A Global Technology Roadmap for Biopharmaceutical Manufacturing: An Update from BPOG Philip McDuff (Biogen) Presentation to ISPE Facility of the Future Meeting 2016
A Global Technology Roadmap for
Biopharmaceutical Manufacturing:
An Update from BPOG
Philip McDuff (Biogen)
Presentation to ISPE Facility of the Future Meeting 2016
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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 dateo Market trends & business drivers
o Biomanufacturing scenarios
o Initial process modelling results
When: Next Steps
Agenda
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Industry collaboration that brings together 33 bio-manufacturers, collaborating in six phorums to accelerate the industry
3
Who is BioPhorum Operations Group (BPOG)
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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
4
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
http://www.biophorum.com/
http://www.biophorum.com/accelerate
ispe.orgConnecting Pharmaceutical Knowledge
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 dateo Market trends & business drivers
o Biomanufacturing scenarios
o Initial process modelling results
• When: Next Steps
Agenda
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© 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
ispe.orgConnecting Pharmaceutical Knowledge
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 dateo Market trends & business drivers
o Biomanufacturing scenarios
o Initial process modelling results
• When: Next Steps
Agenda
ispe.orgConnecting Pharmaceutical Knowledge
© 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
• Delays in approval have major impact
• 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 different end user requirements; company to company
• Risk-reward balance is poor
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Complex industry has traditionally held back innovation….
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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 date
o Market trends & business driverso Biomanufacturing scenarioso Initial process modelling results
• When: Next Steps
9
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Following the Lead from other Industries…..Using method from University of Cambridge’s Institute for Manufacturing
Semiconductor Industry
NASA
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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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Biopharmaceutical
Company Members
Supply Partner
MembersAbbvie GE Healthcare Life
SciencesAstraZeneca Kaiser Optical Systems
Bayer Millipore Sigma
Biogen Novasep
Fujifilmdb PM Group
GSK Sartorius Stedim
Immunogen Thermo Fisher Scientific
Janssen
Lonza
Lilly
Merck MSD
EMD Serono
Pfizer
Roche
Sanofi
Shire
Takeda
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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 date
o Market trends & business driverso Biomanufacturing scenarios
o Initial process modelling results
When: Next Steps
12
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© BioPhorum Operations Group Ltd
High level Technology Roadmap structure and approach
Speed Cost Flexibility Quality
Diversification
of product groups
Payer
pressure on cost
In region manufacturing
Personalised
medicine
Inline
Monitoring & Real time
Release
Industry Trends
Business
Drivers
Biomanufacturing
scenarios
Enabling
Technologies
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Drug Substance – Large scale stainless steel
Drug Substance – 2K scale SUS Continuous USP
Drug Substance – 2K scale SUS Batch USP
Drug Substance – <500L scale Continuous
Process
Technologies
Modular &
mobile
Automated
Facility
Knowledge
Management
Supplier
Partnerships
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Evaluating Biopharmaceutical Market Trends
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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
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Collective Brainstorming by Industry Experts
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The team have focused on 4 biomanufacturing scenarios
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Scenario Typical Products
1 Stainless Steel > 10K, Batch – Batch /Continuous
Mab’s, Mab Fusions, rec Proteins,
2 Disposable ~ 2K, Continuous– Semi Continuous/ Continuous
Unstable Products e.g. Factor VIII, Therapeutic Enzymes, Viral Vaccines, Allogenic Cell Therapy
3 Disposable ~2K, Batch –Semicontinuous/ Batch
Mab’s, Mab Fusions, rec Proteins, Viral Vaccines
4 Disposable < 500L, Continuous -Continuous
Biologics on Demand, Bioproduction at Bedside, Typically recombinant proteins and viral vaccines in microbial systems. Cell/Gene Therapy
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Cross Industry Collaboration = Substantial Benefits
Roadmap Team Vision Benefit
Process
Technology
Process Intensification
• Reduction in facility size • Reduced capital investment
• Speed to market
Continuous Processing
• Flexibility for smaller patient populations• Speed
• Reduced cost
In-line
Monitoring and
Real-time
release
Process control and assurance of product quality
• Tighter product and process control
• Reduced cost of quality• Enables real time release
Global regulatory testing standards, advanced
process control strategies and raw material characterization.
• Eliminate $Bn’s of inventory
• Product released 1-2 days after mfg• Reduce quality costs
Modular and
MobileManufacturing systems using ‘plug and play’
standard designs
• Scalable capacity
• Manufacturing process available in weeks rather than years.
Fully
Automated
Facility
Scale up from development to manufacturing in a
fully automated facility.
