The presentation given by Rajesh Beri at The Biomanufacturing Summit 2016

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Technology Roadmapping
Introduction
Rajesh Beri, Lonza Biologics Inc
Steve Jones, BPOG,
18-20 May 2016

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The executive team
May 2016Technology Roadmapping 2
SC + Roadmap team
Steering Committee

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Technology Roadmapping Steering Committee
 Developed a strong
Steering Committee
• Drive Road Mapping
• Decision Making
• Access External Experts
 18 companies on the
Steering Committee
• We expect more to make
the commitment
3
Company
Abbvie
AstraZeneca
Baxalta
Bayer
Biogen
Fujifilmdb
GSK
Immunogen
Janssen
Lonza
Lilly
Merck & Co
EMD Serono
Pfizer
Roche
Sanofi
Shire
Takeda
May 2016Technology Roadmapping

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Agenda
Why technology roadmapping is needed for the industry?
What is the ambition, process, structure?
What is the progress & plan forwards?
Technology Roadmapping May 2016 4

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Complex industry structure has traditionally held back innovation
 Biomanufacturers
• Develop new technology in isolation
• Standardisation after the technology is
launched
 Suppliers find it difficult to
innovate
• Have to guess end user requirements
• Risk-reward balance is poor
 New technology that makes it
onto commercial programs is
often removed to de-risk
 Everyone wants to be
a Fast Second
May 2016Technology Roadmapping 5
BioManufacturers
Suppliers

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The next wave of capacity expansion cannot only use large scale facilities
Extremely high CAPEX
• Increasing Payer & Biosimilar
cost pressure
Long build time
• Forecasts will never match
real demand and
• Delays time to market
Inflexible
• Pipeline trends  many more
products in lower quantity
• Eventually towards
personalised medicine
Technology Roadmapping May 2016 6

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Agenda
Why technology roadmapping is needed for the industry?
What is the ambition, process, structure?
What is the progress & plan forwards?
Technology Roadmapping May 2016 7

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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
 Determine precompetitive critical needs and drivers,
 Identify technology and/or manufacturing targets, and
 Assess / Model potential solutions
Goals:
 Focus an industry community
 Provide direction
 Identify critical needs for a specific timeframe by
consensus
Technology Roadmapping May 2016 8

9. Technology Roadmapping
What will the output look like?
Contents
Market trends & Business
drivers
• Analysis
• Metrics
Future Biomanufacturing
scenarios
• Assessment
New technology &
enablers
• Needs
• Difficult challenges
• Potential solutions
NASA
Semiconductor
May 2016 9

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What is the scope of the Technology Roadmapping process?
Technology Roadmapping
What it is?
 Process
• Engage and align industry stakeholders
• Define future needs of the industry,
difficult challenges & potential solutions
 Stakeholders –
• Biomanufacturers, Supply partner,
Regulatory, Academia input
 Communication
• The needs, challenges and potential solutions to
industry stakeholders to guide innovations
 Monitor industry progress
What it is not?
 Actual implementation –
• Responsibility of the industry once the
consensus on requirements is clear
 Focused on short term tactical needs
• Roadmap provides a long term, big
picture view of industry requirements
May 2016 10

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Collaborating on an Industry Technology Roadmap will enable company
technology strategy
Technology Roadmapping 11
BioPhorum
Industry
Roadmap
• Collaboration of bio-pharmaceutical
companies at an industry level engages
regulators and supply partners on
common industry need / position
Company
Strategic
Roadmap
• Adaptation to company
specific perspectives
and business strategy
Company
Site
Roadmap(s)
•Application of
company technology
strategy and sets
priority at the site level
Note: A lot of companies are
investing in a formal “Technology
strategy” role in their
organisations. These are the
perfect people / roles to contribute
to the roadmap process
May 2016

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Building the industry strategic landscape
Technology Roadmapping May 2016 12

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Kick-off meeting Feb 2015 - 19 companies contributed to a high level
industry roadmap, identifying focus topics for the technology roadmap
Technology Roadmapping
Advanced
integration of
current platform
Speed to clinic
Diversification
of product
groups
Payer pressure
on cost
In region
manufacturing
Personalised
medicine
Portable
modular
manufacturing
Human
resources &
talent
Global
regulatory
strategy
Supplier
management
Inline
monitoring
Real-time
release
Fully automated
robotic facility
Process
intensification
Knowledge
management
Continuous
processing
Modular and
mobile
Modelling data
& integration
Regulatory
harmonisation
Sensing
technology
Vendor
interaction
Multi-use and
flexible facilities
Technology
standards
Keep workforce
capable
Preparing the
next generation
capabilities
Industry Trends & Drivers
Roadmap Focus Topics
Capabilities and Enablers
May 2016 13

