what is biophorum and how does it work?

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What is BioPhorum and how does it work?BioPhorum Showcase

Tokyo, 5 November 2019

2© BioPhorum Operations Group Ltd

What is BioPhorum?

7 Phorums

>60 industry changing initiatives

80+ member companies

2500+ active participants

7 thriving communities

1 Phorum for change

Unique global collaboration

Powerful vehicle for change

Industry leaders and experts working in concert

Delivers results by pooling knowledge, practices and ideas

© BioPhorum Operations Group Ltd 3

BioPhorum mission

To create an environment where the global biopharmaceutical industry can collaborate and accelerate their rate of progress, for the benefit of all

Making the journey better, faster, cheaper

We do this by

Bringing leaders together to create future visions that focus the industry’s energy on the key emerging opportunities

Mobilizing communities of the top experts around these opportunities, up and down the biopharma value chain

Creating partnerships that enable change and provide the quickest route to implementation and results

Replacing isolation with collaboration so that the industry shares, learns and builds the best solutions together

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Membership includes most of the top biopharma manufacturers

© BioPhorum Operations Group Ltd

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...and many of the key industry supply partners

© BioPhorum Operations Group Ltd


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


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

Regulatory Interaction

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

ReliabilityDisposables –

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 changeProcess

DevelopmentProcess

Technology ILM & RTR Modular & Mobile Automated Facility Knowledge Management

Supply Partnership Management

Operations, Quality & Compliance

SPITDGFFDSTR RIC&GT

High Level Analytics

Regulatory Strategy

Validation

Commercialization C&GT Manufacture

EHS & BioSafetyRaw Materials

Sourcing, Quality & Volume


Cell & Gene Therapy 2019 Program – V5 June 2019

Leaders Emerging issues and direction setting

WorkstreamsImportant subjectsSmaller audiencesOn-line if possible

CGT 0325 – 26 April Boston, MA

ValidationRaw Materials

Programme update2 days

Planning meetingsJan, Feb, Mar

On-line

To comeCommunities of Practice

To comeKey linkages

High Level Analytics

Regulatory Strategy

Commercialization – CGT Manufacture

Validation

Raw Materials – sourcing, quality and volume

Environmental Health and Safety, Biosafety

Planning meetingsJun, Jul, Aug

On-line

CGT 0417-19 September

Durham, NC

EHS/BioSafetyCommercializationProgramme update

2.5 days inc. site tour

BioPhorumLink with strategic workstreams

BioPhorum Regulatory Interaction


Cell and Gene Therapy – Highlights 2018 to Mid 2019

CGT01 Foundation

CGT02High Level Analytics

and Regulatory Strategy

CGT03 Raw Materials and

Validation

2018

2019

Work Stream Outputs to date Q3 2018 – Mid 2019

High Level Analytics CQAs listed and linked to FDA/CBER guidelines for cell and gene therapyFor Cell Therapy; CT CQA data pack (Phase appropriate guidance, Methods to select to test each CQA )Potency survey base data

Regulatory Strategy Highlighted initial gaps & differences in agency guidelinesEstablished contacts/communication with NIST & EDQM.

Validation Draft Validation process map to allow focus on CGTIdentified specific concerns & risk for CGT validation - survey

Raw Materials, Sourcing, Quality and Volume

Key questions identified that should be addressed when ordering raw materials for key CGT materials Key Suppliers for CGT identified

Environmental Health and Safety/BioSafety

10 key risk areas identified linked to NIH guidelines

Commercialization –CGT Manufacture

CGT Bibliography & Glossary files Initial draft CGT process maps – manufacture & patient

Charter Development

Best PracticeHarmonization


CGT04 17-19 September 2019

The 4th meeting of the BioPhorum Cell and Gene Therapy Group brought together 53 participants in Durham, North Carolina USA. They represented 17 companies

The second face to face meeting of the year focused onFacility Tour – 36 Team members enjoyed a tour of the bluebird bio facility. Opened in March 2019, the 125,000-square-foot facility includes warehouse and quality control testing laboratories and three manufacturing suites capable of producing lentiviral vector (LVV) @ 200 litre volume. LVV produced here will be for the company’s investigational gene and cell therapies bb2121 and bb21217 for the treatment of multiple myeloma, and potentially LentiGlobin™ for the treatment of transfusion-dependent β-thalassemia (TDT) and sickle cell disease. Thanks to Tom Jede and the bluebird team Day 1 – Commercialization-CGT Manufacture workstreamDay 2 – Environmental Health and Safety and BioSafety (EHS/BioSafety) workstream

