which continues
to expand its capacity and capabilities for mammalian and mi-crobial API production. “In our mammalian manufacturing areas, we are enhancing our single-use process technologies with anadditional manufacturing suite, including both 200 L and 2000L bioreactors, as well as kSep 400 single-use centrifuge systems.The kSep technology greatly improves harvest and clarificationoperations in single-use workflows as compared to depth fil-tration alone,” said Tim Kelly, vice president, biopharmaceuticaldevelopment, KBI Biopharma, Inc. Dr. Kelly also noted that KBIcontinues to make substantial investments in process develop-ment and laboratory automation technologies to enhance itsprocess and product development capabilities. KBI also addedmicrobial fermentation capacity through its acquisition of Merck
& Co. Inc.’s microbial process development and manufacturingoperations in Boulder, CO, last year. The Boulder facility is fully
on line, according to Dr. Kelly, who also said that thisfacility has extensive refolding capacity for E. coli inclu-sion body production processes and comprehensive
process development, analytical development, and pro-tein characterization capabilities. Earlier this year, JSRCorporation, along with CMIC Holdings Co. Ltd. andInnovation Network Corporation of Japan, acquiredKBI Biopharma.
On a smaller scale, Biotechpharma UAB recently in-stalled an additional 200 L single-use bioreactor in itsnon-GMP process development department. “Because
we have the same type of bioreactor also in our GMP-plant, we can horizontally transfer the process later toGMP, or directly up-scale to 1000 L in our GMP-plant,”said Andre Markmann, vice president, business devel-opment, Biotechpharma UAB. “We have expanded our
production area by adding a new building includingclean rooms and we will increase our microbial GMP-production capabilities, offering our clients increased
production volumes.” Dr. Markmann, also noted they have in-augurated a new stem cell-research facility to support customerrequirements.
Also adding capacity through both acquisitions and internalinvestment is Fujifilm Diosynth Biotechnologies. In December2014, Fujifilm Diosynth Biotechnologies acquired Kalon Bio-therapeutics based in Texas. “We are excited about the potentialopportunities in the area of viral vaccines and the facility in Texasprovided us with a great opportunity to quickly expand in the
vaccine area,”said Steve Bagshaw, chief executive officer, Fujifilm
Diosynth Biotechnologies. “We have very significant investmentsunderway there, which will be coming online in 2016 and soadding to our continually increasing capabilities for all the ma-
jor forms of biopharmaceuticals, API, process development, ana-lytical development and manufacturing, covering mammalian,microbial and viral.”Fujifilm Diosynth Biotechnologies recentlyadded 2000 L single-use bioreactors at both their North Carolina,U.S., and Billingham, UK sites. Fujifilm Diosynth Biotechnologyis also expanding its process and analytical development capabil-ity. This expansion includes a brand new state-of-the-art tech-nology center at its North Carolina site.
CONCLUSION
The biopharmaceutical contract manufacturing market contin-ues to expand, and it appears that this growth will continue overthe next few years. CMOs are seeing higher levels of request forproposals from their pharmaceutical and biotechnology clients.In response to this growth, we are seeing CMOs expand theircapacity through either internal capital programs or acquisitions.Over the next five years, HighTech Business Decisions expectsthe biopharmaceutical contract manufacturing market to grow ata compound annual rate of 8%. CP
WILLIAM DOWNEY is the president of HighTech Business Decisions, a mar-
ket research and consulting company that has been publishing reports on
the biopharmaceutical contract manufacturing market since 1997. For moreinformation, visit www.hightechdecisions.com or call (408) 978-1035.
FIGURE A: Worldwide Biopharmaceutical Contract Manufacturing Capacity
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 57/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 58/132
58 Contract Pharma contractpharma.com June 2015
W ith an estimated $67 billion worth of patents on bio-logical products expiring before 2020 and governmentspressured to reduce rapidly rising health care costs,1
biosimilars represent a major opportunity for the pharmaceu-tical industry. The growing interest in biosimilars is evident bythe approximately eightfold increase in the number of biosimilarclinical trials between 2007 and 2014 (Figure 1). Market growthof biosimilars is expected to increase significantly, worth approxi-mately $2 billion by 2018.2
A biosimilar is a biological product highly similar to an approvedbiological product, known as a reference product, with no clinicallymeaningful differences in terms of safety and effectiveness. In theU.S., if a biological compound demonstrates comparable data to a
U.S. Food and Drug Administration (FDA)-licensed product fromanalytical, preclinical and clinical studies, it will be accepted as a
biosimilar after expiration of innovator patents through an abbre- viated route. Interchangeable biological products are also biosimi-lars, but must meet additional criteria to match the reference prod-uct. Interchangeables can be substituted for the reference product
without a prescription from a health care provider.Over the past ten years, regulatory authorities worldwide have
been focusing on developing guidelines for biosimilars. However,until a global development strategy is adopted, regulatory, thera-peutic and legal challenges remain. While the prospect of costsavings and efficiency make the biosimilar market attractive, com-panies and their outsourcing partners planning to enter this mar-ket must be aware of current regulations and issues in the globalmarketplace and be prepared to respond quickly to changes. As
the regulatory landscape evolves, it is vital for clients to approachregulators early to validate their intended development plan.
Challenges in Global Biosimilar Development:
A Regulatory PerspectiveMore than $60 billion worth of patents on biological products are expiring before 2020, representing a major opportunity for the pharmaceutical industry.
Joan Boren, ManagerRegulatory Affairs, PPD
Costantino CongiatuPrincipal Specialist, Regulatory Affairs, PPD
Patricia Hurley Associate Director, Regulatory Affairs, PPD
Photo courtesy of PPD
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 59/132
BIOSIMILAR GUIDELINES
June 2015 Twitter : @ContractPharma Contract Pharma 59
This article addresses current regulations and challengesimpacting the development of biosimilars. Early awareness ofchanges and challenges will allow biosimilar developers to move
more quickly into key markets.
GLOBAL REGULATIONS:
WHERE DO WE STAND?
The FDA approval of the first U.S. biosimilar product—Zarxio (fil-grastim) from Sandoz—in March 2015 marked a major milestonein the biopharmaceutical industry. Still, the U.S. lags behind oth-er countries in biosimilar development, with the approval comingnearly a decade after the first biosimilar drug was approved inEurope, and five years after the Biologics Price Competition andInnovation Act (BPCI) of 2009 was passed and went into effect in2010, providing a legal framework for the 2012 FDA draft guide-lines. The guidelines propose steps for comparability and encour-
age early engagement with the agency. Data demonstrating bio-similarity to the reference product must be based on analytical,preclinical and clinical studies, including pharmacokinetic (PK),pharmacodynamic (PD) and immunogenicity assessments.3 TheFDA released final guidance documents on biosimilar productson April 28, 2015, that address comments from the industry andare intended to provide predictability and clarify the scientific andregulatory considerations for sponsors initiating biosimilar devel-opment programs. 4, 5, 6
The European Medicines Agency (EMA) was the first author-ity to issue guidelines for biosimilars, which came into effect in2005.7 The guidelines included requirements for quality, safetyand efficacy, and clearly defined the distinction between the de-
velopment of biosimilars and generics. These were followed byguidelines on nonclinical, clinical and quality issues as well asproduct-specific guidance, which were updated in 2013.8 The
World Health Organization (WHO) published its own guide-lines in 2009 and these, together with European and U.S. guide-lines, are being used as a reference in many countries, from Latin
America to Asia Pacific and the Middle East. As outlined in Table 1, several countries have issued guidelines
for biosimilars in line with EMA and WHO principles, requiringfull quality information on the biosimilar and side-by-side com-parative characterization with the reference product. Australiaand Malaysia adopted the EMA guidance. The biosimilar guide-line released in February 2015 by the Chinese Regulatory Author-
ity (CFDA) shares similar principles with EMA, FDA and WHO.9
However, key differences exist among countries with regard tothe choice of reference product and extrapolation of indicationsfrom the innovator.
The draft guideline of the Colombian agency proposes anabbreviated pathway for biosimilar evaluation as well as a com-parability pathway. However, there is criticism that developerschoosing the abbreviated pathway will not be in line with WHOguidelines and may put patients at risk. To date, Russia has notdeveloped specific biosimilar guidelines, but is gradually adopt-ing global standards.
In the U.S., the approval of the first biosimilar may trigger adeluge of many biosimilar drugs currently available in other parts
of the world. Apotex, Hospira and Celltrion have submitted ap-plications to the FDA for biosimilar products, and Novartis is
working on five other biosimilars. In Europe, 21 biosimilars havebeen approved by the EMA since 2006, with 19 still marketed,and have shown a significant reduction in cost compared to theirreference products. Biosimilar products have also been registeredin Australia, Canada, India, Japan and South Korea.
CLINICAL DEVELOPMENT
Clinical trials for biosimilars must demonstrate comparable safe-ty and efficacy to the reference product, including sequential PK/PD and efficacy/safety trials. Regulators anticipate PK/PD com-parability data from a Phase I trial will support further efficacy/safety assessments in pivotal Phase III trials. Stand-alone Phase
III studies or combined Phase I/III designs without supportingPK data are unlikely to be accepted. Clinical comparability re-quirements may vary on a case-by-case basis subject to a risk-based approach. Three-arm Phase I trials are increasingly beingused to demonstrate comparability between the biosimilar andtwo licensed versions of the same reference product that may ex-ist in different markets, allowing developers to proceed with piv-otal trials using a single version of the reference product.
Due to potential differences between the biosimilar and refer-ence product, immunogenicity profiling is the primary safety as-pect that must be assessed from the outset of the investigation. InEurope, if immunogenicity has proven not to be a serious risk, theEMA may accept six-month data on the day of filing, with addi-
tional six-month data to be submitted during the review period.10
India is an appealing market for developing biosimilar prod-ucts because of its large potential patient pool, but newly revisedlegislation has limited the number of clinical trials an Indian in-
vestigator can be involved with to three at any one time. In Bra-zil, the recently released clinical dossier of drug development(CDDD) will be similar to an IND filing process and help reduceapproval timelines of clinical trials. Similarly, implementation ofa new European clinical trials regulation in 2016 will affect the
way applications for interventional trials are managed in Europe.
REGULATORY CHALLENGES
As global regulations and guidelines progress, questions such as
the following are broadly being debated in the pharmaceuticalindustry:
FIGURE 1: Number of biosimilars clinical trials started between 2007 and 2014
Source: Citeline.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 60/132
BIOSIMILAR GUIDELINES
60 Contract Pharma contractpharma.com June 2015
• Should interchangeability and automatic substitution be al-lowed?
• Should biosimilars have the same international non-proprie-tary name as the reference product?
• How much longer will patent litigation hinder the U.S. market?
In countries without biosimilar guidelines, interaction withregulators can be challenging. It is advisable to approach agen-
cies proactively for scientic advice to avoid potential questions
and delays in clinical trial approval. In most cases, reviewers needto be guided through the FDA, EMA and PMDA (Japan) guide-lines. This is important in order to receive agency validation ofthe development program, discuss issues, identify gaps in thesubmission package, review the protein characterization stepsconducted, agree on the source of the reference product and fa-miliarize the assessors with the biosimilar product before submit-ting clinical trial applications.
Biosimilar developers and their outsourcing partners must beaware of the chosen country’s regulatory landscape, and have ex-tensive knowledge of any existing biosimilar approval pathwayand the latest regulatory agency guidelines. Providing regulatoryauthorities with certicates of analysis (CoA) for a U.S.-marketed
comparator could be challenging. Contrary to European practice,U.S. manufacturers tend not to make CoAs available to parties
involved in the supply chain or support the development of acompetitor by releasing CoAs for batches purchased for clinicaltrials. Providing pedigree statements for the reference product
usually is accepted as an alternative.Companies should evaluate the feasibility of routes to mar-
ket when considering key countries for clinical trials. Regulationsand laws favoring local businesses exist in emerging markets,and approval for clinical trials may not be conducive to successfulmarketing. Conditions favorable to local development also playa major role in China. In these countries, developers may benetfrom partnering with local companies.
The provisions made in the Brazilian Productive DevelopmentPartnership (PDP) legislation and by the Scientic and Techno-logical Research Council of Turkey (TUBITAK) regulate the tech-
nology transfer from foreign to local companies and the jointdevelopment between public institutions and private entities. In
return, participating developers benet from an expedited regu-latory process, access to restricted funding and exclusive access
to public tenders. Companies outside these agencies are lockedout of public tenders and conned to sell only to the retail marketin Brazil and Turkey. In Russia, innovative conversion and devel-opment of the local pharmaceutical industry is supported by thePharma 2020 strategy.
The number of clinical studies required to support marketingauthorization in Europe varies greatly depending on the prod-uct. Minimally, Phase I and Phase III studies must be includedin the marketing authorization application. When the referenceproduct is approved for multiple indications, claims for the sameindications must be justied based on safety and efcacy data. If
claimed indications were not part of the biosimilar clinical pro-gram, extrapolation may be accepted. In Europe, extrapolation
claims are possible as long as similar mechanisms of action andreceptors are common across indications, and studies involve themost sensitive population.
FUTURE REGULATORY LANDSCAPEDened regulatory pathways for biosimilars are slowly pavingthe way toward the goal of pharmaceutical industry stakehold-ers: automatic substitution at the pharmacy level. Legislators inthe U.S. and Japan have made provisions for interchangeability,but the FDA has not claried how this can be scientically dem-
onstrated, and Japan has discouraged automatic substitution. The
FDA has indicated that interchangeability will be granted in thepost-approval setting. The EMA guidelines have not addressedinterchangeability or substitution, which are left to member statesto determine. In Germany, automatic substitution is acceptableprovided the production of original and biosimilar products oc-curred at the same manufacturer site following the same process.
In France, substitution is allowed, provided the prescribingphysician has not marked the prescription as “non-substitutable,”substitution takes place when initiating a course of treatment (orto allow the continuation of a treatment started with that bio-
similar), and the biosimilar belongs to the same “similar biologicgroup” as the prescribed product as established by the Frenchregulatory authority (ANSM). ANSM criteria for inclusion in this
group, a detailed procedure for the registration by pharmacistsin the biosimilar register, and more precise conditions for substi-
TABLE 1: Countries with specific biosimilars guidelines, and year in which
guideline was published in each country
Year of publication Country with specific biosimilars guidelines
2005 European Union
2007 Australia
2008
Malaysia
Turkey
Taiwan
2009
Japan
Korea
Singapore
(World Health Organization)
2010
Brazil
Canada
Saudi ArabiaSouth Africa
2011
Argentina
Cuba
India
Iran
Mexico
Peru
2012
Colombia (draft)
Egypt (draft)
Jordan (draft)
Thailand (draft)
United States (draft)
2014 European Union (revised guidelines)
2015 China
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 61/132
BIOSIMILAR GUIDELINES
June 2015 Twitter : @ContractPharma Contract Pharma 61
tution are expected to be further defined once legislation is ap-proved by the French Supreme Court’s decree. When this is recti-fied later in the year, France is well placed to be the first member
state to open the door to biosimilar substitution despite the fierceattempt by the pharma industry to derail the change.11
LOOKING AHEAD
Currently there are more than 150 reference products for biosimi-lars to emulate, including about 40 with sales in the blockbuster(more than $1billion per year) revenue range. Even 10 percent ofthis market could be enough for biosimilars to be profitable. Withbiosimilars as marketing opportunities, it makes sense for com-panies to outsource their development if it can be demonstratedcost effective.12
In terms of regulatory progress, the number of agencies thathave adopted key principles from the U.S. and/or EU guidances
on biosimilars is steadily increasing. The common principles un-derpinning these provisions are effectively contributing to theglobal alignment on the development of biosimilars, with Latin
America becoming a key market for pharmaceutical and biotech-nology companies. However, until specific guidelines are estab-lished in other major markets, such as Russia, it will continueto be difficult for manufacturers to define a truly global devel-opment strategy. How biosimilars will ultimately be regulated,defined and marketed and how current issues will be resolvedremains to be seen. CP
References
1. GaBI online. June 29, 2012. http://gabionline.net/Biosimilars/General/US-
67-billion-worth-of-biosimilar-patents-expiring-before-2020 2. Markets and Markets report. Nov. 18, 2013. http://www.marketsandmar-
kets.com/PressReleases/global-biosimilars-product-market-worth-19.4-
billion-by-2014.asp
3. US FDA. Guidance for Industry, Clinical Pharmacology Data to Support
a Demonstration of Biosimilarity to a Reference Product, Draft Guidance,
FDA Center for Drug Evaluation and Research (CDER), Center for Biolog-
ics Evaluation and Research (CBER), May 2014.
4. US FDA. Scientific Considerations in Demonstrating Biosimilarity to a
Reference Product. http://www.fda.gov/downloads/drugs/guidancecompli-
anceregulatoryinformation/guidances/ucm291128.pdf
5. US FDA. Quality Considerations in Demonstrating Biosimilarity of a
Therapeutic Protein Product to a Reference Product. http://www.fda.gov/
downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidanc-es/UCM291134.pdf
6. US FDA. Biosimilars: Questions and Answers Regarding Implementation
of the Biologics Price Competition and Innovation Act of 2009. http://www.
fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM444661.pdf
7. EMA. Guideline on Similar Biological Medicinal Products, CHMP/437/04,
2005. www.ema.europa.eu
8. EMA. Guideline on Similar Biological Medicinal Products, CHMP/437/04
Rev 1, 2014. www.ema.europa.eu
9. CFDA. Technical Guideline for Development and Evaluation of Biosimi-
lars, CFDA, China, 28 February 2015.
10. Presentation by Andrea Laslop, Scientific Office, AGES, Austria, Biosimilar
Global Congress 2014 Europe, London, UK, September 17-19, 2014.11. Fierce Pharma. ( www.fiercepharma.com/story/big-pharma-tries-short-
circuit-frances-move-towards-biosimilar-substitution/2014-04-14 ).
12. Langer ES and Rader RA. Biosimilars Improving Efficiency, Cost for All
Biologics. BioPlan Associates. Accessible at: http://www.contractpharma.
com/issues/2015-04-01/view_columns/biosimilars-improving-efficiency-cost-for-all-biologics
PATRICIA HURLEY, PH.D., associate director, regulatory affairs,
joined PPD in 2011 as a manager in global regulatory development.
In her present role, she provides global strategic regulatory advice to
external and internal clients to determine the most appropriate strat-
egy for their projects.
JOAN BOREN, PH.D., manager, regulatory affairs, joined PPD in
2012. Since then, he has performed and coordinated global clinical
trial applications on a range of therapeutic indications for different
product types, providing global regulatory strategy and advice onstudy documents.
COSTANTINO CONGIATU, PH.D., principal specialist, regulatory
affairs, joined PPD in 2013 and supports clients with regional and
country regulatory expertise impacting strategic and operational ex-
ecution of clinical trials milestones. His contributions earned him the
TOPRA Regulatory Excellence Horizon Award in 2014.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 62/132
62 Contract Pharma contractpharma.com June 2015
B y 2020, the U.S. patent will expire on an estimated 12 pat-ented biologics worth approximately $67 billion. This createstremendous opportunity for drug companies developing
biosimilars as well as patients seeking more affordable biologicdrugs. With the introduction of the Patient Protection and Afford-
able Care Act, the U.S. federal government outlined an approvalpathway that will help ensure biosimilar products have the neces-sary level of efficacy and safety as reference biologic drugs.
Among its many provisions, the new health care law specificallyrequires clinical studies that include a comparative assessment ofpharmacokinetics (PK) and immunogenicity to the original refer-ence biologic drug. This comparison makes it possible to deter-mine structural differences that may not be detected via traditionalanalytical means.
Even with updated guidance on the biosimilar regulatory path- way, determining the structural and functional similarity between abiosimilar and its reference drug can be challenging. Unlike a smallmolecule whose structure can be precisely reproduced, a biosimi-
lar’s structure is unlikely to be identical to that of the reference drugdue to the inherently complex nature of proteins. These structuraldifferences arise primarily from the differences in manufacturingprocesses—different cloning systems, cell expression systems,post translation modification differences—used in the referencebiologic drug, where the processes are proprietary and not pub-licly shared. Therefore, characterizing the structural and functionaldifferences between the biosimilar and the reference drug are ofthe utmost importance, as such differences can affect the protein’ssafety or efficacy. However, current limitations in analytical tech-nologies inhibit the ability to definitively determine the structuralcomparability between the reference and biosimilar drugs.
To establish biosimilarity, FDA guidelines mandate that PK and
immunogenicity comparability between the reference biologic drugand the biosimilar be established. Client and industry focus has beenon the clinical studies to demonstrate this comparability. However,non-clinical studies can bring to light unanticipated structural dif-ferences and sometimes reveal information that guides future bio-similarity clinical trials. Our data support the recommendation ofconducting a non-clinical study that compares both PK and immu-nogenicity responses to comprehensively assess biosimilarity priorto initiating a costly and lengthy clinical study.
IMPORTANCE OF PK AND IMMUNOGENICITY ASSAYS
PK is sometimes described as what the body does to the drug. It isa measure of how the drug is absorbed, how long it remains in the
body and in what concentrations, where the drug goes in the body,and how the drug is removed from the body. Immunogenicity is the
ability of a biologic drug to induce an immune response in the body ofan animal or human. There are two kinds of immunogenicity: wantedimmunogenicity, in the case of vaccines and cancer immunotherapy,and unwanted immunogenicity against a therapeutic biologic, whichresults in anti-drug antibodies (ADA). The production of ADA canrender the biologic drug inactive, thus decreasing efficacy and PK,and in rare cases result in adverse events in the human or animal.
How should CROs properly develop pharmacokinetic and
immunogenicity assays to compare the reference product andthe biosimilar within clinical and non-clinical samples? Namely,should researchers use two separate, product-specific assays or asingle assay using one entity as reference?
The one-assay approach eliminates the concern of variabil-ity across data from the reference to the biosimilar as the samplesare not analyzed across two assays (Liu, et al. 2015). The alterna-tive—one assay for the reference drug and a separate assay for thebiosimilar—gives no such benefit. Added benefits of the one-assayapproach are the cost savings associated with method development,
validation and sample analysis that only require one assay formatinstead of two, plus streamlined sample analysis. We have outlinedpoints for consideration when developing an immunogenicity as-
say in Table 1. For full descriptions of the technical advantages anddisadvantages of the one or two assay approach for PK and ADA,
A Case for One Assay Analysis of
PK and Immunogenicity in Biosimilar ResearchMoving forward clinical studies will have to include a comparative assessment of pharmacokinetics and immunogenicity to the original reference biologic drug
Stephanie MowerySenior Scientist, AIT Bioscience
Sherri RinkerSenior Scientist, AIT Bioscience
Franklin SpriggsLigand Binding Assay Group Leader, AIT Bioscience
Bo Kowalcyk Vice President of Business Development, AIT Bioscience
FIGURE 1: Example of reference drug and biosimilar dose response relationship
from Case 1
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 63/132
BIOSIMILAR RESEARCH
June 2015 Twitter : @ContractPharma Contract Pharma 63
please refer to Marini et al. 2014 and/or Liu, et al. 2015, respectively.Below are two examples of how AIT Bioscience has used the
one-assay approach: first applied to a PK and immunogenicity
method for one biosimilar, and the second applied to a non-clin-ical immunogenicity method for a different drug program.
CASE 1: PK AND IMMUNOGENICITY IN A STANDALONE STUDY
AIT Bioscience used a one-assay approach to develop both the PKand an ADA assay for a biosimilar drug program in a standalonestudy. Lacking historical information about the reference drug’s as-say format as well as platform and reagents used in its development,
we selected an electrochemiluminescence base (ECL) format usingthe Meso Scale Discovery (MSD) platform for both the PK and ADAassay formats as this technique offers a large dynamic range.
We developed a sandwich ECL ELISA method to quantitatethe drug. We optimized this assay with the reference material be-
fore the biosimilar drug was available and held off on evaluatingthe specificity of critical reagents to the biosimilar until the end ofmethod development, thereby saving method development time.
Once the biosimilar was available, it demonstrated close agreement with the reference drug in their respective dose-response relationshipsin the ligand binding assay.Comparative statistics, as recommended byMarini et al. 2014 to establish bioanalytical similarity, were not appliedto determine how closely they agreed as the biosimilar PK assay wasnot developed to support regulated clinical or non-clinical bioanalyti-cal sample analysis; however, the biosimilar and reference drug curvesdemonstrate nearly overlapping dose responses (Figure 1).
A one-assay approach was also used to develop a bridging ECLELISA ADA assay format where the biosimilar drug was conjugated
with ruthenium or biotin to generate detection and capture criticalreagents, respectively (Figure 2). We evaluated a set number of drug-naïve individuals with either the reference drug or the biosimilaradded in excess. We determined the parametric 0.1% false positiveerror rate confirmation cut point for both the reference drug and the
biosimilar to be 71.4% and 67.5% , respectively. These results sug-gest the reference drug and the biosimilar drug have similar reactiv-ity. A potential disadvantage of using the two assay approach would
have been the time and cost to generate an independent surrogatecontrol antibody to the biosimilar, as the positive control antibodydescribed in the one assay approach had reactivity to both the refer-ence and biosimilar drug.
CASE 2: IMMUNOGENICITY IN A NON-CLINICAL STUDY
In the second example, AIT Bioscience again applied a one-assayapproach to a different drug program to support a non-clinicalanalysis for the presence of ADA. We again developed a bridgingECL ELISA on the MSD platform for this method. The biosimilarand the reference drug concurrently underwent non-clinical analy-sis for ADA responses while utilizing an anti-reference antibody togenerate the positive controls. Upon evaluation of the drug, naïve
animals in both the presence and absence of the reference materialand the biosimilar material, a parametric 0.1% false positive errorrate confirmation cut point was determined for both the referencedrug and the biosimilar to be 25.5% and 35.2%, respectively.
Upon analysis of 30 animal samples (10 control animals, 10 ani-mals dosed with the biosimilar drug and 10 animals dosed with thereference drug), one animal in the biosimilar group had a responseabove the tier 1 screening cut point with a 5.0% false positive errorrate. We initiated confirmation testing and evaluated this sample twice
within the same assay: 1.) In the presence of excess biosimilar drugand 2.) In the presence of excess reference drug on the same plate.The putative positive sample continued to elicit ADA responses abovethe biosimilar and the reference drug’s confirmation cut points with a
0.1% false positive error rate. Therefore the ADA present in this ani-mal, which received the biosimilar, were reactive to both the biosimilarand reference drug suggesting structural similarity.
DISCUSSION
When differences in immunogenicity results arise, structural dif-ferences may be gleaned from animal studies. AIT Bioscience typi-cally recommends this step since differences in immunogenicityresults might indicate structural or functional differences betweenthe two products otherwise undetectable by other analytical meth-ods (April 2015 FDA Guidance). Therefore, conducting an ADAassessment in a non-clinical study of a biosimilar can indicate earlyon potential differences between the biosimilar and the reference
drug, which may result in reduced safety or efficacy. In the caseof the second example presented above, the animal dosed withthe biosimilar had an ADA response to both the biosimilar andthe reference drug. This result supports a structural and functionalsimilarity between the biosimilar and reference drugs.
Minor structural differences, including certain post-translationmodifications, can dramatically affect a biotherapeutics’ efficacyor safety. Therefore, a clear difference in preclinical immunoge-nicity could be a sensitive indicator of an unanticipated structuraldifference. Thus, rather than a ‘check-box’ activity, animal studieshave the potential to reveal vital information about the biosimi-larity of a biotherapeutic and guide future clinical studies. CP
For references and a table showing consideration points for one vs. two-assay approach forimmunogenicity assessment, visit the online version of this story at www.contractpharma.com.
FIGURE 2: Example of a bridging ECL ELISA format
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 64/132
64 Contract Pharma contractpharma.com June 2015
A lthough the concept of single use is not
new, and has become standard practice forproducts such as filter capsules and storage
bags, today’s single-use processes are much morecomplex than conventional production strategiesand comprise an integrated model—particularly innew facilities—that often involve the replacement ofstainless steel equipment.
Single-use technology is already understood toreduce the danger of cross-contamination, decreaseinvestment risk, offer high levels of flexibility andprovide cost-effective drug development optionsfor investigational products. Considering that, forexample, single-use bioreactors didn’t exist 20 years
ago, the technology has gone from evolution to rev-olution in less than two decades.
More recently, as a result of optimized strains andimproved culture media in the field of monoclonalantibody (mAb) production, the productivity of fed-batch mammalian cell culture systems has increasedsignificantly. Biomass concentrations have increasedfrom 1–3 g/L to 7–10 g/L, which facilitates the use ofsmaller-scale production vessels and, at the same time,also poses a downstream challenge.1,2 Higher, moreconcentrated yields are difficult to process with depthfilters. For volumes greater than 500 L, the use of cen-trifuges has become essential to reduce both produc-
tion costs and waste. However, the introduction of aready-to-use clarification system that enables single-use processing at volumes of up to 2,000 L may pro-
vide a commercially viable solution that replaces bothcentrifuges and depth filters in a single step.
HARVESTING TECHNOLOGIES
High product titers derived from increased cell den-sities, as opposed to increased specific productivitiesper cell, result in a considerable solid mass that chal-lenges commonly used harvesting techniques. Cur-rently the most widely applied single use harvestingtechnology is depth filtration. However, depth filters
tend to block at lower loading capacities with higherbiomass concentrations.
Single-Use Clarification System
for High-Density Cell CulturesContinuous improvements in growth media and cell line viability have resulted in
increased biomass concentrations in biopharmaceutical production processes, makingthe downstream purification step more challenging. Body feed filtration has proven to be
a successful method of solving similar issues in other industries. This robust technology is now available as a harvesting solution for biotechnology applications.
Tjebbe van der MeerProduct Manager Purification Technologies, Sartorius Stedim Biotech
Photo courtesy of Sartorius
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 65/132
BODY FEED FILTRATION IN BIOTECH APPLICATIONS
June 2015 Twitter : @ContractPharma Contract Pharma 65
Higher contaminant concentrationsalso make depth filters more sensitiveto batch variation, which can lead to an
oversizing of the filter area (up to 50%) tocompensate for fluctuating filtration ca-pacities. Single-use cell removal solutionssuch as centrifugation are available, but as
yet lack capacity, which drives up costs andincreases waste.
A solution is, however, available. Sar-toclear Dynamics from Sartorius StedimBiotech is a new single use technology forharvesting animal cell cultures with highcell densities. Offering consistent results,ease of use, speed and flexible scalability,this ready-to-use clarification system—in-
spired by the blood plasma fractionationindustry—is based on the principles of bodyfeed filtration (BFF). Able to process capaci-ties of up 2,000 L, it can replace both centri-fuges and depth filters in a single step. Thekey factor is the addition of a highly porousfilter-aid to the feed stream, which increasesthe permeability of the filter cake and pre-
vents the filter from becoming blocked.
BODY FEED FILTRATION
Body feed filtration uses filter-aids such as diatomaceous earth(DE) to increase filter capacities, which has a long history of use.3
DE, diatomite or kieselgur/kieselguhr, is a naturally occurring,soft, siliceous sedimentary rock with a typical particle size 10–200µm. Composed of the shells or exoskeletons of fossilized diatoms(microscopic, single-cell algae) and benefiting from a very porousstructure and inert character, DE is often used in the biotechnol-ogy industry in depth filters during the harvesting stage. DE isadded to the cell culture broth where it plays a dual role: it sievesout sub-micron particles and creates a permeable filter cake thatimproves filter throughput. The minute filter-aid particles providecountless microscopic channels that entrap suspended impuritiesbut allow clear liquid to pass through without clogging.
HOW BFF WORKS
A number of products are now manufactured using BFF-basedsystems, including intravenous immunoglobulin (IVIG), albumin
and certain clotting factors, that are based on the principles ofselective pH-induced precipitation, ionic strength, the addition ofalcohol and temperature shifts.4–6 The precipitates are removedby DE-enhanced depth filtration.
In practice, when the solid concentration becomes too highin biological process fluids that need clarification, the filter cakeon the surface of a filter becomes impermeable (Figure 1). Add-ing a filter-aid, such as DE, creates a more permeable filter cake,
which prevents blockage. The amount of DE required dependson the particle concentration. To achieve ideal results and to useas little DE as possible, pre-conditioning the cell culture fluid is
recommended. Flocculants can be added orthe pH can be lowered, which will create ag-
gregates that are too big to migrate into thefilter cake. As such, the cake stays permeableand the DE: biomass ratio can be reduced toabout 1:4.
And, although a wide range of DE grades, which differ in purity and permeability, areavailable for different applications, SartoriusStedim Biotech selected Celpure C300 as thebest filtration aid for mammalian cell cultureprocedures. Designed specifically for phar-maceutical applications and produced usinga patented manufacturing process, CelpureC300 is a highly purified form of DE that of-
fers improved operational consistency. For a variety of tested cultures, media and viabili-
FIGURE 1: Dynamic body feed filtration (BFF) with diatomaceous earth (left) and conventional filtration (right).
Sartoclear Dynamics from Sartorius Stedim Biotech is a new single use technology for harvesting animal cell
cultures with high cell densities was inspired by the blood plasma fractionation industry and is based on theprinciples of body feed filtration (BFF). (Photo courtesy of Sartorius)
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 66/132
BODY FEED FILTRATION IN BIOTECH APPLICATIONS
66 Contract Pharma contractpharma.com June 2015
ties, the optimum DE concentration was found to be 40–50% of
the wet cell weight (WCW), which could be reduced to 20–30% ifthe pH was lowered to 5.
BENEFITS OF LOW-PH PRECIPITATION
Performance differences in cell removal technologies such asmicrofiltration and depth filtration can be attributed to the pre-cipitation of smaller particles at low pH levels (pH 4.3–5.5).4,5 Celldebris, DNA and host-cell proteins all become less soluble inacidic conditions.6 Plus, lowering the pH leads to the formationof larger particles and makes the submicron particles present atpH 7.0 completely disappear (Figure 2). Similarly, BFF also ben-efits from lower pH conditions: tested cell culture supernatants inacidic conditions showed much clearer filtrates than their neutral
counterparts (data not shown).It is thought that large particles (>0.4 μm) become entrapped
in the DE, lowering its overall permeability and filtration capacity.By increasing the DE concentration, it is possible to improve itscapacity to retain small particles without losing the required cakepermeability. And, although most antibodies are stable at acidicconditions, some are likely to co-precipitate.5,6 In laboratory scaleBFF tests at low pH values, recovery rates of greater than 85%
were achieved (data not shown).
PRACTICAL APPLICATION
As BFF has become more frequently usedas a substitute cell culture harvesting so-
lution, Sartorius Stedim Biotech, together with Rentschler Biotechnologie GmbH,attempted to evaluate the technology as apotential single-use alternative to centri-fuges and depth filters.7 Optimized con-ditions in a 600 L cell culture productionprocess were tested to assess the scalabilityof BFF technology. Using Sartoclear Dy-namics products, which are designed to beused for the clarification of mammalian cellcultures in pharmaceutical production pro-cesses, the results obtained from a number
of cell lines and culture media are described.
Pilot-scale production tests were done using a high cell den-sity Chinese hamster ovary (CHO) cell fed-batch culture (17.6 x106 cells/mL, 95% viability, 1000 L).8 The largest BFF test involved600 L at pH 5.0 (WCW = 8%). During the scale-up experiment,seven process-scale modules with a total filtration area of 1.61m2 in a universal stainless steel holder were used.
