A Global Technology Roadmap for Biopharmaceutical Manufacturing… · 2018-11-11 · A Global...
Transcript of A Global Technology Roadmap for Biopharmaceutical Manufacturing… · 2018-11-11 · A Global...
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
A Global Technology Roadmap for Biopharmaceutical Manufacturing: An Update from BPOG
Presentation to Bioprocess International (BPI)Boston, MA 2016Bert Frohlich, Thomas Ryll
5th October 2016
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Agenda
▪Who is BPOG
▪What is a Technology Road Map:Introduction to the Biopharmaceutical Industry Collaboration
▪Why a Road Map is needed. Why now…
▪How is the Map Created: The Methodology
▪Now!: Overview of key roadmap content to dateoMarket trends & business driversoBiomanufacturing scenariosoInitial process modelling results
▪When: Next Steps
27/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Who is BioPhorum Operations Group (BPOG)Industry collaboration that brings together 33 bio-manufacturers, collaborating in six phorums to accelerate the industry
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Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
6 Phorums covering all aspects of operations and accelerating biopharma industry’s journey to maturity
4
Drug Substance
DevelopmentGroup
Fill Finish Information Technology
TechnologyRoad Map
Supply Partner Phorum
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http://www.biophorum.com/
http://www.biophorum.com/accelerate
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Agenda
▪Who is BPOG
▪What is a Technology Road Map:Introduction to the Biopharmaceutical Industry Collaboration
▪Why a Road Map is needed. Why now…
▪How is the Map Created: The Methodology
▪Now!: Overview of key roadmap content to dateoMarket trends & business driversoBiomanufacturing scenariosoInitial process modelling results
▪When: Next Steps
57/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
What is a Technology Road Map?!
An industry technology roadmap is –
a dynamic and evolving collaborative technology management process
For:
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▪determining precompetitive critical needs and drivers,
▪ identifying technology and/or manufacturing targets, and
▪assessing/modeling potential solutions
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Agenda
▪Who is BPOG
▪What is a Technology Road Map:Introduction to the Biopharmaceutical Industry Collaboration
▪Why a Road Map is needed. Why now…
▪How is the Map Created: The Methodology
▪Now!: Overview of key roadmap content to dateoMarket trends & business driversoBiomanufacturing scenariosoInitial process modelling results
▪When: Next Steps
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Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
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 8
Complex industry has traditionally held back innovation….
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Audacious goal:
▪ Focus the industry on longer term strategy & 10+yr time horizon
▪ provide direction, and
▪ defining needs, difficult challenges and potential solutions
▪ resolve those critical needs
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Revolutionise the way the industry develops longer term
transformational manufacturing and technology capabilities
,
To agree an industry technology strategy
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Why is this approach different this time?
▪More collaborative cross-company/institution approach
▪ To include all stakeholders…
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10
May 2016
BioManufacturers
Suppliers
BioManufacturers
Regulators
Academia
Suppliers
• Cultural and Behavioral
• Regulations and compliance
▪ Longer-term view (we’re all better off in the long run if we work together…)
▪ Addressing barriers to implementation:
Academia
Regulators
BEFORE AFTER
• Commercialization timeline risks
• Product comparability risk
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Agenda
▪Who is BPOG
▪What is a Technology Road Map:Introduction to the Biopharmaceutical Industry Collaboration
▪Why a Road Map is needed. Why now…
▪How is the Map Created: The Methodology
▪Now!: Overview of key roadmap content to dateoMarket trends & business driversoBiomanufacturing scenariosoInitial process modelling results
▪When: Next Steps
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Technology Roadmapping © BioPhorum Operations Group Ltd
Following the Lead from other Industries…..Using method from University of Cambridge’s Institute of Manufacturing
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Semiconductor Industry
NASA
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Technology Roadmapping Steering Committee
▪ Developed a strong Steering Committee
• Required decision making
• Driving roadmap
• Subject matter experts access
▪ Diverse participants
• 17 biomanufacturers
• 6 supply partners recently joined (and growing)
• Academics & regional centres, e.g. MIT, AMBIC, CPI, SEDB, NIIMBL
▪ Over 130 people involved globally
