bioLOGIC Europe 2004

Day one Tuesday 22 June 2004

8:50 Moderator’s opening remarks
Amir London, Partner, Tefen

9:00 Keynote presentation: forecasting capacity demand versus process improvements
· The success rate for biologics in the pipelines
· Process efficiency or titer of commercial processes
· Physical capacity if used for multiple products
· Overall regulatory approval time lines for bulk process changes
Dr Wolfgang Berthold, Senior Vice President, Biopharmaceutical Sciences, Biogen Idec

ACHIEVING OPERATIONAL EXCELLENCE FOR COMPETITIVE ADVANTAGE

9:30 Utilising modelling to design, improve and implement biopharmaceutical processes
· Targeting limited development resources and increasing their impact by utilising modelling tools
· Unifying process data with mechanistic and phenomenological models
· What this means for understanding production processes and productivity improvements
· Examples of process mapping exercises that have improved productivity
Dr Blair Okita, Senior Vice President, Therapeutics Manufacturing and Development, Genzyme Corporation

10:00 Fine-tuning manufacturing operations to reduce cycle time
· Mapping the entire cycle time from raw material to finished product
· What are Lean Operations concepts?
· Monitoring lot progress through the entire plant using tracking tools
· Opportunities in the planning function to reduce inventory levels
· How to reduce changeover time in filling lines
Glenn Brame, Site Head, Neuchatel Facility, Baxter Bioscience

10:30 Morning coffee

11:30 Panel session: internal and external collaboration capabilities for increased efficiency
· The key components of a robust collaborative solution
· Knowledge management strategies to ensure all intellectual capital is captured
· Creating a value chain with partners, all concentrating on core competencies
· How to align your collaborative tools with business objectives
· Measuring success: proof points
Panellists:
Dr Blair Okita, Senior Vice President, Therapeutics Manufacturing and Development, Genzyme Corporation
Dr Wolfgang Berthold, Senior Vice President, Biopharmaceutical Sciences, Biogen Idec
Glenn Brame, Site Head, Neuchatel Facility, Baxter Bioscience

12:15 Adapting process technology to manufacturing large volume biologics
· Process development strategies
· Impact on products
· Transfer to manufacturing operations
· Building capacity for large volumes
Dr Avinoam Kadouri, Bioprocess Technology Development Director, Serono International

12:45 Approaches to capacity planning and scheduling work load in biopharmaceutical quality control labs
· Planning for optimal utilisation of capacity with respect to workload and existing constrains
· Utilising enterprise systems to support planning and scheduling
· Prioritisation of sample testing based on business drivers
· Tracking laboratory performance
Andreas Kyriacou, Director, Corporate Quality Laboratories, Amgen

13:15 Lunch

SUSTAINING A BIOLOGICS PIPELINE THROUGH TO MANUFACTURING

14:45 Moderator’s opening remarks
Dr Monica Darnbrough, CBE, Director, BioScience Unit, HM Government Department of Trade & Industry, UK

15:00 Establishing a high yielding biomanufacturing technology platform to meet the (changing) market demands
· The biopharmaceutical market and the expected demand for manufacturing capacity
· Options to meet demand
· Process improvement technology
· Expansion of manufacturing capacity
· The need for flexibility and operational excellence
André Bos, CEO, DSM Biologics

15:20 Value added in biopharmaceutical manufacturing
· Investment strategy
· Capacity utilisation
· Productivity increase
· Inventory management
Professor Rolf Werner, Corporate Director, Corporate Division Biopharmaceuticals, Boehringer Ingelheim

15:40 Building value during biopharmaceutical development
· Impact on development cycle
· Product valuation
· Technology transfer
· Personalised medicines
Dr Crawford Brown, Director, Eden Biopharma Group

