lifesciences.knect365.com/bpieurope

Connecting Science, Technology and Business to Optimise Bioprocessing

Pre-Conference Workshops - Monday 11 April 2016

8:15 - 8:45

Registration

Workshop by Ypso-Facto: Continuous Processing – Challenges, Microbial Manufacturing

Technologies, Processes, Economics & Strategy

8:45 - 8:45 8:45 - 12:00

Workshop by Ypso-Facto: Continuous Processing – Challenges, Microbial Manufacturing

Technologies, Processes, Economics & Strategy

Technologies & Processes This session will comprise a series of presentations and in-depth

Motivations for continuous bioprocessing

Definitions discussion on the production, recovery, analysis and formulation of

Process designs of a typical mAb production process microbial-based production methods.

Landscape of continuous processing technologies

In-line dilution

Perfusion cultures Sustainable Biomanufacturing using Microalgae as the

Continuous chromatography

Production Platform

Continuous TFF

Continuous centrifugation, reactions; etc. In an ideal world, we would like a biological production platform to

Process integration enable high enough product titres to be obtained with sufficient

control of the process to minimise production variations. Microalgae

From batch to continuous ... Is it the right question? The unit

have interesting characteristics to enable us to develop them as

sustainable biomanufacturing platforms. The pros and cons of this

operation perspective

proposition will be discussed in this presentation.

A few trivial considerations on reactions and Dr. Seetharaman Vaidyanathan, Senior Lecturer, Department of

chromatography in batch or continuous mode

Chemical & Biological Engineering, Advanced Biomanufacturing

Basic chemical engineering lessons for reactors, liquid-liquid

Centre, The University of Sheffield, UK

extraction and chromatography

Further insights on chromatography

From unit operations to complete processes

Process Development and Scale-Up of Recombinant

Economical evaluations CRM197 as a Carrier Protein for Polysaccharide Vaccines

CRM197 is the genetically inactivated form of the diphtheria

toxin produced by C. diphtheriae. It is used as a carrier

protein for capsular polysaccharide vaccines. The

Existing facilities presentation will describe how a high-yield fermentation

process was developed for producing a soluble periplasmic

Design of new facilities

CRM197 by using a recombinant E. coli strain. Further

Example of cost studies of a mAb process

technology optimizations were integrated during scaling-up

Day-to-day challenges during implementation of continuous

in order to obtain a robust commercial scale process leading

processes

to a very high purity product.

Batch definition

Process control strategy - PAT

Cleaning strategy

Process validation Thomas Cornet, Scientist, GlaxoSmithKline, Belgium

Feedback from Past Workshop Attendees Process Improvement of Legacy Microbial Process with

"A thorough overview of how to apply a continuous process to the Implementation of Single-Use Technology

• Implementation single-use technology for process

development of an API using relevant case study examples. What are improvement of a legacy microbial process

the considerations and challenges" • Process re-development and validation

(UCB, 2015)

• Regulatory considerations

• Extractables and leachables

• Process economics, etc.

"A great top level overview of continuous processing"

Ying Gao, Production Technical Support Specialist, Porton

+44(0)20 7017 7481

(Actavis, 2015) Biopharma Ltd, UK

Margit Holzer,

Scientific Director and Exclusive Consultant, Upstream Production Strategies

Ypso-Facto, France Improving expression platforms

Roger-Marc Nicoud, Improving product yields for microbial systems - What titres

can we expect?

Founder & CEO, Bioreactors design and usability for microbial based systems

Ypso-Facto, France

Downstream Production Strategies

Purification strategies for non-antibody products

Cell secretion

Refolding from inclusion bodies

Interactive Group Discussion: Common Challenges of using

Microbial Expression Systems

This session will evaluate the top 5 challenges facing the development

and manufacture of microbial-based production systems and discuss

strategies to overcome them.

Seetharaman Vaidyanathan,

Senior Lecturer,

The University of Sheffield

Thomas Cornet,

Scientist, TP Fermentation, Drug Substance, Technical R&D,

GSK Vaccines

Ying Gao,

Production Technical Support Specialist,

Porton Biopharma Ltd

12:00 - 1:00

Lunch Followed by Choice of Three Site Visits

Option 1: *SOLD OUT* Site Visit to Option 2: Site Visit to BOKU and acib Option 3: Site Visit GE Healthcare’s Cell

Boehringer Ingelheim (Austrian Centre of Industrial Culture facility

Biotechnology)

1:00 - 1:00 1:00 - 1:00 1:00 - 1:30

Site Visit Boehringer Ingelheim Site Visit BOKU and acib (Austrian Centre of Site Visit GE Healthcare’s Cell Culture

** SOLD OUT ** Industrial Biotechnology) Facility

The University of Natural Resources and Life The European distribution and

Sciences, Vienna, the Alma Mater Viridis, is manufacturing site for HyClone is centrally

The site in Vienna is specialised in the an education and research centre for located in Pasching, Austria. This modern

biotechnology. The department of

facility has similar functionality and quality

development and manufacture of

biotechnology has strong research activities

systems in place as the Center of Excellence

biopharmaceuticals derived from microbial

in the field of biopharmaceutical

for manufacturing of cell culture media and

fermentation technology. Committed to

manufacturing and related fields. A fully

buffers in Utah, United States. To expand the

technology leadership, it is applying high-

automated pilot plant is available for training

global fottprint of HyClone products, buffers

yield expression systems (bacteria and

and research purposes. BOKU is also co-

and process liquids are now being produced

yeast), media design, matrix assisted

owner of the research centre Austrian Centre

in the Pasching facility. HyClone liquid and

refolding, crystallisation and efficient

of Industrial Biotechnology (acib).

powder cell culture media will follow shortly.

downstream processing for the production of

In addition, the successful rapid-turnaround

plasmid DNA products, proteins, antibody

prototype manufacturing services will be

fragments and protein scaffolds.

Agenda:

launcged during spring 2016. The Austrian

Introduction to the Department of

location of the site further establishes a

reliable supply chain for global

Biotechnology (Florian Rüker)

Today, the company operates 3 GMP plants biopharmaceutical companies and serves as

Introduction to Austrian Centre of

+44(0)20 7017 7481

with a capacity of up to 12,000 L. The

facilities are approved “multi-product”

facilities for the manufacture of products

registered with EMEA and the FDA.

Proposed Agenda:

Presentation of Boehringer

Ingelheim, regional center

Vienna and the facility Rolling site visits in three groups:

process science upstream, process

science downstream as well as an

overview of the pilot and production

plant from the visitor base. Each

visit will be accompanied by

explanations from specialist Networking drinks and small buffet

Industrial Biotechnology

(Alois Jungbauer) Tour through the pilot plant

(Markus Luchner) CHO genome-scale science

(Nicole Borth) Continuous manufacturing research

program (Alois Jungbauer)

an additional logistics hub for distribution

to our European customers.

Proposed Agenda**

Introduction to the Pasching

facility and GE Healthcare Cell

culture and Process Liquids Invited speaker: Andrew

Falconbridge, Head of Downstream

processing, Alvotech Iceland Site tour of pilot and production

plant including powder mill and

large scale liquid filling production

suits. Dinner with GE Healthcare

senior leaders in Vienna

* Limited number of spaces available. **Journey to the Pasching facility takes

approximately 2 hours. Presentation will

be given on bus and snacks will be

served on the return journey. BPI Europe Day 1 - Tuesday 12 April 2016 7:30 - 8:20 Registration

Plenary Session: Industry Innovation - New Products, New Processes, New Technologies 8:20 - 8:25

Kevin Bailey, Chairperson's Opening Remarks

Former Vice President, Process Development, Regeneron Pharmaceuticals, USA

Process Development for Emerging Therapies - Early to Late-Stage Technical Development 8:25 - 8:55

Nicola Beaucamp ,

Keynote

Head of Process Research, Pharma Research

Early Development Strategies for Innovative Therapeutic Molecules

and Early Development, ,

A number of novel antibody formats have been advanced into clinics Roche Innovation Center Penzberg, Germany

by Roche pRED.

In order to discover and develop differentiated monoclonal antibodies

Roche's strategy is based on engineering technologies which bear

several challenges for technical development. Examples on innovative

therapeutic molecules for ADCC-enhancement, multi-pathway-

inhibition, specific tumor-targeting will be given.

8:55 - 9:25

Keynote Future Challenges and Exciting Opportunities in Bioprocessing The Pharma industry is continuously looking for better molecules

to even more effectively fight against various diseases. The view

has been broadened and is increasingly considering rare disease

indications as well, i.e. besides the big “classical” therapy areas. +44(0)20 7017 7481

Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany

Molecule formats have changed to more complex. This implies a big

challenge also for bioprocess development and commercial

manufacturing. So far established platform processes and

technologies have to be refined and, simultaneously, acceleration

strategies are needed to make new drugs with high quality earlier

available for the patient. This in turn requires rearrangement or

shortening of process development timelines. Experience, expertise

and creativity are required to encounter these challenges which are

opportunities for innovation and progress at the same time.

Bringing Keytruda to Market 9:25 - 9:55

Gargi Maheshwari ,

Keynote

Executive Director, Biologics Process

KEYTRUDA – Acceleration of a Breakthrough Therapy…What to

Development and Commercialisation, ,

Do When CMC is on the Critical Path MSD

9:55 - 10:25 Thought Leaders Discussion Panel Thought Leaders Discussion Panel: From

Research to Commercialisation Topics to Discuss include:

Biology vs Process Platform development for new formats Challenges when moving from phase I to clinical

development , to commercialisation

Kevin Bailey, Former Vice President, Process Development, Regeneron Pharmaceuticals, USA Nicola Beaucamp , Head of Process Research, Pharma Research and Early Development, , Roche Innovation Center Penzberg, Germany Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany Gargi Maheshwari , Executive Director, Biologics Process Development and Commercialisation, , MSD

10:25 - 11:25

Morning Coffee

Cell Culture Media and Feed Downstream Processing CMC Strategies for Biosimilars BPI Theatre Interactive Sessions

Optimisation

11:25 - 11:55 11:25 - 11:55 11:25 - 11:45 11:25 - 12:25

The Potential of Small The Future of Downstream Moving from the First Wave to Technology Transfer and

Molecules to Modulate Processing the Third Wave of Biosimilars Outsourcing

Glycosylation · Balancing the need between

Part One: Technology Transfer

Carsten Brockmeyer,

A large number of recent innovation and development

Programme

CEO,

publications demonstrate the

timelines

Formycon, Germany management – how do

effect of cell culture media on

· Regulatory pressures vs. you identify all the

glycosylation of recombinant

hazards, information and

proteins. This study aims to

price pressures

11:45 - 12:05

equipment gaps

extend the toolbox of media

· Platform development for

Understanding the Influence of Checking the checklist

design beyond the commonly

novel therapies

Regulatory expectations

known media components. The

Process Development on

when outsourcing

cells were cultivated in fed-batch

Product Quality in Biosimilar

· DSP in a flexible facility How much information

mode cultures using shaking 96-

Development

model is appropriate to share

deepwell plates and spin tubes.

without damaging the

Process performance such as

transfer

viable cell density, viability and

Software to create real-

product titer were monitored.

time tech transfer

+44(0)20 7017 7481

The addition of the supplements

at the beginning of the culture

exhibited significant changes of

the glycosylation profile of the

expressed protein. These

results show that media design

alone is sufficient to specifically

modulate some of the essential

protein quality attributes, which

circumvents the need of

modifying the gene expression

of the cell line.

David Brühlmann, Merck Serono | Biotech Process Sciences 11:55 - 12:25 Media Development for

Control of Charge Variants

Chris Kwiatkowski, Engineer, Biopharmaceutical Development, Biogen Idec 12:25 - 12:55 One-Step Seed Train:

Efficiency in Operation and

Decreased Cost This talk describes a method for

intensification of the seed-train

process using a high-density cell

bank and a perfusion-based

seed process strategy. The

described method enabled

reducing the process time,

simplified the operations and

generated opportunities to

increase the annual batch

throughput. Process economy

implications will be discussed.

