10/19/2011

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IPEC General Update

September 28, 2011

Update Topics

• Meeting schedule for 2012• ICH Q3D update• ExcipientFest 2012• EXCiPACT• EXCiPACT• ANSI NSF 363• NSF• IID update• FDA Spectral Library update

DECEMBER 7TH

BOARD OF TRUSTEE MEETINGWEDNESDAY NIGHT 5:30WEDNESDAY NIGHT 5:30

IPEC Meetings 2012

February May September December

Executive Committee11 ‐ 5

21Tuesday

14Monday

24Monday

3Monday

QbD (am)Exc. Comp (pm)

22Wednesday

15Tuesday

22Tuesday

4Tuesdayp (p ) y y y y

GMP  (am)Exc. Comp (pmGeneral Update

23Thursday

16Wednesday

23Wednesday

5Wednesday

QbD (am)Exc. Comp (pm

24Friday

17Thursday

24Thursday

6Thursday

ICH Q3DMetal Impuritiesp

ICH Q3D• Guidance is making progress• To Do List

– Still need data from IPEC members (especially on items with mineral‐based excipients) or other non‐Rx products to help drive realistic metal limits

• Ie toothpaste

• IPEC is planning on a workshop for 2012 to gather and review additional data

• M = each ingredient used to manufacture the dosage form• CM = element concentration in component M (μg/g)• WM = weight of component in the maximum total weight of the drug 

product administered in a daily dose (g/day)

( ) ∑ ⋅≥M

MM WCdaygPDE μ

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Metal Permitted Daily Exposure, μg/day Permitted Concentration, μg/g (assuming 10g maximum dose)

As 15 1.5Cd 5 0.5Hg 50 5Pb 10 1Al 5000? 500?Ni 250 25Co 0Sn 0Sb 0Tl 0Ba 0Ag 0Rh 100 10Ru 100 10Ru 100 10Mo 250 25B 0Ir 100 10Os 100 10Se 0Pt 125 12.5Pd 100 10Cr 250 25V 250 25Li 430 43Cu 750 75Mn 2500 250Au 0W ** **

Event History

Europe(Ireland)2007 & 2009US

(Baltimore)2011 Asia

(China) 2012

Americas (Puerto Rico)2001 – 20102012

2012

Development of concept / business plan by EXCiPACTTM GSC April 2011

Cross referenced acceptance of Rx360 and EXiPACTTM by 3.Q. 2011

Trademark protection by 2Q. 2011

EXCiPACTEXCiPACTTMTM CertificationCertificationKey Milestones for Implementation

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p y

Acceptance and acknowledgement by IPEC, CEFIC... by 3Q. 2011

• Base funding completed by 90% by 3Q. 2011

• Hiring of staff, establishement of the advisory board by 1.Q 2012

• Start of operations by 1Q. 2012

EXCiPACTTM - Minimise the Risks, Maximise the Benefits

EXCiPACTTM CertificationThe process and relationship

EXCiPACTTM 3rd Party Audit Organisation

Excipient user

ExcipientSupplier

Supplier passes on audit reportUser can verify audit report and

certificate with EXCiPACTTM

Agreement with supplierProvides audit report

and Certificate

Legal Agreement with3rd party auditOrganisations

Publish list and list of Certificates / validity on website

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g ppExcipient

user

EXCiPACTTM - Minimise the Risks, Maximise the Benefits

ANSI NSF 363 Excipient GMP

• 1st draft written and under review by committee– Dale Carter, Dave Klug, Ann VanMeter, Kathie Ulman Irwin Silverstein Chris Moreton JeffUlman, Irwin Silverstein, Chris Moreton,  Jeff Brambora, Ian Moore, Steve Moss, Sidney Goode

• January 2012 – Public Draft published for comments

• 2nd Q 2012 – Final Standard Published

NSF InternationalA Global Leader in Public Health and Safety

Corporate Overview

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A Little History…

• Americans began dining out in the late 1930’s.• State health officials monitored food service establishments

for sanitation using a variety of criteria.• Inconsistent rules and regulations arose, varying from town

to town, state-to-state. Hence…A need for uniform national standards; NSF brings regulators• A need for uniform national standards; NSF brings regulators, industry, consumers and public health officials together.

