A Technology Roadmapping Process to Transform the Biopharmaceutical … · A Technology Roadmapping...
Transcript of A Technology Roadmapping Process to Transform the Biopharmaceutical … · A Technology Roadmapping...
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A Technology Roadmapping Process to Transform the Biopharmaceutical Manufacturing Industry
Stewart McNaull, PhD
KBI BioPharma Inc.
BPI West Conference. Mar 02, 2017
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Agenda
Introduction to BPOG
How will a Technology Road Map help the industry ?
What does the Map entail? The Methodology
Overview of Key Roadmap Content
• Market Trends and Business Drivers
• Biomanufacturing Scenarios
• Workstream Outputs
• Scenario Modeling
Plans for publication and industry utilization
BPOG Introduction March 17 2
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Our members manufacture >90% of US and European biotech drugs
March 17 BPOG Introduction 3
BPOG is a collaboration of the World’s top biopharma manufacturers and supply partners
Mission: To create an environment where the global biopharmaceutical industry can collaborate and accelerate their rate of progress, for the benefit of all
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Agenda
Introduction to BPOG
How will a Technology Road Map help the industry ?
What does the Map entail?: The Methodology
Overview of Key Roadmap Content
Plans for publication and industry utilization
BPOG Introduction March 17 4
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What is BPOG?
Unique global collaboration
Powerful vehicle for change
6 Phorums
>50 industry changing initiatives
Industry leaders and experts working in concert
Delivering results by pooling knowledge, practices and ideas
March 17 BPOG Introduction 5
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Why is a Technology Roadmap needed for the Biopharm Industry?
Complex global regulatory environment • Multiple jurisdictions
• Varying requirements
Biomanufacturers are risk averse • The penalties are severe for delays and setbacks in drug commercialization
• Uncertainty around product comparability between scales and process changes
• New technology may not be adapted because of perceived risks to program
• Everyone wants to be a Fast Second!
Biomanufacturers and Suppliers develop technologies in isolation
Technology standardisation usually only occurs after the technology is launched
Suppliers find it difficult to innovate • Have to guess end user requirements
• Risk-reward balance is poor
Technology Roadmapping 6
Complex industry has traditionally held back innovation….
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What is the scope of the Technology Roadmapping process?
Technology Roadmapping
What it is
Process to engage and align industry stakeholders to define future needs of the industry, difficult challenges & potential solutions
Involves cross industry, supply partner, regulator, academia input
Communication of the needs, challenges and potential solutions to industry stakeholders to guide innovations
Process to monitor industry progress
What it is not
Actual implementation – that is the responsibility of the industry once the consensus on requirements is clear
Focused on short term tactical needs – the roadmap provides a long term, big picture view of industry requirements
Jan 2017 7
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Agenda
Introduction to BPOG
How will a Technology Road Map help the industry ?
What does the Map entail? The Methodology
Overview of Key Roadmap Content
Plans for publication and industry utilization
BPOG Introduction March 17 8
Following the Lead from other Industries….. Using method from University of Cambridge’s Institute of Manufacturing
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Semiconductor Industry
NASA
10 March 17 BPOG Introduction
Technology Innovation
Overview of Methodology for Technology Roadmap Construction
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Evaluate Biopharmaceutical Market Trends
Identify Main Business Drivers & Metrics
Identify/prioritize Advantages / disadvantages
Develop Representative Scenarios
Identify/prioritize Opportunities for Improvement
Model Facility Types Fix: Process/Facility Type
Vary: Throughput, utilization, product mix
Identify Potential Solutions and Alternatives
Define Development Timelines and Pathways
Technology Roadmap
Define Scenario/Options Matrix and Objectives
Business Scenarios (Key Drivers)
vs.
Biomanufacturing Facility Type Scenarios (Options)
Define
Objectives
Model Business Scenarios Fix: Throughput, Product mix Vary: Process/facility design
1
3
5
2
4
Identify Potential Solutions and Alternatives
Define Development Timelines and Pathways
Model
Analyze
Plan
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7
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Building the industry technology roadmap
BPOG Introduction March 17 12
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Agenda
Introduction to BPOG
How will a Technology Road Map help the industry ?