Olof Larsson, Research Scientist , GE Healthcare Life Sciences

Stefan Hepbildikler, Director Pharma Biotech Development, Recovery&Downstream Processing, Roche Pharmaceuticals 11:55 - 12:25 Top 5 Obstacles DSP

Needs to Overcome-

Discussion Panel and Poll

DSP investment over

the next 3 years Online monitoring for real

time release – what is

the value for DSP, how

will it be integrated?

Alternative processing

steps and the coming of

continuous DSP

Improvements in DSP

and how the industry can

take advantage

Increasing capacity Reducing steps Harvest steps Improving

cycle times

Improving flow

rates

Alois Jungbauer, Professor , ACIB, BOKU, Austria Georg Klima, Executive Director, Process Science, , Boehringer Ingelheim, Austria Todd M. Przybycien, , Professor, Biomedical Engineering and Chemical Engineering Carnegie Mellon University Will Lewis Head of Purification Research , Biopharm Process Research RD Biopharm R&D, GSK, The UK Michel Eppink, Head, DSP, Synthon, The Netherlands 12:25 - 12:55 Custom Affinity

Chromatography, From

Diversity to Platform

Laurens Sierkstra , Business Leader , Thermo Fisher Scientific

Joey Studts, Global BioProcess & Pharmac. Dev, , Boehringer Ingelheim, Germany 12:05 - 12:35 Impact of Glycan Variation

on the Biological Activity of

Biosimilar Monoclonal

Antibodies

Daniel Galbraith, Chief Scientific Officer, Sartorius Stedim BioOutsource Limited.

Manufacturing Strategies 12:35 - 1:05 The Impact of Recent

Regulatory Trends on the

Pharmaceutical Manufacturing

Process and Quality Enterprise On-going industry consolidation

and the growth of contract

manufacturing in recent years,

coupled with an increasing focus

on quality and risk by regulatory

agencies, has highlighted the

need to promote data-driven

collaboration across the

manufacturing process and quality

enterprise, including outsourced

operations (CMO’s). A recent

industry survey highlighted the

problems of multiple disparate

quality systems and data sources,

along with the lack of an effective

quality culture and the lack of

quality metrics, as the top

challenges for shortening time to

market. These represent needless

barriers to improved process

understanding and control of

variability, because they impede

the implementation of role-based

process monitoring with

automated alerts for review-by-

exception to improve process

performance and compliance with

Continued Process Verification

(CPV), and Manufacturing Quality

Metrics (MQM) initiatives. They

can be removed by eliminating

labor intensive, error-prone

spreadsheet methods and instead

providing end users with easy

access to all process and quality

data in disparate sources in a

readily usable form that takes

process genealogy into account.

This presentation will describe

how leading life science

between external and

internal sites – vendors

and experience

Part Two: Problem

Solving “What Would you

Do in this Situation?”

Scenario-Based Activity This session looks at a

hypothetical situation where

a CMO can no longer fulfil its

obligation on a clinical supply

agreement. How should the

sponsor react and resolve

this problem?

Part 1: What has

gone wrong? Part 2: What should

the sponsor do in this

situation? Part 3: What should

the CMO do in this

situation? Part 4: How to

achieve best outcome

+44(0)20 7017 7481

companies have accomplished

this by using a validated

environment for self-service, on-

demand access to process and

quality data, integrated with

collaborative capabilities for

report creation, editing, tracking,

auditing, archiving and retrieval.

Justin O. Neway,

Managing Director - Process

Production Operations, Senior

Fellow - BIOVIA Science Council,

Dassault Systèmes BIOVIA

1:05 - 2:15

Lunch in the Exhibition Hall and Live Labs

Cell Culture Media and Raw High-Throughput Process Manufacturing Strategies BPI Theatre Interactive Sessions

Material Variability Control Development

2:15 - 2:45 2:15 - 2:45 2:15 - 2:35 2:15 - 3:45

Cell Culture Media and Feed High Throughput Screening Lean in Vaccine Development: Objective Derivation of the

Optimisation to Enhance Technologies Implemented in From Improving Knowledge Control Strategy

Product Quality and

Process Development of

Management to Supporting QbD

Productivity Biotherapeutic Proteins Richard Dennett,

Director,

Deborah Hol, Michel Eppink, Voisin Consulting Life Sciences

PhD Senior Research Scientist Head, DSP,

Upstream Process Development, Synthon, The Netherlands

Synthon Biopharmaceuticals BV Sarah Mercier ,

Scientist USP,

2:45 - 3:15

Janssen, Pharmaceutical

2:45 - 3:15

HTPD: Beyond Screening and Companies of Johnson and

Johnson

POLOXAMER 188: Critical Raw Scouting.

Material Risk Mitigation

Edward Koepf ,

2:35 - 2:55

Marion Glenn,

Process Development Scientist,

Disposable Manufacturing -

Senior Engineer, Process Biochemistry ,

Case Study from BMS

Genentech, Inc. Biogen Idec, USA

Ron Bates,

3:15 - 3:45

3:15 - 3:45

Director ,

ambr® 250 modular: An Afternoon Spotlight BMS, USA

advanced Tool to Develop Cell Presentation - A Representative

Culture Small-Scale Models from Asahi Kasei 2:55 - 3:15

Representing Manufacturing-

Scale Operation BPOG’s Best Practice Guide for

Single Use Leachable Studies -

Nicolas Marceau, Risk Assessment, Leachable

Study Design and Leachable

USP Laboratory Head,

Test Method(s)

SANOFI

Ken Wong,

Deputy Director ,

Sanofi Pasteur

Kathryn McGohan,

Associate Scientist II,

Bristol-Myers Squibb

3:15 - 3:45

Refolding of Biopharmaceuticals

with FOLDTEC® - Novel

Approach for Efficient

Manufacturing in Commercial

Scale

+44(0)20 7017 7481

While Wacker’s own technology

ESETEC® has proven highly

efficient in producing soluble

proteins and antibody fragments

via secretion, poorly soluble

substances form aggregated

inclusion bodies within the cell,

which contain incorrectly and or

incompletely folded target

proteins. Recently Wacker

Biotech introduced FOLDTEC®,

its novel refolding technology for

bioengineered pharmaceutical

proteins. With this new

technology biopharmaceuticals

that tend to aggregate can be

efficiently produced in their

soluble-active form in high

yields. The proprietary process

utilizes specifically developed

and optimized bacterial strains

and a patented, antibiotic-free

expression system.

Furthermore, Wacker Biotech

offers extensive expertise in the

iterative screening of optimum

refolding conditions in order to

convert the insoluble target-

protein aggregates into a

biologically active form.

Here we present a recent case

study on recombinant expression

and in vitro refolding of a difficult-

to-manufacture protein for medical

use. Finally we will provide

insights in state-of-the-art

microbial manufacturing of a

commercial biopharmaceutical by

refolding at Wacker Biotech.

Nicole Peuker,

Scientific Specialist,

Wacker Biotech GmbH

3:45 - 4:15

Afternoon Break

Cell Culture Process Controls Downstream Processing Continuous Manufacturing BPI Theatre Interactive Sessions

and Real-Time Monitoring

Methods

4:15 - 4:45 4:15 - 4:45 4:15 - 4:45 4:15 - 5:15

Upstream Process Development Facing the Challenge of Highly Continuous Manufacturing, the Roundtable Discussion

Strategies at Eli Lilly Diverse Products – Can we still Economics Upstream vs. Facilities of the Future

Accelerate Process Downstream Understanding the

Sinead Heuston , Development? Drivers The Future of Biologic

Manufacturing

Technical Individual needs of highly diverse Our experience of modelling

Services/Manufacturing Science

products challenge both - up and continuous bioprocess

Representative,

downstream processing. operations allow us to provide How will facilities look in

Eli Lilly

Interconnection of bioprocess insights into the status of 5-10 years’ time?

and purification strategies at continuous bioprocessing. This

4:45 - 5:15 early stage and screening allows us to identify those factors

The biomanufacturing

platforms enabling high flexibility that require

Advances in Cell Culture Process during process development are optimization/development and to market – from large

Controls and Multicomponent an adequate answer. We present understand the potential now scale production to niche

Monitoring Methods a miniaturized platform for and for the future. In particular players

+44(0)20 7017 7481

Jonathan Bones, NIBRT

parallel screening of the entire

downstream process

compatible with the DoE

concept and potential for

interlinkage to upstream.

Astrid Dürauer , Laboratory of Protein Technology and Downstream Processing, Departement of Biotechnology, , BOKU Vienna 4:45 - 5:15 A One-Stream Approach

to Downstream Process

Development

Will Lewis Head of Purification Research , Biopharm Process Research RD Biopharm R&D, GSK, The UK

we focus on the influence of

upstream versus downstream and

the implication of technology

trends on the value proposition for

continuous operation.

Andrew Sinclair, President, Founder, Biopharm Services, UK 4:45 - 5:00 A Rationale Approach for

Comparing Different Affinity

Chromatographic Processes

for the Capture of a

Monoclonal Antibody Due the increasing number of

chromatographic media and

ways of implementation (single

column used in a batch mode or

several columns being

connected and used for more or

less continuous production; in

parallel or continuous counter-

current mode), the down-stream

developer is confronted to a

continuously growing number of

options.

Developing, optimizing and then

comparing all possible options is

almost impossible. An alternative

is to perform a limited number of

well-defined experiments, and

then use process simulation tools

to orient decisions.

Process simulation requires the

knowledge of physico-chemical

parameters, characterization of

molecule adsorption, mass

transfer and kinetics. Tests to

gather this information can be

performed at laboratory scale

followed by computer modeling

using tools like

ChromworksTM, enabling to

predict front propagations

inside chromatographic

column(s) and the influence of

operating parameters. This

allows simulating single or

more complex multiple column

(MCC) systems.

Using a monoclonal Antibody

capture on affinity

chromatography, we propose an

approach associated with

process modeling to assess

standard single column systems

and also new innovative

multicolumn systems like the Bio

Modular vs.

Stainless steel

Regulatory

expectations for 21st

biological production

Manufacturing

strategies for entering

emerging markets:

Priority areas and

local support

What can biotech learn

from other industries to

improve manufacturing

Kumar Dhanasekharan, Director of Process Development, Cook Pharmica LLC

+44(0)20 7017 7481

Simulated Moving Bed

(BioSMBTM), the Sequential

Multi-Column Chromatography

(SMCC-BioSCTM), the 3 or 4

Column Periodic Counter Current

System (3C-PCC TM or 4C-PCC

TM) or the CaptureSMB.

The computer modeling approach

has the big merit of rationalizing

such typical multi-variate

processes and allows one for

comparing complex systems in

order to evaluate their merits

and/or drawbacks with minimal

experimental efforts.

Margit Holzer, Scientific Director and Exclusive Consultant, Ypso-Facto, France

5:00 - 5:15

Continuous Processing

and Facility Design -

Discussion Panel

Business drivers for

continuous processing

Facility design to

enable continuous

processing and

process intensification

Designing a facility for

continuous processing

– considerations and

options Facility modifications to

optimise throughput

Regulatory challenges

for continuous

processing Process validation

Andrew Sinclair, President, Founder, Biopharm Services, UK

Margit Holzer, Scientific Director and Exclusive Consultant, Ypso-Facto, France

Miriam Monge , Director of Marketing Integrated Solutions, Sartorius Stedim Biotech

Closing Plenary Session: From Molecular Medicine to Patient 5:15 - 5:45

Keynote +44(0)20 7017 7481

From Molecular Medicine to Patient At the Institute of Molecular Biotechnology 13 independent

groups work on various basic research topics in biomedicine. Penninger’s group investigates, among other projects, pathways how

the immune system fights cancer via checkpoint blockades like Cbl-b. Another important research area is focusing on the various

functions of the protein RANKL. This contributed to the development of Denosumab, a

human monoclonal antibody to RANKL.