16:00 Session Q&A

16:15 Afternoon tea

17:00 The future of biopharmaceutical products and pipelines
· Trends in manufacturing for existing product classes
· Yield improvements
· Transgenics
· Challenges for purification
· New locations
· New product classes – biogenerics, gene therapy and novel vaccines, tissue engineering and cell therapy
· New formulations and delivery systems
Dr Sharon Grimster, Director, Westerly Projects, Chair, Manufacturing Committee, BIA

17:30 Optimising manufacturing of early phase biopharmaceuticals
· Coping with a diverse range of products
· Strategies for fermentation process development
· The value of a co-ordinated multidisciplinary approach
Amanda Weiss, Associate Director, Fermentation, Cobra Biomanufacturing

18:00 Outsourcing demand versus capacity – an update on global capacity issues
· Size of the global biopharmaceutical industry (including forecasts)
· Demand vs capacity: contract vs in-house
· Outsourcing trends
· Plans for multi-use facilities and transgenic technologies
Dr Suzanne Griffiths, Senior Consultant, Pharmaceuticals and Biotechnology, Wood Mackenzie

18:30 Close of day one

Day two Wednesday 23 June 2004

UPSTREAM YIELD IMPROVEMENT

8:50 Moderator’s opening remarks
Bill Thompson, Partner, Rotherwood Associates

9:00 Concept for PAT and PIMS supported HPT development of mammalian cell culture processes
· Two ways of increasing the throughput rate in development:
- increase the number of parallel experiments
- decrease the duration of the experiments
· Using a combination of PAT and PIMS tools to follow both ways in parallel
· Increasing the number of experiments per unit time by "telescoping" experiments by automation (PIMS)
· Avoiding waiting periods for results of lab based off-line analytics (PAT)
· Reducing the duration of the development
Dr Christian Leist, Head of Bioprocess and Technology Development, Leading Scientist, Novartis Pharma

9:20 Case study: scale up of microbial manufacturing processes for antibody fragment production
· Monoclonal antibody supply challenges
· Microbial expression technology to produce humanised Fab fragments
· Ways to effectively recover these fragments
· Scale-up for GMP manufacture
Dr Andrew Chapman, Head of BioProcess Research, Celltech R&D

9:40 Optimisation of upstream processes for antibody production from mammalian cell culture
· Optimisation of expression technology
· Cell line selection / screening
· Optimisation of the fermentation process
· Impact of upstream process on recovery steps
Professor John Birch, Chief Scientific Officer, Lonza Group

10:00 Session Q&A

10:15 Morning coffee

11:00 Lessons learned in optimisation of media and processes for improved productivity
· Focus of traditional methods of media development
· Impact on yields of the use of rich basal media and rich feed supplements in fed batch systems
· How to simplify basal media and feed supplements to improve the efficiency of fed batch systems resulting in improved product yield
· Problems and solutions in optimising fed batch culture systems
Dr Stephen Gorfien, Director, Industrial Applications (GIBCO™ Cell Culture R&D), Invitrogen Corp.

11:30 Case study: E.coli for high-level production of vaccine antigens
· Versatile expression system for either intracellular or periplasmic localisation of product
· Multiple construct screening to obtain stable high production clones
· Use of the periplasmic space to protect sensitive products from proteolysis
· Rapid product capture from the periplasmic space using homogenisation in combination with expanded bed chromatography
Dr John Brehm, Senior Scientist, Health Protection Agency (Porton Down)

12:00 Panel session: transgenics versus mammalian cell culture – what are the advantages of each expression system?
· The ability of transgenics to produce proteins and antibodies that are difficult to express in bioreactors
· Parameters to be discussed for each system:
- economics - safety
- regulation - intellectual property
- ethical and public acceptance - costs
- downstream processability - capital

Panellists:
Dr Barry Holtz, President and CEO, Inflexion Therapeutics
Professor John Birch, Chief Scientific Officer, Lonza Group
Dr Steven Burton, Executive Vice President, ProMetic Biosciences
Dr Greg Liposky, Senior Vice President, GTC Biotherapeutics
Dr Christian Leist, Head of Bioprocess and Technology Development, Leading Scientist, Novartis Pharma

