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January 2020

Technology RoadmappingProgram pack

© BioPhorum Operations Group Ltd 2

The seven Phorums provide benefits across the biopharma supply chain

Drug Substance, Fill Finish,

Development Group, Information Technology,

Cell & Gene Therapy

• Accelerating the way the industry delivers near term results,

making best practice development and implementation faster,

cheaper and smarter

Supply Partners

• Creating the supply chains the industry needs; defining,

developing and implementing solutions for business processes,

systems and culture

Technology Roadmapping

• Revolutionizing the way the industry develops longer

term transformational manufacturing and technology capabilities

• Focusing on strategy and ten year time horizon, defining needs,

difficult challenges and potential solutions

Regulatory Interaction

• Enable engagement and alignment with Regulatory

Stakeholders in order to accelerate adoption and successful

implementation of advances in manufacturing

Facilitation

• Ensures 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

3© BioPhorum Operations Group Ltd

Buffer Preparation

Standard Facility Design

Continuous Downstream Processing

Microbial ControlContamination Free

Process

Lean Qualification / Validation

Disposables –Change Notification

Deviation Management System

Post Approval Supplement Strategies

Human Performance

Continued Process Verification

QC Stability

Reliability

Alternatives & Rapid Micro Methods

Container Closure Integrity Testing

EM in a Modern DP Facility

Sterile Filtration QRM (formerly PUPSIT)

Visual Inspection / Particulate Control

Lyophilization Digital Plant Maturity

Smart Maintenance

Compliant Multi-Source Analytics

Viral Clearance

Formulation

Development Outsourcing

CMC Regulatory

Host Cell Proteins

Cell Line Stability(previously

Demonstration of Monoclonality)

Qualification of Small Scale Models

Forced Degradation Studies

BioAssay

Knowledge Management in Development

CMC Considerations for Expedited Development

Programs

Analytics


Rapid Methods for Adventitious Detection & Assurance

Harvest ClarificationRapid Release Testing through Inline Monitoring

Knowledge Management

Big Data to Smart Data

Robotics

Plug and Play

Disposables –Supply Base

Reliability

Disposables –Testing, Validation & Release Standards

Storage & Transport

Supply Chain Visibility – CMO

Integration

Raw Material Variability

Disposables – E&L

Disposables – SUS URS

Closed Systems

Multi-Product Facilities

Supply Agility New Product

Introduction

Risk Management & Business

Continuity Planning

Joint Audit Program

Aggregated Biopharma

Capacity Analysis

Microbial ControlOperational

Harmonization

Cybersecurity/Plant Resilience, Recovery

Strategic Supply Chain Control

PAT Monitoring and Control

Isolator Good Operating Practice

Agile in GxPPlaybook

QMS Simplification -Change Control

Supply Chain Mapping

Forecast & Demand Planning

Phorums working together in a coordinated program of industry change

Process Development

Process Technology

ILM & RTR Modular & Mobile Automated FacilityKnowledge

ManagementSupply Partnership

ManagementOperations, Quality

& Compliance

SPITDGFFDSTR RIC&GT

High Level Analytics

Regulatory Strategy

Validation

Commercialization C&GT Manufacture

EHS & BioSafetyRaw Materials

Sourcing, Quality & Volume


The program pack is there to provide phorum specific information, and is 1 of 3 packs to help you manage your engagement with BioPhorum

Account pack

Tracks your company engagement

Refreshed before each of our

account calls

• Discussion points and actions

• Phorum

• Activities

• Program slide

• F2F meetings calendar

• Comms/publication plans

• Support and implementation plans

• Your

• Status of invitees to F2F meetings

• List of representatives

• Workstream and participation status

• Alignment model score and plans

• Access to iMeet Central

Program pack

Tracks the Phorum program

Refreshed before any leadership

governance meeting or quarterly

• Phorum

• Mission

• Program slide

• Comms/publication plans

• Support and implementation plans

• Workstream

• Charters

• Plans

• Linkages

• Deliverable trackers

Deliverables pack

Records BioPhorum’s delivery

Refreshed annually ready for year

end reviews

• Description of all the resources

delivered by BioPhorum in the previous

12 months, including

• Benchmarks

• Guidance

• Position papers

• User requirements

• Proof of concepts

• Studies and results


BioPhorum monthly newsletter

• Sign up to ensure you are:

• informed of any new BioPhorum

publications that can be downloaded

using the link provided

• aware of imminent face to face

meetings, topics, locations and dates

• informed of new companies joining

the BioPhorum collaboration

• To register:

• click HERE to navigate to the

BioPhorum home page

• scroll to the bottom of the page and

fill in your email address in the

Newsletter subscribe section

• you will then receive an email asking

you to confirm subscription via the

link provided.

http://www.biophorum.com/


Mission and program plan


Mission of the Technology Roadmapping phorum:To accelerate industry innovation

The BioPhorum technology roadmapping process

is – a dynamic and evolving collaborative

technology management process for:

• determining pre-competitive critical needs and

drivers

• identifying technology and/or manufacturing

targets

• assessing/modeling potential solutions

• coordinating implementation projects

to

• focus an industry community,

• provide direction,

• resolve those critical needs for a specific

timeframe by consensus, and

• ensure that technologies are delivered and

adopted


Uncertainty

▪ Regulatory approvals

▪ Demand variability

▪ Competition

Cost pressure

▪ Payer pressure

▪ Biosimilars

▪ Development

Market Growth

▪ Emerging markets

▪ Global reach

▪ In region manufacture

New Product Classes

▪ Non-mAbs, ADCs

▪ Gene therapy

▪ Cell therapy

Modular and

Mobile- 70% build time

- 75% CAPEX

▪ Quick to configure

& scale

▪ Standard designs

▪ Streamlined

validation

Automated Facility− 50% Facility

Build Speed

− 50% OPEX

costs from current

▪ Agile, high quality,

and robust

biomanufacturing

▪ Plug and Play

▪ Open data

standards

▪ Interoperability

Knowledge

Management‒ Cost of process

development

– Time to introduce a

change to an

existing process

to 1 Month

– Cost of Non-

Quality

to 2% of

operating costs

• Efficient tech.

transfer

• Integrated

knowledge

• Quality throughout

lifecycle

Supply

Partnership

ManagementSafe, innovative supply

chains:

− Cost of quality

− Time

▪ Partnerships with

quality built in

▪ Standard working,

integration and real

time Electronic

Data Exchange

▪ Shared Planning

Market Trends & Business Drivers – The Why

Enabling Technologies & Capabilities – The How

Speed

-70% build time

-80% lead time

Cost

-90% manufacturing cost

-90% CAPEX

Flexibility

-90% changeover

Demand response

Quality

10x robustness

-90% cost of quality

Drug Product

High volume

Drug Product

Low volume

Scale Distributed

1. Large-scale Stainless Steel Fed Batch

2. Intermediate-scale Single-use Perfusion

3. Intermediate-scale Multi-product Single-use Fed Batch

4. Small-scale <500L Portable Facility

Biomanufacturing scenarios – The What

(Facility types)

5. Small-scale <50L for Personalized Medicine

Technology Roadmap Vision

Inline Monitoring

and Real time

Release- Product Release

1-2 day

+ ↑ Quality, Efficiency

& Supply

▪ Enhanced In-Line

Monitoring

▪ Indirect and

Multivariate

Sensors

▪ Multivariate

Analysis and

Predictive

Modeling

Process

Technologies- 90% CoGs

- 90% process

investment

▪ Process

Intensification &

combination of unit

operations

▪ Continuous

processing

technologies

coupled with

advanced process

control

Digital

Technologies

Content generation

taking place during

2020

Continuous

Downstream

Processing• Recommend

industry strategy

for implementation

of continuous

downstream

processing

• Identify

collaboration

opportunities to

move industry

forwards at pace

• Identify business

drivers for

continuous

processing


Technology Roadmapping activities – 2020 structure

Steering CommitteeGovernance, strategy, program decisions

Technology Roadmapping

workstreams

Technology Development

workstreams

Technology Adoption

workstreams

• Roadmap document

production

• Prioritization of

recommendations

• Roadmap document review

• Impact of roadmap program

on industry

• Collaborative requirements

specifications

• Proof of concepts and

technology demonstrators

• Draft standards and

guidelines

• White papers

• Best practices

• Adoption case studies

• Cross-functional

collaborations to accelerate

operational adoption of

technologies

• Digital Technologies Roadmap

• Impact of the roadmapping

program on industry

• Buffer Preparation

• Plug and Play Technologies

• Big Data to Smart Data

• Inline Monitoring & Realtime

Release

• Rapid methods for detection

of adventitious virus &

mycoplasma – collaborative

validation

• Standard Facility Design

• Knowledge Management

• Continuous Processing

Process Design

• Robotic control of single use

consumables

• Best practice in adoption of

new technologies

• Adoption of ILMRTR cross-

phorum program

Communities of Practice:

Harvest Clarification

Obje

ctives

2020 w

ork

str

eam

s


Technology Roadmapping 2020 Program – v1 January 2020

10

Roadmapping strategy and governance

Digital technologies roadmap development

TR11

UK

TR12

TBC

Technology

Roadmapping

workstreamsTopic scoping and

content development

Leaders Resolution of significant

issues and governance,

including voting

All Phorums

Key linkages

Technology development workstreams– see slide 2

Technology

Development

workstreams• Transformational for

the industry

Tokyo

Best practice in new technology adoption

Roadmap impact survey and review phase 2

Technology

Adoption

workstreams• Embedding change into

the industry

Roadmap review strategy

Adoption of ILMRTR (cross-phorum program led by Drug Substance)


Technology Roadmapping 2020 Program – v1 January 2020

11

Big Data to Smart Data PoC

Knowledge Management Implementation

Guide and System URS

Rapid release testing through in-line monitoring

Standard Facility Design - CGT model

Buffer Preparation

Plug and Play Hardware PoC, developing and implementing a standard


Robotics

Communities of Practice

All Phorums

Key linkages

Rapid methods for detection of adventitious virus & mycoplasma – collaborative validation

Technology

Development

Workstreams• Transformational for

the industry

• Co-implementation of

URS and whitepapers

• Standard frameworks

• Driving towards proof

of concepts (PoCs)

Continuous Processing Process Design

Robotic control of single use consumables


Value tracker and benefits


Technology

Roadmap

workstream

Technology

Development

workstream

Deliverable Available Company Benefit When

Digital

TechnologiesN/A

• To create a vision for a standardized digital

infrastructure

• To identify specific digital technology needs

and capability gaps over the short and medium

term

• To create a common understanding of the

digital components of process technology

• This analysis will describe a digital infrastructure that enables the technology

objectives for current and future biomanufacturing scenarios

• It will identify major digital technology/ capabilities gaps & timelines for closing

those gaps

• It will support the co-ordination of implementation activities over the short and

long term, both in digital technology and between digital and other technology

efforts

Q4

2020

Continuous

Downstream

Processing

Continuous

Processing Process

Design

Team to be initiated in Q1. Expected deliverables

to include process design guidelines, process

control and process validation guidelines for

continuous processing.

• To be confirmed for each new activity. TBC

Process

TechnologyBuffer Preparation

Development, PoC demonstration and publication

of specifications for buffer preparation systems

that enable:

• Reduction in buffer prep footprint

• Reduction in buffer labor

• Reduction in buffer costs

• Reduction in buffer preparation time

• Buffer is not a facility capacity bottleneck

• Minimal facility footprint <50% of process footprint

• Enable inline testing & release of buffers

• 50% reduction in number of buffers

• 50% reduction in volume of buffer per kg product

• Reduce buffer labour by 90%

• Buffer capital- operating costs reduced by 75%

Q3

2020

In Line

Monitoring and

Real-time

Release

Rapid release

testing through

inline monitoring

White paper with URSs to guide the development

of new in-line, at-line and on-line technologies,

focused on highest impact CQAs and IPCs.

Inform industry of which CQA’s & IPC’s to be targeted for transition to in-line, on-

line or at-line monitoring which will lead to development of technology & tools to

gain a

o Reduction in cost of supply

o Reduction in cost of non-quality

o Reduction in time to release product from 4-6 weeks to 1-2 days

Q1

2020

Rapid methods for

detection of

adventitious virus

& mycoplasma

– collaborative

validation

• Develop User Requirement Specifications for

adventitious virus and mycoplasma alternative

RMM

• Develop AV and mycoplasma collaborative

validation guidebook for alternative RMM

(multi-site, multi-company)Draft mycoplasma

RMM validation case study

• Meet with regulatory agencies to obtain

feedback on guidebook

• Publish URS, guidebook and case study

• Speed up product release from 35 to ≤2 days for mycoplasma/virus testing

• Enable adoption of rapid methods suited for lot release testing

• Faster access for life changing therapies for human health conditions.

• Guidebook will be applicable for today and tomorrow’s yet to be discovered

methods

Q2

2021

TRM Value Tracker – Deliverable and Benefits

Updated by the Phorum Lead


Roadmap

chapter

Technology

Development

workstream


Automated Facility

Big data to smart data

• Industry standard taxonomy / indexing for data

sources that supply data for manufacturing

• Architecture for solution for adding context to data

sources that can’t add in context when data created

• Proof of concept to provide tangible example of

setting up for Smart Big Data usage.

• Reduce time to assemble data (80% to 10%), increase time

to process data (20% to 90%)

• Direct benefits is reduction in time for investigations by having

contextualized data available.

• Indirect benefits by providing contextualized data to other

work streams (like MVA, PAT, CPV, etc.) enabling them to

implement solutions quicker with less costs.

Q2 2021

Plug & Play

• Proof of concept, connect skid control system to

PCS with soft simulation of skid equipment.

• Definition of 3 data models – Bioreactor,

Chromatography, Normal Flow Filtration

• Speed - faster build times and reconfiguration times, delay

decision to build.

• Cost - eliminate development costs for custom interfaces.

• Quality - Reduced verification and variability.

• Flexibility - Ability to easily switch unit op technology to best in

class.

Q2 2021

Robotic control of

single use consumables

• User requirement specification detailing needs for robotics hardware associated with pick and play for single use consumables.

• TBCTBC

Modular and MobileStandard Facility

Design

Define user requirements and standard facility options

to rapidly respond to biologics manufacturing

production needs (less than 1 year response time).

• Speed of deployment, including design and build

• Speed of product launch

• Flexibility to use the site for multi-purpose and multi-product

• Cloning and copying of the site also for in-country/for country

installations

• Capacity flexing or scaling without interruption of existing

processes

• Mobility, if needed to bring capacity to the location of demand

Q2 2020

Knowledge

Management

Knowledge

Management

Develop framework for biopharm industry describing

standardised approach to managing product and

process knowledge across lifecycle.

• Higher process capability (RFT, lower OOS)

• More informed and faster decision making

• Enablement of ICHQ8-12

• Process improvements introduced faster.

• Better understanding of correlations between CMAs, CPPs

and CQAs leading to improved process control.

• Improved Speed and Quality.

• More knowledge is re-used.

• Greater ability to measure the performance of knowledge

flow. Including modelled productivity improvement, e.g. FTEs

per filing or MPV on a product, PPQ success rate?

Q1 2020

All

Best Practice in

Adoption of New

Technologies

Shared case studies on good practice.

Collaborative white paper detailing best practice in

adoption of new technologies into manufacturing.

• Guidance on stakeholder engagement and risk management

• Best practice in business case build across multiple functions,

to be applied both within an organization, and collaboratively.

Q3 2020

TRM Value Tracker – Deliverable and Benefits



Participation matrix


TRM company support plans


Company supports the

workstream to the extent that

they have provided resource to

the working teams.