Josef Penninger, Scientific Director, IMBA, Austria

5:45 - 6:15

Keynote Meeting the Challenges of a Rapidly Changing Bioproduction

Industry with Single Use Technology- Past, Present and Future

Projected Biopharm market size growth

Key trends shaping the industry The evolution of single use technology Current state of the art on single use hardware

and consumables Enhancing plant flexibility and capacity with single

use technology

Michael Goodwin , R&D Director, Thermo Fisher Scientific

6:15 - 6:20

Alois

Jungbauer, Closing Remarks from the Chair Professor , ACIB, BOKU, Austria

6:20 - 7:50 Networking Drinks and Evening Reception Upstream Processing - Tuesday 12 April 2016 7:30 - 8:20 Registration

Plenary Session: Industry Innovation - New Products, New Processes, New Technologies 8:20 - 8:25

Kevin Bailey, Chairperson's Opening Remarks

Former Vice President, Process Development, Regeneron Pharmaceuticals, USA

Process Development for Emerging Therapies - Early to Late-Stage Technical Development 8:25 - 8:55

Nicola Beaucamp ,

Keynote

Head of Process Research, Pharma Research

Early Development Strategies for Innovative Therapeutic Molecules

and Early Development, ,

A number of novel antibody formats have been advanced into clinics

Roche Innovation Center Penzberg, Germany

by Roche pRED.

In order to discover and develop differentiated monoclonal antibodies

+44(0)20 7017 7481

Roche's strategy is based on engineering technologies which bear

several challenges for technical development. Examples on

innovative therapeutic molecules for ADCC-enhancement, multi-

pathway-inhibition, specific tumor-targeting will be given. 8:55 - 9:25

Keynote Future Challenges and Exciting Opportunities in Bioprocessing The Pharma industry is continuously looking for better molecules to

even more effectively fight against various diseases. The view has

been broadened and is increasingly considering rare disease

indications as well, i.e. besides the big “classical” therapy areas.

Molecule formats have changed to more complex. This implies a big

challenge also for bioprocess development and commercial

manufacturing. So far established platform processes and

technologies have to be refined and, simultaneously, acceleration

strategies are needed to make new drugs with high quality earlier

available for the patient. This in turn requires rearrangement or

shortening of process development timelines. Experience, expertise

and creativity are required to encounter these challenges which are

opportunities for innovation and progress at the same time.

Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany

Bringing Keytruda to Market 9:25 - 9:55

Gargi Maheshwari ,

Keynote

Executive Director, Biologics Process

KEYTRUDA – Acceleration of a Breakthrough Therapy…What to

Development and Commercialisation, ,

Do When CMC is on the Critical Path MSD

9:55 - 10:25 Thought Leaders Discussion Panel Thought Leaders Discussion Panel: From

Research to Commercialisation Topics to Discuss include:

Biology vs Process Platform development for new formats Challenges when moving from phase I to clinical

development , to commercialisation

Kevin Bailey, Former Vice President, Process Development, Regeneron Pharmaceuticals, USA Nicola Beaucamp , Head of Process Research, Pharma Research and Early Development, , Roche Innovation Center Penzberg, Germany Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany Gargi Maheshwari , Executive Director, Biologics Process Development and Commercialisation, , MSD

10:25 - 11:25 Morning Coffee

9:28 - 9:28 Morning Chairperson

Cell Culture Media and Feed Optimisation 11:25 - 11:55 The Potential of Small Molecules to Modulate Glycosylation

+44(0)20 7017 7481

A large number of recent publications demonstrate the effect of cell

culture media on glycosylation of recombinant proteins. This study

aims to extend the toolbox of media design beyond the commonly

known media components. The cells were cultivated in fed-batch

mode cultures using shaking 96-deepwell plates and spin tubes.

Process performance such as viable cell density, viability and

product titer were monitored. The addition of the supplements at the

beginning of the culture exhibited significant changes of the

glycosylation profile of the expressed protein. These results show

that media design alone is sufficient to specifically modulate some

of the essential protein quality attributes, which circumvents the

need of modifying the gene expression of the cell line.

David Brühlmann, Merck Serono | Biotech Process Sciences

11:55 - 12:25

Chris Kwiatkowski, Media Development for Control of Charge Variants Engineer, Biopharmaceutical Development,

Biogen Idec 12:25 - 12:55 One-Step Seed Train: Efficiency in Operation and Decreased Cost This talk describes a method for intensification of the seed-train

process using a high-density cell bank and a perfusion-based seed

process strategy. The described method enabled reducing the

process time, simplified the operations and generated opportunities

to increase the annual batch throughput. Process economy

implications will be discussed.

Olof Larsson, Research Scientist , GE Healthcare Life Sciences

12:55 - 2:05

Lunch in the Exhibition Hall and Live Labs

9:28 - 9:28

Afternoon Chairperson Harald Bradl,

Director Cell Culture Development ,

Boehringer Ingelheim Pharma GmbH & Co. KG

Cell Culture Media and Raw Material Variability Control

2:05 - 2:35 Deborah Hol,

Cell Culture Media and Feed Optimisation to Enhance Product

PhD Senior Research Scientist Upstream

Quality and Productivity

Process Development,

Synthon Biopharmaceuticals BV

2:35 - 3:05 Marion Glenn,

POLOXAMER 188: Critical Raw Material Risk Mitigation

Senior Engineer,

Genentech, Inc.

3:05 - 3:35 ambr® 250 modular: An advanced Tool to Develop Cell Culture

Small-Scale Models Representing Manufacturing-Scale Operation

Nicolas Marceau, USP Laboratory Head, SANOFI

3:35 - 4:05 Afternoon Coffee

+44(0)20 7017 7481

Cell Culture Process Controls and Real-Time Monitoring Methods

4:05 - 4:35

Upstream Process Development Strategies at Eli Lilly Sinead Heuston ,

Technical Services/Manufacturing Science

Representative,

Eli Lilly

4:35 - 5:05 Jonathan Bones,

Advances in Cell Culture Process Controls and Multicomponent

NIBRT

Monitoring Methods

Closing Plenary Session: From Molecular Medicine to Patient

5:05 - 5:35 Josef Penninger,

Keynote

Scientific Director,

From Molecular Medicine to Patient

IMBA, Austria

At the Institute of Molecular Biotechnology 13 independent groups

work on various basic research topics in biomedicine.

Penninger’s group investigates, among other projects, pathways how

the immune system fights cancer via checkpoint blockades like Cbl-b.

Another important research area is focusing on the various functions

of the protein RANKL.

This contributed to the development of Denosumab, a human

monoclonal antibody to RANKL.

5:35 - 6:05 Michael Goodwin ,

Keynote

R&D Director,

Meeting the Challenges of a Rapidly Changing Bioproduction

Thermo Fisher Scientific

Industry with Single Use Technology- Past, Present and Future

• Projected Biopharm market size growth

• Key trends shaping the industry

• The evolution of single use technology

• Current state of the art on single use hardware and consumables

• Enhancing plant flexibility and capacity with single use technology

6:05 - 6:10 Alois Jungbauer,

Closing Remarks from the Chair

Professor ,

ACIB, BOKU, Austria

6:10 - 7:40

Networking Drinks and Evening Reception

Downstream Processing - Tuesday 12 April 2016

7:30 - 8:20

Registration

Plenary Session: Industry Innovation - New Products, New Processes, New Technologies

8:20 - 8:25

Chairperson's Opening Remarks

+44(0)20 7017 7481

Kevin Bailey, Former Vice President, Process Development, Regeneron Pharmaceuticals, USA

Process Development for Emerging Therapies - Early to Late-Stage Technical Development 8:25 - 8:55

Nicola Beaucamp ,

Keynote

Head of Process Research, Pharma Research

Early Development Strategies for Innovative Therapeutic Molecules

and Early Development, ,

A number of novel antibody formats have been advanced into clinics Roche Innovation Center Penzberg, Germany

by Roche pRED.

In order to discover and develop differentiated monoclonal antibodies

Roche's strategy is based on engineering technologies which bear

several challenges for technical development. Examples on innovative

therapeutic molecules for ADCC-enhancement, multi-pathway-

inhibition, specific tumor-targeting will be given.

8:55 - 9:25

Keynote Future Challenges and Exciting Opportunities in Bioprocessing The Pharma industry is continuously looking for better molecules to

even more effectively fight against various diseases. The view has

been broadened and is increasingly considering rare disease

indications as well, i.e. besides the big “classical” therapy areas.

Molecule formats have changed to more complex. This implies a big

challenge also for bioprocess development and commercial

manufacturing. So far established platform processes and

technologies have to be refined and, simultaneously, acceleration

strategies are needed to make new drugs with high quality earlier

available for the patient. This in turn requires rearrangement or

shortening of process development timelines. Experience, expertise

and creativity are required to encounter these challenges which are

opportunities for innovation and progress at the same time.

Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany

Bringing Keytruda to Market 9:25 - 9:55

Gargi Maheshwari ,

Keynote

Executive Director, Biologics Process

KEYTRUDA – Acceleration of a Breakthrough Therapy…What to

Development and Commercialisation, ,

Do When CMC is on the Critical Path MSD

9:55 - 10:25 Thought Leaders Discussion Panel Thought Leaders Discussion Panel: From

Research to Commercialisation Topics to Discuss include:

Biology vs Process Platform development for new formats Challenges when moving from phase I to clinical

development , to commercialisation

Kevin Bailey, Former Vice President, Process Development, Regeneron Pharmaceuticals, USA Nicola Beaucamp , Head of Process Research, Pharma Research and Early Development, , Roche Innovation Center Penzberg, Germany Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany

+44(0)20 7017 7481

Gargi Maheshwari , Executive Director, Biologics Process Development and Commercialisation, , MSD

10:25 - 11:25 Morning Coffee

Downstream Processing 11:25 - 11:55

The Future of Downstream Processing Stefan Hepbildikler,

Director Pharma Biotech Development,

Balancing the need between innovation and development Recovery&Downstream Processing,

Roche Pharmaceuticals

timelines

Regulatory pressures vs. price pressures

Platform development for novel therapies

DSP in a flexible facility model

11:55 - 12:25 Top 5 Obstacles DSP Needs to Overcome- Discussion Panel and Poll

DSP investment over the next 3 years Online monitoring for real time release – what is the value

for DSP, how will it be integrated? Alternative processing steps and the coming of

continuous DSP Improvements in DSP and how the industry can

take advantage Increasing capacity

o Reducing steps o

Harvest steps o Improving cycle times

o Improving flow rates

Alois Jungbauer, Professor , ACIB, BOKU, Austria Georg Klima, Executive Director, Process Science, , Boehringer Ingelheim, Austria Todd M. Przybycien, , Professor, Biomedical Engineering and Chemical Engineering Carnegie Mellon University Will Lewis Head of Purification Research , Biopharm Process Research RD Biopharm R&D, GSK, The UK Michel Eppink, Head, DSP, Synthon, The Netherlands

12:25 - 12:55

Custom Affinity Chromatography, FromDiversity to Platform Laurens Sierkstra ,

Business Leader ,

Thermo Fisher Scientific

12:55 - 2:05 Lunch in the Exhibition Hall and Live Labs

High-Throughput Process Development 2:05 - 2:35 High Throughput Screening Technologies Implemented in

Process Development of Biotherapeutic Proteins +44(0)20 7017 7481

Michel Eppink,

Head, DSP,

Synthon, The Netherlands

2:35 - 3:05 Edward Koepf ,

HTPD: Beyond Screening and Scouting

Process Development Scientist, Process

Biochemistry ,

Biogen Idec, USA

3:05 - 3:35

Afternoon Spotlight Presentation - A Representative from Asahi Kasei

3:35 - 4:05

Afternoon Coffee

Downstream Processing

4:05 - 4:35 Astrid Dürauer ,

Facing the Challenge of Highly Diverse Products – Can we still

Laboratory of Protein Technology and

Accelerate Process Development?

