WHEN, WHY AND HOW TO OUTSOURCE BIOMANUFACTURING: THE ROLE OF SINGLE USE TECHNOLOGIES

Transcription

1 WHEN, WHY AND HOW TO OUTSOURCE BIOMANUFACTURING: THE ROLE OF SINGLE USE TECHNOLOGIES John Coyne Sr. Manager: Bioprocessing Research and Development Manufacturing Pfizer, Inc. 23 Years Industry Experience, 8 Years with Pfizer 01Nov16

2 Innovating to bring therapies to patients that significantly improve their lives. We make medicines and vaccines that help people when they are sick and prevent them from getting sick in the first place.

3 Silk Stockings and Biopharmaceuticals Ludwig VonMises.the queen of England and silk stockings.

4 Drivers (1 of 2) Economic 1.3 billion people in billion in USA 312/321 GDP per capita $5575 PP $7808 in 2015 (40% increase). USA $49k/$55k 12% increase $7.3T GDP second largest. (2011) $10.7 T in 2015 USA $15.5 / $17.9T 5.1% of GDP healthcare spending third largest pharma market in the world

5 Pharma Revenue by Country 2012 Global: Pharmaceutical Market Growth, 2012 Global: Pharmaceutical Market Size, 2012 Venezuela Argentina China (Hospital) Latin America Brazil India (Retail) Australia / New Zealand Mexico Japan (including Hospitals) Germany North America United States Europe (Top 5) France Canada United Kingdom Italy Spain (% Change) North America United States Europe (Top 5) Japan (including Hospitals) China (Hospital) Latin America Germany France Brazil Canada Italy United Kingdom Spain Australia / New Zealand India (Retail) Mexico Venezuela Argentina ($B) Note: Percent change in retail drug sales for the 12 months to October Note: Market sizes are from retail drug sales for the 12 months to October Source: Decision Resources. Based on data released December 2012 from IMS Health DR / Decision Resources, LLC. 5

6 Drivers (2 of 2) Regulatory Chinese specific Clinical Trials Long review times (Changing) 4-6 years. Ongoing reforms Clinical reviews / data integrity 13 th 5 year plan focus on technology, including biotech. Ongoing smaller reforms. Unwritten expectations.

7 Why does it take so long? Small Scale POC Site Selection Funding Approval Regulatory Engagement De Risk TT to China Mfg IND lots Analytical Characterization Stability Reg / Tox Study CTA Submission CTA Review DS Facility Facility Infrastructure DP facility Stick Build TT to new facility Pilot Lots Training Mfg Clinical Lots Clinical Lot release Clinical Phase 1 (+report) Clinical Phase 3 (+report) Manufacture PV PV Stability NDA Review GMP Inspection Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3Q4Q1Q2Q3 CFDA Approval 7

8

9 GE Value Direct Benefits.. Process Development GE Marlboro Scale down and Disposables conversion GE Shanghai Mfg Reg/Tox/ lots for CTA application to take off critical path DS Facility Build KuBio Greenfield 18 months from PO to OQ complete Provides equipment SOPs Allows new team to focus on DP facility startup GE Shanghai Operator training in parallel to construction on exact equipment and procedures Tech Transfer GE Marlboro Support 200L xfer to Shanghai Support 2000L xfer to Greenfield site GE Shanghai Support startup in Greenfield site China Knowledge 100 years in China Long Term View GE Govt/Reg Affairs Sophisticated / Experienced strategists GE Finance Experienced with tax and financing IP Protection Established controls and firewalls in place already

10 Facility Implications Lower cost become cost effective at making small batches. Biggest impact when looking at whole operation Multiproduct Design = Volume Family Approach Contamination control In an integrated development process, less TT time Low Cost Cheap (Opportunity) No CIP / SIP More replication Technology progression drives improvement AND cost reduction. Hotel phone call cell phone Face Time Platforms easier to support Continuous Manufacturing out not up PAT and continuous verification Single use Many examples one can Google 38.1% single-use products offer a cost savings % indicate the high cost was a challenge to using single-use products 2 Time savings and flexibility key in decision process 2 Footnotes: 2. BioPharm International, Rita Peters, Jan Aspen Brook survey, 90 respondents

11 Problem statement: high level n NPV = t=0 R t (1+i) t Where: t = time of cash flow i = discount rate, opp cost R t = net cash flow at time (t) Year 1 Year 2 Year 3 Year 4 Year 5 Year 6 Year 7

12 Faster to Market Realize revenue stream earlier While standard construction benefits exist. Construction times shorter Modular approach (building and unit op) lots of already installed capacity. Reduce need for facility controls through engineering Yes No other areas offer larger opportunity Integrated Development Transportability of data Common platform easier support (more next page) Move the facility Development work before construction

13 Process transfer to Fast Trak Team in China GE s Currently Fast Trak working Asia and with US GE teams Fast collaborating/training Trak team MBO for during further the batches 200 L single-use to buy down production regulatory batches risk Marlborough, MA, U.S.A. Shanghai, China Q Ian Read Review_vF.pptx 13

14 Outsourcing Process development GE s Fast Trak Services PROJECT NEEDS Design scope of work Convert from conventional to single-use technologies Scale-up from 10 L to 200 L, with ultimate target of 2000 L, bioreactor for two biosimilar mab molecules Deploy a global, flexible, scalable, costeffective biosimilar manufacturing platform under aggressive timelines Be first to market in emerging regions Process transfer to customer s site in emerging region PROJECT DELIVERABLES Aggressive timelines: completion of work in less than six months Molecule biosimilarity comparison after process transfer to single-use technology Process and equipment design Protection of customers intellectual property (IP) Communication with and alignment of global teams Real-time scope/process changes and definition phase progressed