Com

panie

s

AbbV

ie

Agile

nt

Applie

d M

ate

rials

Asahi K

asei

Astr

aZ

eneca

Avanto

r/V

WR

Bayer

Bio

gen

bio

Merieux

Boehringer

Ingelh

eim

Chugai P

harm

aceutic

al

Cold

er

CR

B

Em

ers

on

Endre

ss+

Hauser

/ K

ais

er

Exyte

Fujif

ilm D

iosynth

GE

Health

care

Gile

ad

GS

K

Honeyw

ell

IPS

Janssen

Lonza

Merc

k K

GaA

(H

ealth

care

), D

arm

sta

dt G

erm

any

Merc

k K

GaA

(Life

Scie

nces),

Darm

sta

dt G

erm

any

Merc

k M

SD

Novasep

Novo N

ord

isk

Pall

Life

Scie

nces

PM

Gro

up

Quart

ic.a

i

Rapid

Mic

ro B

iosyste

ms

Regenero

n

Roche

Rockw

ell

Auto

matio

n

Sanofi

Sart

orius S

tedim

Schneid

er

Ele

ctr

ic

Sie

mens

Therm

o F

isher

Pharm

a S

erv

ices

Therm

o F

isher

Scie

ntif

ic

WL G

ore

& A

ssocia

tes

Automated Facility 18 0 1 0 0 1 0 0 1 0 0 0 1 0 1 1 1 1 0 0 1 0 1 1 0 0 2 1 0 1 1 1 2 1 0 0

Best Practice in New Technology 19 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Big Data to Smart Data 20 0 1 0 0 1 1 0 0 1 0 0 0 1 0 0 1 1 1 0 0 1 0 0 1 1 0 0 0 1 1 1 1 1 1 1 1 1 0 0

Buffer Preparation 24 1 1 0 0 1 0 1 0 1 1 1 1 0 2 1 0 1 1 0 1 1 1 0 1 1 1 0 1 1 0 1 1 0 1 1 0 0

CGT Roadmap Scoping 19 1 1 1 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 1

Continuous Downstream Processing31 1 0 1 1 1 1 1 0 1 1 1 0 1 1 1 1 1 1 0 1 1 1 1 1 1 1 1 1 0 1 0 1 1 1 0 1 1 1

Digital Technology Roadmap 20 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1

Harvest Clarification 13 0 0 1 1 0 1 1 0 1 0 0 0 0 0 0 1 0 1 0 0 0 0 1 1 0 0 1 0 1 0 0 1 1 0 0 0

Inline Monitoring and Real-time Release24 0 1 0 0 1 0 1 1 0 1 1 0 0 1 1 0 1 1 1 0 0 1 1 1 1 1 0 0 1 0 1 1 1 0 0 1 1 1 1 0

Knowledge Management 20 1 1 0 1 1 1 1 0 1 0 0 0 1 0 0 1 1 1 0 1 0 0 0 0 1 0 0 1 0 1 1 0 1 1 1 1 0 0

Plug and Play 20 0 0 0 0 0 1 0 0 1 0 0 0 1 0 1 1 1 1 1 0 1 1 0 1 1 0 0 1 1 1 1 1 1 1 1 0 0

Rapid Methods for Adventitious Virus 19 0 0 0 1 0 1 1 1 1 1 0 0 0 0 0 1 0 1 1 0 0 1 1 1 1 1 0 1 1 0 1 1 0 0 0 0 0 1 0

Robotic Technologies 8 0 0 0 0 0 0 0 0 0 0 0 0 0 1 0 0 0 0 1 1 0 1 0 0 0 0 1 1 1 0 0 1 0 0 0

Standard Facility Design 22 1 0 0 1 0 0 0 0 1 1 1 1 0 0 1 1 1 1 0 0 1 1 0 0 1 0 0 1 1 1 1 1 0 1 1 1 1 0


Participation matrix – BiomanufacturersAttendance at team meetings

Please note that this data may differ from the data in the company support plan and in your account packs.

Company support plan / Account pack: shows commitment to a project by which companies are signed up to

the iMeet collaboration space

Participation data: shows which companies are actively participating and attending collaboration calls, as

measured across the last 6 call opportunities. A darker color denotes more active engagement.


CompanySC, Last 6

callsAF Plug & Play Robotics

Big Data to

Smart DataILM / RTR

ILM / RTR

RAVnSKM

Standard

Facility

Design

Buffer PrepConti

Processing

Digital

Technologies

CGT

Scoping

Technology

Adoption

Abbvie 1 0 0 0 0 0 0 0 6 0 0 2 0 0

AstraZeneca 7 0 0 0 0 8 4 0 1 0 0 3 0 0

Bayer 10 1 2 3 4 0 2 1 0 0 14 3 0 0

Biogen 4 0 0 0 0 4 0 1 0 3 6 3 0 1

Boehringer Ingelheim 8 1 1 0 4 0 6 2 7 0 4 3 0 0

Chugai 2 0 0 0 0 4 3 0 1 0 3 0 0 0

Fujifilm Diosynth

Biotechnologies

6 3 0 0 4 5 4 2 0 0 4 4 0 0

GSK 8 0 2 0 0 3 6 0 0 1 2 2 2 2

Gilead 3 0 0 0 0 0 0 0 0 0 0 0 0 0

Janssen 4 0 0 0 1 1 2 2 1 0 0 0 0 0

Lonza 6 4 2 2 0 6 1 0 1 3 0 2 1 0

Merck KGaA

(Healthcare)

3 2 0 0 0 0 3 0 0 0 0 0 0 0

Merck MSD 7 11 11 0 2 4 5 0 0 4 5 0 0 0

Novo Nordisk 0 0 0 0 0 0 5 0 0 0 0 0 0 0

Regeneron 2 0 1 0 0 0 1 0 1 0 4 0 0 0

Roche 5 4 4 6 1 6 8 0 0 0 0 2 1 0

Sanofi 5 0 1 0 0 0 1 0 0 2 0 5 0 1

Thermo Fisher Pharma

Services

8 0 0 0 1 8 0 0 0 1 9 0 2 0

UCB 0 0 0 0 0 0 0 0 0 0 0 0 0 0


Participation matrix – Supply PartnersAttendance at team meetings

Please note that this data may differ from the data in the company support plan and in your account packs.

Company support plan / Account pack: shows commitment to a project by which companies are signed up to

the iMeet collaboration space

Participation data: shows which companies are actively participating and attending collaboration calls, as

measured across the last 6 call opportunities. A darker color denotes more active engagement.


CompanySC, Last 6

callsAF Plug & Play Robotics

Big Data to

Smart DataILM / RTR

ILM / RTR

RAVnSKM

Standard

Facility

Design

Buffer PrepConti

Processing

Digital

Technologies

CGT

Scoping

Technology

Adoption

Agilent 2 0 0 0 0 0 0 0 0 0 0 0 0 0Applied Materials 1 2 0 0 8 0 0 3 0 0 0 0 0 0Asahi Kasei 4 0 0 0 0 0 0 0 0 0 2 0 0 0Avantor 8 4 0 0 2 0 0 4 0 7 5 0 2 2BioMerieux 1 0 0 0 0 0 0 0 0 0 0 0 0 0CPC 4 0 0 0 0 0 0 0 2 0 0 0 1 0CRB 0 0 0 0 0 0 0 0 0 0 0 0 0 0Emerson 5 9 11 0 4 12 0 5 0 0 6 5 2 1Endress+Hauser /

Kaiser

0 0 0 0 0 1 0 0 0 0 1 4 0 0

Exyte 5 0 0 0 0 0 0 0 2 0 3 0 0 0GCON 1 0 0 0 0 0 0 0 0 0 0 0 0 0GE Healthcare 5 10 7 2 3 10 0 3 4 3 2 0 0 0Honeywell 2 0 0 0 0 0 0 0 0 0 0 0 0 0IPS 3 0 0 0 0 0 0 0 0 0 5 0 1 0Merck KGaA (Life

Sciences)

5 0 8 2 6 0 2 0 0 2 0 1 2 0

NIIMBL 3 0 0 0 0 0 0 0 0 4 0 0 0 0Novasep 2 0 0 0 0 0 0 0 0 0 4 0 0 0Quartic.ai 4 0 0 0 0 0 0 0 0 0 0 0 0 0Pall 4 9 6 0 0 1 5 0 0 3 3 2 2 0PM Group 2 5 3 5 0 0 0 0 1 5 0 8 0 0Rockwell 8 8 8 2 4 0 0 2 0 5 5 2 1 2Sartorius Stedim 5 1 1 0 0 4 0 0 2 0 3 1 0 0Siemens 3 5 4 3 1 0 0 4 0 0 0 2 0 0Thermo Fisher Scientific 8 0 0 0 0 11 3 0 1 3 0 0 1 2WL Gore 4 0 0 0 0 0 0 0 0 0 5 0 1 0


F2F meetings calendar


Future Meetings Calendar

Meeting Date Location Topic and Purpose

BUFP07 -

Performance

Testing Set

Up

Jan NOTE THAT

NIIMBL ARE

CURRENTLY

REVIEWING THIS

AND DATES ARE

UNCLEAR WHILE

THEY DO THIS

Universiy Delaware Performance Testing will involve resources from member companies

working to a rota to execute Realization Protocol at UD. (DW to visit UD to

set up lab, receive and install prototype. Greet test teams, kick off, take

pictures then leave them to it!)

BD01 4-6 Feb Raleigh, NC To simulate the aggregation of batch and equipment data in a Big Data to

Smart Data demonstration and learning opportunity.

BUFP07 -

Performance

Testing Set

Up

Feb NOTE THAT

NIIMBL ARE

CURRENTLY

REVIEWING THIS

AND DATES ARE

UNCLEAR WHILE

THEY DO THIS

University Delaware Performance Testing will last for several weeks and then be followed by

releasing the skid to Gold Level Participants wishing to ship it to their own

facility or test at UD. (Visit to UD at end of testing to ensure data capture is in

hand, close test and be part of arrangements for subsequent skid travelling to

oter member companies.)

BUFP08 March NOTE THAT

NIIMBL ARE

CURRENTLY

REVIEWING THIS

AND DATES ARE

UNCLEAR WHILE

THEY DO THIS

University Delaware Evaluating Test Data and Authoring Buffer Prep White Paper Addendum

TR11 21-23 April Darlington, UK TR11 will be co-located with Drug Substance BPOG35. Key themes will

include Technology Adoption and Resource Management, as well as face to

face porfolio management decisions.

KM03 Q2 2020 East Coast USA Finalise RFP, inititate PoC, charter update, future direction

SFD05 Q2 2020 East Coast USA Close addendum paper writing, inititate URS/RFP discussion. future

direction


Future Meetings Calendar

Meeting Date Location Topic and Purpose

BUFP09 Q2/Q3 2020 Best guess, one further F2F in 2020 after BUFP08

RAV01 Q2 2020 East Coast USA

DTR01 Q2 2020 Europe DTR authoring of sections for Digital Roadmap

ILM03 Q2 2020 TBD ILM/RTR F2F team meeting

ILM04 Q2 2020 TBD Topic to be defined

PP04 Jun-20 East Coast Finalise and demonstrate implementation of SUB, NFF and Chrom Interface

Specifications. Next steps in Specifications.

Conti

workstream 3

TBC

Q3 2020 East Coast Topic to be defined

Conti

workstream 1

TBC

Q2 2020 East Coast USA Topic to be defined

Conti

workstream 2

TBC

Q2 2020 East Coast USA Topic to be defined

BD02 Q3 2020 Europe Plan and start to deliver the Big Data Proof of Concept.

PP04 Q3 2020 Europe Finalise and demonstrate implementation of SUB, NFF and Chrom Interface

Specifications. Next steps in Specifications.

DTR02 Q3 2020 East Coast Due to deliver Q3...unlikely but will need a F2F.

TR12 October / November TBC Portfolio review and 2021 program decisions; proof of concept outputs and

value

BD03 Q4 2020 East Coast Review the Phase 1/2 results of the Proof of Concept and plan forward

delivery.


Communications plan


Technology Roadmapping activity


BioPhorum linkages matrix


BioPhorum TRM Program Linkages https://bpog.imeetcentral.com/p/aQAAAAADg1FF

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ub

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h

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art

ne

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Th

era

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Re

gu

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tera

ctio

n

TRM Governance

CGT / E2E roadmap scoping

Digital Technologies Roadmap


Technology Adoption

Buffer Preparation

Reduce release testing

Rapid Methods for Adventitious Virus



Robotics

Plug and Play


Harvest Clarification CoP

PHORUMSTRM WORKSTREAMS

https://bpog.imeetcentral.com/p/aQAAAAADg1FF


Projects funding tracker


Technology Roadmapping Funding Tracker

Project Funding body Requirement Status Next action

Buffer

Preparation

NIIMBL Funding for

prototype

development and

testing.

Agreed outline proposal

and timeline with

NIIMBL. BioPhorum and

Member Companies

contracting with NIIMBL

on legal and financial

undertaking

• NIIMBL demo unit build

• BUFP06 Dec 2019, Uni

Delaware

Plug and Play Proposed

BioPhorum

members

consortium

Funding for VPN to

enable remote PoC

To be presented as

proposal to Steering

Committee 18th

December

• Steering committee voting


Project Charter Packs

CONNECT

COLLABORATE

ACCELERATE TM

Charter Pack

Buffer Preparation


Charter – Buffer Preparation – v4 October 2019

Problem

• Large footprints associated with

buffers

• Buffer prep can easily become a

bottleneck for production due to

volumes & complexity

• High levels of capex required to

improve

• High levels of labor needed to

manage current workflows

Impact

• Lack of awareness of buffer

management impact in industry.

Deliverables• Develop use cases and definitions

• Assess economic benefits for each of the scenarios

• Develop User Requirements and Concept Design

• Develop an Implementation, including estimate for building a prototype

• Get feedback/review

Goals

• Development of specifications for buffer

preparation systems that enable reduction

in preparation, footprint, labor, costs and

preparation time.

• Reduce obstacles to implementation by

sharing prototype data which demonstrates

the applications of a BSB skid and its

benefits.

Benefits

• Buffer not a facility capacity bottleneck

• Minimal facility footprint <50% of process

footprint.

• Enable inline testing and release of

buffers.

• 50% reduction in number of buffers.

• 50% reduction in volume of buffer per kg

product.

• Reduce buffer labor by 90%

• Buffer capital- operating costs reduced by

75%

• Enable SU bags of less than 2000L to be

used in place of large SS tanks at a saving

of perhaps ~$20MM to $50MM per facility

built. Labor requirements will also be

greatly reduced, and buffer preparation

can be reduced from a 3 x 7 day operation

to a 1 x 5 day operation in each facility.

• Potentially enable the transition from a

predominately SS facility common today to

a predominately SU facility of the future,

with a capital reduction of ~$100MM to

>$300MM per facility built in the future.

Facilitator [email protected] Roadmapping

OUT OF SCOPE

• Buffer chemistry, unit operation

optimization, chromatography,

perfusion vs fed batch feeds,

materials logistics, raw materials

supply chain, caustic supply, water

production, media

IN SCOPE

• Large scale stainless steel

production facilities

• Intermediate scale single use

production facilities

• mAb production

INTERNAL LINKAGES

• Other project teams: Conti Processing,

M&M, ILM, Plug and Play

• Drug Substance Closed Systems team

Submittals

Skid Development and Fabrication

White Paper

EXTERNAL LINKAGES

• NIIMBL; The University of Delaware.

Economic Modelling

Publish White Paper

Skid Delivery

Protocol Writing

Performance

Testing

Publish Addendum

Publish COG Paper

Q2 Q3 Q4 Q1 2020


Open source collaborative technology development leveraging NIIMBL $$$ funding matched to member resources and $$

9 Biomanufacturers

12 Supply Partners

1 Innovation Hub


Development of specifications

for buffer preparation systems

that enable:

• Reduction in buffer prep

footprint

• Reduction in buffer labor

• Reduction in buffer costs

• Reduction in buffer

preparation time

Implementation of buffer stock blending systems can greatly reduce the capital and operating costs of

biotechnology facilities designed and built in the future. The technology will enable SU bags of less than

2000L to be used in place of large SS tanks (often over 12,000L), at a savings of perhaps ~$20MM to

$50MM per facility built. Labor requirements will also be greatly reduced, and buffer preparation can be

reduced from a 3 x 7 day operation to a 1 x 5 day operation in each facility. The technology may also

enable the transition from a predominately SS facility common today to a predominately SU facility of the

future, with a capital reduction of ~$100MM to >$300MM per facility built in the future.• Buffer is not a facility capacity bottleneck

• Minimal facility footprint <50% of process footprint

• Enable inline testing & release of buffers


• 50% reduction in volume of buffer per kg product


• Buffer capital - operating costs reduced by 75%

2020

↑Speed

↓Cost

↑Flexibility

Facilitator [email protected]

Buffer Preparation

https://www.linkedin.com/company/biophorum-operations-group/

ScopeRequire

mentsDesign

Funding

Proposal

Vendor

SelectionWhite

Paper

Build

and

Test

Addendum Adoption

URS RFP FS Skid Delivery Publish




Phase/

ActivityDeliverables Business Benefit Measures and Targets Owner

2018

Q3

2018

Q4

2019

H1

2019

H2

Design Buffer Groups

List; P&ID

Diagram;

Controls

Design Collaboration targeting the

following benefits:

• Reducing buffer manufacturing facility

footprint

• Reducing buffer manufacturing and

holding equipment and capital

requirements

• Reducing labor cost associated with

buffer manufacture

• Reducing complexity and scheduling

constraints of buffer manufacturing

• Buffer is not a facility capacity

bottleneck

• Minimal facility footprint <50% of

process footprint

• Enable inline testing & release of

buffers


• 50% reduction in volume of buffer

per kg product


• Buffer capital- operating costs

reduced by 75%

Natraj

Ramx

Content

Authoring

Specification

Document

Kevin

Gibson

x

NIMBL

Collaboration

NIMBL

Contract

Lab space at the University of Delaware

enables build supported by UD

infrastructure. NIIMBL funds enable

vendor selection enabling project to use

a commercial vendor to execute design

and providing project management

resource.

Investment from member companies

of $150K and investment from NIMBL

for $700-$1m with initial agreements

signed byb Nov 2018 and vendor

identified and contracted to build

prototype by Feb 2019 (build then 6-9

mths)

Melissa

Scott x

Vendor

Selection

Jeff

Johnson x

Prototype Jeff

Johnson x

Results Test Data

Evaluation

Test dataset and modelling

demonstrates value of BSB skid.

Dataset represents an successful design

and build and proves the xxx of the

design. Modelling adequately describes

multiple scenarios in which the BSB skid

can deliver the benefits described.

White Paper downloads.

Member company adoption. Open

source design and dataset combine to

overcome hurdles to adoption across the

industry.

Kevin

Gibson x

Publication White Paper Outlining the proposal to eliminate

buffer prep bottleneck and introduce

protoyping project.

Additional scenarios and evaluation of

challenges and opportunities for the

industry.

Natraj

Ram

x

Addendum Publishing results and proposing next

steps for adoption.TBD

Risks

Vendor unable to deliver design as specified or on time.

Anticipated benefits not adequately illustrated by dataset.