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CompanyAbbvieAstraZenecaBayerBiogenFujifilmdbGSKImmunogenJanssenLonzaLillyMerck MSDEMD SeronoPfizerRocheSanofiShireTakeda
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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 TypesFix: 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 ScenariosFix: Throughput, Product mixVary: Process/facility design
1
3
5
2
4
Identify Potential Solutions and Alternatives
Define Development Timelines and Pathways
Model
Analyze
Plan
6
7
8
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Agenda
▪Who is BPOG
▪What is a Technology Road Map:Introduction to the Biopharmaceutical Industry Collaboration
▪Why a Road Map is needed. Why now…
▪How is the Map Created: The Methodology
▪Now!: Overview of key roadmap content to dateoMarket trends & business driversoBiomanufacturing scenariosoInitial process modelling results
▪When: Next Steps
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Technology Roadmapping © BioPhorum Operations Group Ltd
Evaluating Biopharmaceutical Market Trends (Step 1)
16Feb 2016Technology Roadmapping
Robust
Pipelines
Biosimilars
Competition
Diversification
of product
groups
Payer
pressure on
cost of drugsIn-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
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Collective Brainstorming by Industry Experts
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Defining Main Business Drivers and High Level Roadmap Structure (Step 2)
Technology Roadmapping Update
Speed Cost Flexibility Quality
Diversification
of product
groups
Payer pressure
on costIn region
manufacturing
Personalised
medicine
Real time
Release
Industry Trends
Technology Areas
Enablers(Examples)
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Modular and mobile
Knowledge management
Process intensification
Continuous processing
Automation
Inline monitoring
Technology
standards
Vendor
interaction
Supplier
Management
Regulatory Harmonisation
Keep
workforce
capable
Multi-use and
flexible
facilities
Business Drivers
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Developing Representative Scenarios (Step 3)
▪Purpose of Business Scenarios
• To help evaluate biomanufacturing strategies and technologies that will have greatest impact for a particular set of business drivers
• Not all companies have the same set of ‘Key’ business drivers or metrics
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▪Purpose of Biomanufacturing / Facility Type Scenarios and Options
• Represent today’s typical facilities (current state-of-art)
• Many companies have existing assets that need to be utilized and even potentially expanded
• Serve as starting point for technology road map
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
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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▪ Limitations of Current Models
• Performance estimates are not absolute. Models are not calibrated to any specific circumstance such as location or specific organizational context
• For relative comparisons only; Default values for base line comparison (e.g. price of raw material costs, equipment and labor, installation factors
▪ Excluded
• Site purchase, staffing cost and raw materials & consumables up to production
• Central development labs and site offices
• Site warehousing
• Black utilities
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Processing Options (and Symbols)
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Stainless Steel (SS)
(Conventional)
Single-use(SU)
(Disposable)
Upstream Process
(Bioreactors)
Downstream Process
(Purification Train)
Batch
(Fed-batch)
Continuous
(Perfusion)
Batch Continuous
Hybrid(SS+SU
(Volume
dependent))
Technology Roadmapping © BioPhorum Operations Group Ltd
Modeling Cases
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SS-B / B
SU-B / C
High-demand Product
(High Volume)
SU-C / B
10,000 kg/yr 1,000 100 10 1 0.1
Low-demand Product
(Low Volume)
Design
SU-B / B
SU-C / C
SS-B / C
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Process Modeling – Biopharm Services using BioSolve Software
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▪ Initial modelling done using a platform mAb process• Targeting 1,000 or 100 kg per year output
• Using 12.5kL SS or 2kL SUB reactor and combinations of B/B, B/C, C/B and C/C processing
• Capital Investment and COG
• Parameter sensitivity analysis
Batch Downstream example
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Overview of modeling 1,000 kg and 100 kg output per year
▪ Next round of modeling will float output assuming more realistic facility designs (“6-pack” facilities)
▪ Initial exercise already useful in pointing to opportunity areas
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9 month duration
1,800 L 600 L
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Modelling 1,000 kg/year Output
▪ Continuous downstream processing reduces COG
▪ Continuous upstream processing has no cost benefit over batch
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Net Present Cost: Scaling up vs. Scaling Out….