Downstream Processing, Departement of

Individual needs of highly diverse products challenge both - up and Biotechnology, ,

BOKU Vienna

downstream processing. Interconnection of bioprocess and

purification strategies at early stage and screening platforms enabling

high flexibility during process development are an adequate answer.

We present a miniaturized platform for parallel screening of the

entire downstream process compatible with the DoE concept and

potential for interlinkage to upstream.

4:35 - 5:05 Will Lewis Head of Purification Research ,

A One-Stream Approach to Downstream Process Development

Biopharm Process Research RD Biopharm R&D,

GSK, The UK

Closing Plenary Session: From Molecular Medicine to Patient

5:05 - 5:35

Keynote From Molecular Medicine to Patient At the Institute of Molecular Biotechnology 13 independent

groups work on various basic research topics in biomedicine. Penninger’s group investigates, among other projects, pathways how

the immune system fights cancer via checkpoint blockades like Cbl-b. Another important research area is focusing on the various

functions of the protein RANKL. This contributed to the development of Denosumab, a

human monoclonal antibody to RANKL.

Josef Penninger, Scientific Director, IMBA, Austria

5:35 - 6:05

Keynote Meeting the Challenges of a Rapidly Changing Bioproduction

Industry with Single Use Technology- Past, Present and Future • Projected Biopharm market size growth • Key trends shaping the industry +44(0)20 7017 7481

Michael Goodwin , R&D Director, Thermo Fisher Scientific

• The evolution of single use technology • Current state of the art on single use hardware and consumables • Enhancing plant flexibility and capacity with single use technology

6:05 - 6:10

Closing Remarks from the Chair Alois Jungbauer,

Professor ,

ACIB, BOKU, Austria

6:10 - 7:40 Networking Drinks and Evening Reception

Manufacturing Strategies - Tuesday 12 April 2016 7:30 - 8:20 Registration

Plenary Session: Industry Innovation - New Products, New Processes, New Technologies 8:20 - 8:25

Kevin Bailey, Chairperson's Opening Remarks

Former Vice President, Process Development, Regeneron Pharmaceuticals, USA

Process Development for Emerging Therapies - Early to Late-Stage Technical Development 8:25 - 8:55

Nicola Beaucamp ,

Keynote

Head of Process Research, Pharma Research

Early Development Strategies for Innovative Therapeutic Molecules

and Early Development, ,

A number of novel antibody formats have been advanced into clinics Roche Innovation Center Penzberg, Germany

by Roche pRED.

In order to discover and develop differentiated monoclonal antibodies

Roche's strategy is based on engineering technologies which bear

several challenges for technical development. Examples on innovative

therapeutic molecules for ADCC-enhancement, multi-pathway-

inhibition, specific tumor-targeting will be given.

8:55 - 9:25

Keynote Future Challenges and Exciting Opportunities in Bioprocessing The Pharma industry is continuously looking for better molecules to

even more effectively fight against various diseases. The view has

been broadened and is increasingly considering rare disease

indications as well, i.e. besides the big “classical” therapy areas.

Molecule formats have changed to more complex. This implies a big

challenge also for bioprocess development and commercial

manufacturing. So far established platform processes and

technologies have to be refined and, simultaneously, acceleration

strategies are needed to make new drugs with high quality earlier

available for the patient. This in turn requires rearrangement or

shortening of process development timelines. Experience, expertise

and creativity are required to encounter these challenges which are

opportunities for innovation and progress at the same time.

Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany

Bringing Keytruda to Market 9:25 - 9:55

Keynote KEYTRUDA – Acceleration of a Breakthrough Therapy…What to Do When CMC is on the Critical Path +44(0)20 7017 7481

Gargi Maheshwari , Executive Director, Biologics Process Development and Commercialisation, , MSD

9:55 - 10:25 Thought Leaders Discussion Panel Thought Leaders Discussion Panel: From

Research to Commercialisation Topics to Discuss include:

Biology vs Process Platform development for new formats Challenges when moving from phase I to clinical

development , to commercialisation

Kevin Bailey, Former Vice President, Process Development, Regeneron Pharmaceuticals, USA Nicola Beaucamp , Head of Process Research, Pharma Research and Early Development, , Roche Innovation Center Penzberg, Germany Wolfgang Kuhne, Vice President, Technical Development Bioprocessing & Clinical Supply,, Roche Diagnostics, Germany Gargi Maheshwari , Executive Director, Biologics Process Development and Commercialisation, , MSD

10:25 - 11:25 Morning Coffee

CMC Strategies for Biosimilars 11:25 - 11:45

Carsten Brockmeyer Moving from the First Wave to the Third Wave of Biosimilars

Formycon, Germany 11:45 - 12:05 Understanding the Influence of Process Development on

Product Quality in Biosimilar Development

Joey Studts, Global BioProcess & Pharmac. Dev, , Boehringer Ingelheim, Germany

12:05 - 12:35 Impact of Glycan Variation on the Biological Activity of

Biosimilar Monoclonal Antibodies

Daniel Galbraith, Chief Scientific Officer, Sartorius Stedim BioOutsource Limited.

Manufacturing Strategies 12:35 - 1:05

The Impact of Recent Regulatory Trends on the Pharmaceutical Justin O. Neway,

Managing Director - Process Production

Manufacturing Process and Quality Enterprise

Operations, Senior Fellow - BIOVIA Science

On-going industry consolidation and the growth of contract Council,

Dassault Systèmes BIOVIA

manufacturing in recent years, coupled with an increasing focus on

quality and risk by regulatory agencies, has highlighted the need to

promote data-driven collaboration across the manufacturing process

and quality enterprise, including outsourced operations (CMO’s). A

recent industry survey highlighted the problems of multiple disparate

+44(0)20 7017 7481

quality systems and data sources, along with the lack of an effective

quality culture and the lack of quality metrics, as the top challenges

for shortening time to market. These represent needless barriers to

improved process understanding and control of variability, because

they impede the implementation of role-based process monitoring

with automated alerts for review-by-exception to improve process

performance and compliance with Continued Process Verification

(CPV), and Manufacturing Quality Metrics (MQM) initiatives. They

can be removed by eliminating labor intensive, error-prone

spreadsheet methods and instead providing end users with easy

access to all process and quality data in disparate sources in a

readily usable form that takes process genealogy into account. This

presentation will describe how leading life science companies have

accomplished this by using a validated environment for self-service,

on-demand access to process and quality data, integrated with

collaborative capabilities for report creation, editing, tracking,

auditing, archiving and retrieval. 1:05 - 2:05 Lunch in the Exhibition Hall and Live Labs

2:05 - 2:25 Lean in Vaccine Development: From Improving

Knowledge Management to Supporting QbD

Sarah Mercier , Scientist USP, Janssen, Pharmaceutical Companies of Johnson and Johnson

2:25 - 2:45

Ron

Bates, Disposable Manufacturing - Case Study from BMS Director , BMS, USA

2:45 - 3:05 BPOG’s Best Practice Guide for Single Use Leachable Studies - Risk

Assessment, Leachable Study Design and Leachable Test Method(s)

Ken Wong, Deputy Director , Sanofi Pasteur Kathryn McGohan, Associate Scientist II, Bristol-Myers Squibb

3:05 - 3:35 Refolding of Biopharmaceuticals with FOLDTEC® - Novel

Approach for Efficient Manufacturing in Commercial Scale While Wacker’s own technology ESETEC® has proven highly efficient

in producing soluble proteins and antibody fragments via secretion,

poorly soluble substances form aggregated inclusion bodies within the

cell, which contain incorrectly and or incompletely folded target proteins.

Recently Wacker Biotech introduced FOLDTEC®, its novel refolding

technology for bioengineered pharmaceutical proteins. With this new

technology biopharmaceuticals that tend to aggregate can be efficiently

produced in their soluble-active form in high yields. The proprietary

process utilizes specifically developed and optimized bacterial strains

and a patented, antibiotic-free expression system. Furthermore, Wacker

Biotech offers extensive expertise in the iterative screening of optimum

refolding conditions in order to convert the insoluble target-protein

aggregates into a biologically active form.

Here we present a recent case study on recombinant expression and in

Nicole Peuker, Scientific Specialist, Wacker Biotech GmbH

+44(0)20 7017 7481

vitro refolding of a difficult-to-manufacture protein for medical

use. Finally we will provide insights in state-of-the-art microbial

manufacturing of a commercial biopharmaceutical by refolding at

Wacker Biotech. 3:35 - 4:05 Afternoon Coffee

Continuous Manufacturing 4:05 - 4:35

Continuous Manufacturing, the Economics Upstream vs. Andrew Sinclair,

President, Founder,

Downstream Understanding the Drivers

Biopharm Services, UK

Our experience of modelling continuous bioprocess operations allow

us to provide insights into the status of continuous bioprocessing. This

allows us to identify those factors that require

optimization/development and to understand the potential now and

for the future. In particular we focus on the influence of upstream

versus downstream and the implication of technology trends on the

value proposition for continuous operation.

4:35 - 4:50 A Rationale Approach for Comparing Different Affinity

Chromatographic Processes for the Capture of a

Monoclonal Antibody Due the increasing number of chromatographic media and ways

of implementation (single column used in a batch mode or

several columns being connected and used for more or less

continuous production; in parallel or continuous counter-current

mode), the down-stream developer is confronted to a

continuously growing number of options.

Developing, optimizing and then comparing all possible options

is almost impossible. An alternative is to perform a limited

number of well-defined experiments, and then use process

simulation tools to orient decisions.

Process simulation requires the knowledge of physico-chemical

parameters, characterization of molecule adsorption, mass

transfer and kinetics. Tests to gather this information can be

performed at laboratory scale followed by computer modeling

using tools like ChromworksTM, enabling to predict front

propagations inside chromatographic column(s) and the

influence of operating parameters. This allows simulating single

or more complex multiple column (MCC) systems.

Using a monoclonal Antibody capture on affinity chromatography,

we propose an approach associated with process modeling to

assess standard single column systems and also new innovative

multicolumn systems like the Bio Simulated Moving Bed

(BioSMBTM), the Sequential Multi-Column Chromatography

(SMCC-BioSCTM), the 3 or 4 Column Periodic Counter Current

System (3C-PCC TM or 4C-PCC TM) or the CaptureSMB.

The computer modeling approach has the big merit of

rationalizing such typical multi-variate processes and allows one

for comparing complex systems in order to evaluate their merits

and/or drawbacks with minimal experimental efforts.

Margit Holzer, Scientific Director and Exclusive Consultant, Ypso-Facto, France

+44(0)20 7017 7481

4:50 - 5:05

Continuous Processing and Facility Design - Discussion Panel Andrew Sinclair,

President, Founder,

• Business drivers for continuous processing Biopharm Services, UK

• Facility design to enable continuous processing and process

intensification

• Designing a facility for continuous processing – considerations and Margit Holzer,

options

Scientific Director and Exclusive Consultant,

• Facility modifications to optimise throughput

Ypso-Facto, France

• Regulatory challenges for continuous processing

• Process validation

Miriam Monge ,

Director of Marketing Integrated Solutions,

Sartorius Stedim Biotech

Closing Plenary Session: From Molecular Medicine to Patient

5:05 - 5:35 Josef Penninger,

Keynote

Scientific Director,

From Molecular Medicine to Patient

IMBA, Austria

At the Institute of Molecular Biotechnology 13 independent groups

work on various basic research topics in biomedicine.

Penninger’s group investigates, among other projects, pathways how

the immune system fights cancer via checkpoint blockades like Cbl-b.

Another important research area is focusing on the various functions

of the protein RANKL.

This contributed to the development of Denosumab, a human

monoclonal antibody to RANKL.

