Biopharmaceutical - Technology Roadmapping

A Global Technology Roadmap for
Biopharmaceutical Manufacturing:
An Update from BPOG
Philip McDuff (Biogen)

Presentation to
ISPE Facility of the Future Meeting 2016
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 drivers
o Biomanufacturing scenarios
o Initial process modelling results
 When: Next Steps
Connecting Pharmaceutical Know ledge ispe.org

Who is BioPhorum Operations Group (BPOG)
Industry collaboration that brings together 33 bio-manufacturers,
collaborating in six phorums to accelerate the industry
Connecting Pharmaceutical Know ledge ispe.org 3

6 Phorums covering all aspects of operations and accelerating biopharma
industry’s journey to maturity http://www.biophorum.com/
http://www.biophorum.com/accelerate
• Drug Substance, Fill Finish, Development Group
and IT Phorums
Drug Development
Substance Group • Accelerate the way the industry delivers near term
results making best practice development and
implementation faster, cheaper and smarter
Fill Information
Finish Technology
• Supply Partner Phorum
• Strategic focus on the wider supply chain needs of the
industry; defining, developing & implementing solutions
• Focus on business processes/systems & culture
Supply Technology The focus for this presentation

Partner Road Map
Phorum • 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
BPOG manages the linkages to ensure • Regulatory Interactions Group

• Decisions are made at the right time, at the right place by the
• Engage and align with Health Agencies in the design
right people
and adoption of advances in manufacturing
• Linkages are made visible to avoid redundancy
• Synergies are leveraged through effective coordination
© BioPhorum Operations Group Ltd

Agenda
 Who is BPOG

• When: Next Steps

What is a Technology Road Map?
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

Agenda
 Who is BPOG


Why is a Technology Roadmap needed for the Biopharm Industry?
Complex industry has traditionally held back innovation….
 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

Agenda
 Who is BPOG



Following the Lead from other Industries…..
Using method from University of Cambridge’s Institute for Manufacturing
Semiconductor Industry
NASA
10
Technology Roadmapping Steering Committee
Biopharmaceutical Supply Partner  Developed a strong Steering
Company Members Members Committee
Abbvie GE Healthcare Life
Sciences • Required decision making
AstraZeneca Kaiser Optical Systems
• Driving roadmap
Bayer Millipore Sigma
• Subject matter experts access
Biogen Novasep
Fujifilmdb PM Group  Diverse participants
GSK Sartorius Stedim • 17 biomanufacturers
Immunogen Thermo Fisher Scientific
Janssen
• 6 supply partners recently joined (and
growing)
Lonza
Lilly • Academics & regional centres, e.g. MIT,
AMBIC, CPI, SEDB, NIIMBL
Merck MSD
EMD Serono  Over 130 people involved globally
Pfizer
Roche
Sanofi
Shire
Takeda

Agenda
 Who is BPOG

 Now!: Overview of key roadmap content to date


High level Technology Roadmap structure and approach
Payer Diversification
pressure on In region Personalised
of product
manufacturing medicine
cost groups
Industry Trends
Business Speed Cost Flexibility Quality
Drivers
Drug Substance – Large scale stainless steel
Drug Substance – 2K scale SUS Continuous USP

Biomanufacturing
scenarios Drug Substance – 2K scale SUS Batch USP
Drug Substance – <500L scale Continuous
Inline
Enabling Process Monitoring & Modular & Automated Knowledge Supplier
Technologies Technologies Real time mobile Facility Management Partnerships
Release

Evaluating Biopharmaceutical Market Trends
Diversification
of product
Personalised groups Strength of
medicine Sales (Biologics)
Robust
Pipelines
New
Treatment
Modalities
Emerging
Markets
Advances
in Systems
Biology
In-region
manufacturing
Payer requirements
pressure on
cost of drugs Complex Global
regulatory
environment
Rising Costs
of Drug
Development Demand
Forecasts
Dose
Biosimilars Requirements
Clinical Failures
Competition
Social / Political Market
Perceptions Share