Charter Activity Tracking – Buffer Preparation


Linkage Phorum Synergies Communication Plan Mode

TR15 Standard Facility

Design

TRM Buffer technology could change facility

requirements.

TRM Facilitation Team Aware

TR21 Plug and Play TRM TRM Facilitation Team Reference

TR1/7 Reduce Release

Testing

TRM Test development may be needed to

release online buffers


TR20 Continuous

Downstream Processing

TRM Carl Carlson and Natraj Ram

authoring buffer considerations piece

for CDP white paper.


Linkages

Modes ofEngagement

Buffer Prep Prototyping and Plug and Play

Aware Buffer Prep and Plug and Play identified each other as having intra-phorum linkages which should be explored as the projects

progressed.

Align The point of alignment is the standard interface requirements specified by the Plug and Play project based on S88 and NAMUR

MTP and the opportunity to use standard services for the Buffer Prep project PLC

connecting to a higher level system.

Reference The use of standard services for the Buffer Prep project PLC connecting to a higher level system provides opportunities for both

projects to cite each other in any publications/communications

Shared Output

Whether the use of the code is entirely successful or provides a set of data/feedback for the Plug and Play team to

work with, the shared outcome is the practical application of a standardized

approach.

Case Study It may be possible for the Buffer Prep or Plug and Play Team to see the application of the standard code as part of adoption of the

BSB Skid by one of the BioPhorum member companies participating in the Prototyping

Project.

Eff

ort

Less

More

Modes ofEngagement

Description

Aware Projects/workstreams who identify each other as having touchpoints/common areas of interest

Align Consideration given to areas where alignment will benefit each workstream/project and BioPhorum as a

whole

Reference Each project is able to identify a significant enough relationship to warrant a reference or citation in each publication

highlighting the synergy or supplementary nature of both pieces of work.

Shared Output

A significant step involving a joint undertaking to deliver an outcome and/or output which supports both pieces of

work.

Case Study A sufficiently successful collaboration between projects and workstreams that should be communicated either as an

example of cross phorum working or synchronized implementation of change


Buffer Prep Comms Plan v3

What is being communicated? The Biophorum Buffer Preparation team has been working on this project for nearly 18 months. The

team has been able to successfully meet its design targets, obtained funding from NIIMBL and a

vendor, IPEC, to build the prototype. The Functionals Specification has been signed off and Pieper

Automation to whom the automation has been outsourced by IPEC, have commenced the software

development. A White Paper describing the Vision and initial work to design and specify the NIIMBL-

BioPhorum Buffer Stock Blending (BSB) System and an associated Cost of Goods paper with an

economic evaluation of the buffer stock blending approach using Biosolve modelling software

(BioPharm Services) will be published by BioPhorum in October. A further paper is to be published in

Q1 2020 to describe the Performance Testing which will have been carried out at The University of

Delaware. The dataset will be evaluated alongside further modelling data to demonstrate that the

design has achieved the expected benefits. A fully tested system with a published report on

performance is intended to influence the industry to adopt BSB systems within a year of completion of

the project. In summary:

• Industry collaboration on requirements (BioPhorum)

• Open architecture – anyone can build and improve

• Signed on consortium (NIIMBL) to build and test prototype

Key Milestones

Funding Agreement (Sept 2018)

Vendor Award (Jan 2019)

Skid Shipped (Dec 2019)

Performance Test (Jan 2020)

Addendum Publication (Q1 2020)

White Paper Publication

COG’s Paper

October 1st 2019

Article in BioPhorum newsletter

Tie in with Funding Partner Communications

White Paper Addendum Publication Q1 2020

Article in BioPhorum newsletter

Communication Channels Conference presentations (link to BioPhorum list):

Presentation and Panel Discussion at BPI East Conference Sept 2019.

Abstract submitted for BPI Europe February 2020.

Interphex, April 28-30 – good timing following publication.

BioPhorum Annual Report 2020

Presentations for BioPhorum phorums/workstreams

Video?

Social Media

CONNECT

COLLABORATE

ACCELERATE TM

Charter Pack



Charter – Continuous Downstream Processing – v6 Mar 2019


Technology Roadmapping Facilitator [email protected]

Revie

w

Problem

• xxx

Impact

• A comprehensive, balanced analysis

would be a valuable resource to

industry partners deciding whether,

why and how to enter this arena.

Benefits

• As an emerging technology, this team is trying to enable acceptance by end users.

OUT OF SCOPE

• Technical solution development

IN SCOPE

• Technology gap analysis

• Automation & control strategies

• Operational impacts

• Possible paths to implementation

INTERNAL LINKAGES

• DS: Validation of Continuous

Bioprocessing

• TRM PT implementation projects

• TRM ILM implementation projects

EXTERNAL LINKAGES

• ICH working group

• ASTM proposals

Goals

• To further the development of “better”

manufacturing in the future

• To gain clear and concise confidence and

support from regulators to reduce any

perceived ‘road block’ to continuous

uptake.

• To present case studies for model

scenarios and demonstrate benefits of

continuous processing

Deliverables• Economic modelling for continuous process models

• X

• Y

Finalize white paper

Economic modelling

Definition & prioritization

of future activities

White paper publication

Project 1 definition

Project 2 definition


Phase/Activity Deliverables Business Benefit Measures Target Owner2018

Q3

2018

Q4

2019

Q1

2019

Q2

Economic

modelling for

continuous

process models

Ecomonic model for

continuous modes of

downstream

processing,

demonstrating the

value of future

technologies

Communicate the

benefits of continuous

processing, and help

biomanufacturers model

when implementation is

appropriate.

Demonstration of ROI for

CDP implementation

• Reduction

in cost of

goods

towards

roadmap

strategy of

90%

reduction

• Facility

footprint

reduction

• Increase in

flexibility

• Metrics to

be

confirmed

from

modelling

activities

Charlie

Heise /

Andrew

Sinclair x

White paper

production

Draft white paper

outlining industry gaps

currently preventing

implementation of

continuous

downstream

To align industry around a

common vision and

message, to accelerate

journey towards

continuous downstream

processing.

On time delivery of

paper.

Mark Brower

x x

Paper review Review of paper draft

and auctioning of

review feedback.

On time delivery of

paper.

Mark Brower

x

Paper publication Final draft paper for

publication

Number of downloads Mark Browerx

Presentation to

regulatory

stakeholders

Meeting with key

regulatory stakeholders

to align towards

continuous

downstream

processing.

To gain clear and concise

confidence and support

from regulators to reduce

any perceived ‘road block’

to continuous uptake.

TBC Mark Brower

x

Definition of

future activities

TBC TBC TBC TBCx

Risks

• The path that has been developed does not meet any of the success criteria. Or that one area overshadows the other i.e. Quality is lost but cost and time is

gained. Ability to effectively describe business case. MITIGATION – Sprint activities around business case modelling. .

• Timing and availability of core authors to complete paper to timelines

Charter Activity Tracking – Continuous Downstream Processing


Linkage Phorum Synergies Communication plan Mode Status update

Continuous

Bioprocessing

Validation

DS Similar themes were raised

in both TRM and DS.

Comparison of charters completed. This team now

integrated into TRM team as per DS governance

voting October 2017.

Collaborate Luc Kupers will provide DS

review to document.

Regulatory Reg Int /

DS

Team requires regulatory

support from members.

Reg Int team members integrated into this team and

leading the regulatory section of text.

Collaborate Reg Int authors for regulatory

section (Pfizer, Novo Nordisk

and GSK).

Inline

monitoring

TRM Strategy on PAT & testing

of viral clearance.

Keep ILM teams informed as to progress. Inform Audrey Chang to review

paper.

Buffers team TRM Buffer requirements Carl Carlson and Jeff Johnson acting as link. Inform Carl Carlson and Natraj Ram

authoring buffer

considerations piece.

Disposables DS SUS vs SS review Jeff Johnson acting as link.

Modular &

Mobile

TRM Conti processing could

alter facility requirements

Jeff Johnson acting as link. Inform

Automated

Facilities

TRM Small team from AF have joined CDP to assist with

drafting automation section of white paper.

Collaborate Bob Lenich and Chad

Beesley authoring

automation consideration

piece.

Development

Phorum

BPDG Both groups wish to open

discussions with FDA late

2018.

BPDG could review TRM white paper. Both groups

looking at similar case studies eg MoBiDiK.

Facilitators to stay close to compare scopes and to

investigate closer sharing with sponsors who are

part of both teams.

Inform Facilitation teams meeting

regularly to review.

Summary

The team has successfully put together a draft paper outlining the challenges associated with continuous

downstream processing. Resource and commitment is required to get the paper completed and into review.

Effort is required to model out a business case that represents industry views, and commitment to CDP03

sprint days required to achieve this.

Linkages

Continuous Downstream Processing – Comms Plan

2 months

pre-publication

(Mar ‘19)

Are there any conferences we should be speaking at or entering a poster for?

Due to momentum of the publication, the team are unlikely to speak at any conferences before this. At this stage the team will be

defining conferences that they wish to speak at following launch in order to plan.

How can we use social media to prepare the audience for the paper?

Use of LinkedIn as soon as the draft is locked to announce the upcoming publication,

How can we socialise our own organisations?

The same LinkedIn piece could be used in member-internal newsletters etc.

What material could go into the BioPhorum newsletter, and when?- In hand with Claire/Emma/Les-

An overview of the paper should go into the nearest newsletter to planned publication (July).

Overview of the project to develop the paper has already featured in newsletters. High level business case could be reviewed

Line up with Andrew Sinclair at BioSolve- link from paper to BioSolve and vice versa. Coordinate when BioSolve will launch

newsletter

Week before

publication

(25th May 2019)

Are there any ‘teaser’ activities we can do?

LinkedIn announcement

Launch /

issue date

(End May ‘19)

Where will the paper be published?

BioPhorum website. Following this, we may choose to develop select topics for external publications - TBC

What launch activity do we want to happen? Press release? Magazine release? Social media? Webinar? Conference presentations

or roundtables?

• Needs table summary launch date announced

• Link with previous roadmaps

• Conference presentations – the team are frequently presenting as individuals, and so there is a need for both dedicated

conference slots, and a slide pack that the team can pull on to include in their own presentations where relevant.

• Follow up launch announcement on LinkedIn.

• We could consider a webinar – interested in knowing the impact / reach of BioPhorum webinars to help this decision

What is being communicated? White paper What is the targeted publication/launch/issue date? May 2019


15 Biomanufacturers

11 Supply Partners

1 Innovation Hub


• Economic modelling for

continuous process

models

• White paper

• Presentation to

regulatory stakeholders

•Contribute to reducing cost of final product from ~$50/g to ~$5/g

•Recommend industry strategy for implementation of continuous downstream

processing and enable consistent and higher quality regulatory interaction

•Identify collaboration opportunities to move industry forwards at pace

•Identify gaps and business drivers for continuous downstream processing

Q1 2019↑Speed

↓Cost

↑Quality

[email protected]



Project scope and

deliverables

Scope

White paper

Economic modelling

White paper generation

Review and publish

Regulator meetings

Chapter

Executive Summary

Introduction

Process description

Technology gaps (Large)

Single use technology

Automation (Large)

Process economics / business case

Regulatory implications

Linkages

References/Citations

Wide ranging white paper, addressing

technology gaps, regulatory

recommendations and typical

anticipated process design, is

complemented by a developing

modelling program supported by

BioPharm Services and using the

Biosolve tool.

↑Flexibility



CONNECT

COLLABORATE

ACCELERATE TM

Charter Pack

Reduce release testing need through use of in-line monitoring and real-time release


Problem

• Majority of testing required for process,

environmental monitoring & testing of

bulk drug substance or drug product is

performed off-line which requires an

additional 4-6 weeks post-production to

complete

Impact

• Total cost of supply is increased

• Total time to release product is

increased

Benefits

• Inform industry of which CQA’s & IPC’s

to be targeted for transition to in-line,

on-line or at-line monitoring which will

lead to development of technology &

tools to gain following improvements:

• Reduction in time to release product

from 4-6 weeks to 1-2 days

• Reduction in cost of non-quality

• Reduction in cost of supply

OUT OF SCOPE

• Drug Product, Environmental

monitoring, Adventitious virus,

Sterility, Bioburden, Endotoxin

IN SCOPE

• mAb, fed batch

• Upstream to Drug Substance

Charter – Reduced release testing through in-line monitoring– v2.8 Dec 2019



INTERNAL LINKAGES

• Fill Finish/ARMM, CCIT

• Drug Substance/Microbial Control

• Regulatory Interaction

• BPIT

EXTERNAL LINKAGES

• Promote project in front of regulators

(FDA, European Medicines Agency ,

etc)

Goals

• Produce a prioritized list of CQA’s &

IPC’s for transition from off-line to in-line,

on-line or at-line monitoring which will be

signed off by Sponsor & TRM-SC

• Generate rationale and business case for

each analytical candidate for conversion

• Develop URS for each analytical

candidate for conversion

• Publish white paper

Deliverables• Selection criteria established for CQA’s and IPC’s

• Prioritized list of CQA’s and IPC’s generated

• Rationale & business case for the selected candidates established

• User Requirement Specs developed

• White paper published

White Paper authoring & review

White Paper published

White Paper approval & publication

TRM SC Stage gate: Justification

Proof of concept scoping for

justification stage gate

(Aggregates monitoring &

automated bioreactor)


Critical linkages (1)


BioPhorum Fill Finish

Adoption of Step attribute Matrix

(SAM) methodology for Drug

Product attributes

Project presented at FF18 where attendees

voted to expand Project 1/7 SAM

methodology to drug product.

CallsOngoing; joining FF ILM call in

Dec ‘19.


Alternative & Rapid Micro

Methods (Environmental

Monitoring), CCIT

Progress on project being shared with FF

through quarterly joint Phorum meetings. FF

seeking ILM rep to attend F2F to discuss DP

ILM

Calls Ongoing

BioPhorumDrug

SubstanceMicrobial Control

Progress on project being shared with

Dawood through calls.Calls Ongoing

BioPhorum BPIT

BPIT can ensure that project 1/7

business case and URS’ gives

full consideration to IT

requirements.

BPIT sub-team contributing to 1/7 URS

development (data integrity piece and

indicative implementation costs)

Joint meetings

starting August

2018

Complete

BioPhorum BPDG

BPDG is developing a charter

for PAT Point Share and need

to ensure there is no overlap

ILM/RTR SME Chairs have presented to

BPDG. Key deliverables being shared

between teams. BPDG member attended

ILM02.

CallsOngoing; joint meeting being

pencilled in for February 2020

BioPhorum TR

ILM/RTR RAVnS

Microbial, virus safety are within

top 10 but are covered in other

BioPhorum workstreams

Both ILM/RTR Project 1/7 and RAVnS

projects meet with Project Sponsor every

quarter and each team will reference other’s

White Paper

Calls Ongoing

BioPhorum TR Continuous Processing

ILM/RTR Project 1/7 rep contributed to Conti

Process White Paper section and list of

prioritized attributes and URSs being

reviewed by CDP team

White Paper Ongoing

BioPhorum Cross-phorum Adoption of ILM This team will be a main contributor to this

activity, which is still in initiate phaseCalls, F2F


Critical linkages (2)


IQ

ConsortiumN.A MVDA model maintenance

IQ are publishing a paper on MVDA model

maintenance in Q2 2019 and this paper will

be referenced by ILM/RTR paper.

Reg Int MeetingIsabelle Lequeux working with the

IQ Consortium

H2020

EXTERNAL:

iMi Horizon

2020 Funded

Project

Development of Innovative

high throughput analytical tools

and methods to characterize

cell culture fluid during

development and commercial

cell culture processes

Lucs Kupers, Sanofi will present at ILM/RTR

team meetings on an annual basis.Team meeting

First presentation held on 28

November 2018 & recording

available. Schedule next

presentation for Nov 2019

Regulatory

Bodies

EXTERNAL:

FDA, EMA,

Canadian,

Japanese

Keep Reg Bodies informed on

the progress of the

project and obtain feedback on

adopted approach

Several conferences targeted for

presentation and regulatory feedback

Conference

presentations

ACS BIOT – presentation (GM)√

Bioprocessing Summit (UA) √

CaSSS CMC Strategy Forum (MA)

√

BPI Boston (UA) √

WCBP 2019 (VL) √


Charter activity tracking

Phase/

activityDeliverables Business benefit Measures Target Team

19Q

3

19Q

4

20Q

1

20Q

2

PHASE 1

WHITE PAPER

White paper with

URS’ written and

published by Feb

2020

White paper will

communicate prioritized

list of attributes and

their rationale that are

considered most critical

in realising the goal of

real-time/rapid product

release to key suppliers

and academic

researchers. The

intention is to allow a

partnership with the

Biopharma industry,

working together more

effectively for the

development of

monitoring and control

tools for prioritized

attributes.

• ASPIRATIONAL: ILM/RTR as a

vision

• Product Release time

• Reduction in cost of non-quality

• (Greater control & detectability)

• Process variability ppk and assay

quality ppk

• Inventory quantity

• Inventory cover

• ASPIRATIONAL:

ILM/RTR as a vision

• 2 weeks (5 yrs)

• ≤2 days (10 yrs)

• To 10% of total

operational costs (5

yrs)

• To 2% (10 yrs)

• >1.5 (5 yrs)

• >1.8 (10 yrs)

• 50% reduction (5 yrs)

• 90% reduction (10 yrs)

• 2 months (5 yrs)

• 2 weeks (10 yrs)

Authors: Uday Aich,

Gunnar Malmquist, Ben

Wilkes, Justin Beller,

Michalle Adkins, Ben

Arriola, David Robbins,

Andre Choo, Ho Ying

Swan, Christian Grimm

PHASE 2

PROOF OF

CONCEPT

Sponsor’s vision

documents for

proposed PoC on

aggregates

monitoring &

automated bioreactor

to enable TRM

Steering Committee

to make a decision

on justification stage

gate.