5:35 - 6:05 Michael Goodwin ,

Keynote

R&D Director,

Meeting the Challenges of a Rapidly Changing Bioproduction

Thermo Fisher Scientific

Industry with Single Use Technology- Past, Present and Future

• Projected Biopharm market size growth

• Key trends shaping the industry

• The evolution of single use technology

• Current state of the art on single use hardware and consumables

• Enhancing plant flexibility and capacity with single use technology

6:05 - 6:10 Alois Jungbauer,

Closing Remarks from the Chair

Professor ,

ACIB, BOKU, Austria

6:10 - 7:40

Networking Drinks and Evening Reception

BPI Europe - Day 2 - Wednesday 13 April 2016

8:25 - 8:30

Chairperson's Opening Remarks

Richard Dennett, Director, Voisin Consulting Life Sciences

Plenary Session: Global Manufacturing Strategies

+44(0)20 7017 7481

8:30 - 9:00 Parrish M. Galliher ,

Keynote

CTO Upstream, Xcellerex ,

Manufacturing Strategies in a Diverse World

GE Healthcare Life Sciences

As worldwide annual sales of biologics increase to the 200 bn USD

mark, so has the diversity of drug pipelines and treatment modalities

increased. The biotech industry began 40 years ago with recombinant

hormones and cytokines and has expanded to include monoclonal

antibodies (MAb), MAb-toxin conjugates, antibody fragments,

multivalent MAbs, cell-based and rDNA vaccines, cell and gene

therapies, therapeutic enzymes, biobetters, biosimilars, and more.

This pipeline diversity has driven the need for more diverse

manufacturing strategies and innovations to accommodate different

process architectures. The presentation will review the diversity of

drug pipelines and manufacturing innovation strategies to meet this

diversity.

9:00 - 9:30 Georg Klima,

Keynote

Executive Director, Process Science, ,

Accelerating the Development of Novel Biotherapeutics in Microbial

Boehringer Ingelheim, Austria

Expression Systems

Novel biotherapeutic formats pose unique development challenges.

Strategies for successful development need to holistically consider all

aspects of biopharmaceutical processes such as expression strategies,

novel unit operations, automated high-throughput process

development, as well as scale up and transfer from bench to large-

scale manufacturing.

9:30 - 10:00 Martin Smith,

Keynote

Chief Technology Officer,

Technology Advances and Considerations for Parallel and

Pall Corporation, USA

Continuous Bioprocessing

10:00 - 10:35

Morning Coffee

Upstream Process Development Downstream Processing Continuous Processing BPI Theatre Interactive Sessions

and High Throughput Models Strategies for Novel Therapies

10:35 - 11:05 10:35 - 11:05 10:35 - 10:55 10:35 - 11:35

Implementation and Translation A Viral Vaccine Production Perfusion Design for Integrated Dirty Data – Cleaning up your

of Predictable Bioreactor Platform - Fast Development Continuous Biomanufacturing Act

Process Scale Down Models and Low COGs Optimal bioreactor design and Are you collecting you

Boehringer Ingelheim is a leading At Janssen a production process choice of key process parameters data properly so that it

biopharmaceutical manufacturer was developed that allows are crucial to ensure and control captures the true

with more than 35 years of intensified manufacturing of viral long-term high cell density multivariate structure of

experience and many successful vaccines. By increasing the perfusion cultures. Requirements your processes and

transferred biopharmaceutical productivity in the PER.C6 when aiming at the direct products?

products to market. Our infection, the optimized process integration to a continuous

expression platform (BI-HEX®) can be used to cost-effectively downstream train will be Does your data suffer

enables fast-track development produce 100 million doses of discussed. from outliers, noise,

of high-quality, high-titer vaccine at 500L production scale. missing samples,

processes for producing It will be presented how the Daniel Karst,

multivariable effects,

biopharmaceuticals from CHO platform was used for rapid process dynamics and

cells. This platform include cell supply of our preventative Ebola The Morbidelli Group, auto-correlated

line engineering, high throughput vaccine and data will be Institute for Chemical and measurements, time

screening by automation, presented on the adaptation for Bioengineering, ETHZ, delays due to analyser

systematic DoE-based Polio vaccine production. Switzerland cycle time or off-line

approaches for media and cell analyses, measurement

culture process development to 10:55 - 11:15

non-linearity, etc?

identify optimal process

parameters for high titer Perfusion Process Development Why is data preparation

processes and strategies for scale After a Decade Focused on Fed- important and critical to

up to clinical and commercial Batch useful predictive data

+44(0)20 7017 7481

scales. The Scale-up and scale-

down of biopharmaceutical

processes is still challenging but

can be facilitated by extensive

hardware characterization for

example by computational fluid

dynamics. Current implementation

of miniaturized small scale

bioreactor systems like ambr15

and ambr250 in process

development has led to additional

challenges in scale-up and scale-

down since more systems and

scales have to fit together with

respect to process performance

and product quality. This

presentation will give insight on

how we predict and qualify scale-

down models for later process

characterization studies but also

present our scale up strategy

supported by CFD data to

optimize the process transfer to

our commercial facilities for the

manufacturing of

biopharmaceutical products.

Harald Bradl, Director Cell Culture Development , Boehringer Ingelheim Pharma GmbH & Co. KG 11:05 - 11:35 Scale Up Strategies for

Scale Down Models

Jinpian Diao, Head of Upstream Development, Process Science and Technology, Sanofi 11:35 - 12:05 Optimized Feed Strategies

for Increased Titer and

Product Quality

Steve Gorfien, Sr. Director, Research and Development, Thermo Fisher Scientific

+44(0)20 7017 7481

Marcel de Voch, At early stage of bioprocess

Associate Director, DSP, science, continuous operations

Crucell, part of the Janssen were the workhorse in the

Pharmaceutical Companies, The industry. Then, for the past 10

Netherlands years, we moved towards fed-

batch operations. Recently,

continuous operations is

11:05 - 11:35 considered again as a lever to

Enhanced IgG Hexamerization boost process productivity and

control product quality. Looking

Potentiates Complement-

at bioprocess history, this

Dependent Cytotoxicity;

presentation will discuss the

Manufacturability of the

reasons of those “back and forth”

HexaBody® platform

trends. It will also present results

Rick Hibbert,

obtained at EMD-Serono using

continuous operations in cell-

Senior Scientist,

culture and also in purification of

Genmab, The Netherlands

biopharmaceuticals. Finally, it will

discuss the challenges and

11:35 - 12:05 opportunities of continuous

operations versus current

Platform Purification of established fed-batch platform.

Antibodies using the High-

Capacity Amsphere(TM) A3

Protein A Resin

Jean-Marc Bielser,

Amsphere(TM) A3 is a next-

generation protein A media with Assistant Scientist, BioProcess

an alkali-stable ligand, exhibiting Science,

unsurpassed capacities across all Merck Serono Switzerland

residence times with agarose-

like HCP clearance. A variety of 11:15 - 11:35

industrial application examples

will be presented, showing the GlycoExpress™: A Toolbox for

advantages of A3 versus other the High Yield Production of

commercial agarose and polymer Glycooptimized Fully Human

Protein-A media for all key Biopharmaceuticals in Perfusion

performance parameters Bioreactors at Different Scales

including llifetime studies for With the GlycoExpress™ toolbox

large scale and long term usage.

(GEX™) we have generated a set

of glycoengineered human cell

lines for high yield production

Geert Lissens,

and for improvement of the

clinical efficacy and side effects

Sales Manager Europe ,

of fully human

JSR Life Sciences

biopharmaceuticals.

GlycoExpress™ cells producing

biopharmaceuticals are

cultivated with perfusion

bioreactor at different scales

systems applying different cell

retention mechanisms such as

centrifugation (centritech™) or

alternating tangential flow

(ATF™) filtration to assure

highest possible product quality

and reproducibility combined

with high yield production

Karina Nawrath, Scientist Platform Development, Glycotope GmbH

11:35 - 12:05

Unlocking the Potential for

Efficiency in Downstream

Bioprocesses

Improvements in productivity

analytics?

Are you getting the most

out of your data through

sophisticated predictive

data analytics?

How do you make sure

you have the ‘data

quality’ to enable you

to build robust models

and validated results? It is critically important to

understand what the data are

telling you. Statistical

manipulation is no substitute

for science and engineering

knowledge. Data Visualisation

is Key.

The workshop will address all

these issues and the maximising

of the information and ‘know-

how’ hidden in your data.

Industrial case studies will be

presented and used in a highly

visual interactive software

tool-set for multivariate data

exploration, pre-processing

and analysis. Julian Morris, Centre for Process Analytics

and Control Technology,

University of Strathclyde, UK

and efficiency are ranked as the

single most important area on

which the biomanufacturing

industry should focus its efforts[1].

These improvements are relevant

for both existing and new facilities,

and agility and flexibility in

production are key elements.

Novel technologies and innovative

process strategies, such as

intensified processing, enable

more efficient biomanufacturing

operations, even for existing

facilities.

This talk will showcase multiple

examples of process

intensification solutions, such as

in-line conditioning and

continuous chromatography, as

means for achieving efficiency in

downstream processes. Case

studies and process economy

gains will be highlighted.

[1] 12th Annual BioPlan

report 2015

[1] 12th Annual BioPlan

report 2015

Madhu Raghunathan , Product Strategy Leader, GE Healthcare Life Sciences

12:05 - 12:35 Lunch and Live Labs

12:35 - 1:05 Poster Presentations Cutting Edge New Science - Poster Presentations

Poster Presentation 1: Development and Characterisation of a Microfluidic Bioreactor for Synthetic Biology Applications

Nelson Andrés Barrientos Lobos, Doctoral Researcher at the Department of Biochemical Engineering, University College London, UK

Poster Presentation 2:

Purification of Virus Like Particles by Monoliths Daniel Burgstaller and Petra Steppert, BOKU, Austria

Poster Presentation 3:

Continuous Desalting of Proteins Nicole Walch, acib, Austria +44(0)20 7017 7481

Poster Presentation 4:

Continuous Flocculation of Culture Broth for Primary Recovery of Antibodies

Peter Satzer, BOKU, Austria

Poster Presentation 5:

Adsorption of VLP of Polymer Grafted Media

Patricia Aguliar (BOKU) and Tobias Schneider, Austria

Upstream Process Development Downstream Processing Continuous Processing BPI Theatre Interactive Sessions

and High Throughput Models

1:05 - 1:35 1:05 - 1:35 1:05 - 1:35 1:05 - 2:05

Integration of Process Analytics Manufacturing Gene Vaccines: Scale Up and Scale Up Criteria Roundtable Discussion:

and Real-Time On-line Strategy to Fast Track supply of for Continuous Precipitation of Improving USP and DSP

Monitoring Methodologies to supercoiled plasmid DNA Recombinant Antibodies Workflow

Enhance Process Productivity Recent advance in the use

Process development

Alois Jungbauer,

Understanding the plasmids as non-viral vectors for and optimisation at the

Professor ,

issues of variability in both gene therapy and genetic interface of USP and

ACIB, BOKU, Austria

products by processing vaccination has resulted in an DSP

Challenges of increasing demand for

implementing robust manufacturing strategies suitable 1:35 - 2:05 How can upstream and

PAT applications for large scale production of

Smart Tools for Process downstream process

Integrating PAT and highly pure pharmaceutical grade development work

process data for plasmid DNA (pDNA). Optimization together to improve

enhanced process Transport of the nucleic acid to

As demands on manufacturing

product quality, yield

understanding and and timelines?

control its site of action is an important efficiency increases many are

Multi-component aspect in the development of a looking at new models and Understanding

multivariable measuring new gene vaccine. Indeed, pDNA process improvements to meet modifications in cell

methods comes in various isoforms such as demands. Market dynamics are culture conditions and

Evaluating online real- for instance open circular, linear changing and many are looking at the implications for

time monitoring and or supercoiled. Because of its what can be learned from other downstream purification

control methods in up- higher transfection efficiency, industries. Particularly around

steam and down-stream the supercoiled isoform is facility utilization and process Moving from upstream

operations considered the desired intensification. This talk will look to downstream

conformation to transfer the at market dynamics influencing

therapeutic gene. The other producers, how to improve Dealing with high titres

Julian Morris, isoforms are categorized as facility utilization to reduce cost – planning for 15g/m

Centre for Process Analytics product impurities. Boehringer and finally look at high cell titres

and Control Technology, Ingelheim established a generic density processes such as

University of Strathclyde, UK process including cell perfusion or continuous as a way Optimising processes to

David Lovett,

disintegration and three column to further increase efficiency. remove cells from the

chromatography steps to yield bioreactor

Managing Director , highly pure supercoiled pDNA. Barbara Paldus,

Perceptive Engineering Ltd Lysis of the cells occurs via a

Combining removal of

CEO ,

semi-continuous automated cells with the first DSP

Finesse Solutions Inc

1:35 - 2:05

process. The clarified lysate is purification step to

further processed through improve recovery

Upstream Single Use: From hydrophobic interaction, anion 2:05 - 2:35

Laboratory To Large Scale exchange and size exclusion

Design Considerations for

Michel Eppink,

Manufacturing chromatography steps followed

by ultra-filtration. The purified Continuous Precipitation Head, DSP,

Despite the introduction of new pDNA contain low amount of Processes Synthon, The Netherlands

technologies, the majority of genomic DNA, RNA, protein and

Biotech processes and facilities endotoxin. An overall 50% yield

still contain a number of stainless can be reached in the desired

steel and multi-use equipment. final buffer. Here, we present a

We have made the decision to strategy for manufacturing Gene

+44(0)20 7017 7481

move away from this traditional

setup and implement full Single-

Use processes at Laboratory and

manufacturing scale. This change

from Multi-use to Single-use was

developed in parallel with the

facility revamping and a global

strategic development of flexible

facilities concepts.