Comprising two polyethylene filter plates, the filter cassettesretain the DE and biomass. Cellpure C300 DE (12 kg) was addedto the 600 L bulk harvest and pre-filled DE bags were connected
with a dust-free adapter to a mixing bag for fast and safe DEtransfer. After 5 minutes of gentle mixing, the DE powder haddissolved in the cell suspension; and, prior to filtration, the pHof the resulting mixture was adjusted to 5.0 and mixed for 2 h at
140 rpm.Figure 3 shows the pressure increase during the process. Filtra-
tion was terminated when a pressure value of 1.3 bar was reachedand the crude harvest had been filtered. A high and stable fluxof approximately 300 L/m2/h was maintained throughout and,overall, a capacity of 311 L/m2 was achieved. Low turbidity levels(5–8 NTU) were recorded in the clarified harvest stream duringfiltration. Following neutralization, the final pool exhibited a tur-bidity of 41 NTU, which was considerably higher, possibly due toinadequate dosing of the neutralization buffer.
FIGURE 2: Mean particle-size distribution of cell-free Chinese hamster ovary (CHO) culture supernatants
from three different harvests: green = pH 7.0, red = pH 5.0. Data recorded with a Mastersizer 2000
(Malvern Instruments).
FIGURE 3: Results of DE body-feed scale-up experiment at reduced pH (5.0) with seven filter modules. Left: filtration performance, pressure (bar), flux (L/m2) and
turbidity during filtration. Right: recovery of IgG1, measured at crude harvest and harvest pool without buffer flush (pool 1), with buffer flush (pool 2), and after
neutralization of harvest fluid (pool 3).
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 67/132
BODY FEED FILTRATION IN BIOTECH APPLICATIONS
June 2015 Twitter : @ContractPharma Contract Pharma 67
In a small-scale parallel test, improving the neutralizationstep prevented the turbidity build up: an integrated ready-to-useprocess skid is under development that will enable controlled
inline pH adjustment. For example, IgG1 recovery was recordedat 85% (Figure 3) and, in the future, an optimised neutralizationprocedure and enhanced post-filtration flushing should furtherimprove mAb recovery. Contaminants such as a host-cell pro-tein and DNA were monitored throughout the process and, inthe final pool (after buffer flush and neutralization), those levels
were reduced from 841 to 629 mg/mL and 13.8 to 5.0 μg/mL,respectively.
RESULTS
Pilot-scale BFF experiments confirmed previously observed labo-ratory based findings: reducing the pH to 5.0 after adding DEto the crude cell-culture supernatant gives the best results in
terms of filtration capacity, flux and contaminant removal. In ad-dition, using only seven filtration modules, a 600 L harvest wasprocessed in 1 h. As a module holder can accommodate up to 33modules, it is estimated that a harvest volume of 3,000 L couldbe filtered in the same time. As such, this method facilitates theeffective clarification of crude, high-density cell culture harvestsin a single-use large-scale setup.
CONCLUSION
Wishing to demonstrate the universal application of a novel sin-gle-use harvest method for high density mammalian cell cultures,tests using crude harvests from different cell lines and cultureconditions enabled the optimal DE concentration as a filter-aid
to be determined. In addition, at low-pH levels, a 50% reductionin the amount of filter-aid required was identified.
A robust and reliable single-use clarification system that elim-inates the use centrifuges and provides consistent results, easeof application, speed and linear scalability, when combined withprecipitation, effectively converts the cell harvesting step from atwo-stage process into a single-stage operation, saving both timeand money.
Scalable technology such as BFF will close one of the biggestgaps in the single-use product market. With 2000 L now estab-lished as the standard size for single-use bioreactors, the elimina-tion of centrifugation to remove cells from such volumes is a hugestep forward for the biopharmaceutical industry, enabling a fully
single-use process, which brings enormous flexibility and signifi-cantly reduces capital investment. Specially designed for cGMPprocessing, Sartoclear Dynamics consists of prefilled single-usebags containing ultrapure diatomaceous earth in a choice of 0.5–10 kg. With a new quick-connect adapter for dust-free powdertransfer, DE can be directly mixed into the cell culture fluid. Thisporous filter aid prevents filter blockage and, as the system main-tains a constant ratio of biomass and filter-aid, users will benefitfrom continuous and optimized filter performance. Able to clarifyeven very dense crude cell harvests at high flow rates, BFF makeseconomic and productivity sense. CP
References
1. B. Kelley, “Industrialization of MAb Production Technology: The Biopro-cessing Industry at a Crossroads,” MAbs 1(5), 443–452 (2009).
2. M. Buttler, “Animal Cell Cultures: Recent Achievements and Perspectives in
the Production of Biopharmaceuticals,” Appl. Microbiol. Biotechnol. 68(3),
283–291 (2005).
3. E.J. Cohn, et al., “Preparation and Properties of Serum and Plasmaproteins, IV: A System for Separation into Fractions of the Protein and Lipopro-
tein Components of Biological Tissue and Fluids,” J. Am. Chem. Soc. 68,
459–475 (1946).
4. J. Curling, et al., Production of Plasma Proteins for Therapeutic Use (Wi-
ley-Blackwell, Hoboken, New Jersey, USA, 2012).
5. J. More, et al., “Purification of Albumin from Plasma,” in J. Harris (Ed.),
Blood Separation and Plasma Fractionation (Wiley-Liss, Hoboken, New
Jersey, USA, 1991).
6. M. Stucki, et al., “Investigations of Prion and Virus Safety of a New Liquid
IVIG Product,” Biologicals 36, 239–247 (2008).
7. M. Westoby, et al., “Effects of Solution Environment on Mammalian Cell
Fermentation Broth Properties,” Biotechnol. Bioeng. 108(1), 50–58 (2011).
8. M. Trexler-Schmidt, et al., “Identification and Prevention of Antibody Di-sulfide Bond Reduction During Cell Culture Manufacturing,” Biotechnol.
Bioeng. 106(3), 452–461 (2010).
TJEBBE VAN DER MEER is product manager of purification tech-
nologies at Sartorius Stedim Biotech.
Trustcan’t bemeasuredin mL.
While working with the world’s leadingpharma companies we’ve learned manyimportant lessons. The most important?Science alone isn’t enough.No formula can capture this essentialtruth: when you choose a partner youare trusting them with your brand.
Choose wisely.
Diana RitchManager of New Customer Business704.939.4329
www.eisolutionworks.com
TOPICAL SEMI-SOLIDS & LIQUIDS
Formulation, Development and Manufacturing
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 68/132
68 Contract Pharma contractpharma.com June 2015
Like all market segments, contract packaging for pharmaceu-ticals has had its peaks and valleys over time. For that rea-son, it is important to continually visit the space and evalu-
ate the external factors influencing growth or contraction of thismarket segment. The Healthcare Compliance Packaging Council(HCPC) contacted a few of its contract packaging members to pro-
vide an overview of the growth opportunities and trends.The U.S. market for pharma contract packaging is currently in
a growth cycle that is estimated to be increasing at 5-8% a year,according to Daryl Madeira, vice president, sales and marketing,QPSI, a global packaging solutions provider that provides con-tract packaging, design, distribution, warehousing and logisticsmanagement. This is consistent with figures quoted by the Con-tract Packaging Association on their web page: “Pharmaceuticaloutsourcing is experiencing a 9.1% global growth rate to reach$374.8 billion by 2018, according to BCC Research in a recentreport.”Pharmaceutical outsourcing trends are generally a goodindicator of outsourced packaging trends.
This current growth in pharmaceutical contract packaging would seem to be a result of the changes and challenges fac-ing pharmaceutical manufacturers today. In the last few years
the landscape for pharma manufacturers has been changing ina significant way. Whether you consider legislative impact from
regulations such as the Drug Quality and Security Act signed byPresident Obama in November 2013, or increasing pressures beingapplied by healthcare in response to implementation of the Afford-able Care Act, or even the long standing trend of brand-to-genericconversions, they all mean the same thing: the pharmaceuticalmanufacturers are seeing increasing pressure to streamline andperform at higher levels. This has come to mean focus on your corebusiness and divest the rest. This attitude has led to a resurgence
in merger and acquisition activity not seen since before the 2008crash. One of those non-core activities being divested from manyof these operations is packaging. Packaging has long been an after-thought of the pharmaceutical process, a cost to be managed notan asset to be cultivated, which is somewhat unfortunate given theimportant role it plays in the supply chain. The disconnect betweenproduct development, marketing and packaging in pharmaceuti-cals has been a focal point for HCPC in its effort to spur the growthof compliance packaging in healthcare.
So how are these changing conditions influencing pharmamanufacturers and their dependence on contract packaging andhow will they affect tomorrow?
THE PATENT CLIFF
One often discussed event or series of events is the “patent cliff”
Walt BerghahnExecutive Director, Healthcare Compliance Packaging Council
Growth Prospects for
PHARMACEUTICAL CONTRACT PACKAGING Spurred by several trends including the patent cliff, new product launches and changes in
healthcare, the contract packaging market is looking at sustained growth in the years ahead
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 69/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 70/132
CONTRACT PACKAGING TRENDS
70 Contract Pharma contractpharma.com June 2015
that has been written about for years. Ba-sically, from 2011 to 2020 almost 50 wellknown, highly prescribed branded drugs
will go off patent with many already passedtheir expiration date (see Table 1). In the
world of contract packaging this createsseveral opportunities. Some of these drugs
will become Rx to OTC switch candidates while others will have a slew of generic drugcompanies straining at the gate, ready tolaunch when the flag officially drops.
In the former case, the package formats re-quired for these OTC switch products are dra-matically different from the branded productdestined for the backroom of the pharmacy.
After all, this package now has to survive on
its own and tempt a consumer to reach for it. Also, this OTC version is more than likely lessprofitable than its branded predecessor so theprospect of buying new packaging equipmentand allocating space to this new less profit-able entity is not appetizing to the manufac-turer. Contract packaging becomes a welcomehome for many of these products. In the caseof generics launching on the heels of thesepatent expirations several things come intoplay. Many of the generic companies operateon tight capital budgets. Drug manufacturingmay be on their list of activities, but packaging
very often is not. Joe Luke, vice president of sales and mar-keting at Reed-Lane, a privately held New
Jersey firm specializing in pharmaceuticalcontract packaging for leading Rx, OTC andgeneric drug manufacturers, said, “Many ofthe generic companies don’t have the ca-pacity or expertise with certain packaging tohandle this increase and turn to contractors.”
Once again, contract packagers becomethe provider of choice. But simply getting thegeneric version to market in a timely fash-ion is not enough to guarantee success. Jus-
tin Schroeder, executive director, marketing,business development and design for PCI,a global leader for drug development andcommercialization of drug products, said,“The WalMart $4 generic program is a greatexample of generic firms looking to capital-ize on some method of differentiation, andpatients are benefitting from that energythrough the use of calendarized medicinesand compliance prompting packaging.”
PRODUCT LAUNCHESOn the opposite end of the spectrum from
the patent cliff are new product launches.These often end up in contract packag-
TABLE 1: Selected Top Brand-Name Drugs with Patient Expirations From 2011-2020
Brand Generic Name ManufacturerExpected
Availability
Aciphex Rabeprazole Eisai 2013
Actos Pioglitazone Takeda 2012
Actoplus Met Pioglitazone/metformin Takeda 2012
AndroGel 1% Testosterone Solvay 2016
Atripla Efavirenz/emtricitabine/tenofovir disoproxil Gilead Uncertain
Avapro Irbesartan Brisstol-Myers Squibb Generic available
Avodart Dutasteride GlaxoSmithKline 2015
Benicar Olmesartan Daiichi Sankyo 2016
Benicar HCT Olmesartan/hyrdochlorothiazide Daiichi Sankyo 2017
Boniva Ibandronate Roche Generic available
Caduet Amlodipine/atorvastatin Pfizer Generic available
Celebrex Celecoxib Pfizer 2014
Combivir Lamivudine/zidovudine GlaxoSmithKline Generic available
Crestor Rosuvastatin AstraZeneca 2016
Cymbalta Duloxetine Lilly 2013
Detrol Tolterodine Pfizer 2012
Diovan Valsartan Novartis 2012
Diovan HCT Valsartan/hydrochlorothiazide Novartis 2012
Evista Raloxifene Lilly 2014
Focalin XR Dexmethylphenidate ER Novartis 2012
Geodon Ziprasidone Pfizer Generic available
Gleevec Imatinib Novartis 2015
Levaquin Levofloxacin Orhto-McNeil-Janssen Generic available
Lexapro Escitalopram Forest Generic available
Lipitor Atorvastatin Pfizer Generic available
Loestrin 24 Fe Ethinyl estradiol/norethindrone acetate/ferrous fumerate Warner Chilcott 2014
Lovaza Omega-3-acid esters GlaxoSmithKline 2015
Lunesta Eszopiclone Sepracor 2012
Lyrica Pregabalin Pfizer 2013
Namenda Memantine Forest 2015
Nexium Esomeprazole AstraZeneca 2014
Niaspan Niacin ER Abbott 2013
Opana ER Oxymorphone ER Endo 2013
OxyContin Oxycodone ER Purdue Pharma 2013
Plavix Clopidogrel Sanofi-Aventis 2012Protonix Pantoprazole Pfizer Generic available
Reyataz Atazanavir Brisstol-Myers Squibb 2017
Sensipar Cinacalcet Amgen 2016
Seroquel Quetiapine AstraZeneca Generic available
Seroquel XR Quetiapine ER AstraZeneca 2017
Singulair Montelukast Merck 2012
Strattera Atomoxetine Lilly 2017
Tricor Fenofibrate Abbott 2012
Viagra Sildenafil Pfizer 2020
Vytorin Ezetimibe/simvastatin Merck 2014
Zetia Ezetimibe Merck 2016
Zyprexa Olanzapine Lilly Generic available
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 71/132
CONTRACT PACKAGING TRENDS
June 2015 Twitter : @ContractPharma Contract Pharma 71
ing space for several reasons. The timing of FDA drug approv-als is unpredictable. Contract packagers by their nature are flex-ible enough to stage product and packaging in anticipation of
launches. They can very often utilize existing packaging linesand be ready to flip the switch upon notice from manufactur-ers or as is often the case pre-produce packaging in anticipationof approval. A more risky prospect but one entertained by manypharma manufacturers. Delays in approval still have an impacton capacity and manpower but if you are the manufacturer theseimpacts are outside your four walls.
Contract packagers are launching products on a fairly regu-lar basis, depending upon the packager. This means they becometuned in to the process and it is a complicated process. Theyhave the ability to train staff in these processes and streamlinethe activities increasing efficiency and reducing launch time. Amanufacturer does not launch products with the frequency of the
average contract packager. Their staff may see a launch once a year or even less frequently. They don’t have the opportunity todevelop a level of comfort with the process that contract packag-ers cultivate over time.
Changes in healthcare due to the Affordable Care ActThe implementation of the Affordable Care Act has put pres-
sure on the healthcare community to improve performance andoutcomes, which includes improving the performance of patients
with pharmaceuticals. Not surprisingly some of that pressure has worked back up the supply chain and pharma manufacturers arebeginning to cooperate with care providers, creating tools to sup-port their products, which in some cases mean special packaging.The industry has seen an increase in utilization of compliance
prompting packaging in support of improving health outcomes.This trend is likely to continue as providers see sustained pres-sure on improving patient performance with drug regimen.
UNIQUE PACKAGING SOLUTIONSThe ACA is by no means the only reason for increasing complexityin packaging. As drug therapies become more complicated so doesthe packaging and accompanying literature required to engage thepatient and caregiver. Physician samples, starter kits and titrationpacks require non-standard packaging processes and are often ac-complished in contract facilities. In many cases the processes in-
volve manual assembly, which requires a flexible workforce.“These solutions tend now to be about providing a sample for the
physician to demonstrate a complicated dosing regimen vs. a samplefor the patient to simply try the drug product,”said Mr. Madeira of
QPSI.“As a result, we will probably see unit-of-use packaging have agreater share in physician sampling.”This type of customization andnon-standardized packaging is difficult to accomplish in the brand
manufacturing environment but is well suited to the contract world where each packaging suite is its own world.
Unique packaging solutions include a move toward morehome based self-administration of injectable therapies. Thismeans fewer vials and more prefilled syringes. In order to servicepatients in the home these syringes are provided in kits with de-tailed instructions.
“For injectable products we are seeing a transition from vialsadministered in clinic to a focus on patient convenience wherebydosing can be done at home,” said PCI’s Mr. Schroeder. “This isleading to a transition to supply prefilled syringes and specializedinjectable devices.”
Again, this unique format fits the contract environment more
so than the manufacturer especially considering that many ofthese unique therapies service small populations and the pros-pect of automating packaging of these kits is impractical.
The Drug Quality and Security Act (DQSA) is a well-recog-nized four-letter word—or more appropriately acronym—thathas prompted much searching for the right contract packagingpartner. Signed in late 2013 by President Obama, DQSA has aninteresting pedigree dating back to the 1987 Prescription DrugMarketing Act, followed a decade and a half later by the 2005Florida Pedigree legislation which set the stage for California’s SB1307 and ultimately pushed Congress to action. It’s been morethan 18 months since it was signed and there may be some outthere—not many—who still don’t believe it will be fully enacted
on the timeline laid out.Maybe so but for manufacturers there is a very clear deadline
looming that has many scrambling to launch internal solutionsand others looking to the contract packaging providers to holdthe bag while they figure out what they want to do in their ownhouse. Most of the contractors I’ve spoken with believed the writ-ing on the wall and they are ready to help their pharma manu-facturer partners.
“Not every manufacturer will have all lines ready. I think there will be a collision of sorts when January 2017 comes,”said Joe Lukeof Reed-Lane.“We do believe there will be opportunities for contractpackagers who are compliant to service customers who can’t get alltheir packaging lines and infrastructure ready.”It is still a daunting
task and time will tell how the initial deadlines will be met.So, these are some of the reasons that we are seeing a sustaineduptick in the contract packaging market in the U.S. The AffordableCare Act, the growth in generics and DQSA are here to stay, andI believe the growth in contract packaging will continue to be af-fected by these items for the foreseeable future. CP
WALT BERGHAHN is executive director of the Healthcare Com-
pliance Packaging Council (HCPC). The HCPC is a not-for-profit
trade association whose mission is to promote the greater use of
compliance prompting packaging to improve patient adherence
and patient outcomes. The HCPC is celebrating its 25th anniver-
sary of improving patient adherence and safety. For more infor-mation on HCPC, please visit our website, www.hcpconline.org.
Walmart announced plans to
incorporate HCPC member Keystone Folding Box Co.’s
Ecoslide-RX 2.0 compliance package into its pharmacies nationwide beginning in 2015.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 72/132
72 Contract Pharma contractpharma.com June 2015
N E W S M A K E R S : P C I
Contract Pharma: How has business beenwith the new site up and running? Bob Misher, senior vice president, PCIClinical Trial Services: We have been
very pleased by the response from our cli-ent base. Having the additional capacityas well as the dedicated returns manage-ment space and personnel has allowed usto keep pace with demand for supporting
international studies, as well as strategyplanning to support future needs for ourclients and their evolving logistical sup-ply strategy needs. We are working withclients to relook at how investigationalstudy medicines are supplied to sites andpatients. There are opportunities to makestudies more effective, including opti-mizing timing, cost and certainly patientbenefit. In addition, we have already beenasked to expand our current capabilitiesinto other cold chain areas such as -40°Cand cryogenic storage at -196°C.
CP: What was the motivating factor(s) be-hind the expansion? Misher: The expansion allowed PCI tohave a dedicated logistical hub for North
America. We had been operating a jointclinical packaging/labeling facility coupled
with storage and distribution functions,but had reached a point where we neededdedicated space for the clinical logisticsoperations. Both the current growth ofour business as well as the anticipated fu-ture growth warranted a strategy whereby
we could devote a dedicated facility anddedicated personnel, with ample capac-
ity to further grow and expand in a flex-ible workspace. Adding 93,000 square feet,complete with extensive yet expandablecold chain support and specialized DEAspace, along with dedicated space for re-turns management, positions us to serveour clients both now and in the future. Thesite is extremely well thought out and pro-
vides a great foundation for meeting the
ever-changing needs of clients.
CP: Talk about some of the broader trends im-pacting the direction of PCI’s business? Brian Keesee, executive director, PCINorth American Clinical Services: Asgrowth in biotech medicines and other de-manding products increases, so too doesthe demand for infrastructure to supportthe logistical requirements of these special-ized and high value therapies around the
world. Often these products warrant coldchain storage and handling, which require
logistical support at 2-8° Celsius (35°F –47°F), -20° Celsius (-4°F), or -80° Celsius(-112°F). Distribution of these medicinesdemand a host of specialized shipping con-tainers and temperature monitoring devic-es as they are destined for investigationalstudy sites around the globe.
The growth of specialized medicinesand narrow therapeutic indications alsodictates expensive active pharmaceuticalingredients and high value drug products.This trend, coupled with growth in painmanagement products often governed
by the U.S. DEA or UK Home Office, hasPCI significantly expanding its storage
capabilities for products requiring highlysecuritized facilities. This includes on-sitestorage of DEA Schedule II and III-V drugproducts in vaults and specialized cages.PCI also operates dedicated stand-alonepotent compound sites in the U.S. andUK for both packaging and distribution ofSafeBridge rated compounds, often oncol-ogy therapies and treatments for autoim-
mune diseases.I’ve spent over 15 years in the pharma-
ceutical industry supporting clinical servicesand pharmaceutical supply chain logistics.The scale of PCI’s new facility, particularlythe cold chain and DEA storage, is impres-sive. It really enables a responsive approachto reducing lead times for investigationalmedicines, being able to package and ex-pedite shipping clinical trial materials toinvestigational sites that are increasingly in
very distant places. We are currently mak-ing hundreds of shipments per day. The site
allows for very efficient logistics as we scaleup with a focus on maintaining high servicelevels for our clients.
CP: What are PCI’s plans for future growth? Dave Lecher, director, global logistics,PCI: As PCI analyzes industry trends andprojects future growth requirements, thecompany had the foresight to plan for fu-ture expansions. The nature of the clinicaltrial services market requires us to providean on-demand service. As clients come tous with special requirements, we have to
be able to respond quickly to ensure thetimeliness of their trial and ultimately
PCI recently completed a North American storage and
distribution facility for clinical trial materials on a 97,000 square
foot site that was constructed to support growth in PCI’s clini-
cal trial services business, which includes drug development and
manufacturing, laboratory services, packaging and storage ser-
vices, global logistics, as well as client supporting consultative
services for executing global investigational studies. The new facil-
ity features storage for investigational supplies at controlled room
temperature, as well as expansions of its cold chain storage capac-
ity. A panel of PCI executives talked with Contract Pharma about
the new facility as well as broader trends impacting the market.
—TW
Keeping Ahead of GrowthPCI execs talk about the recent opening of the company’s new North American clinical facility, as well as
other trends in the market
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 73/132
June 2015 Twitter : @ContractPharma Contract Pharma 73
N E W S M A K E R S : P C I
increase their speed-to-market for com-mercialization. In some instances this maybe a sizeable Phase III study with sig-
nificant capacity needs. Our new site wasbuilt greenfield, with the anticipation thatgrowth could begin to consume this newfacility very quickly. With that in mind weplanned for very rapid expansion of bothour cold chain and controlled substancesstorage areas. For cold chain, that meantbuilding specialized flooring for the tem-perature demands and utilities require-ments to quickly turn on a request foradditional capacity. We can then expandmodularly and very quickly. Likewise,this consideration was given with our
controlled substances storage areas. Con-struction of these types of facilities requirestrict interpretation of DEA standards.
We have essentially pre-built our expan-sion into the facility, with floors and wallsbuilt at this time to adhere to DEA codeahead of the desired expansion. This willdramatically reduce the construction andapproval lead time for expansion as com-pared to building from scratch. This allowsus to support our client requirements rap-idly, which is the name of the game.
CP: What about unmet needs in the market? Misher: Consideration was also given tounmet needs in the industry, particularlyfor returned investigational drugs. At thecompletion of investigational studies par-tially used and unused medication needsto be returned and reconciled. Often thisis an overlooked aspect of trial manage-ment and can create regulatory headachesfor sponsor companies. PCI has built adedicated facility along with a dedicatedstaff for processing and storage of re-turned drug product. This includes provid-
ing accountability down to the individualunit dose level. Returned investigationalmedicines can be kept in storage until thecompletion of the investigational study, ormay be designated for destruction uponreconciliation. PCI’s new site accommo-dates both options.
With an increasing regulatory focus,ensuring IMP is returned, reconciled, de-stroyed and properly documented canpresent significant challenges. Sponsorcompanies are under tremendous pres-sure to initiate trials as quickly as possible
once approved. Once the trials are under way the focus is on assuring a continu-
ous supply, but often fail to give adequateplanning to the management of the returnIMP throughout the duration of the study.
We can be their central return drug centerfor all clinical studies to help them workthrough the logistics of getting the prod-uct back to the designated return drug site,performing the appropriate level of recon-ciliation, identifying discrepancies, andultimately how to disposition the studymedicine. This assures that the return drugprocess is performed consistently acrossall studies with no issues when regulatorsreview this data during their NDA productapproval process.
CP: How is PCI leveraging its current technology? Greig Ross, manager, clinical tech-nology, PCI: The processes involved inmoving clinical materials to and from in-
vestigational sites within the global clini-cal supply chain create opportunities toimprove both efficiency and precision. PCIhas analyzed industry trends and thenevaluated technologies and best practicesfor the online consumer retail market toevaluate where there may be overlap withthe potential of addressing unmet needs.Increasingly we are embracing technology
to provide a more efficient way of workingfor us and our customers.
Order fulfilment is a core service in which performance is measured in speedand accuracy. Using technology to inte-grate with our upstream partners allows di-rect order entry into both our PCI systemsas well as our couriers, resulting in a quickturnaround and assurance that the supplies
will be delivered to the exact destination. After order entry, the use of 2D data matrixbarcode scanning during the pick, pack andship steps eliminates human error and en-
sures order accuracy is preserved through-out the order processing. When the sponsor has finished recruit-
ment and the patients have progressedthrough the treatment period, attentionshifts to the close out activities includingreturns and reconciliation. Again this is anarea where we have looked beyond ourimmediate market to embrace technolo-gies that offer new solutions for our studyadministrators. Consumer retail readilyallows a customer to quickly and conve-niently process a product return and we
wanted to provide that same experience. We have recently launched an online ser-
vice to allow sites to log a return and printthe courier box label in a simple one stepprocess. This new service has enhanced
the customer experience in two aspects.The user processing the return, typically asite monitor with a CRO, can now quicklyand conveniently complete the steps in-
volved to initiate a return. Secondly thesponsor organization benefits from the
visibility of knowing when each returnhas been initiated, giving them increasedawareness of the study close out steps.
CP: What are some other recent PCI investments? Ravi Nalliah, director, global strategydevelopment, PCI: In fall of 2014 PCI
made two large strategic acquisitions toexpand its current service offerings. In Au-gust PCI acquired Penn Pharma, a lead-ing provider of manufacturing services forboth clinical studies as well as commercialmedicines. This move significantly ex-panded PCI’s ability to support formula-tion development, early stage analytical ac-tivities, clinical scale manufacturing, as wellas supporting the transition to successfulcommercialization of pipeline drugs. PennPharma also offers specialized services indevelopment, manufacture and packaging
of potent compounds by virtue of its expertstaff and award winning specialized con-tained manufacturing facilities in the UK.
Subsequent to the Penn Pharma acquisi-tion in 2014, PCI acquired UK-based BiotecServices International. With the additionof Biotec, PCI greatly expanded its abilityto support international studies requiringcold chain packaging, labeling and logistics.Biotec’s expertise includes support for coldchain materials with controlled temperaturerequirements down to -196°C, and comple-mented PCI’s established cold chain services
in North America and Europe.The clinical trial manufacturing sectorincorporating finished dosage manufac-turing, primary and secondary packag-ing and labeling, along with comparatorsourcing is the greatest cost in clinical trialsupply and logistics, accounting for morethan two thirds of outsourcing revenue inthis sector.
Current statistics illustrate around 80%of clinical trials enroll patients behindschedule and as many as 30% of patientsin phase III drop out. As a result, timing
and accuracy of the supply chain is there-fore absolutely critical. CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 74/132
74 Contract Pharma contractpharma.com June 2015
Girish Malhotra
President, EPCOT International
Traditions, their preservation and change, are part of humanheritage. They provide comfort until a “creative destruc-tionist”comes along and tips over the apple cart. A recent
Wall Street Journal article1 mentions “continuous processing”asa way to bring about change to pharmaceutical manufacturing.The benefits are enormous but we have to concede that we willneed to rethink and modify the current business model, operat-ing philosophies, process equipment and regulations. Changes
will be needed to the current landscape and that may not be easy.The application and adoption of different manufacturing tech-
nologies and operating philosophies is an uphill task in pharma-
ceuticals. Active pharmaceutical ingredients (APIs) can be formu-lated continuously but as discussed later will require additional
work to suit the dose and demand needs. Selective application ofcontinuous API manufacturing is definitely possible.2, 3, 4, 5
This article reviews the business and process considerationsfor continuous processes. They are very different for the manufac-ture of APIs and their formulations. Any and every improvementfrom the current practices will lower product costs, make pro-cesses sustainable, improve product quality and profitability andexpand the patient base. Companies could through improvedbatch and continuous processes lower global pharma costs by asmuch as $200 billion dollars per year6 and add close to a billionpatients on a global basis to the customer base that cannot afford
drugs. An unrecognized benefit of the continuous processes isthe flexibility they offer to ramp production up and down to meet
CONTINUOUS PROCESS in
PHARMACEUTICAL MANUFACTURING:Considerations, Nuances and Challenges
A review of the business and process considerations for continuous processing in pharma manufacturing
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 75/132
CONTINUOUS PROCESSING
June 2015 Twitter : @ContractPharma Contract Pharma 75
varying demands of drugs. Such pro-cesses can alleviate shortages.
CURRENT REALITYUnless there is a very compelling jus-tification, pharmaceuticals will notchange their API manufacturing andformulation processes for the existingproducts because the changes have tobe approved by the regulatory bodies.7 Regulations as they exist freeze8 theprocesses once submitted/approved.No one wants to spend money for theperceived financial gains even if theyare significant because the drug per-formance has to be reconfirmed. Asso-
ciated re-approval costs are unknownand thus are a deterrent. We have toaccept the current reality. However,
we still need to do our best to inno- vate new manufacturing technologies.
WHAT IS CONTINUOUS?
Continuous processing is being prac-ticed in many industries includingpharma’s older cousin—the chemicalindustry—for more than sixty years.Before we push “continuous” on anyaspect of pharmaceutical manufacturing, one needs to under-
stand the definition of continuous. A continuous process operates24 hours per day, seven days per week and 50 weeks of the year
with two weeks of holidays. Such an operation would be produc-ing quality products for 8,400 hours per year. Industry generallytakes 15% downtime for planned maintenance and unscheduledshutdowns. This means 7,140 hours being available to produce asingle product per year. Anything short of these operating hoursis not a continuous operation by classical definition.
An important aspect of a continuous process is that if a pro-cess in total involves multiple steps, each step has to be oper-ated as rest of the process for the times defined above. A process
would not be called a continuous process if it operates e.g. 500hours once or twice per year and shut down for rest of the time
of the year or some other product is produced in the same equip-ment. Such an operation might fit certain operating philosophybut does not fit the continuous process definition. An “on and off”process is similar to a batch process and will suffer from the wrathof the regulations.
Continuous processes are not mentioned in FDA regulationtexts. However, cGMP practices will always be necessary. It is anexcellent opportunity for the companies operating such process-es to show how they can create processes that require minimumregulatory oversight by producing quality products all the time.
Going from batch to continuous in pharma demands that thepharmaceutical industry think differently 9 about the manufactureof APIs and their formulations. Understanding of science, thought-
ful application of applied science along with business innovationis necessary. Careless attempts will result in failures and will give
naysayers an opportunity to say, “I told you so”, and will result in API manu-facturing and their formulations stay-
ing inefficient with patients picking upthe tab through mutually subsidizedsystems or from their own pockets.
CURRENT TRADITIONS
AND LANDSCAPE
It would be worth reviewing why thecurrent traditions and regulations de-
veloped and why we are comfortablein the current landscape.
We have to recognize that the ac-tive pharmaceutical ingredients arespecialty/fine chemicals that have a
disease curing value. Since the reactivemolecule chemistries and processingmethods—unit processes and unitoperations—are the same for major-ity of the chemicals, pharma industry
very wisely used the available process-ing equipment. It is my conjecture thatsome of the following factors influ-enced manufacturing decisions:1. Since the pharmaceutical compa-nies originated in then developingcountries—now the developed coun-
tries—the majority of the market was in these countries. Lack
of drug affordability led to subsidized healthcare programs.Usage increased. Still the market most likely constituted lessthan 25% of the global population. Only rich patients, a verysmall population, of the remaining 75% could afford thedrugs and paid from their own funds.
2. Since the drugs are used in varying milligram quantities, an-nual API quantities needed for the population are signifi-cantly lower than traditional chemicals. Pharmaceutical com-panys’ focus was to get the product to the market rather thanhave cost effective and innovative manufacturing processes.
As a result, to assure product quality, many of the regulationsand guidances came about.
3. APIs were formulated using traditional unit operations that
were used in the chemical industry.10
Processes for dispens-able dose compaction and ease of consumption developed asbetter excipients (chemicals) developed.
4. Since API manufacturing and their formulation are batchprocesses, testing methods were developed to meet theneeds of the time. Lack of command of the processes led torigorous in-process testing resulting in supply chain issuesand inefficient asset utilization. The need for simple, repeat-able and reliable processes that delivered defect-free qualityproducts the first time were never a must. Since drugs wereneeded to extend life, their cost was not a consideration.
5. Focus of pharma companies was to develop drugs for thediseases that were spreading rather than improving inef-
ficiency of manufacturing processes as the focus was lifeextension rather than making drugs affordable.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 76/132
CONTINUOUS PROCESSING
76 Contract Pharma contractpharma.com June 2015
All of the above works well for brand drugs and fulfills theneed. Additional factors e.g. WTO agreements and brand drugsbecoming generic either due to patent expiration or being nul-
lified have led to significant landscape changes. As a result, thenumber of companies producing APIs and formulating genericdrugs has dramatically increased.
In addition, with lower production volume compared to brand volume most of the producers use manufacturing methods thatare equally or more inefficient. Since the selling prices comparedto branded products are lower, a misconception has prevailedthat generics use better manufacturing technologies and busi-ness practices. Some companies have developed better methodsbut their number is small. To retain profitability short cuts takencan affect overall product quality. Regulatory compliance andquality issue incidents have increased with time.
Increased numbers of brand and generic drug suppliers have
made regulatory compliance and monitoring difficult. Regulatorybodies through regulations, directives, guidances and harmoni-zation efforts have tried and are trying to cajole the industry toinnovate their manufacturing practices so that quality drugs areproduced from the onset rather than through repeated analysis.Lack of processes that produce quality drugs with minimal post-production analysis is costing the global healthcare system asmuch as 25% or more of the global revenue.11 Unless the industrytakes a self-look at its practices, not much will change. Anotherfactor that has deterred the pharmaceutical industry from self-examination is the revenue they generate measures their perfor-mance rather than how many people can afford their drug. Drug
Value Index12 could be used as a measure—a lower index number
would indicate widespread use and affordability of the drugs.