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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 © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Batch versus Continuous, 1,000 kg using 2,000L scale
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A few Results of the Initial Process Parameter Sensitivity Analysis
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▪Upstream and Downstream Yields are major cost drivers
0
20
40
60
80
100
120
140
0 5 10 15 20
CO
G (
$/g
)
Titer (g/L)
12.5k B/B
12.5k B/C
2k B/B
2k B/C
0
20
40
60
80
100
120
140
60 70 80 90 100
CO
G (
$/g
)
% Yield
ProA Yield
Polishing Yield
ProA Yield 100kg
Polishing Yield 100 kg
100 kg/year
1,000 kg/year
Cell Culture Yield Downstream Recovery
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Interaction between Perfusion Rate and Cell Concentration and Productivity
▪ Cell specific perfusion rate and perfusion media costs are major cost driver
▪ If cell specific perfusion rate is increased, higher cell mass and higher specific productivity is required to maintain cost
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Initial Flags for Technology Opportunities
▪Upstream batch titer• 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
▪ Production cell lines• Cell specific productivity• Impurities and product quality features (glycans)• Harmonized expression system
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Conclusions and Next steps
▪Significant progress has been made in bringing the industry together for this precompetitive collaboration
▪A work in progress, More work to be done
▪Will take some time and a few iterations. First time this is being done with wide industry participation
▪Vendor and academic partner participation
▪Technology innovation opportunities are beginning to be identified
▪More modeling to be done to help assess value and prioritize
▪Plan to publish completed road map before mid of 2017
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Acknowledgements
▪Andrew Sinclair
▪Alan Calleja
▪Paul Ilott
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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!
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
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.
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▪Back-Up Slides
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Modelling 100 kg/year Output
▪ Continuous downstream processing reduces COG
▪ Continuous upstream processing has no cost benefit over batch
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Could go out
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Batch versus Continuous
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Roadmap plan through to publication
2016 2017
A M J J A S O N D J F M A M J
Face to face meetings
Review points
Steering committee contribution
Roadmap Team (RT) activity
Industry stakeholder engagement
Communications
Final approvals
TR03 – Roadmap team meeting (12-14 Apr’16)
TR04 – Finalising the roadmap (20-22
Sep’16)
TR05 – Implementation planning and Industry
Response
BPI article
1. Summary document
review
2. Detail document
review
Freeze document Publish
Roadmap revision 2Support / co-ordinate
implementation
SummaryVision, Map,
Scope, Linkages
DetailNeeds,
Challenges, Solutions
OverviewMarket Trends, Product Classes,
Business Drivers, Scenarios, Modelling
Final modifications and
input from industry
stakeholders
Implementation planning and
industry responseChallenges, Solutions
Revie
w t
o c
larify
focu
s,
linkages
& s
pot
gaps
Pre
para
tion for
TR04. Lis
t to
p p
oin
ts t
o
add v
alu
e, is
sues,
debating p
oin
ts
Det
ail r
evie
w f
ollo
we
d b
y fi
nal
ch
ange
s to
do
cum
ent
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38
BPI article
BPI article
BPI conference
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
6 Phorums covering all aspects of operations and accelerating biopharma industry’s journey to maturity
▪ Drug Substance, Fill Finish, Development
Group and IT Phorums
• Accelerate the way the industry delivers near term
results making best practice development and
implementation faster, cheaper and smarter
▪ Supply Partner Phorum
• Strategic focus on the wider supply chain needs of the
industry; defining, developing & implementing
solutions
• Focus on business processes/systems & culture
The focus for this presentation▪ Technology Roadmapping
• Revolutionise the way the industry develops
longer term transformational manufacturing
and technology capabilities
• Focus on longer term strategy & 10+yr time
horizon, defining needs, difficult challenges
and potential solutions
▪ Regulatory Interactions Group