ALL

Risks

Risk of white paper timescale slipping

Status key

On-time or complete

Delayed, recovery plan

Delayed, no recovery plan


Reduced release testing through in-line monitoring

16 Biomanufacturers

8 Supply Partners

1 Innovation Hub

Scope mAb,batch

Step Attribute Matrix

Current & Desired

stateRanking

URS, Business Case &

White Paper

Proof of Concept

development

Deliverable Available Company Benefit

White paper with User Requirement

Specifications for ten attributes to guide the

development of new in-line, at-line and on-

line technologies, focused on the highest

impact CQAs and IPCs

Benefit Low Medium High Comments

Cost <$1M $1-5M >$5MBenefits selected by assuming Scenario 2 of the TRM Biomanufacturing RM &

implementation of full wish list to achieve the ultimate goal of ILM and RTR

Quality Maintain Improve Game ChangerILM will enable tighter monitoring of processes with feedback control resulting

in improved consistency, impacting manufacturing and other areas

Speed Weeks Months Years Goal is to reduce product release times from weeks to 1-2 days

FlexibilityChangeover: Weeks

Utilization: <70%

Days

70-90%

Hours

>90%

ILM/RTR will enable quicker TAT enabling more flexibility on the

manufacturing floor. Ability to react faster to recovery of an error.

Cost to

implement

Site FTEs

Capital <$10k

Business FTEs

Capital $10-50k

Industry FTEs

Capital >$50k

Technology innovation and development required. Adoption and regulatory

hurdles to overcome

Likelihood

of success<75% 75-95% >95%

This addresses the success of the ultimate goal of ILM/RTR and will perhaps

move to high likelihood for individual proof of concept elements of the program

Workstream benefits and value based on a ‘typical site’ Workstream general estimate of value Member Co. estimate of value

Last update: December 2019



ILM/RTR Project 1/7 – Comms Plan

Pre-publication

CaSSS CMC Strategy Forum Presentation, Jul 2018 (Michalle Adkins) √

BioProcessing Summit 2018 presentation, (Uday Aich) √

BPI Boston presentation, Sept 2018 (Uday Aich) √

WCBP presentation, Jan 2019 (Vaho Loladze) √

BioProcessing Days presentation, Germany, Feb 2019 (Christian Grimm) √

IFPAC presentation, Mar 2019 (Christian Grimm) √

BPI West presentation, Mar 2019 (Uday Aich) [remote presentation] √

Interphex Apr 2019 (Michalle Adkins) √

BioPharma Asia webinar (Uday Aich) Aug 2019 √

BioProcessing Summit Aug 2019 presentation, (Uday Aich) √

Week before

publication (Feb 20)

LinkedIn posts to promote imminent launch.

Launch /

issue date

(Feb 20)

Publish White Paper and URS documents on BioPhorum website

Link to White Paper from CaSSS website

BioPhorum newsletter draft text for January/ February 2020 issue

Press release in online industry papers

LinkedIn posts

Collect feedback and comments

What is being communicated? White Paper & URS documents

What is the targeted publication/launch/issue date? February 2020

CONNECT

COLLABORATE

ACCELERATE TM

Charter Pack

Development & Validation of Rapid Tests for Sterility & Adventitious Virus


Charter – Rapid methods AV & mycoplasma– v2 September 2019



Problem

• Testing of biopharmaceutical

intermediates and final product to

ensure absence of adventitious virus &

mycoplasma requires lengthy culture-

based assays delaying disposition of the

product by multiple weeks

• Scientific advances are providing new

and better RMMs that potentially offer

the same or increased detection but the

lack of a pathway for regulatory

acceptance is a key challenge

Impact

• Product yields and lost batches

• Process deviations

• Investigation /reporting of deviations

• Implementation of supply changes

• Technical requirements

• Compliance risks

Benefits

• Speed up product release from 35 to ≤2

days for mycoplasma/virus testing

• Enable adoption of rapid methods

suited for lot release testing

• Faster access for life changing

therapies for human health conditions.

• Guidebook will be applicable for today

and tomorrow’s yet to be discovered

methods

OUT OF SCOPE

• Endotoxin, Bioburden, Sterility as

covered by other Phorums

IN SCOPE

• Biologics: mAbs, CGT

INTERNAL LINKAGES

• Fill Finish/ARMM

• Drug Substance/Microbial Control

• Regulatory Interaction

• TRM Big Data to Smart Data

• ILM/RTR Technology Adoption

EXTERNAL LINKAGES

• FDA

• PDA

• EMA

• US Pharmacopoeia

Goals

• Develop and publish the Rapid Viral and

Mycoplasma Assay Collaborative

Validation Framework Guidebook (multi-

site / multi-company) with endorsement

by regulatory agencies

• Execute validation for mycoplasma PCR

method as a case study

• Develop considerations for complex

method validation e.g. NGS

• Delivery of URS documents for

Adventitious Virus and Mycoplasma

rapid tests

Deliverables• URS Mycoplasma, Adventitious Virus rapid tests

• Rapid Viral and Mycoplasma Assay Collaborative Validation Framework

Guidebook

• Execution of guidance for mycoplasma PCR

• Development of guidance for NGS

URS development & feedback

Draft outline & content for validation guidebook

Update

guidebook

Agency meeting preparation with Regulatory Interaction Group

Mycoplasma

study


Charter activity tracking: RAVnS project phase 2 (1)

Phase/

Activity

Deliverables (date of

completing deliverable

in bold text)

Business benefit Measures Target Team

19

Q4

20

Q1

20

Q2

Meeting with

Biophorum

Regulatory

Interaction group

Nov 2019

A plan for Reg Int group

involvement in project and

preparation for agency

meetings and agreed format

of product to present to

agency

• Agreed approach

between BioPhorum

teams on how to

interact with regulators

to increase chance of

success for project

• Completed regulatory risk

assessment for project

• Plan developed for

effective communication

with regulatory agencies

• Completed map of related

external activity space

• Product Release

time for AV &

mycoplasma

reduced from 35

days to ≤ 2 days

Audrey Chang, Scott

Hooper, Michael Ruffing,

Sylvanie Cassard

URS

Dec 2019

URS for AV RMM and

mycoplasma RMM

• URS’ to inform & assist

suppliers in technology

development

• URS documents drafted Myco: AuC, KMc, SH, MB,

CP, CD, SD, HMM, JA,

ETG,

AV: SH, KMc, MB, CP, CB,

SC, SD, HMM

URS

Feb 2020

Updated URS documents

based on feedback from

wider industry

• Gather feedback on

URS’ from wider

BioPhorum group

• URS documents finalized

Draft outline &

format of

guidebook

Nov 2019

Format, structure and

section plan agreed

• Multi-site / multi-

company collaborative

validation guidebook

outline defined

• Skeleton format defined

and section plans

completed

MM, KMc, CP, MR, SH, RG,

MS, AS, WN, SD, HMM

Draft content

collaborative

validation

guidebook

May 2020

‘Agency ready’ draft of AV

& mycoplasma multi-site/

multi-company validation

RMM Guidebook

• Multi-site / multi-

company collaborative


content agreed

• Validation guidebook

drafted

MM, KMc, CP, MR, SH, RG,

MS, AS, WN, SD, HMM

Execution of

mycoplasma inter

company study

June 2020

Data generation using

protocol from member

laboratories qPCR

• Demonstration of using

the guidebook for a

mycoplasma RMM

case study

• Data generated by labs tbc

Status key

On-time or complete




Phase/

ActivityDeliverables Business Benefit Measures Target Team

20

Q3

20

Q4

21

Q1

21

Q2

Update guidebook

Sept 2020

Compile data into Final

Report for Mycoplasma

Draft NGS Protocol

• Stimuli paper to gain

feedback from

industry

• Final Report

• NGS protocol

drafted

• Product Release time

for AV & mycoplasma

reduced from 35 days

to ≤ 2 days

tbc

Case study and

NGS Protocol

Dec 2020

‘Agency ready’ case study

demonstrating executed

validation protocol for

mycoplasma RMM and NGS

Protocol

• Share with agencies

as pre-read to F2F

meeting

• Case study and

validation

protocols

available in format

for agency

meetings

tbc

Regulatory agency

meeting

Feb 2021

Meeting with agencies to

obtain feedback on guidebook

& case study.(Provisional

plan for team F2F meeting

after regulatory meeting at

USP facility)

• Regulatory agency

feedback on multi-

site/ multi-company

collaborative


• Event report

including outputs,

feedback from

meeting and next

steps

tbc

Update and

publish URS,

guidebook, case

study

Jun 2021

Update & publish all

documents after agency

feedback

• multi-site/ multi-

company

collaborative


endorsed by

agencies

• Guidebooks and

URS’ published

tbc

Risks

Charter activity tracking: RAVnS project phase 2 (2)

Status key

On-time or complete




Critical linkages



Alternative & Rapid Micro

Methods (Environmental

Monitoring)

Monthly catch-up calls in progress; team

member common to both groups

F2F meetings

Facilitator calls

Draft ARMM paper shared with

TRM team.

Next call in November

BioPhorum Drug Substance Microbial ControlPhase 2 plan to be shared as part of

awareness building

Facilitator calls

BioPhorumTechnology

RoadmappingILM/RTR Prioritization project

Keep aware of status. White paper was

shared.Joint calls

BioPhorum Cross-Phorum

ILM/RTR Tech Adoption

program Facilitator calls

BioPhorumDevelopment

Group

PAT monitoring & control

workstream

Monthly catch-up calls in progress; white

paper was shared; joint team meeting

pencilled in for February to update on status

Joint calls Monthly catch-up calls in progress

BioPhorumRegulatory

Interaction

Work with Reg Int group on

guidebook framework and

agency meeting preparation

Joint calls Joint meeting held in November ‘19

BioPhorumTechnology

Roadmapping

Continuous Downstream

ProcessingMaintain awareness of workstream activity Facilitator calls Awareness of status at TR10

Regulatory

BodiesFDA, USP, EMA

Stimuli paper with USP

F2F meetings with agencies

USP will be invited to team meetings.

Reg Int group will assist in securing

meetings with agencies

F2F meetings,

USP team

members

Awaiting MoU and NDA before

USP join meetings


[email protected]

Rapid methods for adventitious virus & mycoplasma detection

17 Biomanufacturers

3 Supply Partners

1 Innovation Hub

User Requirement Specifications

Draft

Collaborative validation

guidebook for RMM

Mycoplasma validation case study

Meeting with regulatory agencies

Publish collaborative

validation guidebook for RMM, URS & case study


Develop User Requirement Specifications

for adventitious virus and mycoplasma

alternative RMM

Develop AV and mycoplasma collaborative

validation guidebook for alternative RMM

(multi-site, multi-company)

Draft mycoplasma RMM validation case

study

Meet with regulatory agencies to obtain

feedback on guidebook

Publish URS, guidebook and case study by

June 2021

Read precursor white paper HERE


Cost <$1M $1-5M >$5M

Benefits selected by assuming Scenario 2 of the TRM Biomanufacturing RM

and 1yr timescale. Freeing up production capacity, increasing throughput &

producing more batches, reducing inventories, responding to events quicker

Quality Maintain Improve Game Changer Specificity and broader spectrum of viruses being detected

Speed Weeks Months Years Speed up product release time for Adventitious virus from 35 days to < 2 days


Utilization: <70%

Days

70-90%

Hours

>90%

Cost to

implement

Site FTEs

Capital <$10k

Business FTEs

Capital $10-50k

Industry FTEs

Capital >$50kEquipment costs, validation costs and time

Likelihood

of success<75% 75-95% >95%


Last update: December 2019

Outputs from industry survey

Key Learning Points:

• Main point of dissatisfaction with current methods was time to result

• Compendial methods are being used for lot release & new technologies are being used as

secondary means

• Mycoplasma testing showing trend to move toward molecular alternative with regulatory acceptance

• 100% believe that RMM will be in place as a release test in 5-10 years

Top 3 concerns: New RMM adoption

Regulatory acceptance

Filing regulatory change control

Time to validation

Top 3 activities: Drive RMM adoption

Comparability studies between methods

Collaboration with agencies

Best practice/ standard protocol

1

2

3

1

2

3

FDA/ BioPhorum Meeting

Q. Current validation principles of RMMs mean

that very similar testing is repeated by each user

of the technology and each company site with

limited value added to assessment of the

technology performance and robustness.

A. Multi-site and collaborative validation

approach for different companies is acceptable

to FDA and recommends to use the DMF

process where proprietary information is shared

by the vendor with the agency, as well as the

qualification data. DMF holder to have

proprietary information + user information.

https://www.biophorum.com/how-to-expedite-the-adoption-of-alternative-rapid-microbiology-methods/

ILM/RTR Project RAVnS – Comms Plan

What is being communicated? • Rapid Viral and Mycoplasma Assay Collaborative Validation Framework Guidebook

• User Requirement Specifications for viral and mycoplasma RMM

• Multi-site/multi-company validation protocol for rapid mycoplasma method

What is the targeted publication/launch/issue date? June 2021

Pre-publication

WCBP, January 2020, Washington DC [Participating in BioPhorum PlenShop session,

Audrey Chang]

CaSSS Bioassays 2020, April 2020, Gaithersburg, MD

MIT CAACB (Consortium on Adventitious Agent Contamination in Biomanufacturing) Spring

2020 [Scott Hooper]

Stimuli Paper with USP September 2020?

PDA Annual Global Conference on Pharmaceutical Microbiology (Oct 2020) [Sven

Deutschmann]

Meetings with regulatory agencies, February 2021

BPI Europe, April 2021 [Cristina Barbirato]

Launch /

issue date

(June 2021)

BioPhorum newsletter

LinkedIn

CONNECT

COLLABORATE

ACCELERATE TM

Charter Pack



Charter – Standard Facility Design – Revised June 2019

Problem

• The biomanufacturing industry has a

need to gain faster capacity increases

without elevated capital costs,

regeneration of design processes (and

costs involved), interruption of existing

processes and lengthy construction

timelines.

Impact

• Rapid, cost-effective capacity addition.

• Reduce time to market / Faster

product launch

• Allow cloning or rapid repurposing of

manufacturing platforms

• Reduce design & qualification time

• Reduce/eliminate disruption to existing

product supply.

• Ability to flexibly scale up, scale out,

and also scale back

• Risk is reduced due to the ability to

flex and repurpose the assets.

Deliverables• Define facility platforms for different applications

• Create guidance/toolkit for designing biopharmaceutical

manufacturing facilities using modular approach and standardized

components

• Illustrate methodology with case study

Goal

Define user requirements and standard facility

options to rapidly respond to biologics m’facturing

production needs (<1 year response time).

Benefits

Ability to execute a project faster, more efficiently,

and with less risk than a traditional construction

approach.

• Speed of deployment - reduce time to

launch/delay investment by 4/5 months

• Flexibility to use site for multi-

purposes/products and mobility to bring

capacity to the location of demand

• Replicating previous job reduce time to

launch/delays investment by 3-6 months

• Capacity flexing or scaling without interruption

of existing processes

• Repurpose (not standing redundant/no

depreciation on unused capacity)

• Risk mitigation if no launch – no redundant

capacity

• $ Defer capital expenditure e.g. 2x2K $20-

80m until product success more certain

• $ Predictability of cost and delivery mitigates

against delays caused by Change

Orders, Drilling, Weather Delays

• $ Bottom Line:

Stick built +/-10%; Factory built +/-5%

Facilitator [email protected] Roadmapping

OUT OF SCOPE

• Equipment design

• Site infrastructure

• Facility shell building

• Plant utilities

• Shared process support

• Consumables

• Other infrastructure eg

warehousing, labs

IN SCOPE

• Process flows

• Materials handling logistics

• Utilities

• Facility platform infrastructures

• Automation architecture & PAT, MES

• Shared language development

• Process equipment scale and range

INTERNAL LINKAGES

• Other 1st edition TRM project teams

(buffers, continuous processing, ILM,

automation)

• Closed Systems

• Disposables program

EXTERNAL LINKAGES

Complete white

paper

Evaluate another (theoretical) example

Prepare for publication

Comms/Conferences

Agree the ‘How’ – standards, catalogues, etc

Publish White Paper

Publish

Case Study - Methodology


Phase/


2018

Q3

2018

Q4

2019

H1

2019

H2

Requirements Standardised

Requirements for

Modularisation

• Speed of deployment, including

design and build

• Flexibility to use the site for

multi-purposes and multi-

products

• Cloning and copying of the site

also for in-country/for country

installations

• Capacity flexing or scaling

without interruption of existing

processes

• Mobility, if needed to bring

capacity to the location of

demand

• Risk mitigation if no launch – no

redundant capacity

• Predictability of cost and delivery

mitigates against delays caused

by

• Change Orders

• Drilling

• Weather Delays

• Reduce time to

launch/delay investment

by 4/5 months

• Replicating previous job

reduce time to

launch/delays investment

by 3-6 months

• Defer capital expenditure

e.g. 2x2K $20-80m until

product success more

certain

• Repurpose (not standing

redundant/no

depreciation on unused

capacity)

• Stick built +/-10%; factory

built +/-5%

These measures relate to

the Business Benefit but are

unlikely to be realized until

the Adoption phase.

x

Design Design

Documentation

(Layout,

Podularization

etc)

x

Content

Authoring

White Paper

Structure

x

Publication Modularisation

Approach

Definition x

Addendum (Theoretical)

Example

• Demonstrating the application of

the modular approach in a

second scenario.

