CBI Biosimilars Workshop


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CBI Biosimilars Workshop

  1. 1. Development and Manufacturing Strategies for Biosimilars Thomas Vanden Boom, Ph.D. Vice President, Hospira Global Biologics R&D CBI’s 5th Summit on Biosimilars and Follow-on Biologics Washington, D.C. October 18, 2010
  2. 2. Overview  Introduction  Biosimilars Process Development  Manufacturing Technology platforms  Key biosimilar development topics – Surveillance of originator lots – Scalability – Optimization of glycosylation profiles – Post-approval CMC landscape for biosimilars  Conclusions
  3. 3. Hospira Biosimilars Business  Only U.S. company marketing a biosimilar – Leading biosimilar EPO IV product, Retacrit™, in the EU with recently approved SC presentation – Biosimilar filgrastim (G-CSF) product, Nivestim™, approved in the EU and Australia  Hospira’s 11-compound biosimilars pipeline is one of the industry’s largest  Key partnerships and licensing deals established to enable development of full range of biologic products
  4. 4. Hospira Global Biologics Development and Manufacturing Network Lake Forest, IL Zagreb, Croatia Rockville, MD (HGS) McPherson, KS Adelaide, Australia South Korea (Celltrion) Germany (Stada) Partner Hospira Facility
  5. 5. Biosimilars Represent a Distinct New Sector of the Biopharmaceutical Industry Biosimilars Originator Products Generics Development Environment Development Environment Probability of Success Cost Time Development Low (~30%)High (~90%) High (>$800 M)Low (<$5 M) Long (8-12 yrs)Short (3-4 yrs) Barriers to Entry Point of Differentiation Other Dynamics HighLow Product profile, marketing Price, breadth of portfolio Competitors Investment Pricing Marketing Few, well differentiated Many, little differentiation HighLow PremiumCommodity Source: FTC Report June 2009 and HSP internal analysis
  6. 6. The biosimilar space is currently defined by regulatory and market uncertainties  Future competitive environment uncertain  World wide Health Authorities and clinicians have limited experience with biosimilar products  Regulatory framework for biosimilars in U.S. is still pending  Complex biopharma patent landscape exists  Companies have limited commercial experience in introducing biosimilar products
  7. 7. What does this mean for biosimilar companies?  The quality and level of the science is critical  Development and manufacturing strategies must be flexible – Manufacturing processes should be designed for ease of scale-up (and scale-down) and technology transfer – Excellence in execution of post-approval CMC changes will offer a competitive advantage to biosimilar developers
  8. 8. Biosimilars Process Development Biosimilar Process Development Phases From cell … … to biosimilar product Genetic and Bioanalytical Characterization Comparability Intellectual Property Clearance Large-scale Process Validation Reverse Genetics Drug Product Development Drug Substance Development Cell Line Development
  9. 9. Current Biologic Production Systems E. coli Yeast Chinese Hamster Ovary (CHO) Cells Approximately 90% of currently approved biologic products are produced from 3 living systems
  10. 10. Alternative Expression Systems  More than 340 new expression technologies currently under development*  Use of alternative systems may be associated with increased technical and regulatory risk –Dramatic changes in expression system may preclude development of product as biosimilar  Significant process improvements possible using current systems *E. Langer, BioPharm International, June 2009
  11. 11. Biosimilar Manufacturing Opportunities  Biosimilar companies have access to modern biologic manufacturing technologies – Lower cost-of-goods – Enhanced process consistency – Reduced facility capital costs  Originator companies may be trapped in legacy manufacturing platforms  Biosimilar and originator companies should be subject to the same regulatory guidelines for implementation of post-approval changes
  12. 12. Emerging Biologic Manufacturing Technologies  Upstream technologies: disposable bioreactors  Buffer dilution systems : alternative to large buffer tank capacity  Bioseparation technologies: membrane chromatography capsules Disposable Bioreactors Buffer Dilution Skid Membrane Chromatography Capsules Example technologies from GE Healthcare, Xcellerex, Technikrom and Pall
  13. 13. Where do new technology platforms fit in the biosimilars space?  The benefits of deploying new technology platforms should be carefully weighed against potential increased technical and regulatory risks  Selective deployment of new technologies will result in higher quality and lower cost biosimilar products  Biosimilar companies with the scientific and regulatory expertise to make effective technology decisions will have a competitive edge
  14. 14. Building Noticeable Differentiation through Incremental Innovation Non-clinical differentiators can be designed into biosimilar offerings to improve on originator products
  15. 15. Key Biosimilar Development Topics  Surveillance of originator lots  Scalability  Optimization of glycosylation profiles  Post-approval CMC landscape for biosimilars
  16. 16. Retacrit® Surveillance of Originator Lots Examination of Manufacturing Batch Consistency using Capillary Zone Electrophoresis epoetin zeta: N = 67 batches epoetin alfa: N = 9 batches epoetin alfa epoetin zeta
  17. 17. Scalability of a Biosimilar MAb Product 70 75 80 85 90 95 100 NormalizedTiter 250 mL 2 L 10 L 15 L 100 L 400 L Scale
  18. 18. Optimization of Glycosylation Profiles for a Biosimilar MAb Product Media Normalized Titer G0 Difference from Reference Product (%) Control 1.0 24.7 A 1.2 4.6 B 1.2 -2.0 C 1.2 -4.2 D 1.1 -6.5 N-acetylglucosamine Fucose Mannose Galactose G0 G1,G2
  19. 19. Post-approval CMC Landscape for Biosimilars  The same regulatory guidelines for post-approval CMC changes are anticipated to apply to biosimilar manufacturers  WHO Guidelines on Evaluation of Similar Biotherapeutic Products (SBPs), October 2009 – “For changes in the manufacturing process ICH Q5E should be followed”  Health Canada Guidance for Sponsors: Information and Submission Requirements for Subsequent Entry Biologics (SEBs), March 2009 – “Comparisons with the original reference biologic drug are not required.”
  20. 20. Conclusions  Biosimilar companies will continue to face significant uncertainties in the near term  Companies with the scientific, technical and commercial competencies to effectively manage these uncertainties will be successful in this space  The benefits of deploying new technology platforms should be carefully weighed against potential increased technical and regulatory risks
  21. 21. Conclusions  Layered incremental innovations to biosimilar products may offer significant value to patients and customers  Extended surveillance and characterization of originator lots is essential to defining “biosimilarity”  The anticipated post-approval CMC landscape will enable biosimilar companies to continue to drive innovation to provide patients with high quality and lower cost biologic products
  22. 22. Acknowledgments Hospira Biosimilars Team Stada Arzneimittel AG