Collective Brainstorming by Industry Experts

The team have focused on 4 biomanufacturing scenarios
Scenario Typical Products

1 Stainless Steel > Mab’s, Mab Fusions, rec Proteins,
10K, Batch – Batch
/Continuous
2 Disposable ~ 2K, Unstable Products e.g. Factor VIII,
Continuous – Semi Therapeutic Enzymes, Viral Vaccines,
Continuous / Allogenic Cell Therapy
Continuous
3 Disposable ~2K, Mab’s, Mab Fusions, rec Proteins, Viral
Batch – Vaccines
Semicontinuous/
Batch
4 Disposable < 500L, Biologics on Demand, Bioproduction at
Continuous - Bedside, Typically recombinant proteins
Continuous and viral vaccines in microbial systems.
Cell/Gene Therapy
16

Cross Industry Collaboration = Substantial Benefits
Roadmap Team Vision Benefit
• Reduction in facility size

Process Intensification • Reduced capital investment
Process • Speed to market
Technology • Flexibility for smaller patient populations
Continuous Processing • Speed
• Reduced cost
In-line • Tighter product and process control

Process control and assurance of product quality • Reduced cost of quality
Monitoring and • Enables real time release
Real-time
Global regulatory testing standards, advanced • Eliminate $Bn’s of inventory
release process control strategies and raw material • Product released 1-2 days after mfg
characterization. • Reduce quality costs
Modular and • Scalable capacity

Manufacturing systems using ‘plug and play’
• Manufacturing process available in
Mobile standard designs
weeks rather than years.
Fully • Consistent high product quality

Scale up from development to manufacturing in a
Automated • Reliable supply
fully automated facility.
• Reduced time to market
Facility
Supplier • Innovative supply partners
Technology development partners for our industry • Industry needs delivered faster and
Management better
Knowledge • Speed to market

E2D integrated knowledge of product and process
• Cross-product learning
Management technology
• Efficiency throughout product lifecycle
17

Modeling bio-manufacturing scenarios can identify areas for
technology innovation
 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

Perfusion ~2kL to DSP sem i Now 5 years 10 years
cont & Cont
Business Drivers
CoGs high Capital Low cost
Cost >110g/L <$70m full
<$30g/L DS
facility
“Why”
Release of Manuf acture to Multiple platforms Release of

f unds to OQ No QC FTE fr Changeover <1 wk f unds to PPQ
Flex release weeks
release
complete to months between platform complete <2 yrs
~ 2 y rs
Manuf acture to
Release in 0 release by RFT
Speed days exception
Perf usion USP Scale-out not

QC testing Fully Multi-product
MVDA / scale-up
in commercial takes weeks Sandbox 2 g/L/d Clinical – integrated Commercial
SBOL processing Facility
Scenario Evolution
(industrial Comm pIII

In clinic
collaborative) at PAT / RTR 2x200L
Continuous not scale Rapid Seamless
for raw SUB to Highly /Fully
y et in clinic Demonstrate changeover buf fer
Clinical PhIII materials
“What”
integrated automation
process 0 extra time operability
f acility in DSP
robustness
production Integrated >1000kg
1x 2000L SUB No clean 2g/L/dat @
Pipeline into knowledge Plug & play
manageme steam or 2000L
platf orm adaptable 4g/L/day
nt autoclave @1000L
Multi Adv anced

Integrated
attribute process
control DP
analy tics
Fully SU Simplify buffer

perfusion Low cost Perfusion to Fully SU USP ↓CSPPR
Process system
Harvest media batch sensors ↑Qp
intensification Reduce number
robust of solutions concentrates comparability Closed 2g/L/dy
< 1VVD
system
Robust
Technology , capabilities & Enablers
Single use DS ProcDev Fully sanitary GMP On demand buffer

3-5 yrs from PhI Optimize media continuous Traceability /
Continuous Limited GMP cell retention
continuous chromo formulation for
process to f or perfusion skids from multiple viral Firewall continuous
processing continuous device commercial vendors
clearance
chromo skids
Standard
Knowledge single use
KM platform
Management assemblies
/connections Supplier
Advanced
“How”
Integrity of SU and how to Integration

Supplier process control Supplier
sy stems (leaks) support and developed USP x integration –
management not assured run them DPS Connecting
equipment
together is
Modular & In-line of complex
mobile QAs/PP
Fully Limited Deviation

integration Multi-attribute management
automated automation for SU analy tics (how much
facility facilities quarantine)
In-line Convert internal
Inf ormatics
monitoring Very limited SU Virus Reg & QA Skills / exp in Process model for
Batch definition CPV
Real-time sensors My coplasma principles & sensors - Models RT R
release Bioburden culture

