Biotech Resources Group was invited to Qingdao (1hr North of Shanghai) to present on the challenges of biosimilars in China given the need to keep pace with increased commercial demand.
2. Introduction
• Biosimilar Drivers & Challenges in China
• Large-Scale Manufacturing Story
• Business Justification - Commercialization (>10 years)
• Key Success Factors
3. Introduction
Robert Valdes (Bob)
GMP Consultant and V.P. Business Development
Biotech Resources, USA
22 years experience in biotechnology: Manufacturing
Human Genome Sciences, Lonza, Charm Sciences
Advisory Board—Johns Hopkins (2011)
Co-Founder—Biotech Resources (2000)
Founder—RRMS Inc. Supporting the MS Community (2002)
BA Microbiology—University of New Hampshire
MSc Biology / BioProcessing—University of Massachusetts
MBA—Johns Hopkins Carey School of Business
4. Biosimilar Drivers & Challenges
Drivers
New Sector / High Economic Potential
• 12th 5-Year Plan: Healthcare Reform
• Expected Discount vs. Innovator
• Rising Prosperity / Treatment naïve
• Customer price sensitivity: High
• Large Market / High CAGR %
• Success, Time, Cost: Favorable
Patent Expiry: $54Bb before 2020
6. Biosimilar Drivers & Challenges
Challenges
• Marketing & Differentiation
• Product Approval does not guarantee revenue
• Innovator has 20 yrs collective experience
• Switching Costs: Physicians need data
• May impede adoption / market penetration / delayed revenue
• Innovatorʼs 2nd/3rd generation Biobetter
7. Biosimilar Drivers & Challenges
Challenges
• Competition: Innovator vs BioSimilar
• Kilograms / Annum: High
• Facility Expansion, Build New or Partnership
• Cost ($/gram) control to hedge against expected discount
and NDRC/NRDL action
• Project: Strict Adherence to Quality/GMP
• Manufacturing Process is complex
8. Large-Scale Manufacturing Story
• Project map: 50,000 ft view
• Business Rationale & Justification
• Core Team Hiring and Training
• Quality Systems
• Design Development—Procurement—Start-up -Comm/Val
• Equipment / New Technologies
• Strategic Alliances & Benchmarking
• BLA Approval & Celebration!
9. Large-Scale Manufacturing Story
Project map: 50,000 ft view
Project Expenditures
100
75
50
25
0
Business Rationale Design & Project Planning Execute Release for GMP
10. Large-Scale Manufacturing Story
Business Rationale & Justification
• Facility: Capital appropriation >$100MM ($1000/ft2 US)
• Working Capital = Raws + WIP +BDS+FDP
• Financial Evaluation: pipeline, customer need (kg), pricing, royalty
burden, 2-4 years, innovator / FOB / BioBetter
• Scenarios: CMO vs Build vs JV
• Scenarios: Scale vs Titer vs $/gram
• Key Success Factor #1: Alignment on cost, time, resources, and risks.
All departments highly participative
11. Large-Scale Manufacturing Story
Core Team Hiring, Ramp-up, and Training
• Key Success Factor #2 : Hire the core team early
• You will always be training / Develop training system with QA
(Quality Assurance) as workers commission the facility.
• Hiring takes time. Training takes time. Priority.
Percentage of Fully Staffed Facility
100
50
0
Core Team Design / Plan Execute GMP (1/2 Max) Full Speed
12. Large-Scale Manufacturing Story
Quality Systems
QSIT (21 CFR Part 820)
Quality Systems Inspection Technique: Evaluate effective implementation of
Quality Systems / Subsystems and satellite programs
• Goal: Determine the firmʼs state of compliance by focusing on the key elements from a
top-down perspective.
• Quality Policy, Quality Plan: translated into procedures/activities/Instructions relevant
to the product produced
• Management Reviews (suitability and effectiveness of the Quality System)
• Evaluate subsystems for adequacy based on findings, trends; Metrics
• Leverage electronic systems early: CAPA, Training, Documents, Metrology, Inventory
• Leverage electronic systems early: Data Monitoring, EBR, Barcode, Wireless Scan
http://www.fda.gov/downloads/ICECI/Inspections/UCM142981.pdf
13. Large-Scale Manufacturing Story
Quality Systems (conʼt)
QSIT (21 CFR Part 820)
Key Success Factor # 3-QA/QC will integrate very early to provide guidance
on design as it pertains to:
• Material Systems
• Facility/Equipment System Management
• Production Systems—Batch Records, Tech Transfer
• Microbiology—Environmental Control, Facility/Personnel Hygiene
• Training (always training)
• Personnel Flow, Waste Flow, Segregation, Facility Protection
• Product Sampling / Testing: Analytical Chemistry, Immunoassay, PCR
14. Large-Scale Manufacturing Story
Design Development
• Conceptual/Prelim Design: Process Description, PFD, Facility Energy/
Utility balances, Major Equipment Lists, General Arrangement , Site Plan,
Design Bases (Piping, Electrical, Equipment, Civil, Structural), Cost
estimate summary
• Detailed Design: Utility Summary, Equipment Specs, Diagrams,
3D-model
• Procurement & Construction Management, Safety, Quality,
and Permitting
• Definitive Cost estimate
• Start-Up/Commissioning / Validation
• Engineering Runs and Release for GMP
15. Large-Scale Manufacturing Story
Equipment and New Technologies
• Manufacturing Strategy must be designed for ease of scale-up
and tech transfer
• Insource and Outsource as part of facility utilization model
• Innovator and Biosimilar companies have access to modern technologies
• Expression systems, Upstream, Bioseparation, etc
• Deploying new technology platforms should have thorough
regulatory review
• Long lead times and price: bioreactors, columns, Centrifuge,
BDS freeze units
• Lead times will force the order of procurement and resource deployment
16. Large-Scale Manufacturing Story
Strategic Alliances & Benchmarking
• Key Success Factor #4: Leverage peerʼs experience to
compress learning curve
• Facility Design: Design ideas / Lessons learned / PAI trends
• Optimize facility utilization and supply continuity
• Internships / Training
17. Large-Scale Manufacturing Story
BLA Approval and Celebration
• >10 years
• Design, Build, Operate 24/7 to provide phase III and commercial supply
• Key Success Factor #5: Celebrate along the way
ASSEMBLE APPROVAL
LAUNCH!
Database Lock BLA Filing PAI
18. Large-Scale Manufacturing Story
Key Success Factors
Key Success Factor #1: Must alignment on cost, time,
resources, and risks. All departments project aware
Key Success Factor #2: Hire the CORE team early
Key Success Factor #3: Integrate with QA/QC early in project
Key Success Factor #4: Benchmark / Learn from peers
Key Success Factor #5: Celebrate along the way
19. Thank You
Robert Valdes (Bob)
GMP Consultant and V.P. Business Development
Biotech Resources, USA
bobv@bobv.net
