Biopharmaceutical Perspectives of Outsourcing: what are supply chain management issues and opportunities

Transcription

1 1 Biopharmaceutical Perspectives of Outsourcing: what are supply chain management issues and opportunities Presented by Dr. Philipp Hess

2 Supply Chain Management Issues and Opportunities 2 1. How do we address health care cost drivers? 2. How do we organize the supply chain? 3. What roles do consultants play? 4. What are the remaining issues and potential solutions? We = Biopharmaceutical Industry

3 Health Care Cost Drivers Are Being Addressed Early in the Product Technology Life Cycle 3 Inventing Optimizing Treatment efficiency Maturing Flanking diagnostics Targeted therapies * G. Pisano, The Development Factory (1997) High potent products Cost of failed drugs Advancement in preclinical assessment Risk mitigation thru risk based funding

4 Antibody Dosages per Patient per Year Page 4 4 Antibodies dosages still many high dosages => did not change from a decade ago

5 Approved/Late Stage ADC 5 ADC dosages are not much lower: LM GV CMC-544 T-DM1 Adcetris About 2 g per patient /year Lorvotuzumab mertansine Phase I / ImmunoGen Glembatumumab vedotin Phase II / Celldex Therapeutics Inotuzumab ozogamicin (CMC-544) / Pfizer Trastuzumab emtansine (T-DM1) / Genentech Mylotarg

6 Health Care Cost Drivers Are Being Addressed Towards the End of the Product Technology Life Cycle 6 Inventing Optimizing Maturing Cost Reduction Bio-similar regulation * G. Pisano, The Development Factory (1997) Better utilization of fixed assets using facility of the future concepts (FoF) Balanced internal/external manufacturing capacity (CMO) Increase plant agility & flexibility

7 Monoclonal Antibody Manufacturing Facilities Are Costly 7 Investment can be deferred using CMO s

8 Manufacturing Locations 8 can be changed but ONLY before phase III production or post-approval

9 SU Bioprocessing Extend the Reach of Clinical Facilities thru lower initial investment, portability, flexible add on capacity 9 kg/year Low (LV), Medium (MV) and High Volumes (HV) single-use bioprocessing facilities HV MV LV

10 Have Small Volume Plant Role for Roche s Product Life Cycles & Volume Requirements 10 Very Large (Multi Ton) Medium to Very Large Volume Conventional Stainless Steel (4-12 Bioreactors 12kL-20kL+ with 1-2 DSP suites) Annual Volume Requirement Medium/Large (250 kg 5 Tons) Small (50 kgs 250 kgs) Very Small (1 kgs 50 kgs) Clinical Launch Small to Large Volume Conventional Stainless Steel ( 3-6 Bioreactors 12kL with 2 DSP suites) Very Small to Small Volume Single Use plant, Modular SS, or Hybrid (Multiple.5kL 2kL Bioreactors ) Commercial Mature Commercial Source: Jim Miller, Vice President & Global Head of Roche/Genentech BDS Manufacturing

11 Supply Chain for Small Biopharm 11 Virtual Regional Imports/Exports Higher Risk Accepted In-line with Partnering Plan Much dependent on single locations or CMO s Small teams

12 Clinical Supply Chain Therapeutic MAb Clinic CMO Owner 12 Cell Culture& Bulk Purification Import&Testing& Release Filling& Packaging Testing& Release for EU and US Studies CMO1 (US) Owner s QC (EU) CMO2 (EU) Owner s QC (EU) CMO3 (EU) Storage& Distribution Clinical Partners (EU/US)

13 Commercial Supply Chain Therapeutic MAb Partner CMO Owner NEW 13 Cell Culture& Bulk Purification Testing& Release Filling& Packaging Testing& Release for US Market CMO4 (US) Owner s QC (US) CMO6 (US) Owner s QC (US) for European Market CMO4 (US) Owner s QC (US) CMO6 (US) Owner s QC (EU) Storage& Distribution Partner (US) Partner (EU)

14 Supply Chain for Large Biopharm 14 High Level of Quality Staffing (e.g. Amgen, J&J) Attention to Risk Management (e.g. Bayer) Use of Platform Technologies (e.g. Roche) Large network of facilities and CMO s CMO s are controlled to be like own facilities (e.g. return corridor at CMC) Project teams on both sides are 3-5 times larger

15 E.g. Roche Genentech Biologics Network 15 Internal: 11 plants at 9 locations External: ~20 CMO partners Hillsboro Vacaville South San Francisco Oceanside a Mannheim Penzberg Basel Basel/Kaiseraugst Singapore Biologics Drug Substance 5 Sterile Biologic Drug Product Source: Roche BDS