PROCESS DEVELOPMENT CONSIDERATIONSFOR CONTINUOUS PROCESSES
A maverick company should review the existing brand/generic
high consumption volume drugs fortheir processes and manufacturingmethods. Companies can also use the
current selling prices, supply chainmargins and processing chemistriesand methods to reverse calculate theopportunities they have for the high
volume generics.12 Such an exercisedefines opportunities. They could alsobring to fore what are the best processtechnologies and what can be simpli-fied/improved to create possibilities of
continuous processes. If such a company decides to commercial-ize some of these products pharma’s global landscape could be-come very different from what it is today.
We all understand value and benefits of continuous processes
but going from batch process that is developed in the laboratoryto a commercial continuous process requires many consider-ations. Each chemist and chemical engineer along with business-person at some point has to use, review and incorporate the fol-lowing in commercialization of their products:1. Process chemistry 2. Process and its economics3. Product volume4. Equipment5. Safe exploitation of science6. Safety considerations7. Sustainability
Process of commercialization has to be envisioned andplanned from day one of the process development of the newmolecule. It has to be completed before the active enters the clin-ical trial phase. If not done by then the regulatory requirements
will discourage changes and innovation. The question remains:“Is a pharma insider or an outsider willing and ready to changethe landscape?”
Using what is outlined I believe that process perfection andthe product quality will be so high that many of the regulatory re-quirements and guidances may not be necessary and that wouldbe something beyond anyone’s imagination.
Be a reactive (API) or a blending (formulation) process, sig-nificant progress has been made in the last one hundred years to
have an excellent understanding and command of the processesthat are safe and sustainable for the desired production volume.The difference between batch vs. continuous processes besidestheir production volume and operating time is that in batch pro-cess quality is tested in product at various steps whereas in a con-
TABLE 1: API Production
Dose, mgTabletsPer day
Days /yr.Patient
PopulationTotal API
needed, Kg
Type of plant
Ideal Actual
1 2 365 1,000,000 859 Batch Batch
10 2 365 1,000,000 8,588 Batch Batch
100 2 365 10,000,000 858,823 Continuous Batch
“Going from batch to continuous in pharma demands
that the pharmaceutical industry think differently about themanufacture of APIs and their formulations. Understanding
of science, thoughtful application of applied science along
with business innovation is necessary.”
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 77/132
CONTINUOUS PROCESSING
June 2015 Twitter : @ContractPharma Contract Pharma 77
tinuous process quality is built in. Final product quality checks arenecessary in both methodologies.
In the process development phase all of the work is done inlaboratory using traditional labware. This is essential as it de-fines the process parameters for the best laboratory process yield.Product volume and process define equipment needs. In gen-eral first preference for the manufacture of reactive and blendedproducts is to use the existing available equipment.
As the product transitions from the laboratory to scale up tocommercial production many of the issues that relate to productquality and regulatory bodies shape and take hold. In the chemi-
cal industry—pharma’s older cousin—regulatory issues intervenein a product’s life but not to the extent they do in pharmaceuti-cals. In pharma, once the product enters the clinical testing phaseprocess changes become progressively difficult, expensive andcumbersome. As a result, processes are frozen.
Factors that do influence the process selection—batch vs.continuous—for the API and formulations are drug dose, globalproduct demand and number of producers. Table 1 is an illustra-tion of drug dose and the resulting process for the API. Underthe current equipment configurations API for 1 and 10 mg wouldbe most suited for batch processes. Ideally a continuous processshould produce API for 100 mg for ten million patients. How-ever, in the current business model this API most likely would
be produced in multiple plants. Every batch process would mostlikely be inefficient—low yield, poor asset utilization with supplychain and logistic issues—and possibly have lower overall yield13
compared to a single continuous plant.Lower volume APIs could be produced using continuous pro-
cess. However, process, type of equipment used and operatingphilosophies will have to be very different from the current think-ing. Economics of such processes and operations will have to be
justified. Potential for campaigned continuous process could befeasible if similar chemistry could be used in the same processequipment. Asset utilization would not be optimum.
Table 2, an illustration, reviews various formulations options.Readers can use similar analysis to rationalize their formulation
options—85% formulation yield and on-stream-time is assumed.For the last one hundred years companies have been formu-
lating and packaging tablets. We have sufficient industry expe-rience to formulate and produce quality tablets. We also haveabundant knowledge about the mutual physical behavior of thecomponents that go in the formulations. We also know how toapply the science to process development and design. Still unlessconstant attention is paid to the process through repeated qualitychecks, product quality slips.
It is my conjecture that the pharmaceutical industry has nev-er been challenged to overcome the status quo or not felt theneed to have operational excellence by applying principles ofengineering and science to commercialize efficient formulation
processes. Commercial formulation equipment and technologiesare available to deliver the dosages needed in Table 2. It is up tothe pharma companies to decide if they want to capitalize on theavailable options to improve their profits and deliver consistentquality products.
I am dismayed that we can send men to the moon and bringthem back safely but cannot blend excipients and APIs to pro-duce quality drugs on an ongoing basis without repeated testing.
We have relied on “in-process”testing to create quality drugs. It isthe industry’s responsibility to correct this anomaly. The questionis: “Are we up to the challenge?”
The presentation of Vertex’s continuous formulation in the Wall Street Journal article1 operating at 100,000 tablets per hour is
interesting. It reaffirms availability of high production rate equip-ment. Analysis in Table 3 suggests that either the production rateis misquoted in the article, or Vertex has overdesigned a plantor their operating regimen is not discussed. The API needed forKalydeco, the cystic fibrosis drug from Vertex, is be about 13,000kg/year. A batch process would produce this. It is my thinkingthat they have invested in the plant and they will be producingdifferent drugs for their allocated time on a campaign basis.
It is essential that chemists and chemical engineers considerand incorporate how they can exploit physical properties of thechemicals15 involved and produced to simplify the process. Thesetraits are not taught but are a combination of our imagination, ex-perience and creativity. Use of multiple solvents has to be limited.
Many would disagree but for simplicity, process costs and sus-tainability this is necessary. Since this is practiced by the chemical
TABLE 2: Formulation Plant Options
Dose, mg. 1 10 100
# Tablets/day 2 2 2
Days/yr. 365 365 365
Population, # 1,000,000 1,000,000 1,000,000
Total tablets needed/yr. 858,823,529 858,823,529 858,823,529
API Kg./yr. 859 8,588 85,882
API Number of plants, Batch process 1 1 1
Continuous formulation (7140 hrs.), Tablets /Hr. 120,283 120,283 120,283
Number of Formulation plants 2 5 10
Tablet production rate/hr.(operating 7140 hr./Yr.) 60,142 24,057 12,028
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 78/132
CONTINUOUS PROCESSING
78 Contract Pharma contractpharma.com June 2015
industry, it can also be donein pharmaceuticals if wemake the effort.
Traditionally chemistsand chemical engineersconsider and use reac-tors and vessels that areavailable to us. We need toconsider how and what allneeds to be done to mini-mize the batch cycle timeand improve process yield by exploiting lab developed operatingparameters. Minimized batch cycle time nudges the process froma batch to a continuous process. In this effort consideration hasto be given to use alternate equipment or use the existing equip-ment in the alternate way.
In recent times micro-reactors are the new buzz in reactionequipment. They are being touted as having the potential to fa-cilitate adoption of continuous processing for the manufactureof APIs. These are expensive and at this point a laboratory curi-osity. In addition, in a commercially profitable business productis produced in kilograms per hour and not grams/microgramsper hour. Plate and frame heat exchangers have been aroundfor more than sixty years. Such exchangers of proper metallurgy
work extremely well and can be readily used. They are idealand economic for large-scale production. We used them in ourprocesses in the early seventies. I want to re-emphasize thatrunning a single step for short time does not make the wholeprocess a continuous process.
In order for any API or the formulation to be produced usingcontinuous processes many of the factors discussed above haveto have “hand and glove fit”. Due to regulatory constraints forthe existing products continuous processes can be commercial-ized only for new brand drug processes. Incorporation of con-tinuous processes for API manufacture and their formulations
would result is a business model that is very different from thecurrent model.
Academia16,17 has done excellent work on improving yield andchemistries of some of the antiretrovirals. They are prime candi-dates for commercialization of continuous processes. A maverickcompany can commercialize continuous processes for Omepra-zole3 , Modafinil4 , Metformin hydrochloride5,18 , Hydrochlorothia-
zide18
and some of the antiretrovirals to name a few. These fit thecriterion described earlier. Their commercialization will have togo through a rigorous process of convincing regulatory bodiesof drug efficacy and performance and that could be a deterrent.Economies of scale and profitability will be the driver.
CONCLUSION
Continuous processing forthe formulations can be eas-
ily done. Judicious review ofthe pharma landscape willshow us many opportuni-ties. Since the volumes of
APIs are not conducive to year round production, al-ternate strategies could beconsidered. Use of modular
equipment could be a possibility. They could come from single API line(s) at the same plant. Business strategies will be very dif-ferent from the current model for such plants.
Continuous processes will make drugs affordable to a sig-nificant patient base that cannot afford drugs or have to choose
between food and life extending drugs.19
Pharma will see higherprofits due to better economies of scale. Continuous processing
will also reduce the excess capacity pharmaceuticals have5 be-cause the production can be ramped to meet the demand.
Pharmaceuticals need process centricity and it will drive com-panies to quality and operational excellence rather than live withregulation centricity.20 Financial justification for manufacturinginnovation exists.21 Without effort nothing will change.
A maverick company should review the existing brand/gener-ic high consumption volume drugs for their processes and manu-facturing methods. Companies can also use the current sellingprices, supply chain margins and processing chemistries andmethods to reverse calculate the opportunities they have for the
high volume generics.12
Such an exercise defines opportunities.They could also bring to fore what are the best process technolo-gies and what can be simplified/improved to create possibilitiesof continuous processes. If such a company decides to commer-cialize some of these products pharma’s global landscape couldbecome very different from what it is today.
There is a distinct opportunity for companies to increase theirprofits by double digits if they selectively implement continuousprocessing strategies in their API manufacturing and formula-tions. The landscape will definitely be different, as companies
with the most competitive technologies will benefit the most.In addition, regulatory and trade barriers that exist and are cre-ated by countries would have to be overcome while global drug
regulatory compliance would be greatly simplified. The benefitsof lower healthcare costs, higher revenue due to a larger patientbase and better quality drugs would be significant.
A maverick company, 23andMe22 has entered the pharmadrug discovery industry using its technologies. My hope is that
TABLE 3: Vertex Formulation Rate Review
Total global CF population14 100,000
Dose, mg per day (two 150 mg tablets per day) * 300
Total # of 150 mg tablets needed per year 85,882,353
Production rate, # of tablets per hr. if operated 24x7x50 Hrs. ~12,030
Number of Production Days needed for CF tablets (rate 100,000/hr.) ~42
“ An unrecognized benefit of the continuous
processes is the flexibility they offer to rampproduction up and down to meet varying
demands of drugs. Such processes can
alleviate shortages.”
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 79/132
CONTINUOUS PROCESSING
June 2015 Twitter : @ContractPharma Contract Pharma 79
they will also look into and commercializebetter manufacturing technologies. That
would be a game changer. CP
References
1. Drug Making Breaks Away From Its Old Ways,
http://www.wsj.com/articles/drug-making-
breaks-away-from-its-old-ways-1423444049 ,
Accessed February 8, 2015
2. Malhotra, Girish: Why Fitting a Square Plug
in a Round hole is Profitable for Pharma and
most likely will stay? Profitability through
Simplicity, http://pharmachemicalscoatings.
blogspot.com/2014/08/why-fitting-square-
plug-in-round-hole.html, August 1, 2014, Ac-
cessed February 24, 2015
3. Malhotra, Girish: Alphabet Shuffle: Moving From QbA to QbD - An Example of Continu-
ous Processing, Pharmaceutical Processing,
http://pharmpro.com/Articles/2009/03/Alpha-
bet-Shuffle---Moving-From-QbA-to-QbD/ ,
February 2009 pg 12-13
4. Malhotra, Girish: Review of Continuous Pro-
cess for Modafinil, Continuous Processing in
the Chemical and Pharmaceutical Industry II,
2009 AIChE Annual Meeting, November 10,
2009, Nashville, TN.
5. Malhotra, Girish: Chemical Process Simplifi-
cation: Improving Productivity and Sustain-
ability, John Wiley & Sons, February 20116. Malhotra, Girish: Are The Savings of $120-
$150 Billions Worth Having? http://pharm-
achemicalscoatings.blogspot.com/2012/08/
are-savings-of-120-150-billions-worth.html ,
August 20, 2012 (Savings were revised up to
$200 billion.) Accessed March 3, 2015
7. Manufacturing the future – The next era of
global growth and innovation, McKinsey & Co.
November 2012, pg 54
8. Singh, R etal: Flexible Multipurpose Con-
tinuous Processing of Pharmaceutical Tablet
Manufacturing Process http://www.gmp-
compliance.org/daten/download/shortpaper_continuousprocessing_muzzio.pdf, Accessed
March 2, 2015
9. Think Different, https://www.youtube.com/
watch?v=nmwXdGm89Tk , Accessed February
18, 2015
10. McCabe, Warren L. & Smith, Julian C: Unit
Operations of Chemical Engineering, Mc-
Graw-Hill & Co. 1967
11. Cost of Poor Quality, www.juran.com/elifeline/
elifefiles/2009/09/Cost-of-Poor-Quality.ppt , Pg
9, Accessed Feb 20, 2015
12. Malhotra, Girish: A Blueprint for im-
proved Pharma Competitiveness, Contract Pharma, http://www.contractpharma.com/
issues/2014-09-01/view_features/a-blueprint-
for-improved-pharma-competitiveness/ Sept
2014, pgs. 46-49
13. Shah, Vibhakar: PAT, QbD and Process Valida-tion – The Enablers of Pharmaceutical Qual-
ity Assurance, CASA/FDA Pharmaceutical In-
dustry Seminar, May 20, 2011,pg 6, Accessed
March 3, 2015
14. Cystic Fibrosis population worldwide http://
www.cfww.org/about/article/400/What_is_
Cystic_Fibrosis Accessed February 24, 2015
15. Malhotra, Girish: Focus on Physical Properties
To Improve Processes, Chemical Engineering,
Pg 63-66, April 2012
16. Brown, David H. et.al: Process Improvements
for the Manufacture of Tenofovir Disoproxil
Fumarate at Commercial Scale, Organic Pro-cess Research & Development 2010, 14, 1194–
1201
17. Longstreet, Ashley R.: Investigating the con-
tinuous synthesis of a nicotinonitrile precursor
to nevirapine, Beilstein J. Org. Chem. 2013, 9,
2570–2578
18. Malhotra, Girish: Strategies to Enhance API
Manufacturing Processes, Business Insights
Ltd., March 2011
19. Malhotra, Girish: Drug Prices: Food vs. Medi-
cine – A Difficult Choice for Some, http://phar-
machemicalscoatings.blogspot.com/2011/06/
drug-prices-food-vs-medicine-difficult.html , June 16, 2011, Accessed March 10, 2015
20. Malhotra, Girish: Regulatory Compliance vs.
Operational Excellence: What Should Hap-
pen First? http://pharmachemicalscoatings.
blogspot.com/2015/02/regulatory-compliance-
vs-operational.html February 3, 2015
21. Malhotra, Girish: How to Justify Innovation
and QbD in Manufacturing, http://www.phar-
mamanufacturing.com/articles/2015/how-to-
just ify-innovation-and-qbd-in-manufactur-
ing/ May 4, 2015
22. 23andMe to Use Genetic Database for
Drug Discovery http://www.wsj.com/ articles/23andme-to-use-genetic-database-for-
drug-discovery-1426161601?mod=WSJ_hpp_
MIDDLENexttoWhatsNewsFifth accessed
March 12, 2015
GIRISH MALHOTRA, president and
founder of EPCOT International, has
more than 45 years of industrial experi-
ence in pharmaceuticals, specialty, cus-
tom, fine chemicals, coatings, resins and polymers,
additives in manufacturing, process and technology
development and business development. [email protected]; Tel: 216-223-8763
AATL Services
• Water Testing• Gas Testing per USP, EP and JP
• Wet Chemistry Testing
• Complete Monograph Testing
per USP, EP and JP
• In-Process/Finished Product Testing
• Stability Storage and Testing
Program
• Container Testing
• Method Development and Validation
per USP <1225> and ICH
• Trending Reports
• Support for Stability
• Pharmaceutical Chemistry
• Lot Release Testing
• Consulting Services
• Microbiology Testing
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 80/132
80 Contract Pharma contractpharma.com June 2015
A
lthough risk-based monitoring (RBM) has been a hottopic in the clinical research community for some time
now, implementation and execution of the strategy inclinical trials is still in the early stages. The traditional standardof on-site visits, combined with 100% source data verification(SDV), has given way to a new mode of thinking at the U.S. Foodand Drug Administration (FDA). The FDA now accepts an ap-proach to clinical studies focused on critical study parameters andrelies on a combination of monitoring activities, including cen-tralized data collection and monitoring.
The FDA’s guidance, “Oversight of Clinical Investigations—ARisk-Based Approach to Monitoring,”acknowledges that clinicaltrials have become much more complex and geographically dis-persed over the last 20 years, even as progress in electronic systemsand records and improvements in statistical assessments have cre-
ated opportunities for alternative monitoring approaches. The FDAemphasizes the underlying intent is, as always, patient safety.
A risk-based approach to monitoring does not suggest anyless vigilance in oversight of clinical investigations. Rather, it
focuses sponsor oversight activities on preventing or mitigat-ing important and likely risks to data quality and to processescritical to human subject protection and trial integrity. Moreover,a risk-based approach is dynamic, more readily facilitating con-tinual improvement in trial conduct and oversight. For example,monitoring findings should be evaluated to determine whetheradditional actions (e.g., training of clinical investigator and sitestaff, clarification of protocol requirements) are necessary to en-sure human subject protection and data quality across sites.
TKL Research recently conducted a Phase II randomized,double-blind study concerning mild to moderate atopic dermati-tis. The study utilized 20 U.S. sites as well as 10 outside the U.S. Atotal of 195 subjects were screened and 121 subjects randomized.
Insofar as was possible, TKL tried to mirror the FDA guidance onRBM in the conduct of this trial. This is our experience.
Lynn KingSenior Director of Clinical Operations and Head of Clinical Monitoring, TKL Research
Applying
Risk-Based Monitoring in the Real World
Implementing an acceptable clinical monitoring plan requires a thorough understandingof the new rules under which we’re operating
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 81/132
RISK-BASED MONITORING
June 2015 Twitter : @ContractPharma Contract Pharma 81
WHAT THE FDA WANTS
The FDA is basically looking at three areas in regard to your cen-tralized RBM strategy: routine review of data, statistical trend
analyses and site performance statistics.Routine review of data means you have a plan to flag missing or
inconsistent data as well as data outliers and protocol deviations. Although with traditional monitoring strategies, we view sta-
tistical trends and anomalies at the end, in RBM approaches, sta-tistical trends are reviewed in real time for range, consistency andcompleteness as well as for unusual distribution of data at onesite and/or across all sites.
Site performance statistics, such as unexpected screen failurerates, high withdrawal rates, eligibility violations or data report-ing delays are also reviewed during the course of the trial, so thatcorrective action, such as additional training or protocol amend-ments, can take place.
Implementing an RBM program affects the development pro-cess in a number of ways. By focusing on critical study parametersand relying on a combination of monitoring activities to overseea study, the roles and responsibilities of everyone involved in thetrial must be discussed and clearly defined.
We found it useful to hold in-depth discussions with all of themembers of the trial team, including the project leader, safety as-sociates, regulatory associates, clinical trial managers, statisticiansand data managers to encourage cooperation and make sure ev-eryone was clear on their roles and responsibilities.
CREATING THE CLINICAL MONITORING PLAN
Following the FDA guidance, our goal was to create a straightfor-
ward, concise clinical monitoring plan (CMP) that eliminated asmuch redundancy as possible and was capable of being altered asthe trial progressed.
One of the key aspects in creating a CMP is assessing risk for allaspects of data collection and trial conduct, including establishingthe chances of an error occurring, the impact of errors on subjectprotection and data integrity, and the organization’s underlyingability to detect these errors. Risk assessment is a complex sub-
ject all on its own, but fortunately there are tools to help you workthrough the process and, for this study, we used the Risk Assess-ment and Categorization Tool (RACT) developed specifically forthe pharmaceutical industry by TransCelerate BioPharma Inc.
Using RACT, we assessed risks of the program and protocol;
identified and documented critical data and processes; assessedpotential risk indicators; and developed a plan for monitoring ex-ecution of the study.
CREATING THE MONITORING STRATEGY
In consultation with the trial team, we developed a list of thecritical variables to monitor during the trial, which included:• Signed informed consent form• PK research sub-study ICF• Childbearing potential• Target lesion identication• Percent of body surface area covered• Inclusion/exclusion criteria
• Adverse events/severe adverse events• Overall investigator global assessment score
• Overall eczema areas and severity index score• Visual analog scale (VAS) pain score• Quality of life assessments
We also developed a monitoring strategy that was divided intothree tiers. Tier 1a included 100 percent SDV of all data variables(critical and non-critical) of the first subject randomized at eachsite; Tier 1b consisted of 100 percent SDV of all data variables(critical and non-critical) of 25 percent of the randomized co-horts; and Tier 2 included collection of only the critical data onthe remaining 75 percent of randomized subjects. Remote moni-toring tasks (date trend analysis, query response review, listingsreview) were also defined and documented in the CMP and in aseparate trip report for remote activities.
Although our use of centralized monitoring techniques waslimited, we did employ a combination of targeted and reduced
monitoring techniques to create an efficient, smooth running trialin alignment with the FDA’s guidance for risk-based monitoring.
KEYS TO A SUCCESSFUL RBM TRIAL
There are a number of valuable lessons research organizationscan learn from our experience that will simplify implementingRBM in future trials.
Be certain the communication pathways between team mem-bers are strong and well-established, and that everyone has aclear understanding of roles and expectations from the outset. Asuccessful RBM-based trial is cross-functional and requires activeparticipation from everyone involved.
The clinical monitoring plan must be clear and concise, but
thoroughly complete, with critical study-specific informationidentified and processes developed to gather, analyze and act ondata during the trial. During training, remember that it’s impor-tant to provide specific examples of the kinds of triggers that willresult in additional monitoring of investigator sites.
Finally, if electronic data collection will be a part of your CMP,it’s important to ensure you have the technical capabilities inplace for a secure capture, monitoring and transfer of data.
CONCLUSION
Sponsors of clinical trials are seeking ways to reduce clinical trialcomplexity and drug development costs while getting more valuefrom limited research and development budgets. Regulatory agen-
cies, such as the FDA, have determined there is a need to find moreefficient ways to approach clinical trials. RBM enables researchersto target and prioritize resources around the identifiable risks thatrelate to the safety of subjects and quality and integrity of clinicaltrial data, and to create monitoring strategies that are aligned withthe risks and purposes of each specific trial. CP
LYNN KING is a veteran research professional with more than 20 years
of experience in the drug-development industry. A proven leader of
projects, teams and individuals, including 18 years of management ex-
perience, King’s experience includes hands-on monitoring and project
management experience as well as coaching, mentoring and training
roles in both the CRO and pharmaceutical environments. She holds a bachelor’s degreein biomedical ethics and public policy and a master’s degree in healthcare administration.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 82/132
82 Contract Pharma contractpharma.com June 2015
In 1965, Gordon Moore, co-founder of Intel, predicted thatthe number of transistors per square inch of integrated cir-cuits would double each year for the foreseeable future. It
was a bold claim—the integrated circuit had only been aroundfor seven years, so there was little history on which to base hisforecast. But it proved accurate for so long and was so remark-able in representing a phenomenon that could transform a tran-sistor that fit in the palm of the hand to something so small that4,000 could fit across the width of a human hair, it became a lawof sorts—Moore’s Law. More an aspiration than a law of nature,Moore’s Law is the definitive benchmark to measure the pro-ductivity gains achieved across a range of technical processes,from developing photo cells to brewing beer.
Moore’s Law has been applied to the life sciences, some-times to great success. For several years in the early 2000s, thecost to sequence the human genome tracked Moore’s Law.The National Human Genome Research Institute calculatedthe cost of sequencing the genome at nearly $100 million in2001. In just six years, that cost dropped to under $10 million,in line with Moore’s Law. Productivity got even better over thenext seven years, when costs dropped to less than $5,000, a farbetter improvement than Moore’s Law would have predicted.
But the wider sphere of drug development has not alwaysenjoyed this type of exponential improvement. For a time,Moore’s Law was applied to drug development in reverse.Calling the phenomenon Eroom’s Law—Moore’s Law spelled
backwards—Jack Scannell wrote in a 2012 paper in Nature Re- views Drug Discovery that the number of new drugs approved
by the FDA per billion of inflation-adjusted U.S. dollars hashalved about every nine years, suggesting that drug develop-ment was worsening. At the 2012 Forbes Healthcare Sum-mit, several pharma execs saw Eroom’s Law ending, due toimproved technology, availability of biomarkers, and insightsfrom genomics. Recent drug approval data give an encourag-ing sign of that improvement, with 41 new drugs approved in2014, the highest level in the past decade.
The trouble is, progress in drug development is increasinglymeasured by more than drug approvals. Successful productstoday demonstrate safety and efficacy, meet an unmet need,achieve favorable reimbursement, and reduce the total cost ofcare—a complicated combination of goals that relate to a sys-
tem of healthcare stakeholders. Achieving one goal while ignor-ing the others reduces the overall impact that promising newtreatments can have on the healthcare system, whether thatimpact is measured in financial returns or lives improved. Con-necting insights across the system helps ensure that the wholeof the healthcare system improves as fast as the sum of its parts.
With homage to Dr. Moore and to the impressive gains thattechnology systems have achieved in 50 years, below are a fewideas to advance an interconnected system of healthcare
PREPARE FOR A NEW HEALTHCARE OPERATING SYSTEM
Containing the cost of healthcare requires new ways of operat-ing, and most stakeholders believe it will come from working
more closely together. In 2013, Quintiles published The Collab-oration Mandate on the impact of healthcare’s changing land-
Moore’s Law for MORE HEALTHThis year marks the semicentennial anniversary of a prediction aboutexponential growth and productivity
Patrick Jordan
Vice President, Payer and Provider Services, Encore Health Resources
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 83/132
MOORE’S LAW
June 2015 Twitter : @ContractPharma Contract Pharma 83
scape on the relationships of providers, payers, and biophar-maceutical companies. According to the surveys, less than 20%of these stakeholder groups thought they were aligned withothers, but well over half expect to be in the next several years.Despite the challenges with aligning around incentives, about75% of the stakeholders believed that working in a system pres-ents an opportunity to improve healthcare. But the stakeholders
need to figure out how to share data to make the system work.More than 70% said transparency around data and informationsharing across stakeholders was vitally important to the suc-cess of an interconnected healthcare system, yet less than halfthought they had the tools or expertise to optimize its use.
BACKWARDS COMPATIBILITY CAN BE THE WAY FORWARD
Oncology is the most prolific therapeutic area in the develop-ment pipeline and one of the most challenging with the low-est likelihood of approval. Challenge creates opportunity, evenin discoveries that first seem like failures. In a recent opinionpiece, Peter Huber and Paul Howard at the Manhattan Insti-tute referred to a 2010 study where more than 90% of bladder
cancer patients failed to respond to an experimental treatment, while one patient had “no evidence of disease” two years lat-er. This positive result arose because of a biomarker found in8% of bladder cancer patients that made her cancer sensitiveto the experimental treatment. Reviewing other failed studies,the National Cancer Institute identified 100 responders wherebiomarkers may revive shelved products, the life sciences equiv-alent of backwards compatibility. As genomic capabilities ma-ture, we can do more to prospectively identify unique patientpopulations and speed development of therapeutics suited forthem. Work is already underway at places like Memorial SloanKettering Cancer Center with “basket trials,”which reverse thetypical process of studying a specific organ first and instead ex-
amine cancers of different organs whose tumors share the samegenetic mutation.
ENGAGE COMMUNITIES
I recently had the privilege to speak with a mother who en-rolled her daughter in a trial to study a treatment for a rare andoften fatal bone disease. Her experience was heart-wrenching,learning during pregnancy that her unborn daughter wouldnot likely live beyond birth. As it was hopeful, with her babygirl beating the odds to survive and ultimately receiving anexperimental treatment that helped her bones harden, makingher capable of not only walking but also running. I asked thismom what more the drug development industry could do to
help her and her inspiring daughter. I expected a request formore research of rare diseases and an impatience among those
in the industry to find cures, both of which are certainly need-ed, but she did not ask for that. Instead, she asked that we helpconnect families going through the same harrowing experi-ence so they can navigate the clinical research and healthcaresystems together. We often first think of science as the meansto take healthcare forward, but community helps make surepatients and families are not left behind.
OPTIMIZE THE EXPERIENCE
Chief Experience Officer sounds more like a role from a techstartup than healthcare. In 2007, Cleveland Clinic was amongthe first major academic institution to appoint a Chief Experi-ence Officer (CXO), in response to having some of the lowestpatient satisfaction scores in the country. In a few years, theclinic would be in the top 8%. Such an improvement is signifi-cant to a hospital’s economics since patient satisfaction scoresare a factor in the amount Medicare reimburses. We wouldalso do well to have CXOs that focus on patient satisfaction inclinical trial design. A recent study of oncology trials indicatedthat physicians under-reported as much as 75% the number of
patients who had six common side effects to chemotherapy. Asdrugs reach the market, side effects drive down drug adher-ence, a problem thought to cost $100-300 billion each year.But patient experience goes beyond economics. One analysisof 55 studies across disease areas found patient experience incare settings to be positively associated with safety and clini-cal effectiveness. Another study of nearly 6,500 patients withacute myocardial infarction found that higher patient satisfac-tion was associated with better guideline adherence and lowerinpatient mortality. We know that physician experience mat-ters, but patient experience matters too.
The Gates Foundation, which focuses on global healthamong other priorities to promote equity for people around the
world, described in its 2015 Annual Letter that it would place abig bet for the future of health. Whereas it previously took 25 years to cut the child death rate in half, the Foundation wouldcut that rate in half again in 15 years, an achievement of expo-nential improvement. It is fitting that the Foundation’s bet restson applying to healthcare “close to the same amount of innova-tion that goes into making computers faster and smaller.”
Healthcare needs this type of systems thinking—and morethan a few bold prognosticators with a vision for the future
where there is a Moore’s Law for more health. CP
PATRICK JORDAN is vice president of payer and provider ser-
vices at Encore Health Resources.
“[P]rogress in drug development is increasingly measured by more than drug ap-
provals. Successful products today demonstrate safety and efficacy, meet an unmetneed, achieve favorable reimbursement, and reduce the total cost of care—a com-
plicated combination of goals that relate to a system of healthcare stakeholders.”
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 84/132
84 Contract Pharma contractpharma.com June 2015
It can be said that imitation is the sincerest form of flattery,but ask any pharmaceutical executive about counterfeiting,and they would prefer that criminals keep their “flattery”
to themselves. Counterfeit pharmaceutical drugs are a globalproblem that pose serious threats to public safety, and it isestimated to be a $75 billion illegal enterprise.1
A growing middle class and aging population has led to morehealthcare consumption and a longer and more complex supplychain allowing greater potential for counterfeiters to strike.
Counterfeiters take many forms and are driven by high de-mand. Fake online pharmacies promising low-cost drugs with-out a prescription, under-regulated wholesalers or distributorsand malevolent criminals taking advantage of consumer trustmake up the counterfeit pharmaceutical landscape.
According to the World Health Organization, counterfeitersoperate without the overhead costs of infrastructure, regula-tory compliance and pricey active ingredients.2 In many cases,the fake drugs they manufacture have incorrect quantities,no active ingredients at all, or even malicious, harmful sub-
stances. As a consequence, counterfeit drugs, if uncontrolled,can destroy lives and public confidence in healthcare systems,suppliers and sellers of authentic drugs, the pharmaceuticalindustry and authorities.
Regulations are in place to help keep consumers safe andcounterfeit drugs out of the supply chain. Those companiesthat leverage such track-and-trace compliance initiatives tomeet broader business goals will be better positioned to enjoylong-term success regionally and abroad.
But no matter what, all parties in the pharmaceutical in-dustry, including logistics providers, have a role to play in anti-counterfeiting measures and protecting the public.
THE STATE OF THE INDUSTRY
In the U.S., counterfeit issues in the pharma industry were
brought to light during the war on illegal drugs in the 1980s, when the drug supply was open to foreign medicines. A lucra-
tive illegal market flourished for counterfeiters with billionsof dollars’ worth of opportunities. A notable example of thisproblem was women in large numbers taking birth controlpills reported becoming pregnant. After thousands of com-plaints and subsequent investigations, it was discovered thatmany women were in fact taking foreign counterfeit pills. 3
U.S. law enforcement enacted the Prescription Drug Mar-keting Act of 1987 to close off the supply chain to counterfeitdrugs, but the pharmaceutical landscape has since changeddramatically. Today’s pharmaceutical supply chain is muchmore complex with changing distribution models such asdirect-to-patient home healthcare, the rise in popularity ofe-commerce, and emerging markets with harsh climates and
limited infrastructure. Pharmaceuticals themselves are alsochanging. In fact, it is expected that by 2018, seven of the top
Combating
‘Super-Agility’ of Counterfeiters in the
PHARMASUPPLY CHAINLeveraging industry best practices to protect consumer safety
Chip MeyersUPS vice president, corporate public affairs
Robin HookerUPS director of healthcare marketing
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 85/132
ANTI-COUNTERFEITING
June 2015 Twitter : @ContractPharma Contract Pharma 85
10 pharmaceutical drugs will be temperature-sensitive.4
To address these changes, the U.S. Congress enactedthe Drug Supply Chain Security Act (DSCSA) in 2014. On
the most basic level, the DSCSA calls for the establish-ment of an interoperable track-and-trace system wheremanufacturers would serialize their product, i.e. a uniquenumerical identifier. The legislation allows the serializa-tion process to develop within 10 years, but once in placeit should allow law enforcement to pinpoint where coun-terfeit product enters the supply chain with the goal ofintercepting and prosecuting traffickers. As serializationprogresses, new advancements such as increased adop-tion of mobile technologies by consumers will likely con-tinue to be game-changers. In this environment, valida-tion systems will need to be implemented, and they mustbe seamless.
Although anti-counterfeiting measures are being tak-en on a national level, there is still a long way to go glob-ally. In India—the world’s largest manufacturer of genericdrugs—adulterated drugs account for 25% of the drugsupply. In Africa, 40% of the drugs are counterfeit. Theopportunities for counterfeiters will only continue to rise
with the increased globalization of healthcare.
SUPER-AGILE AND SUPER-RISKY
Professor Hau Lee at Stanford coined the term “super-agility”to describe the nimble ability of counterfeiters to react to mar-ket opportunities and capitalize on legitimate brand equity.The agility counterfeiters have to exploit the brand reputation
of big pharmaceutical companies is real, fast-moving and hasthe inherent capability to be one step ahead. Anywhere there is brand cachet and high product demand,
counterfeit risks are high. Direct-to-patient advertising hasmade pharmaceuticals such as Humira and Abilify householdnames. It has also made consumers and practitioners betterpartners in fighting disease and chronic illness, but on the flipside, it gives counterfeiters more knowledge and opportunityto undermine consumer safety.