Roadmap teams are developing the strategic technology needs,
challenges, and potential solutions (Draft - Illustrative)
Unit Operation Scenario 1 Scenario 2 Scenario 3 Scenario 4A Scenario 4B
Bioreactor SS >10kL BXRs Disposable 2kL Disposable 2kL Disposable <500 Disposable <500
Volume BXRs BXRs BXRs BXRs
Bioreactor Mode Batch Continuous 1 Batch2 Continuous1 Batch/Continuous
DSP Mode Batch/Continuous Semi-continuous/ Batch/Semi- Continuous Batch/Continuous
Continuous continuous
Description
Facility Design Segregated suites/ Moderate footprint/ Moderate footprint/ Small Small
Large footprint Ballroom Ballroom footprint/Ballroom footprint/Ballroom
Processing Low Bioburden Closed Closed Closed Closed
Product mAb and other CHO mAb and other CHO mAb and other CHO mAb and other CHO Cell/Gene Therapy
TPs TPs TPs TPs
Comment Adaptions on current Continuous protein High titer batch USP Highly productive Deployed at point-of-
facility production through processes to match deployable facilities use
designs/retrofits purification productivity of 10kL SCENARIO(S)
Current 2019 2022 2026
(Metric1) CoG BXRs
Inoculum
(Metric2) Preparation
Quality Cryobags to reduce Cryobags to reduce Cryobags to reduce Cryobags to reduce
(Metric3) Speed time to production / time to production time to production / time to production /
(Metric4) Flexibility N-1 Perfusion N-1 Perfusion N-1 Perfusion
Production Cell Cell Density >15MM cells/mL >60MM cells/mL >60MM cells/mL >60MM cells/mL
NEED Improved reliability qofp current in-line sensors>40pg/cell/day
Culture >40pg/cell/day >40pg/cell/day >40pg/cell/day All
CHALLENGE The current processTiter/
parameter sensors are still
Productivity not reliable and some of them
3-5g/L need offline
2-3g/(L·day) 30-50g/L 3-6 g/(L·day)
recalibration during the process. The number of the ports in the bioreactor are limited. The
Product getting
disposable sensors reliability Quality
better, but still have room to improve. Consistant throughout batch duration
Media Reliable and robustMedia
POTENTIAL sensors (pH, DO, CO2, T) Defined/Stable / Low Defined
without recalibration/correction during/the
Stable / Defined / Stable /
Defined / Stable /
Upstream
SOLUTION process, forming sensors, Disposible sensors;cost

multifunction sensors. Balanced / Low cost Balanced Balanced / Low cost
Viral Safety HTST or low cost Disposable HTST / Disposable HTST /
Disposable HTST /
viral filter low cost viral filter low cost viral filter
low cost viral filter
Cell Retention N-1 Microfiltration Disposable filtration Disposable filtration /
disposable filtration
(non-fouling) / Acoustic wave (non-fouling) /
Acoustic wave Acoustic wave
Bioreactor Design Reactor Design Easily cleanable / Long duration, robust Robust films Long duration, robust
Rapid Changeover films and seals films and seals
Polymers New elastomers not Defined and Defined and Defined and
requiring repeatable E&L repeatable E&L repeatable E&L
replacement profiles profiles profiles
Sensors Multi-function; Increased robustness (e.g. SU glucose, lactate, cell mass, pCO2 etc.)
Harvest Primary Disc-stack See cell retention Flocculation / Cell See cell retention
Recovery centrifugation / above Settling / above
Flocculation / Microfiltration /
Harvest
Acoustic wave / Acoustic wave /

Disposable Disposable
Centrifugation centrifugation
Clarification Re-usable depth Gamma compatible Re-usable depth Gamma compatible
filtration depth filtration filtration depth filtration
Agenda
 Who is BPOG


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 TR03 – Roadmap team TR04 – Finalising the TR05 – Implementation
meeting (12-14 Apr’16) roadmap (20-22 planning and Industry
meetings Sep’16) Response
1. Summary 2. Detail Freeze
Review points document document document Publish
review review
Steering Final approvals