• White Paper downloads

• Feedback from members

companies

• Prolifieration of tools on the

market

• Increased standardization

by vendors

x

Case Study • Showing the application of the

modular approach using a tool

available on the market.x

Tool

(Guidance)

‘How’ • Practical help to improve the

level and pace of adoption

• Adoption of Tool

• Projects Completed

Risks

Critical that requirements are driven by biomanufacturers – quorum of at least 5 in the team agreed.

Charter Activity Tracking – Standard Facility Design


Linkage Phorum Synergies Communication Plan Mode Status Update

TR6 Buffer

Prep

TRM Buffer technology could change

facility requirements.

TRM Facilitation Team Consult Potential linkage identified but not yet

explored

TR21 Plug

and Play

TRM Teams presented progress to each

other at MM01/AF01

TRM Facilitation Team Consult Discussions opened between the 2

groups; charters and objectives shared

TR20 Conti

Processing

TRM Conti processing could alter facility

requirements

TRM Facilitation Team Collaborate Potential linkage identified but not yet

explored

Drug

Substance

Phorum

DS Closed Systems - David Estape is

link to Standard Facility Design

Disposables - 1st Edition needs fed

into DS disposables 5yr strategy.

TRM Facilitation Team

Derek to reach out to

Daniele

Collaborate Discussions opened between the 2

groups; charters and objectives shared.

TR09 being co-located with BPOG33

Key Linkages


Phorums working together in a coordinated program of industry change

Buffer Preparation




process

Lean Qualification / Validation

Disposables –Change Notification

Deviation Management System

Post Approval Supplement Strategies

Human Performance


QC Stability

Reliability

Alternatives and Rapid Micro Methods

Container Closure Integrity Testing

(CCIT)

EM in a Modern DP Facility

Sterile Filtration Quality Risk Management

(formerly PUPSIT)

Visual Inspection / Particulate Control

Lyophilization Digital Plant Maturity

Smart Maintenance

Compliant Multi-Source Analytics

Viral Clearance

Formulation

Development Outsourcing

CMC Regulatory

Host Cell Proteins

Cell Line Stability(previously

Demonstration of Monoclonality)

Qualification of Small Scale Models

Forced Degradation Studies

Bioassay

Knowledge Management in Development

CMC Considerations for Expedited Development

Programs

Analytics


Rapid Methods for Adventitious

Detection and Assurance

Harvest ClarificationRapid Release Testing through Inline Monitoring



Robotics

Plug and Play

Disposables – Supply Base Reliability

Disposables –Testing, Validation & Release Standards

Storage & Transport

Supply Chain Visibility – CMO

Integration

Raw Material Variability

Disposables – E&L

Disposables – SUS URS

Closed Systems

Multi-product Facilities

Supply Agility New Product

Introduction

Risk Management and Business

Continuity Planning

Joint Audit Program

Aggregated Biopharma

Capacity Analysis

Microbial ControlOperational

Harmonization

Cybersecurity/ Plant Resilience, Recovery

Strategic Supply Chain Control

PAT Monitoring and Control

Isolator Good Operating Practice

Agile in GxPPlaybook

QMS Simplification -Change Control

Supply Chain Mapping

Forecast and Demand Planning

SPITDGFFDSTR RI

Process Development

Process Technology

Inline Monitoring & Real Time Release

Modular & Mobile Automated FacilityKnowledge

ManagementSupply Partnership

ManagementOperations, Quality

& Compliance


Draft Standard Facility Design Linkages

Buffer Preparation


Closed Systems

Plug and Play


RoboticsMulti-product

Facilities

Disposables – E&LDisposables – SUS

URS



process

Rapid Methods for Adventitious Detection

and Assurance

QC Stability

Digital Plant Maturity



Smart Maintenance

Rapid Release Testing through

Inline Monitoring

Numerous touchpoints – opportunities to

standardize in many projects to support

and enable the modular approach.


Standard Facility Design Comms Plan 2019-20 v3

Publication Process

March/April

Presentation at TR09

Austin Lock, PM Group

Week before

Publication

Personal LinkedIn posts to promote imminent launch?

Discuss on industry chat forums e.g. ISPE

Publication Date Press release in online industry papers, BioPhorum website, LinkedIn posts


1st June Article in BioPhorum newsletter

Throughout June BioPhorum Internal Comms – Linkage PM Web Component Standardization. Present to

C&GT Phorum, Single Use and Closed Systems. Charles Heffernan

Throughout June Reach out to major vendors such as GE, G-CON, Millipore, Sartorius and see if they will

put a link on their website.

Conferences PDA Europe BioManufacturing, 03-04 Sep 2019, Munich, Germany Maik Jornitz

BioProcess International (BPI) Conference & Exhibition, Boston, 09-12 Sep 2019 Jayanthi

Grebin

PMMI Pack Expo, Las Vegas, NV USA, September 23—25, 2019

ISPE Annual Meeting and Expo 2019, Las Vegas, Nevada 27-30 Oct 2019

Peptalk, San Diego, USA, 20-24 Jan 2020

ISPE Facility of the Future Conference, Las Vegas, February 2020

Bioprocessing Summit Europe, Barcelona, Spain, 24-26 Mar 2020, Jayanthi Grebin

Interphex 2020, New York, 28-30 Apr 2020 Maik Jornitz

ISPE Facilities of the Future Conference, Amsterdam, Netherlands. 18-20 Mar 2020

Phacilitate Leaders World and World Stem Cell Summit, Miami, 20-24 January 2020

Dennis Powers and Maik Jornitz

Other thoughts Life Sciences Connect Electronic Journal https://www.lifescienceconnect.com/

A few smaller intimate shows such as:

https://www.bioprocessingsummit.com/

https://10times.com/biomanufacturing-world-summit

Senior level summits such as Generis https://biomanamerica.com/

https://10times.com/sandiego-us/conferences

https://10times.com/usa/conferences

https://10times.com/barcelona-es/conferences

https://10times.com/spain/conferences

https://10times.com/amsterdam-nl/conferences

https://10times.com/netherlands/conferences

https://www.lifescienceconnect.com/

https://www.bioprocessingsummit.com/

https://10times.com/biomanufacturing-world-summit

https://biomanamerica.com/


5 Biomanufacturers

9 Supply Partners

0 Innovation Hub


Define user requirements and

standard facility options to

respond to biologics

manufacturing production needs

using single use technologies to

be established in less than 1

year.

Define further layout as a

second example of application of

modular approach and publish in

Addendum with Case Study

illustrating a tool available on the

market enabling modular facility

design.

The value in the standardized modular approach to facility design and construction lies within its

ability to execute a project faster, more efficiently, and with less risk than a traditional construction

approach.

• Speed of deployment - reduce time to launch/delay investment by 4/5 months

• Flexibility to use site for multi-purposes/products and mobility to bring capacity

to the location of demand

• Replicating previous job reduce time to launch/delays investment by 3-6 months

• Capacity flexing or scaling without interruption of existing processes

• Repurpose (not standing redundant/no depreciation on unused capacity)

• Risk mitigation if no launch – no redundant capacity

• Defer capital expenditure e.g. 2x2K $20-80m until product success more certain

• Predictability of cost and delivery mitigates against delays caused by Change

Orders, Drilling, Weather Delays

• Bottom Line: Stick built +/-10%; factory built +/-5%

Q2 2019

↑Speed

↓Cost




The Standard Facility Design team has benefitted from additional team members

and is now ‘quorate’ with biomanufacturers.

The White Paper has been completed and is with the BioPhorum Publications

Team. SFD03 is planned for June 2019 and will enable the team to develop

another theoretical example and a case study.

The team are now interested in exploring further the linkages between Standard

Facility Design and other key projects across TRM and the Drug Substance

phorum.

↑Flexibility

ScopeStandard

ReqLayout

Modular

Design

Approach

White

Paper

Example

Case

Study

‘How’

GuidanceAddendum Adoption



CONNECT

COLLABORATE

ACCELERATE TM

Charter – Big Data to Smart Data

Version Date: 2 Aug 2019

Facilitator: Robin Payne

Version Change: Updated sequence and removed Risk Flag



Problem• The data required to improve

process performance and make

better manufacturing operational

decisions exists today but is

scattered across multiple systems,

in a wide variety of formats and is

difficult to assemble into context for

evaluation, reporting and decision

support.

• Production / operations / quality

management personnel spend the

majority of their time in gathering

and contextualizing data rather

utilizing consolidated data in

context for operational

improvements

Impact• Affects manufacturing

operations, quality,

maintenance

Goals• Industry standard taxonomy /

indexing for data sources that

supply data for manufacturing

• Architecture for solution for

adding context to data

sources that can’t add in

context when data created

Benefits • Direct: reduction in time for

investigations by having

contextualized data available

• Indirect: providing

contextualized data to other


enabling them to implement

solutions quicker with less

costs


OUT OF SCOPE

• Data Integrity, security and storage

• How to implement context

• Product stage needs not related to use

cases

IN SCOPE

• Use case applications

• Product stages including: process

development, clinical

manufacturing, commercial

manufacturing, packaging

INTERNAL LINKAGES

• BPIT Workstreams

• TR: Plug & Play

• IT: Knowledge Management

• TR: Real-time Release

EXTERNAL LINKAGES

• Allotrope Foundation

• ISA-95

• NAMUR 148

• Wand

Align on Use Cases

Use Case Data Map

Map to Activities and Sources

Resolve with IT via BPIT

Joint Planning with BPIT

© BioPhorum Operations Group Ltd

F2F Meeting Publication Target

NIIMBL Concept

Paper



Problem• The data required to improve

process performance and make

better manufacturing operational

decisions exists today but is

scattered across multiple systems,

in a wide variety of formats and is

difficult to assemble into context for

evaluation, reporting and decision

support.

• Production / operations / quality

management personnel spend the

majority of their time in gathering

and contextualizing data rather

utilizing consolidated data in

context for operational

improvements

Impact• Affects manufacturing

operations, quality,

maintenance

Goals• Industry standard taxonomy /

indexing for data sources that

supply data for manufacturing

• Architecture for solution for



context when data created

Benefits • Direct: reduction in time for

investigations by having

contextualized data available

• Indirect: providing

contextualized data to other


enabling them to implement

solutions quicker with less

costs


OUT OF SCOPE

• Data Integrity, security and storage

• How to implement context

• Product stage needs not related to use

cases

IN SCOPE

• Use case applications

• Product stages including: process

development, clinical

manufacturing, commercial

manufacturing, packaging

INTERNAL LINKAGES

• BPIT Workstreams

• TR: Plug & Play

• IT: Knowledge Management

• TR: Real-time Release

• TR: Buffer Prep

EXTERNAL LINKAGES

• Allotrope Foundation

• ISA-95

• NAMUR 148

• Wand

0. Set up PoC

Phase 1: Thirty 30L

batches

Phase 2: Model

and taxonomy

Phase 3: Up to

30 batches

5. Comms



Q1 2020 Q2 2020 Q3 2020 Q4 2020

Draft created by Robin Payne: 15th Oct 2019.

For TR10 Steering Committee Meeting.

NIIMBL Detailed

PoC Plan

Phase 4: Capturing

learning

Q2 2021


Phase /

Activity

Deliverables Business Benefit Acceptance Criteria Owner(s) 19

Q1

19

Q2

19

Q3

19

Q4

Align on

use cases

List of use cases and

descriptions

Confirm scope of

project

Agreement across user roles for

key manufacturing needs

Team

• Data map for all the use

cased identified

• Map sources and align on

scope

Aligned and unified

overviews

All use case needs and

documented

Team

X

Data Map to

activities

and sources

Map data to activity and

sources including functional

groups as first proposal

Systematic

prerequisites for

discussion with IT

All use case needs and

documented

Bob Lenich

X

Resolve

with IT

organization

s in

member

companies

Review Map Data, activities

and sources with BPIT

• Systematic

prerequisites for

discussion with IT

• Aligned view with

BPIT

• Approved by BioPhorum

• Approved by BPIT

Derrick

Tapscott

X

Define

Activities

Joint agreement with BPIT /

BPOG about next activities

• Common plan to

work on

• Plan set-up ready TeamX

PoC Align with key stakeholders:

• BPIT model for DPMM

• BioPhorum “plug & play”

to understand data

context requirements

• Tangible example

of setting up for

Smart Big Data

usage.

• Set linkage to Plant

maturity model

• Set linkages to Plug & Play

model

Team

X

Write a

White

Paper

• A paper capturing an

account of the PoC with

captured learning. This

became the NIIMBL

Concept Paper.

• Enhanced potential

to implement Big

Data to Smart

Data solutions.

• Actionable learning points for

all member companies.

Philippe

Eberhard

x

Charter – Big Data to Smart Data Project



Plug & Play

With

Big Data to Smart

Data

TR The outputs of the

Software Simulation will

be used as input data for

the Big Data Software

Simulation

Key to this is a check that

contextual requirements

are met by the Plug and

Play interface

specification and data

models.

1. Members of the Big Data

team are also part of the Plug

and Play team.

2. Updates will take place on

Automated Facility Full Team

calls.

3. Robin Payne facilitates both

projects.

4. Bob checking details of the

SUB data model.

Direct

engagement

and updates on

calls.

Unlikely that data will come from Plug

and Play in a reasonable timescale for

Big Data to work with it. Real Data

might come at the end of 2019, or

more likely into 2020.

Big Data with Buffer

Prep

TR Opportunity for Big Data

to work with data from the

Buffer Prep prototype

skid.

1. Robin to discuss with

facilitator Daniele Wiseman.

Linkages


5 Biomanufacturers

6 Supply Partners

4 Innovation Hub


Industry standard

taxonomy / indexing for

data sources that supply

data for manufacturing.

Architecture for solution for



context when data created.

PoC – Tangible example

of how to set up for

Smart Big Data usage.

Direct benefits is reduction in time for investigations by having contextualized data available.

Indirect benefits by providing contextualized data to other work streams (like MVA, PAT, CPV, etc.)

enabling them to implement solutions quicker with less costs.

• Reduce time to assemble data (80% to 10%)

• increase time to process data (20% to 90%)

Q3 2019

Q2 2020 –

Q2 2021

↑Speed

↓Cost

↑Quality

[email protected]


Align on use cases

Use case data map

Resolve activities and sources with member IT orgs

Proof of ConceptWhite paper publication

↑Flexibility

The Big Data to Smart Data team

have produced:

1. A table of important use

cases for the improved

application of Big Data, and

focused in on Continued

Process Verification, with the

potential ideal state of

‘closed-loop’ process control;

2. A standard taxonomy (or

‘Data Dictionary’) for

contextualising data, with a

recommended process for

governing contextualisation;

3. And is designing a systems

architecture as the basis for

Proof of Concept in 2019.

Table of Important Use Cases Standard Taxonomy for Context PoC Execution



Plug & Play

With

Big Data to Smart

Data

TR The outputs of the

Software Simulation will

be used as input data for

the Big Data Software

Simulation

Key to this is a check that

contextual requirements

are met by the Plug and

Play interface

specification and data

models.


team are also part of the Plug

and Play team.


Automated Facility Full Team

calls.

3. Robin Payne facilitates both

projects.

4. Bob checking details of the

SUB data model.

Direct

engagement

and updates on

calls.

Unlikely that data will come from Plug

and Play in a reasonable timescale for

Big Data to work with it. Real Data

might come at the end of 2019, or

more likely into 2020.

Big Data with Buffer

Prep

TR Opportunity for Big Data

to work with data from the

Buffer Prep prototype

skid.

1. Robin to discuss with

facilitator Daniele Wiseman.

Linkages


BioPho

rum

TRM

BioPhor

um IT

Synergies Communication

Plan

Mode/R

ACI

Status Update

Automated

Facility; Big

Data

(Robin)

Smart

Maintenance

; Phase 2

(Jon)

• Use of IoT, enterprise data and

artificial intelligence.

• Potential to share on Use-Cases /

Pilot.

• Standards (e.g. ASTM).

• Other organisations – e.g. Allotrope

Foundation

Ongoing updates with TRM

team

Discuss with Robin Payne -

monthly (15/5/19 & 20/6/19).

Plan follow up post BD01 PoC

to NIIMBL; keep IT and TRM

SMEs informed

Collaborate Potential linkages identified

and being further defined.

Potential to link individuals to

BD01 F2F (Nov. 12-14) +

BTEC/Applied Materials.

Supply

Chain

Visibility;

CMO

Integration

(Jon)

• Use of Big Data across

Manufacturers and CMOs

• Findings from ‘Sprints’

CMO Integration W/S may

launch after CMO Summit

12-14 November 2019.

Compliant

MSA (Tim)

• Big Data has the Use case of CPP

development and CPV, with the

potential to close the loop on process

control.

• Allotrope

• Robin talks with Tim Horton

(BPIT facilitator on a monthly

basis)

• Likely exchange of

presentations or shared call –

Q2 2019

• Seek ongoing support and

right SMEs from BPIT Leaders

Engagement

at

appropriate

times in the

project

lifecycle.

Intending to share progress

on Contextualisation and

design of a PoC, including

the architecture for data

analysis across the lifecycle

of the product.