15 Outsourcing Process Development GE s Fast Trak Services Initial scope 4 10 L single-use runs Process transfer Generation of protocols solution records bill of materials Process confirmation Technology Transfer Another set of 10 L single-use runs were performed Process transfer Generation of protocols solution records bill of materials Proof of concept Scale-up L single-use runs Generation of protocols solution records bill of materials Process scaled from a vial to complete purification of two biosimilar mab molecules with the goal to manufacture at 2000 L scale Pfizer Confidential. For Internal Use Only. Q Ian Read Review_vF.pptx 15

16 Conversion to Single-use GE s Fast Trak Services Upstream process Downstream process Critical parameters: Seed train, agitation rates, ph, dissolved O 2, sparge pore size, feed, gassing, and bioreactor control strategies. Critical parameters: Velocities, resin binding capacities, collection criteria, flux rates, temperatures, pressures, ph, conductivity, hold times, storage conditions. Q Ian Read Review_vF.pptx 16

17 Product A & B: upstream process results Product A 10 L confirmation run 200 L run L run 2 Maximum cell density M cells/ml M Cells/mL M Cells/mL Product titer 2.4 mg/ml 3.3 mg/ml 3.2 mg/ml Comparable to client data Product biosimilarity confirmation Low but acceptable Yes Yes Confirmed Confirmed Confirmed Product B 10 L confirmation run 200 L run L run 2 Maximum cell density M cells/ml M cells/ml M cells/ml Product titer 3.4 mg/ml 3.4 mg/ml 3.9 mg/ml Comparable to client data Product biosimilarity confirmation Yes Yes Yes Confirmed Confirmed Confirmed Q Ian Read Review_vF.pptx 17

18 Product A: downstream process results Product A 10 L confirmation run Step recovery 200 L run 1 Step recovery 200 L run 2 Step recovery Clarification 86% 88% 88% Protein A +VI 93% 102% 91% Anion exchange 89% 86% 99% UFDF 95% 98% 97% Total process recovery 68% 76% 73% Comparable to client data Product biosimilarity comparison Yes Yes Yes Confirmed Confirmed Confirmed Q Ian Read Review_vF.pptx 18

19 Product B: downstream process results Product B 10 L confirmation run Step recovery 200 L run 1 Step recovery 200 L run 2 Step recovery Clarification 84% 85% 93% Protein A +VI 114% 98% 95% Anion exchange 93% 86% 93% Cation exchange 73% 78% 79% UFDF 95% 94% 96% Total process recovery 62% 53% 65% Comparable to client data Product biosimilarity comparison Yes Yes Yes Confirmed Confirmed Confirmed UFDF = ultrafiltration/diafiltration Q Ian Read Review_vF.pptx 19

20 Fast Trak Project outcomes More products addresses probability nature of revenue stream to some degree Conversion from conventional to single-use technology and scale-up from 10 L to 200 L Project completed in 5 months (incl. completion of 6 10 L batches, L batches, generation of > 50 process documents, and 4 complete bills of materials. Customer internal timeline for similar scope of work was estimated to 18 months. Black box approach to protect customer s intellectual property (IP) (initially, culture media and feeds, several process solutions, and biosimilarity analytics were unknown). Succeeded in titer requirement of 3 4 g/l. Product met biosimilarity requirements.

21 Process transfer to China GE s Local Fast Trak services teams support process transfer to emerging regions, sourcing of local raw materials, and understand local government and regulatory requirements FAST TRAK MANUFACTURING SERVICES At GE Process development Analytical development Scale-up Documentation preparation cgmp manufacturing Train/educate customer team TransPlant PROCESS ANALYTICAL DOCUMENTATION TRAINING START-UP Single-use FlexFactory platform KUBio facility cgmp = current good manufacturing practices 21

22 Replication Ability to ensure consistent supply Quality implications (positive) counter to distributed control Regulatory? Aspiration Copy Exactly & Leverage Typically based on physical location now. Stability for filing Center support for remotely run plants?

23 Innovation anticipating market changes Technology Transfer Process development Global Support, Troubleshooting, Data Acquisition and Analysis Pfizer Confidential. For Internal Use Only. Q Ian Read Review_vF.pptx 23

24 28Jun16 Hangzhou Site Groundbreaking Ceremony

25 Parcel 1 Block and Stack (Phase 1) 1) 中国杭州辉瑞生物科技工业中心

26 Site Rendering Dragon Well 26

27 KUBio manufacturing facility The KUBio facility is GE s cgmp-compliant process solution for mab production. The modular units are factory-built, final assembly on customer site. Because different parts are developed concurrently, your KUBio facility is fully operational in just 18 to 24 months. Assembled on brown or greenfield site Built, assembled, qualified, and ready-torun within 18 to 24 months Includes FlexFactory single-use platform L to L facilities Segregated up- and downstream operations, including gowning

28 Multiproduct facilities More products addresses probability nature of revenue stream to some degree Flexible for future needs that are unknown today As volume of finished goods per plant gets smaller what is our role as manufacturers?

29 Approaches on Modular addresses all above Bios DS - several options mabs have a fairly common platform Cell Lines and development work to switch No platform for vaccines Aseptic Reduce clean room size / number Why Grade C outside of an isolator? Why isolator engineering solutions in development Drug development why vials or syringes? o Other delivery methods that don t require sterile dosage forms.

30 Conclusion China is pulling us into the Future The role of pharmaceutical manufacturing will change to reflect business & technical drivers Facilities will evolve accordingly Our role today is to anticipate those needs