We have developed an integrated

USP & DSP that offers significant

practical and economic

advantages without sacrificing

performance and robustness. This

new holistic process can be run in

either batch or continuous mode

of operation. This single use

leverages existing technologies

with the potential to “change the

game”. A fed-batch process was

performed in different types of

disposable bioreactors in parallel

with the revamping and installation

of our hybrid facility. The process

performances compared single

use, glass and stainless steel

bioreactors of different sizes

including 3L, 50L, 200L, 1,250L,

and 2,000L. Our study

demonstrated the benefits of using

disposable equipment in several

key areas with a particular focus

on Upstream activities. The

comparison of stainless steel,

glass and disposable equipment

showed how comparable they are

regarding titers, molecule

quality…and how different they

are regarding organization and

financial aspects. The integration

of a new train at 2,000L scale in a

flexible factory is presented as

well as future development in

flexible factories modular-based. Aurore Lahille , Head of Process Development

and Center of Expertise , Merck Biodevelopment

facility in Martillac, France 2:05 - 2:20 Development of a Perfusion

System in a Microbioreactor

using Sedimentation as a

Scale Down Tool for ATF

Perfusion Bioreactor Batch or fed-batch bioreactors

can be successfully represented

in a small scale with sufficient

throughput for early stage

process development, the 1 L

benchtop bioreactor remains the

Vaccines employing a scalable

process, which neither requires

animal-derived materials nor

detergents nor organic solvents

thereby meeting all standards

for therapeutic applications.

Cécile Brocard, Head Downstream Development, Boehringer Ingelheim, Austria 1:35 - 2:05 Multi Column Chromatography – Solving Complex Challenges

in Downstream Processing The increased demand for drug

substance for clinical trial and

commercial launch have resulted

in a significantly increase of the

size of upstream batches, either

by increase of titer or installing

larger bioreactor capacity or

applying perfusion mode. The

bottleneck of Manufacturing of

drug substance is now to high

extend the Downstream

Processes, where continuous

processing based on existing unit

operations, is one way to

introduce higher capacity. The

introduction of a two-column

system for continuously Protein A

Chromatography, results in a

significantly higher utilization of

the load capacity and better

separation of product- and

process related impurities.

Simon Bergmann, Principal Scientist, Downstream Process Development, CMC Biologics 2:05 - 2:35 Improved Process

Productivity using Linked

Flow through Processing

David Gruber, Senior R&D Manager , MedImmune, UK 2:35 - 3:05 Afternoon Spotlight

Presentation This slot is reserved for Parker

Todd M. Przybycien, , Professor, Biomedical Engineering and Chemical Engineering Carnegie Mellon University 2:35 - 3:05 Techniques for Fast

Characterisation of

Biopharmaceuticals by

Capillary Electrophoresis Higher throughput is a continuing

requirement of both process

development and quality control

departments of the

pharmaceutical industry. This

presentation will start by

highlighting the benefits of using

capillary electrophoresis (CE) as

an automated, quantitative, high-

resolution antibody-purity analysis

tool replacing SDS-PAGE in mass

profiling protein based

biopharmaceuticals and

shortening sample analysis time.

Immunogenic responses from

non-human glycosylation of

biologics are a real threat to the

marketability of biotherapeutics.

We will then discuss how the

same system uses CE to help

catalogue glycosylation sites of

biopharmaceuticals and show

how recent advances in sample

preparation can help to increase

sample throughput and provide a

fast and automated approach to

profiling these glycan variants.

Finally we will highlight how CE

can be used for fast charge

state heterogeneity mapping

and how CE can be coupled to

mass spectrometry to help

identify sites of glycan variation

as well as other modifications

sites sometimes present in

biotherapeutics.

Stephen Lock, Marketing Development Manager Separations EMEAI, SCIEX

+44(0)20 7017 7481

smallest scale down unit for

perfusion culture. Here, we

demonstrate the development

of a sedimentation based

perfusion system in the single-

use ambr system with good

comparability to 1 L ATF

perfusion bioreactors when

comparing cell growth, viability

and product quality, especially

glycosylation, for GlycoExpress

(GEX) and CHO cells.

Steffen Kreye, Scientist, Glycotope, Germany 2:20 - 2:35 Case Study: Development of

a Continuous mAb Upstream

Production Process with

Focus on Product Quality It is essential to supply clinical

trials with sufficient amounts of

product in adequate quality,

meeting the requirements of

safety and efficacy. The broadly

neutralizing anti-HCV antibody

e137 is a promising candidate for

the prophylaxis and treatment of

hepatitis C virus diseases. Using

a high producing CHO cell line,

the initial goal was to develop a

simple fed-batch process, but

characterization of culture

supernatants revealed that up to

10 % of the antibody was cleaved

in the CDR3 loop by an

extracellular protease. Scientific

and risk-based considerations

were applied to produce a

homogeneous product and to

mitigate the risk of impairing the

functional properties of the

antibody which might influence

binding capabilities and thereby

the therapeutic efficacy. We could

develop a continuous perfusion

process using the existing

upstream platform of Polymun

which revealed a culture

supernatant with about 1 g/l mAb

in the desired quality.

Katharina Fauland, Head of Fermentation Development, Polymun Scientific 2:35 - 3:05 Afternoon Spotlight

Presentation This slot is reserved for

technology and service

providers, please contact +44(0)20 7017 7481

james.miguel@informa.com

for more info.

Willie Hesselink, R&D Manager & Application Project Manager, Avantor Performance Materials

3:05 - 3:50

Afternoon Tea and BPI Poster Winner Announced Cell Culture/Cell Line Development Downstream Processing / Continuous Processing

3:50 - 4:20 3:50 - 4:20

Keynote A Novel PAT Tool for Impurity Monitoring

The mTORC1 Pathway as a Central Co-Ordinator of Therapeutic

The development and control of biopharmaceutical processes is still a

Protein Production in Industrially Relevant CHO Cells

time extensive and complex task. This contribution proposes a novel

The mTORC1 pathway integrates multiple inputs from the cellular approach using direct measurements of CQAs. We propose a CQA

environment – inputs that present as key facets in industrial-scale analyzer, which is based on a HPLC principle combined monolithic

bioprocessing. This presentation will describe chemical and genetic columns, which is used horizontally along the entire process, from

interventions that allow dissection of the significance of specific upstream to downstream processing. Together with advanced data

components downstream of mTOR1 towards directed enhancement science algorithms, the method allows to track host cell impurities

of cell biomass and specific productivity. CQAs in a timely controlled way. Hence we present a PAT tool as per

original definition.

Alan Dickson, Key Learning Objectives of this lecture are:

Professor of Biotechnology, Faculty of Life Sciences, · Move from process parameter to direct critical quality attribute

University of Manchester

monitoring

· Identify the right harvesting time point in recombinant protein

4:20 - 4:50

production

Keynote

· Enable control strategies using CQA PAT tools

Engineering CHO Cell Factories by Directed Evolution

· Use CQA analyzers to enable robust integrated and continuous

David James, bioprocessing

Professor of Bioprocess Engineering, Department of Chemical and

Biological Engineering,

University of Sheffield

Christoph Herwig, Professor, Vienna University of Technology, Austria

4:20 - 4:50

Next Generation Biopharmaceutical Downstream Process

Tibor Doles , Scientist DSP, Sandoz Biopharmaceuticals, Slovenia

4:50 - 4:50

End of BPI Europe Congress

Upstream Processing - Wednesday 13 April 2016

8:25 - 8:30

Chairperson's Opening Remarks

Richard Dennett, Director, Voisin Consulting Life Sciences

Plenary Session: Global Manufacturing Strategies

8:30 - 9:00

Keynote +44(0)20 7017 7481

Manufacturing Strategies in a Diverse World As worldwide annual sales of biologics increase to the 200 bn USD

mark, so has the diversity of drug pipelines and treatment

modalities increased. The biotech industry began 40 years ago with

recombinant hormones and cytokines and has expanded to include

monoclonal antibodies (MAb), MAb-toxin conjugates, antibody

fragments, multivalent MAbs, cell-based and rDNA vaccines, cell

and gene therapies, therapeutic enzymes, biobetters, biosimilars,

and more. This pipeline diversity has driven the need for more

diverse manufacturing strategies and innovations to accommodate

different process architectures. The presentation will review the

diversity of drug pipelines and manufacturing innovation strategies

to meet this diversity.

Parrish M. Galliher , CTO Upstream, Xcellerex , GE Healthcare Life Sciences

9:00 - 9:30

Georg Klima,

Keynote

Executive Director, Process Science, ,

Accelerating the Development of Novel Biotherapeutics in Microbial

Boehringer Ingelheim, Austria

Expression Systems

Novel biotherapeutic formats pose unique development challenges.

Strategies for successful development need to holistically consider all

aspects of biopharmaceutical processes such as expression strategies,

novel unit operations, automated high-throughput process

development, as well as scale up and transfer from bench to large-

scale manufacturing.

9:30 - 10:00 Martin Smith,

Keynote

Chief Technology Officer,

Technology Advances and Considerations for Parallel and

Pall Corporation, USA

Continuous Bioprocessing

10:00 - 10:35

Morning Coffee

Upstream Process Development and High Throughput Models

10:35 - 11:05 Harald Bradl,

Implementation and Translation of Predictable Bioreactor Process

Director Cell Culture Development ,

Scale Down Models

Boehringer Ingelheim Pharma GmbH & Co. KG

Boehringer Ingelheim is a leading biopharmaceutical manufacturer

with more than 35 years of experience and many successful

transferred biopharmaceutical products to market. Our expression

platform (BI-HEX®) enables fast-track development of high-quality,

high-titer processes for producing biopharmaceuticals from CHO

cells. This platform include cell line engineering, high throughput

screening by automation, systematic DoE-based approaches for media

and cell culture process development to identify optimal process

parameters for high titer processes and strategies for scale up to

clinical and commercial scales. The Scale-up and scale-down of

biopharmaceutical processes is still challenging but can be facilitated

by extensive hardware characterization for example by

computational fluid dynamics. Current implementation of

miniaturized small scale bioreactor systems like ambr15 and ambr250

in process development has led to additional challenges in scale-up

and scale-down since more systems and scales have to fit together

with respect to process performance and product quality. This

presentation will give insight on how we predict and qualify scale-

down models for later process characterization studies but also

present our scale up strategy supported by CFD data to optimize the

process transfer to our commercial facilities for the manufacturing of

biopharmaceutical products.