In today’s highly marketed pharmaceutical environment,consumers are inundated with information about drugsthrough broadcasted advertising and digital channels. In fact,by 2018, an estimated $2.2 billion will be spent on pharma-
ceutical and healthcare-related digital advertising in the U.S.alone.5 Counterfeiters are now leveraging increased brandrecognition among consumers via media and the internet tobring fake products into the drug supply.
Recently, the FDA alerted practitioners that counterfeit Bo-tox entered the U.S. market. The packaging is almost identicaland doses appear to be the same. A key difference is that themanufacturing date is not printed on the outer carton. Man-ufacturers and practitioners can’t rely on the fact that coun-terfeiters won’t start packaging the same way. Distinguishingcounterfeit drugs could become almost impossible without labtesting because of this super-agility.
COMBATING COUNTERFEITING
In the 1960’s, Charles Hummel introduced the idea of the “tyr-
anny of the urgent” to describe the tension between thingsthat are urgent and things that are important—and far toooften, the urgent wins. This concept can be applied to anti-counterfeiting. To succeed against counterfeiters, businessesmust think big-picture and long-term. The firms that will bemost effective will leverage anti-counterfeiting tactics to meetadditional business objectives such as returns and recalls, in-
ventory management and risk mitigation.Consider these five anti-counterfeiting best practices:• Tap into knowledge partners. Healthcare companies are
realizing they are not alone in the anti-counterfeiting battle. According to the most recent UPS Pain in the (Supply)Chain survey—which surveys healthcare logistics decision-makers globally on their top supply chain pain points andopportunities—65% of healthcare executives have usedlogistics and distribution partnerships to overcome chal-lenges accessing global markets and new customer bases.6 Companies that embrace collaboration to implement bettersupply chain visibility measures and thwart counterfeiterscan focus more on core business strategies.
• Engage legislators. As a collective voice, third party logis-tics providers, wholesalers and manufacturers can accom-plish a lot more. Through organizations like the Center forSafe Internet Pharmacies, the Pharmaceutical Technology
Association, the Healthcare Distribution Management Association, Rx360 and Fight the Fakes, the industry canmake legislators aware of pain points and concerns thatneed to be addressed. Firms must be more vocal aboutproblems they are facing. There needs to be some trans-parency to share best practices and new models in orderto enact real change. As a 3PL to the healthcare industry,UPS works to remove barriers and excess costs by gettinginvolved with anti-counterfeiting measures. UPS engages
legislative officials to impact policies and ensure there isa voice for what is important to our customers and the
“ Although anti-counterfeiting measures
are being taken on a national level, there isstill a long way to go globally. In India—the
world’s largest manufacturer of generic
drugs—adulterated drugs account for 25%
of the drug supply. In Africa, 40% of the
drugs are counterfeit. The opportunities for
counterfeiters will only continue to rise with
the increased globalization of healthcare.”
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 86/132
ANTI-COUNTERFEITING
86 Contract Pharma contractpharma.com June 2015
industry. UPS was also a champion of the Drug SupplyChain and Security Act.
• Understand global compliance. Businesses with littleunderstanding of regulatory laws across borders enablesuper-agile counterfeiters to reach markets more quicklyand effectively. Only 12% of senior logistics executivespolled by UPS reported they were satised with theircompanies’ performance in addressing the challenge ofregulatory compliance.6 Firms adding in-house regulatorystaff or plugging into regulatory experts have reported be-ing more successful on this front.
• Educate inwardly and outwardly. Educating all users ofthe supply chain, both internally and externally, is critical.
Implementing an ongoing educational program that worksacross the industry and engages all stakeholders—poli-cies and action committees, federal agencies, supply chainoperations, law enforcement—needs to be solid andtransparent. Ensuring that all parties understand emerg -ing economies and the compliance environment, operateoutside of silos and understand business goals will helpchip away at this complex problem.
• Stretch investments. Monetize the investment in compli-ance systems to hit other business goals such as recallsand expired pharma expenses. Companies that realizeDSCSA has big data value for inventory managementcould plug into that data and create micro shifts that
would move inventory away from existing channel part-ners within the supply chain and into areas where it will
move more quickly. Expired pharma-ceuticals is a huge revenue leakagethat companies face.
Having the ability to monitorproduct down to the pill bottle levelcould allow a rm to move inventoryin danger of expiring into the handsof their sales team, for example.They would have the ability to getthe supply into the hands of partiesinterested in using it more quickly.Ultimately the business value wouldbe running leaner inventory and lessexpired pharmaceutical products.
‘IT’S A PATIENT, NOT A PACKAGE’Mitigating risks in the pharmaceu-tical supply chain is essential, espe-cially as new healthcare demandscontinue to grow globally. Compa-nies should not underestimate thepotential impacts of counterfeiterson their business and should ensurethat their company hasn’t fallen intoa state of complacency.
Collaboration is key. UPS’s man-tra for healthcare shipments is, “It’sa patient, not a package,” and the
DSCSA and drug makers embody the same principle. Thismeans that each bottle of medication or syringe represents aperson with specialized and important health needs.
Let’s stay invigorated and engaged as an industry to thwartthe impacts of counterfeiters. Let’s make it difcult, painfuland unprotable for counterfeiters, and let’s do it for the pa-tient on the other end. This is how we can all win the battle tokeep our global healthcare supply chain safe. CP
References
1. Source: Fake pharmaceuticals are a $75 billion global industry, by Market-
place World
2. Source: General Information on Counterfeit Drugs, World Health Organi-
zation3. Source: The Counterfeit Drug Problem, by Pharmaceutical Research and
Manufacturers of America
4. Source: World Preview 2013, Outlook to 2018: Returning to Growth, by
EvaluatePharma
5. Source: Healthcare and pharmaceutical industry digital advertising spend-
ing in the United States from 2011 to 2018, by Statista
6. Source: UPS Pain in the (Supply) Chain survey, conducted by TNS
CHIP MEYERS is vice president of corporate public af-
fairs for UPS.
ROBIN HOOKER is director of healthcare marketing
for UPS.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 87/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 88/132
88 Contract Pharma contractpharma.com June 2015
E ven primary packaging that has been manufactured andstored properly can release substances into the drug for-mulation. For this reason, pharmaceutical manufacturers
are required to conduct extensive studies on “Extractables andLeachables”(E&L). The compounds found in such studies de-pend not only on the ingredients of the packaging materials,such as antioxidants, plasticizers, antistatic agents, catalysts
and cross-linking agents, but also reflect how the packagingcomponents were treated. This study demonstrates the influ-
ence of the type of sterilization on the resulting extractionprofiles based on the example of bromobutyl rubber stoppers.This demonstrates that more than validated analysis is essen-tial to obtain meaningful results. The correct study design andcomprehensive know-how on the entire life cycle of commer-cially available primary packaging—from the raw materials toprocessing and use—are crucial to determining the origin of
found substances.Packaging systems often consist of many different compo-
SCHOTT Pharma Services
Thorsten Sogding, Daniel Canton, Daniel Haines, Uwe Rothhaar
How Sterilization of
PRIMARY PACKAGINGInfluences the Results of E&L Studies
As the demands that are being placed on the quality and stability of medications contin-ue to increase, the interactions that take place between the primary packaging container and filled drug product are becoming increasingly important
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 89/132
STERILIZATION OF PRIMARY PACKAGING
June 2015 Twitter : @ContractPharma Contract Pharma 89
nents and materials, like glass, metal, plastic, rubber, adhe-sives or lubricants. Extractables are determined by subjectingthe packaging material to aggressive conditions such as dif-ferent solvents at elevated temperature for extended times,resulting in substances that elute from these packaging sys-tems. By contrast, leachables are substances that migrate intoa pharmaceutical formulation under normal preparation and
storage conditions. A study on extractables represents a worstcase scenario to identify as many substances as possible thatcould conceivably enter into the medication.
Leachables are usually, but not always, a subgroup of ex-tractables; for instance, a substance contained in the drugproduct formulation can react with a constituent contained inthe packaging and form an entirely new species that is lateridentified in a leachable study, but wouldnot be present in an extractable study.
Pharmaceutical manufacturers are re-quired to perform E&L studies to excludepossible harmful interactions between thepackaging materials and the medication.
The primary sources of organic extractablesand leachables are elastomeric and poly-meric materials like rubber and plastics,because they contain additives that allowfor them to have beneficial properties, suchas greater chemical stability and increasedmanufacturing yield. Here, it is impor-tant to know the exact composition of thepackaging material in order to be able toperform E&L studies efficiently. Neverthe-less, this type of information often cannotbe obtained from the material suppliersdue to the complexity of the manufactur-
ing processes, desire to protect their ownprocess know-how, and potential upstream
changes in raw materials. To address this is-sue, most testing laboratories that performE&L studies have built up comprehensive
databases on materials and additives.Most people are less aware of the fact
that the original composition of the packag-ing system alone is not mainly responsiblefor what substances are found as E&L. Oneadditional influencing factor is the steriliza-tion process. As is well known, gamma ir-radiation can lead to polymer and additivedegradation (e.g. crosslinking and scission),
whereas steam sterilization can alter themechanical and chemical properties as well(e.g. softening).
The following study is focused on
changes in the E&L profiles of commonbromobutyl stoppers caused by differentsterilization procedures.
REGULATORY REQUIREMENTSPharmaceutical companies need to conductleachable studies to prove that no harmful
substances will penetrate from the primary packaging into thedrug during appropriate use of the drug in the respective dos-age under normal storage conditions. This procedure is speci-fied in a number of guidelines or regulations for the UnitedStates/Canada1-6 and for Europe.7-8
It is important for pharmaceutical manufacturers to be able
to come up with this proof as cost effectively as possible. Ex-tractable studies help them to achieve this goal because theyenable the toxicological assessment of possible Leachablesand identity the number of substances that need to be tested
with validated methods in the subsequent leachable stud-ies. The flow charts from recommended E&L study plans areshown in BPSA’s Extractables and Leachables Subcommittee,
FIGURE 1: Exemplary HS-GC/MS-chromatograms (140 °C / 45 min) of unsterilized (center),
steam-sterilized (below) and gamma-sterilized (above) sample D.
FIGURE 2: Concentration of isobutene, bromomethane, and acetone out of sample A after different
sterilization procedures found by HS-GC/MS after incubation at 140 °C (45 min).
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 90/132
STERILIZATION OF PRIMARY PACKAGING
90 Contract Pharma contractpharma.com June 2015
“Recommendations for Extractables and Leachables Testing,Part Two: Executing a Program,” BioProcess Int. 6(1) 2008:44-52; and “Best Practices for Extractables and Leachables inOrally Inhaled and Nasal Drug Products: An Overview of the
PQRI Recommendations,” by Norwood, Paskiet and RubertoPharmaceutical Res. 2008; 25(4):727-739.9-10
Toxicological assessments are performed for substancesfound above the Analytical Evaluation Threshold (AET). 9 This
AET value is expressed as the amount of given extractableper mass of component or leachables per drug product and
is determined with respect to the Permitted Daily Exposure(PDE), known from toxicological exposure studies. If toxico-
TABLE 1: Qualitative results of HS-GC/MS (VOC) analyses of samples A to E upon various sterilization processes.
Sample Not Sterilized Steam-Sterilized Gamma-Sterilized Gamma- and Steam-Sterilized
A
Significant signals:
- Bromomethane
- Acetone
- tert-Butanol
- Methylcyclopentane
- C13H24 and C21H40 cyclic rubber oligomers
and brominated derivates
- Various hydrocarbons and unidentified
compounds
Significant signals:
- Bromomethane
- Acetone
- tert-Butanol
- Methylcyclopentane
- C13H24 and C21H40
cyclic rubber oligomers and
brominated derivates
- Various hydrocarbons and
unidentified compounds
New significant signals:
- Isobutene
- Diisobutene
- Various saturated and unsaturated
hydrocarbons
Increasing signals:
- Acetone
- Bromomethane
- Various unidentified compounds (e.g. rubber
fragments)
General observations:- Compared to gamma-sterilized sample, no
new signals observed
- Decreasing intensity of most signals, espe-
cially low boiling substances (e.g. isobutene or
bromomethane)
General observations:
- Compared to gamma-sterilized sample, no
new signals observed
- Slightly decreasing intensity of some signals,
especially low boiling substances (e.g. isobutene
or bromomethane)
B
Significant signals:
- Acetone
- 2- and 3-Methylpentane- Methylcyclopentane
- C13H24 and C21H40 cyclic rubber oligomers
and brominated derivates
- Various hydrocarbons and unidentified
compounds
General observations:
- No new signals observed
- Slightly decreasing
intensity for some single
signals, especially low boiling
substances (e.g. acetone or
methylpentane)
New significant signals:
- Isobutene
- Diisobutene
- Bromomethane
- Various saturated and unsaturated
hydrocarbons
Increasing signals:
- Acetone
- Various hydrocarbons and some unidentified
compounds (e.g. rubber fragments)
General observations:
- Compared to gamma-sterilized sample, nonew signals observed
- Slightly decreasing intensity of some signals,
especially low boiling substances (e.g. isobutene
or bromomethane)
C
Significant signals:
- Bromomethane
- Hexane
- Cyclooctane
- Some unidentified compounds, probably rubber
oligomers or fragments
General remark:
- Lowest amount of VOC compared to othersamples
General observations:
- No new signals observed
- Decreasing intensity of
most signals, especially
low boiling substances (e.g.
bromo-methane, hexane or
cyclooctane)
New significant signals:
- Isobutene
- Diisobutene
- Various hydrocarbons and some unidentified
compounds (e.g. rubber fragments)
Increasing signals:
- Bromomethane
- Various hydrocarbons and unidentified com-pounds (e.g. rubber fragments)
New significant signals:
- Isobutene
- Diisobutene
- Various hydrocarbons and some unidentified
compounds (e.g. rubber fragments)
Increasing signals:
- Bromomethane
- Various hydrocarbons and unidentified com-pounds (e.g. rubber fragments)
D
Significant signals:
- Bromomethane
- Acetone
- C13H24 and C21H40 cyclic rubber oligomers
and brominated derivates
- Various hydrocarbons and unidentified
compounds
General observations:
- No new signals observed
- Slightly decreasing intensity
of some signals, especially
low boiling substances (e.g.
bromomethane or not further
specified hydrocarbons)
New significant signals:
- Isobutene
- Diisobutene
- Various saturated and unsaturated
hydrocarbons
Increasing signals:
- Acetone
- Bromomethane
- Various unidentified compounds (e.g. rubber
fragments)
General observations:
- Compared to gamma-sterilized sample, no
new signals observed
- Decreasing intensity of most signals, espe-
cially low boiling substances (e.g. isobutene or
bromomethane)
E
General observations:
- Compared to gamma-sterilized sample, no new
signals observed
- Decreasing intensity of most signals, espe-
cially low boiling substances (e.g. isobutene or
bromomethane)
General observations:
- No new signals observed
- Decreasing intensity of most
signals, especially low boiling
substances (e.g. acetone or
bromomethane)
New significant signals:
- Isobutene
- Diisobutene- Various saturated and unsaturated
hydrocarbons
Increasing signals:
- Acetone
- Bromomethane
- Various unidentified compounds (e.g. rubber
fragments)
General observations:
- Compared to gamma-sterilized sample, no
new signals observed
- Decreasing intensity of most signals, espe-
cially low boiling substances (e.g. isobutene or
bromomethane)
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 91/132
STERILIZATION OF PRIMARY PACKAGING
June 2015 Twitter : @ContractPharma Contract Pharma 91
logical data are not available, then the AETcan be developed using the Safety ConcernThreshold (SCT)10 of 0.15 μg/day along with
the dosing regimen.The guidelines and regulations men-
tioned do not include any specific instruc-tions on how to perform E&L studies,however. A working group at the ProductQuality Research Institute (PQRI) based in
Arlington, VA, has developed detailed rec-ommendations on a special group of phar-maceutical products in which the risk of in-teractions with the packaging is consideredto be particularly high. Some examples arepublished with respect to the dosage form:This includes nasal sprays, oral inhalation
aerosols12
and parenteral liquids13
, as well asbest practices for representative parenteraland ophthalmic packaging materials14. TheUSP is in the process of finalizing guidancechapters for extractables <USP 1663>6 and leachables <USP1664>.7
Without going into details, the following aspects of extract-able studies are particularly important:1. Extraction should take place using a plurality of solvents
of different polarities and using several different types ofextraction methods. Prior working knowledge of pharma-ceutical formulations and packaging materials can help tominimize these efforts and choose the right solvents and
methods.2. Several different analytical techniques should be em-
ployed. Common suitable methods are: Headspace GC/MS (gas chromatography/mass spectrometry) for volatileExtractables, GC/MS for semi-volatile, LC/MS (liquidchromatography/mass spectrometry) for non-volatileor polar Extractables, and ICP-MS (inductively coupledplasma/mass spectrometry) for analyzing elemental impu-rities, e.g. metals from organic pigments or polymerizationcatalysts. With the increasing regulatory requirements, theanalytical capabilities need to be improved and updated inshort cycles especially with respect to lower detection andquantification limits.
3. Extensive experience, appropriate databases and referencematerials, high qualified laboratory staff and proper qual-ity control helps to interpret the data correctly to draw theproper conclusions and avoid mistakes.
After the extractable studies have been performed, sub-stances (above AET) are selected on the basis of a toxicologi-cal assessment. For this selection suitable methods need tobe developed and validated for a subsequent leachable studyaccording to ICH15. Here, the leachable profile of the phar-maceuticals stored is detected using these validated methodsin appropriate intervals—for example, 1, 3, 6, 12, 18, 24, 36months—under ICH conditions. Furthermore, screenings are
performed in parallel with the same methods to detect anypossible modified or derived substance.
STUDY DESIGN ON THE IMPACT OF STERILIZATION
The study was designed to investigate the impact of varioussterilization techniques onto the extraction profile of com-mercially available stoppers made of bromobutyl rubber foruse in syringes. The sterilization of the stoppers is mandatorybefore they can be used for medical purposes. Three variantsof sterilization were chosen: Steam sterilization (autoclaving,121 °C for 30 minutes), gamma sterilization (40 kGy), and acombination of the two techniques gamma-irradiation (first)
and steam-sterilization (second).The study included five different stoppers from three dif-
ferent manufacturers. A set of state of the art chromatographictools from Shimadzu (GCMS-QP210 Ultra, LCMS-IT-TOF
with ESI and APCI source) was used to conduct the analysesof the Extractables according to the following procedure:1.Volatile organic compounds (VOC) were analyzed by
headspace GC/MS after incubation of about 2 g of stoppermaterial at 140°C for 45 min. Quantification was per-formed semi-quantitative against the relative response ofthe internal standard toluene-D8.
2. Semi-volatile (SVOC) and non-volatile (NVOC) organiccomponents were determined after exhaustive reflux
extraction of the stopper for 8 hours with three differentsolvents (100 cm2 stopper surface area per 200 mL). Thesolvents used were isopropanol (IPA), dichloromethane(DCM) and ultrapure water. The aqueous extracts weretransferred to DCM extracts by liquid-liquid extraction.The analysis of all of these extracts was conducted usingGC/MS and LC/MS. Quantification was performed semi-quantitative for GC/MS (SVOC) using the response factor(RF) of the internal standard 2-fluorobiphenyl. Quantita-tive values for LC/MS (NVOC) were calculated using theindividual substance response factor derived from refer-ence material measurements.
This procedure was applied to stoppers without steriliza-tion (reference) and after sterilization with the variants de-
FIGURE 3: Concentration of DCM-extractable BHT, Irganox 1010, or Irganox® 1076 out of samples A - C
after different sterilization procedures found by LC/MS.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 92/132
STERILIZATION OF PRIMARY PACKAGING
92 Contract Pharma contractpharma.com June 2015
TABLE 2: Qualitative results of GC-MS (SVOC) and LC/MS (NVOC) analyses of different extracts of samples A to E upon various sterilization processes
(general statements).
Sample Not Sterilized Steam-Sterilized Gamma-Sterilized Gamma- and Steam-Sterilized
A
Significant signals:
- Butylated hydroxytoluene
- Palmitic and stearic acid
- C13H24 and C21H40 cyclic
rubber oligomers and bromi-
nated derivates
- Various unidentified com-
pounds, e.g. rubber fragment or
additive degradation products
General observations:
- Tendency for increasing
amount of extractable SVOC
Increasing signal:
- Butylated hydroxytoluene
(slightly)
Decreasing signals:
- Palmitic and stearic acid
(slightly)
General observations:
- No significant change in sum of extractable SVOC compared to
unsterilized sample
New significant signals:
- Heptadecane
- Various unidentified compounds, e.g. rubber fragments
Decreasing signals:
- Butylated hydroxytoluene (loss of more than 50 %)
Increasing signals:
- Palmitic and stearic acid (slightly)
General observations:
- No significant new signals observed
- Slight tendency for decreasing sum
of SVOC observed (compared to only
gamma-sterilized sample)
Decreasing signals:
- Palmitic and stearic acid (slightly; com-
pared to gamma-sterilized sample)
Increasing signal:
- Butylated hydroxytoluene (slightly; com-
pared to only gamma-sterilized sample)
B
Significant signals:
- Irganox® 1010
- Palmitic and stearic acid
- C13H24 and C21H40 cyclic
rubber oligomers and bromi-
nated derivates
- Various unidentified com-
pounds, e.g. rubber fragment or
additive degradation products
General observations:
- Slight decrease of extract-
able SVOC observed
- No significant new signals
were found
Decreasing signals:
- Palmitic and stearic acid
(slightly)
General observations:
- Slight increase of extractable SVOC observed
New significant signals:
- Pentadecane
- Heptadecane
Decreasing signals:
- Irganox® 1010 (loss of more than 60 %)
Increasing signals:
- Palmitic and stearic acid (slightly)
- 7,9-Di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione
(aqueous extract)
General observations:
- No significant new signals observed
- Slight tendency for decreasing sum
of SVOC observed (compared to only
gamma-sterilized sample)
Decreasing signals:
- Palmitic and stearic acid (slightly,
depending on solvent)
- 7,9-Di-tert-butyl-1-oxaspiro(4,5)
deca-6,9-diene-2,8-dione (aqueous
extract)
C
Significant signals:
- Irganox® 1076
- 2-Chloro-4-tert-pentylphenol- Palmitic and stearic acid
- C13H24 and C21H40 cyclic
rubber oligomers and bromi-
nated derivates
- Various unidentified com-
pounds, e.g. rubber fragment or
additive degradation products
General observations:
- Slight decrease of extract-
able SVOC observed
- No significant new signals
were found
Decreasing signals:
- Palmitic and stearic acid
(slightly)
General observations:
- Slight decrease of extractable SVOC observed
New significant signals:- Heptadecane
- Unsaturated cyclic hydrocarbons (e.g. from rubber degradation)
Decreasing signals:
- Irganox® 1076 (loss of more than 75 %)
Increasing signals:
- Palmitic and stearic acid
General observations:
- No significant new signals observed
- Sum of SVOC is comparable to unsteril-
ized material
D
Significant signals:
- Butylated hydroxytoluene
- Palmitic and stearic acid
- C13H24 and C21H40 cyclic
rubber oligomers and bromi-
nated derivates- Various unidentified com-
pounds, e.g. rubber fragment or
additive degradation products
Not tested
General observations:
- Slight increase of extractable SVOC observed
New significant signals:
- Heptadecane
- Various unidentified compounds, e.g. rubber fragments
Decreasing signals:
- Butylated hydroxytoluene (loss of more than 50 %)
Increasing signals:
- Palmitic and stearic acid (slightly)
General observations:
- No significant new signals observed
- Slight tendency for decreasing sum
of SVOC observed (compared to only
gamma-sterilized sample)
Decreasing signal:
- Palmitic and stearic acid (slightly; com-
pared to only gamma-sterilized sample)
E
Significant signals:
- Butylated hydroxytoluene
- Palmitic and stearic acid
- C13H24 and C21H40 cyclic
rubber oligomers and bromi-
nated derivates
- Various unidentified com-
pounds, e.g. rubber fragment or
additive degradation products
General observations:
- Tendency for increasing
amount of extractable SVOC
Increasing signal:
- Butylated hydroxytoluene
(slightly)
Decreasing signals:
- Palmitic and stearic acid
(slightly)
General observations:
- Slight increase of extractable SVOC observed
New significant signals:
- Heptadecane
- Various unidentified compounds, e.g. rubber fragments
Decreasing signals:
- Butylated hydroxytoluene (loss of more than 50 %)
Increasing signals:- Palmitic and stearic acid (slightly)
General observations:
- No significant new signals observed
- Slight tendency for decreasing sum
of SVOC observed (compared to only
gamma-sterilized sample)
Decreasing signals:
- Palmitic and stearic acid (slightly; com-
pared to only gamma-sterilized sample)
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 93/132
STERILIZATION OF PRIMARY PACKAGING
June 2015 Twitter : @ContractPharma Contract Pharma 93
scribed. The substances detected in thechromatograms and the respective frag-mentation patterns were identified using a
combination of commercially available da-tabases and our internal reference databaseon packaging products and additives.
SUMMARY OF THE RESULTS
Because of the study design—5 stoppers,3 different sterilization variants, 3 solventsand headspace—a large data set was gener-ated that cannot be fully reported here; (thefull study can be obtained by request fromthe authors). Therefore, a comprehensivesummary is given for each stopper type (A
– E) in Tables 1 and 2 and some exemplary
chromatograms and evaluation diagramsfor selected extractables are depicted inFigures 1-4.
General observations• The total content of organic compo-
nents (VOC, SVOC, and NVOC) deviates quite significant-ly between various bromobutyl stoppers from differentmanufacturers.
• In most cases, acetone (residual solvent or rubber oxida-tion product) and bromomethane (radical rubber degrada-tion product) can be found prior to any sterilization. Theirconcentration significantly increases upon gamma-steril-ization (Fig. 2).
• The total amount of SVOC from samples A – E stronglydepends on the applied extraction solvent and method.Concerning extraction of rubber oligomers, rubber degra-dation products and antioxidants extraction in dichloro-methane is most efcient. In most cases, extraction of fattyacids—e.g. from palmitic or stearic acid derivates—seemsto be more efficient using isopropanol—probably depend-ing on kind of derivate (e.g. zinc stearate, etc.) containedin rubber formulation.
• A steric hindered phenolic antioxidant can be found inall stoppers—e.g. BHT (sample A, D, E), Irganox® 1010(sample B) or Irganox® 1076 (sample C). Extraction ofthese antioxidants was most pronounced using dichloro-
methane as extraction solvent (Fig. 3).
Observations demonstrating the impact of sterilization• Sum of VOC out of all samples signicantly increases upon
gamma-sterilization.• Signicant amounts of isobutene and other unsaturated
hydrocarbons (e.g. rubber pyrolysis products) out of allstoppers can be observed only after gamma-sterilization(Fig. 1-2).
• Generally, the sum of VOC decreases upon steam-ster-ilization of unsterilized and gamma-sterilized stoppers.That effect is also observed for single substances likeisobutene, bromomethane, and acetone. (Fig. 2)
• The concentration of extractable antioxidants out of allsamples significantly decreases upon gamma-sterilization
(loss of 50 % and more). Steam-sterilization had no sig-nicant inuence on antioxidant concentration. In somecases, a slight tendency for an increasing concentration ofextractable antioxidants can be estimated (Fig 3).
• Extractable heptadecane—as well as some other saturatedand unsaturated hydrocarbons—out of all samples can befound only upon gamma-sterilization and gamma—withadditional steam-sterilization (Tab. 1).
• In general, the total amount of extractable palmitic andstearic acid (fatty acids) out of all stopper types increasedupon gamma-irradiation. In most cases a more or lesspronounced decrease of extractable fatty acids can beobserved after steam-sterilization of unsterilized and gam-ma-sterilized. This observation was strongest for extractsin DCM and ultrapure water. The use of ultrapure waterseems to result in extraction of (most probably) surface-orientated fatty acids, rather than extraction out of thedepth of the material.
• After gamma-sterilization of sample B, the concentra-tion of water-extractable 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione—one possible Irganox® 1010
degradation product—increases. This substance should beestimated as a potential Leachable, especially into aque-ous drug formulations. (Fig. 4).
• A signicant inuence or trend of sterilization on theconcentration of extractable cyclic rubber oligomers—e.g.C13H24 and C21H40—was not observed for any exam-ined sample (Tab. 2).
As exemplary shown in Figure 1 (only VOC), compounds were found in different amounts depending on the steri liza-tion method. In a subsequent toxicological evaluation, any ofthose Extractables would be assessed by reviewing availabletoxicological data and coming up with a realistic PDE limit
based on exposure routes (oral, inhalation, dermal, ophthal-mic, injection). To show the general procedure acetone can be
FIGURE 4: Concentration of water-extractable Irganox 1010 and degradation products out of sample B
after different sterilization procedures found by LC/MS or GC/MS (depending on analyte).
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 94/132
STERILIZATION OF PRIMARY PACKAGING
94 Contract Pharma contractpharma.com June 2015
taken as an example, defined by USP <467> as a Class 3 re-sidual solvent16 , the PDE is limited to not more than 50 mg perday; the maximum amount after gamma sterilization found in
this study was 2.5 µg / stopper, which demonstrate that ac-etone is not critical in this case. Applying the same procedureonto other extractables (e.g. bromo organic substances) maygenerate a different risk profile.
CONCLUSION
The results of the study clearly demonstrate that sterilizationof polymer components influences the respective extractionprofile quite significantly. Thus, we can expect that the amountand the kind of leachables from a primary packaging prod-uct that comes into contact with a pharmaceutical formulationalso depends on the sterilization processing.
It was observed that some of the stopper additives, like anti-
oxidants, were degraded upon gamma sterilization. This mightinfluence the stability of the base polymer material and lead toformation of pyrolysis or radical degradation products of thebasic polymer, e.g. formation of isobutene or bromomethane.Conversely, the steam sterilization seems to have a “cleaning”effect with regards to VOC, some SVOC and fatty acids.
While this kind of study is useful for giving trends, it istoo general to fulfill the specific needs of an individual drugproduct/container system. Therefore, customized E&L inves-tigations, considering the drug composition and processing as
well as the packaging properties, should be executed on thebasis of best practices extractables guidelines. CP
References1. US Government Printing Office, Equipment Construction, “Code of Fed-
eral Regulations, Food and Drugs,” Title 21, Part 211.65.
2. FDA Guidance for Industry “Container Closure Systems for Packaging
Human Drugs and Biologics,” May 1999.
3. FDA Guidance for Industry “Nasal Spray and Inhalation Solution, Sus-
pension and Spray Drug Products,” July 2002.
4. Draft FDA Guidance for Industry “Metered Dose Inhaler (MDI) and
Dry Powder Inhaler (DPI) Drug Products,” October 1998.
5. European Commission, “Good Manufacturing Practices, Medicinal
Products for Human and Veterinary Use,” Volume 4, 1998.6. USP <1663> Assessment of Extractables associated with Pharmaceuti-
cal Packaging/Delivery Systems
7. USP <1664> Assessement of Drug Product Leachables associated with
Pharmaceutical Packaging/Delivery Systems
8. EMEA Guideline on “Plastic Immediate Packaging Materials,” Decem-
ber 2005.
9. BPSA Extractables and Leachables Subcommittee, “Recommendations
for Extractables and Leachables Testing, Part Two: Executing a Pro-
gram,” BioProcess Int. 6(1) 2008: 44-52.
10. Norwood DL, Paskiet D, Ruberto M, et al., “Best Practices for Extract-
ables and Leachables in Orally Inhaled and Nasal Drug Products: An
Overview of the PQRI Recommendations,” Pharmaceutical Res. 2008;
25(4):727-739.11. Scott Keith “Extractables and Leachables Testing of Polymer Device
Components” 2007 Proc. Pharm. Polym. Paper 12, June 20-21 Basel
Switzerland.
12. Ball D, Blanchard J, Jacobson-Kram D, et al. “Development of Safety
Qualification Thresholds and Their Use in Orally Inhaled and Nasal
Drug Product Evaluation,” Toxicol Sci. 2007; 97(2):226-236.
13. Paskiet D, Jenke D, Ball D, Houston C, Norwood D, Markovic I. “The
Product Quality Research Institute (PQRI) Leachables and Extractables
Working Group Initiatives for Parenteral and Opthalmic Drug Product
(PODP)” PDA J. Pharm. Sci. Technol. 2013, 67(5), 430-447.
14. Jenke D, Castner J, Egert T, Feinberg T, Hendriker A, Houston C, Hunt
DG, Lynch M, Shaw A, Nicholas K, Norwood DL, Paskiet D, Ruberto
M, Smith EJ, Holcomb F. “Extractables Characterization for Five Ma-terials of Construction Representative of Packaging Systems Used for
Parenteral and Opthalmic Drug Products” PDA J. Pharm. Sci. Technol.
2013, 67(5), 448-511.
15. www.ich.org (accessed 2/6/2014).
16. http://www.usp.org/sites/default/files/usp_pdf/EN/USPNF/general-
Chapter467Current.pdf (accessed 2/6/2014).
COMING NEXT MONTH
TOP COMPANIES REPORT:
Contract Pharma’s
Annual Report on the
Top 25 Pharma/Biopharma firms
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 95/132
June 2015 Twitter: @ContractPharma Contract Pharma 95
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 96/132
96 Contract Pharma contractpharma.com June 2015
$395 ATTENDEE FEE INCLUDES ALL CONFERENCE SESSIONS,160-COMPANY EXHIBIT HALL, BREAKFAST, LUNCH AND NETWORK RECEPTION!
14th Annual Contracting & OutsourcingConference & Tabletop Exhibition!
The premier Pharma/Biopharma outsourcing event, Contracting & Outsourcing, will be held on September
17-18, 2015 at the Hyatt Regency New Brunswick, NJ, located in the heart of New Jersey’s pharmaceutical
industry! The tabletop exhibition will be one day only on Thursday, September 17th with additional
conference sessions held on Friday, September 18th.
CONFERENCE SPEAKERS INCLUDE:Scott GottliebLeading Expert in Health Policy and ResidentFellow, American Enterprise Institute
Kurt WieditzDirector/Team Leader Global External Supply,Pfizer
Douglas KovacsSupervisory Consumer Safety Officer, FDA
Jim MillerPresident, PharmSource Information Services, Inc.
Ajai ChaudharyDirector & External Capabilities Delivery Lead,Merck
John AvellanetFounder & Principal, Cerulean Associates
TOPICS INCLUDE:
Trends in the Contract Services Industry
Forces Driving the Transformation of
Healthcare
Quality Agreements with CMOs
Inspection Trends with CMOs
R&D Outsourcing Trends
Quality/Compliance in Tough Economic Times
Serialization Track & Trace
Globalization and Drug Discovery
Outsourcing
ONE-DAY TABLETOP EXHIBITION: SEPTEMBER 17!The Contracting & Outsourcing 2015 Conference and Tabletop Exhibition provides a venue for easy,
informal discussions among outsourcers and potential contractors for manufacturing, packaging, distribution,
laboratory services, and more. Domestic and international contractors will be present. The one-day Tabletop
Exhibition on September 17 offers high-quality contact between top decision-makers and contractors. Inprevious years, exhibitors have said that they made more qualified contacts in one day at Contracting &
Outsourcing than in several days at larger exhibitions.
The Venue
Hyatt Regency New Brunswick
The conference room rate is $199 single/double per night.