Drafting ‘foundation

guidance’

IT / TRM Linkages (v170719)

Comms Plan – Knowledge Management

15-1 months

pre-publication

BPI West presentation, Mar 2019 – Bob Lenich

BPI Europe presentation, - Viktor Sander

Week before

publication


Launch /

issue date



LinkedIn posts


What is being communicated? White PaperWhat is the targeted publication/launch/issue date? September 2019

CONNECT

COLLABORATE

ACCELERATE TM

Charter Pack

Robotic Technologies


Charter – Robotic Technologies – v11 Oct 2019



Problem

• high Labor Costs in BioMF - 40 to 50% of

OPEX

• highest demand for robotics for moving or

manipulating steps is unknown.

•scale-out of Cell Therapy is proving

problematic

•no industry wide plan to harmonise

communication between robots and the

equipment they will be interacting with.

Impact

• missed opportunities to deploy

robotics solutions

• a lack of a communication standard

will result in expensive integration

efforts by the end user.

Benefits

• acceleration of the adoption of robotics

in Biopharma to:-

• reduced health and safety

risks to personnel

• more efficient use of personnel

• greater throughput /

productivity

• reduction in errors

• improve quality of operations.

OUT OF SCOPE

• Drug Product

• Technology Development

• BPOG TR Scenario 5 – ‘very small

scale manufacturing

IN SCOPE

• DS Manufacturing

• Drug Substance

INTERNAL LINKAGES

• Plug and Play

• Modular and Mobile

EXTERNAL LINKAGES

• Robotic Industry Assoc (RIA)

• FDA ETT, EMA

• ARM (Advanced Robotics for

Manufacturing Institute)

Goals

• end-user interviews

• list of prioritised targets

• plan for the 1st prototype

• 1st annual “Robotics in Bipharma”

conference

Deliverables• industry survey

• prioritised list of targets

• a working prototype

• a new conference

Robotics

conference

Recommend

prototypes

Interviews with

robotics visionaries

Review

Develop chosen

business cases

Review

Develop URS/

prototype


Phase /

Activity

Deliverables Business Benefit Acceptance

Criteria

Owner(s) 19

Q1

19

Q2

19

Q3

19

Q4

• Identify repetitive

& non-ergonomic

tasks

• Detailed spread sheet

outlining all manual tasks

performed in Bio facilities

• Common structure to identify

labour intensive tasks

• Classify the labour intensive

tasks with respect to

BioManufacturing scenarios

Hierarchy of tasks

acceptance

RB, DW, MB,

CC

x

• Survey of Bio

facility Heads

• Anonymous survey • Identify Top Needs / Demands

to be targeted for automating

via Robotics

Minimum 30 responses

Verify survey findings

with BPOG members

BPOG Fac,

TBD x x

• Evaluate

Technical

Feasibility to

satisfy top

Demands

• Identify available

technologies

• Perform TRL assessments

of technologies

• Public challenge

• Publicize to end users and

suppliers (e.g. Dissemination

event) so solutions can be fully

developed for implementation

CC, MB

x x

• Estimate top

business cases

• Quantified benefits and

costs

• BPOG Presentations and

Publications

• ROI estimation

• Opportunity for OPEX

reduction

CC, TBD

x x

• 1st annual

Robotics in

Biopharma

conference

• Conference • Bring together suppliers and

end users focussing on

standardisation, regulation and

applications

Cc, DW

x

• Creation of

prototype (s)

Working prototype (s) • enable suppliers to create

working examples that can

help create the communication

standards

CC, DW

2020

Charter – Robotic Technologies – July 2019


Linkages:


AF

With

Operator of the

Future (coalition of

the willing)

NIIMBL

Technical

Universities-

TUD/UCD

Buffer Prep

University of

Delaware

Plug and Play

Cell and Gene

Therapy

Logistics

QC/analytics

Enterprise Ireland

NIBRT

TRM

BPIT

External

TRM

External

TRM

TRM

OpF provides

indication of

use cases for

Robotics

ARM

1. Share OpF sheet of cases with Robotics.

2. Robotics envisages solutions.

3. Robotics shares back with OpF CoW.

4. University of Delaware

Facilitators

Specification

call.

Ongoing.

Robotic Technologies – Comms Plan

Robotics conference

Pull together a conference on Robotics in Biopharma – 1st week in December

How can we use social media to prepare the audience for the conference?

Use of LinkedIn as soon as the draft is locked to announce the upcoming publication,

How can we socialise our own organisations?

The same LinkedIn piece could be used in member-internal newsletters etc.

Use of groups social contacts to attract speakers, suppliers and sponsorship.

What is being communicated? BPI paper and white paper What is the targeted publication/launch/issue date? Mar 2109


[email protected]

Robotic Technologies

3 Biomanufacturers

5 Supply PartnersID repetitive

tasksSurvey Bio-

facility headsID problem

areasFurther detailed

interviews


• Working Prototypes

• Automation conference

• Case studies

• URS/ business plans


Cost <$1M $1-5M >$5M

Quality Maintain Improve Game Changer

Reduction in errors

Improve quality of operations

Reduced health and safety risks to personnel

Speed Weeks Months Years Greater throughput / productivity


Utilization: <70%

Days

70-90%

Hours

>90%

Cost to

implement

Site FTEs

Capital <$10k

Business FTEs

Capital $10-50k

Industry FTEs

Capital >$50k

Likelihood

of success<75% 75-95% >95%


Stakeholder Engagement

Functional

Engagement

Required

Criticality

(H)

MSAT/Operational High

Procurement High

Quality High

Regulatory Medium

What does implementation mean?

• based on clear business case with benefits and

risks identified

• systems installed and working on production

line

• confidence in robustness and benefits to be

realized

•

Features:

• Identify end-user high-level needs

• Understand and prioritize concepts

• Business case

• prototype

Last update: 30 July 2019

Business case,

solutions & prototypePrioritized

concepts

CONNECT

COLLABORATE

ACCELERATE TM

Plug and Play

Charter Pack


Charter – Plug and Play

ProblemA move to single use equipment

which allows flexible and multi

molecule facilities where the

lack of equipment and

automation standardisation

leads to:

• Inability to easily switch unit

op technology

• High cost of automation

integration

• Each interface is a unique

development effort

• Each effort is sequential and

puts automation on the

critical path

• High maintenance cost of

custom engineered interface

Impact• Reduced flexibility

• Long build times

• High cost of integration

• High cost of maintenance

Goals• Proof of concept, connect skid control

system to PCS with soft simulation of

skid equipment.

• Definition of 3 data models –

Bioreactor, Chromatography, Normal

Flow Filtration

BenefitsThis project will significantly affect:

• Speed - faster build times and

reconfiguration times, delay

decision to build.

• Cost - eliminate development costs

for custom interfaces.

• Quality - Reduced verification and

variability.

• Flexibility - Ability to easily

switch unit op technology to

best in class.

1. White Paper

2. Standard V1

B-Interface


OUT OF SCOPE

• SIP, CIP considerations

• Vendor IP

IN SCOPE

• Single use highly modular

equipment packages.

INTERNAL LINKAGES

• Modular & Mobile

• Upstream/Downstream

• Big Data.

EXTERNAL LINKAGES

• Open Process Automation Forum

• NAMUR



Governance

Hardware Testing3. Demonstration /

Implementation

PP02 PP03

Opportunity: Fully aligning with NAMUR MTP is now

Agreed in Team.


Charter – Plug and Play

Problem

A move to single use equipment

which allows flexible and multi

molecule facilities where the lack of

equipment and automation

standardisation leads to:

• Inability to easily switch unit op

technology

• High cost of automation

integration

• Each interface is a unique

development effort

• Each effort is sequential and

puts automation on the critical

path

• High maintenance cost of

custom engineered interface

Impact

• Reduced flexibility

• Long build times

• High cost of integration

• High cost of maintenance

Goals

• Proof of concept, connect skid control

system to PCS with soft simulation of skid

equipment.

• Definition of 3 data models – Bioreactor,

Chromatography, Normal Flow Filtration

Benefits

This project will significantly affect:

• Speed - faster build times and

reconfiguration times, delay

decision to build.

• Cost - eliminate development costs for

custom interfaces.

• Quality - Reduced verification and

variability.

• Flexibility - Ability to easily switch

unit op technology to best in class.

4. Communications – Papers / Conferences

1. Standards for More Unit Operations – NFF,

Chrom, SFF?

3. B-Interface


OUT OF SCOPE

• SIP, CIP considerations

• Vendor IP

IN SCOPE

• Single use highly modular

equipment packages.

INTERNAL LINKAGES

• Modular & Mobile

• Upstream/Downstream

• Big Data.

EXTERNAL LINKAGES

• Open Process Automation Forum

• NAMUR / VDI

© BioPhorum Operations Group LtdF2F Meeting Publication Target

2. Governance – Align to NAMUR MTP – Syntax / Publication

Process

Hardware TestingDemonstration /

Implementation

PP04

Q1 2020 Q2 2020 Q3 2020 Q4 2020

1. Standards for More Unit

Operations - Downstream

VPN - $24k for

2yrs

End User on site

Implementation

Alarms and

Condistions


Phase / Activity Deliverables Business Benefit Acceptance Criteria Owner(s) 19Q1 19Q2 19Q3 19Q4

1. White Paper • Document describing the

set up and outcomes of

the Software Simulation.

• A basis for

implementing Plug and

Play, enabling:

• Faster build times;

• Reduced start-up costs;

• Increased flexibility.

Authors and reviews

approve the paper.

Keith

Morris /

Gene Tung

x

2. End User

Standard

• SUB Data Model (then

others) Standard control

parameters for bioreactor,

chromatography and

normal flow filtration.

• A basis for

implementing Plug and

Play, enabling:

• Faster build times;

• Reduced start-up costs;

• Increased flexibility.

Interface

components align

with NAMUR MTP.

Context content

aligns with Big Data

to Smart Data.

Includes Validation

Strategy.

Rex Polley

x X

3.

Implementation

Tracking

• A tool for assessing

implementation and benefit

across the industry.

• Benchmarking;

• Benefit and impact

tracking across the

industry.

x

Charter – TRM Plug and Play

Opportunity

to

accelerate

progress

with Data

Models!

Across DS

manufactur

e and into

DP?


7 Biomanufacturers

10Supply Partners

1 Innovation Hub


White paper / URS for a

plug and play prototype

demonstrating how

automation can: reduce

build and reconfiguration

times, improve efficiency

and reduce the cost of

quality. Supplier

members aligning to

deliver the prototype.

•Speed - faster build times and reconfiguration times, delay decision to

build

•Cost - eliminate development costs for custom interfaces

•Quality - reduced verification and variability.

•Flexibility - ability to easily switch unit op technology to best in class

Q3 2019

↑Speed

↓Cost

[email protected]

Plug & Play Technologies


Current team activities include:

1. Initial standard data models for:

• Bioreactor – team focus;

• Normal Flow Filtration.

• Chromatography;

• Small Flexible Filler – Opportunity?

N.B. End User Standardization is critical to the

success of implementation in this project

2. Initial Vendor Interface model.

N.B. Success depends on PoC1 going well and

End User Standardization in the longer run.

3. Draft white paper with Test Plan for software

simulation (PoC1 @AF02: 13-15th Nov. 2018,

Portsmouth UK).

4. Terms of Reference for a hardware simulation

(PoC2: Early Q2 2019).

Software simulation

White paper End user standardHardware simulation

White paper

↑Flexibility

↑Quality



© BioPhorum Operations Group Ltd 82Technology Roadmapping


Big Data

to Smart

Data

TRM The outputs of the Plug and

Play standard data models

are being used as input data

for the Big Data contextual

standard information.


team are also part of the

Plug and Play team.


Automated Facility Full

Team calls.

Direct

engagement

and updates on

calls.

Ongoing.

Buffer

Prep

TRM Alignment on interface

specification model.

Potential case study.

1. Initial link meeting to explore

the opportunity.

Critical linkages : TRM KM

BioPhorum

TRM

BioPhorum

IT

Synergies Communication Plan Mode/RACI Status Update

Automated

Facility: Plug

and Play

BPIT09:

Modular

Manufacturing

• IT issues and challenges • Via interaction between TRM SMEs

and sub-group of BPIT Leaders

Initially Inform,

with joint next

steps


7 Biomanufacturers

10Supply Partners

1 Innovation Hub


White paper / URS for a

plug and play prototype

demonstrating how

automation can: reduce

build and reconfiguration

times, improve efficiency

and reduce the cost of

quality. Supplier

members aligning to

deliver the prototype.

•Speed - faster build times and reconfiguration times, delay decision to

build

•Cost - eliminate development costs for custom interfaces

•Quality - reduced verification and variability.

•Flexibility - ability to easily switch unit op technology to best in class

Q3 2019

↑Speed

↓Cost

[email protected]

Plug & Play Technologies


Current team activities include:

1. Initial standard data models for:

• Bioreactor – team focus;

• Chromatography;

• Normal Flow Filtration.

N.B. End User Standardization is critical to the

success of implementation in this project

2. Initial Vendor Interface model.

N.B. Success depends on PoC1 going well and

End User Standardization in the longer run.

3. Draft white paper with Test Plan for software

simulation (PoC1 @AF02: 13-15th Nov. 2018,

Portsmouth UK).

4. Terms of Reference for a hardware simulation

(PoC2: Early Q2 2019).

Software simulation

White paper End user standardHardware simulation

White paper

↑Flexibility

↑Quality




15-1 months

pre-publication

BPI West presentation, Mar 2019 – Gene Tung

Week before

publication


Launch /

issue date



LinkedIn posts


Presentations at the ISPE’s Annual Meeting – Gene Tung, Keith Morris, Michel Claes

What is being communicated? White PaperWhat is the targeted publication/launch/issue date? September 2019

CONNECT

COLLABORATE

ACCELERATE TM


Charter Pack


Charter – Knowledge Management

Problem

• Product knowledge poorly managed

across life cycle.

• Links between CQAs, CPPs and

CMAs managed ad hoc.

Impact

• Inefficient and underutilized existing

knowledge assets, especially for

Tech Transfer, Change Control,

Investigations, process improvement,

etc).

• Unable to measure the use of

knowledge in key situations like an

investigation;

• Ability to demonstrate process

knowledge to regulators is impaired.

• Effort involved in reporting is greater

than necessary.

• Upskilling and on-boarding staff is

impaired.

• Opportunities for product and

process improvement are missed,

including across programs.

• Ability to innovate is hindered

• Opportunities to make the most of

increasing volumes of data and

emerging PAT are missed.

Goals

• Develop framework for biopharm industry

describing standardised approach to managing

product and process knowledge across

lifecycle.

KM Benchmarking and Maturity Assessment - Hold

Benefits

• Better product knowledge flow leading to

greater efficiency/effectiveness in

development and manufacturing.(including

cross program learning):

• Higher process capability



• Process improvements introduced faster

• Better understanding of correlations

between CMAs, CPPs and CQAs leading to

improved process control

• Improved Speed and Quality

• More knowledge is re-used

• Greater ability to measure the performance

of knowledge flow, including modelled

productivity improvement

1. K-Mapping - Paper 1

2. URS – Paper 2

Use Cases,

Bus Case,

Metrics and

Solutions

3. Proof of Concept

- Paper 3?

Implementation Tracking


OUT OF SCOPE

• The detailed design of a technical

solution.

IN SCOPE

• mAb Platform

• R&D and Manufacturing product

related workflows for data,

information and knowledge

towards key decision points.

INTERNAL LINKAGES

• TR: Data Management, ILM/RTR.

• IT: Data Management

• DG: KM in Development

• DS: CPV Process Flow

EXTERNAL LINKAGES

• ICH Q12

• FDA and EMA

• APQC


Implementation

Guidance



Charter – Knowledge Management

Problem

• Product knowledge poorly managed

across life cycle.

• Links between CQAs, CPPs and

CMAs managed ad hoc.

Impact

• Inefficient and underutilized existing

knowledge assets, especially for

Tech Transfer, Change Control,

Investigations, process improvement,

etc).

• Unable to measure the use of

knowledge in key situations like an

investigation;

• Ability to demonstrate process

knowledge to regulators is impaired.

• Effort involved in reporting is greater

than necessary.

• Upskilling and on-boarding staff is

impaired.

• Opportunities for product and

process improvement are missed,

including across programs.

• Ability to innovate is hindered

• Opportunities to make the most of

increasing volumes of data and

emerging PAT are missed.

Goals

• Develop framework for biopharm industry

describing standardised approach to managing

product and process knowledge across

lifecycle.

3. Communications

Benefits

• Better product knowledge flow leading to

greater efficiency/effectiveness in

development and manufacturing.(including

cross program learning):

• Higher process capability



• Process improvements introduced faster

• Better understanding of correlations

between CMAs, CPPs and CQAs leading to

improved process control

• Improved Speed and Quality


• Greater ability to measure the performance

of knowledge flow, including modelled

productivity improvement

2. PoC – Harvesting Prior Knowledge

4. Close to

CoP

1. K-Mapping Implementation and Tracking


OUT OF SCOPE

• The detailed design of a technical

solution.

IN SCOPE

• mAb Platform

• R&D and Manufacturing product

related workflows for data,

information and knowledge

towards key decision points.

INTERNAL LINKAGES

• TR: Data Management, ILM/RTR.

