Pda2012 talk

The MIT Consortium on Adventitious Agent Contamination in

Biomanufacturing

A Center For Biomedical Innovation Initiative

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Consortium Goals

● Provide collaborative environment for companies to share experiences

● A forum for companies to network, develop collaborations and synergize

● To identify and benchmark against best industry practices

● To sponsor collaborative research activities and initiatives

● To promote generation and application of new technologies

● To make public a summary of consortium findings and recommendations

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Consortium ActivitiesConsortium

Operations & Activities

Purposes Participants

Steering Committee Meetings

•To evaluate, revise and approve CAACB strategic plans•To identify, recommend and prioritize future projects

Representatives of Member Companies

Consortium Task Force Meetings

•To evaluate and recommend potential future projects to the Steering Committee•To assist in analysis of project findings and/or technology advances in relevant fields


Consortium Workshops &

Symposia

•To learn of advances in selected technology areas•To contribute to the understanding of anonymous data collected from CAACB projects•To exchange ideas, experience and knowhow of industry practices

Delegates of Member Companies, Invited MIT faculty

Consortium General Meetings

•To report progress and future plans of CAACB to consortium body•To highlight technology advances and policy changes relevant to mission of CAACB

Delegates of Member Companies, Invited guests

Consortium Sponsored Meetings

•Forum to promote CAACB mission Public

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Key Components of Consortium

Consortium Operations & Management

● MIT CAACB Team● Program Director: Dr. Stacy Springs

● Lead Investigators: Michael Wiebe and James Leung

● MIT Faculty Investigator: Anthony J. Sinskey

● MIT Faculty & Staff: As Needed Per Consortium Projects

● Steering Committee● One individual from each member company

● Advisory Board● Kurt Brorson, FDA (CDER)

● Marshall Dinowitz, Consultant

● Jim Gombold, Charles River Laboratories

● Bill Lucas, WuXi AppTec

● Ray Nims, Consultant

● Carol Marcus-Sekura, Consultant

● Anton Steuer, BioReliance

● Hannelore Willkommen, Consultant

● Ruth Wolff, Consultant

Fee-based Membership● Full Members

● Manufacture Biologics● Steering Committee

representation● Active participants in all

consortium projects including data contribution, results interpretation and report generation

● Associate Members● Do not manufacture Biologics (e.g.

Service Providers & Technology Companies)

● Active participants in projects focusing on technologies and methods assessments & development, roles to be defined

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● Consortium Mission & Goals● Consortium Organization

● Organization● Deliverables● Protection of Confidential Information

● Consortium Activities● Projects & Meetings● Schedule for 2011/2012

● Benefits of Joining● Update of CAACB Inaugural Project

● Virus Contaminations In Biomanufacturing

● How to Join

Outline

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1. To provide a safe and collaborative environment for companies to share their experiences, lessons learned and the operational approaches to control and mitigate the risk of adventitious agent contamination in biomanufacturing.

2. To provide a forum for companies to network, develop collaborations and synergize their activities to reduce adventitious agent contaminations risk.

3. To identify best industry practices currently utilized by biomanufacturing companies.

4. To provide opportunities for companies to benchmark their own adventitious agent control and risk mitigation strategies against best industry practices.

5. To sponsor collaborative research activities and initiatives that promote a better understanding of how to address adventitious agent contamination.

6. To promote the generation and application of new technologies to detect and identify adventitious agents; and to mitigate the risk of contamination.

7. To make public a summary of consortium findings and recommendations.

Consortium Goals

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Key Components of Consortium Consortium Operations & Management

● MIT CAACB Team● Program Director: Dr. Stacy Springs

● Lead Investigators: Michael Wiebe and James Leung

● MIT Faculty Investigator: Anthony J. Sinskey

● MIT Faculty & Staff: As Needed Per Consortium Projects

● Steering Committee● One individual from each member company

● Advisory Board● Kurt Brorson, FDA (CDER)

● Marshall Dinowitz, Consultant

● Jim Gombold, Charles River Laboratories

● Bill Lucas, WuXi AppTec

● Ray Nims, Consultant

● Carol Marcus-Sekura, Consultant

● Anton Steuer, BioReliance

● Hannelore Willkommen, Consultant

● Ruth Wolff, Consultant

Fee-based Membership● Full Members

● Manufacture Biologics● Steering Committee

representation● Active participants in all

consortium projects including data contribution, results interpretation and report generation

● Associate Members● Do not manufacture Biologics (e.g.