2 Albany Street, New Brunswick, NJ 08901
Tel: 888-421-1442
Web: newbrunswick.hyatt.com
conference.contractpharma.com • www.regonline.com/cp2015
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 97/132
June 2015 Twitter : @ContractPharma Contract Pharma 97
THURSDAY, SEPTEMBER 17
CONFERENCE AGENDA
September 17th and 18th, 2015 • Hyatt Regency, New Brunswick, NJ
14th Annual
2015 CONTRACTING ANDOUTSOURCING CONFERENCE
AND TABLETOP EXHIBITION
8:30-9:15 Continental Breakfast
9:15-9:20 Opening remarks Moderator Dr. Frank A. Chrzanowski
9:20-10:00 CONFERENCE KEYNOTE Scott Gottlieb • American Enterprise Inst. Forces Driving the Transformation of Healthcare
10:00-11:15 Mid-morning break in Exhibit Hall
11:15-12:00 FDA KEYNOTE Quality Agreements with CMOs TBD • CDER/FDA (invited)
12:00-1:30 Luncheon in Exhibit Hall
1:30-2:15 PFIZER KEYNOTE Serialization Track & Trace Kurt Wieditz • Pfizer
2:15-3:00 Trends in the Contract Services Industry Jim Miller • Pharmsource
3:00-4:00 Break in Exhibit Hall
4:00-5:15 Networking and Cocktail Reception
7:30-8:30 Continental Breakfast
8:30-9:15 Quality and Compliance in Tough Economic Times John Avellanet • Cerulean Associates
9:15-9:45 FDA KEYNOTE Douglas Kovacs • FDA NJ Inspection Trends with CMOs
9:45-10:00 Mid-morning Break
10:00-10:30 Effects of Globalization on Drug Discovery Outsourcing Ajai Chaudhary • Merck
10:30-11:15 R&D Outsourcing Panel Participants: Pfizer, Teva (more TBD)
11:15-11:45 TBD TBD
11:45-12:00 Closing remarks Moderator Dr. Frank A. Chrzanowski
*speakers, topics and timeline subject to change
FRIDAY, SEPTEMBER 18
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 98/132
98 Contract Pharma contractpharma.com June 2015
14th Annual Contracting & OutsourcingConference & Tabletop Exhibition!
The premier Pharma/Biopharma outsourcing event, Contracting & Outsourcing, will be held on September
17-18, 2015 at the Hyatt Regency New Brunswick, NJ, located in the heart of New Jersey’s pharmaceutical
industry! The tabletop exhibition will be one day only on Thursday, September 17th with additional
conference sessions held on Friday, September 18th. Thank you to our 2015 Conference Sponsors!
Exhibitors3C! Packaging
A&Z Pharmaceutical Inc
AbbVieABC Laboratories
Advanced Analytical Testing Labs
Advantar Laboratories, Inc.
AEK Packaging
Aenova
AI BioTech
Alliance Contract Pharma
Althea CMO
Andler South CorporationAnovaFill
Apex Graphics
Aphena Pharma Solutions
ARx, LLC
Ascendia Pharmaceuticals
Asterand Bioscience
AustarPharma, LLC
Avomeen Analytical Services
Baxter (BioPharma Solutions)
Bellwyck Packaging
Biddle Sawyer
Bilcare Research Inc.
BioSurplus, Inc.
Boston Analytical
Camargo Pharmaceutical Services
Catalent Pharma SolutionsCharles River
Chemic Laboratories, Inc.
Chemical Solutions Ltd.
Cirrus, a Kemwell company
Citra LaboratoriesCoating Place Inc.Coldstream Laboratories, Inc.Constantia Flexibles
Contract Pharmaceuticals LimitedCook PharmicaCorden Pharma
CoreRx, Inc
Cytovance Biologics, Inc.
Dalton Pharma Services
DPT LaboratoriesEi - A Pharmaceutical Solutionworks
Emergent BioSolutions, Inc.Enco Pharmaceutical Development
Eurofins Lancaster Laboratories
EuTech Scientific Services, Inc.
FAREVA
Federal Equipment Company
Fette Compacting America, Inc.
Formex LLC
Formulated Solutions
Fresenius Kabi Product Partnering
Frontage Laboratories, Inc.
Fujifilm Diosynth Biotechnologies
Future Pak, Ltd.
Gateway Analytical
Gibraltar Laboratories Inc.
Glatt Air Techniques, Inc.
GlaxoSmithKline
Grand River Aseptic ManufacturingGRIFOLS INTERNATIONAL, S.A.
Groupe Parima, Inc.
H&M Analytical Services
Halo PharmaceuticalHetero CPS
Horizon Pharmaceuticals, Inc.
Hospira One 2 OneHowell Packaging
IGI Labs
Impact Analytical
Importfab Inc
Intergel Pharmaceutics
INTERPHEX
Irvine Pharmaceutical ServicesJames Alexander Corp.
Jeiven Pharmaceutical Consulting
JH Bertrand Inc
Jones Contract Packaging ServicesJubilant HollisterStier
Kamat Pharmatech LLC
KORSCH America, Inc.
Lifecore Biomedical
LSNE Contract Manufacturing
Lyophilization Technology, Inc.
MedPharm Ltd.
Metrics Contract Services
Mikart, Inc.
MJS Packaging
Norwich Pharma Services
O.Berk Company
Pace Analytical Life Sciences, LLC
Pacific BioLabs
Packaging Coordinators, Inc.Patheon
Perritt Laboratories
PfizerPharma International
Pharma Packaging Solutions
Pharma Spray Drying, Inc.
Pharma Tech IndustriesPharmasol Corporation
Pharmatek
Pii
Pillar5 Pharma Inc.
Piramal Healthcare
Platinum Press
PYRAMID Laboratories, Inc.
Q Laboratories, Inc.
QS Pharma
QuaDPharma, LLCQuality Chemical Laboratories
Quantex Laboratories
QuickLabel Systems
Recipharm AB
Reed-Lane, Inc.
Reig Jofre group
Robertson Microlit Laboratories Inc.
Ropack Inc.Rottendorf Pharmaceuticals Inc
Rovi Contract Manufacturing
Rx Pharma-Pack, Inc.
SGS Life Science ServicesSharp Packaging Services
Siegfried (previously Alliance Medical
Products)
SNOWBELL MACHINES PVT LTD
Source BioScience
Sovereign Pharmaceuticals, LLC
Sterigenics
Tarmac Products Inc
Tedor Pharma Inc.
Tekni-Plex
Tergus Pharma
tesa Labtec GmbH
Therapure Biopharma Inc.Time-Cap Labs, inc.
Trillium Health Care Products
UPM Pharmaceuticals, Inc.
Ursatec Verpackung - GmbH
Vetter Pharma International GmbH
VMRD
VxP Pharma
WellSpring Pharma ServicesWest Pharmaceutical Services
WHEATON
Whitehouse Laboratories
XcelienceZyleris PharmaTech
$395 Attendee Fee includes all Conference Sessions & Exhibit Hall,
breakfast, lunch and Networking Reception!Register online at www.regonline.com/cp2015
Services ervic
a So ut onsa ons verer
a orator es, Inc.a or
o ut ons Lt .o ut ons Lt .
mwe company mpa
ator es e Inc.e Inc.
IncInc
ntergel PharmaceuticsPha ics
INTERPHEXEX
Irvine Pharmaceutical Servicesarm al SJames Alexander Corp.and orp.
Je ven P armaceut cJ aceut
JH BertranJH ertran
ono
e, Inc.c.
eig Jofre groupig Jo up
Robertson Microlit Laboratories Inc.erts olit L ories
Ropack Inc.R ck IRottendorf Pharmaceuticals IRo dor ace
Rovi Contract ManuRov ntract Man
Rx Pharma-PRx
SGSS
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 99/132
June 2015 Twitter : @ContractPharma Contract Pharma 99
Conference Attendee Registration Fee:Includes meeting materials, continental breakfasts, lunch, coffee breaks, reception, and entrance to exhibits.
Industry $395.00
Hotel Room Reservations: Please call the Hyatt Regency New Brunswick at 888-421-1442. Mention the Contract Pharma Conference to receive the Conference room rate of $199 single/double.
Please attach business card or type/print (ink only) legibly.
Company Name: ______________________________________________________________________________________________The above will appear as is in all Contract Pharma listings. Please provide appropriate capitalization and punctuation.
Address: ____________________________________________________________________________________________
City, State, Postal Code, Country: ________________________________________________________________________Telephone:____________________________________________ Fax: __________________________________________
Email:_______________________________________________________________________________________________
Website Address: _____________________________________________________________________________________
Contact Name: _____________________________________________Title: __________________________________________Will receive all future correspondence and mailings.
Name Badge
Full Conference: __________________________________________________________
Method of Payment:
Check # _______ Checks must be drawn on a US bank in US dollars. Please make checks payable to Contract Pharma LLC.
American Express MasterCard VISA
Acct #:____________________________________________ Expiration Date: ___________ Billing Postal Code:_________
Name on card (print or type): ____________________________________________________________________________
Signature: ____________________________________________________Amount Authorized: $ _____________________
Send or Fax completed form to: Contract Pharma , 70 Hilltop Rd, Ste 3000, Ramsey, NJ 07446 Attn: Conference Dept • Phone: (201) 825-2552 • Fax: (201) 825-0553
Cancellation Policy: Cancellation on or before 8/21/15 is subject to a 50% cancellation fee.Cancellations must be in writing and received at the Contract Pharma office by 8/21/15.
Please note: you will receive an email confirmation once your registration is processed.
This form may be copied for additional registrations.
September 17th and 18th, 2015 • Hyatt Regency, New Brunswick, NJ
14th Annual
2015 CONTRACTING ANDOUTSOURCING CONFERENCE
AND TABLETOP EXHIBITION
R e g i s t e r 3
G e t 1 F R E E
!
This application will become a contract upon receipt of full payment & counter signature of Contract Pharma management.
For Contract Pharma Use Only
Payment Received _________________________________________ Date Received _________________________
Accepted by _______________________________________________ Date _________________________________
REGISTER NOW ONLINEwww.regonline.com/cp2015
Or fax this form to register (201) 825-0553
Contract Pharma, 70 Hilltop Rd, Ste 3000, Ramsey, NJ 07446Phone: (201) 825-2552 • Fax: (201) 825-0553 • Email: [email protected]
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 100/132
100 Contract Pharma contractpharma.com June 2015
I N D U S T R Y N E W S
Janssen Supply Chain has furtheredits strategic partnership with the RutgersUniversity School of Engineering, provid-
ing more than $6 million to expand ongo-ing research efforts to support Janssen’sintroduction of continuous manufacturingtechniques for pharmaceuticals.
The funds will increase R&D efforts forStructured Organic Particulate Systems (C-SOPS) for the next several years. The center isalso helping Janssen transition several prod-ucts to continuous manufacturing, includingdeveloping a specially designed manufactur-ing line at its facility in Puerto Rico.
The funding from Janssen began five years ago and focuses on technical de-
velopment of continuous processing, anemerging advanced pharmaceutical man-ufacturing method.
As part of this collaboration, Rutgers en-gineers built one of the first full production-scale continuous direct compression solidoral dosage manufacturing facilities, which
was used as the model for the Janssen pro-duction line in PR and is also being used as amodel by other pharma manufacturers. Thisdirect compression tableting line, located atthe engineering school campus in Piscat-away, has now been expanded to include
wet and dry granulated products and canaccommodate tests of multiple productionroutes under automated control.
“Our collaboration with the RutgersEngineering School has been very produc-tive in helping us to prepare for the futurein delivering the highest quality medicinesin the most efficient way,” said MauricioFutran, vice president, advanced technol-ogy, Janssen Manufacturing & TechnicalOperations. “We look forward to con-tinuing to work closely with Rutgers and
with regulators on the advancement and
implementation of this important manu-facturing technology.”
Amarantus, Catalent InkcGMP Mfg. Pact
Amarantus BioScience has entered a
manufacturing agreement with CatalentPharma Solutions for clinical-grade pro-duction of MANF (mesencephalic-astro-cyte-derived neurotrophic factor). Catal-ent will provide all cell line engineering,process development and cGMP bioman-ufacturing activities for the developmentof a high performance cell line expressingMANF protein that will then be advancedinto scale up for cGMP production.
Catalent will use its GPEx technology,designed to create high-expression, stablecell lines quickly and efficiently. Applying
GPEx technology spans from early feasi-bility studies to clinical manufacturing andcommercial scale production.
MANF is a naturally-occurring pro-tein that reduces and prevents apoptosis(programmed cell death) in response toinjury or disease. Amarantus is developingMANF for the treatment of orphan ocularindications, including retinitis pigmentosa(RP), and recently received orphan drugdesignation for RP in the U.S. and Europe.In preclinical models MANF proteins havealso demonstrated potential to treat a
wide range of conditions including retinalartery occlusion, glaucoma, Parkinson’sdisease, diabetes and ischemic heart dis-ease, among others.
“We selected Catalent as our develop-ment and manufacturing partner becausethey have the cGMP capabilities, expertiseand proprietary technologies required toefficiently synthesize and scale up MANFproduction for human clinical use,” saidGerald E. Commissiong, president andchief executive officer of Amarantus.“Advancing MANF, our first internally-
discovered therapeutic product candidate,into human clinical studies will be a ma-
jor advancement for the Company. Rapidproduction of MANF in collaboration withCatalent will enable us to achieve this ob-
jective as quickly and in the most cost-ef-fective manner possible. The Company iscurrently targeting the orphan ocular in-dication retinitis pigmentosa (RP) for first-in-man studies, expected to start in 2016.”
Hospira, Theradiag Enter Assay KitSupply PactHospira will provide LISA TRACKER’sinfliximab assays and anti-infliximab an-tibodies assays kits in Europe, Canada and
Australia to give clinicians and patientshigh level biological information regard-
ing the treatment with the biosimilar ofinfliximab (Remicade). Hospira has se-lected Theradiag as its exclusive providerof monitoring tools.
Theradiag will supply Hospira withLISA TRACKER monitoring kits and willalso ensure installation and training inlabs, as well as provide information andfollow-up with clinicians on behalf ofHospira. LISA TRACKER’s infliximab kitshave been validated for use with Inflectra.
“This partnership marks a significantchange in how pharmaceutical companies
view theranostics and is a formidable op-portunity to promote the monitoring ofbiotherapies. For the first time, a pharma-ceutical company will be pairing our mon-itoring kits with their treatments. This willbuild greater awareness within the medi-cal and patients’ community regarding thebenefits of biotherapy monitoring, whichimprove patient care while cutting health-care spending,”said Michel Finance, chiefexecutive officer of Theradiag.
Hospira commercializes Inflectra (a bio-logic equivalent to Remicade). It’s the first
biosimilar monoclonal antibody to be ap-proved by the EMA, and is indicated for the
Janssen Expands Continuous Mfg.
Initiative with Rutgers Amarantus, Catalent ink cGMP manufacturing pact
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 101/132
June 2015 Twitter : @ContractPharma Contract Pharma 101
I N D U S T R Y N E W S
treatment of rheumatoid arthritis, Crohn’sdisease, ulcerative colitis, ankylosing spon-dylitis, psoriasis and psoriatic arthritis.
Pharmatek Expands SprayDrying CapabilitiesPharmatek has completed installation ofa GEA Niro Mobile Minor for the GMPmanufacture of amorphous spray drieddispersions and is currently completingequipment validation. The spray dryercomplements the company’s purchase ofa Gerteis MINI-PACTOR last year.
GMP spray drying capabilities will in-clude aqueous and solvent processing in aclosed loop system. The spray dryer will be
installed in the company’s high contain-ment manufacturing facility, allowing forthe manufacture of highly potent and cy-totoxic compounds.
“Spray drying has become an essentialoption for anyone specializing in the de-
velopment of poorly soluble compounds.Over the past five years, we’ve developed atremendous amount of expertise in amor-phous dispersion development for poorlysoluble compounds,”said Jeffrey Bibbs, chiefexecutive officer and chief scientific officer ofPharmatek. “This increased capacity allows
Pharmatek to offer spray drying supportthrough Phase IIb clinical studies.”
Lannett Acquires SilarxPharmaceuticalsLannett Company has signed a definitiveagreement to acquire privately held Si-larx Pharmaceuticals, a manufacturer andmarketer of liquid generic pharmaceuticalproducts. The transaction is expected toclose in early June 2015. Strategic ben-efits of the acquisition include an FDA-approved manufacturing facility, research
and development expertise and addeddiversity to Lannett’s portfolio of existingand pipeline products.
“We look forward to welcoming Silarxto the Lannett family,” said Arthur Bed-rosian, chief executive officer, Lannett.“Upon closing, the acquisition will add ahigh quality, talented research team andmanufacturing capacity. In addition, al-though the acquisition is not expected tohave a significant impact on our finan-cial results of operations during the nexttwelve months, Silarx brings an exciting
pipeline and a number of complementaryproducts to our offerings.”
Bedrosian noted that Silarx has a longhistory of outstanding regulatory com-pliance. The company’s entire senior
management team will remain with thecombined company and no layoffs or fa-cility closings are planned. Silarx recentlymoved into a 110,000 square foot facilitylocated in Carmel, NY.
Baxter Gains Approval forSabinanigo Mfg. FacilityBaxter International Inc. received FDA ap-proval for its supplemental drug applica-tion to establish its Sabinanigo, Spain,facility as an approved manufacturing sitefor 0.9% Sodium Chloride Injection, USP,
for the U.S. market.The approval includes product presen-
tations in 250 mL, 500 mL and 1000 mL, which Baxter has been distributing in theU.S. to alleviate a drug shortage with theknowledge of the FDA. These three prod-uct presentations of 0.9% Sodium Chlo-ride Injection, USP, known as saline, havebeen in short supply the past two years.
“The approval of an additional manu-facturing site for Sodium Chloride Injec-tion in the U.S. gives us greater flexibilityto respond to market demand fluctuations
and will help as we continue to meet pa-tient and healthcare provider need for thiscritical product,”said Brik Eyre, presidentof Baxter’s Hospital Products business.“FDA was quick to recognize the benefitof addressing industry demand for sterileIV solutions in collaboration with compa-nies like Baxter.”
DIR Tech, Pfizer Ink Inspection PactDIR Technologies, a provider of qualityand process control solutions for pharma-ceutical primary packaging, has signed a
five-year agreement with Pfizer providingPfizer with access to DIR Technologies’ in-spection and quality control solutions, andsets the stage for joint projects pertainingto both product production and packagingline QA/QC processes.
Among the solutions involved in theagreement is DIR Technologies’ flagshipInduction Integrity Verification System(I2VS). Introduced just over a year ago, thesystem is the first in the global pharma-ceuticals market to perform in-line inspec-tion on 100% of induction sealed bottles
at the speed of the machine throughput.The I2VS is a workflow solution as well
as an inspection device: the source of anypotential faulty seals is indicated in realtime, yielding a high degree of process un-
derstanding and the ability for operatorsto not only help fix potential faulty sealsimmediately, but oftentimes prevent themfrom occurring in the first place.
“Obviously, Pfizer is a well-establishedleader in pharmaceuticals manufactur-ing and part of our excitement in work-ing with Pfizer is the company’s dedica-tion to also being an industry pioneer interms of technological advancement,”saidRoni Mansur, chief executive officer, DIRTechnologies. “Pfizer’s methodology ofcontinuous improvement drives it to test
and implement the best of cutting-edgesolutions. It takes a true entrepreneurialspirit to lead the way and make a change,to implement technology that is differentfrom the industry norm.”
Whereas sampling has been the stan-dard methodology, the I2VS enables anew level of quality assurance and processcontrol, according to the company. Afteran extensive trial, Pfizer recently decidedto adopt DIR’s inspection technology onselect packaging lines.
DIR Technologies and Pfizer also will
be working together on the developmentof a new inspection technology based onDIR’s advanced high-speed imaging ca-pabilities. The new system is intended toperform 100% in-line inspection of tabletsand capsules.
SAFC Completes St. LouisMfg. ExpansionSAFC Commercial, the custom manufac-turing services business unit of Sigma-Al-drich Corp., has completed the expansionof its St. Louis facility to support commer-
cial-scale antibody drug conjugate (ADC)manufacturing. The facility is in final vali-dation and expected to go online in 3Q15.
The St. Louis expansion, designed tomeet SafeBridge category 4 compoundhandling to safely accommodate usage ofhighly-active compounds, creates com-mercial-scale manufacturing capacity for
ADCs and other targeted therapies. Theexpanded capabilities in St. Louis furtherthe company’s commercial capacity forhighly-active manufacturing and storageat its Madison, WI facility.
“The ADC market is a growing market,and is expected to expand over the next
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 102/132
102 Contract Pharma contractpharma.com June 2015
I N D U S T R Y N E W S
few years. This strategic expansion is thelatest in a series of enhancements in our
ADC offering designed to support this
important therapeutic area and to helpour customers to seamlessly scale ADCproduction from preclinical to commer-cial phases,”said Gilles Cottier, presidentof SAFC. “Our offer can bring customers’molecules to the clinic faster, with the easeof working with one supplier from start tofinish. With the added support of our re-cently launched ADC Express service, webelieve SAFC presents the most compre-hensive offer in the contract manufactur-ing market.”
SAFC is also expanding its facility in
Carlsbad, CA to further enhance clini-cal and commercial bulk drug productioncapabilities, as well as fill/finish of viralproducts for its gene therapy, viral vaccineand immunotherapy customers.
“Gene therapy is an emerging technol-ogy, and our SAFC and BioReliance sitesin Carlsbad, Rockville, MD and GlasgowScotland, have supported this growing in-dustry for years,”said Gilles Cottier, presi-dent of SAFC. “This investment is pivotalto our customers and reflects SAFC’s con-tinued dedication to providing the infra-
structure customers need to bring theirdrugs to market.”The investment was driven by contin-
ued interest in targeted gene therapies forindications such as hemophilia and cancerimmunotherapies (CAR-T cells). Utilizingthe biosafety testing expertise of BioReli-ance, the Carlsbad facility provides a fullrange of GMP manufacturing and testingservices.
Pfizer Acquires Interest in AM-Pharma
Pfizer has acquired a minority equity inter-est in AM-Pharma and secured an exclusiveoption to acquire the company. AM-Phar-ma is a privately held Dutch biopharmacompany focused on the development ofrecombinant human Alkaline Phosphatase(recAP) for inflammatory diseases.
Pfizer has made an upfront payment of$87.5 million for the minority interest andexclusive option, with additional potentialpayments of up to $512.5 million upon thepotential launch of any product from thisagreement. Pfizer may exercise the option
upon completion of a Phase II trial of recAPin the treatment of Acute Kidney Injury
(AKI) related to sepsis, for which there areno drugs currently approved. Results fromthe Phase II trial are expected in 2H16.
“Pfizer is committed to advancing thescience to address the high unmet medi-cal need in Acute Kidney Injury,” saidMikael Dolsten, M.D., Ph.D., president,
Worldwide R&D at Pfizer. “Clinical datafor recAP show the potential to uniquelyaddress Acute Kidney Injury in the settingof sepsis, and we look forward to work-ing with our partners at AM-Pharma as
we aim to accelerate the development ofrecAP into a potential first-in-class treat-ment for patients.”
Erik van den Berg, chief executive of-
ficer of AM-Pharma said, “This agreementis a significant step for AM-Pharma, and
we welcome Pfizer as a shareholder anddedicated partner. This deal not only pro-
vides good shareholder value, but providesthe next step in the development of recAPas a potential treatment for patients with
Acute Kidney Injury and other inflamma-tory diseases.”
Perrigo Acquires Patheon’sMexican OpsPerrigo Company has acquired the Mexi-
can operations of Durham, NC-basedPatheon for $34 million in cash.Perrigo chairman, president and chief
executive officer Joseph C. Papa said, “Weare pleased to announce this transactionand are excited by the many importantbenefits it provides to the Company. Per-rigo has long desired to be a prime manu-facturer of softgel products and we believethe acquisition of Patheon’s Mexican op-erations serves as an ideal entry point intothe space. Additionally, and importantly,
we believe Perrigo is uniquely positioned
to maximize the potential of the businessby leveraging our own Mexican operationsto drive growth and value for our custom-ers and shareholders. This acquisitionserves as yet another example of Perrigo’scommitment to provide Quality Afford-able Healthcare Products® to consumersaround the world, and we look forward tofurther executing on this mission.”
West Invests in Global Site Expansions West Pharmaceutical Services, Inc. hasmade a multi-year investment to add capa-
bilities to all of its global Packaging SystemsR&D facilities and develop two new R&D
Centers of Excellence (CoE) in the AsiaPacific and in Europe, to leverage regionalcapabilities in parenteral drug packaging.
The facility in Europe will serve as thecompany’s CoE for drug vial and cartridgeseals, plastic technology and packagingcomponent materials development, and
will be on line by the end of 2016. The lo-cation in the Asia Pacific region will serveas a CoE for innovation across all tech-nologies specific to the emerging markets,and is expected to be operational by theend of 2015.
“For more than 90 years, West’s focuson innovation, science and service hasmade us a trusted partner for pharmaceu-
tical and biopharmaceutical companies worldwide,” said Karen Flynn, president,Pharmaceutical Packaging Systems, West.“Our enhanced R&D Development Cen-ters—in all regions of the globe—will fur-ther our commitment to our customersby providing world-class, science-basedprocess and product development thatenables us to quickly and efficiently an-ticipate and respond to changing marketneeds with new, innovative solutions.”
Siegfried Acquires BASF’s Pharma
Supply AssetsSwiss-based Siegfried Group signed anagreement to acquire significant segmentsof BASF’s pharmaceutical supply busi-ness and related chemical-pharmaceuticalproduction units in Germany, France andSwitzerland. The transaction, subject tocustomary closing conditions, is expectedto close in fall 2015. The three sites, withover 800 employees, reported total salesfor 2014 of approximately $300 million.
The BASF business unit produces APIsand intermediates to the pharma industry,
complementing Siegfried’s business.Siegfried chief executive officer, RudolfHanko, said, “Through this acquisition,Siegfried will reach the critical size to play aleading role in the supplier market as a rec-ognized partner for the pharma industry.This acquisition demonstrates the growthpotential for the Siegfried Group.”
Siegfried will continue operations atthe three sites and will review its existingand new production sites for efficiency andsynergy potential in order to raise com-petitiveness. In the new constellation, the
Zofingen, Switzerland site will remain theGroup’s headquarters. CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 103/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 104/132
104 Contract Pharma contractpharma.com June 2015
C R O N E W S
Quintiles has expanded its bioana-
lytical lab services with the establishmentof a GLP-compliant bioanalytical liq-
uid chromatography-mass spectrometry(LC-MS) lab in Oss, the Netherlands. TheOss lab is led by Dr. Benno Ingelse, anindustry expert with more than 15 yearsof bioanalytical experience. Additionally,the new lab will enhance Quintiles’ clini-cal trial lab services.
“Adding this capability in Europe isa key step for our bioanalytical businessand supports the strategy to increase ourparticipation in the substantial Europeanbioanalytical market,”said Costa Panagos,senior vice president and global head of
Global Central Laboratories at Quintiles.“This is an exciting milestone for Quintil-es and specifically our lab business as weexpand our capabilities while continuingto provide the value and high-quality ser-
vice our customers require.” Currently, Quintiles’ bioanalytical and
ADME capabilities are managed out ofthree lab sites in the U.S. The new lab willbe fully integrated with Quintiles’ exist-ing laboratory in Ithaca, NY, enabling thetransfer of assays back and forth to ac-commodate global studies. The Oss lab
will become part of the recent clinical tri-als lab services joint venture with QuestDiagnostics. That transaction is antici-pated to close in 3Q15.
“The Oss lab will further enhance thescale, clinical trial expertise and diversetherapeutic experience that will be a cor-nerstone of the proposed joint venture
with Quest Diagnostics,” said Panagos, who will serve as the new joint venture’schief executive officer upon completionof the transaction. “The addition of theOss laboratory is integral to the contin-
ued evolution of our laboratory businessand we’re excited about the benefits it
can provide as part of a globally scaledand agile business for our customers to-day as well as in the future.”
Quotient Clinical CompletesJanssen’s FIH ProgramQuotient Clinical has announced the re-sults from an Enabled-First-in-Human(Enabled-FIH) program conducted forthe Janssen WAVE Early Developmentunit. The first-in-human clinical program
was designed to develop an optimal oralformulation, in parallel with the assess-ment of single and multiple dose safety,pharmacokinetics and pharmacodynam-ics of a highly selective small molecule
c-Met tyrosine kinase inhibitor.The clinical phase, which was con-
ducted under a single, adaptive protocol, was completed in six months. The singleascending dose phase began with a sim-ple solution, and the protocol includedthe option to assess the relative bioavail-ability of up to two solid oral dosage for-mulations. The transition from solutionto a solid dosage form was successfullyachieved and this product was used tocomplete the remaining single and mul-tiple doses. The clinical protocol also
included flexible options to assess foodeffect, dosing frequency and administra-tion to older subjects. Dose proportionalincreases in exposure were observed andall doses were safe and well tolerated.
“We were very pleased to undertakethis program. This is an excellent exam-ple of how our innovative Enabled—FIHservice can support and accelerate anearly development program,” said MarkEgerton, chief executive officer, Quo-tient Clinical. “Timelines are shortenedand the consumption of drug substance
is reduced by more than 85% comparedto a conventional program, delivering
significant cost savings. We believe thatEnabled-FIH represents an importantstep forward in helping the industry to
improve overall R&D productivity.”
Theorem To Open New ClinicalSupplies FacilityTheorem Clinical Research will open anew clinical supplies facility in Frankfurt,Germany, in June. The cGMP-compliantfacility will triple the company’s currentclinical supplies capacity, with space for2,700 square meters of ambient (15 to25°C) and refrigerated (2 to 8°C) space.The facility will also serve as a clinicalsupplies hub near the Frankfurt Airport.
“We’re excited to have the additionalmanufacturing and warehousing spaceand, more importantly, an infrastructureto deliver the flexibility our clients relyon,” said John Potthoff, Theorem presi-dent and chief executive officer. “The newfacility will enhance speed and scalabil-ity while preserving the versatility of oursupply solutions.”
The new facility enhances currentpractices, such as its 24/7/365 storage,continuous monitoring and backup, andprovides space for future expansion.
Frontage Expands Clinical Ops in NJFrontage has opened a new facility in Se-caucus, NJ, expanding its clinical researchservices. The new 36,000-sq.-ft., 160-bedclinical research center complementsthe company’s existing center in nearbyHackensack.
The Secaucus facility has the capabili-ties to conduct a wider range of clinicalstudies including multiple concurrentstudies and Phase II-IV studies involv-ing patient populations. This expansion
will nearly triple the company’s clinicalcapacity in the U.S.
Quintiles Expands
Bioanalytical CapabilitiesQuotient Clinical completes Janssen’s FIH program
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 105/132
June 2015 Twitter : @ContractPharma Contract Pharma 105
C R O N E W S
“We are excited to operate a secondfacility in New Jersey as it has been anideal location for our clinical research due
to the immediate access to the medicalcommunities as well as subject and pa-tient populations,” said Eileen McAuley,senior vice president of Clinical Services.
“Frontage’s ability to provide compre-hensive support to our clients and theirneeds in the early drug developmentstage is greatly enhanced by our invest-ment in facility expansion and clinicalservices infrastructure,” said Dr. Song Li,chief executive officer of Frontage.
PPD Opens Central Lab in Shanghai
Pharmaceutical Product Development,LLC (PPD) has opened a central labora-tory in Shanghai, China to meet growingclient demand for these services in China.The new facility, which has been estab-lished in association with Shanghai Clin-ical Research Center (SCRC), is equipped
with new analytical equipment to providehigh-quality data across a wide rangeof technologies and applications for allphases of development.
PPD’s central lab service offeringincludes safety and general lab testing,
specialized testing, biomarker testing,and custom assay development and test-ing services. This new operation providesthe same services as PPD’s other cen-tral labs in Brussels, Belgium; HighlandHeights, Kentucky; and Singapore. Allof PPD’s central labs use identical test-ing platforms, calibrators and reagentsfor all laboratory assays. In addition, thesame lot numbers of standards for cali-bration are used across all labs, ensur-ing identical results regardless of wheretesting is performed.
“Our global network of central labs iscommitted to bringing value across theproduct development continuum,” said
Andrew Cunningham, vice president ofglobal laboratory services at PPD. “We de-liver world-class scientific expertise, in-novative platforms, flexible service mod-els and operational efficiencies to ensuresuccessful execution across every step ofthe development process. The standard-ized, global platforms and web-baseddatabase of our central labs ensure supe-rior service, quality data, and exceptional
speed and flexibility for our clients.”The new facility is accredited via
SCRC’s medical license issued by China’sMinistry of Health, as well as the Collegeof American Pathologists, NGSP and ISO
15189 certifications—all of which are cru-cial to conducting clinical trials in Chinasuccessfully.
In addition to central labs, PPD alsohas good manufacturing practices (GMP)labs in Athlone, Ireland, and Middleton,
WI; bioanalytical labs in Middleton andRichmond, VA; and vaccine sciences labsin Richmond and Wayne, PA.
inVentiv Health ExpandsCompliance ServicesinVentiv Health has expanded its compli-
ance services to assist biopharma com-panies conducting non-interventionalstudies (NIS) or observational studies, in52 countries around the world. Clients ofthe new services will have access to anNIS Regulatory Intelligence Databaseaimed at clarifying the new EU regula-tion No 536/2014, scheduled to take ef-fect in May 2016.
Vague regulatory language aroundthe new regulation is expected to causeconfusion about the conduct of non-interventional trials, as well as the need
for every EU country to review and alterexisting national regulations to assurealignment with EU regulation. The newregulation also creates an entirely newcategory of trial with its own compliancerequirements.
“The impending regulatory changeis happening at the very moment whenreal-world data from non-interventionalstudies has never been more impor-tant,”said Lynn Okamoto, executive vicepresident of Late Stage, inVentiv HealthClinical Division. “Data obtained from
patients in real-life conditions is now es-sential for building the evidence requiredby payers for payment and reimburse-ment decisions.”
The new services will address Regula-tory Affairs, Medical Affairs, QA Audit-ing, Project Management, Pharmacovigi-lance, as well as the design or conductof NIS requiring detailed, country-levelinformation to assure compliance.
INC Implements DrugDev’sSiteCloud Platform
INC Research has entered a strategic col-laboration with DrugDev aimed at driv-
ing increased efficiencies in clinical trialsthrough greater access to and manage-ment of critical investigator and site data.
INC Research has completed integrationand implementation of DrugDev’s Site-Cloud platform, the same technologyused by TransCelerate’s Investigator Reg-istry (launching later this year) and theInvestigator Databank, to facilitate moreefficient feasibility, site selection andstudy start-up processes.
Using a universal identifier known asthe DrugDev Golden Number, the Site-Cloud platform matches and mastersdata from numerous disparate sources(such as INC’s internal experience, the
DrugDev Network of 80,000 opted-inglobal investigators across 115 countriesand trusted third-party resources) to cre-ate a virtual private database (VPD) withprecise site and investigator profiles that
will be used to make evidence-based de-cisions. SiteCloud enables INC to makeevidence-driven site selection decisions,
while the DrugDev Golden Number en-ables INC to collaborate and integratemore efficiently with pharma customers.
