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Technology Roadmapping –Collaborating to accelerate innovation in biopharmaceutical manufacturing
Paul Ilott
March 2017
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Agenda
▪ Introduction to BPOG
▪Ambition, process and structure
▪Content of the Technology Roadmap
▪How to get involved
Technology Roadmapping March 2017 2
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Our members manufacture >90% of US and European biotech drugs
March 2017Technology Roadmapping 3
BPOG is a collaboration of the World’s top biopharma manufacturers and supply partners
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Drug Substance
Development Group
FillFinish
Information Technology
TechnologyRoadmapping
Supply Partner
BPOG has 6 Phorums covering all aspects of biopharma operations
Technology Roadmapping 4
Drug Substance, Fill Finish, Development, Information Technology
Accelerating the way the industry delivers near term results, making best practice development and implementation faster, cheaper and smarter
Supply Partner Phorum
Creating the supply chains the industry needs; defining, developing and implementing solutions for business processes, systems and culture
Technology Roadmapping
Revolutionising the way the industry develops longer term transformational manufacturing and technology capabilities
Focusing on strategy and 10yr time horizon, defining needs, difficult challenges and potential solutions
Regulatory Interaction
Ensure efforts to design and adopt advances in manufacturing are aligned through engagement with Health Agencies
BPOG Facilitation
Decisions are made at the right time, at the right place by the right people
Linkages are made visible to avoid redundancy
Synergies are leveraged through effective coordination
March 2017
© BioPhorum Operations Group Ltd
Agenda
▪ Introduction to BPOG
▪Ambition, process and structure
▪Content of the Technology Roadmap
▪How to get involved
Technology Roadmapping March 2017 5
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Audacious goal: To agree an industry technology strategy
An industry technology roadmap is a dynamic and evolving collaborative technology management process for
▪ determining precompetitive critical needs and drivers,
▪ identifying technology and/or manufacturing targets, and
▪ assessing/modeling potential solutions
to
▪ focus an industry community,
▪ provide direction, and
▪ resolve those critical needs for a specific timeframe by consensus
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A strong collaboration, bringing the industry’s top people together to contribute to & benefit from the technology roadmap
▪ Developed a strong Steering Committee
• Required decision making
• Driving roadmap
• Subject matter experts access
▪ Diverse participants
• 32 member companies from across biomanufacturers and supply partners
• Academics & regional centres, e.g. MIT, AMBIC, CPI, SEDB, NIIMBL
▪ Over 170 people involved globally
7March 2017Technology Roadmapping
© BioPhorum Operations Group Ltd
Agenda
▪ Introduction to BPOG
▪Ambition, process and structure
▪Content of the Technology Roadmap
▪How to get involved
Technology Roadmapping March 2017 8
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High level Technology Roadmap structure
Speed Cost Flexibility Quality
UncertaintyCost pressure Market GrowthNew Product
Classes
Inline
Monitoring &
Real time
Release
Industry Trends
Business Drivers
Biomanufacturing
Scenarios
Enabling
Technologies &
Capabilities
9
Process
Technology
Modular &
Mobile
Automated
Facility
Knowledge
Management
Supply
Partnership
Management
March 2017Technology Roadmapping
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
Evaluating Biopharmaceutical Market Trends
10
Robust
Pipelines
Biosimilars
Competition
Diversification
of product
groups
Payer
pressure on
price
In-region
manufacturing
requirements
Personalised
medicine
Complex Global
regulatory
environment
Strength of
Sales (Biologics)
New
Treatment
Modalities
Emerging
Markets
Social / Political
Perceptions
Clinical FailuresDose
Requirements
Market
Share
Demand
Forecasts
Rising Costs
of Drug
Development
Advances
in Systems
Biology
March 2017Technology Roadmapping
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Collective Brainstorming by Industry Experts
11March 2017Technology Roadmapping
© BioPhorum Operations Group Ltd
High level Technology Roadmap structure
Speed Cost Flexibility Quality
UncertaintyCost pressure Market GrowthNew Product
Classes
Inline
Monitoring &
Real time
Release
Industry Trends
Business Drivers
Biomanufacturing
Scenarios
Enabling
Technologies &
Capabilities
12
Process
Technology
Modular &
Mobile
Automated
Facility
Knowledge
Management
Supply
Partnership
Management
March 2017Technology Roadmapping
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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The team agreed a range of biomanufacturing scenarios that would be important over the next 10 years
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• Figure shows an approximate range of production rates typical for a given scenario and facility type.• A technology determined to have high impact across multiple scenarios would reinforce importance
to the industry.• Quantitative computational models provide valuable insight in estimating the value of a technology
or process innovation that would otherwise be difficult to predict.