• Engage and align with Health Agencies in the
design and adoption of advances in
manufacturing
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Drug Substance
DevelopmentGroup
Fill Finish
Information Technology
TechnologyRoad Map
Supply Partner Phorum
BPOG manages the linkages to ensure
• 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
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http://www.biophorum.com/
http://www.biophorum.com/accelerate
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Business drivers
Driver Metric Description 5 yr Target 10 yr Target
Cost Total cost to supply COGs - Labour, materials, utilities, variable costs, delivery rejects. $50/gm (mAbs) $10/gm (mAbs)
Reduction of total cost to supply from 2015 values 50% 90%
Cost of upfront investment in manufacturing
Total capital cost of facility to supply 1,000,000 doses / year$100M DS facility$50M DP facility
$50m DS facility$25M DP facility
Cost of developmentStart of phase 3 process analytical formulation development to launch (1st major market approval) - reduction from 2015 levels
25% 75%
SpeedTime to make product (End to end speed)
Time from initiating Drug Substance Production (vial thaw) to completing Drug Product Production
2 months 1 month
Time from initiating Drug Substance Production (vial thaw) to completing DP Production - reduction from 2015 levels
50% 75%
Time to release product (End to end speed)
Time from completion of Drug Product production to full release of Drug Product
2 weeks 1 day
Time to produce first GMP material for the clinic
Time from DNA (molecule selection) to material available to clinic 12 months 8 months
Speed to market Time from release of phase 1 material to launch 5 years 3 years
Time to introduce a change to an existing process
Time to introduce a process change (specifically new DS site, new resin, etc)
2 months 1 month
Time to introduce a process change (eg new DS site, new resin, etc) 18 months 6 months
Facility build speed Time from build decision to ready for first PPQ batch 2 years 1 year
Flexibility Number of platforms per suite The ability to change to different platforms (eg, CHO, E. coli, yeast, gene therapy) within a suite.
3 >5
Titer Range in upstream that is directly accommodated by downstream facility fit
The ability to manage higher and wider titer ranges in both fed-batch (FB) and perfusion (P).
FB: 1 – 10g/LP: 0.5 - 5g/L/day
FB: 2 -40g/LP: 0.5 - 10g/L/day
Facility production per unit time -Utilization percentage
Time facility in use for production (rather than product changeover, cleaning, shutdown / maintenance)
>85% >95%
Quality Cost of Non-QualityDiscard rate, investigation resources. Batch record rework. Includes RMs
10% of operating costs 2% of operating costs
Assay qualityProcess Variability
Measure of process reliability.PPK for assay for all measures (release tests, CQAs, CPPs)
>1.5 >1.8
Product availability Inventory level50% reduction
2 months90% reduction
2 weeks
March 2016Technology Roadmapping 40
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Map as a Guide to Execution
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Identify Potential Solutions and Alternatives
Define Development Timelines and Pathways
Define Unions and Decision Points
Performance Metrics
Achieved?
Technology Roadmap
Direct / Recommend Collective Resource Distribution
Monitor and Redirect
• Collective Resourcing
• Collaborative Funding
• Supplier-based Funding
• Academic Collaborations
• Crowd Sourcing
Benefit Realized
Initial Roadmap
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Roadmap Teams, comprising experts from across the bio-pharmaceutical companies, have been formed to define the detailed technology needs, challenges and solutions to deliver the bio-manufacturing vision
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Roadmap Team Vision
Process Technology
Process Intensification: Intensifying production through highly concentrated reactants and products and combining unit operations into single units.
Continuous Processing: New separation and media technologies, coupled with advanced automation and process control.
In-line Monitoring and Real-time release
Process control and assurance of product quality through advanced monitoring devices, in-direct or multi-attribute sensors and PAT.
Global regulatory testing standards, advanced process control strategies and raw material characterization.
Modular and Mobile
Manufacturing systems that are quick to configure and assemble using ‘plug and play’standard designs.
Fully Automated Facility
Scale up from development to manufacturing, 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 the development, manufacturing and commercial value streams.