“INC Research is continuously look-ing to advance clinical research and
patient and site engagement throughinnovation,”said Clare Grace, vice presi-dent, Site and Patient Access. “DrugDevprovides cutting-edge solutions thathelp drive the biopharmaceutical indus-try forward. Cloud-based offerings likeSiteCloud are the latest examples of thetools and resources INC uses to sharecritical investigative site data with ourcustomers and drive increased efficien-cies at critical points along the drug de-
velopment continuum.”“Real change will only come to the
clinical research industry through mean-ingful collaboration and the widespreadadoption of technology standards suchas the DrugDev Golden Number, sonaturally we could not be more excited to
work with INC Research on this essen-tial initiative,” said Ibraheem Mahmood,president and chief executive officer ofDrugDev. “As a platform-agnostic leader,INC is committed to leveraging future-proof technologies that best meet cus-tomer requirements, and we are honoredthat they have chosen SiteCloud as their
preferred platform for site and investiga-tor data sharing and management.”CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 106/132
106 Contract Pharma contractpharma.com June 2015
C O L L A B O R A T I O N S & A L L I A N C E S
Janssen Pharmaceuticals, Inc., a John-
son & Johnson company, has entered intoan exclusive worldwide license and collab-
oration agreement with Achillion Phar-maceuticals to develop and commercializeone or more of Achillion’s lead hepatitis C
virus (HCV) assets, which include ACH-3102, ACH-3422 and sovaprevir.
The companies will work to developa short-duration, highly effective, pan-genotypic, oral regimen for the treatmentof HCV. Achillion’s ACH-3102, an NS5Ainhibitor currently in Phase II studies hasbeen granted Fast Track designation by theFDA. An initial regimen will explore thecombination with an NS3/4A HCV pro-
tease inhibitor plus an NS5B HCV poly-merase inhibitor from the collaboration. Janssen will have an exclusive, world-
wide license to develop and commercial-ize HCV products and regimens contain-ing one or more of the licensed HCVassets. Achillion will be eligible to receivedevelopment milestones and royalties onfuture worldwide sales.
“Despite recent treatment advances,there remain significant unmet needsto effectively address the burden whichhepatitis C inflicts on both patients and
society. Janssen is committed to optimiz-ing outcomes and the new collabora-tion with Achillion offers the potentialto develop a new, simplified treatmentoption for those affected by hepatitisC,”said Lawrence M. Blatt, Ph.D., globaltherapeutic area head, Janssen InfectiousDiseases and Vaccines, and president andchief executive officer of Alios BioPhar-ma, Inc.
In addition, and separate to the collab-oration arrangement, Johnson & JohnsonInnovation, Inc. will make an equity in-
vestment in Achillion. The transactions aresubject to customary closing conditions.
Boehringer, PharmaxisBoehringer Ingelheim has exercised theoption under its Pharmaxis alliance to ac-
quire the investigational drug PXS4728Afor the treatment of the liver-related con-dition NASH. PXS4728A is a Semicarba-zide-Sensitive Amine Oxidase/Vascular
Adhesion Protein-1 (SSAO/VAP-1) Inhib-itor that works as an anti-inflammatory,and in Phase I studies, demonstrated oralbioavailability, long-lasting target inhibi-tion and good safety and tolerability.
Pharmaxis will receive $39 million up-front and is eligible for development andcommercialization milestones. Boehringer
will be responsible for all development,
regulatory, manufacturing and commer-cialization activities. Boehringer has alsoacquired other SSAO/VAP-1 inhibitormolecules related to PXS4728A and asso-ciated patents.
NASH is the progressive form of non-alcoholic fatty liver disease (NAFLD), themost common liver disorder in Westernindustrialized nations, and is a majorcause of fibrosis and cirrhosis of the liver.Type 2 diabetes and obesity can also leadto NASH. It’s currently an area of high un-met clinical need.
Pharmaxis chief executive officer GaryPhillips said, “This is a transformationalevent for Pharmaxis. With a total potential
value in excess of $750 million, it is a glob-ally competitive deal and significant forthe Australian biotech sector. BoehringerIngelheim’s clinical expertise will now beapplied to the development of this drug
which has the potential to make a real dif-ference in the treatment of diseases withhigh unmet clinical need.”
Glyn Parkin, senior vice president andMetabolism head at Boehringer Ingelheim
said, “We have ambitious strategic goals indiabetes and metabolism and this Phase I
asset acquisition fits well into our devel-opment portfolio. We are pleased to haveachieved access to Pharmaxis’ research ex-
cellence and innovative approach to treat-ments for NASH.”
Ablynx, Genzyme Ablynx has entered into an exclusive re-search collaboration with Genzyme, aSanofi company, to investigate Nanobod-ies against a multiple sclerosis (MS) targetthat relates to Genzyme’s early-stage MSresearch programs involving neuroprotec-tion and CNS repair.
Existing drugs do not directly treat theneurodegeneration in MS. Genzyme’s re-
search efforts aim to target the underlyingcauses of MS disease progression and de- velop treatments to protect neurons andpromote repair.
Genzyme will perform in vitro and in vivo research with Ablynx’s Nanobodies inMS-relevant models in return for an exclu-sivity fee. Once the studies are completed,Genzyme will have the option to negotiatea license agreement. Ablynx has alreadygenerated potent Nanobodies against thespecific target of interest and confirmedtheir activity in preclinical models.
Dr. Edwin Moses, chief executive offi-cer of Ablynx, said, “As a leading biotechcompany, Genzyme is an ideal partnerto demonstrate the potential value of
Ablynx’s versatile Nanobody technologyplatform in MS. The formatting flexibil-ity of Nanobodies makes them promisingcandidates for combining antibody-likeselectivity and multi-specificity in a sin-gle molecule. We are looking forward to
working for the first time with Genzyme.” Johanne Kaplan, vice president, Neuro-
immunology Research, Genzyme, said, “We
look forward to collaborating with Ablynxto evaluate the potential of Nanobod-
Janssen, Achillion in HCV
Development PactBoehringer acquires NASH drug under Pharmaxis alliance
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 107/132
June 2015 Twitter : @ContractPharma Contract Pharma 107
C O L L A B O R A T I O N S & A L L I A N C E S
ies against this CNS target, as this projectsupports our research that includes the ex-ploration of novel therapeutic platforms to
address unmet needs in multiple sclerosis.”
Lilly, Sanford-BurnhamEli Lilly and Co. and Sanford-BurnhamMedical Research Institute will collaborateto discover and develop immunologicaltherapies using biotechnology approachestargeting multiple immune checkpointmodulators for the treatment of diseasessuch as lupus, Sjögren’s Syndrome, in-flammatory bowel disease and other au-toimmune disorders.
Lilly will contribute its biotechnology
capabilities and expertise in immunology,and Sanford-Burnham will apply its ex-pertise in cellular pathways regulating theimmune system focusing on the immunecheckpoint networks. The research col-laboration will be co-chaired by Thomas F.Bumol, Ph.D., senior vice president, bio-technology and immunology research atLilly, and Carl Ware, Ph.D., director, Infec-tious and Inflammatory Diseases Centerat Sanford-Burnham.
“Immunology is an important researcharea of focus for Lilly, and through this
exciting collaboration with Sanford-Burn-ham, our scientists can discover and devel-op new medicines together in a seamless
way that takes advantage of each group in afamily of key targets,”said Dr. Bumol.
“The Lilly-Sanford-Burnham collabo-ration is precedent setting in scope andits potential to advance discoveries to thepatient more efficiently,” said Sanford-Burnham chief executive officer PerryNisen, M.D., Ph.D. “By combining the deepknowledge of human biology and diseasemechanisms among Sanford-Burnham
scientists, in particular our expertise in thefield of checkpoint regulators in the im-mune system, and Lilly’s leadership posi-tion in the development of biologics andlarge molecules, we are forging the path todevelop the next generation of transforma-tive treatments for autoimmune disease.”
Advaxis, Sorrento Advaxis, a clinical-stage biotechnologycompany developing cancer immunother-apies, has entered into a non-exclusiveresearch and clinical trial collaboration
agreement with Sorrento Therapeutics toevaluate combinations of Advaxis’s Lm-
LLO cancer immunotherapy technologyplatform, including ADXS-HPV, ADXS-PSA and ADXS-HER2, with Sorrento’s
fully human antibodies targeting immunecheckpoints, including GITR, OX40, LAG-3 and TIM-3.
Advaxis’s preclinical program for ADXS-HPV previously examined itstherapeutic potential in combination withagonistic research antibodies, includ-ing anti-OX40 and anti-GITR. Preclinicaldata demonstrated that the combinationof ADXS-HPV with agonistic researchantibodies led to significant inhibition oftumor growth and prolonged survival intumor-bearing mice. Complete regression
of established tumors occurred in 40%and 60% of animals treated with ADXS-HPV in combination with anti-OX40 andanti-GITR antibodies, respectively (AACR
Abstract #LB-229).“Leveraging Sorrento’s fully human
antibody library and Advaxis’s Lm-LLOimmunotherapy technology offers a sig-nificant opportunity to target multiplecancer indications and extend the poten-tial of our respective company’s technolo-gies,”said Daniel O’Connor, president andchief executive officer, Advaxis.
According to the agreement, Advaxis will conduct the studies and the companies will equally share the expenses. The com-panies want to begin the first of the twoplanned combination studies in 2016. Re-sults from the studies will be used to deter-mine whether further clinical developmentof specific combinations is warranted.
“Clinical collaborations are an integralpart of Sorrento’s strategy to accelerate thedevelopment of our diverse portfolio of im-muno-oncology antibodies against a broadrange of cancers,” said Henry Ji, president
and chief executive officer, Sorrento.
GSK, Emergent, Oxford U A new Phase I study has begun at the Uni- versity of Oxford that will investigate the useof a modified vaccinia Ankara (MVA) EbolaZaire vaccine candidate (MVA EBOZ) as aprime-boost to GSK’s Chimp Adenovirustype 3 (ChAd3) Ebola vaccine candidate.The study, being conducted by the clinicalresearch group of Professor Adrian Hill ofthe Jenner Institute, has received regulatoryapproval to begin from the UK’s Medicines
and Healthcare Products Regulatory Agency(MHRA). The phase 1 study has a planned
enrollment of 38 volunteers of which 6 willreceive MVA EBOZ only while the other 32
will receive ChAd3-EBO-Z prime followed
by MVA EBOZ boost.Emergent BioSolutions manufactured
the supply of MVA EBOZ that will be usedin the Phase I study, which is being con-ducted in the UK with support from the
Wellcome Trust and the U.K. Departmentfor International Development.
Professor Adrian Hill, director of the Jenner Institute at Oxford University, said,“Production of the first ever batch of MVAfor a clinical trial using a cell line is a mile-stone in the development of this impor-tant vaccine technology. This new process,
which will allow very large-scale produc-tion, will be of value not only for Ebolaprevention, but also for a wide range ofother disease indications including ma-laria and tuberculosis vaccination.”
Dr. Moncef Slaoui, chairman of vac-cines, GSK, said, “We believe there isbenefit in exploring different approachessuch as a prime-boost strategy as we con-tinue to develop our ChAd3 Ebola candi-date vaccine. This ChAd3 Ebola candidate
vaccine has shown encouraging immuneresponses and an acceptable safety and
reactogenicity profile in ongoing PhaseI trials to date. Together, these differenttrials will provide important informationabout the vaccine and its potential to helpcombat this or future Ebola outbreaks.”
Daniel J. Abdun-Nabi, president andchief executive officer of Emergent Bio-Solutions, said, “Emergent is pleased tobe part of this collaboration by leveragingour unique capabilities to manufactureand supply MVA EBOZ for evaluation inthis Phase I study. Our ability to quicklyperform proof-of-concept work and man-
ufacture MVA EBOZ at a 200L scale inan avian cell line is a result of our long-standing expertise in MVA-based vaccinedevelopment and manufacturing, fueledby our desire to have a positive, meaning-ful impact in finding a solution to this life-threatening disease.”
Lilly, BioNTechEli Lilly and Co. and BioNTech AG haveentered a research collaboration to dis-cover novel cancer immunotherapies. Thecompanies will collaborate to identify and
validate tumor targets and their corre-sponding T cell receptors (TCRs) in one or
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 108/132
108 Contract Pharma contractpharma.com June 2015
C O L L A B O R A T I O N S & A L L I A N C E S
more types of cancer. These tumor targetsand TCRs may then be engineered anddeveloped into potent and selective can-
cer therapies.BioNTech will receive a $30 million
signing fee and for each potential drug,and is eligible for more than $300 millionin development, regulatory and commer-cial milestones, as well as royalty pay-ments. Additionally, Lilly will make a $30million equity investment in BioNTech’ssubsidiary, Cell & Gene Therapies GmbH,
which specializes in TCR and chimeric an-tigen receptor immunotherapeutics. Fur-ther financial terms were not disclosed.
“In the past few years, we’ve seen some
amazing breakthroughs in immuno-on-cology; however, we believe these are justthe tip of the iceberg,”said Greg Plowman,M.D., Ph.D., vice president of Lilly Oncol-ogy Research. “Lilly’s partnership with Bi-oNTech represents the next wave of can-cer immunotherapy and is focused on theidentification of functional T cell receptorsthat can be used to redirect a patient’s nat-ural immune system to fight cancer.”
Ugur Sahin, chief executive officer ofBioNTech, said, “We are very pleased tocollaborate with a leading oncology com-
pany such as Lilly. Lilly’s expertise andtrack record make it an ideal collabora-tor for both companies to leverage thefull power of BioNTech’s functional T cellreceptor technologies to develop novelcancer therapies that harness the immunesystem. This alliance is in line with ourstrategy to collaborate with companiesthat have a similar drive and commitmentin developing and commercializing trulyinnovative and disruptive immunothera-pies for the treatment of cancer.”
TetraLogic, MerckTetraLogic Pharmaceuticals Corp. andMerck have entered an oncology clinicalstudy collaboration to evaluate the safetyand efficacy of birinapant, TetraLogic’sSMAC-mimetic, in combination with KEY-TRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with relapsed orrefractory solid tumors. The Phase I study isexpected to begin in late 2015.
KEYTRUDA and birinapant target dif-ferent elements of cancer’s block againstthe immune system. The collaboration
is based on preclinical data that sug-gest SMAC-mimetics have the potential
to enhance existing immuno-oncologyagents, such as KEYTRUDA. The compa-nies will collaborate on an initial Phase
I dose-escalation study of birinapant incombination with KEYTRUDA in patients
with relapsed or refractory solid tumors.TetraLogic will fund the study and Merck
will provide KEYTRUDA. A Joint Develop-ment Committee to oversee the conductof the study. Results from the study will beused to determine further clinical devel-opment of the combination.
“We are very excited to work withMerck to evaluate birinapant in combina-tion with KEYTRUDA,”said J. Kevin Bu-chi, president and chief executive officer of
TetraLogic. “Both molecules are designedto help the body’s immune system betterattack cancer cells, and we think the com-bination could be very promising.”
“We are establishing a broad base ofclinical evidence with our anti-PD-1 ther-apy, KEYTRUDA, as monotherapy acrossdifferent types of cancer,”said Dr. Eric Ru-bin, vice president and therapeutic areahead, oncology early-stage development,Merck Research Laboratories. “We believethere is great potential to advance ourclinical program and the field of immuno-
oncology research through strategic col-laborations and synergistic combinations,such as with KEYTRUDA and birinapant.”
Immunocore, MedImmuneImmunocore and MedImmune, the globalbiologics R&D arm of AstraZeneca, haveentered into a second collaboration toconduct combination trials in melanoma.Immunocore will conduct a Phase Ib/IItrial combining MedImmune’s investiga-tional checkpoint inhibitors MEDI4736(anti-PD-L1) and/or tremelimumab (anti-
CTLA-4) with IMCgp100, its lead T-cellreceptor, for the potential treatment of pa-tients with metastatic melanoma.
MedImmune has an exclusive relation-ship with Immunocore for the develop-ment of IMCgp100 in combination withMEDI4736 and/or tremelimumab, and willhave first right of negotiation for the futurecommercial development of these combi-nations for tumors expressing gp100. Thecompanies will collaborate to establish adosing regimen for IMCgp100 combined
with MEDI4736 and/or tremelimumab,
as part of the Phase Ib study. The Phase IIstudy will assess the safety and efficacy of
the different combinations.“We are pleased to expand our part-
nership with Immunocore, a leader in the
discovery and development of novel T-cellreceptor-based drugs, to include this com-bination clinical trial in melanoma,” saidDr. Ed Bradley, senior vice president andhead of the Oncology Innovative Medi-cines unit, MedImmune. “Our partnership
with Immunocore is further evidence ofour belief that combination therapies havethe potential to be one of the most effec-tive ways of treating cancer.”
“We are excited to deepen our rela-tionship with MedImmune through thiscombination study agreement. We look
forward to a successful partnership in thedevelopment of novel combination treat-ments in metastatic melanoma, which webelieve have the potential to be best-in-class treatments,” said Eliot Forster, chiefexecutive officer of Immunocore.
The companies entered a researchcollaboration and licensing agreementin January 2014 to develop novel cancertherapies using Immunocore’s ImmuneMobilizing Monoclonal T-Cell Receptor
Against Cancer (ImmTAC) technology.
Aptuit, Axxam Aptuit LLC and Axxam SpA have entereda strategic alliance to provide integrateddrug discovery and development servicesfrom gene to candidates and beyond. Ad-ditionally, the companies’ began their firstsignificant joint integrated project with alarge pharma company.
Aptuit provides drug discovery and de- velopment services for early discovery tomid-phase and Axxam is a discovery com-pany with expertise in target biology and abroad range of early phase discovery services.
Jonathan Goldman, chief executiveofficer, Aptuit said, “We serve biophar-maceutical companies in the discovery ofsmall molecules in a broad range of thera-peutic areas. Our alliance with Axxam ispart of our growth strategy. This best-in-class partnership broadens Aptuit’s sci-entific excellence in advanced integrateddiscovery by leveraging Axxam’s capabili-ties in early discovery. In particular we areexcited to enhance our hit identification,
validation, and expansion services, by al-lowing seamless and very high quality de-
livery of an asset from target to candidatenomination.”CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 109/132
Signature:______________________________Date:________________
Telephone:_______________________Fax:________________________
Email:____________________________________________________________
Name:_________________________________Title:_________________
Company:___________________________________________________
Address:____________________________________________________
City:__________________________State:_________Zip:_____________
Country:______________________
SIGN UP FOR YOUR FREE SUBSCRIPTION TODAY!
SUBSCRIBE now and stay on top with the latest news and trends in
Pharmaceutical and Biopharmaceutical Contract Services and Outsourcing!
YES! Please enter my FREE subscription to Contract Pharma. __No
Contract Pharma, LLC70 Hilltop Road, Ste. 3000, Ramsey, NJ 07446
Tel: 201-825-2552 | Fax: 201-825-6582Web: www.contractpharma.com | E-mail: [email protected]
What is your function? (check only one):
A __ Research & Development
B __ Quality Assurance/Control/Validation
C __ Business Development
D __ Contract Management
E __ Project Management
F __ Corp. Mgt. (including CEO, CFO, VP Op/Mfg.)
G __ Regulatory Affairs
H __ Engineering
J __ Purchasing
K __ Clinical ResearchL __ Production/Manufacturing (including packaging)
N __ Sales/Marketing
O __ Lab Manager/Tech Service
P __ Financial
R __ Legal
Z __ Other __________________
What is your firm’s primary business? (check only one):
01__ Pharmaceutical Manufacturing
02__ Biopharmaceutical Manufacturing
08__ Specialty Pharmaceutical Company
03__ Contract Manufacturing/Services
04__ Laboratory Services
05__ Contract Research
09__ Drug Delivery Company
06__ Government
10__ Financial Institution
11__ Law Firm
07__ Consulting
99__ Other _____________________
FAX BACK TO
201-825-6582
TODAY!
MAG SUB
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 110/132
110 Contract Pharma contractpharma.com June 2015
P R O M O T I O N S & M O V E S
EMD Serono: Alise Reicin, MD , hasbeen appointed senior vice president,head of Global Clinical Development at
the U.S. biopharmaceutical business ofMerck KGaA, Darmstadt, Germany. Dr.Reicin will report to Luciano Rossetti,head of Global R&D, and serve as a mem-ber of the R&D executive leadership team.She will be based in Billerica, MA.
Dr. Reicin will oversee the ClinicalDevelopment organization, includingTherapeutic Areas; Evidence Value andDevelopment; Biostatistics; Clinical Op-erations; and both the Japan and ChinaR&D Hubs. In this capacity, she will leadthe biopharmaceutical business of Merck
KGaA, Darmstadt, Germany’s portfolio ofpipeline programs.
Dr. Reicin brings research and early/lateclinical development expertise, includingexperience in oncology and immunology.For the past 10 years she served as a vicepresident in various capacities across R&Dat MSD (Merck Sharp & Dohme). Herexperience complements Merck KGaA’sR&D strategy, which focuses on oncol-ogy, immuno-oncology and immunology,
with several high-priority programs in latedevelopment, such as evofosfamide (TH-
302) and avelumab (anti-PD-L1).“We are honored to have Alise join us,”said Luciano Rossetti, head of Global Re-search and Development. “Her impressiveexperience across diverse areas of clinicalresearch and operations will bring signifi-cant value to our organization. She is an ac-complished executive whose leadership willserve to significantly advance our clinicaldevelopment efforts and our strong commit-ment to enhance our R&D operating model.”
Theorem: Scott P. Treiber, Ph.D. , has
been appointed executive vice presidentand general manager. Dr. Treiber will
oversee all aspects of Theorem’s biophar-maceutical development, including earlyphase first-in-human and proof-of-con-cept studies and Phase II-IV studies acrossa wide range of therapeutic areas.
Previously, Dr. Treiber held executive po-sitions within the CRO and pharma indus-
tries. Dr. Treiber is a founding member of theClinical Research Exchange and is active in
the Chicagoland Chapter of the Associationof Clinical Research Professionals.
“Scott is an extraordinary individual with valuable experience in clinical development,medical affairs, data management and otherareas of biopharmaceutical development,”said John Potthoff, Theorem president and
chief executive officer. “He brings expertisein central nervous system, oncology, cardi-
Pfizer Appoints Worldwide
R&D LeadersEMD Serono appoints global clinical SVP
Pfizer has made two strategic appointments in its Worldwide R&D organiza-
tion. Michael D. Ehlers, M.D., Ph.D., has been named group senior vice president
and head of BioTherapeutics R&D and site head for Pfizer’s Cambridge and Boston,MA locations. Dr. Ehlers will report directly to Mikael Dolsten, M.D., Ph.D., president of
Worldwide R&D.
Also, John Lin, M.D., Ph.D., has been appointed senior vice president and chief
scientific officer of Rinat. Dr. Lin will report directly to Robert T. Abraham, Ph.D., group
senior vice president for Oncology-Rinat R&D.
Dr. Ehlers will continue to serve as chief scientific officer of Pfizer’s Neuroscience and
Pain Research Unit and will oversee the entire BioTherapeutics R&D organization. Dr.
Ehlers will be based in Cambridge. Prior to joining the company, Dr. Ehlers spent 12
years as the George Barth Geller Professor of Neurobiology and as a Howard Hughes
Medical Institute Investigator at Duke University.
“It’s a privilege to see extraordinary scientific talent rise to the opportunity to grow within
our organization and lead the future of Pfizer’s key R&D areas,” said Dr. Dolsten. “Mike is a
world-class talent who has made significant contributions in advancing our neuroscienceresearch efforts and is now poised to lead BioTherapeutics Research & Development into
the next era of potential breakthroughs for patients, not only in neuroscience and pain,
but in rare diseases, and also at Pfizer’s Centers for Therapeutic Innovation.”
Rinat is Pfizer’s biotechnology unit within the Worldwide R&D organization, located
in South San Francisco, CA. Dr. Lin joined Rinat in 2002 and continued in his role when
acquired by Pfizer in 2006. Since 2011, he has served as vice president of Experimental
Medicine with responsibility for overseeing immuno-oncology and discovery and valida-
tion biology efforts with particular expertise in cellular, molecular and in vivo neurobiology.
“John’s expertise in advancing differentiated antibody programs in both oncology
and non-oncology indications is at the core of Rinat’s proven track-record of bringing
potential therapies such as tanezumab, ponezumab and bococizumab into the clinic,”
said Dr. Abraham. “I am fully confident that he will continue to leverage Rinat’s unique
entrepreneurial culture to help us build a strong portfolio of cancer immunotherapeu-tics, and to help optimize their development in combinations with targeted therapies.
These contributions from Rinat will be critical to our overarching goal of delivering po-
tential durable or even curative therapies to cancer patients.”
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 111/132
June 2015 Twitter : @ContractPharma Contract Pharma 111
P R O M O T I O N S & M O V E S
ology, infectious diseases, respiratory andother prime therapeutic areas. We couldn’thave asked for a more perfect fit.”
Horizon Pharma: Brian K. Beeler hasbeen appointed general counsel, reportingto Timothy P. Walbert, chairman, presidentand chief executive officer. Mr. Beeler has also
joined the company’s Executive Committee.Mr. Beeler joined the company in 2013
as associate general counsel and chiefcompliance officer and was promoted tosenior vice president, legal and chief com-pliance officer in January 2015. He hasmore than 15 years of experience provid-ing counsel to businesses in the healthcare
and life sciences industries.Previously, Mr. Beeler served as associ-
ate general counsel for Fenwal, Inc., a glob-al life sciences manufacturer of productsfor transfusion medicine, and was seniorcounsel, business development, commer-cial and R&D at TAP Pharmaceuticals andTakeda Pharmaceuticals North America.
“Since Brian joined Horizon Pharma,he has been instrumental in guiding ourlegal and compliance functions, which are
vital to our long-term success,”said Timo-thy P. Walbert, chairman, president and
chief executive officer, Horizon Pharmaplc. “I have absolute confidence that asgeneral counsel, Brian will continue toprovide exemplary guidance and to helpus navigate our growing business.”
Also, Tim Ayers has been named vicepresident and chief compliance officer.Mr. Ayers has extensive experience in thebiopharma industry, and most recentlyserved as a principal and vice president atthe legal practice of Porzio, Bromberg &Newman in the Life Sciences Compliance,Commercialization and Regulatory Coun-
seling Department. Previously, he servedas vice president and chief compliance of-ficer at Dendreon Corp.
Immunomic Therapeutics (ITI): Lou-ise Peltier has been appointed vice presi-dent of regulatory affairs. ITI is a privately-held biotechnology company developing
vaccines based on its LAMP technology.Ms. Peltier has more than 30 years of
experience in the regulatory space and has worked both as a consultant and in-houseat PharmAthene, Northwest Biotherapeu-
tics, Caris Life Sciences, Guilford Pharma-ceuticals and Centocor, where she oversaw
regulatory filings, meetings and pharmaco- vigilance, in both the U.S. and abroad.
“Louise has experience both in-house
and consulting and understands the ever-evolving regulatory environment,”said Wil-liam Hearl, Ph.D., chief executive officer ofITI. “As ITI continues to develop as a com-pany and we continue to take our productsthrough the regulatory process, we look for-
ward to success under Louise’s guidance.”
Advaxis: Thomas W. Hare has beenappointed vice president, Clinical Opera-tions. Mr. Hare has more than 28 years ofexperience in the biopharmaceutical andCROs industries overseeing the manage-
ment of global commercial and clinicaloperations, data management, outsourc-ing and medical writing groups.
Mr. Hare will oversee clinical opera-tions for the company’s multiple Lm-LLOcancer immunotherapy clinical programs,and will report to Advaxis’s executive vicepresident, chief medical officer, David J.Mauro, MD, Ph.D.
Advaxis initiated three new trials, in-cluding the combination study involving
ADXS-PSA and Merck’s PD-1 checkpointinhibitor KEYTRUDA (pembrolizumab).
The company also expects to initiate fiveadditional trials by the end of year to eval-uate its Lm-LLO immunotherapy.
Most recently, Mr. Hare served as vicepresident, Drug Development Opera-tions for Incyte Corp. He joined Incyte in2004 and was responsible for the strategicgrowth and development of a team, whichimplemented Phase I - Phase III multina-tional trials in cancer immunotherapy andcancer inflammation clinical trials.
Prior to Incyte, Mr. Hare was directorof operations at PRA International and
served as vice president, Clinical Opera-tions Division for Premier Research andas clinical manager/senior clinical scientistfor Bristol Myers-Squibb.
“Adding an individual of Thomas’sexpertise comes at a pivotal moment for
Advaxis as we continue to advance severalclinical programs during 2015, includingthe initiation of five new clinical trials,”said Daniel J. O’Connor, president andchief executive officer of Advaxis. “Thomasbrings a wealth of experience overseeingthe design, conduct and management of
resources for clinical trials. His expertise will be essential as we look to expand our
clinical development program, while en-suring we remain on budget and on track.”
Recipharm Italia: Giorgio Bruno hasbeen appointed general manager and
will serve as chief executive officer for thecompany’s Italian operating companies,
which employs 257 people at three sites.Dr. Bruno has senior management ex-
perience in the pharmaceutical industry,particularly in the area of manufactur-ing. He has worked in both Italian andmultinational pharmaceutical companiescovering a wide range of disciplines withresponsibility for quality and manufactur-ing at companies including Parke Davis,
AstraZeneca and Corden Pharma.“Commenting on the appointment,
Thomas Eldered, chief executive officer ofRecipharm said, “I am very pleased to wel-come Dr. Bruno to the Recipharm team.
We are very fortunate to have been ableto attract such a competent and highly ex-perienced manager to this important posi-tion and I look forward to him bringing hisexpertise to bear across our Italian opera-tions for which he is now responsible.”
AIT Bioscience: Terri Pascarelli has
been appointed chief executive officer andmember of the board of directors. Ms. Pas-carelli brings extensive business and en-trepreneurial leadership to the company’sexecutive management team.
Ms. Pascarelli has held leadership posi-tions with life science companies for morethan 25 years. Prior to joining the compa-ny, she was vice president of client devel-opment for YourEncore, Inc., a consultingfirm. She held executive leadership rolesas president and chief operating officer ofan Idiana-based pharma company and for
a privately held Midwest medical lab. Shealso held leadership roles in strategy, salesand marketing, managed markets, R&Dand commercial operations at BoehringerIngelheim, Roche and AstraZeneca.
“When it comes to supporting bio-pharma drug development, AIT is capableof finding the best solution for the situa-tion, be it using LC-MS/MS for small mol-ecule analysis or ligand binding analysismethods for large molecule analysis, orboth,”said Ms. Pascarelli. “Delivering highquality bioanalytical service that is defined
from the customer’s point of view is a bigreason why I joined the company.”CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 112/132
112 Contract Pharma contractpharma.com June 2015
F I N A N C I A L R E P O R T S
Gilead1Q Revenues: $7.6 billion (+52%)1Q Earnings: $4.3 billion (+95%)
Comments: Antiviral product sales were$7.0 billion in the quarter, up 56% driv-en by the company’s newest HCV drugHarvoni ($3.6 billion in sales), which
was approved in the U.S. and Europe in4Q14, partially offset by a decrease insales of Sovaldi, down 57% to $972 mil-lion. In the HIV franchise, Truvada sales
were $771 million, up 1%; Atripla sales were down 6% to $734 million; Stribildsales were up 66% to $356 million; Com-plera sales were up 27% to $320 million;and Viread sales were $234 million, up
11%. Other product sales, which includeLetairis, Ranexa and AmBisome, were$417 million in the quarter, up 15%.
Pfizer1Q Revenues: $10.9 billion (-4%)1Q Earnings: $2.4 billion (+2%)Comments: Established product sales
were down 10% to $5.0 billion in thequarter, primarily due to the loss of ex-clusivity for Celebrex in the U.S., as wellas generic competition for Zyvox IV in
the U.S., and for Lyrica in certain devel-oped European markets. These declines were partially offset by performance inemerging markets, where revenues in-creased 10% operationally, primarilydriven by Lipitor, Viagra and Norvasc.Global Vaccine sales were up 44% to $1.3billion. Consumer Healthcare sales wereup 6% to $808 million. Global Oncologysales were $528 million up 8%. R&D Ex-penses were up 16% to $1.9 billion.
Merck1Q Revenues: $9.4 billion (-8%)
1Q Earnings: $953 million (-44%)Comments: Pharmaceutical sales were$8.3 billion, down 2% in the quarter.
JANUVIA/JANUMET sales were $1.4 bil-lion, up 4%. ZETIA/VYTORIN sales weredown 9% to $887 million. REMICADEsales were down 17% to $501 million. IS-ENTRESS sales were $385 million, down1%. GARDASIL / GARDASIL 9 sales
were down 6% to $359 million. PRO-QUAD, M-M-R II and VARIVAX sales
were up 24% to $348 million. AnimalHealth revenues were up 2% to $829 mil-lion. Results include a 5% negative im-pact from foreign exchange and a 9% un-favorable impact from the divestiture of
the Consumer Care business and selectproducts, partially offset by the acquisi-tion of Cubist Pharmaceuticals.
Novartis1Q Revenues: $11.9 billion (-7%)1Q Earnings: $2 .3 billion (-6%)Comments: Pharmaceutical sales were$7.1 billion in the quarter, down 9%,and included the new oncology assetsacquired from GSK (sales of $0.2 billionin March), offset by the negative im-
pact of generic competition, largely forDiovan, Exforge and Vivelle-Dot in theU.S. Growth Products, which includeGilenya, Afinitor, Tasigna, Galvus, Lu-centis, Xolair, the COPD portfolio, and
Jakavi - generated $2.9 billion, up 25%. Alcon sales were $2.6 bill ion, down 3%in the quarter. Sandoz sales were $2.2billion, down 3%. U.S. sales of genericsand biosimilars were up 13% (cc), drivenby continuing strong performance fromrecent launches and Fougera sales. Thecompany gained three approvals in on-
cology in the quarter: Jakavi in polycy-themia vera (EU), Farydak in multiple
myeloma (U.S.) and Jadenu for chroniciron overload (U.S.).
Bristol-Myers Squibb1Q Revenues: $4.0 billion (+4%)1Q Earnings: $1.2 billion (+27%)Comments: U.S. revenues were up16% to $2.0 billion in the quarter. In-ternational revenues decreased 2% to$2.0 billion. Eliquis sales were $355 mil-lion, up from $106 million in 1Q14. Yer-
voy sales were up 20% to $325 million.Orencia and Sprycel grew 10% to $400million and $375 million, respectively.Daklinza and Sunvepra had combined
sales of $264 million and Opdivo hadsales of $40 million. R&D expenses wereup 7% to $1.0 billion in the quarter.
Hospira1Q Revenues: $1.2 billion (+12%)1Q Earnings: $75.6 million (+11%)Comments: Growth in the quarter
was driven by sales of Specialty Inject-able Pharmaceuticals (SIP) in the U.S.(+17% to $665.5 million), as well as bio-similar sales in the Europe, Middle East
and Africa (EMEA) segment. GlobalSIP sales were $808.5 million, up 13%.Sales growth offset the decl ine Precedex,
which lost market exclusivity in 2H14.
Lilly1Q Revenues: $4.6 billion (-1%)1Q Earnings: $529.5 million (-27%)Comments: Revenue in the U.S. in-creased 6% to $2.2 billion, driven byincreased volumes for Cyramza ($67.5million), and the inclusion of revenue
from Novartis Animal Health ($749.8million, up 42%). Revenue outside the
Quarterly ReportsGilead’s Harvoni drives growth but offsets Sovaldi sales
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 113/132
June 2015 Twitter : @ContractPharma Contract Pharma 113
F I N A N C I A L R E P O R T S
U.S. decreased 6% to $2.4 billion due tounfavorable impact of foreign exchange.Lingering effects of U.S. patent expira-
tions for Cymbalta (-40% to $287 mil-lion) and Evista (-55% to $66.8 million)continue to negatively impact results.Zyprexa sales were down 22% to $219.5million. Alimta sales were $573.0 mil-lion, down 9%. Cialis sales were up 1%to $538.3 million. Humalog sales wereup 5% to 684.0 million.