Overview
Preparation for TR04. List top points to
Detail review followed by final

add value, issues, debating points
Market Trends, Product Classes,
committee Business Drivers, Scenarios, Final
changes to document
contribution Modelling modifications and
Summary input from
Detail industry Roadmap revision 2
Review to clarify focus,
Vision,
linkages & spot gaps
Roadmap Team Map,
Needs,
stakeholders Support / co-ordinate
Challenges,
activity Scope,
Solutions
implementation
Linkages
Implementation
planning and
Industry Challenges, industry response
stakeholder Solutions
engagement
BPI ISPE
Communications conference
Article CASSS BPI BPI
article article

Two year cycle of roadmapping - example
2016 2017 2018

TR04 TR05 TR06 TR07 TR08
Finalising the Implementation plan Industry response and Industry response & Industry response &
roadmap & Industry Response Roadmap production Roadmap production Roadmap production
Sep’16 Apr’17 Oct’17 Apr’18 Oct’18
Roadmap 1st Edition Comms, planning, industry response & review

BPI BPI BPI
Conference Publish Conf CASSS BIO Conference
Articles Oct’16 CASSS May’17 BIO Oct’17 Oct’18
Articles & conferences
Feedback
Scope & Teams & basic Detailed Publish
scenarios roadmap roadmap 2019
Next roadmap 2nd Edition

• Edits, revisions and progress updates to existing roadmap
• New modalities and product groups
• Disruptive technologies
• Adjacent process areas

Thank You!
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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A Global Technology Roadmap for

Philip McDuff (Biogen)

 Why a Road Map is needed. Why now…

 How is the Map Created: The Methodology

 When: Next Steps

Connecting Pharmaceutical Know ledge ispe.org

Connecting Pharmaceutical Know ledge ispe.org 3

Supply Technology The focus for this presentation

• Focus on longer term strategy & 10+yr time horizon,

BPOG manages the linkages to ensure • Regulatory Interactions Group

Connecting Pharmaceutical Know ledge ispe.org 4

© BioPhorum Operations Group Ltd

 Why a Road Map is needed. Why now…

 How is the Map Created: The Methodology

• When: Next Steps

Connecting Pharmaceutical Know ledge ispe.org

An industry technology roadmap is –

a dynamic and evolving collaborative

Connecting Pharmaceutical Know ledge ispe.org 6

© BioPhorum Operations Group Ltd

 Why a Road Map is needed. Why now…

 How is the Map Created: The Methodology

• When: Next Steps

Connecting Pharmaceutical Know ledge ispe.org

 Biomanufacturers are risk averse

 Biomanufacturers and Suppliers develop technologies in isolation

 Technology standardisation usually only occurs after the technology

Connecting Pharmaceutical Know ledge ispe.org 8

© BioPhorum Operations Group Ltd

 What is a Technology Road Map:

 Why a Road Map is needed. Why now…

 How is the Map Created: The Methodology

 Now: Overview of key roadmap content to date

• When: Next Steps

Connecting Pharmaceutical Know ledge ispe.org 9

© BioPhorum Operations Group Ltd

Connecting Pharmaceutical Know ledge ispe.org 11

© BioPhorum Operations Group Ltd

 What is a Technology Road Map:

 Why a Road Map is needed. Why now…

 How is the Map Created: The Methodology

 Now!: Overview of key roadmap content to date

 When: Next Steps

Connecting Pharmaceutical Know ledge ispe.org 12

© BioPhorum Operations Group Ltd

Drug Substance – Large scale stainless steel

Drug Substance – 2K scale SUS Continuous USP

Drug Substance – <500L scale Continuous

Connecting Pharmaceutical Know ledge ispe.org 13

© BioPhorum Operations Group Ltd

Connecting Pharmaceutical Know ledge ispe.org 14

Connecting Pharmaceutical Know ledge ispe.org 15

© BioPhorum Operations Group Ltd

Scenario Typical Products

© BioPhorum Operations Group Ltd

Roadmap Team Vision Benefit

• Reduction in facility size

In-line • Tighter product and process control

Modular and • Scalable capacity

Fully • Consistent high product quality

Knowledge • Speed to market

© BioPhorum Operations Group Ltd

• e.g. compare estimated Cost of Goods using different process formats

• Process parameter sensitivity analysis