What does the Map entail?: The Methodology
Overview of Key Roadmap Content
• Market Trends and Business Drivers
• Biomanufacturing Scenarios
• Workstream Outputs
• Scenario Modeling
Plans for publication and industry utilization
BPOG Introduction March 17 13
Evaluating Biopharmaceutical Market Trends
14 Feb 2016 Technology Roadmapping
Robust
Pipelines
Biosimilars
Competition
Diversification
of product
groups
Payer
pressure on
cost of drugs In-region
manufacturing
requirements
Personalised
medicine
Complex Global
regulatory
environment
Strength of
Sales (Biologics) New
Treatment
Modalities
Emerging
Markets
Social / Political
Perceptions
Clinical Failures Dose
Requirements
Market
Share
Demand
Forecasts
Rising Costs
of Drug
Development
Advances
in Systems
Biology
Business Drivers
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High level Technology Roadmap structure
Speed Cost Flexibility Quality
Uncertainty Cost pressure Market Growth New Product
Classes
Inline
Monitoring &
Real time
Release
Industry Trends
Business Drivers
Biomanufacturing
scenarios
Enabling
Technologies
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Process
Technology
Modular &
mobile
Automated
Facility
Knowledge
Management
Supply
Partnership
Management
March 17 BPOG Introduction
Drug
Product
High volume
Drug
Product
Low volume
Scale Distributed
1. Large-scale Stainless Steel Fed Batch
2. Intermediate-scale Single-use Perfusion
3. Intermediate-scale Multi-product Single-use Fed Batch
4. Small-scale <500L Portable Facility
5. Small-scale <50L for Personalized Medicine
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Expert teams developed roadmaps for six key enabling technology areas
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Roadmap Team Vision / Key Themes
Process Technology
• Process Intensification - combining multiple USP/DSP unit operations • Continuous Processing: New separation and media technologies,
coupled with advanced automation and process control • Disruptive technologies and streamlined implementation/validation
Modular and Mobile
• Quick to configure manufacturing w/ ‘plug and play’ standard designs • Facility as Equipment – modular and rapid expansion. • Flexibility- expand on demand, regional deployment
In-line Monitoring & Real-time release
• Process control and product quality through advanced monitoring devices, indirect or multi-attribute sensors and PAT
• Global regulatory testing standards, advanced process control strategies and raw material characterization
Fully Automated Facility
• Scale up with a focus on automation, equipment and biology results in a fully automated facility
Supplier Management
• Suppliers become technology development partners for our industry, collaborating to solve problems
Knowledge Management
• Integrated knowledge of product and process technology across development, manufacturing and commercial value streams
March 17 BPOG Introduction
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Example of Technology Opportunities: Process Technology Workstream
Production cell lines • Cell specific productivity • Impurities and product quality features (glycans) • Harmonized expression system
Upstream batch titer • Cell line specific productivity • Perfusion applications to batch culture • Culture duration
High downstream step yields • Purity and impurity profiles (simple and robust product modalities) • Resin features (capacity and impurity clearance)
Perfusion media costs and specific perfusion rate • Media design and waste product formation • Highly concentrated and balanced media of low cost
Consumables cost • Improved filter capacity and production processes
Buffer production strategy • Buffer concentrates and in-line dilution
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Agenda
Introduction to BPOG
How will a Technology Road Map help the industry ?
What does the Map entail?: The Methodology
Overview of Key Roadmap Content
• Market Trends and Business Drivers
• Biomanufacturing Scenarios
• Workstream Outputs
• Scenario Modeling
Plans for publication and industry utilization
BPOG Introduction March 17 19
Manufacturing Scenarios and Linkage to Business Drivers
20 March 17 BPOG Introduction
Scenario Manufacturing Description Facility Type
1 Large-scale Stainless Steel 6 x 15kL SS
2 Single-use (SU) Perfusion 2 x 2kL SU
3 SU fed-batch/intensified fed-batch 6 x 2kL SU
4 Small scale SU perfusion <500L
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Defining Objectives and Options for Modeling (Step 4)
Purpose of Modeling
• Identify areas of opportunity for improvement within a given scenario / facility type.
• Compare performance between options within a scenario or between scenarios relative to a given metric
o e.g. compare estimated Cost of Goods using different process formats
• Process parameter sensitivity analysis
• Identify bottlenecks in throughput and breakpoints in technology strategy/selection.
• To evaluate the technology improvements proposed by the roadmap teams
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Modeling Approach
• Modeling approach used the manufacturing facility scenarios as a basis to ground the modeling work to industry needs.
• Biosolve software was used along with current and future state parameter inputs to calculate the COGs for each scenario.
• Mfg throughput ranges were varied to represent quantities required for clinical trials or launch stages of development.
• COGs analysis does not provide the full cost of manufacture due to differences in the upfront capital investment. Future modeling efforts may incorporate NPV based analysis to allow more comparisons across the scenarios.