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Founded in 1944 to Develop Standards, Certify Equipment

• NSF was founded as the National Sanitation Foundation in the University of Michigan’s School of Public Health in 1944.

• Today, we are known as NSF International, with a corporate headquarters in Ann Arbor, MI, USA, and operations in 120 countries.

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• Launch Foodservice Equipment Program

• NSF Testing Labs• Launch Swimming

Pool Safety• Launch Plastic

Piping Program

• NSF-ISR launched

• NSF becomes W.H.O. Collaborating Centre

• NSF Shanghai & NSF Mexico

• Davis Fresh acquired• CMi acquired (UK,

Chile, Peru, Italy, Spain, S. Africa, Czech Republic)

• David Begg & Associates (UK, Boston)

• 80,000 sq. ft lab expansion completed

NSF Growth: Organic and Acquisitions

1944 1970s1980s

2001-2005

2008-2011

1950s1960s 1990s 2006-

2007

• NSF founded Ann Arbor, MI

• Develop National Drinking Water Standards

• Bottled Water Certification

• NSF Brussels, Belgium opens to serve Europe

• Cook and Thurber acquired

• Launch Dietary Supplement Program

• QAI acquired• NSF Brazil open• Deloitte & Touche

Quality Registrar acquired (Canada)

• NSF Thailand & NSF India open

• NSF Surefish • Toy Safety• Trucost partner• NSF Costa Rica• Shanghai Lab• NSF Pharmalytica• AQA International

acquired

Bringing Industry, Regulatory and Consumers Together

USDA, EPA, FDA, HC, State, Local

Food, Water, Consumer Goods Media, Educators,Consumer Groups

Consumers

Regulators

Industry

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Today, NSF is a Global Leader in Public Health and Safety

• Developer of over 72 national consensus standards.• Steadfast ties with key associations and govt. agencies.• A Collaborating Centre for the World Health Organization.• Service provider to thousands of organizations in 120 countries.

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NSF Around the Globe

Americas EMEA AsiaUnited States Belgium Poland ChinaBrazil Czech Republic South Africa IndiaCanada France Spain JapanChile Germany Switzerland South KoreaCosta Rica Greece United Kingdom TaiwanMexico Israel ThailandPeru Italy Turkey

Netherlands Vietnam

NSF International OfficesGlobal Partners

NSF International Offices

Global Partners

Laboratories

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An Unmatched Professional Staff and Facility

• 1,200+ experienced professionals: microbiologists, toxicologists, chemist, engineers and public heath experts.

• 165,000 square feet of state-of-the-art laboratories in Ann Arbor and Shanghai, China, plus partner labs around the world.I ti I f ti T h l biliti• Innovative Information Technology capabilities.

NSF Collaborations

• NSF is a World Health Organization Collaborating Centre for: – Food Safety– Water Safety

• Drinking Water Quality Guidelines• Recreational Water Safety Guidelines

– Indoor Environment– Indoor Environment

• Works closely with International, Federal State and Local Regulators:– FDA– USDA– EPA– U.S. Government/Legislature– And many more…

NSF International Accreditations and Certifications Include

U.S. Canada Europe

ISO 14001 ISO 17025

NSF Capabilities/Services

NSF Core Business Units

NSF

Water Food Safety Sustainability

DietarySupplements

/Pharma

ISR

ConsumerProducts

/PLA/ Toy Safety

Food Safety and Quality Services

• Food Safety Systems through the supply chain– GFSI: SQF, BRC, FSSC 22000, GlobalGAP, IFS– Growers, producers, processors, distributors,

retailers• Produce Safety via NSF Agriculture

– Field evaluations, testing, consulting and training for growers, processors, distributors and retailers

• Other Food Safety Systems:– HACCP, Tesco Nurture, Tesco Nurture Organic, LEAF

• Seafood Safety & Quality via NSF Surefish– Seafood inspection, testing and consulting (MSC, ACC, HACCP).