Service Providers & Technology Companies)

● Active participants in projects focusing on technologies and methods assessments & development, roles to be defined

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GeneralMember

(Data Contributor)GeneralMember





(Data Contributor)

Consortium Organization & Deliverables

Steering Committee

AdvisoryBoard

Public ReportsSummary of Findings

Public Presentations Summary of Findings

Deliverables Available to CAACB Members

Web Resource Center

Project Reports:Data Analysis &

Recommendations

Technology Research Proposals

CAACBWorkshop

Proceedings

Anonymous Project Data

MIT CBI/CAACB Team

Project Data

Collection & Coding

Data Management

Data Analysis:Trend & Risk Analysis, etc.

AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

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Consortium Information DomainGeneralMember






(Data Contributor)

Consortium Information Flow & Confidentiality Space

Steering Committee

AdvisoryBoard


Web Resource Center


Recommendations


CAACBWorkshop

Proceedings


MIT CBI/CAACB Team

Project Data

Collection & Coding

Data Management


AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember



Preview, ReviewAuthorize by Steering

Committee

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GeneralMember






(Data Contributor)

Company Specific Information: MIT-Member NDA Confidentiality Space

Steering Committee

AdvisoryBoard




Web Resource Center


Recommendations


CAACBWorkshop

Proceedings


MIT CBI/CAACB Team

Project Data

Collection & Coding

Data Management


AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

Data Protected by Individual NDAs between

Companies and MIT

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GeneralMember






(Data Contributor)

Company Specific Information: Confidentiality Protection

Steering Committee

AdvisoryBoard




Web Resource Center


Recommendations


CAACBWorkshop

Proceedings


MIT CBI/CAACB Team

Project Data

Collection & Coding

Data Management


AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

Confidentiality Barrier & Filter

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Consortium Information DomainGeneralMember






(Data Contributor)

Confidential Information Is Protected

Steering Committee

AdvisoryBoard


Web Resource Center


Recommendations


CAACBWorkshop

Proceedings


MIT CBI/CAACB Team

Project Data

Collection & Coding

Data Management


AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember

AssociateMember



Preview, ReviewAuthorize by Steering

CommitteeConfidentiality Barrier & Filter

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Consortium Projects with Confidential Information – Deliverables and Access by CAACB Participants

Raw data collected from Participating Members &

Partners

Anonymous data pool - annotated

and collated

Research tools: e.g. data

collection instrument,

questionnaire

Research resource with processed data, interpretation from CAACB forum (MIT

Team & Industry Members)

Full research reports to include all methods, data

analyses, findings, recommendations

Access Available to:

Full Members

CAACB Research & Ops Team with MIT

NDA coverage ONLY

Full Memberscontributing data

Full Members participating in project

Full Members

ALL: Internal & External of CAACB

Associate Members

Associate Members

contributing dataAssociate Members Associate Members

Research summary reports: major findings and

recommendations without data details

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Consortium Activities

Consortium Operations &

ActivitiesPurposes Participants

Steering Committee Meetings

•To evaluate, revise and approve CAACB strategic plans•To identify, recommend and prioritize future projects


Consortium Task Force Meetings

•To evaluate and recommend potential future projects to the Steering Committee•To assist in analysis of project findings and/or technology advances in relevant fields


Consortium Workshops &

Symposia

•To learn of advances in selected technology areas•To contribute to the understanding of anonymous data collected from CAACB projects•To exchange ideas, experience and knowhow of industry practices

Delegates of Member Companies, Invited MIT faculty

Consortium General Meetings

•To report progress and future plans of CAACB to consortium body•To highlight technology advances and policy changes relevant to mission of CAACB

