A Global Technology Roadmap for Biopharmaceutical ... · PDF fileA Global Technology Roadmap for Biopharmaceutical Manufacturing: An Update from BPOG Philip McDuff (Biogen) Presentation

A Global Technology Roadmap for

Biopharmaceutical Manufacturing:

An Update from BPOG

Philip McDuff (Biogen)

Presentation to ISPE Facility of the Future Meeting 2016

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


Industry collaboration that brings together 33 bio-manufacturers, collaborating in six phorums to accelerate the industry

3

Who is BioPhorum Operations Group (BPOG)


© 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

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

http://www.biophorum.com/

http://www.biophorum.com/accelerate


Who is BPOG







• When: Next Steps

Agenda



What is a Technology Road Map?

An industry technology roadmap is –

a dynamic and evolving collaborative technology management process

For:

6

determining precompetitive critical needs and drivers,

identifying technology and/or manufacturing targets, and

assessing/modeling potential solutions


Who is BPOG








Agenda



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

8

Complex industry has traditionally held back innovation….



Agenda

Who is BPOG




Now: Overview of key roadmap content to date

o Market trends & business driverso Biomanufacturing scenarioso Initial process modelling results


9

ispe.orgConnecting Pharmaceutical Knowledge 10

Following the Lead from other Industries…..Using method from University of Cambridge’s Institute for Manufacturing

Semiconductor Industry

NASA



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

11

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



Agenda

Who is BPOG




Now!: Overview of key roadmap content to date

o Market trends & business driverso Biomanufacturing scenarios


When: Next Steps

12



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

13

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


Evaluating Biopharmaceutical Market Trends

14

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



Collective Brainstorming by Industry Experts

15



The team have focused on 4 biomanufacturing scenarios

16

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

16



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

1717



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

18



19

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



Roadmap teams are developing the strategic technology needs,

challenges, and potential solutions (Draft - Illustrative)

20

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


N-1 Perfusion

Cryobags to reduce


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 /


Disposable HTST /


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.


Who is BPOG







When: Next Steps

Agenda



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



Two year cycle of roadmapping - example

23

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



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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Documents

A Global Technology Roadmap for Biopharmaceutical ... · PDF fileA Global Technology Roadmap for Biopharmaceutical Manufacturing: An Update from BPOG Philip McDuff (Biogen) Presentation