• IT: Data Management

• DG: KM in Development

• DS: CPV Process Flow

EXTERNAL LINKAGES

• ICH Q12

• FDA and EMA

• APQC



Q1 2020 Q2 2020 Q3 2020 Q4 2020


Phase / Activity Deliverables Business Benefit Acceptance Criteria Owner(s) 19Q1 19Q2 19Q3 19Q4

1. K-Mapping –

Paper 1

A BioPharmaceutical, Industry

Level Knowledge Map for

Development, including the

development of CQAs, CPPs

and CMAs. The Map will act as

a standard.

A white paper that describes the

process of developing the map

and learning from it.

An enabler of internal system

assessment, efficient and

effective capture and use of

corporate knowledge.

Greater, clarity of

nomenclature across

Research, Development and

Manufacturing activities.

Improved opportunities for

process improvement,

including PAT applications.

Improved ability to respond

to regulatory requirements.

A clear report with

recommendations

that can be

implemented to

significant benefit

across the industry.

Includes ability to

assess efficiency and

effectiveness.

• Rob

x

2. User

Requirements

Specification for

a prototype KM

System.

URS covering use cases.

Use cases:

Identifying SMEs in Analytical

Method Development;

Gathering prior product and

platform knowledge.

Improve ability to design a

KM system and commission

an IT solution from vendors.

Benchmark URS

documentation.

All members of the

team sign off on the

content of the URS

as part of a

descriptive paper.

• ?

X

3. Proof of

Concept

Early thinking:

May use iKnow as a basis for

connecting with additional

suppliers of solutions.

May focus on pre-competitive

gathering of product and platform

knowledge.

Enhanced visibility of

suppliers and solutions.

A business process model

related to gathering product

and platform knowledge.

PoC for the implementation

of tools related to gathering

product and platform

knowledge.

Steering committee

sees a PoC like this

of value.

Members of the team

are willing to invest

time in the PoC.

Write up is approved

by all contributing

companies.

Not

Started

Q2

2020

Charter – TRM KM

© BioPhorum Operations Group Ltd 89Technology Roadmapping


ILM / RTR TR KM aims to identify gaps

in knowledge and hence

data, that could be used

by ILM to prioritize

technologies into the

future.

Inform / Consult. Facilitators assess linkage

during ILM02.

KM seems unlikely to

reach the level of specific

CQAs and CPPs, so the

linkage may be redundant.

Big Data to

Smart Data

TR Requirements for CPP

identification, CPV and

Prior Knowledge.

Inform / Consult. Facilitator assessing value

of K-Mapping results for

Big Data project. Sharing

URS from KM may be

useful.

Critical linkages : TRM KM


BioPhorum

TRM

BioPhorum

IT

Synergies Communication Plan Mode/RACI Status Update

Knowledge

Management

(Robin/Phil

from 10/19)

Smart

Maintenance;

Phase 2 (Jon)

• Life-Cycle management for equipment

(existing and new technology)

• Learning from Development to Manufacturing

• Support for investigations, deviations etc.

• Building of databases for APM

• Applications for AI/ML to access information

• Share White Paper

• Keep BPIT SHARE file updated;

link to ‘iKnow’ website

Awareness for

now

Supply Chain

Visibility; CMO

Integration

(Jon)

• Potential Case Studies Share

information

Compliant MSA

(Tim)

• Requirements for future management of big

data sets.

• Continuous Learning

• TRM Focus on prior knowledge (P3K); use of

NLP, AI/ML

• Facilitator planning in 19Q1.

• CoP?

• Action: Create ‘Dependency

diagram’ ahead of BPIT10/TRM

Inform /

Consult.

CoPs?

‘Compare and

share’

Facilitators discussing opportunity

to share URS from KM.

IT / TRM Linkages (v170719)


TRM/DG Link Work:

Activity Purpose Owner Timeline Next Steps

Transfer knowledge

mapping methodology

from TRM to KM in

Development team

Enable KM in Development team

to use methodology to complete

more detailed mapping within the

Development area

Louise/

Rob

April/ May (to

start

transfers)

• Arrange dates for handover

Scope options:

• Development team to identify which areas/

processes to focus on for further k-mapping (look

into survey results?, look at TRM map and take

to further detail, pain points around ELN)

• Important to get started on one area - can pull out

generic issues/ fixes

Approach:

• Individual organizations and results brought back

to the team?

• F2F workshop?

• GTM meeting?

• Addition to BPDG F2F meeting?

Technology Roadmap Team to review roadmap and

identify any actions that can be

taken from development

perspective

Louise April • Team to comment on doc

Review TRM white

paper

Provide additional SME

perspective from Development

team

Robin/

Louise

April/ May • TRM to send white paper to KM in Development

team when ready for review

• Louise to identify 4 or 5 reviewers from

Development team

Case studies Share case studies of interest

across the teams

Ongoing


8 Biomanufacturers

9 Supply Partners

2 Innovation Hub


Standard framework to

map and manage

knowledge workflows,

culminating in a

technology demonstrator.

Opportunity to transform

business speed, cost and

product quality

• Higher process capability (RFT, lower OOS)



• Process improvements introduced faster.

• Better understanding of correlations between cmas, cpps and cqas

leading to improved process control

• Improved speed and quality


• Greater ability to measure the performance of knowledge flow

Q4 2018

↑Speed

↓Cost

↑Quality

[email protected]



In October 2019, the team met to develop a

framework for knowledge management in

the BioPharmaceutical Industry, delivering:

• Knowledge Maps associated with the

creation of a Control Strategy;

• A comprehensive inventory of Control

Strategy related Knowledge Assets was

created;

• A range of opportunities to improve

Knowledge Flow in the industry, including

two high priority opportunities: Company

Analytical Method Expertise, and Prior

Knowledge across Products and Platforms;

• The framework for a White Paper was

established, along with next step and longer

term plans.

• The team plans to implement improvements,

by clarifying user requirements and the

evaluation of solutions, which will include

humanistic approaches and advanced

technological ones.

Benchmarking survey & maturity

assessment

K-mappingImplementation

guidanceBusiness

justificationUser requirements for prototype KM system

Scope of Knowledge Mapping

Knowledge Capture Method

Prior Knowledge Process Flow

List of

Knowledge

Assets




15-1 months

pre-publication

BPI West presentation, Mar 2019 – Bert Frohlich

Week before

publication


Launch /

issue date



LinkedIn posts


What is being communicated? White PaperWhat is the targeted publication/launch/issue date? July 2019

CONNECT

COLLABORATE

ACCELERATE TM

Digital Technologies

Charter Draft


Charter – Digital Technologies Roadmap

Deliverables• Develop use cases and definitions

• Assess economic benefits for each of the scenarios

• Develop User Requirements and Concept Design

• Develop an Implementation, including estimate for building a prototype

• Get feedback/review

Vendor

Contract

FAT Preparation and

Execution

Submittals

Skid Development and Fabrication

White Paper

White Paper –

Data Release

Economic Modelling

Award Vendor

Publish White Paper

Q4 Q2 2020


OUT OF SCOPE

• Drug discovery

• Drug product to patient distribution

(non-manufacturing business

processes e.g. Marketing)

• Product development/discover

molecule data outputs

• Patient facing digital tools and use of

patient data for manufacturing

optimisation

• Data Analytics

IN SCOPE

The following Scenarios:

• Technology Roadmap First Edition Scenarios

• Single Use (providing opportunity to look at Supply

Chain consumables and flexibility of this approach)

• C&GT (autologous processes)

• Consideration of brownfield projects

• Real-Time Quality and Development

• Scheduling and Control Systems inc. RTR Strategy

• Supply Chain Journey inc. Shipping, Personalized

Medicine Identifiers, Serialization and Traceability

• Process development data outputs, QC Processes etc.

• Digital Fundamentals e.g. Cybersecurity, Data Integrity

and Connectivity


INTERNAL LINKAGES

• Link to BPIT digital plant maturity model

• Project teams are examples of applications, e.g.; ILM/

RTR (consider how to standardise hardware)

• Plug & Play, ILM/ RTR could provide key objectives

• Facility life cycle management – standard facility

design, BPIT preventative maintenance

• Big Data has already defined some use cases

Problem

• First edition does not describe digital

technology needs in the context of an

end to end, overlying infrastructure

for biomanufacturing.

• This means it is difficult to

understand where technology gaps

and interdependencies exist and it is

challenging to co-ordinate

implementation activities across

functional areas.

• Biomanufacturers needs some

clarity, preferably through

standardization, regarding the needs

and implementation of digital

technologies across the industry.

Goals


infrastructure

• To bring together the digital technology aspects of

existing roadmaps (BioPhorum and others) and

identify gaps

• Introduce a body of knowledge describing best

practice to address the needs identified:

• Overlying infrastructure to use as a common

understanding for technology adoption

• Ensuring successful and secure accessibility of

transactional data (mapping interdependencies

and interactions)

• Identify capabilities along the value stream to

leverage digital technologies

• Disruptive process definition at a digital level

(process introduction, improvement/simplification

and optimisation due to digital technologies)

• How to use the device driven technologies and

the data driven applications within

biomanufacturing in a compliant way

• Deliver value by developing tools and standards to

support the transformation of the biomanufacturing

industry.

Impact/Benefits

• This analysis will describe a digital

infrastructure that enables the

technology objectives for current

and future biomanufacturing

scenarios

• It will identify major digital

technology/ capabilities gaps and

timelines for closing those gaps.

• It will support the co-ordination of

implementation activities over the

short and long term, both in digital

technology and between digital

and other technology efforts

Digital Technologies Roadmap Vision, Charter and Chapter Outline

Charter Review

Q3 Q1 2020

TR10/BPIT10,

Santa Monica

Authoring

First Draft

Conference

Presentations

Meeting with Health

Authority (e.g FDA)

Vision

• Provide an industry ‘Digital Roadmap’ which facilitates

a common understanding of how digital technology

can enable a future in which the biomanufacturing

industry is flexible, efficient and capable of leveraging

the value of innovation.

• Leverage digital technology through successful

collaboration and co-operation to deliver an industry of

the future which is both resilient to change, adaptable

and responsive to how new technologies and

innovations are introduced in a highly regulated

environment.

EXTERNAL LINKAGES

• ISPE Factory of the Future

• Data & hardware standards from other

industries

• Current publications

• External know how, e.g.; aerospace


11 Biomanufacturers

10 Supply Partners

0 Innovation Hub


Detailed analysis of digital technology needs for

biomanufacturing -

• to identify digital technology needs and

capabilities in the context of an over-arching digital

infrastructure


infrastructure

• To identify specific digital technology needs and

capability gaps over a 10 year horizon.

• To create a common understanding of the digital

landscape and enabling technologies.

This analysis will describe a digital infrastructure that enables

the technology objectives for current and future

biomanufacturing scenarios

• It will identify major digital technology/capabilities gaps

and timelines for closing those gaps.

• It will support the co-ordination of implementation activities

over the short and long term, both in digital technology and

between digital and other biomanufacturing technology

efforts.

• It will identify interdependencies and ensure coordination

of implementation activities across functional areas (i.e.

how does it all fit together?)

2020

Facilitator: [email protected]

Digital Technologies


MobilizationCharter Review

TR10/BPIT10Author Digital Technologies

RoadmapPublication

↑Speed

↓Cost

↑Quality

↑Flexibility

• The Steering Committee for these projects has

agreed the BioPhorum First edition does not

describe digital technology needs in the context of

an end to end, overlying infrastructure for

biomanufacturing.

• This means it is difficult to understand where

technology gaps and interdependencies exist and it

is challenging to co-ordinate implementation

activities across functional areas.

• BioPhorum is now leveraging it’s subject matter

experts in a cross-phorum collaboration to deliver a

document which describes an end to end framework

to support digitalization across multiple scenarios.

Background TR10/BPIT10 Meeting Plan

http://www.biophorum.com

First Edition Documents

Identify processes

Consider requirements

Digital Enablers

StandardInfrastructure/Solutioning

Map Path to Value

Challenges/Obstacles

Planthen

Author

© BioPhorum Operations Group Ltd5

DPMM –one page overview

Level1Pre-digitalPlant

Level2DigitalSilos

Level3ConnectedPlant

Level4PredictivePlant

Level5AdaptivePlant

PrimarilyPaper-basedprocesses

Predominatelymanualprocessing.

Lowlevelofautomation.

BasicPLCcontrols.

Applicationsarestand-alonewith

minimalornointegration.

“Islandsofautomation”

Somemanualprocesses.

Batchrecordsmaybesemi-electronic

or“paperonglass”

Localbatch-recipesysteminterfaced

toPLCsSite-specific

systems;limitedintegrationacross

functionalsilosAnalyticson

demand,“whydidithappen?”high

manualeffort

VerticalIntegrationERP,LES,MESand

Automationlayerarefullyintegratedto

supportdigitizedbusinessprocesses.

FullElectronicBatchrecordwithreviewby

exception.Standardapplication

platformadoptedacrossplantnetwork

Islandsofreal-timeProcessanalytics

Analyticssemi-automated;“where

elsecanithappen?”

EnterpriseIntegration-internalintegrationofplanttovaluechain

IntegrationofProductDevelopmentandManufacturing

(PLMwithRecipeManagement)End-to-endsupplychainvisibility

withlimitedexternalcollaborations(suppliers/CMOs).

Online/At-linequalitytestingwithRealTimeRelease.

Simulationusedforprocessmodelingandimprovements

IntegratedReal-timeProcess

analyticsandsimulationProactiveanalyticsacrossplant

andinternalvaluechain;“whatcanhappenandwhen?”

Fullend-to-endvalue-chainintegrationfromsupplierstopatients

ITsupportsmultiplemanufacturingmodes:Modular,mobile,continuous…

“Plug-n-playeverything”fromaninstrumenttoaproductionscaleoraCMO

Zerosystemdown-time(includingupgrades)–

continuousevolution.In-line,real-time,continuous,closedloop,

processverificationandcontrolwithautomatedreal-timequalityrelease

Self-aware,continuouslyadaptive,“Autonomous”plant;exceptionconditions

handledbyremoteexpertsPervasiveuseofadaptiveanalyticsandSelf/

Machinelearningacrossvaluechain.

© BioPhorum Operations Group Ltd 5© BioPhorum Operations Group Ltd


Uncertainty

§ Regulatory approvals

§ Demand variability

§ Competition

Cost pressure

§ Payer pressure

§ Biosimilars

§ Development

Market Growth

§ Emerging markets

§ Global reach

§ In region manufacture

New Product Classes

§ Non-mAbs, ADCs

§ Gene therapy

§ Cell therapy

Modular and Mobile

- 70%â build time- 75% â CAPEX

§ Quick to configure &

scale§ Standard designs

§ Streamlined validation

Automated Facility

− 50%â Facility Build Speed

− 50% â OPEX costs from current

§ Agile, high quality, and

robust biomanufacturing

§ Plug and Play§ Open data standards

§ Interoperability

Knowledge

Management

‒ â Cost of process development

– Time to introduce a change to an existing

process â to 1 Month– Cost of Non-Quality

â to 2% of operating costs

• Efficient tech. transfer• Integrated knowledge

• Quality throughout lifecycle

Supply Partnership

ManagementSafe, innovative supply

chains:

− â Cost of quality− â Time

§ Partnerships with

quality built in§ Standard working,

integration and real

time Electronic Data Exchange

§ Shared Planning

Market Trends & Business Drivers – The Why

Enabling Technologies & Capabilities – The How

Speed

-70% build time

-80% lead time

Cost

-90% manufacturing cost

-90% CAPEX

Flexibility

-90% changeover

Demand response

Quality

10x robustness

-90% cost of quality

Drug Product

High volume

Drug Product

Low volume

Scale Distributed

1. Large-scale Stainless Steel Fed Batch

2. Intermediate-scale Single-use Perfusion

3. Intermediate-scale Multi-product Single-use Fed Batch

4. Small-scale <500L Portable Facility

Biomanufacturing scenarios – The What

(Facility types)

5. Small-scale <50L for Personalized Medicine

This is the first edition phase of the program….. 2015 2017

Inline Monitoring and

Real time Release

-â Product Release 1-2 day

+ ↑ Quality, Efficiency & Supply

§ Enhanced In-Line

Monitoring§ Indirect and

Multivariate Sensors§ Multivariate Analysis

and Predictive Modeling

Process Technologies

- â 90% CoGs- â 90% process

investment

§ Process Intensification & combination of unit

operations§ Continuous processing

technologies coupled with advanced process

control

Technology Roadmap First Edition

Digital PlantMaturityMatrix

TechnologyRoadmap

Capablities

DigitalEnablement

Menu

ILM/RTR TechnologyAdoption

Digital Transformation

Case Studies

Author

BioPhorum

Information

Technology

(BPIT)

Technology

Roadmapping

Phorum

(TRM)

Linkages




Phase/


2019

Q3

2019

Q4

2020

H1

2020

H2

Mobilization SME Onboarding This analysis will describe a digital

infrastructure that enables the

technology objectives for current

and future biomanufacturing

scenarios:

• It will identify major digital

technology/capabilities gaps and

timelines for closing those gaps.

• It will support the co-ordination of

implementation activities over

the short and long term, both in

digital technology and between

digital and other

biomanufacturing technology

efforts.

• It will identify interdependencies

and ensure coordination of

implementation activities across

functional areas (i.e. how does it

all fit together?)