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Uncertainty
▪ Regulatory approvals
▪ Demand variability
▪ Competition
Cost pressure
▪ Payer pressure
▪ Biosimilars
▪ Development
Market Growth
▪ Emerging markets
▪ Global reach
▪ In region manufacture
New Product Classes
▪ Non-mAbs, ADCs
▪ Gene therapy
▪ Cell therapy
Inline Monitoring and
Real time Release- Product Release
1-2 day
+ ↑ Quality, Efficiency &
Supply
▪ Enhanced In-Line
Monitoring
▪ Indirect and
Multivariate Sensors
▪ Multivariate Analysis
and Predictive
Modeling
Process Technologies- 90% CoGs
- 90% process
investment
▪ Process Intensification
& combination of unit
operations
▪ Continuous processing
technologies coupled
with advanced process
control
Modular and Mobile- 70% build time
- 75% CAPEX
▪ Quick to configure &
scale
▪ Standard designs
▪ Streamlined validation
Automated Facility− 50% Facility Build
Speed
− 50% OPEX costs
from current
▪ Agile, high quality, and
robust
biomanufacturing
▪ Plug and Play
▪ Open data standards
▪ Interoperability
Knowledge
Management‒ Cost of process
development
– Time to introduce a
change to an existing
process to 1 Month– Cost of Non-Quality
to 2% of operating costs
• Efficient tech. transfer
• Integrated knowledge
• Quality throughout
lifecycle
Supply Partnership
ManagementSafe, innovative supply
chains:
− Cost of quality− Time
▪ Partnerships with
quality built in
▪ Standard working,
integration and real
time Electronic Data
Exchange
▪ Shared Planning
Market Trends & Business Drivers – The Why
Enabling Technologies & Capabilities – The How
Speed
-70% build time
-80% lead time
Cost
-90% manufacturing cost
-90% CAPEX
Flexibility
-90% changeover
Demand response
Quality
10x robustness
-90% cost of quality
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
Biomanufacturing scenarios – The What
(Facility types)
5. Small-scale <50L for Personalized Medicine
Roadmap Vision
March 2017Technology Roadmapping 14
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Process Technologies example - Process technology developments are at the heart of any
efforts to increase the productivity and robustness of biopharmaceutical manufacturing. While incremental improvements to current processes will make a difference, real breakthroughs in effectiveness will come from disruptive process changes
Priority technologies & capabilities:▪ Media performance - Richer, chemically defined medias, feeds and
supplements that enable higher cell densities, higher titers, simplified media make-up, and longer media stability.
▪ Robust harvesting - Scalable harvest technologies and cell retention devices that minimize large capital investments and can handle ever increasing cell densities.
▪ Viral clearance - Standardized modular claims that provide streamlined regulatory processes and ease process development.
▪ Buffer management approaches that reduce operational constraints and space requirements for buffer preparation.
▪ Single use technologies to increase flexibility and improve closed systems, resulting in decreased capital cost, and decreased total cost of goods over the lifetime of a product.
March 2017Technology Roadmapping 15
Process
TechnologiesBenefits:
90% CoGs
90% process
investment
Key themes:
▪ Process
Intensification -
Intensifying production
through highly
concentrated reactants
& products, combining
unit operations into
single units
▪ Continuous
Processing - New
separation & media
technologies, coupled
with advanced
automation & process
control
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The collaboration can explore options for biomanufacturing in more detail (eg Net Present Cost: Scaling up vs. Scaling Out )
16March 2017
Conventional
“Six-pack”
Facility
6 x 15,000L Stainless Steel
Bioreactors
Expanded or
Multi-Facility
6 x 2,000L Single-use
Bioreactors
Total Facility Output (kg/yr)
Technology Roadmapping
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Agenda
▪ Introduction to BPOG
▪Ambition, process and structure
▪Content of the Technology Roadmap
▪How to get involved
Technology Roadmapping March 2017 17
© BioPhorum Operations Group Ltd
Roadmap edition 1 will be published on the BPOG Technology Roadmapping website and available to anyone who registers
▪Edition 1 will be published ~June’17, and can be accessed by registering on the BPOG website
• The edition 1 document will be free of charge
▪Published material (egarticles, conference presentations) can be accessed from the website
www.biophorum.com
March 2017Technology Roadmapping 18
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Strategic cycle of Technology RoadmappingValue continues to grow through 2017
2017 provides an opportunity to exploit a strong position and accelerate change in the industry.