• Processor Safety & Quality Services through NSF Cook & Thurber – Consulting/auditing for food, beverage, animal feed and packaging

industries.• Organic Certification through QAI

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Food Safety and Quality Services

• Retail Food Safety Services– Customized auditing & consulting for

restaurants, supermarkets and retail foodservice

• Foodservice Equipment Certification• Nonfood Compounds Registrationp g• Beverage Quality Certification

– Bottled water, packaged ice, flavored water and functional beverages to US FDA & EU Regulations

– Food Equipment/Nonfood Compounds Cert

• Food Safety Training and Education Programs– classroom, online, video, live webinars and on-site training

Water and Wastewater Systems – Major Program Areas

NSF developed many public health standards adopted by the US EPA to protect drinking water; and standards promoting pool/spa safety. NSF tests and certifies products to those standards:

• Water Treatment Distribution Components & Chemicals ( S / S 60 61)(NSF/ANSI 60 and 61)

• Mech. Plumbing Devices (faucets, valves) (NSF/ANSI 61, Sec. 9)

• Plastic Piping & Components (NSF/ANSI 14) • Drinking Water Treatment Units (RO, Softeners, filters,

pitchers) (NSF/ANSI Stds 42, 44, 53, 53, 55, 58, 62, 177)• Onsite Wastewater Treatment Devices

(NSF/ANSI Stds 40, 41, 46 and 245) • Recreational Water – Pool/Spa Safety (pumps, drains,

pool covers, filters) (NSF/ANSI 50)

Health Sciences (Dietary Supplements and Pharma)

NSF developed the only American National Standard for for Dietary Supplements in 2001 (NSF/ANSI Standard 173).

Di t S l t C tifi ti P• Dietary Supplement Certification Program– GMP audits; Toxicology, Label & Contaminant Reviews

• Athletic Banned Substance Certification Program: – Adds screening for 140 banned substances to the above– MLB, NFL,PGA, LPGA, NYPD, and Canadian Centre for Ethics in Sport

• NSF Pharmalytica – GLP and GMP Lab• analytical testing, consulting, training, registration and research and development

• DBA (David Begg Associates) - Pharma Training & Consulting• DBA Analytical – Biotech, Tox, GMP training

Toys & Residential Consumer Products Safety; Protocols

• NSF is accredited to test and certify toys and children’s products to the Consumer Product Safety Improvement Act.

• NSF develops protocols and standards for residential kitchen items and other household appliances.

• NSF tests a wide range of consumerNSF tests a wide range of consumer products to verify safety, quality and performance.

Sustainability and ISO/Strategic Registrations

• Sustainability Solutions– GHG verification– Environmental Claims verification– Trucost foot printing (carbon, water)– ISO 14001 (Environmental), R2, RIOS– Sustainable Forestry Initiative Sus a ab e o es y a e– Chain of Custody

• Strategic Registrations (ISO):– ISO 9001 (Quality)– ISO 22000 (Food Safety) – ISO 27000 (Information Security) – ISO 13485 (Medical Devices)– And more!

NSF’s Training and Education: A Cornerstone of NSF’s Health-Based Mission

• NSF’s Training and Education Division has a global network of technical experts available to deliver training around the globe for industry, consumers, regulators and pubic health officials.

• Training forms: online, food safety videos/DVD, guidebooks, live webinars and customized on-site training.

• Topics:– Food Safety & Quality

• Agriculture Producers, Food and Beverage Processing, Organic Certification, Seafood Safety and Quality, Restaurants and Supermarket Food Safety, Hotel and Hospitality Safety

– Sustainability, Social Accountability and Environmental management– Pharmaceuticals & Dietary Supplements Safety– Management Systems/ISO Registration – Drinking Water Systems

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Projects with IPEC –• Host midwest meetings• Partner for training programs• IPEA joint venture for EXCiPACT / ANSI

audits

Inactive Ingredient Database (IID) – Recent Issues affecting ANDA

SponsorsSponsorsDavid R. Schoneker

Vice Chair of Scientific & Regulatory PolicyIPEC Americas

Director of Global Regulatory AffairsColorcon

Email: dschoneker@colorcon.com

Issues

• New developments at FDA related to the IID – problems for ANDA Sponsors

• FDA’s Substance Registration System (SRS)

• Impact on the Inactive Ingredient Database

• Example - HPMC Grade Issue

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Impact to the IID Assessment

• The SRS nomenclature is being used to add new item listings in the IID which are grade specific with whatever levels happen to be in the NDA or ANDA which triggers inclusion

• These specific references to the grades are now being used by FDA OGD reviewers as a precedence level when evaluating precedence of use at the Gatekeeper point when a ANDA is filed

• Many times the levels listed for the specific grades are much lower that what has traditionally been used

• ANDA sponsors are getting caught in the middle and don’t always know which listing to reference, especially for materials where they have been using non-grade specific references with higher levels in the past

• Triggering refuse to file letters unless additional safety data is provided

Impact to the IID Assessment

• Many times safety data is not readily available from suppliers or the data is old or for a family of materials rather than specific to a grade

• IPEC Americas is trying to set up a meeting with FDA OGD to discuss solutions to this problemdiscuss solutions to this problem

• FDA has agreed to meet with IPEC. Date is being determined. Should be established soon!