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In summary, the 4 main market trends affecting the industry
May 2016Technology Roadmapping 14
New product
classes
Market growth
Volume / year / drug
Number of drugs supplied
Global reach and emerging markets
Cost
Payer pressure
Biosimilars
Cost of clinical Failure
Uncertainty of
approvals and sales
Market
Trends
Thanks to Bert Frohlich

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Capacity Needs
May 2016Technology Roadmapping 15
 Decentralized Production
 Personalized Medicine
20 50 200 500 1000 2000 5000 10000 20,000 40,000
 Economies of Scale
 Increased Control / Consistency
Market Forces
Nominal Bioreactor Capacity Requirement for Product Manufacture
Frequency
(Number of
Products
Produced)
Limit of SUT
Future? Multi-modal?
Current Capacity Distribution
Thanks again to Bert Frohlich

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Business drivers
Cost
• Cost per dose
• Cost of development
Flexibility
• Batch size
• Number of platforms
• Changeover time
Quality
• Cost of quality
• Variability
Speed
• End to end cycle time
• Launch speed
• Speed to clinic
May 2016
Cost
Flexibility
Speed
Quality
Technology Roadmapping 16

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The teams have focused on 4 Biomanufacturing scenarios
May 2016Technology Roadmapping 17
Scenario – USP DSP Typical Products
1 Stainless Steel >
10K, Batch
Batch /Continuous Mab’s, Mab Fusions, rec Proteins,
2 Disposable ~ 2K,
Continuos
Semi Continuos /
Continuos
Unstable Products e.g. Factor VIII,
Therapeutic Enzymes, Viral Vaccines,
Allogenic Cell Therapy
3 Disposable ~2K,
Batch
Batch
Semicontinuous
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

18. © BioPhorum Operations Group LtdMay 2016 18
ScenarioEvolution
“What”
Technology,capabilities&Enablers
“How”
BusinessDrivers
“Why”
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
facility
Single use cell
retention
device
Capital <$70m
full facility
No QC FTE fr
release
CoGs high
>110g/L
Release of funds
to OQ complete
~ 2 yrs
2 g/L/d
In clinic
Manufacture to
release weeks to
months
Perfusion USP in
commercial
Fully
integrated
processing
Multi-product
Commercial
Facility
Rapid
changeover
0 extra time
Seamless
buffer
operability
Highly/Fully
automation
Integrated
knowledge
management
Plug & play
adaptable
>1000kg
2g/L/dat @ 2000L
4g/L/day @1000L
Multi
attribute
analytics
Advanced
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
Manufacture to
release by
exception
Release of funds
to PPQ complete
<2 yrs
RFT
MVDA /
SBOL
2x200L SUB
to integrated
DSP
No clean
steam or
autoclave
PAT / RTR
for raw
materialsClinical PhIII
facility in
production
1x 2000L SUB
QC testing takes
weeks
Continuous not
yet in clinic
Sandbox (industrial
collaborative) at
scale
Demonstrate
process
robustness
Pipeline into
platform
Simplify buffer
system
Reduce number of
solutions
Low cost
media
concentrates
DS ProcDev
3-5 yrs from PhI
process to
commercial
Optimize media
for perfusion
Perfusion to
batch
comparability
Limited GMP
continuous
chromo skids
KM platform
Integrity of SU
systems (leaks)
not assured
Limited integration
automation for SU
facilities
Virus
Mycoplasma
Bioburden
Batch definition
Informatics
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
analytics
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 - Models
Process model for
RTR
Technology Roadmapping

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Substantial benefits can be gained through a cross industry collaboration
on the roadmap team topics
19
Roadmap Team Vision Benefit
Process
Technology
Process Intensification - Intensifying production
through highly concentrated reactants and products
and combining unit operations into single units
• Reduction in facility size
• Reduced capital investment
• Speed to market
Continuous Processing - New separation and media
technologies, coupled with advanced automation and
process control
• Flexibility for smaller patient populations
• Speed
• Reduced cost
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.
• 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 manufacture
• Reduce quality costs
Modular and
Mobile
Manufacturing systems that are quick to configure and
assemble 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, with a
focus on automation, equipment, and biology, results
in a fully automated facility.
• Consistent high product quality
• Reliable supply
• Reduced time to market.
Supplier
Management
Suppliers become technology development partners
for our industry, collaborating to solve problems.
• Innovative supply partners
• Industry needs delivered faster and better
Knowledge
Management
Integrated knowledge of product and process
technology across the development, manufacturing
and commercial value streams
• Speed to market
• Cross-product learning
• Efficiency throughout product lifecycle.
May 2016Technology Roadmapping

