connecting science, technology and business to … science, technology and business to ......
TRANSCRIPT
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
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 [email protected] 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