Biomanufacturing Vision for the Future

Transcription

1 Biomanufacturing Vision for the Future Shou-Bai Chao, Ph.D. Senior Vice President Global Manufacturing and Technical Operations MedImmune (a Div of AstraZeneca) NIPTE/FDA Research Conference Future of Pharmaceutical Manufacturing Rockville, MD, June 18-19, 2013 The views and opinions are those of the speaker and do not necessarily reflect those of MedImmune or AstraZeneca.

2 Manufacturing Success Cost Effective On Time Manufacturing Success Quality Quantity 2

3 BUSINESS CONSIDERATIONS

4 Biologics Versus Small Molecules Share of Revenue: Bio vs. Small Molecules 5% 95% 50% 50% Biologics Small Molecules Percent of Pipeline 43% 20% 57% Biologics 80% Small Molecules DATAMONITER- Pharmaceutical Key Trends 2011 Pharmaceutical Industry Infrastructure Overview HC

5 Shift to Biologics Higher success rates for large molecules Source: KMR Group, April

6 Patent Expiry Adds to Market Source: Pharmaceuticals, 2012 By 2016, total mab sales are expected to surpass $65B Source: Datamonitor, PharmaVitae Explorer 6

7 Driving Forces for Biomanufacturing of the Future Productivity (0.1 g/l to 10g/L) Market Segmentation (e.g. PHC) Globalization Addition of ROW (emerging and developing) markets as more important for biologics than in the past Uncertainty of product approvals 7

8 The Capacity Conundrum Uncertainty of product approvals Delta = Available Capacity - Demand Start building Too much capacity Reduce Less utilization 8 Low capacity

9 Managing The Capacity Paradox Betaseron revenues (Projected vs. actual) Enbrel revenues (actual vs potential) $300M 250 Projected (1993) $3.0B Unconstrained/ potential Actual/ forecast 50 Actual Chiron built a plant it never used and was eventually sold Wyeth & Immunex (now Amgen) lost potential sales in US and delayed launch in EU as US sales surpassed worldwide sales within 6 months of launch 9 Adapted from Kamarck & Skibo, DCAT, 2012

10 Additional Challenges High degree of pipeline attrition - Demand modeling - Integrating manufacturing strategy into pipeline planning - Planning for success upsides have usually hurt manufacturing networks more than downsides Technical Leaps - Yield enhancements in mab production - Most plants designed with <1 g/l productivity - Currently averages are 3-6 g/l range with some in approaching 10 g/l - Related challenges; Domino effects - Changes are not unilateral - Upstream improvements may have downstream bottlenecks - Goal is overall optimal productivity 10

11 Late Phase Clinical Material in Commercial Manufacturing Facility Many bio products need large scale production for Phase III Desire to make Phase III in commercial launch/ equivalent site Time/ quantity drivers different but overall manufacturing optimization issue is same Manufacturing needs to consider not only bulk but Drug Product, Packaging and supporting analytical/ QC requirements Flexible manufacturing network can also be built with - Partnerships - CMO s 11

12 Globalization Future may mean less mega sites and more regional sites for market access - Process intensification - Smaller nimble facilities - Cost manufacturing at region More common for packaging/labeling globally Drug product fill/finish - Global emerging market technical changes Comparable major supply sites in Asian, MENA and EU markets 12

13 Other Challenges; Diversification of Product Categories We have made mab processing fairly standard, and achieved consistency..however in near future not all biotech new products would be traditional mabs. Fragmented mabs peptides Antibody drug conjugates oligonucleotides polyclonal Personalized medicines Need new Manufacturing paradigm and new characterization technologies 13

14 Considerations for New Product Categories New product categories - Traditional production facility concept may not work Need smaller modular facilities e.g. for cell therapy - Combination of biotech/ synthetic products Mix of potent facility/ API type facility for Antibody drug conjugates Synthetic manufacturing peptides and oligonucleotides - Combination products Novel devices and delivery systems 14

15 Facility of the Future Smaller, more focused markets As market demand decreases, and titers/yields increase, batch size decreases Flexibility must increase - Disposables Efficiency must increase - Operational Excellence (OE) Downstream processes must improve More nimble, standardized and modular - Platform processes - Simpler processes less unique - Appropriate automation Balance flexibility with consistency - Single use or disposable processing 15

16 TECHNOLOGY SOLUTIONS

17 New Biomanufacturing Technologies process intensification doing more in less Buffer handling - Key limitation in high volume Mab products - More justification for in-line buffer dilution - Save on making and storing high volume buffers Higher throughput processing - Flow through membrane based separation technologies - Potential for faster processing Continuous processing - DS processes alternate perfusion type processes - Continuous purification processes Simulated moving beds Flow through schematics 17