11:05 - 11:35

Scale Up Strategies for Scale Down Models

+44(0)20 7017 7481

Jinpian Diao, Head of Upstream Development, Process Science and Technology, Sanofi

11:35 - 12:05

Steve Gorfien, Optimized Feed Strategies for Increased Titer and Product Quality Sr. Director, Research and Development,

Thermo Fisher Scientific 12:05 - 12:35 Lunch and Live Labs

12:35 - 1:05 Poster Presentations Cutting Edge New Science - Poster Presentations

Poster Presentation 1: Development and Characterisation of a Microfluidic Bioreactor for Synthetic Biology Applications Nelson Andrés Barrientos Lobos, Doctoral Researcher at the Department of Biochemical Engineering, University College London, UK

· Poster Presentation 2:

Purification of Virus Like Particles by Monoliths Daniel Burgstaller and Petra Steppert, BOKU, Austria

· Poster Presentation 3:

Continuous Desalting of Proteins

Nicole Walch, acib, Austria

· Poster Presentation 4: Continuous Flocculation of Culture Broth for Primary Recovery of Antibodies Peter Satzer, BOKU, Austria

· Poster Presentation 5: Adsorption of VLP of Polymer Grafted Media Patricia Aguliar (BOKU) and Tobias Schneider, Austria Upstream Process Development and High Throughput Models 1:05 - 1:35

Integration of Process Analytics and Real-Time On-line Monitoring Julian Morris,

Centre for Process Analytics and Control

Methodologies to Enhance Process Productivity

Technology, University of Strathclyde, UK

• Understanding the issues of variability in products by processing

• Challenges of implementing robust PAT applications

• Integrating PAT and process data for enhanced process David Lovett,

understanding and control

Managing Director ,

• Multi-component multivariable measuring methods

Perceptive Engineering Ltd

• Evaluating online real-time monitoring and control methods in up-

steam and down-stream operations

+44(0)20 7017 7481

1:35 - 2:05 Upstream Single Use: From Laboratory to Large

Scale Manufacturing Despite the introduction of new technologies, the majority of Biotech

processes and facilities still contain a number of stainless steel and

multi-use equipment. We have made the decision to move away from

this traditional setup and implement full Single-Use processes at

Laboratory and manufacturing scale. This change from Multi-use to

Single-use was developed in parallel with the facility revamping and a

global strategic development of flexible facilities concepts.

We have developed an integrated USP & DSP that offers significant

practical and economic advantages without sacrificing performance

and robustness. This new holistic process can be run in either batch

or continuous mode of operation. This single use leverages existing

technologies with the potential to “change the game”. A fed-batch

process was performed in different types of disposable bioreactors

in parallel with the revamping and installation of our hybrid facility.

The process performances compared single use, glass and

stainless steel bioreactors of different sizes including 3L, 50L, 200L,

1,250L, and 2,000L. Our study demonstrated the benefits of using

disposable equipment in several key areas with a particular focus

on Upstream activities. The comparison of stainless steel, glass and

disposable equipment showed how comparable they are regarding

titers, molecule quality…and how different they are regarding

organization and financial aspects. The integration of a new train at

2,000L scale in a flexible factory is presented as well as future

development in flexible factories modular-based.

Aurore Lahille , Head of Process Development and Center

of Expertise , Merck Biodevelopment facility in

Martillac, France

2:05 - 2:20 Development of a Perfusion System in a Microbioreactor using

Sedimentation as a Scale Down Tool for ATF Perfusion Bioreactor Batch or fed-batch bioreactors can be successfully represented in a

small scale with sufficient throughput for early stage process

development, the 1 L benchtop bioreactor remains the smallest scale

down unit for perfusion culture. Here, we demonstrate the development

of a sedimentation based perfusion system in the single-use ambr

system with good comparability to 1 L ATF perfusion bioreactors when

comparing cell growth, viability and product quality, especially

glycosylation, for GlycoExpress (GEX) and CHO cells.

Steffen Kreye, Scientist, Glycotope, Germany

2:20 - 2:35 Case Study: Development of a Continuous mAb Upstream

Production Process with Focus on Product Quality It is essential to supply clinical trials with sufficient amounts of

product in adequate quality, meeting the requirements of safety and

efficacy. The broadly neutralizing anti-HCV antibody e137 is a

promising candidate for the prophylaxis and treatment of hepatitis C

virus diseases. Using a high producing CHO cell line, the initial goal

was to develop a simple fed-batch process, but characterization of

culture supernatants revealed that up to 10 % of the antibody was

cleaved in the CDR3 loop by an extracellular protease. Scientific

and risk-based considerations were applied to produce a

homogeneous product and to mitigate the risk of impairing the

functional properties of the antibody which might influence binding

capabilities and thereby the therapeutic efficacy. We could develop

a continuous perfusion process using the existing upstream

platform of Polymun which revealed a culture supernatant with

about 1 g/l mAb in the desired quality.

Katharina Fauland, Head of Fermentation Development, Polymun Scientific

+44(0)20 7017 7481

2:35 - 3:05 Afternoon Spotlight Presentation This slot is reserved for technology and service providers,

please contact james.miguel@informa.com for more info.

Willie Hesselink, R&D Manager & Application Project Manager, Avantor Performance Materials

3:05 - 3:50

Afternoon Tea and BPI Poster Winner Announced

Closing Session: Cell Culture/Cell Line Development

3:50 - 4:20

Alan Dickson,

Keynote

Professor of Biotechnology, Faculty of Life

The mTORC1 Pathway as a Central Co-Ordinator of Therapeutic

Sciences,

Protein Production in Industrially Relevant CHO Cells University of Manchester

The mTORC1 pathway integrates multiple inputs from the cellular

environment – inputs that present as key facets in industrial-scale

bioprocessing. This presentation will describe chemical and genetic

interventions that allow dissection of the significance of specific

components downstream of mTOR1 towards directed enhancement

of cell biomass and specific productivity.

4:20 - 4:50 David James,

Keynote

Professor of Bioprocess Engineering,

Engineering CHO Cell Factories by Directed Evolution

Department of Chemical and Biological

Engineering,

University of Sheffield

4:50 - 4:50

End of BPI Europe Congress

Downstream Processing - Wednesday 13 April 2016

8:25 - 8:30

Chairperson's Opening Remarks

Richard Dennett, Director, Voisin Consulting Life Sciences

Plenary Session: Global Manufacturing Strategies

8:30 - 9:00 Parrish M. Galliher ,

Keynote

CTO Upstream, Xcellerex ,

Manufacturing Strategies in a Diverse World

GE Healthcare Life Sciences

As worldwide annual sales of biologics increase to the 200 bn USD

mark, so has the diversity of drug pipelines and treatment modalities

increased. The biotech industry began 40 years ago with recombinant

hormones and cytokines and has expanded to include monoclonal

antibodies (MAb), MAb-toxin conjugates, antibody fragments,

multivalent MAbs, cell-based and rDNA vaccines, cell and gene

therapies, therapeutic enzymes, biobetters, biosimilars, and more.

This pipeline diversity has driven the need for more diverse

manufacturing strategies and innovations to accommodate different

process architectures. The presentation will review the diversity of

drug pipelines and manufacturing innovation strategies to meet this

diversity.

9:00 - 9:30

Keynote

Accelerating the Development of Novel Biotherapeutics in Microbial

Expression Systems

+44(0)20 7017 7481

Novel biotherapeutic formats pose unique development challenges.

Strategies for successful development need to holistically consider

all aspects of biopharmaceutical processes such as expression

strategies, novel unit operations, automated high-throughput

process development, as well as scale up and transfer from bench

to large-scale manufacturing.

Georg Klima, Executive Director, Process Science, , Boehringer Ingelheim, Austria

9:30 - 10:00

Martin Smith,

Keynote

Chief Technology Officer,

Technology Advances and Considerations for Parallel and

Pall Corporation, USA

Continuous Bioprocessing

10:00 - 10:35

Morning Coffee

Downstream Processing Strategies for Novel Therapies

10:35 - 11:05 Marcel de Voch,

A Viral Vaccine Production Platform - Fast Development and Low

Associate Director, DSP,

COGs

Crucell, part of the Janssen Pharmaceutical

At Janssen a production process was developed that allows Companies, The Netherlands

intensified manufacturing of viral vaccines. By increasing the

productivity in the PER.C6 infection, the optimized process can be

used to cost-effectively produce 100 million doses of vaccine at 500L

production scale. It will be presented how the platform was used for

rapid supply of our preventative Ebola vaccine and data will be

presented on the adaptation for Polio vaccine production.

11:05 - 11:35 Rick Hibbert,

Enhanced IgG Hexamerization Potentiates Complement-Dependent

Senior Scientist,

Cytotoxicity; Manufacturability of the HexaBody® Pllatform

Genmab, The Netherlands

11:35 - 12:05 Geert Lissens,

Platform Purification of Antibodies using the High-Capacity

Sales Manager Europe ,

Amsphere(TM) A3 Protein A Resin

JSR Life Sciences

Amsphere(TM) A3 is a next-generation protein A media with an alkali-

stable ligand, exhibiting unsurpassed capacities across all residence

times with agarose-like HCP clearance. A variety of industrial

application examples will be presented, showing the advantages of A3

versus other commercial agarose and polymer Protein-A media for all

key performance parameters including llifetime studies for large scale

and long term usage.

12:05 - 12:35

Lunch and Live Labs

12:35 - 1:05

Poster Presentations

Cutting Edge New Science - Poster Presentations

· Poster Presentation 1: Development and Characterisation of a Microfluidic Bioreactor for Synthetic Biology Applications Nelson Andrés Barrientos Lobos, Doctoral Researcher at the Department of Biochemical Engineering, University College London, UK

· Poster Presentation 2: +44(0)20 7017 7481

Purification of Virus Like Particles by Monoliths Daniel Burgstaller and Petra Steppert, BOKU, Austria

· Poster Presentation 3:

Continuous Desalting of Proteins

Nicole Walch, acib, Austria

· Poster Presentation 4: Continuous Flocculation of Culture Broth for Primary Recovery of Antibodies Peter Satzer, BOKU, Austria

· Poster Presentation 5: Adsorption of VLP of Polymer Grafted Media Patricia Aguliar (BOKU) and Tobias Schneider, Austria Downstream Processing 1:05 - 1:35

Manufacturing Gene Vaccines: Strategy to Fast Track Supply of Cécile Brocard,

Head Downstream Development,

Supercoiled Plasmid DNA

Boehringer Ingelheim, Austria

Recent advance in the use plasmids as non-viral vectors for both gene

therapy and genetic vaccination has resulted in an increasing demand

for manufacturing strategies suitable for large scale production of

highly pure pharmaceutical grade plasmid DNA (pDNA).

Transport of the nucleic acid to its site of action is an important aspect

in the development of a new gene vaccine. Indeed, pDNA comes in

various isoforms such as for instance open circular, linear or

supercoiled. Because of its higher transfection efficiency, the

supercoiled isoform is considered the desired conformation to

transfer the therapeutic gene. The other isoforms are categorized as

product impurities. Boehringer Ingelheim established a generic

process including cell disintegration and three column

chromatography steps to yield highly pure supercoiled pDNA. Lysis of

the cells occurs via a semi-continuous automated process. The

clarified lysate is further processed through hydrophobic interaction,

anion exchange and size exclusion chromatography steps followed by

ultra-filtration. The purified pDNA contain low amount of genomic

DNA, RNA, protein and endotoxin. An overall 50% yield can be

reached in the desired final buffer. Here, we present a strategy for

manufacturing Gene Vaccines employing a scalable process, which

neither requires animal-derived materials nor detergents nor organic

solvents thereby meeting all standards for therapeutic applications.