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Process Technology - Scenario Needs (1 of 2): (Draft - Illustrative)
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Unit Operation Scenario 1 Scenario 2 Scenario 3 Scenario 4A Scenario 4BD
esc
rip
tio
nBioreactor Volume SS >10kL BXRs Disposable 2kL BXRs Disposable 2kL BXRs Disposable <500 BXRs Disposable <500 BXRs
Bioreactor Mode Batch Continuous1 Batch2 Continuous1 Batch/Continuous
DSP Mode Batch/Continuous Semi-continuous/
Continuous
Batch/Semi-continuous Continuous Batch/Continuous
Facility Design Segregated suites/
Large footprint
Moderate footprint/
Ballroom
Moderate footprint/
Ballroom
Small
footprint/Ballroom
Small
footprint/Ballroom
Processing Low Bioburden Closed Closed Closed Closed
Product mAb and other CHO
TPs
mAb and other CHO
TPs
mAb and other CHO
TPs
mAb and other CHO
TPs
Cell/Gene Therapy
Comment Adaptions on current
facility
designs/retrofits
Continuous protein
production through
purification
High titer batch USP
processes to match
productivity of 10kL
BXRs
Highly productive
deployable facilities
Deployed at point-of-
use
Up
stre
am
Inoculum Preparation Cryobags to reduce
time to production /
N-1 Perfusion
Cryobags to reduce
time to production
Cryobags to reduce
time to production /
N-1 Perfusion
Cryobags to reduce
time to production /
N-1 Perfusion
Production Cell
Culture
Cell Density >15MM cells/mL >60MM cells/mL >60MM cells/mL >60MM cells/mL
qp >40pg/cell/day >40pg/cell/day >40pg/cell/day >40pg/cell/day
Titer/ Productivity 3-5g/L 2-3g/(L·day) 30-50g/L 3-6 g/(L·day)
Product Quality Consistant throughout batch duration
Media Media Defined/Stable / Low
cost
Defined / Stable /
Balanced / Low cost
Defined / Stable /
Balanced
Defined / Stable /
Balanced / Low cost
Viral Safety HTST or low cost viral
filter
Disposable HTST / low
cost viral filter
Disposable HTST / low
cost viral filter
Disposable HTST / low
cost viral filter
Cell Retention N-1 Microfiltration Disposable filtration
(non-fouling) /
Acoustic wave
Disposable filtration /
Acoustic wave
disposable filtration
(non-fouling) /
Acoustic wave
Bioreactor Design Reactor Design Easily cleanable / Rapid
Changeover
Long duration, robust
films and seals
Robust films Long duration, robust
films and seals
Polymers New elastomers not
requiring replacement
Defined and repeatable
E&L profiles
Defined and repeatable
E&L profiles
Defined and repeatable
E&L profiles
Sensors Multi-function; Increased robustness (e.g. SU glucose, lactate, cell mass, pCO2 etc.)
Har
vest
Harvest Primary Recovery Disc-stack
centrifugation /
Flocculation / Acoustic
wave /
Disposable
Centrifugation
See cell retention
above
Flocculation / Cell
Settling /
Microfiltration /
Acoustic wave /
Disposable
centrifugation
See cell retention
above
Clarification Re-usable depth
filtration
Gamma compatible
depth filtration
Re-usable depth
filtration
Gamma compatible
depth filtration
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Process Technology - Scenario Needs (2 of 2): (Draft - Illustrative)
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Pu
rifi
cati
on
Viral Clearance Detergent / Solvent
Virus InactivationNovel sewerable detergent
Primary Purification
(eg affinity chromatography)
• Resin cross-use• Ultra-high capacity • SS Continuous
Chromatography (eg GE PCC)
• Infinite lifetime adsorbents
• Disposable Continuous Chromatography (egPall BioSMB)
• Resin Cross-use• Ultra-high capacity• Infinite lifetime
adsorbents
• Resin Cross-use• Ultra-high capacity• Continuous
Chromatography• Infinite lifetime
adsorbents
• Disposable Continuous Chromatography (egPall BioSMB)
• Resin Cross-use• Ultra-high capacity• Infinite lifetime
adsorbents
Viral Clearance pH Viral Inactivation Modular claim • Low pH, short time• Modular claim
Modular claim • Low pH, short time• Modular claim
Secondary Purification 1 & 2 • Novel chromatography materials (Flow through or bind & elute)• Universal negative chromatography ligands (HCP/DNA scavengers)• High capacity membrane adsorbers (Flow through and bind & elute)• Low holdup scalable membrane devices for membrane adsorbers
Viral Clearance Viral Filtration • High capacity – re-usable viral filters• Absolute virus rating to streamline virus safety
Ultra-filtration /
Dia-filtration
Ultrafiltration Membrane cross use
Increased membrane
lifetime
• Membrane cross use
• Robust single pass TFF