Baxter1Q Revenues: $3.8 billion (-2%)1Q Earnings: $430 million (-23%)
Comments: Sales in the U.S. grew 4%to $1.7 billion, while international sales
were $2.1 billion, down 6%. Excludingthe impact of foreign currency, Baxter’ssales grew 4% in the quarter. Baxter’sBioScience business generated revenuesof $1.4 billion, up 2% driven by immu-noglobulin treatments for primary im-munodeficiency (PI), hemophilia andinhibitor therapies, and certain biothera-peutics. Medical Products sales were $2.4billion, down 5%. Excluding foreign cur-rency, sales increased 2%. Results include
separation-related costs of $117 millionfor the planned separation of Baxter’sbiopharmaceutical and medical productsbusinesses and charges of $18 million re-lated to the integration of Gambro.
Biogen1Q Revenues: $2.6 billion (+20%)1Q Earnings: $823 million (+71%)Comments: Total multiple sclerosisproduct sales were $2.1 billion comparedto $1.7 bil lion in 1Q14. TECFIDERA rev-
enues were $825 million, up 63%. Inter-feron revenues, including AVONEX andPLEGRIDY, were flat at $755 million.TYSABRI revenues were $463 million,up 5%. Revenues relating to RITUXANand GAZYVA from Biogen’s unconsoli-dated joint business arrangement were$331 million, up 11%.
Amgen1Q Revenues: $5.0 billion (+11%)1Q Earnings: $1.6 billion (+51%)
Comments: Product sales were up 13%driven by Enbrel (+13% to $1.1 billion),
Prolia (+39% to $170 million), EPOGEN(+16% to $534 million), Sensipar (+24%to $241 million) and XGEVA (+22% to
$245 million). Neulasta/NEUPOGENsales were flat at $1.1 billion. Unfavor-able changes in foreign exchange ratesimpacted revenue by 2 percentagepoints. R&D expenses were down 14%to $856 million.
Catalent3Q Revenues: $446.6 million (+8%)3Q Earnings: $31.5 million (earnings
were $6.7 mil lion 3Q14)YTD Revenues: $1.3 billion (+1%)
YTD Earnings: $58.5 million (loss of$11.0 mill ion YTD14)Comments: Growth was driven by theOral Technologies segment ($284.0 mil-lion, +10% at constant currency) andincreased demand for analytical servicesintegrated operations within its Develop-ment and Clinical Services segment with$103.7 million for the quarter, up 4% atconstant currency. Revenue from theMedication Delivery Solutions segment
was $61.2 million, up 2% at constantcurrency. In the quarter, the company
acquired Pharmapak Technologies, andcompleted a large-scale expansion at the Winchester, KY manufacturing facility.
Sanofi1Q Revenues: €8.8 billion (+12%)1Q Earnings: €1.1 billion (flat)Comments: Pharmaceutical sales were€7.5 billion, up 2% at Constant ExchangeRates (CER). Diabetes sales were €1.8 bil-lion, down 3% reflecting expected pricingimpact on Lantus in the U.S. Vaccines
sales were €697 million, down 5% due toexpected delay in Southern Hemisphereinfluenza campaign. Genzyme sales were€821 million, up 31% mainly driven by
Aubagio. Animal Health sales were up14% driven by NexGard.
AMRI1Q Revenues: $81.8 million (+38%)1Q Loss: $2.2 million (earnings were$3.5 million in 1Q14)Comments: Contract revenue in the
quarter was $75.1 million, up 47% drivenby the Drug Product business, increased
capacity utilization, and the benefit of costreduction initiatives and facility optimiza-tion. Discovery and Development Services
contract revenue was $19.3 million, up1%. API contract revenue increased 27%to $37.8 million, which includes the addi-tion of Cedarburg Pharmaceuticals. DrugProduct Manufacturing revenue increased$15.7 million to $18.0 million, reflectingthe addition of OsoBio acquired in July2014, and the Glasgow, UK injectable drugproduct formulation business acquiredin January 2015. During the quarter, thecompany recorded $2.5 million of impair-ment and $1.3 million of restructuringcharges related to ceasing operations at
its Holywell, UK facility. Royalty revenue was $6.7 million, down 19% due to lowerroyalties on Allegra (fexofenadine) prod-ucts. Royalty revenue includes $3.8 millionfrom the fexofenadine products and $2.9million from the sales of certain amphet-amine salts sold by Actavis.
Alkermes1Q Revenues: $161.2 million (+24%)1Q Loss: $30.7 million (loss of $24.4million in 1Q14)
Comments: Manufacturing and roy-alty revenues from the company’s long-acting atypical antipsychotic franchise,RISPERDAL CONSTA and INVEGASUSTENNA/XEPLION were $46.9 mil-lion, down 5%. Manufacturing and roy-alty revenues from AMPYRA/FAMPYRA
were $36.5 million, up 77%. Sales of VIVI-TROL were $31.1 million, up 82%. R&Dexpenses were up 35% to $70.3 million.
Teva
1Q Revenues: $2.6 billion (+9%)1Q Earnings: $444 million (-40%)Comments: Generic revenues were $2.6billion, up 9%. U.S. revenues were $1.4billion, up 37% mainly from the launchof esomeprazole (a generic of Nexium).European revenues were $680 million,down 17% mainly from the company’sstrategy of pursuing sustainable businessin the region, with significant decreasesin Spain and France, offset by increasesin Italy and Germany. ROW revenues
were $502 million, down 6%. API sales
to third parties were $157 million, down12%. Specialty medicines revenues were
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 114/132
114 Contract Pharma contractpharma.com June 2015
F I N A N C I A L R E P O R T S
$2.0 billion, down 7% primarily due tolower sales of Copaxone, which werepartially offset by higher revenues of re-
spiratory products. U.S. specialty medi-cines revenues were $1.5 billion, down3%, and European revenues were $405million, a decrease of 16%. ROW sales
were $72 million, down 29%.
West1Q Revenues: $335.9 million (-3%)1Q Earnings: $32.9 million (+10%)Comments: Currency translation im-pacted growth by 10%. Sales at constantcurrency grew 6% due to an increase in
high-value packaging component sales.Pharmaceutical Packaging Systems(PPS) sales were $242.5 million, up 8%at constant currency. PharmaceuticalDelivery Systems (PDS) sales were $93.5million, up 3% at constant currency.
Charles River Laboratories1Q Revenues: $320.4 million (+7%)1Q Earnings: $31.6 million (-3%)Comments: Research Models and Ser-
vices (RMS) revenue was $120.0 million,
down 9%, primarily due to the Geneti-cally Engineered Models and Services(GEMS) business and lower sales of re-search models in Europe. Discovery andSafety Assessment (DSA) revenue was$140.0 million, driven primarily by theEarly Discovery acquisitions, which con-tributed 23% to DSA revenue growth.Revenue for the Manufacturing segment
was $60.4 mil lion, down 2%. Foreign ex-change reduced revenue growth by 8%.On a constant-currency basis, growth
was 6%, with the Endotoxin and Micro-
bial Detection (EMD) business up 10%.This was partially offset by a slow startto the year for the Biologics Testing So-lutions business.
Quintiles1Q Revenues: $1.0 billion (+2%)1Q Earnings: $86.4 million (-4%)Comments: Product Development ser-
vice revenues were $749.5 million in thequarter, down 3%, negatively impactedforeign exchange. Integrated Health-
care Services revenues increased 20% to$280.5 million, with increases in com-
mercial solutions in Japan and North America, along with growth in real- world and late phase research services.
New business amounted to $1.35 billionin the quarter, up 6%, representing a1.31 book-to-bill ratio.
INC Research1Q Revenues: $211.5 million (+15%)1Q Earnings: $25.3 million (loss of $1.7million 1Q14)Comments: New business awards were$255.5 million in the quarter, as com-pared to $280.9 million in 1Q14, and abook-to-bill ratio of 1.2x. Service rev-
enue was $211.5 million in the quarter,up 15%, with particularly strong growthin CNS, Oncology and other complextherapeutic areas.
ICON1Q Revenues: $388 million (+11%)1Q Earnings: $56 million (+55%)Comments: Gross business wins were$516 million in the quarter, represent-ing a book to bill of 1.33. Net business
wins were $454 million, representing a
net book to bill of 1.17.
Alexion1Q Revenues: $600.3 million (+6%)1Q Earnings: $91.3 million (-43%)Comments: Sales of Soliris were $600.3million, up 6%. The company enteredthree agreements in 1Q for the clinicaldevelopment and commercialization ofdrug products and recorded R&D ex-pense for upfront payments of $112.0million. Restructuring expenses in the
quarter related to the relocation of itsEuropean headquarters from Lausanneto Zurich, were $7.1 million.
Johnson & Johnson1Q Revenues: $17.4 billion (-4%)1Q Earnings: $4 .3 billion (-9%)Comments: Pharmaceutical sales were$7.7 billion, down 7% in the quar-ter. RISPERDAL CONSTA sales weredown 18% to $254 million. VELCADEsales were down 17% to $339 million.
OLYSIO/ SOVRIAD sales were down34% to $234 million, due to generic
completion. REMICADE sales were $1.6billion, down 0.6%. STELARA sales were$549 million, up 20%. CONCERTA sales
were $224 million, up 49%. SUSTENNA/ XEPLION sales were $441 million up10%. During the quarter, the FDA ap-proved IMBRUVICA for the treatment of
Waldenström’s Macroglobulinemia andfor PREZCOBIX in combination withother antiretroviral medicinal productsfor the treatment of HIV-1. WorldwideConsumer sales were $3.4 billion in thequarter, down 5%.
WuXi PharmaTech
1Q Revenues: $180.0 million (+23%)1Q Earnings: $17.8 million (flat)Comments: Laboratory Services grew21% to $114.3 million in the quarter.Small-Molecule Manufacturing Servicesincreased 15% to $45.5 million. BiologicsServices revenues were up 75% to $14.4million.
PRA Health Sciences1Q Revenues: $388.6 million (+10%)1Q Earnings: $17.2 million (loss of
$10.0 million 1Q14)Comments: Service revenue was $332.0million in the quarter, up 7%. Net newbusiness for the quarter was $398.0 mil-lion representing a book-to-bill ratioof 1.2 for the period. This new businesscontributed to an ending backlog of $2.2billion at March 31, 2015.
ANI Pharmaceuticals1Q Revenues: $18.8 million (+72%)1Q Earnings: $4.4 million (+30%)
Comments: Generic sales were up 52%to $12.3 million primarily due to in-creased sales of EEMT, as well as Meth-azolamide and Etodolac products, whichlaunched in 4Q14 and 1Q15, respec-tively. Branded pharmaceutical sales in-creased 452% to $4.3 million, driven bysales of Lithobid and Vancocin, which
were acquired in 3Q14. Contract manu-facturing revenue was down 26% to $1.2million as a result of timing of customerorders. Contract services and other reve-nues increased 136% to $1.1 million due
to royalties from the authorized genericof Vancocin. CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 115/132
June 2015 Twitter : @ContractPharma Contract Pharma 115
A S S O C I A T I O N S & E V E N T S
T
he 2015 BIO International Convention will take place June15-18, at the Pennsylvania Convention Center in Phila-delphia, PA. BIO represents biotechnology companies,
academic institutions, state biotechnology centers and relatedorganizations across the U.S., as well as more than 30 other na-tions. Members are involved in the research and development ofinnovative healthcare, agricultural, industrial and environmentalbiotechnology products.
The annual convention showcases the latest biotechnologyinnovations, as well as insight into biopharma industry trendsand challenges around drug discovery and development, manu-facturing, regulations, and business development.
The exhibition will feature more than 1,800 exhibitors withina Domestic and International Pavilion broken down into ProductFocus Zones including Academics, BIO IT, BIO Member Services,BIO Process, Business Services, Contract Services, Digital Health,
Discovery, and Innovation.
Session HighlightsTuesday’s Keynote Luncheon will feature Tom Brokaw inter-
viewed by Jim Greenwood, President & CEO, BIO. A journalis-tic icon, Tom Brokaw has traveled the globe to cover elections,summits, political turmoil, war, and major news stories of everydescription. He’ll share his observations on the state of the U.S.and the world—and the people behind the headlines. Tuesday,
June 16, 12:00 p.m. – 1:30 p.m. Wednesday’s Keynote Luncheon will feature Dr. Eric J. Topol,
the Dean of Digital Medicine and well-known speaker on thefuture of healthcare. He was voted the #1 Most Influential Physi-
cian Executive in the U.S. in a poll conducted by Modern Health-care. Dr. Topol is widely recognized as the leading authority ondigital medicine and its impact on every branch of healthcare.
June 17, 12:00 p.m. –1:30 p.m.The conference program will also feature Super Sessions focus-
ing on analysis, forecasts and discussions on industry hot topics.
Ensuring Patient Access to Innovative Medicines , the panel will iden-tify the root of these access challenges and discuss potential pol-icy implications in addressing these challenges. Tuesday, June 16,10:00 a.m. – 11:30 a.m.
Speakers: Randy Beranek, president and CEO, National Psoria-sis Foundation, Arthur Caplan, PhD, Director, Division of Medical
Ethics, New York University Langone Medical Center; and RichardPops, Chairman and Chief Executive Officer, Alkermes, Inc.
M&A and Capital Allocation: Everything Old is New Again , this panelbrings together CEOs and other senior leaders with firsthandexperience navigating the deal landscape while balancing theoften conflicting demands of investors, patients, employees and
regulators. The panel will be supplemented with data from recentErnst & Young (EY) research on M&A statistics, firepower andactivism. Tuesday, June 16, 2:00 p.m. – 3:30 p.m.
Speakers: Geno Germano, Group President, Global Innova-tive Pharma Business, Pfizer and David Pyott, Former Chairmanof the Board and Chief Executive Officer (1998-2015), Allergan
Investment Incentives to Combat Antimicrobial Resistance (AMR) , Antimicrobial resistance has become a significant public health is-sue, affecting all countries and causing increasing hospitalizations,extended illness, and escalating healthcare costs. Panelists will dis-cuss various global initiatives and what incentives will best encour-age industry R&D. Wednesday, June 17, 10:00 a.m. – 11:30 a.m.
Speakers: Julie Gerberding, MD, Executive Vice President,Strategic Communications, Global Public Policy, and PopulationHealth, Merck & Co., Kenneth J. Hillan, Chief Executive Officer,
Achaogen
Accelerating Innovation in the 21st Century , Policymakers and regu-lators in the U.S. and Europe are increasingly considering howbest to accelerate innovation. Panel participants will have a robustpolicy discussion that considers some of the challenges, identifies
what has worked well. Wednesday, June 17, 2:00 p.m. – 3:30 p.m.Moderator: Paul Hudson, President, AstraZeneca U.S. and Ex-
ecutive Vice President, North America, AstraZeneca
Riding the Bull Market: What’s in Store for Biotech Dealmakers in 2015? Campbell Alliance and BIO will present updated findings from
2015 BIO Convention
Heads to PhillyNotes and news highlights from INTERPHEX 2015
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 116/132
116 Contract Pharma contractpharma.com June 2015
A S S O C I A T I O N S & E V E N T S
A S S O C I A T I O N S & E V E N T S
INTERPHEX 2015 was held April 21-22, at the Javits Cen-
ter in New York. The show covered the latest in pharma andbiopharma manufacturing trends and solutions to process all
dosage forms and featured the latest equipment designs, contract
manufacturing and technology, as well as single-use technology.The event drew more than 12,000 global pharma and biopharma
Notes & News Highlights fromINTERPHEX 2015Event showcased the latest Pharma and biopharma manufacturing trends while drawing12,000+ professionals
Advantar Labs 631
Alfa Wassermann Separation Technologies 5117 Alliance Pharma 5129
AMRI 727
Avid Bioservices, Inc. 533
Bachem Americas, Inc. 539
BioPharm International 638
BioTechnique 5216
BRI Biopharmaceutical Research Inc. 840
Case Western Reserve University School 541
of Medicine Innovations
Coldstream Laboratories 730
Contract Pharma 1526Cook Pharmica 734
GCT 5019
Germfree Laboratories 640
GlaxoSmithKline Biopharmaceuticals 349
HiQScreen 739
Institute of Industrial Organic 735
Chemistry Branch Pszczyna
Jubilant HollisterStier 637
KBI Biopharma, Inc. 743
Lab Support 834
LSNE Contract Manufacturing 741Lyophilization Technology, Inc. 737
mtibio 844
MultiLing 838
NEUROSERVICE 738
Ohio Clinical Trials Collaborative (OCTC) 543
OnPoint CRO 644
Paragon Bioservices, Inc. 527
PolyPeptide Group 635
Worldwide Clinical Trials 842
WuXi AppTec, Inc. 643
Company Booth Company Booth Company Booth
2015 Exhibitors: Contract Services Zone (As of 05/15/15)
two forward-looking measures of deal-making in the industrybased on a survey of more than 150 industry executives and busi-ness development professionals. This session provides insight
into what will likely drive the industry’s partnering and M&A ef-forts moving forward, and the implications for deal-making overthe next year or more. Thursday, June 18, 10:00 a.m. – 11:30 a.m.
Moderators: Sougato Das, Director, Partnering, BiotechnologyIndustry Organization and Neel Patel, Director, Corporate Devel-opment, Campbell Alliance
Speaker: David H. Donabedian, Ph.D, Vice President, Head of Ventures & Early Stage Collaborations, AbbVie Inc. The Next Step: How Companies Build Successful Therapeutic Fran-chises from the Ground Up , Building a franchise in a new thera-peutic area from the ground up raises a host of questions: howmuch risk should be accepted, how quickly, and how large, whatcapabilities are needed, and is a partner needed to fully lever-
age the opportunity. Panelists will provide real life examples of what it takes to build a therapeutic franchise through a moder-ated panel discussion. Thursday, June 18, 12:00 p.m. – 1:30 p.m.
Scientific American WORLDVEW , What is happening in biotech-nology and life science development on the global stage? Whichissues will bring all nations together in the future? Panelists at thisannual SCIENTIFIC AMERICAN Worldview will examine the fu-
ture of global innovation. Thursday, June 18, 2:00 p.m. – 3:30 p.m.Moderator: David Brancaccio, Host, American Public Media’s
Marketplace Morning Report
Networking EventsMonday, June 15: Kickoff Concert at Liacouras Center will featureRoots, Boyz II Men and Kool and the Gang, 7:00 p.m. – 9:00 p.m.
Wednesday, June 17: Unplugged Pre-Party + Reading TerminalReception in the Grand Hall will offer drinks, music, and enter-tainment from 6:30 p.m. – 7:30 p.m., followed by the Reading Ter-minal Market Reception, a block party to sample Philadelphia’sfinest 7:30 p.m.– 9:30 p.m.
Wednesday, June 17: The Exhibitor Hospitality Receptions, the showslargest networking event, will take place in the exhibit hall with food,
drinks, entertainment and giveaways from 5:00 p.m. – 6:30 p.m.
Exhibit ScheduleTuesday, June 16, 9:30 a.m. – 5:30 p.m.
Wednesday, June 17, 9:30 a.m. – 5:30 p.m. Exhibitor Hospitality Receptions: 5:00 p.m. – 6:30 p.m.Thursday, June 18, 9:30 a.m. – 5:30 p.m.
For more information visit: convention.bio.orgCP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 117/132
June 2015 Twitter : @ContractPharma Contract Pharma 117
A S S O C I A T I O N S & E V E N T S
professionals along with 600 suppliers. Addition-ally, sessions addressed manufacturing challenges,best practices for quality agreements, regulatory
concerns, supply chain initiatives, and overcom-ing packaging challenges, among others.
SGS Completes Mumbai ExpansionSGS Life Science Services completed a majorexpansion at its Mumbai, India, facility with
validation of new equipment currently under- way. The expansion has seen the previous 1,393square meter lab space more than double insize, and, once validation is completed, the lab
will act as a dedicated cGMP pharmaceuticaltesting site. Investment at the lab focused on in-creasing stability chamber capacity and in sup-
porting chromatography equipment, includingnew UPLC capabilities.
Vetter Serializes Product forSouth Korean Market
Vetter has manufactured the first commercialbatches with single-use identification numbers inaccordance with serialization requirements of the South KoreanMinistry of Food and Drug Safety (MFDS). Vetter introduced itsserialization service last year, and has now implemented productserialization for secondary packaging for a top pharma company.
Catalent Launched Advasept Lock Technology
Catalent launched Advasept Lock, a stopper-less, glass- andneedle-free vial for the delivery of injectable medications. Adva-sept Lock attaches to a luer syringe, combining a safe, convenientand functional container closure with the security of an advancedaseptic filling solution. Advasept Lock addresses sterile manufac-turing challenges by automating the container formation and fill-ing of the drug product into a glass-free container closure, elimi-nating glass particulates and delamination issues, and reducingthe risk of foreign particle and microbial contamination.
Metrics Adds Analytical Lab EquipmentMetrics Contract Services invested about $200,000 to add a Ther-mo Scientific iCAP Q ICP-MS mass spectrometer and a Mile-
stone UltraWAVE Single Reaction Chamber digestion vessel toits analytical lab. The investment follows substantive changesfrom the USP concerning the testing of elemental impurities. Thenew USP 232 and 233 guidelines, which take effect in December,require that finished drug products meet stricter minimal con-tamination levels for elemental impurities.
MG America Launched MultiNETTMG America introduced the on-board MultiNETT Weight Con-trol System for capsule manufacturing lines. MultiNETT is a 100%
weight control system that monitors and reports the net weightof each dosed capsule. It can check product micro-dosages anddifferent components in various dosage combinations, and ac-
cording to the company, achieves the highest degree of accuracy,even for low-dose applications.
Fette Introduced the FE75Fette Compacting America introduced the FE75 Tablet Press, adouble-sided rotary press that can be equipped with up to 115punch stations to produce more than 1.6 million tablets per hour.Ideal for the premium production of large batches, the FE75’sfour compression rollers feature a special control system for di-
rect compression, enabling the machine to operate with two in-termediate pressures.
Rondo-Pak Introduced Shock-resistant CartonRondo-Pak introduced a shock- and vibration-resistant foldingcarton for steriles or liquids that require extra protection. RondoSafepack is designed to naturally dissipate vibration resulting inreduced breakage potential for glass or other contents, and fea-tures a double-walled construction and auto-actuating cushionflaps on its top and bottom that protect against severe impact andprovide higher crush resistance.
Thermo Scientific Launched Next-Gen Single-Use Mixers
Thermo Scientific introduced HyPerforma Single-Use Mixers(SUM) with advancements that address the requirements ofsingle-use bioprocessors from scale-up to cGMP manufactur-ing. According to the company, new features include optimizedtubing management, advanced clean-in-place sterilization, rapidset-up and turn-around times, and streamlined handling of haz-ardous materials. The new HyPerforma range provides six capac-ity options: 50L, 100L, 200L, 500L, 1000L and 2000L, simplifiedset-up and cleaning, and easy loading of bioprocess containers,according to the company.
For Contract Pharma’s full INTERPHEX coverage, including videos from the show floor, visit: shows.contractpharma.com/
conf/interphex2015 CP
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 118/132
118 Contract Pharma contractpharma.com June 2015
R E A D E R S H O W C A S E
Sartorius Stedim Biotech has launched
a new version of its stainless steel fermen-tor/bioreactor BIOSTAT D-DCU. The
compact and modular, in-situ sterilizablesystem is suitable for microbial and cellcultures and is supplied in working vol-umes of 10 to 200 liters. Typical applicationareas for the BIOSTAT D-DCU includethe process development and productionof small-batch biopharmaceuticals, vac-cines, enzymes, along with antibiotics andother secondary metabolites.
The modular design of the BIOSTATD-DCU enables flexible configuration ofthe bioreactor system and available op-tions range from a basic batch set-up to
sophisticated configurations supportingadvanced gassing and feeding strategies,
WIT-Ready filter housings and automatictransfer of seed to a larger bioreactor orsterile harvest into a stainless steel vesselor single-use bag.
With its standardized componentsand functions, design lead times are ab-breviated, which results in faster systemdeliveries, according to the company. Thebioreactor’s control unit is available in a
single- or twin version and can drive oneor two culture vessels simultaneously and
independently of each other and they havea 19”intuitive touch screen. In addition tocontrolling relevant process parameterslike temperature, agitator speed and pres-
sure, pH and DO (pO2), optical densityetc., the system features fully automaticsterilization and cleaning functions.
More info: www.sartorius.com
Grifols Introduces New AutomatedFilling LineGrifols has introduced an automated,fully-integrated filling line for vials from5mL to 50mL with intermediate volumesfilling and automatic machine inspection(particulate matter, filling volume, glassdefects and capping), as well as one line
for labeling and packaging.Technical features include:
• Washing process with WFI80• Depyrogenation ensuring at least 3 log
reductions in endotoxin levels.• Filling through peristaltic pump
(four vial fillers) to achieve the mostdemanding requirements in terms ofdose limit and timing.
• Laser edging of vials after capping – Provides a Unique Identification
Number for every single vial – Ensures traceability – Permits flexibility in shipping
without label if needed• Automated visual inspection of printing • Terminal sterilization• Capability to allocate different types of
glass and plastic vials
The new filling line was designed atGrifols Engineering, S.A., allowing the
SAFC LAUNCHES NEW EX-CELL PRODUCTSFOR BIO-MANUFACTURING
SAFC Commercial, the custom manufacturing services business unit of Sig-
ma-Aldrich Corp., has launched the new EX-CELL Advanced product line designed to
address evolving industry needs for speed, increased performance, regulatory compli-
ance, and supply chain security.
The first EX-CELL Advanced product is the batch media system developed for a
range of widely used industrial CHO cell lines, including SAFC’s CHOZN cell line. During
testing, the EX-CELL Advanced CHO Fed-batch System outperformed other commer-
cially available equivalents displaying significantly higher titers, according to the compa-
ny, with robust scale up and adaptation and protein quality in the development process.
“At SAFC we recognize our customers’ needs are constantly changing”, said Deb
Stutz, director of Biopharm Marketing. “Our team has utilized unique expertise in raw
material science, understanding of process knowledge and decades of experience in
cGMP manufacturing in development of the new EX-CELL Advanced line. We are de-lighted to launch this product in response to market needs for new levels of speed and
performance, while continuing to provide the confidence of a secure and transparent
supply chain.”
EX-CELL Advanced products are available now as catalog products in a range of
pack sizes.
More info: www.sigma-aldrich.com/CHOperformance
Sartorius Launches
BIOSTAT D-DCUSAFC launches new EX-CELL products for bio-manufacturing
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 119/132
June 2015 Twitter: @ContractPharma Contract Pharma 119
R E A D E R S H O W C A S E
development of a high-tech solution thatcomplies with the strict manufacturingstandards required by health authoritiessuch as FDA and EMA.
More info: www.grifolsengineering.com
Romaco Launches Noack 900 SeriesBlister MachinesRomaco North America has launched
the Noack 900 Series of Blister Machinesoffering high levels of automation withservo and automated controls to ensureoperator-independent precision. The No-ack 900 series Blister Machines comprisestwo models: the 930, which can produceas many as 480 blisters per minute in amaximum of four rows within a formingarea of 155x180 mm; and the Noack 960,
which can produce 700 blisters per minute with as many as six rows, with a maximumforming area of 225x180 mm. Both are ca-pable of a forming depth of up to 12 mm.
Both machines in the 900 series can besupplied with either platen or rotary seal-ing and include a balcony structure thatensures cGMP compliance, as well as in-tegrated track & trace and containment.
Additional features include:• QuickFeed, an interchangeable
feeding system allows quick productchangeovers.
• The automatic station control systemQuickAdjust provides continuous ad-
justment of sealing, coding perforationand cutting for short run-in times and
consistent processes.• QuickTransfer utilizes a servo-driven
blister transfer and incorporates a
servo-controlled de-stacking indepen-dent of specific blister formats
• QuickClean reduces cleaning times with easy access, and surfaces withoutedges and corners designed to elimi-nate entrapment of product.
• QuickAdmin insures reproducibleprocesses from the HMI panel withintuitive visualization and navigation
More info: www.romaco.com
Lonza Introduces CytoSMART Systemfor Live Cell Imaging
Lonza has released the CytoSMARTSystem, a live cell imaging system thatenables researchers to take time-lapse
videos and images of their cell culture without needing to manually inspect theircells. The images are transmitted into thecloud, allowing researchers to view theircell culture outside of the actual cell cul-ture lab at any time.
The CytoSMART System offers assur-ance that cells are safe without having tobe in the lab and provides functions, suchas reporting ongoing cell confluency via a
graphical readout, while automatic emailalerts can be set to inform the user when
milestones are reached (for example, once
the cell culture has reached a certain con-uency). The CytoSMART Connect CloudProject page allows users to view anddownload all the videos and images con-nected with their project.
“Researchers that have tested the Cy -toSMART Prototype have used it for a va-riety of different applications, such as cellculture monitoring and documentation,migration and scratch assays and cell cul-ture standardization. Stem cell researchers
were specifically interested in document-ing the generation of induced pluripotent
stem cells via video recordings, while labsthat grow cells under hypoxic or GMPconditions greatly appreciated the abilityto remotely monitor their cell cultures,”said Herbert Mueller-Hartmann, head ofR&D at Lonza Bioscience Solutions.
“As the standard determination ofcell culture confluency is through visualinspection, which is highly user depen-dent, many labs also valued the email alertfunctionality. This allows users to be noti-fied once a culture had reached a certainconfluency, saving them from manually
checking their cells,” he continued. More info: www.lonza.com/cytosmart. CP
SHIMADZU RELEASES SPECTROFLUOROPHOTOMETER
Shimadzu Scientific Instruments has released its high-performance RF-6000 spectrofluorophotometer incorporatingnew intuitive LabSolutions RF software, and offering high speed, stability and sensitivity performance for challenging applications in the
life sciences sector.
The RF-6000 offers high sensitivity and signal-to-noise ratio (SNR) of (SNR ≥1,000 RMS and ≥350 peak-peak), according to the
company, which allows for very low limits of quantitation and achieving quantitation of fluorescein to concentrations of 1 × 10-13 mol/L.
It features an auto-gain control function to ensure measurements are performed without influence of environmental factors. As a result,
the system can perform quantitative measurements over a wide six-order dynamic range, from 10-13 to 10-7 mol/L.
Also, the high-speed 3D scanning of 60,000 nm/min enables acquisition of a 3D fluorescence spectrum in a short time, with indi-
vidual scans acquired in just one second, according to the company. An extended upper wavelength range to 900nm ensures mea-
surements of substances that exhibit fluorescence at longer wavelengths. The instrument’s xenon lamp features a 2,000-hour service
life and auto alignment technology for less frequent maintenance.
The RF-6000 comes with Shimadzu’s LabSolutions RF software that features functionality ranging from standard fluorescence to 3D
measurements of fluorescence spectra at any wavelength interval, according to the company. The software also features a spectrum
correction routine to automatically calculate corrected excitation and emission spectra.More info: www.shimadzu.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 120/132
120 Contract Pharma contractpharma.com June 2015
I N D U S T R Y C A L E N D A R
June 10, 2015Placebo Trials for Medical Devices:FDA’s Steps to Ensure Reliability of
Medical DevicesContact: Barnett International
Phone: 781-972-5400
Website: www.barnettinternational.com
June 14 - 18, 2015DIA 2015 Annual MeetingLocation: Washington, DC
Contact: Drug Information Association (DIA)
Phone: 215-442-6100
Website: www.diahome.org
June 15 - 18, 2015
BIO 2015 Annual MeetingLocation: Philadelphia, PA
Contact: Biotechnology Industry
Organization (BIO)
Phone: 202-962-9200
Website: convention.bio.org
June 18, 2015The CRA Role in Risk-BasedMonitoring: Strategies for EffectiveRemote MonitoringLocation: interactive web seminar
Contact: Barnett International
Phone: 800-856-2556
Website: www.barnettinternational.com
June 22 - 26, 2015Biodefense World SummitLocation: Bethesda, MD
Contact: Knowledge Foundation
Phone: 617-232-7400
Website: www.knowledgefoundation.com
July 15 - 16, 2015Clinical Regulatory MedicalWriting ForumLocation:
Philadelphia, PA Contact: ExL Events
Phone: 212-400-6244
Email: [email protected]
Website: www.exlevents.com
July 15 - 16, 2015Rare Disease Collaboration SummitLocation: Philadelphia, PA
Contact: ExL Events
Phone: 212-400-6244
Email: [email protected]
Website: www.exlevents.com
August 11 - 12, 20154th Clinical Trials InspectionReadiness SummitLocation: Philadelphia, PA
Contact: ExL Events
Phone: 212-400-6244
Website: www.exlpharma.com
August 12 - 13, 2015Clinical Trials InspectionReadiness SummitLocation:
Philadelphia, PA Contact: ExL Events
Phone: 212-400-6244
Email: [email protected]
Website: www.exlevents.com
August 27 - 28, 20152nd Rare Disease Collaboration SummitLocation: Philadelphia, PA
Contact: ExL Events
Phone: 212-400-6244
Website: www.exlpharma.com
September 1 - 2, 20152nd Annual Bioequivalence SummitLocation: Cambridge, MA
Contact: ExL Events
Phone: 212-400-6241
Website: wwww.exlpharma.com
September 15-16, 2015Access to Safe Medicines EuropeLocation: London, UK
Contact: Nick Tidmarsh
Phone: +44 (0)1932 785 680
Email: [email protected]
Website: www.accesstosafemedicines.com
Industry EventsCONTRACT P HARMA tells you where to go, what it’s about, when it’s held and whom to contact
MAJOR MEETINGS AT A GLANCE
June 14-18: DIA 2015 Annual Meeting • Washington, DC • Contact: Drug
Information Association (DIA) • Phone: 215-442-6100 • www.diahome.org
June 15-18: BIO 2015 Annual Meeting, Philadelphia, PA • Contact:
Biotechnology Industry Organization (BIO) • Phone: 202-962-9200 • convention.bio.org
July 26-29: Controlled Release Society, 2015 Annual Meeting, Edinburgh,
Scotland • Contact: CRS • Phone: +1-651-454-7250 • www.controlledreleasesociety.org
Sept. 17-18: Contract Pharma’s 14th Annual Contracting & Outsourcing
Conference & Tabletop Exhibition, Hyatt Regency, New Brunswick, NJ • Contact:
Kristin Brooks • Phone: 201-880-2226 • email: [email protected]
www.conference.contractpharma.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 121/132
June 2015 Twitter: @ContractPharma Contract Pharma 121
CONTRACT PHARMA
COMPANY
SHOWCASELEARN MORE ABOUT OUR SPONSORS
ALMAC
Almac, a financially secure organization with over 3,000 employees, provides inte-grated services enabling accelerated devel-opment to commercialization to over 600global companies.