1:35 - 2:05 Multi Column Chromatography – Solving Complex

Challenges in Downstream Processing The increased demand for drug substance for clinical trial and

commercial launch have resulted in a significantly increase of the

size of upstream batches, either by increase of titer or installing

larger bioreactor capacity or applying perfusion mode. The

bottleneck of Manufacturing of drug substance is now to high

extend the Downstream Processes, where continuous processing

based on existing unit operations, is one way to introduce higher

capacity. The introduction of a two-column system for continuously

Protein A Chromatography, results in a significantly higher

utilization of the load capacity and better separation of product-

and process related impurities.

Simon Bergmann, Principal Scientist, Downstream Process Development, CMC Biologics

+44(0)20 7017 7481

2:05 - 2:35 Improved Process Productivity using Linked Flow

through Processing

David Gruber, Senior R&D Manager , MedImmune, UK

2:35 - 3:05 Afternoon Spotlight Presentation This slot is reserved for Parker. 3:05 - 3:50 Afternoon Tea and BPI Poster Winner Announced

Closing Session: Downstream Processing / Continuous Processing 3:50 - 4:20

A Novel PAT Tool for Impurity Monitoring Christoph Herwig,

Professor,

The development and control of biopharmaceutical processes is still a Vienna University of Technology, Austria

time extensive and complex task. This contribution proposes a novel

approach using direct measurements of CQAs. We propose a CQA

analyzer, which is based on a HPLC principle combined monolithic

columns, which is used horizontally along the entire process, from

upstream to downstream processing. Together with advanced data

science algorithms, the method allows to track host cell impurities

CQAs in a timely controlled way. Hence we present a PAT tool as per

original definition.

Key Learning Objectives of this lecture are:

· Move from process parameter to direct critical quality attribute

monitoring

· Identify the right harvesting time point in recombinant protein

production

· Enable control strategies using CQA PAT tools

· Use CQA analyzers to enable robust integrated and continuous

bioprocessing

4:20 - 4:50

Next Generation Biopharmaceutical Downstream Process Tibor Doles ,

Scientist DSP,

Sandoz Biopharmaceuticals, Slovenia

4:50 - 4:50 End of BPI Europe Congress

Continuous Manufacturing - Wednesday 13 April 2016 8:25 - 8:30 Chairperson's Opening Remarks Richard Dennett, Director, Voisin Consulting Life Sciences

Plenary Session: Global Manufacturing Strategies 8:30 - 9:00

Parrish M. Galliher ,

Keynote

CTO Upstream, Xcellerex ,

Manufacturing Strategies in a Diverse World

GE Healthcare Life Sciences

As worldwide annual sales of biologics increase to the 200 bn USD

mark, so has the diversity of drug pipelines and treatment modalities +44(0)20 7017 7481

increased. The biotech industry began 40 years ago with

recombinant hormones and cytokines and has expanded to include

monoclonal antibodies (MAb), MAb-toxin conjugates, antibody

fragments, multivalent MAbs, cell-based and rDNA vaccines, cell

and gene therapies, therapeutic enzymes, biobetters, biosimilars,

and more. This pipeline diversity has driven the need for more

diverse manufacturing strategies and innovations to accommodate

different process architectures. The presentation will review the

diversity of drug pipelines and manufacturing innovation strategies

to meet this diversity.

9:00 - 9:30

Georg Klima,

Keynote

Executive Director, Process Science, ,

Accelerating the Development of Novel Biotherapeutics in Microbial

Boehringer Ingelheim, Austria

Expression Systems

Novel biotherapeutic formats pose unique development challenges.

Strategies for successful development need to holistically consider all

aspects of biopharmaceutical processes such as expression strategies,

novel unit operations, automated high-throughput process

development, as well as scale up and transfer from bench to large-

scale manufacturing.

9:30 - 10:00 Martin Smith,

Keynote

Chief Technology Officer,

Technology Advances and Considerations for Parallel and

Pall Corporation, USA

Continuous Bioprocessing

10:00 - 10:35

Morning Coffee

Continuous Processing

10:35 - 10:55 Daniel Karst,

Perfusion Design for Integrated Continuous Biomanufacturing

The Morbidelli Group,

Optimal bioreactor design and choice of key process parameters are Institute for Chemical and Bioengineering,

ETHZ, Switzerland

crucial to ensure and control long-term high cell density perfusion

cultures. Requirements when aiming at the direct integration to a

continuous downstream train will be discussed.

10:55 - 11:15 Jean-Marc Bielser,

Perfusion Process Development After a Decade Focused on Fed-

Assistant Scientist, BioProcess Science,

Batch

Merck Serono Switzerland

At early stage of bioprocess science, continuous operations were the

workhorse in the industry. Then, for the past 10 years, we moved

towards fed-batch operations. Recently, continuous operations is

considered again as a lever to boost process productivity and control

product quality. Looking at bioprocess history, this presentation will

discuss the reasons of those “back and forth” trends. It will also

present results obtained at EMD-Serono using continuous operations

in cell-culture and also in purification of biopharmaceuticals. Finally, it

will discuss the challenges and opportunities of continuous operations

versus current established fed-batch platform.

11:15 - 11:35 GlycoExpress™: A Toolbox for the High Yield Production

of Glycooptimized Fully Human Biopharmaceuticals in

Perfusion Bioreactors at Different Scales With the GlycoExpress™ toolbox (GEX™) we have generated a

set of glycoengineered human cell lines for high yield production

and for improvement of the clinical efficacy and side effects of fully

human biopharmaceuticals. GlycoExpress™ cells producing

Karina Nawrath, Scientist Platform Development, Glycotope GmbH

+44(0)20 7017 7481

biopharmaceuticals are cultivated with perfusion bioreactor at

different scales systems applying different cell retention

mechanisms such as centrifugation (centritech™) or alternating

tangential flow (ATF™) filtration to assure highest possible product

quality and reproducibility combined with high yield production. 11:35 - 12:05 Unlocking the Potential for Efficiency in Downstream Bioprocesses Improvements in productivity and efficiency are ranked as the single

most important area on which the biomanufacturing industry should

focus its efforts[1]. These improvements are relevant for both

existing and new facilities, and agility and flexibility in production are

key elements. Novel technologies and innovative process

strategies, such as intensified processing, enable more efficient

biomanufacturing operations, even for existing facilities.

This talk will showcase multiple examples of process

intensification solutions, such as in-line conditioning and

continuous chromatography, as means for achieving efficiency in

downstream processes. Case studies and process economy

gains will be highlighted.

[1] 12th Annual BioPlan report 2015

Madhu Raghunathan , Product Strategy Leader, GE Healthcare Life Sciences

12:05 - 12:35 Lunch and Live Labs

12:35 - 1:05 Poster Presentations Cutting Edge New Science - Poster Presentations · Poster Presentation 1: Development and Characterisation of a Microfluidic Bioreactor for Synthetic Biology Applications Nelson Andrés Barrientos Lobos, Doctoral Researcher at the Department of Biochemical Engineering, University College London, UK

· Poster Presentation 2: Purification of Virus Like Particles by Monoliths Daniel Burgstaller and Petra Steppert, BOKU, Austria

· Poster Presentation 3:

Continuous Desalting of Proteins

Nicole Walch, acib, Austria

· Poster Presentation 4: Continuous Flocculation of Culture Broth for Primary Recovery of Antibodies Peter Satzer, BOKU, Austria

· Poster Presentation 5: Adsorption of VLP of Polymer Grafted Media Patricia Aguliar (BOKU) and Tobias Schneider, Austria Continuous Processing +44(0)20 7017 7481

1:05 - 1:35 Scale Up and Scale Up Criteria for Continuous

Precipitation of Recombinant Antibodies

Alois Jungbauer, Professor , ACIB, BOKU, Austria

1:35 - 2:05 Smart Tools for Process Optimisation As demands on manufacturing efficiency increases many are looking at

new models and process improvements to meet demands. Market

dynamics are changing and many are looking at what can be learned

from other industries. Particularly around facility utilization and process

intensification. This talk will look at market dynamics influencing

producers, how to improve facility utilization to reduce cost and finally

look at high cell density processes such as perfusion or continuous as a

way to further increase efficiency.

Barbara Paldus, CEO , Finesse Solutions Inc

2:05 - 2:35

Todd M. Przybycien,

, Design Considerations for Continuous Precipitation Processes Professor, Biomedical Engineering and Chemical

Engineering Carnegie Mellon University

2:35 - 3:05 Techniques for Fast Characterisation of

Biopharmaceuticals by Capillary Electrophoresis Higher throughput is a continuing requirement of both process

development and quality control departments of the

pharmaceutical industry. This presentation will start by highlighting

the benefits of using capillary electrophoresis (CE) as an

automated, quantitative, high-resolution antibody-purity analysis

tool replacing SDS-PAGE in mass profiling protein based

biopharmaceuticals and shortening sample analysis time.

Immunogenic responses from non-human glycosylation of biologics are

a real threat to the marketability of biotherapeutics. We will then discuss

how the same system uses CE to help catalogue glycosylation sites of

biopharmaceuticals and show how recent advances in sample

preparation can help to increase sample throughput and provide a fast

and automated approach to profiling these glycan variants.

Finally we will highlight how CE can be used for fast charge state

heterogeneity mapping and how CE can be coupled to mass

spectrometry to help identify sites of glycan variation as well as

other modifications sites sometimes present in biotherapeutics.

Stephen Lock, Marketing Development Manager Separations EMEAI, SCIEX

3:05 - 3:50 Afternoon Tea and BPI Poster Winner Announced

Closing Session: Downstream Processing / Continuous Processing 3:50 - 4:20

A Novel PAT Tool for Impurity Monitoring Christoph Herwig,

Professor,

The development and control of biopharmaceutical processes is still a Vienna University of Technology, Austria

time extensive and complex task. This contribution proposes a novel

approach using direct measurements of CQAs. We propose a CQA

analyzer, which is based on a HPLC principle combined monolithic

columns, which is used horizontally along the entire process, from

upstream to downstream processing. Together with advanced data

science algorithms, the method allows to track host cell impurities

CQAs in a timely controlled way. Hence we present a PAT tool as per

+44(0)20 7017 7481

original definition. Key Learning Objectives of this lecture are: · Move from process parameter to direct critical quality attribute

monitoring · Identify the right harvesting time point in recombinant protein

production · Enable control strategies using CQA PAT tools · Use CQA analyzers to enable robust integrated and continuous

bioprocessing

4:20 - 4:50

Next Generation Biopharmaceutical Downstream Process Tibor Doles ,

Scientist DSP,

Sandoz Biopharmaceuticals, Slovenia

4:50 - 4:50 End of BPI Europe Congress

Post-Conference Workshop - Thursday 14 April 2016 8:30 - 9:00 Registration

ADC Chemistry, Production and Manufacturing 9:00 - 3:00

ADC Chemistry, Production and Manufacturing Jens Lohrmann,

Technical Project Leader,

A full focus day made up of presentations and in-depth discussions on Novartis

preparing and optimising processes, characterisation techniques and

manufacturing facilities for ADC products.

Benjamin Hutchins ,

Senior Scientist,

Take Home Messages: ImmunoGen, Inc

With limited CMO capacity, how are companies preparing

processes and manufacturing facilities for ADC production

internally?

Unique production strategies facing the production and

characterisation of ADCs

ADC production to deliver consistent, stable products

Optimising process development for ADCs

Filing a successful ADC CMC package

Preparation for the increasingly potent, complex and non

native conjugated molecules emerging from R&D

departments

Challenges & Lessons Learned in ADC CMC Development &

Outsourcing

Buy vs. make: Considerations & critical success factors

Scale up and site transfer of a conjugation process with

impact on key product quality attributes: A case study

Analytical transfers: considerations & lessons learned from a

challenging assay transfers

Jens Lohrmann, Technical Project Leader Novartis

Developing Optimised, Scalable Conjugation Processes for

Multi-Product Facilities

+44(0)20 7017 7481

A review of evolving ADC process development concepts and

scale-up considerations that lead to well characterized conjugates

and strong CMC regulatory packages. Benjamin Hutchins, Senior Scientist, ImmunoGen, Inc. USA 3:00 - 3:05 End of Workshop