Membrane cross use
Increased membrane
lifetime
• Membrane cross use
• Robust single pass TFF
Diafiltration Single-Pass Diafiltration High area disposable TFF Single-Pass Diafiltration
Buffer Management • Buffer on Demand• Buffer Dilution• Novel: Inprocess DSP Formulations
• Buffer consolidation• Increased column binding capacity
USP
+ D
SP
Novel Technologies • Affinity Partitioning• In-Situ Capture• Expanded Bed
Adsorption• High resolution
product related impurity separations
• Continuous Crystallization
• High resolution product related impurity separations
• Novel cell retention devices
• Aqueous 2 phase separation
• Protein Crystallization• Affinity Partitioning• In-Situ Capture• Expanded Bed
Adsorption• High resolution
product related impurity separations
• Novel cell retention devices
• Continuous Crystallization
• High resolution product related impurity separations
• Novel cell retention devices
General Needs • Cross-use of consumables among different molecules• Enhanced PAT tools• Advanced process control (eg. Multivariate statistical process monitoring
with feedback adaptive control)
• Rapid methods for column lifetime and cleaning studies\
• Standardization of connectors (both traditioanal and aseptic)
• Simplified viral clearance validation
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Inline Monitoring and Real-time Release: (Draft - Illustrative)
457/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Modular & Mobile: (Draft - Illustrative)
467/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Automated Facility: (Draft - Illustrative)
▪Full integration across all systems
▪ In-line, real time monitoring
▪Management of data
▪High availability automation systems
▪Reduction of manual labour through the use of robotic systems
▪New technologies and inclusion of robotics
477/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Knowledge Management: (Draft - Illustrative)
487/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Supply Partner Management: (Draft - Illustrative)
▪Openness & Trust
▪EDE & Supplier Integration
▪Standardisation
▪Quality Built-in
▪Forecasting & Demand Planning
497/6/2017
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Regulatory Interaction: Regulatory Engagement Plans
Target Objective Contact Timing Achievements / Next Steps
FDA CDER ETT
• Introduce BPOG and plans for Technology Roadmap• Request Industry Meeting as part of TR Implementation• Involve in TR Meetings (e.g. TR04)
Dr Sau (Larry) Lee, FDA
Q4, 2016 • Introductory TCs• Sent TR update• Agreed principle of an Industry Meeting with ETT
FDA CDER OPQ OBP
• Introduce BPOG and TR•Provide education session for Reviewers• Invite to attend TR04
Chikako Torigoe, FDA
26th
September 2016
• Introductory TCs and discussed potential topics• Sent TR update and discussed specifics• Education Session 26th September 2016
MHRA Strategy & Innovation
• Introduce BPOG and TR• Determine potential of joint interest• Agree further meetings
Ian Rees,MHRA
Q4, 2016 • Sent BPOG W/S and TR update• Met F2F in March 2016• Agreed to hold Periodic Review
ANVISA • Industry Meeting to address issues with long approval lead-times• Identify other opportunities towork together
PAS (Robin), BPOG
2nd August 2016
• PAS/ANVISA Meeting held 2nd August 2016• Further engagement agreed (e.g. Workshops)• Opens updebate on next LATAM country
FDA • Education Session of PAT for Lyo PAT for Lyo(Dawood), BPOG
September 2016
• Determined Regulatory approach and content for FDA audience
CASSS • Establish closer working relationship• Determine how to plan for BPOG sessions in CASSS Events
Nadine Ritter, CASSS
January 2017
• Agreed to collaborate on topics and events• Session planned at WCBP for January 2017. Need to prioritise topics
CORE Plan a session with ASEAN Silke Vogel Q2 2017 • Discuss follow up from BPOG Singapore
7/6/2017Reg Int Strategy September 2016 50
Technology Roadmapping © BioPhorum Operations Group Ltd© BioPhorum Operations Group Ltd
Emerging Regulatory Themes
▪Making the right connections at the right time with Regulators
▪Opportunities for Training/Education
▪ Industry Adoption/Implementation of Current Best Practice
▪Enhanced Support to Supply and Patient Challenges
▪Further development of Standards and Harmonisation
▪Global Approach to support robust and reliable supply chains
▪Align on Language and Definitions
517/6/2017