• To create a vision for a standardized

digital infrastructure

• To bring together the digital

technology aspects of existing

roadmaps (BioPhorum and others)

and identify gaps

• Introduce a body of knowledge

describing best practice to address

the needs identified:

• Overlying infrastructure to use as

a common understanding for

technology adoption

• Ensuring successful and secure

accessibility of transactional data

(mapping interdependencies and

interactions)

• Identify capabilities along the

value stream to leverage digital

technologies

• Disruptive process definition at a

digital level (process introduction,

improvement/simplification and

optimisation due to digital

technologies)

• How to use the device driven

technologies and the data driven

applications within

biomanufacturing in a compliant

way

• Deliver value by developing tools and

standards to support the

transformation of the

biomanufacturing industry.

x

Charter

Review

Charter

x

TR10/BPIT10 Process

Landscape;

Digital

Requirements;

Digital Enablers;

Value Path;

Challenges;

Plan.

x

Author Digital

Technologies

Roadmap

Section Drafts

x x

Publication Roadmap Publish the Digital Technologies

Roadmap meeting a need across

the biomanufacturing industry for

an overall end to end infrastructure

and evaluation of gaps and

dependencies in implementing a

digital transformation.

x

Technology adoption through

implementation projects to further

define how to implement digital

technologies that deliver value to

the business.

X

Risks

Scope creep

Don’t need just another roadmap – needs to be implementable.

Charter Activity Tracking – Digital Technologies Roadmap


Linkage Phorum Synergies Comms Plan Mode

Digital Technologies Roadmap will look to leverage linkages with all TRM projects and also those in other phorums which are looking to TRM for an overall strategy, in the form of the Technology Roadmap and Digital Technologies Roadmap. These phorums are using the Technology Roadmap as a reference and sharing the BioPhorum approach to Technology Adoption.

TRM Digital technologies underpin the end to end biomanufacturing process. The Technology Roadmap, although providing a strategy for the process technology capabilities and needs, did not provide an approach to digitilization or the tools to implement enabling technologies. They will seek to understand from the Digital Technologies Roadmap how to overcome hurdles to digitilization and deliver value to the business.

L1’s/L2’s

SME’sFacilitators

Aware

Digital Technologies Roadmap Linkages


During BioPhorum 2019, held recently in Lausanne, there was a discussion on the subject of how to accelerate the

Industry Adoption of the Technology Roadmap (TRM), starting with ILM/RTR

• Strongly align workstream targets across the

BioPhorum collaboration to the TRM vision• Provide quarterly progress reports to L1s

• Write explicit story to show how the TRM vision enables performance improvement, for example reduction of

cost of goods by 90%• Use an L1 Advisory Board to check out ideas to

accelerate adoption.

The L1 advisory board meetings were held over the last

few weeks

• The following slide provides an initial draft view of how workstream activity aligns to adoption of ILM/RTR

• There are BPIT activities that support ILM/RTR and our connection to this work will be discussed further in

BPIT10 and future meetings

Technology Roadmap adoption – In-line monitoring / Real time release

There is some great work happening to implement TR capabilities (eg ILM/RTR), and

we recognize the important contribution

“digital” has in adoption of the TR capabilities

6

7.0 Reg

considerati

ons

5.0 Linkages

to other

roadmap

teams

4.7 Mature

IT/Automation

4.6 Advanced

process

control +

predictive

analytics

4.5 DP

Considerati

ons

4.4 End-

product

testing

4.3 In-process

measurement

upstream,

downstream

4.2 Raw

Material

character

4.1 Utility +

environme

ntal

Ac

tiv

e a

nd

ali

gn

ed

Str

en

gth

en

Ali

gn

me

nt

GA

P

In-line water

bio-durdenFF

Automated colony

counters FF

Direct micro detection in air

Plug + play data standards (+big

data)

Application of MAM for raw

materials

Availability of eCoAs

Q + D: Risk assessment tool

Microbial control

contamination free process

RMW: cell, culture, media +

imdrolysates

SFQRM (pupsit)

PAT monitoring+

control

Cell based potnry –

global reg acceptance.

Gene activation assays, parallel testing –

red/yellow red/yellow

Fluorescence based

plate assays, respirometry

microflow imaging, flow cytomotry –bioburden. -

red

Osmolality: TBD ?? – red

Protein conc. In-

line using stope

spectroscopy, Raman

- yellow

Rapid sterility inc.

advantitiousvirus.

FF

Time to release +

assay quality – improve

vision systems. –red/yellow

Reduced testing for quality

attributesMA methods

loads of specific tests! – yellow

P22

ILM endotoxin in H20

Raw mat S, Q, + Vol

EDE (in-bound raw materials)

ILM prioritization

project

Rapid methods

for AV + Mylo

Develpoment of methods for DP

Visual

inspection particle control FF

Closed container

integrity testing FF

DPs ILM/RTR Roadmap

Digital tech

roadmapping(DPMM + input)

BPIT –Compliance: multi-

source analytics/continuo

us learning systems

Continued process

verification

PPAR MVDA training

Implement harmonisedretrospective

(statistical) ‘Q+D’

Improvement harmonised

MVDA approach

Pre-deviation alert

management

Robotics

Quality review process changes

to enable real time batch

release

BPIT - Batch release:

definitions, release by

exception

EBR/data management to check complete of all in-process

+ test criteria

Integration of multiple systems

for EBR (technical +

coord. challenges

BPIT – Batch release: electronic

batch records, data flows

TRM big data PoC

May contribute to ILM/RTR

Dependent on ILM/RTR

Viral clearance

HCP

(Robotics SFF) M+M

What not to test

Knowledge management: characterisation, Q

+ D, product/process knowledge

Supply partnership

measurement: CQA, RM

characterization, ILM/RTR in supply base, Raman RM

ID Testing, analytical data

packages

Modular + mobile: SUS instruments.

Automated facilities:

MES, LIMS, Plug +

play, automated sampling, big data,

data analytics, Muda, EBR. - G

Process tech:

intensification,

continuous, small facilities/C+ GT

Conti process

roadmap

All other TRM

projects

Adventitious virus

detection + Mylo

PPARMVDA

training

ID opp. for use of ILM/RTR for CMO of bio products

Lean validation + qualification

Risk assessment for

release and process control – consistent w/

ICHQ9

Coverage

quality metrics data to ID

shared sources of variability to

platform products to

reduce deviations

ID specific country/region impediments to RTR –diverse global reg req.

Quality review process change

to sensible real time batch

release

All SPP w/s

All D6 pointshares

except PAT

monitoring and control

Batch record review – closed

DS w/s

Colour: spec

methods-

yellowRapid/auto

turbidity. - redSurfact

ant refractive index - red

Time to release

– assay quality. Spectroscopy based

sensors. -

yellow

MA sensors – surface

plasmon resonance, nanosensors, proton arrays –

red/yellow

Detailed ILM/RTR Scope – Update on Technology Roadmap adoption

SPITDGFFDSTR RIC&GT

TR

M r

ef.

Linkages

Requirements

Using ILM/RTR adoption needs as an example, we can see how digital is a key enabler, but don’t yet fully understand the requirements

and challenges to be addressed for full value realisation

TRM ILM/RTR has been working with the Drug Substance phorum on Technology Adoption identifying ande valuating

the gaps which they did digital enablers to deliver.


Digital Technologies Roadmap Comms Plan

What is being communicated? • The Digital Technologies Roadmap is in the Initiate Phase and therefore key messages remain that

a team of biomanufacturers, suppliers and IT Strategy Leads has been mobilized in a collaboration

between the Technology Roadmapping Phorum and BPIT. The Charter identifies that the First

Edition Technology Roadmap does not describe digital technology needs in the context of an end

to end, overlying infrastructure for biomanufacturing. This means it is difficult to understand where

technology gaps and interdependencies exist and it is challenging to co-ordinate implementation

activities across functional areas.

• The Digital Technologies Roadmap team will come together in Santa Monica this Fall to collaborate

on mapping the process landscape, digital requirements and digital enablers with workshops to

consider the value proposition and challenges associated with implementation.

• The authoring of the Digital Technologies Roadmap will take place during the first half of 2020 with

publication in Q3.

Key Milestones22-24th October TR10/BPIT10, Santa Monica, CA

Q3 2020 Digital Technologies Roadmap Publication

End Q1 2020 F2F?

End Q2 2020 Annual Report 2020

Communications Channels TBD

CONNECT

COLLABORATE

ACCELERATE TM

October 2019

Best Practice in New Technology Adoption


Charter – Best practice in new technology adoption – v0.1 September 2019 DRAFT



White paper

drafting

Mobilization

and case study

sharing

Problem

The biopharmaceutical industry is risk-

averse when considering adoption of new

technologies onto production lines. Key

contributors to this have been identified as

including:

• a need for improvement in business

case assessment,

• a need for better alignment of

stakeholders throughout the technology

adoption process, both within

organisations (business vs. R&D vs.

operations) and across multiple orgs;

• a perception that working with regulatory

agencies can be challenging;

Impact

A high level ‘swim-lane’ process has been

scoped out (in collaboration with the DS

community), and has been used to design

an ILM/RTR Adoption Program proposal

that has been presented to L1s; there is

opportunity to further define this by

detailing stakeholder interactions and

hand-offs.

There is an opportunity to enhance

definition of this process by creating a

collaborative best practice guide to

adoption of new technologies

Benefits

• Guidance on stakeholder engagement

and risk management

• Best practice in business case build

across multiple functions, to be applied

both within an organization, and

collaboratively.

OUT OF SCOPE

• Project / program management

practice and process

• Specific technologies

• Development processes

IN SCOPE

• Stakeholders, RACI

• Leadership

• Key principles at pre-adoption

• Strategy dev’ment & deployment

• Business case & risk management

Case Studies – ILM/RTR

• Benchmarking maturity

model/scorecard survey

INTERNAL LINKAGES

• ILMRTR Adoption Program

• Cross-phorum L2 communities

• L1 community

EXTERNAL LINKAGES

Goals

• Collaborative white paper detailing best

practice in adoption of new technologies

into manufacturing.

Deliverables• Shared case studies on good practice.

• Collaborative white paper detailing best practice in adoption of new

technologies into manufacturing.

Review and

publication


APPENDIX

BioPhorum policies


Anti-Trust Compliance Statement v4.0

It is the clear policy of BioPhorum that BioPhorum

and its members will comply with all relevant anti-

trust laws in all relevant jurisdictions.

All BioPhorum meetings and activities shall

be conducted to strictly abide by all applicable

antitrust laws. Meetings attended by BioPhorum

members are not to be used to discuss prices,

promotions, refusals to deal, boycotts, terms and

conditions of sale, market assignments, confidential

business plans or other subjects that could restrain

competition.

Anti-trust violations may be alleged on the basis of

the mere appearance of unlawful activity. For

example, discussion of a sensitive topic, such as

price, followed by parallel action by those involved or

present at the discussion, may be sufficient to infer

price-fixing activity and thus lead to investigations by

the relevant authorities.

Criminal prosecution by federal or state authorities is a

very real possibility for violations of the antitrust laws.

Imprisonment, fines or treble damages may ensue.

BioPhorum, its members and guests must conduct

themselves in a manner that avoids even the

perception or slightest suspicion that antitrust laws are

being violated. Whenever uncertainty exists as to the

legality of conduct, obtain legal advice. If, during any

meeting, you are uncomfortable with or questions arise

regarding the direction of a discussion, stop the

discussion, excuse yourself and then promptly consult

with counsel.

The antitrust laws do not prohibit all meetings and

discussions between competitors, especially when the

purpose is to strengthen competition and improve the

working and efficiency of the marketplace. It is in this

spirit that the BioPhorum conducts its meetings and

conferences.


Minutes and communication of F2F meetings v1.2

Minutes

The BioPhorum facilitator(s) will capture the key

discussions, proposals and decisions in an Event

Report. This report will act as the Minutes of the

meeting and will

• detail the objectives, attendees and agenda

• include hyperlinks to all the materials shared in

the event and an executive summary. All

materials shared via hyperlinks will be in pdfs to

lock down the contents in their presented form.

• Contain photos of the presenters and the team to

help participants put names to faces after the

event. If you do not want to be photographed

please let the facilitator know.

Our aim is to circulate the Event Report in draft

form within six working days of the meeting, to all

the participants. A final draft will then be made

available to all other workstream reps and Phorum

Leaders (L2s).

Circulation to guests will be at the discretion of the

facilitator(s) and team.

Photos of presentations must only be taken with the

express agreement of their author.

Communication

Often discussions in meetings are exploratory and

involve testing ideas, solutions and approaches.

We ask that all representatives in the meeting and

dialling in respect the unformed state of discussions

and agree not to comment on the discussions

publicly on social media or report on the discussions

on open public channels, during the meeting and

until the final draft of the Event Report has been

circulated and any messaging and communications

strategy of the team has been agreed.

This is not a bar to representatives communicating

about the meeting with peers, colleagues and

stakeholders in their own organisation, this is very

much encouraged.


Supplier interactions policy v3.0

The BioPhorum Operations Group (BioPhorum) facilitates a cross

industry collaboration process for Biopharmaceutical developers and

manufacturers with the aim of accelerating the rate at which the

biopharma industry attains a mature and lean state benefitting patients

and stakeholders alike. Collaboration modes include best practice

sharing, benchmarking, joint-solution development to common

challenges, definition of standards requirements and formation of

collective perspectives to mutual opportunities and regulatory

guidelines.

Biopharmaceutical developers and manufacturers recognize the legally

enforceable duties they have including the responsibility to control the

quality of materials from their suppliers. From time to time BioPhorum-

facilitated collaboration requires, and benefits from, supplier

interaction.

Suppliers are providers of supply chain materials such as chemicals,

glass, components, excipients, and media. They are also providers of

process equipment such as single use systems, engineering parts and

consumables. BioPhorum-facilitated supplier interactions may involve:

harmonizing manufacturer requirements and communicating these to

suppliers; seeking feedback on proposed standards; gaining opinions

and ideas related to business process improvement; use of problem

solving tools; and gaining support for new ways of working.

The ultimate goal of the BioPhorum collaboration is to strengthen

competition, assure product quality and protect patient supply.

The purpose of this document is to set out the principles and policies

that BioPhorum follows to ensure that BioPhorum-facilitated supplier

interactions are conducted in the correct and appropriate way to meet

all legal and business compliance requirements.

Underlying Principles and Policies

Competition Laws: All supplier interactions will comply with anti trust and competition laws and have regard to BioPhorum’s anti-trust compliance statement

Member responsibilities: Individual biopharma companies are responsible for defining their requirements of suppliers.

Innovation and commercial interests: All supplier interactions will recognise and respect the need for suppliers to innovate and pursue their own commercial interests.

Intellectual Property: All supplier interactions will respect suppliers’ intellectual property rights.

Confidentiality / Non Disclosure: All supplier interactions will take into account, respect and encourage compliance with confidentiality and non-disclosure agreements.

Equal Treatment: All suppliers will be treated equally

Communication: These principles, policies and procedures will be communicated to BioPhorum members and suppliers whenever supplier interactions are planned or are taking place.

BioPhorum responsibilities

• It is the responsibility of BioPhorum Directors to ensure that these principles and policies are upheld and procedures are in place to support them.

• BioPhorum will educate and train its staff so they understand and follow these principles and policies and are able to communicate them when needed.

• BioPhorum documentation will reference or directly include relevant parts of the Supplier Interaction Policy.

• BioPhorum will establish and maintain records to demonstrate compliance with these principles and policies.


Code of Conduct – BioPhorum information sharing v2.0

IntroductionThe BioPhorum Operations Group (BioPhorum) is a cross industry collaboration with the aim of sharing best practice in the area of Operational Excellence.

Participation in BioPhorum is restricted to authorized member company representatives as described in the Principles of Membership Agreement.

While sharing information is central to the process of this collaboration, it is important to understand what information is appropriate to share. Our companies have a great deal of confidential information and intellectual property that should not be shared within BioPhorum.

This document seeks to guide the reader so that the individuals and companies involved follow the correct code of conduct and problems are avoided.

It is the clear and stated intention of BioPhorum that the Group and its activities are conducted at all times in full compliance with relevant completion/anti-trust rules.

ResponsibilitiesIt is the responsibility of every person who participates in a BioPhorum event or sharing activity to make sure they are aware of what information is appropriate to share. Furthermore, all participants are responsible for vetting any information to be shared via their company’s public disclosure review processes and that all information shared is free of any “Confidential” stamps or markings.

The key contact (L2) for each member company should ensure confidentiality and that IP issues are highlighted to their colleagues and all applicable company policies regarding external collaboration and public disclosure are adhered to.

The BioPhorum facilitators are responsible for reminding all participants of their obligations with respect to information sharing.

Sharing informationThe following list is representative of the types of disclosures commonly allowed by corporate policies. BioPhorum participants should review their company policies to ensure they are in compliance prior to any disclosures. Information in the following areas is typically allowed:

• Operational excellence best practice models• Management approaches and philosophies• Organizing and planning ways of working• Non-product or process specific generic operating procedures • Information in the public domain• Information provided by suppliers which would ordinarily be shared

with customers• Non-product or process specific generic engineering or technical

information relating to process equipment • General learning and ‘context’ conclusions from QA and Regulatory

activity

Information from the following areas is typically prohibited by corporate policies

• Product related information• Product related process data which constitutes intellectual property• Specific audit or regulatory inspection findings or observations• Product specific analytical methods• Specific cost numbers where a market advantage may result or a

supplier might be disadvantaged• Information that is marked as confidential by the member company or

a supplier• Price information of any type• Proprietary information including intellectual property and patented

processes and equipment

BioPhorum event participants should direct all questions regarding information disclosure to their L2 BioPhorum representatives or corporate legal departments.