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Scenarios Used for Modelling COGs
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Scenario number
Reactor volumes
Production methods 250kg/yr 500kg/yr 3.5t/yr*
1 a 6x15kL SS Batch / Batch x x x
b Batch / Continuous x x x
2 a 2 x 2kL SU Perfusion / Batch x x x
b Perfusion / Continuous x x x
3 a 6 x 2kL Batch / Batch x x x
b Batch / Continuous x x x
4 a 2x200L Continuous / Continuous x x x
b Batch / Batch x x x
Sensitivities run at 80% utilization *Model multi products at 3.5t/yr - 1, 3, 5
October 2016
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Manufacturing Scenarios COGs Summary and Throughput Impact
March 17 BPOG Introduction 23
Table 3 Comparison of Scenarios COGs at 80% plant utilization
Scenario
(batch or continuous DSP)
Cost per gram
($/g)
Annual Facility Output
(kg)
6x15KL fed-batch $43-46 2974
6x2KL fed-batch $71-79 405
6x2KL conc. fed-batch $55-59 1805
2x2KL perfusion $73-88 452
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Manufacturing Scenarios COGs Summary and Throughput Impact
Scenario
(batch or continuous DSP)
High Throughput
(1805-2974 kg/yr)
Low Throughput
(250-450 kg/yr)
Cost per gram ($/g)
6x15KL fed-batch $43-62 $199-362
2x2KL perfusion $72-92 $73-120
6x2KL fed-batch $75-83 $71-109
6x2KL conc. fed-batch $55-59 $105-168
March 17 BPOG Introduction 24
Table 4 Comparison of Scenarios COGs at High and Low Product Throughput
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Sensitivity parameters
25 October 2016
Sensitivity Range
Base - Base Base + 5 Years 10 Years
Cell line productivity (pcd) 15 20 25 30 60
Fed-batch titer (g/L) 1.5 3 5 10 20
Fed-batch media cost ($/L) 30 15 10 7.5 5
Fed batch culture duration (days) 12 14 16 10 7 Perfusion steady state cell mass (million/mL) 30 60 80 100 120
Perfusion media cost ($/L) 15 10 7.5 5 2.5 Concentrated Fed-batch (CFB) perfusion rate over last 10 days (reactor volumes per day) 2 1
Concentrated fed-batch peak cell mass (E06 per mL) 80 120
Concentrated fed-batch specific productivity (PCD) 20 60
Conc’d fed-batch titer (g/L normalized for cell mass) 12 36 ProA resin capacity 30 35 45 60 80 CEX resin capacity 60 90 120 AEX resin capacity (FT) 200 500 800 Chrom cycles number ProA 2 4 6 8 16 Chrom cycles number Polishing steps 1 2 3 4 8 Viral filter loading (kg/m2) 5 20 50 UF/DF loading (L/m2) 400 1000 5000 Chrom Cycle Time, ProA (hours) 12 24 36 32 48 Chrom Cycle Time, Polishing (hours) 3 6 9 12 18
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Scenario 1a & 1b – all unit operations
26 November 2016
6X15kL Batch USP & Continuous DSP Facility Annual Thoughput: 2974 Kg/yr
6X15kL Batch USP & Batch DSP Facility Annual Throughput: 2974 Kg/yr
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Scenario 1e & 1f – all unit operations
27 November 2016
2X2kL Perfusion USP & Continuous DSP Facility Annual Thoughput: 451 Kg/yr
2X2kL Perfusion USP & Batch DSP Facility Annual Thoughput: 451 Kg/yr
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Scenario 1c & 1d – all unit operations
28 November 2016
6X2kL Batch USP & Continuous DSP Facility Annual Thoughput: 405 Kg/yr
6X2kL Batch USP & Batch DSP Facility Annual Thoughput: 405 Kg/yr
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Scenario 1g &1h – all unit operations
29 November 2016
6X2kL Conc. Fed-Batch USP & Batch DSP Facility Annual Thoughput: 1805 Kg/yr
6X2kL Conc. Fed-Batch USP & Continuous DSP Facility Annual Thoughput: 1805 Kg/yr
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Agenda
Introduction to BPOG
How will a Technology Road Map help the industry ?
What does the Map entail?: The Methodology
Overview of Key Roadmap Content
Plans for publication and industry utilization
BPOG Introduction March 17 30
Example technology roadmap report
Contents
• Summary
• Introduction; vision, scope & benefits
• Needs, challenges & potential solutions
• Disruptive technologies
• Regulatory considerations
• Conclusions and recommendations
31 March 17 BPOG Introduction
Selected pages from the Modular and Mobile roadmap
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Timing of publication, communications & feedback mechanism
1st edition published in May 2017, freely available on BPOG website • http://www.biophorum.com/category/resources/technology-roadmapping-
resources/roadmap/
Complemented by broad communications mix • Webinars, conference presentations, articles, newsletters
Request input on roadmap’s content & scope of future editions • Individual comments or formal response from your organisation • Your organisation becoming active members of the
collaboration
Roadmapping is about stimulating an industry response, encouraging required innovation to happen
What solutions can you bring to overcome difficult challenges facing the industry?
March 17 BPOG Introduction 32
Communications
2016 2017 2018
Articles Articles & conferences
CASSS Publish 1st Edition
May’17 CASSS BIO
Engagement & feedback
Publish 2nd Edition
BPOG Website
Conference presentations
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Acknowledgements: The Technology Roadmapping teams
Jan 2017 Technology Roadmapping 33
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Disclaimer
This presentation was prepared by the BPOG Consortium. The opinions and views expressed are from the BPOG Consortium and do not reflect the views of individual member companies
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Thank You!