▪ Publish roadmap edition 1 and plan / track industry response• Receive feedback and challenge from across the industry to further improve
the roadmap document• Work closely with supply partners, academia and regional hubs for rapid
demonstration of innovations and development of new technologies to address fundamental challenges
• Influence fundamental R&D that is required to deliver vision• Together use combined knowledge and experience to address the regulatory
challenges identified
▪ Roadmap edition 2• Continue to build a valuable coalition for change in the industry• Leverage the roadmapping structure and capability into adjacent squares and
deeper into critical areas
March 2017Technology Roadmapping 19
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QUESTIONS
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Anti-Trust Compliance Statement v4.0
▪ It is the clear policy of BioPhorum that Biophorum and its members will comply with all relevant anti-trust laws in all relevant jurisdictions
▪ All BioPhorum meetings and activities shall be conducted to strictly abide by all applicable antitrust laws. Meetings attended by BioPhorum members are not to be used to discuss prices, promotions, refusals to deal, boycotts, terms and conditions of sale, market assignments, confidential business plans or other subjects that could restrain competition.
▪ Anti-trust violations may be alleged on the basis of the mere appearance of unlawful activity. For example, discussion of a sensitive topic, such as price, followed by parallel action by those involved or present at the discussion, may be sufficient to infer price-fixing activity and thus lead to investigations by the relevant authorities..
▪ Criminal prosecution by federal or state authorities is a very real possibility for violations of the antitrust laws. Imprisonment, fines or treble damages may ensue. BioPhorum, its members and guests must conduct themselves in a manner that avoids even the perception or slightest suspicion that antitrust laws are being violated. Whenever uncertainty exists as to the legality of conduct, obtain legal advice. If, during any meeting, you are uncomfortable with or questions arise regarding the direction of a discussion, stop the discussion, excuse yourself and then promptly consult with counsel..
▪ The antitrust laws do not prohibit all meetings and discussions between competitors, especially when the purpose is to strengthen competition and improve the working and efficiency of the marketplace. It is in this spirit that the BioPhorum conducts its meetings and conferences.
March 2017Technology Roadmapping 21
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Back-up slides
March 2017Technology Roadmapping 22
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Six Enabling Technologies & Capabilities have been mapped in detail
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Enabling Technologies & Capabilities
Vision Benefit
Process Technology
Process Intensification - Intensifying production through highly concentrated reactants and products and combining unit operations into single units
• Minimalized capital investment• Streamlined validation processes• Decreased total cost of goods
Continuous Processing - New separation and media technologies, coupled with advanced automation and process control
• Flexibility for smaller patient populations• Speed• Reduced cost and reduced facility size
In-line Monitoring and Real-time release
Enhanced in-line monitoring unlocks potential for robust material characterisation, process control and assurance of product quality
• Enabler of Real Time Release; Product Released in 1-2 Days• Improved Product Quality, Operational Efficiency and
Reliable SupplyHardware for advanced in-line monitoring devices including indirect and multi-attribute sensors
Software to enable multivariate analysis, predictive models and closed feedback control loops
Modular and Mobile
Manufacturing systems that are quick to configure, assemble, scale and relocate, using ‘plug and play’ standard designs and standard validation approaches
• Rapid tailoring of capacity to meet demand• Manufacturing process available in weeks • Mobility of facilities through lifecycle• Reduction in capital expenditure
Fully Automated Facility
Plug and play for fast response to capacity demands, with minimal staff, time to change over, and regulatory observations, that delivers products of lowest cost and highest quality, from receipt of raw materials to final drug product.
• Quicker and cheaper facility builds and lower lifecycle costs• Readily available and usable data• Reduced mfg. deviations and non-conformances• Streamlined real-time release• OPEX reduction
Supply Partnership Management
Supply Partnership Management undertaken in a spirit of openness and trust to drive successful collaboration making best use of technology and integration of systems and processes
• Lower cost/quality ratio for raw materials, services and capex investment
• Faster to develop, produce and make changes• Safe, innovative supply chains
Knowledge Management
Integrated knowledge of product and process technology across the development, manufacturing and commercial value streams
• Accessible and applicable biomanufacturing information and knowledge, driving down development costs
• Efficiency and quality throughout product lifecycle.
Example “Enabling Technologies and Capabilities” roadmap report
Contents
• Summary
• Introduction, vision, scope & benefits
• Needs, challenges & potential solutions
• Disruptive technologies
• Regulatory considerations
• Conclusions and recommendations
24March 2017Technology Roadmapping
Selected pages from the Modular and Mobile report
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In-Line Monitoring and Real Time ReleaseEnhanced in line monitoring is a fundamental enabler of Real Time release and unlocks the potential for robust process control while improving operational efficiency, product quality and reliable supply to patients. Goals include a step change in lead-times for batch release from weeks to days.