Key conclusions for Work Stream Follow-upUser requirements are a critical starting point for good facility design.Media preparation is a critical aspect requiring improvements, such as automation, to close the system and reduce ergonomic risks.A wide range of approaches exist across many CGT topics and so there is still a lot to learn and benefit from sharing across the sector to solve universal problems.Consider standardised documentation for risk assessments around EHS/BioSafetyBioSafety Surveillance could be a future focus area


Cell and Gene Therapy – Mid 2019 onwards

CGT04 Commercialization and EHS/BioSafety

CGT05….CGT062019

2020

Work Stream Future Deliverables/Focus Areas

High Level Analytics For Gene Therapy; Phase appropriate guidance, Methods to select to test each CQAStrategy for methods that have limited sample volumes, are time limited or measure sterility. Strategy for validation of methodologyStable formulation data whether in house or outsourced, what are the issues and concerns and future needs (completed)Potency publication – adoption and acceptance of matrix approach

Regulatory Strategy Risk-based approach with the regulatory guidelines.Multi-product CGT facility design considerations.Facility, equipment and IT requirements for CGT IND & BLA submission discussionFeedback on EMA 2025 strategy & on ATIMP clinical trials List of CGT-focused organizations

Validation CGT specific challenges for validation.CGT NPI Client CMO Kick-off meeting agendaCGT NPI Client CMO Roles & Responsibilities CGT Viral clearance validation aspects

Raw Materials, Sourcing, Quality and Volume

Risk matrix/assessment methodology for Raw material sourcingStandardized release specifications; beginning with plasmidsStandardized training for visual inspection for particulatesExploration of the potential for linking with suppliers for shared forecasting

Environmental Health and Safety/BioSafety

Publication focusing on Operator safety during the Large Scale manufacture of Viral Vectors and Cell Therapy productsAdoption of environmental policies to reduce impact of CGT industry

Commercialization – CGT Manufacture

CGT Closed Systems – mock CT process & risk assessmentCell Therapy Process mapsGene Therapy process maps

Best PracticeHarmonization


The face to face Phorum meeting program is taking shape for 2020

Development Group

Drug Substance

Fill Finish

Information Technology

Supply Partner

Technology Roadmap

Regulatory Interaction

Cell & Gene TherapyCGT05 CGT06

BPDG28 BPDG30BPDG29

BPOG35 BPOG36

FF22 FF23

BPIT11 BPIT12

SPP10 SPP11

TR11 TR12

RI04 RI05 RI06


BioPhorum is facilitated by dedicated professionals

Clients tell us that our facilitation is unique, critical to success and highly valued

BioPhorum facilitators are:

Always present and never deflected by competing priorities back at ’base’ as volunteer leaders can be

Neutral with no agenda they have just one boss – their team, and one goal –their team’s mission

Guardians of the collaborationensuring equal contributions, open debate, and driving ambition, belief and implementation

Process managersconstantly designing and adjusting the way teams interact, share, debate, and build solutions to make the collaboration effective

Situational leadersalways understanding needs, the community’s energy and thinking how to move the engagement onto the next level of industry value


iMeet Central is BioPhorum’s online collaboration platform

iMeet Central

• members only area password controlled

• searchable database > 11,000 documents

• member only whitepapers

• detailed benchmarks

• events reports from every F2F meeting

• all meeting minutes

• contact details of all BioPhorum reps

• workstream charters and executive dashboard

• Ask BPOG facility and 2000 mini benchmarks


Ask BPOG – The industry leading online Q&A tool

Go the next step Our facilitators will help you

• phrase the question to get the best response

• search the database of over 2000 benchmarks

• go beyond the database and connect you directly to the industry’s top practitioners on 1 to 1 calls

> 2000 benchmarks searchable on iMeet Central

Watch the Video

On iMEET CentralConnect directly to 100s of industry experts FAST and• benchmark and compare practices • check you are making good decisions• answer unexpected audit challenges


Implementation and benefit realization

In BioPhorum the publication is not the END butthe START of industry change and benefit realization

• engage and align the power of all stakeholders across the biologics industry

• drive appropriate synchronized change to create value across the biologics industry

• provide long term support to sustain and grow industry value realization


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.


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 PoliciesCompetition Laws: All supplier interactions will comply with anti trust and competition laws and have regard to BioPhorum’s anti-trust compliance statementMember 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 equallyCommunication: 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 v3.0

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 competition/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

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

what is biophorum and how does it work?

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