12:30 Plant transgenics: beating the barriers to PMB development
· Has the industry met the challenges regarding the contamination of other crops?
· Where do good agricultural practices (GAP) end and good manufacturing practices (GMP) begin?
· Where worries over glycosylation differences were overrated?
· Downstream innovations expected from manufacturing-scale PMB operations
Dr Barry Holtz, President and CEO, Inflexion Therapeutics

13:00 Lunch

KEY TRENDS IN DOWNSTREAM PROCESSING TECHNOLOGIES

14:30 Moderator’s opening remarks
Dr Keith Chidwick, Pharmaceutical Assessor, Medicines and Healthcare Product Regulatory Agency (UK)

14:40 Downstream processing 2003+: recovery and polishing
· Innovation and risk tolerance in the downstream arena
· Current trends and techniques: generic platforms vs DOE screening, conti vs batch, disposables vs multi-use, beads vs membranes, crystallisation vs separation, virus removal vs inactivation etc
· Novel virus filters and specialised modes of operating next-generation ultra-filtration membranes
· Improved process economy with whole process design and integrated unit operations
· Risk management and comparability aspects in DSP
Dr Uwe Gottschalk, Vice President, Purification Technologies, Sartorius AG--Biotechnology

15:10 Design and material selection of disposable systems for cell culture media and other sterile liquids
· Design considerations for flexible, disposable container systems
· Container film is the critical component that dictates container performance
· Five key performance requirements –
- container geometry
- operating environment
- permeability
- material compatibility
- transportation
· Assessment of commercially available flexible, disposable systems
Steven Giovanetto, Director, Programme and Core Competency Management, Medical Plastics Technology Group, Baxter Healthcare Corporation

15:40 Case study: a disposable manufacturing concept facility
· State-of-the-art facility design optimised for disposable technologies
· Kleenpak disposable Aseptic Connector and Biosafe sterile fluid transfer technology – impact on layout
· Modular building approach for reliability, highest quality and safe secured fast implementation
· Impact of disposables within a modular multi-product plant
· Facility cleandown and turnaround time, labour, throughput, COG analysis
Miriam Monge, Marketing Director, Europe, Stedim S.A.
Dr Björn Hammarberg, Key Account Executive, Pharmadule

16:10 Afternoon tea

17:00 Process development for the reduction of manufacturing costs and maximisation of revenues
· Benefits of improving product capture steps
· Benefits of improving process yield and reduction of facility residence times, utilisation of factorial experimental design and scaled down process models
· Rationalisation of product supply strategies and tactics
· Disaster recovery scenarios and realities
Dr Richard Francis, Director, Process Development and Technical Support, Protherics

17:30 Is affinity chromatography a general solution for protein purification?
· Identification of the best affinity ligand
· Development of a qualified binding assay
· cGMP production concept for the affinity matrix up to industrial scale
Dr Ulf Bethke, Plant Manager, Miltenyi Biotec Contract Manufacturing Division

18:00 Status and trends in scale up of membrane chromatography for protein and virus processing
· Impact of different adsorber matrices on the mass transfer effects and binding kinetics
· Advantages, limitations and future perspectives of membrane adsorber technology
· Critical parameters and features of materials, functions and device and system design for membrane chromatography
· Theoretical and practical scale up considerations
· Evaluation of in-situ sterilisation methods on the performance of membrane chromatography
Dr Oscar-Werner Reif, Vice President, R&D and Technology, Sartorius AG