New in 2013:Now open – US commercial packaging
facility in Audubon, PA. The state-of-the-art facility offers quality driven, flexiblecommercial packaging solutions for solidoral and sterile biopharmaceutical drugproducts. New non-GMP pharmaceuti-cal development facility, enhancing speedand flexibility, providing streamlined pro-gression between development and GMPphases of projects
2661 Audubon RoadAudubon, PA 19403Tel: +1 (610) 666 9500 (US)Tel: +44 (0)28 3836 3363 (Europe)[email protected]
C O M P A N Y S H O W C A S E
B. BRAUN OEM DIVISION
B. Braun supplies healthcare markets worldwide and is employing approx. 54,000individuals. The company is currently rep-resented in more than 62 countries andthe portfolio comprises more than 120,000pharmaceutical and medical articles. Basedon the synergy of this concentrated ex-pertise the B. Braun OEM Division offersa broad range of standard products and
contract manufacturing services for medi-cal devices and pharmaceutical solutionsfor the healthcare industry.
B. Braun Melsungen AGOEM Division EuropeCarl-Braun-Strasse 134212 MelsungenGermanyPhone: +49 5661 [email protected] http://www.bbraunoem.comwww.kitpacking-bbraun.com
ASH STEVENS
Ash Stevens is a contract manufacturingorganization (CMO) offering drug sub-stance development and active pharma-ceutical ingredients (APIs). With more than50 years of experience, it has received 12FDA approvals for innovator small mol-ecule APIs, including four fast-track ap-
provals for oncology drugs. A multi-milliondollar expansion completed in 2013 addedlarge-scale capacity to its commercial-scalefacility in Riverview, Michigan, which offersprocess development, cGMP manufactur-ing, potent compound handling, and com-prehensive analytical and regulatory sup-port. Contact: James M. Hamby, Ph.D., VicePresident, Business Development.
18655 Krause StreetRiverview, MI 48193Tel: [email protected]
ADVANCED ANALYTICAL
TESTING LABORATORIES
Advanced Analytical Testing Laboratories,Inc. is a contract testing facility thatoffers the following testing services: RawMaterials, Gases,Water, In-Process/Fin-ished Products, Method Development an-dValidation per USP, Complete Monograph
Testing per USP/EP/JP, Stability Storageand Testing Program.Microbiological Test-ing Capabilities Include:MicrobiologicalTesting of Water, Microbial Limits TestingUSP <61>, <62>, Preservative Efficacy Test-ing USP <51>, Antibiotic Assay USP <81>
525 Milltown RoadSuite 403-404North Brunswick, NJ 08902Tel: 732-253-7373Fax: 732-253-7371www.advancedanalyticallabs.com
CONTRACT PHARMA
COMPANY
SHOWCASELEARN MORE ABOUT OUR SPONSORS
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 122/132
122 Contract Pharma contractpharma.com June 2015
C O M P A N Y S H O W C A S E
EI, INC.
Ei excels by employing a complete turnkeyapproach to your project. Our mission isto improve products, strengthen brandsand create better lives by setting anew standard in topical semi-solid and liq-uid pharmaceutical developmentand manufacturing.
2865 North Cannon BoulevardKannapolis, NC 28083Tel: 704-939-4300Fax: 704-933-1010www.eisolutionworks.com
COOK PHARMICA
Cook Pharmica LLC is an integrated con-tract development and manufacturing or-ganization providing the pharmaceuticaland biopharmaceutical industry with drugsubstance manufacturing from mamma-lian cell culture, analytical & formulation
development, aseptic filling in both vialsand syringes, lyophilization, and second-ary packaging. Cook Pharmica’s missionis to simplify your contract manufactur-ing needs into one source at one location.Founded in 2004, Cook Pharmica is a pri- vately held, wholly-owned subsidiary ofCook Incorporated.
1300 S. Patterson DriveP.O. Box 970Bloomington, IN 47402-0970Tel: [email protected] www.cookpharmica.com
COATING PLACE INC.
Coating Place is the leader inWursterfluidbed formulation development andmanufacturing.CPI provides a completerange of services from bead layering,extrusion/spheronization, and rollercompaction to capsule filling and tableting.
We process both solvent and aqueousformulations. Facilities are DEA licensedand FDA registered.
200 Paoli St.Verona, WI 53593Tel: 608-845-5002Fax: 608-845-9526www.encap.com
CHEMIC LABORATORIES
Chemic Laboratories, Inc. is a full servicecGMP/GLP contract analytical chem-istry facility. Chemic provides an arrayof R&D and cGMP contract testing ser- vices including; Extractables/Leachablesanalysis, CMC Method Development& Validation,Quality Control analysis,Release testing, Raw Materials analy-sis, Small Scale Manufacturing/OrganicSynthesis/Formulation Development &
ICH Stability testing. Contact: LisaWalsh,Director,QAU and Regulatory Affairs.
480 Neponset Street, Bldg 7Canton, MA 02021Tel: [email protected]
CATALENT
Catalent Pharma Solutions offers end-to-end solutions for development, analysisand clinical and commercial manufactur-ing for oral solid manufacturing of potentcompounds. The acquisition of MicronTechnologies allows the company to un-dertake particle size engineering of potentcompounds, complementing handlingand manufacturing facilities at Somer-set, NJ, where expansion and investmentin additional capabilities has created aCenter of Excellence for potent handlingacross the company’s portfolio of oral sol-id dose forms.
14 Schoolhouse RoadSomerset, NJ, 08873Tel: 1-888-765-8846www.catalent.com
BIOTECHNIQUE
BioTechnique is a CMO specializing inthe sterile fill-finish of cytotoxic inject-able drugs for oncology applications. Ourfacility is purpose-built for cytotoxic andhighly potent drugs and can accommodateliquid or lyophilized products. Our ISO 5/Class 100 cleanroom can handle the latestin nanocarriers and antibody drug conju-gate technology. BioTechnique can scale upfill-finish services to meet customer needs – from investigational and clinical batchesthrough commercial production.”
5501 Research Park Blvd.Madison, WI 53719Phone: [email protected]
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 123/132
June 2015 Twitter : @ContractPharma Contract Pharma 123
C O M P A N Y S H O W C A S E
HOSPIRA
Hospira’s One 2 One™ business is a globalleader in injectable product contract manu-facturing. One 2 One™ brings more than20 years of experience in biologics andsmall molecule fill and finish manufactur-ing, in-depth knowledge of the lyophili-zation process and expertise in multipledrug-delivery technologies.
Hospira One 2 One275 North Field DriveD-0988, Bldg. H-1Lake Forest, IL 60045U.S. Phone: 1-224-212-2267Europe Phone: +44 (0) 1926 835 554
Japan Phone: +81-(0)6-4560-2074US Fax: [email protected]
HETERO USA
With over $1.5 billion in sales, Hetero isamong the ten largest pharmaceuticalcompanies in India. Hetero provides bulk API/RSM, as well as API/formulationcontract manufacturing and development.Hetero has over 200 US DMF’s in a widerange of therapeutic categories, andover 60 US ANDA’s. All 20 of Hetero’s
manufacturing facilities are cGMPcompliant. Nine sites are FDA approved,including two multi-billion-unit OSD sites inNew York, USA. From high volume to nicheproduction, Hetero gets it done right forless. Do you know Hetero? The Hetero
CPS Value Proposition: Reliable, Capable, Value Driven
1031 Centennial AvePiscataway, NJ 08854Cell: +1 (646) [email protected]
GRAND RIVER ASEPTIC
MANUFACTURING
Grand River Aseptic Manufacturing is aparenteral contract development and man-ufacturer providing small-scale clinical trialand commercial materials aseptically filledinto vials, as well as lyophilization for thepharmaceutical and biopharmaceuticalmarkets. In addition to sterile manufactur-
ing, services include formulation develop-ment, process development, analytical/microbiological testing, packaging andregulatory support.
140 Front Avenue SW, Suite 3Grand Rapids, MI 49504Tel 616-331-6983Fax 616-776-5584grandriverasepticmfg.com
FEDERAL EQUIPMENT
COMPANY
As a world leader in pharmaceuticalprocess and packaging equipment, FederalEquipment Company has the equipmentinventory that contract manufacturersand contract packagers need to win newprojects and meet customer expectations.Our inventory is available immediately ata fraction of the price of new equipment. Visit us at www.fedequip.com
8200 Bessemer AveCleveland, OH 44127Tel: 216-271-3500Toll free: 800-652-2466Fax: 216-271-5210www.fedequip.com
CANGENE BIOPHARMA
(D/B/A EMERGENT BIOSOLUTIONS)
Emergent BioSolutions (formerly CangenebioPharma) provides contract manufacturingservices for the aseptic fill/finish of vials andsyringes: liquid and lyophilized products.Emergent’s sterile injectable manufacturingfacility (located in Baltimore, MD) currentlyproduces 20 commercial products and since1990 has contributed to the developmentand production of over 200 clinical products.
1111 S. Paca StreetBaltimore, MD 21230Tel: [email protected]
EMD MILLIPORE
EMD Millipore, the Life Science divisionof Merck KGaA, Germany, supporting re-search, development and production ofbiotech and pharmaceutical therapies, in-cludes Drug Discovery and DevelopmentSolutions, the premier large molecule-fo-cused bioanalytical service provider. Since2003, we have supported our clients withquality, customized immunogenicity, PK,
potency/stability and biomarker servicesfor exploratory and regulated studies. Us-ing the latest instrumentation and tech-niques, our experienced UK and US-basedlaboratory teams are committed to support your studies.
15 Research Park DriveSt. Charles, MO, 63304Tel: 1-866-441-8400www.emdmillipore.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 124/132
124 Contract Pharma contractpharma.com June 2015
C O M P A N Y S H O W C A S E
PHARMA PACKAGING
SOLUTIONS
Pharma Packaging Solutions is an agile,compliant and innovative contract packag-er and folding carton producer, serving thehealthcare and specialty food markets. Wedeliver primary and secondary packaging
in the forms of: bottle filling, blister pack-aging, folding carton production, pouch-ing, repackaging, cold chain packaging andcompliance packaging. We serve marketssuch as: pharmaceuticals (Rx, OTC), per-sonal care, nutritionals, medical device and veterinary care. We also serve the privatelabel and contract manufacturers, as wellas retail pharmacies.
First Quality DrivePO Box 1219Norris, TN 37828Tel: 865-494-6000Fax: 865-494-6050www.pharmapacksol.com
PATHEON
Patheon is a leading provider of contractdevelopment and commercial manufacturing(CDMO) services to the global pharmaceuticalindustry for a full array of solid and steriledosage forms. Patheon, a DPx businessunit, encompasses the combined CMOcapabilities and pharmaceutical productdevelopment services (PDS), as well as the
Biosolutions and Biologics business.
4721 Emperor Blvd, Suite 200Durham, NC, 27703Tel: [email protected]
PACKAGING
COORDINATORS, INC.
PCI is the global leader for packaging ser- vices, supporting our customers in eachstage of the development and commercial-ization of drug products. A trusted partnerto the world’s largest and most successfulpharmaceutical firms, we offer services
from early phase clinical studies throughlarge scale Phase III/IV, commerciallaunch, and ongoing supply. We partner with manufacturers, offering insight andexpertise, combined with innovative tech-nologies and an uncompromising com-mitment to exceptional service and quality.
3001 Red Lion RdPhiladelphia, PA 19114Tel: [email protected]
MIKART
Since 1975, Mikart has been a recognizedleader in providing contract development,manufacturing and packaging services to thepharmaceutical industry. We offer a broadrange of capabilities including formulationdevelopment, analytical services, solidand liquid dose manufacturing, packaging(bottles, blisters, and multi-laminatepouches) and regulatory services.
1750 Chattahoochee AveAtlanta, GA 30318Tel: 888-4MIKARTFax: 404-350-0432www.mikart.com
LSNE CONTRACT
MANUFACTURING
LSNE Contract Manufacturing is a CMO with a proven regulatory history special-izing in a wide range of services includingprocess development, fill/finish and lyoph-ilization. Through the thoughtful integra-tion of three processing facilities, qualifiedstaffing and an extensive manufacturinghistory, LSNE is strategically positioned toprovide uninterrupted material for clinicalthrough commercial use. Our flexibilityand responsiveness allow us to make your
batch our top priority so we can meet yourtimelines and exceed your expectations.
25 Commerce DriveBedford, NH 03110Tel: 603-668-5763www.lyophilization.com
JUBILANT
HOLLISTERSTIER
Jubilant HollisterStier Contract Manufac-turing & Services is an integrated contractmanufacturer, able to manufacture ster-ile injectable, solid and semi solid dosageforms. Our facilities across North Americaand India provide specialized manufactur-ing services for the pharmaceutical andbiopharmaceutical industries. We pro- vide a full-range of support and servicesto streamline the manufacturing process,
such as on-site assistance from processqualifications and regulatory submittalsthrough product release.
3525 N. Regal St.Spokane, WA 99207Tel: 800-655-5329Fax: [email protected]
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 125/132
June 2015 Twitter : @ContractPharma Contract Pharma 125
C O M P A N Y S H O W C A S E
VETTER PHARMA
Vetter is a leading contract developmentand manufacturing organization (CDMO)that specializes in the aseptic filling of sy-ringes, cartridges and vials. The companyhas extensive experience with biologicsand other complex compounds, includingmonoclonal antibodies, peptides, inter-ferons and vaccines. Collaborating with
pharma/biotech clients worldwide, Vettersupports products from preclinical devel-opment through global market supply.
Vetter Pharma International GmbHEywiesenstraße 588212 RavensburgGermanyTel: +49 751 3700-0www.vetter-pharma.comUS inquiries: [email protected] inquiries: [email protected] inquiries:[email protected]
SANDOZ
Sandoz is one of the leading companies inproduction of recombinant proteins, usingmicrobial as well as mammalian cell cul-ture technologies. Sandoz offers contractmanufacture in FDA approved facilities in Austria with scales of 1,300L to 40,000L(microbial) and 3,000L – 13,000L (mamma-lian). Excellent technology transfer experi-ence, flexibility of production capabilities
and fully integrated services accompanied with a highly skilled and customer-orient-ed team makes Sandoz an ideal partner indevelopment and cGMP manufacture ofrecombinant products.
Sandoz GmbHBiochemiestrasse 10A 6250 Kundl/AustriaTel: +43 5338 200 2609Fax: +43 5338 200 442Email: [email protected]: www.sandoz.com
SAMSUNG BIOLOGICS
Samsung BioLogics is a world class, full serviceprovider of quality driven contract processeddevelopment and cGMP manufacturing to theglobal biopharmaceutical industry. Establishedin April 2011, Samsung BioLogics will trans-form the global healthcare industry over thenext decade, through our Quality, technology,and innovation. Our facilities are custom de-signed for monoclonal & recombinant produc-tion with maximum flexibility. Our integrated
services include process, analytical methoddevelopment, analytical services (characteriza-tion, comparability, IPC, lot release & stability)clinical and commercial cGMP manufacturingof Drug Substance and Drug Product and Ex-cellence in Quality Assurance, Quality Control, worldwide regulatory compliance & regula-tory support for our clients. We are centrallylocated in the heart of Asia, within 20 minutesof Incheon International Airport.
125 Cheomdan-daeroYeonsu-gu, Incheon, 406-840South KoreaTel: +82 32 455 3302www.samsungbiologics.com
REED LANE INC.
Reed-Lane’s contract packaging capabili-ties include solid dose bottle filling. ther-moform and cold form blister packaging,pouching for solid dose, convenience vialfilling, and services for compliance andsecondary packaging such as wallet cards,blister cards and cartons. With over 35 ded-icated production suites for Rx and OTCpackaging, Reed-Lane offers rooms forindividual air handling and HEPA filtrationsystems in primary suites, temperature-
controlled storage for bulk and finishedgoods, and strict environment and securitymonitoring throughout.
359 Pompton Tpke.Wayne, NJ 07470Tel: [email protected]
PLATINUM PRESS
Platinum Press is a leading supplier ofhealthcare packaging solutions for thepharmaceutical, medical device and animalcare sectors. The company’s extensive lineof printed packaging components includeslabels, ECLs, folding cartons, blister pack-aging and printed literature such as inserts,outserts and medication guides. PlatinumPress has become particularly well knownfor its innovative combination products,such as the ‘Combination Label’ and ‘Com-bination Carton’; each consolidates two ormore printed components into a single unit.
920 Avenue R, Suite 200Grand Prairie, TX 75050Tel: [email protected]
PHARMA TECH
INDUSTRIES
The largest contract manufacturer andpackager of powder products in the world,Pharma Tech Industries (PTI) has beenproviding product development, manufac-turing, packaging, and technology transferservices to leading global pharmaceuticaland personal care companies for over 40 years. PTI produces over 300 SKUs of pow-ders, effervescent and solid dose products,capsule filling, cotton swabs, injection-
molded components, and medical devicesacross two cGMP facilities in Royston, GAand Union, MO.
272 West Hancock AvenueSuite 300DAthens, Georgia 30601Tel: 706-353-7200Fax: [email protected]
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 126/132
126 Contract Pharma contractpharma.com June 2015
C OM P A N Y S H O W C A S E
XCELIENCE
Xcelience® Suite Science – Xcelience of-fers a suite of services enabling clients topartner with a single CDMO for all of theirclinical outsourcing needs. Services includepreformulation, analytical services, formu-lation development, cGMP manufacturing,small-scale commercial manufacturing,and global clinical supplies packaging andlogistics. Xcelience takes pride in deliver-ing the highest standard in science and ser- vice with an emphasis on quality, cost andspeed. Xcelience has 4 locations in Tampa,Florida and 1 location in the UK.
Contact information: Sharon BurgessSVP, Business DevelopmentTel: [email protected]
WELLSPRING
PHARMACEUTICAL
Whether you’re an emerging pharma-ceutical company, start-up, or a multi-national pharmaceutical organization, WellSpring is passionate about turning your product concept into commercialreality. Our dedicated technical and projectmanagement professionals are with youevery step throughout the developmentpathway to ensure that every detail is met with careful consideration and preciseexecution at our FDA inspected and HealthCanada licensed facility. Find out how
WellSpring delivers the right solution for virtually any challenge today.
400 Iroquois Shore Rd.Oakville, ONL6H 1M5 CanadaTel: 1-844-879-7427www.wellspringcmo.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 127/132
June 2015 Twitter : @ContractPharma Contract Pharma 127
C L A S S I F I E D
Clinical Packaging & Supplies
Grand River Aseptic Manufacturing . . . . . . . . . . 616-331-6980
140 Front Avenue SW, Ste. #3, Grand Rapids, MI 49501
Contract Laboratory Services
Catalent Pharma Solutions . . . . . . . . . . . . . . . . . . . 866-720-3148
14 School House Rd., Somerset, NJ 08873
Packaging Coordinators Inc. . . . . . . . . . . . . . . . . .815-484-8900
4545 Assembly Dr., Rockford, IL 61109
Contract Manufacturing Services
Advanced Analytical Testing Laboratories, Inc. . . .732-253-7373
525 Milltown Rd., Ste. 403-404, North Brunswick, NJ 08902
BioTechnique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608-204-9224
5501 Research Park Blvd., Madison, WI 53719
Catalent Pharma Solutions . . . . . . . . . . . . . . . . . . . . . . .866-720-3148
14 School House Rd., Somerset, NJ 08873
Chemic Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . . . . .781-821-5600480 Neponset St., Bldg. 7C, Canton, MA 02021
Coating Place, Inc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608-845-9521
200 Paoli Dr., Verona, WI 53593
Ei, A Pharmaceutical SolutionWorks . . . . . . . . . . . . . 704-939-4300
2865 N. Cannon Blvd., Kannapolis, NC 28083
Emergent BioSolutions . . . . . . . . . . . . . . . . . . . . . . . . . . 800-441-4225
3403 American Dr., Mississauga, Ontario, Canada L4V 1T4
Grand River Aseptic Manufacturing. . . . . . . . . . . . . .616-331-6980
140 Front Avenue SW, Ste. #3, Grand Rapids, MI 49501
Halo Pharma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 973-428-4087
30 N. Jefferson Rd., Whippany, NJ 07981
Hetero USA, Inc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 646-226-16341031 Centennial Ave., Piscataway, NJ 08854
Hospira One 2 One . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .224-212-2267
275 N Field Dr., Dept. 0988, Lake Forest, IL 60045
Jubilant HollisterStier
Contract Manufacturing & Services . . . . . . . . . . . 800-655-5329
3525 N. Regal St., Spokane, WA 99207
LSNE Contract Manufacturing . . . . . . . . . . . . . . . . . . 603-626-5763
One Sundial Ave., Ste 112, Manchester, NH 03103
Mikart, Inc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404-351-4510
1750 Chattahoochee, Atlanta, GA 30318
Patheon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .919-226-3200
PO Box 110145, Research Triangle Park, NC 27709Pharma Tech Industries (PTI) . . . . . . . . . . . . . . . . . . . .706-246-3555
545 Old Elbert Rd., Royston, GA 30662
Samsung Biologics . . . . . . . . . . . . . . . . . . . . . . +82 2 2255 8500 / 8501
27F, 1320-10, Seocho 2-dong, Seocho-gu, Seoul 137-965,
Korea (CPO Box 170)
Sandoz GmbH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43 5338 200 680
Biochemiestrasse 10, A6250 Kundl, Austria
Vetter Pharma International GmbH . . . . . . . . . . .0049-751-3700-0
Eywiesenstrasse 5, 88212 Ravensburg, Germany,
WellSpring Pharmaceuticals . . . . . . . . . . . . . . . . . . . . .905-337-4500
400 Iroquois Shore Rd., Oakville, Ontario, Canada L6H 1M5
Consulting Services
Contract Packaging
Catalent Pharma Solutions . . . . . . . . . . . . . . . . . . 866-720-314814 School House Rd., Somerset, NJ 08873
Grand River Aseptic Manufacturing . . . . . . . . . . 616-331-6980140 Front Avenue SW, Ste. #3, Grand Rapids, MI 49501
Contract Research Organization
EMD Millipore . . . . . . . . . . . . . . . . . . . . . . . . . . . . 866-441-840015 Research Park Dr., St. Charles, MO 63304
Xcelience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813-286-04045415 West Laurel St., Tampa, FL
Custom Manufacturing
B. Braun . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . +49 5661 71 28 2634212 Melsungen, Germany
Cook Pharmica LLC . . . . . . . . . . . . . . . . . . . . . . 877-312-COOK
1300 S. Patterson Dr., Bloomington, IN 47402
Formulations
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 128/132
128 Contract Pharma contractpharma.com June 2015
C L A S S I F I E D
Packaging
Pharma Packaging Solutions . . . . . . . . . . . . . . . . .888-700-9002
First Quality Dr., Norris, TN 37828
Platinum Press . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201-848-1010
920 Ave. R, Building 200, Grand Prairie, TX 75050
Reed Lane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 973-709-1090
359 Newark Pompton Tpk, Wayne, NJ 07470
Used Processing Equipment
Tell Us What You Have For Sale
We Buy Equipment!We Are “Sniffing Out”
Quality Packaging Equipment> Cartoners
> Blister Equipment
> Solid Dose
> Wrappers
> Vial / Ampoule Inspection
> Tube Fillers
> Related Packaging Equipment
or call: 855-722-4174
www.aaronequipment.com/sniff
Fluid Bed Dryers
Chilsonators
Coating Pans
Mixers
Tablet Presses
Mills
Ovens
Bin Blenders
Capsule Fillers
Scales
Autoclaves
Hydraulic Presses
CIP Systems
Dedusters/Polishers
Dust Collectors
WWW.FEDEQUIP.COM +1 877 536 1538
When you
think equipment,
think Federal
Equipment
WE SELL and deliver high quality machinery
WE BUY and remove surplus equipment
Manager/Senior Manager Business Development
Jubilant Pharma-Spokane, WA
This position is responsible for developing and maintaining
business relationships with existing and potential clients. (TheSenior Manager will also oversee the Business Development
Managers, as required). Essential responsibilities include:
1. Develop business proposals for new clients which includePrice Quotation, Supply Agreement and Quality Agreement
2. Develop business proposals for existing clients for change inproject scope, or client initiated changes
3. Act as liaison and champion for both Jubilant HollisterStierand the client
4. Participate in marketing efforts such as trade show
participation, development and Jubilant HollisterStierbranding efforts, etc.
5. Communicate quality and/or manufacturing issues to the client6. Attend client business and/or quality meetings involving
Jubilant HollisterStier7. Participate in Change Management Program Requests
(CMPR) for both clients and the facility8. Work with customers to establish manufacturing forecasts
and revenue generation forecasts
9. Work with client Planning group to schedule client batchesto be produced
10. Understand and balance clients’ needs versus JubilantHollisterStier priorities
11. Schedule and oversee all client site visits (such as person- in-plant, pre-approval inspections, and business meeting
participation)
12. Work with Project Teams as ad-hoc team member tomaintain project scope and serve as resource during
execution of projects13. Interface with all departments of Jubilant HollisterStier
which provide input into the contract business14. Supervise the Project Management Organization (PMO)
and the Client Relations Associates, as required
Qualifications:• Bachelors Degree in hard science or other technical eld
– AND – a minimum of 1 year related experience, to includeworking knowledge of manufacturing, validation, and Quality
processes
• Prior Supervisory experience desired• Prior Pharmaceutical experience desired
• Prociency in Microsoft Word, Excel and Project required.(Working knowledge of SAP desired)
• Must have knowledge of cGMP’s, regulatory requirements,relevant USP chapters, and scientic principles associated with
clean room operations, media lls, sterility testing, sterilization
practices, and aseptic operations• Physical Requirements: 20/30 near-point corrected vision.
Prolonged sitting. Moderate travel required (between 10%and 40%)
Please send your resume to Theresa DiBiase [email protected] for consideration.
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 129/132
Company Page Phone Web Site
June 2015 Twitter : @ContractPharma Contract Pharma 129
A D V E R T I S E R I N D E X
AAPS Annual Meeting and Expo . . . . . . . . . . . . . . . 55. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . www.aaps.org
Advanced Analytical Testing Laboratories, Inc. . . . . 79. . . . . . . . . . . . . . . 732-253-7373 . . . . . . . . . . . . www.advancedanalyticallabs.com
B. Braun . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19. . . . . . . . . . . . . +49 5661 71 28 26 . . . . . . . . . . . . . . . . . . . www.bbraunoem.com
BioTechnique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35. . . . . . . . . . . . . . . 608-204-9224 . . . . . . . . . . . . . . . . . . . . www.biotechnique.com
Catalent Pharma Solutions . . . . . . . . . . . . . . . . . Cov. 4 , 29 . . . . . . . . . . . 866-720-3148 . . . . . . . . . . . . . . . . . . . . . . . . www.catalent.com
Chemic Laboratories . . . . . . . . . . . . . . . . . . . . . . . . . 51. . . . . . . . . . . . . . . 781-821-5600 . . . . . . . . . . . . . . . . . . . . . . www.chemiclabs.com
Coating Place, Inc. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11. . . . . . . . . . . . . . . 608-845-9521 . . . . . . . . . . . . . . . . . . . . www.coatingplace.com
Coldstream Laboratories . . . . . . . . . . . . . . . . . . . . . . 49. . . . . . . . . . . . . . . 859-257-5288 . . . . . . . . . . . . . . . . . . www.coldstreamlabs.com
Cook Pharmica LLC . . . . . . . . . . . . . . . . . . . . . . . . . 31. . . . . . . . . . . . . . 877-312-COOK . . . . . . . . . . . . . . . . . . www.cookpharmica.com
Ei, A Pharmaceutical SolutionWorks . . . . . . . . . . . . 67. . . . . . . . . . . . . . . 704-939-4300 . . . . . . . . . . . . . . . . . www.eisolutionworks.com
EMD Millipore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23. . . . . . . . . . . . . . . 866-441-8400 . . . . . . . . . . . www.emdmillipore.com/gyromark
Emergent BioSolutions . . . . . . . . . . . . . . . . . . . . . . . .9 . . . . . . . . . . . . . . . 800-441-4225 . . . . . . . . . . . . . www.emergentbiosolutions.com
Federal Equipment Company . . . . . . . . . . . . . . . . . . .7 . . . . . . . . . . . . . . . 800-652-2466 . . . . . . . . . . . . . . . . . . . . . . . . www.fedequip.com
Grand River Aseptic Manufacturing . . . . . . . . . . . . 33. . . . . . . . . . . . . . . 616-331-6980 . . . . . . . . . . . . . www. grandriverasepticmfg.com
Halo Pharma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 . . . . . . . . . . . . . . . 973-428-4087 . . . . . . . . . . . . . . . . . . . . www.halopharma.com
Hetero USA, Inc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37. . . . . . . . . . . . . . . 646-226-1634 . . . . . . . . . . . . . . . . . . . . www.heterodrugs.com
Hospira One 2 One . . . . . . . . . . . . . . . . . . . . . . . . . . 13. . . . . . . . . . . . . . . 224-212-2267 . . . . . . . . . . . . . . . . . . . . www.one2onecmo.com
Jubilant HollisterStier
Contract Manufacturing & Services . . . . . . . . . .5 . . . . . . . . . . . . . . . 800-655-5329 . . . . . . . . . . . . . . . . . . . . . . . . . www. jublHS.com
LSNE Contract Manufacturing. . . . . . . . . . . . . . . . . 41. . . . . . . . . . . . . . . 603-626-5763 . . . . . . . . . . . . . . . . . . . www.lyophilization.com
Mikart, Inc. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43. . . . . . . . . . . . . . . 404-351-4510 . . . . . . . . . . . . . . . . . . . . . . . . . www.mikart.com
Packaging Coordinators Inc. . . . . . . . . . . . . . . . . . . . 21. . . . . . . . . . . . . . . 815-484-8900 . . . . . . . . . . . . . . . . . . . . . . www.pciservices.com
Patheon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Cov. 2 . . . . . . . . . . . . . 919-226-3200 . . . . . . . . . . . . . . . . . . . . . . . . www.patheon.com
Pharma Packaging Solutions . . . . . . . . . . . . . . . . . . 61. . . . . . . . . . . . . . . 888-700-9002 . . . . . . . . www.PharmaPackagingSolutions.com
Pharma Tech Industries (PTI) . . . . . . . . . . . . . . . . . . 45. . . . . . . . . . . . . . . 706-246-3555 . . . . . . . . . . . . . . . . . . . . www.pharma-tech.com
Platinum Press . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47. . . . . . . . . . . . . . . 201-848-1010 . . . . . . . . . . . . . . . . . . . www.platinumpress.com
Reed Lane . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17. . . . . . . . . . . . . . . 973-709-1090 . . . . . . . . . . . . . . . . . . . . . . . . www.reedlane.com
Samsung Biologics . . . . . . . . . . . . . . . . . . . . . . . . . Cov. 3 . . . . . . . . . +82 2 2255 8500 / 8501 . . . . . . . . . . . . www.samsungbiologics.com
Sandoz GmbH . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25. . . . . . . . . . . . . . 43 5338 200 680 . . . . . . . . . . . . . . . . . . . . . . . . www.sandoz.com
Vetter Pharma International GmbH . . . . . . . . . . . . 39. . . . . . . . . . . . . .0049-751-3700-0 . . . . . . . . . . . . . . . . . www.vetter-pharma.com
WellSpring Pharmaceuticals . . . . . . . . . . . . . . . . . . . 15. . . . . . . . . . . . . . . 905-337-4500 . . . . . . . . . . . . . . . . . . . www.wellspringcmo.com
Xcelience. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27. . . . . . . . . . . . . . . 813-286-0404 . . . . . . . . . . . . . . . . . . . . . . . www.xcelience.com
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 130/132
130 Contract Pharma contractpharma.com June 2015
B A C K P A G E
I
t is critical to prepare and manage forthe future—especially one made moreuncertain in 2015 given likely changes
to our healthcare system under new Re-publican majorities. The challenge for ourindustry is it can take more than a decadeand more than $2.5 billion to get a drug tomarket. Even if successful, a molecule de-
veloped this year might not reach patientsuntil 2025. That’s longer than the develop-ment of a new car—and automakers don’tface the same regulatory hurdles.
This is an annual list of trends thatI feel will continue to affect the emerg-ing biotech and generic drug industriesthroughout 2015:
1. Plan for drug development, includinggenerics, to take longer and cost more. As companies pursue increasinglychallenging illnesses and conditions,the science, techniques and themolecules themselves will likewise getmore complex. Biotechs should lookfor CROs and CMOs that continuallyinvest in new technology and in ongo-ing training for its staff so that theycan conduct cutting-edge science.
2. Despite GDUFA’s promise to speedup the approval process, there is a
two-year backlog. The backlog is sosevere—the Abbreviated New Drug Application (ANDA) backlog alone ex-
ceeds 2,800 applications—that the goalof the FDA’s Office of Generic Drugs(OGD) is to act on them by 2017. Even
if your drug is ready today, the FDA won’t act on it for another 24 months.
3. Business plans should account forincreased risk. Apart from the timeand money required for drug devel-opment itself, there are regulatoryburdens including facility fees that canreach $220,000 annually. That doesn’tinclude fees mandated by GDUFA,
which raises fees for applicationsand Drug Master Files (DMFs). If
your business plan does not antici-pate these fees and the fact that even
generic drugs have only a 50% chancefor approval, it will be difficult to sur- vive long enough to be successful.
4. The barriers to entry favor big pharmaover small biotechs. The approval delays,facility fees, and rising DMF fees alltip the field in favor of big pharma.There is a concern that as big pharmacontinues to move into Massachusetts,one of the most vibrant life scienceshub in the world, it will push out smallbiotechs. Perhaps reflecting this trend,Boston-area real estate available for lab
space has tightened, with vacancy ratesbelow 10%, according to a TranswesternRBJ report. And a recent Boston Globearticle wondered whether the influx ofbig pharma and the number and size of“biotech deals could diminish entrepre-neurial culture.”That is a risk.
5. More small biotechs could drop out.More manufacturers could follow thelead of Ben Venue Laboratories andHospira and will get out the business
while major players look to product orcorporate acquisitions as patent-cliff
protection. With approvals so backedup, biotechs need to build a business
case that the additional wait until after2017 is worth the investment.
6. Drug prices will increase to offset risk.
The easiest way to offset increased riskis to raise drug prices. Expect morecompanies to raise prices. That mayprovide generic drug makers with anopportunity but the risks associated
with generics are increasing, too.7. Marketing will become more impor-
tant. Even if your drug gets approved,several other competing genericscould hit the market simultaneously.
While they can’t market the drugbefore FDA approval and need to fit
within FDA guidelines, biotechs need
to make sure they understand themarket they plan to enter.8. Increased inspections of international
facilities will increase costs of usingIndian and other offshore providers.There was an increase in 2014 in thenumber of inspections of Indian drugand API manufacturers, and PCI ex-pects that to continue in 2015. OffshoreCMOs will need to make significantinvestments to improve their facilitiesto meet FDA standards; those costs willbe quickly passed along to customers.
Additionally, wage inflation and turn-over continue to increase in India andChina, raising costs, causing delays asnew team members have to be foundand trained. Ultimately, we think this
will lead to more biotechs consideringbringing back work to U.S. CMOs.
9. Demand for U.S. manufacturing willincrease. Wage inflation in India andChina that continues to jump, increasedfacility costs to meet FDA inspections,and different cultural expectations thatled to bribery investigations are all
helping biotechs to consider bringingback work to U.S. CMOs. CP
Edward S. Price
PCI Synthesis
Edward S. Price is the co-chair of
New England CRO/CMO Council
and the president of PCI Synthesis, a 16-year-old
custom chemical manufacturer of new chemical
entities (NCEs), generic active pharmaceutical ingre-dients (APIs), and other specialty chemical products.
Drug Development Costs
Continue to IncreaseGDUFA still won’t speed approvals
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 131/132
7/23/2019 Contract Pharma
http://slidepdf.com/reader/full/contract-pharma 132/132
