Case Study: How to Succeed in Vaccine Externalization and Technology Transfer Fi Alonso-Caplen, Ph.D. Senior Director, Biotherapeutics & Vaccines Outsourcing 21-Jul-2014 CMC Strategy Forum This document provides an outline of a presentation and is incomplete without the accompanying oral commentary and discussion . Conclusions and/ or potential strategies contained herein are NOT necessarily endorsed by Pfizer management. Any implied strategy herein would be subject to management, regulatory and legal review and approval before implementation. Today’s Agenda • Background – Vaccine Project – Why Outsource? • CMO Selection • Contract Negotiations – Service Agreement – Quality Agreement • Technology Transfer – Project Management – Production Processes – Analytical Test Methods • Lessons Learned 2 Background – Vaccine Project • LP2086 Protein: – Surface-exposed lipoprotein present in all meningococcal strains examined – Binds human factor H, a negative regulator of complement, important for survival of the organism in vivo – Bactericidal activity demonstrated against 125 different clinical Neisseria meningitidis Group B isolates • MnB Vaccine: – For adolescent and infant indications – Bivalent, rLP2086 A and B subfamily lipoproteins – rLP2086 highly purified (>98%) from E. coli Mascioni, et al. JBC 2009 3 Serogroup B is Now the Predominant Remaining Meningococcal Serogroup in Many Parts of the World Y (3%) Other (13%) Y (13%) B (54%) C (17%) Other (4%) C (20%) Other (9%) B (35%) Y (25%) B (76%) Canada26 2006 n = 210 Other A (1%) (2%) European Union14 2006 n = 5,223 C (31%) United States 200824, 25 n = 1,172 W135 (31%) Other (1%) W135 (8%) Y W135 (2%) (2%) C (26%) Taiwan27, 8 2001 n = 43 B (52%) Y (11%) C (3%) A (91 %) B (69%) African Meningitis 2006 8 n = 2,192 Latin America and the Caribbean* 2005 n = 1,391 Belt28 Australia29 2007 n = 304 Other C (6%) (11%) Other C (9%) (8%) B (84%) B (83%) New Zealand 30 2007 n = 105 Note: *Number of cases is an average of 2002-2005. Isolates were collected from 19 countries and the Caribbean Epidemiological Center. Most isolates were from Brazil and Chile. Source:14 EU-IBIS (2006); 24CDC (2010) MMWR 57(54); 25CDC ABCs Reports; 26Public Health Agency of CA (2009) CCDR; 27Chiou, CS. et al. (2006) BMC Infect Dis; 8Harrison, LH et al. (2009) Vaccine; 28WHO, Africa (2009); 29AU Government Department of Health and Aging (2009); 30NZ Ministry of Health (2008). Media Coverage Princeton University Meningococcal B Outbreak Media Coverage UC Santa Barbara Meningococcal B Outbreak Background – Why Outsource? • Quicker to clinic is key, without sacrificing quality! – Aggressive time line – Lack of internal capacity • Scope of Work – Production and testing of Phase III Drug Substance – Analytical test methods qualification – Process and methods validation – Commercial manufacturing and testing • Very important: Collaborative effort between Development (PreCommercial) and Manufacturing (Commercial) groups 7 Today’s Agenda • Background – Vaccine Project – Why Outsource? • CMO Selection • Contract Negotiations – Service Agreement – Quality Agreement • Technology Transfer – Project Management – Production Processes – Analytical Test Methods • Lessons Learned 8 CMO Selection Initial List Initial Short List Final Short List Finalist Request for Information Request for Proposal •CMO 2 •CMO 1 •CMO 1 •CMO 2 •CMO 2 Technical Evaluation and GMP Audit •CMO 3 •CMO 4 •CMO 1 Boehringer Ingelheim Vienna, Austria •CMO 2 •CMO 4 •CMO 5 Issues Issues •CMO 3 •CMO 4 •CMO 5 Examples of issues: • New facility / suite not commercially approved • Potential for ownership change • No equipment