docBiomanufacturing capacity for biosimilars: Is there enough?
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Biomanufacturing capacity for biosimilars: Is there enough?
Biomanufacturing Capacity for Biosimilars: Is there enough? Cambridge Healthtech Institute’s Third Annual BIOAnalytical Summit 2012 Mar 19-22 Baltimore, MD BioProcess Technology Consultants www.bptc.com Increasing Sales of Biopharmaceutical Products From Clone to Clinic® Biologic Products – Current and Future Ref: Stout, J. BPI Conference 2011 From Clone to Clinic® What Are Biosimilars? Successor to an innovator product for which patent protection no longer applies Complex molecules manufactured by recombinant DNA technology Comparable with the innovator product in terms of quality, efficacy, and safety EU draft general guidelines adopted 2004 First biosimilar somatropin approved and launched in EU 2005 Somatropin ‐ first biosimilar approved worldwide (Australia) 2006 First biosimilar EPO approved and launched in EU 2007 First biosimilar filgrastim approved and launched in EU 2008 2010 2009 Japan regulatory guidelines US regulatory pathway First biosimilar somatropin approved and launched in Japan & Canada From Clone to Clinic® Biosimilars Are Reality and Growing… Today relatively simple proteins ‐‐ tomorrow, more complex proteins Biosimilar products currently approved in Europe Product Name Abseamed Binocrit Epoetin alfa Hexal Biograstim Filgrastim Hexal Filgrastim Ratiopharm Nivestim Ratiograstim Tevagrastim Zarzio Omnitrope Valtropin Retacrit Silapo Active Substance Epoetin alfa Filgrastim Somatropin Epoetin zeta Ref: http://www.gabionline.net/Biosimilars/ General/Biosimilars‐approved‐in‐Europe Company Medice Arzneimittel Pütter Sandoz Hexal CT Arzneimittel Hexal Ratiopharm Hospira Ratiopharm Teva Generics Sandoz Sandoz BioPartners Hospira Stada From Clone to Clinic® Adoption Rates of Biosimilars in Europe Biosimilar Share of Innovator Product Sales (March 2011) Country Somatropin (1) Erythropoietin (5) Filgrastim (6) Austria 6% 50% 52% France 20% 11% 42% Germany 12% 65% 45% Greece N/A 67% 53% Italy 12% 7% 18% Poland 7% 62% 38% Romania 34% 58% 77% Spain 15% 16% 24% Sweden 21% 63% 45% UK 4% 9% 80% EU Total 13% 18% 38% 6 From Clone to Clinic® Biosimilar Development Is Lengthy And Expensive Generics* US$ 2 – 3m Biosimilars* US$ 100 - 150m Innovator* US$ 800m Development Investment 2 – 3 yrs 7 – 8 yrs 8 – 10 yrs Time to market 20 – 50 pts ~ 500 pts 800 – 1000 pts # of patients for approval *Industry average Ref: Visser, J. BPI Europe 2010 From Clone to Clinic® Monoclonal Antibodies Will Be The Next Wave Many blockbuster MAbs will be off patent in the next few years • Biosimilar MAbs already available in India and China Monoclonal antibody products soon to be off patent: Product Name Active Substance Company Avastin Bevacizumab Roche/Genentech Enbrel Etanercept Amgen Erbitux Cetuximab Eli Lilly Herceptin Trastuzumab Roche/Genentech Humira Adalimumab Abbott Lucentis Ranibizumab Roche/Genentech Remicade Infliximab Johnson & Johnson Rituxan Rituximab Roche/Genentech Ref: http://www.gabionline.net/Reports/Top‐25‐biotech‐ drugs‐the‐next‐biosimilars‐targets From Clone to Clinic® Product Demand Greatest for Monoclonal Antibodies Demand for existing commercial antibody products will nearly double by 2016 ~8.3 metric ton ~13.4 metric tons (2010) Product Demand for Commercial Antibody Products (2016) 2010 requirements for each of the top five monoclonal antibody products ranged from 1.0 – 2.3 metric ton All others (27) 26% Remicade 17% 2010 demand for all other monoclonal antibody products combined was approximately 2.5 metric tons Anticipated demand for new monoclonal antibody products approved between now and 2016 is expected to be <5 metric tons/year/MAb Avastin 16% Herceptin 12% Enbrel 13% Rituxan 16% From Clone to Clinic® Demand for Biomanufacturing Capacity Growing Driven by growing market for approved products, large number of products in clinical development, and growing interest in biosimilars Volumetric requirements will almost double by 2016, leaving companies and markets without capacity scrambling for resources From Clone to Clinic® Distribution of Mammalian Cell Culture Capacity From Clone to Clinic® Geographic Distribution of Cell Culture Capacity Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate From Clone to Clinic® Balance of Supply and Demand Assumes no increase in current titers Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate From Clone to Clinic® Product Companies Control ~70% of Capacity 4,500 Installed Capacity 3,600 2,700 1,800 900 0 2010 2011 CMO 2012 2013 XS 2014 2015 2016 Product Co. Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate From Clone to Clinic® Ten Companies Control >75% of Capacity 2010 Volume (1,000s L) 2016 Volume (1,000s L) Roche 525 600 4 J&J 230 230 3 5 Boehringer Ingelheim 216 216 4 6 Amgen 198 198 5 3 Lonza 150 232 6 8 Pfizer 139 149 7 2 Sanofi‐Aventis 133 263 8 ‐ Novartis 125 ‐ 9 10 Lilly 122 137 10 7 Biogen Idec 106 196 ‐ 9 Celltrion ‐ 140 All Others 614 1,070 2010 Rank 2016 Rank 1 1 2 Company Perfusion capacity adjusted to equivalent fed‐batch capacity where appropriate From Clone to Clinic® Capacity Distribution by Bioreactor Scale From Clone to Clinic® Source of Uncertainty When Developing a Mfg Strategy 17 From Clone to Clinic® Drivers for Build, Buy, Acquire Decision Core Competency Assessment • • We’re Good At It Not Many Others Are Is “Buy” an Option? • Technology Requirements • Scale • Capacity Availability – Supply vs. Demand Strategic Fit • • • Pipeline Competitive Advantage Development Stage Risk Management • Control • Cost and Probability of Failure Financial Considerations • Return on Capital • Cost of Capital • Operating Costs From Clone to Clinic® Product Lifecycle Drives Make vs. Buy Decisions Make Buy Make or Buy Product Launch Product Launch Maturity Product Life Cycle Maximizing Control • • Manufacturing costs set at decision point RISK RISK Manufacturing costs set at decision point Development Market Uncertainty Uncertainty Buy or Make Development Uncertainty Market Uncertainty Maturity Product Life Cycle Conserving Capital “Make” strategy during highest risk period to maximize control of supply • “Buy” strategy during highest risk “Buy” strategy may make sense once product lifecycle stabilizes, risk decreases, and control less important • “Make” strategy may be attractive period to conserve capital once product lifecycle stabilizes, capital becomes more available, and risk reduced From Clone to Clinic® Biopharmaceutical Industry Moving to Outsourcing CMO’s are a long‐term sustainable strategy • Many large pharmaceutical companies are moving away from internal manufacturing and relying on CMO’s • Outsourcing to an experienced CMO presents a faster, more economical approach to market entry Strategic outsourcing improves flexibility and minimizes capital outlays allowing • • Access to new or different technology as well as expertise and experience Reduces development time and provides maximum flexibility during development Risk mitigation and financial flexibility • • • Maintain low overhead and minimize cash flow Minimizes company infrastructure Eliminates capital investment in manufacturing assets From Clone to Clinic® Advantages to Outsourcing The vast and complicated development activities required for biologics are often best outsourced, including • • • Cell line construction, banking, and characterization Process development, formulation development, analytical methods development GMP manufacturing Product availability Capital Investment Required Technology transfer/ process development Cost per lot Company commitment (FTE) Risk of process failure In‐House CMO 24 – 30 months 18 – 24 months $10+ Million <$1 Million $1 – 2.5 Million $1.5 – 3 Million $1 – 5 Million $1 – 5 Million 20 – 30 3 – 4 Company CMO/Company From Clone to Clinic® Trends in Biomanufacturing – Facilities of the Future Designed for modern, state‐of‐the art processes • Cell culture titers of titer >5 g/L • Smaller bioreactors will produce similar quantities to today’s “six pack” facilities • Multi‐product capabilities and flexibility will become increasingly important Expanded use of new technologies to reduce capital investment, increase flexibility, and compress timelines • Disposable technologies will become increasingly prevalent • Continuous processing, PAT and other modern manufacturing methods will be incorporated into bioprocessing From Clone to Clinic® Thank You! Patricia Seymour pseymour@bpc.com 1.617.417.9240 BioProcess Technology Consultants, Inc. 12 Gill Street, Suite 5450 Woburn, MA 01801 Follow us… www.bptc.com www.bioprocessblog.com bptcGlobal www.linkedin.com/company/bioprocess-technology-consultants-inc.