18 Single-Use Technology Single-use bioprocessing equipment is providing the biopharmaceutical industry with cost-effectiveness and flexibility 1 Greater flexibility 1 - purchase, ship, store and install complete manufacturing systems as needed Cost of manufacturing reduction - No steam/clean/sterilize equipment 1 - Cheaper equipment (plastics vs. stainless) 1 - Waste management: Cost to incinerate disposables is a fraction of production cost and waste water treatment % of companies report current in-house use of single-use bioreactors (however, no mainstream biopharmaceutical product is manufactured using this equipment) 1 Supplier management is a key success factor for disposable technology due to extractables concerns E. Langer, President, BioPlan Associates, Inc., Biomanufacturing Morphs, (a summary of 8 th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production): BioPlan Associates, April S. Aldridge, Biopharm turns plastic, March 1, Pat Sacco, Shire presentation at Biophorum 2013

19 Changing Face of Biotech Drug Substance Facilities Conventional Plants Future Plants Large, single product dedicated plants Built for blockbusters Inflexible, fixed pipe Costly to modify Few products, large volumes Lower capital cost Lower operating cost Disposable Flexible Many products, smaller volumes 19

20 New Trend: Single Use/Disposables 1000L Single Use Bioreactor 250L Stainless Steel Bioreactor 20

21 NETWORK FLEXIBILITY

22 Lifecycle of Biomanufacturing Collaborations (The next chapter) - Industry maturation established industry leading Biologics products - Strategic collaborations taking form, global capabilities established - Product differentiation based on therapeutic performance and end user experience - Mfg processes in large are using similar medias, incoming material specifications, and equipment to achieve common cost point - Standardized facilities and convergence to platform technologies (processes and analytics) Enhanced process yields & controls enabled via process characterization Enables broader use of available capacity to hedge portfolio risk 22 Adapted from Kamarck & Skibo, DCAT, 2012

23 Opportunity - TPN TPN Trusted Partner Network Flexible Manufacturing Network - Share capacity to better balance the demand curve - Closer relationship than traditional CMO relationship 23

24 Manufacturing Capacity Sharing Model A Relationship Built on Trust & Transparency A capacity consortium sharing available manufacturing capacity - Enabled by facility and process similarities - Partnership across a portfolio of programs rather than ad-hoc product based agreements - Open book capacity requirements for small network of partners - Biosimilars may offers broader portfolios for entry into multi-product manufacturing collaborations Business Benefits - Financially responsible use of available capacity Increase ROA - Hedging pipeline risk across broader portfolio of opportunities Managing the Capacity Paradox - Capital avoidance/deferral - Aligned incentives to maximize asset utilization - drives innovation 24

25 25 Merck Signs 15 Year Manufacturing Capacity Sharing Agreement with MedImmune

26 26 Frederick Manufacturing Center - Building 633

27 Business Case (Why now for MedImmune?) Three to five year delay in delivering on the commercialization of products - Contrary to original plan, plant would not be fully utilized until 2022 Under-utilization would leave it empty until Result: $100M annual depreciation to manufacturing Best in Class facility and staff would be in hot standby status for five years 27

28 28 Manufacturing Process: Bioreactors

29 Manufacturing Process: Purification Commercial Scale 1.4 meter diameter columns Pilot Scale 60 cm diameter columns 29

30 Why Did Merck Choose MedImmune? Licensure achieved in June, 2011 as planned >ZERO 483 s ISPE Facility of the Year Award (FOYA) for Project Execution >Jan 2011 Near Perfect Production startup records 30

31 Maintain High Quality While Reducing Cost of Goods (COGS) Cost containment/reduction will always be important to our continued business But our industry requires and assumes 100% reliable Quality as a foundation for survival of the Enterprise $ Q 31

32 Understand Cost Components to Identify Areas of Potential Reduction that Do Not Impact Quality 100 COGM Percent COGM (%) OpEx Raw Materials FTEs Best Target After understanding is gained, COGM components identified as low hanging fruit can be addressed 32

33 Summary Biomanufacturing for the future will need to manage significant pipeline output with monoclonal antibodies but need to be responsive to disruptive efficiency improvements. Flexibility to be managed with technology and strategy Product mix in the next 20 years may be completely different than platform monoclonal antibodies smaller modular and even more responsive manufacturing networks will be needed 33

34 34 Thank you!