Priority technologies & capabilities:• Raw Materials: Characterisation and Control
• Hardware: Advanced in-line monitoring devices including indirect and multi-attribute sensors
• Software: Enable multivariate analysis, predictive models and closed feedback control loops
• Technology: Advancements in rapid analytical testing for biological assays
• Quality and Business Systems: Integrated and streamlined to enable batch review by exception
• Regulatory: Contemporary and enabling Strategies
March 2017Technology Roadmapping 25
In-Line Monitoring
and Real Time
Release
Benefits
- Reduce Product Release
time from weeks to 1-2 day
+ ↑ Improved product Quality,
process efficiency and
reliability of supply
Key Themes
▪ Enhanced In-Line
Monitoring
▪ Indirect and Multivariate
Sensors
▪ Multivariate Analysis and
Predictive Modeling
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Modular & MobileBiopharmaceutical products are currently produced in fixed facilities that require significant upfront, at-risk capital investment. Modular and Mobile concepts offer an opportunity to shift to networks of smaller, standardized manufacturing facilities that can be built in less than half the time.
March 2017Technology Roadmapping 26
Modular and Mobile
Benefits:
- 70% build time
- 75% CAPEX
Key themes
▪ Flexibility:
Manufacturing systems
that are quick to
configure, assemble,
scale and relocate,
using ‘plug and play’
configurations
▪ Standard designs:
Interchangeability and
multi-supplier market
▪ Standard validation
approaches:
Harmonized approach
to validation of facilities
Priority technologies & capabilities:▪ Standardisation
• Creation of equipment standards• Enable multi-supplier
environment• Regulatory harmonisation
▪ ‘Facility as Equipment’• Management of validation, capital
& speed to install• Eliminate non-value add activity
(manufacturers & regulators)▪ Standardisation
• Quick, easy scale up of processes & facilities
• Bring production to where mostneeded – closer to patients
• Speed to market
‘Russian Doll’ model of a modular and
mobile facility, showing different layers of
facility and kit management
© BioPhorum Operations Group LtdMarch 2017Technology Roadmapping 27
Automated Facility Plug and play for fast response to capacity demands, with minimal staff, time to change over, and regulatory observations, that delivers products of lowest cost and highest quality, from receipt of raw materials to final drug product.
Automated Facility− 50% Facility Build
Speed
− 50% OPEX costs
from current
Key themes
▪ Agile, high quality, and
robust
biomanufacturing
▪ Plug and Play
▪ Open data standards
▪ Interoperability
Priority Technologies and Capabilities• Full integration across all
systems (manufacturing execution system (MES), process control system (PCS), laboratory information management system (LIMS)) results in quicker and cheaper facility builds and lower lifecycle costs
• High availability of automation depends on automation IT systems and databases. Work with supply partners is critical in this space.
• Data management for readily available and usable data
• Robotics and Mechanization toreduce manufacturing deviations and non-conformances and OPEX reduction
S95 System Levels
© BioPhorum Operations Group LtdMarch 2017Technology Roadmapping 28
Knowledge ManagementIntegrated knowledge of product and process technology across the development, manufacturing and commercial value streams
Knowledge
Management‒ Cost of process
development
– Time to introduce a
change to an existing
process to 1 Month– Cost of Non-Quality to 2% of operating costs
Key themes• Knowledge as an asset
• People, process,
content, and technology
• Efficient technology
transfer
• Integrated knowledge
• Quality throughout
lifecycle
Priority Technologies and Capabilities• Cost: The embedded use of knowledge management tools for product and
process knowledge and structured lessons learned results in efficient manufacturing processes, less errors, and reduced cost of supply/development.
• Speed: Well-structured and coordinated product/process information management (findability of information) can significantly impact time to release product and time to introduce changes to an existing process.
• Quality: Improved management of multiple knowledge formats and easy access to information increases capability to understand how critical process parameters impact critical quality attributes, improves control, and reduces the occurrence of manufacturing out of specification product.
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Supply Partnership ManagementThe supply chains to support the Technology Road map need to be safe and innovative and based on supply partnerships undertaken in a spirit of openness and trust to drive successful collaboration making best use of technology and integration of systems and processes
March 2017Technology Roadmapping 29
Supply Partnership
Management
Safe, innovative supply
chains:
− Cost of quality− Time
Key Themes:
▪ Partnerships with
quality built in
▪ Standard working,
integration and real
time Electronic Data
Exchange
▪ Shared Planning
29
Priority technologies & capabilities:
▪ Openness & Trust – Information sharing for mutual benefit
▪ Quality Built-In – ‘Right first time’ and removal of duplication
▪ Forecasting & Demand Planning – Consolidated industry plans
▪ Standardisation – ‘Plug and Play’ and simplification
▪ Electronic Data Exchange & Supplier Integration – Speed & time
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▪ Approach to modeling (using the BioSolve Software)
• 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.
• Evaluate the technology improvements proposed by the roadmap
Modeling the bio-manufacturing scenarios can identify areas for technology innovation
30March 2017Technology Roadmapping
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