redundancy • High commercial COGS per dose • Regulatory / Quality / Technical Strengths 9 Today’s Agenda • Background – Vaccine Project – Why Outsource? • CMO Selection • Contract Negotiations – Service Agreement – Quality Agreement • Technology Transfer – Project Management – Production Processes – Analytical Test Methods • Lessons Learned 10 Contract Negotiations: Agreements • Service Agreement – Success Criteria – Milestones and Deliverables – Persons-in-Plant – Steering Committee – Language – Regulatory Support • Quality Agreement – Pre-Commercial and Commercial – Subcontractors – Definition of Terms 11 Today’s Agenda • Background – Vaccine Project – Why Outsource? • CMO Selection • Contract Negotiations – Service Agreement – Quality Agreement • Technology Transfer – Project Management – Production Processes – Analytical Test Methods • Lessons Learned 12 Technology Transfer – Project Management • Joint Project Team – Project Managers (CMO, Sponsor) – JPT Members (CMO, Sponsor) • Process • Analytics • Quality • Regulatory (ad hoc) • Communications – Face-to-Face Meetings – JPT Teleconferences / Webex – Documentation • Joint Steering Committee – Issue Resolution – Governance 13 Process Tech Transfer • Process Transfer – 100L Scale – 2000L Scale • Documentation Examples – Batch Records – Process Descriptions – Data Capture Spreadsheets – Technical Transfer Plan • Hands-on Training • Communications 14 Process Tech Transfer - Deliverables • 3 x 20L Tech Transfer Runs per protein • 3 x 2300L Engineering Runs per protein • 3 x 2300L GMP Runs per protein • 3 x 2300L Process Validation Runs per protein 1Q-08 Jan 2Q-08 Feb Mar Apr May Jun 3Q-08 4Q-08 Jul Aug Sept Oct Nov Dec Jan 1Q-09 Q2-09 Q3-09 Q4-09 Feb Mar Apr May Jun July Aug Sept Oct Nov Dec 1Q-10 2Q-10 Jan Feb Mar Apr May Jun 15 Technology Transfer – Analytical Test Methods • Method Transfer – – – – • In Process Test Methods Characterization Test Methods Release Test Methods Stability Test Methods Documentation Examples – – – – – Analytical SOPs Sampling Plans Specification Reports Method Transfer Plan Method Qualification Reports • Hands-on Training • Communications 16 Today’s Agenda • Background – Vaccine Project – Why Outsource? • CMO Selection • Contract Negotiations – Service Agreement – Quality Agreement • Technology Transfer – Project Management – Production Processes – Analytical Test Methods • Lessons Learned 17 Fi’s Top 10 Lessons Learned 10. For Phase III and beyond, involve commercial Outsourcing colleagues in CMO selection 9. Proactive Outsourcing – perform Technical Evaluation and Quality Audit of shortlisted CMOs. 8. Include Success Criteria, Persons-in-Plant, Language in Service Agreement. 7. Subcontractor Expectations are important for Quality Agreement; PreCommercial and Commercial QA involvement. 6. Project Management function is a critical component of Tech Transfer Team – single Point-of-Contact with CMO. 5. A Joint Steering Committee is highly recommended for governance and issue escalation. 4. Schedule F2F Joint Project Team meetings for kick-off, deliverables review, and lessons learned. 3. Train JPT members upfront on roles and responsibilities, and in case of global contracts, provide Business Across Borders training. 2. Plan for at least 2 Tech Transfer pilot-scale runs and at least 2 Engineering fullscale runs prior to cGMP manufacture. 18 1. Outsourcing is still a risky business. 19 Acknowledgement Bernie Huyghe Ali Javadian Pat Droege Tom Mueller Gretchen Peck Sonia Kansal Mary Solomita Vinnie Turula La Jolla, California St. Louis, Missouri Pearl River, New York Biotherapeutics & Vaccines Outsourcing 20