20. Process Technologies
Please define what your
sensors need to measure
- - Product quality
- - media
Before Continuous,
need full
automation of unit
ops
TOP
5
Scenario 2 + 3
2k Batch/Perfusion
Upstream
Does PD have
impact on pdt
quality – start &
end?
+ intensified
------------
Perfusion
[10 days]
+ perfusion
------------
Continuous
Harvest
Media
Seed Train
Production
Bioreactors
Harvest
Facility/
Automation
Consumables
RM
Regulatory
Personal exchange between
Biopharma/Medium vendor to
develop customised medium
Host cell line
development
for Rolling Seed
technology
Closed
Scale-up
Foam-sensing
vision system
for automated
controll
ATF 2k
Fully disposable;
Robustness
Improved
Shaken & Stirred
bioreactor for
high turnaround
- one bioreactor
Improved
filter for
venting
Media most
input on ACQA
Improved media
sterilization
-improved filters
- alternate tech.
2k Batch
Disposable HTST for
media
Other treatments
(virusfilter)
Alternate CO2
removal strategy
to enable O2 only
gassing & no foam
Standard seed
train
1:10 split
More robust
tech.
Better weldevs
½-1”
Improved
foam
reduction
technology
Design product for
high perf mfg
Increase bag
customize speed by
vendor
(ie <2 months)
Number of
ports in bag
Bag reliability;
Lot-to-lot
variability
Minimal bag material
concern (leachables) &
proper control/defect
strategy
Robust bag
packaging &
delivery from
vendor
Economical
single-use
centrifuge
Ergonomic but smallest
possible layout
configurations for lowest
cost facilities
Supporting data for
fully closed
‘connectors’ for use in
non-classified space
EoL
Consolidated list of
compounds/test could lower
cost for academia to research
5g/L
10 day
Seed train &
prod
Closed processing
- Production bioreactor unclassified
- including scale-up
- Downstream bioreacto Class D or E
Process
Automation;
Reduced
intervention
Harvest to
support high
density
Faster
changeover
‘limited’
changeover
Reduce or
eliminate IP
sampling
Implement
disposable
probes
Faster, robust
RM testing /
release
Faster cycle
times
<10d Prod. Brx
Reduced lot-
to-lot
varibaility
Media High
concentrations
Liq-liquid reduced
components
Improved mass
transfer
matches cell
type/density
Robotic cell
scale-up in
isolator
Proper gassing
strategy for high
density process
Reduced cost
of filter for cell
sep.
Improved inline
disp. Sensors
-DO, cell density
TOP
5
Large cell bags
-Robust
-Low temp
-P/T
-automatic dispensing
R-T stable
Media
Microbial
media?
Storage of high
vol. cell bags
Reliable bio-mass
probes (wide
dynamic range)
pH
measurement
w/o offline
correction
Single-use
harvest
technology
TOP
5
Improved
filtration (body
feed)
Acoustic
separator
blank
Robustness
bag film - leaks
Ballroom Concept
- No segregation
classified in F
Reliability of
bag ‘integrity’
Reliability of
bag film
(leachables)
TOP
5
Real-time
release –
1 day
High potency
products
Managing data &
using it to inform
process with
enhanced PAT
tools
Inline
characterization
of product quality
Sensors for
BM+
metabolite
ATF
Disposable
PAT
20 yrs
Sensor
do all-in-1
Ballroom
-closed system
upstream &
downstream
Single
bioreactor
scale-up
100ml-500L
Need simple in-
line conditioning
(not a chromo
skid)
Single use of
ATF for N-1
perfusion
Robust
disposable
pump, not
peristaltic
Real-time
reconstitution
of medium
(powder) -
liquid
Microbial
fermentation/
synthetic biologics
not detailed
Single use, robust,
low cost harvest
tech
10-20g/L
10 day
process
Max. seed
expansion efficiency
(high density cell
bank w/ good vol.)
Multi-product
Parallel
streams
Interchangeable
bags
Not Vendor
Specific
Target MAB
$1/gm
No
changeover
Online
sensors
Raw
materials –
electronic
cofa
Min testing
Same-day
release
Mnimal / No. release
testing
-Qdb, well controlled,
well characterized
process
TOP
5
Minimal
tech
transfer
<1 month
Upstream
Team
20

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Supply partners and academics provided input and ideas to the roadmap
team
Technology Roadmapping 21May 2016

22. © BioPhorum Operations Group Ltd
Agenda
Why technology roadmapping is needed for the industry?
What is the ambition, process, structure?
What is the progress & plan forwards?
Technology Roadmapping May 2016 22

23. © BioPhorum Operations Group Ltd
Technology Roadmap plan – 2016 activities
2016
D J F M A M J J A S O N D
Face to face meetings
Roadmap Team (RT) activity
Industry stakeholder
engagement in roadmapping
Roadmap content development
Communications
Publish industry roadmap
Stakeholder engagement and input to the roadmap
Chapter detailing Chapter finalising
Final approvals
Mobilise RT’s
TR03 – Roadmap team
meeting (12-14 Apr’16)
TR04 – Finalising the
roadmap (20-22 Sep’16)
Comms strategy
and channels
Comms for progress and launch of roadmap
1st Level
Map
2nd
Level Map
SC
input
Draft
due
SC
review
Press release
Technology Roadmapping May 2016 23

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Technology Roadmapping May 2016 24