• IPEC Regulatory Affairs Committee will be developing the agenda and speaker list for this meeting on Thursday

Discussion and Questions

FDA Spectral Library CALL TO IPEC

• Butylated Hydroxyanisole

• Gelatin• Povidone• Butylated

H d t l

• Maltodextrin• Sorbitol• Croscarmellose• Microcrystalline

Cellulose

• Calcium Stearate• Hydroxy Propyl

Methyl Cellulose• Shellac• Carboxymethyl

C ll l Hydroxytoluene• Glycerin• Pregelatinized

Starch• Calcium

Phosphate (Dibasic)

• Hydroxy Propyl Cellulose

• Propylene Glycol (liquid and solid) 41

• Starch (Corn)• Crospovidone• Polyethylene

Glycol, liquid and solid

• Stearic Acid• Ethylcellulose• Polysorbate 80 • Talc• Titanium Dioxide

Cellulose • Lactose• Silicon Dioxide• Castor Oil• Magnesium

Stearate• Sodium Starch

Glycolate• Cresol

FDA Spectral Library – Participation Benefits

1. An inspector can make an immediate determination as to whether or not laboratory analysis is necessary by performing a screening test. This approach would reduce delays associated with sending samples to a laboratory.

2. Knowledge that FDA is screening excipients and that excipients are receiving a higher level of scrutiny should provide deterrence and add a layer of difficulty for anyone trying to infiltrate the supply chainfor anyone trying to infiltrate the supply chain.

3. All parties can have an increased level of confidence that the material being identified is indeed from the qualified supplier.

4. Materials that are different from the spectral reference standards can be flagged for additional investigation and, if warranted, subsequently added to the library.

5. All parties will have increased assurance that goods were not tampered with, substituted or otherwise falsified with regard to their origin during distribution.

6. Screening and surveillance activities can enable rapid response to concerns of contamination, adulteration and/or substitution in the supply chain reported to or identified by FDA.

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FDA Spectral Library – Participation Benefits

1. An inspector can make an immediate determination as to whether or not laboratory analysis is necessary by performing a screening test. This approach would reduce delays associated with sending samples to a laboratory.

2. Knowledge that FDA is screening excipients and that excipients are receiving a higher level of scrutiny should provide deterrence and add a layer of difficulty for anyone trying to infiltrate the supply chainfor anyone trying to infiltrate the supply chain.

3. All parties can have an increased level of confidence that the material being identified is indeed from the qualified supplier.

4. Materials that are different from the spectral reference standards can be flagged for additional investigation and, if warranted, subsequently added to the library.

5. All parties will have increased assurance that goods were not tampered with, substituted or otherwise falsified with regard to their origin during distribution.

6. Screening and surveillance activities can enable rapid response to concerns of contamination, adulteration and/or substitution in the supply chain reported to or identified by FDA.

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IPEC ‐ FDA QbD Excipient Workshop White Oak ‐ December 5th

9am ‐ Noon

• Speakers– Brian Carlin  (FMC)

– Dave Schoneker  (Colorcon)

Chris Morton (FinnBrit Consulting)– Chris Morton (FinnBrit Consulting)

– Graham Cook (Pfizer ‐ possibly by videoconference if he cannot attend)

– Tom Schultz (J&J)

– FDA perspective

– Others … other

Agenda

• Introduction to IPEC and IPEC Guideline

• Types and Sources of Excipient Variability

• Performance related properties (compositional and physical)

• Limitations of possible controls in chemical plants

• Communication between maker and user

P d i t ti f i i t• Proper design space expectations for excipients

• Misunderstandings of what types of samples will be available for experimentation

• Concepts for design space development

• Advanced concepts for future improvements

• Panel discussion Q&A