• Consistent high product quality
• Reliable supply• Reduced time to market
Supplier
ManagementTechnology development partners for our industry
• Innovative supply partners
• Industry needs delivered faster and better
Knowledge
ManagementE2D integrated knowledge of product and process
technology
• Speed to market
• Cross-product learning• Efficiency throughout product lifecycle
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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
• 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 teams
Modeling bio-manufacturing scenarios can identify areas for
technology innovation
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Sce
na
rio
Evo
lution
“Wh
at”
Te
ch
no
logy , c
ap
abili
tie
s &
En
ab
lers
“Ho
w”
Bu
sin
ess D
rive
rs
“Wh
y”
Now 10 years5 years
Cost
Flex
Speed
Low cost
<$30g/L DS
Scale-out not
scale-up
Clinical –
Comm pIII
Continuous processing
Supplier management
Modular & mobile
Real-time release
Knowledge Management
Fully automated
facil ity
Single use cell retention
device
Capital <$70m full
facil ity
No QC FTE frrelease
CoGs high
>110g/L
Release of
f unds to OQ complete ~ 2 y rs
2 g/L/dIn clinic
Manuf acture to
release weeks to months
Perf usion USP
in commercial
Fully
integrated processing
Multi-product
Commercial
Facility
Rapid
changeover0 extra time
Seamless
buf fer operability
Highly /Fully
automation
Integrated
knowledge manageme
nt
Plug & play
adaptable
>1000kg2g/L/dat @
2000L4g/L/day
@1000L
Multi
attribute analy tics
Adv anced
process control
Integrated
DP
Process intensification
In-line monitoring
Fully sanitary GMP
continuous chromo
skids from multiple
vendors
Robust continuous
viral
clearance
Deviation
management
(how much
quarantine)
Perfusion ~2kL to DSP semi
cont & Cont
Release in 0 days
Multiple platforms
Changeover <1 wk
between platform
Manuf acture to
release by exception
Release of
f unds to PPQ complete <2 yrs
RFT
MVDA / SBOL
2x200L
SUB to integrated
DSP
No clean
steam or autoclave
PAT / RTR for raw
materialsClinical PhIII
f acility in production
1x 2000L SUB
QC testing
takes weeks
Continuous not
y et in clinic
Sandbox
(industrial
collaborative) at
scale
Demonstrate
process robustness
Pipeline into
platf orm
Simplify buffer
system
Reduce number
of solutions
Low cost media
concentrates
DS ProcDev
3-5 yrs from PhI
process to
commercial
Optimize media
f or perfusion
Perfusion to batch
comparability
Limited GMP continuous
chromo skids
KM platform
Integrity of SU
sy stems (leaks) not assured
Limited
integration
automation for SU
facilities
Virus
My coplasmaBioburden
Batch definition
Inf ormatics
CPV
Convert internal
Reg & QA
principles &
culture
Standard single use
assemblies
/connections
and how to
support and run them
Fully SU perfusion
Harvest
robust
Very limited SU
sensors
In-line of
QAs/PP
Multi-attribute
analy tics
Advanced
process control
developed USP x
DPS
Supplier Integration
Fully SU sensors
Closed
system
USP ↓CSPPR
↑Qp
2g/L/dy
< 1VVD
Supplier
integration –
Connecting
equipment
together is
complex
Traceability / Firewall
On demand buffer
formulation for
continuous
Skills / exp in
sensors - ModelsProcess model for
RTR
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Roadmap teams are developing the strategic technology needs,
challenges, and potential solutions (Draft - Illustrative)
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Unit Operation Scenario 1 Scenario 2 Scenario 3 Scenario 4A Scenario 4B
De
scri
pti
on
Bioreactor
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
purif ication
High titer batch USP
processes to match
productivity of 10kL
BXRs
Highly productive
deployable facilities
Deployed at point-of-
use
Up
str
eam
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 f ilter
Disposable HTST /
low cost viral f ilter
Disposable HTST /
low cost viral f ilter
Disposable HTST /
low cost viral f ilter
Cell Retention N-1 Microfiltration Disposable f iltration
(non-fouling) /
Acoustic wave
Disposable f iltration /
Acoustic wave
disposable f iltration
(non-fouling) /
Acoustic wave
Bioreactor Design Reactor Design Easily cleanable /
Rapid Changeover
Long duration, robust
f ilms and seals
Robust f ilms Long duration, robust
f ilms 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.)
Harv
es
t
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
Clarif ication Re-usable depth
f iltration
Gamma compatible
depth f iltration
Re-usable depth
f iltration
Gamma compatible
depth f iltration
Current 2019 2022 2026 SCENARIO(S)
(Metric1) CoG
(Metric2) Quality
(Metric3) Speed
(Metric4) Flexibility
NEED Improved reliability of current in-line sensors All
CHALLENGE The current process parameter sensors are still not reliable and some of them need offline
recalibration during the process. The number of the ports in the bioreactor are limited. The
disposable sensors reliability getting better, but still have room to improve.
POTENTIAL
SOLUTION
Reliable and robust sensors (pH, DO, CO2, T) without recalibration/correction during the
process, forming sensors, Disposible sensors; multifunction sensors.
ispe.orgConnecting Pharmaceutical Knowledge
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 dateo Market trends & business drivers
o Biomanufacturing scenarios
o Initial process modelling results
When: Next Steps
Agenda
ispe.orgConnecting Pharmaceutical Knowledge
© BioPhorum Operations Group Ltd
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
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
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,
ModellingFinal
modifications and input from industry
stakeholders
Implementation planning and
industry responseChallenges,
Solutions
Revi
ew
to c
larify
focu
s,
linka
ges
& s
pot gaps
Pre
para
tion for TR04. Li
st top p
oin
ts to
add v
alu
e, is
sues,
debating p
oin
ts
Deta
il re
view
follo
wed b
y fin
al
changes to d
ocum
ent
22
BPI article
CASSS
BPI conference
ISPE
BPI article
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Two year cycle of roadmapping - example
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TR04Finalising the
roadmapSep’16
TR05 Implementation plan & Industry Response
Apr’17
TR07 Industry response & Roadmap production
Apr’18
TR08Industry response & Roadmap production
Oct’18
2016 2017 2018
Next roadmap 2nd Edition
Publish2019
Scope & scenarios
Teams & basic roadmap
Detailed roadmap
• Edits, revisions and progress updates to existing roadmap• New modalities and product groups• Disruptive technologies
• Adjacent process areas
Articles
BPI Conf
Oct’17
BPI Conference
Oct’16
BPI Conference
Oct’18Articles & conferences
Feedback
CASSS BIOPublishMay’17
TR06 Industry response and Roadmap production
Oct’17
Roadmap 1st Edition Comms, planning, industry response & review
CASSS BIO
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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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