16 Supply Chain for The Vaccine Field 16 Demand vs. Capacity XXX - Projection with existing facility and capacity MLF year Focus is on Robustness, Efficiency, Capacity and Release Lead times

17 Focus on Productivity Internal Changes; % indicating Greater / Much Greater 17 NOT just about Cost anymore It s about Productivity Source Eric Langer: 9 th Annual Report and Survey of Biomanufacturing, BioPlan Associates, Inc, April 2012

18 Consultant s Role - Supporting Make or Buy Decisions 18 Input Product Program Projections Process Assumptions Output Process Model Investment plan Projected COG

19 Consultant s Role - Selecting the CMO 19 Input Product Program Technology Match Evaluation Criteria EVALUATION CRITERIA CMO 1 CMO 2 CMO 3 CMO 4 CMO 5 CMO 6 CMO 7 CMO 8 Output RFP / Pre-contract Audit Evaluation / Contracting Project Management POINT 0-3 (3 Best) Very important Small company (therefore 3 nimble, flexible 3 and cost-effective); Speak the same language 2 (& similar 3culture); Cooperation / client oriented 3 / fast response Regulatory track record 2/ cgmp compliance Appropriate capacity, scale 3 and technology Experience with clinical 1and commercial 3 manufacturing? for 1US Possibility to have a clinical 2 release 3performed by 3 QP Quotation Important Geographically close (2h 3 train ride); Simple and efficient Quality 2 system Project schedule Capabilities for additional 2 services Less Important Prior knowledge of (similar) 3 product Capability to become future 1 strategic 1 partner Stable business

20 Consultant s Role - Increasing Efficiency 20 Input Current Best Practices Current Gaps/ Pain Points Process Map (as-is processes) Output Key Metrics (e.g. deviations, cycle times) Track & Trace Training Barcoding & RFID IT Roadmap Manufacturing IT EBR Support Computer Systems Validation Project Management Process Map (to-be MES processes) Business Case / Roadmap SOP & Operation Process Automation SAP Integration

21 Consultant s Role - Increasing Efficiency Result 21 MES systems were adopted earlier for low margin high volume products

22 Consultant s Role Managing Quality 22 Input Objectives Existing Audits Quality Metrics Items of that major BPR 4 2 MM 2 0 PD 2 0 PP 6 1 PM 4 1 QUAL 3 2 Q SYS 10 1 SOP 9 3 TRAINING 10 2 TOTAL Output GAP Analysis Risk Profiling Quality Hyper Care

23 Quality Target of Industries is: 6σ 23 DPMO (defectsper million opportunities) ,1 0,01 Restaurant bills Airlines baggagecheck in Best-in-class 2σ 3σ 4σ 5σ 6σ 7σ Egypt Air (5,8σ) Air India(5,8) Lufthansa (6,6σ) Quantas, SAS Source: Motorola, Air Safety Online

24 Quality Status of Bio-Pharmaceutical Manufacturing: 2-3σ 24 DPMO (defectsper million opportunities) ,1 0,01 Restaurant bills Airlines baggagecheck in Best-in-class 2σ 3σ 4σ 5σ 6σ 7σ Egypt Air (5,8σ) Air India(5,8) Lufthansa (6,6σ) Quantas, SAS Source: Motorola, Air Safety Online

25 Patient Quality Expectation However is : 6σ 25 DPMO (defectsper million opportunities) ,1 0,01 Restaurant bills Airlines baggagecheck in Best-in-class 2σ 3σ 4σ 5σ 6σ 7σ Egypt Air (5,8σ) Air India(5,8) Lufthansa (6,6σ) Quantas, SAS Source: Motorola, Air Safety Online

26 What Does 2-3σ Mean 26 Sigma ppm Defects Yield Cost of Quality Current Mfg 2σ 3σ 308,537 66, % 93.3% 25-35% 20-25% 4σ 6, % 12-18% Quality provided to patients 5σ 6σ % % 4-8% 1-3% Data from:dr. Doug Dean & Frances Bruttin, PriceWaterhouseCoopers

27 Consultant s Role Supporting Lean 6 σ Projects 27 Input Target Processes Toolbox Process visualization Output Evaluation / Benchmarking New procedures / Ways of Working Change Management

28 Remaining Issued and Potential Solutions 28 Closing the GAP early/late and small/large Platform Processes Number of Manufacturing Sites GAP will not be fully closed between due to the different company objectives Closing the GAP intrinsic/policed quality PAT (example Pfizer NEWCON) QbD See us or contact us after the meeting