18:30 Close of day two

Day three Thursday 24 June 2004

IMPROVING COMPLIANCE AND AVOIDING DEVIATION

8:50 Moderator’s opening remarks
Dr Sharon Grimster, Director, Westerly Projects

9:00 The impact of the EU Clinical Trials Directive and other recent regulatory changes on the manufacture of biopharmaceuticals
· Comparison of the different regulatory policies
· Potential impact of these policies on the production and cost of biopharmaceutical clinical trial materials and market supplies
· Capital resources needed to fully implement and comply with the new requirements
· Impact on the financing and timing of new product development
· Strategic options for contract manufacturers and impact of the regulations on global capacity
· Timelines for compliance with these new guidelines
Dr Howard Levine, President, BioProcess Technology Consultants

9:30 Meeting the regulatory challenge of releasing clinical trial material into Europe in light of the new EU Clinical Trials Directive
· How does GMP relate to investigational medicinal products?
· Manufacturing and analytical requirements
· Batch release
· Dealing with products manufactured outside the EU
Dr Philippa Whiteside, Associate Director, Regulatory Affairs, Europe, ERA Consulting Group

10:00 Improving validation through regulatory initiatives
· FDA update: new GMP guidance and initiatives
· Validation essentials, establishing protocols, cleaning and processes
· Computerised system validation requirements in manufacturing
· Enhancing manufacturing techniques with PATs and real time monitoring
· Implementation of effective investigation with a CAPA programme
Invited speaker:
FDA representative

10:30 Morning coffee

11:30 Panel session: how can risk management be integrated into decisions regarding quality including compliance?
· Harmonised, risk-based, science-based quality systems for the 21st century
· What is risk management and what is the FDA’s definition?
· Developing quality by design initiatives and implementing manufacturing science principles
· Regulation assessment versus inspection issues
· Technology integration: enhancing QA and compliance in biopharmaceutical manufacturing
Panellists:
Dr Howard Levine, President, BioProcess Technology Consultants
Dr Hannalore Willkommen, Vice President of Regulatory Affairs, Europe, Clearant

12:15 Leveraging supplier data and services to speed compliance
· Generating qualification data for equipment components
· Documentation for automated systems
· Outsourcing process validation to equipment suppliers
· Scale up implications for filtration and separation systems
Jerold Martin, Senior Vice President, Global Technical Director, Pall Life Sciences

12:45 Lunch

PREPARING FOR A FUTURE OF BIOGENERICS

14:15 Moderator’s opening remarks: factors affecting consideration of biogenerics
· The science of well-characterised biologics
· Recent FDA restructuring and EU institutions’ initiatives
· Industry and international trends
· Public policy trends
Dr David Shoemaker, Vice President, Regulatory Affairs and Project Management and Managing Director, Cato Research

14:45 Comparison of European and US legal frameworks for obtaining marketing authorisation for a biogeneric
· What will be necessary to show essential similarity?
· Is the possibility of using the well-established route procedure a practical one?
· If so, how will you show that the product is similar to one with well-established use?
· What features of the specific biological product will determine what might be the most appropriate route?
· How will things change under the new European legislation?
Nicola Dagg, Partner, Intellectual Property, Lovells

15:15 Afternoon tea

15:45 Regulatory and legal considerations for biogenerics in Europe
· The revision of Directive 2001/83 and the recent adoption of the update of the Annex I of that Directive
· The legal basis for the review of marketing authorisation applications
· Is the approval of biosimilar products by the EU institutions inevitable?
· Barriers to biogenerics
Dr Enrico Polastro, Vice President, Arthur D. Little Benelux S.A./N.V.

16:15 Panel session: are biogenerics coming?
· Challenges presented for safety assessment programs for biologics as compared to small molecules
· Unique biologic product development issues
· Key aspects of a product comparability programme to prove therapeutic equivalence
· Scientific issues that bear on safety considerations for follow-on (generic) biologics
Panellists:
John Marugg, Marketing Director, DSM Biologics
Nicola Dagg, Partner, Intellectual Property, Lovells
Dr Enrico Polastro, Vice President, Arthur D. Little Benelux S.A./N.V.

17:00 Close of conference