technology roadmapping - biophorum trends & business drivers •analysis •metrics future...

© BioPhorum Operations Group Ltd

Technology Roadmapping Introduction

Rajesh Beri, Lonza Biologics Inc

Steve Jones, BPOG,

18-20 May 2016


The executive team

May 2016 Technology Roadmapping 2

SC + Roadmap team

Steering Committee


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 2016 Technology Roadmapping


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


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


BioManufacturers

Suppliers


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



Agenda






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

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

http://www.nasa.gov/offices/oct/home/roadmaps/index.html

https://www.dropbox.com/sh/6xq737bg6pww9gq/AABhWzoZdwYaemQc6bZKzvena/2013Litho_Summary.pdf?dl=0


What is the scope of the Technology Roadmapping process?


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


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


Building the industry strategic landscape



Kick-off meeting Feb 2015 - 19 companies contributed to a high level industry roadmap, identifying focus topics for the technology roadmap


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


In summary, the 4 main market trends affecting the industry


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


Capacity Needs


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


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


The teams have focused on 4 Biomanufacturing scenarios


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

© BioPhorum Operations Group Ltd May 2016 18

Scen

ario

Evo

lution

“What”

Te

chn

olo

gy , c

apa

bili

tie

s &

En

ab

lers

“How”

Bu

sin

ess D

rive

rs

“Why”

Now 10 years 5 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

materials Clinical 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



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 2016 Technology Roadmapping

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


Supply partners and academics provided input and ideas to the roadmap team

Technology Roadmapping 21 May 2016


Agenda






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



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technology roadmapping - biophorum trends & business drivers •analysis •metrics future...

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