Delegates of Member Companies, Invited guests

Consortium Sponsored Meetings

•Forum to promote CAACB mission Public

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Consortium Activities & Participations

Consortium Operations & Activities

FullMember

s

Associate

Members

MIT Faculty/Staff by Invitatio

n

External

Expertsby

Invitation

Non-memb

er Entitie

s

Steering Committee Meetings ✔

Consortium Task Force Meetings ✔ ✔

Consortium Workshops & Symposia ✔ ✔ ✔

Consortium General Meetings ✔ ✔ ✔ ✔

Consortium Sponsored Meetings ✔ ✔ ✔ ✔ ✔

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Consortium Schedule 2012

●Jan. – June 2012● Workshop on Media Treatment for Viral Inactivation

● Steering Committee Meeting

●July – Sept. 2012● CAACB General Meeting

● Symposium on New Virus Testing & Identification

Technologies

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Consortium Benefits to Member Companies

1. Learning from industry-wide experience and solutions, as compared to only learning from your company’s experience

2. Benchmarking your adventitious agent contamination strategy against best industry practice

3. Networking and establishing collaborations with individuals in other companies, to address similar adventitious agent issues and solutions

4. Learning first-hand how others have addressed adventitious agent contaminations, decontaminated facilities and implemented corrective and preventive actions.

5. Learning of cutting edge technologies that can be applied to virus testing and contamination risk reduction, and providing guidance to technology providers as to when new technology applications are ready for implementation.

6. Identification of best strategies to obtain regulatory approval for testing and process changes.

7. Sharing best approaches to making risk-based management decisions for implementation of improvements (or corrective actions) to mitigate low risk, high impact events.

8. Promotion of higher industry standards through consortium recommendations to implement scientifically reasonable and beneficial testing and process improvements, without being compelled to implement low value and potentially burdensome changes.

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Overview of Inaugural Project

Project: The Collection and Analysis of Virus Contamination Data in

Biomanufacturing

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The confidential collection of industry-wide viral contamination data and a subsequent risk analysis assessment would be a highly valuable “lessons learned” exercise for industry, and could guide companies in best practices to mitigate the risks that lead to these events.

Premise

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● Potential Issue For Patient Safety● Production Shutdown● Product Stock Out● Lost Product And Lost Sales● Expense Of The Comprehensive

Investigation Required● Delay In Product Approval● Exposes Company To Intense

Regulatory Scrutiny● Changes Public Perception Of

Product Quality

● Requires Development Of Comprehensive Plan For Corrective And Preventive Actions

● Manufacturing Plant Decontamination

● Encourages The Competition ● Complicates Partnerships And

Contractual Agreements● Exposes Company To Lawsuits● Diverts Focus Of Company

Leadership

Impact of Virus Contaminations

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Virus Cell Year Company Reported By

EHDV CHO 1988 Bioferon GmbH Bioferon GmbH

MMV CHO 1993 Genentech Genentech

MMV CHO 1994 Genentech Genentech

ReovirusHuman

1˚Kidney1999 Abbott Labs FDA

Reovirus CHO ? ? BioReliance

Cache Valley CHO 1999 Amgen / CMO Amgen

Cache Valley CHO 2000 ? BioReliance

Vesivirus 2117 CHO 2003 Boehringer-Ingelheim

Boehringer-Ingelheim



Hu Adenovirus HEK 293 ? Eli Lilly Eli Lilly

MMV CHO 2006 Amgen Amgen

Vesivirus 2117 CHO 2008 Genzyme, Belgium

Genzyme

Vesivirus 2117 CHO 2008 Genzyme, USA Genzyme

Vesivirus 2117 CHO 2009 Genzyme, USA Genzyme

MMV CHO 2009 Merrimack Merrimack

PCV-1 Vero 2010 GlaxoSmithKline GlaxoSmithKline

Virus Contaminations: An Industry-Wide Issue

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● Many companies have not publically disclosed virus contamination events● No obligation to disclose unless the contamination results in a “material

change” to the business● Motivated by concerns for negative publicity.● This is well known in the industry.● Some companies do not notify regulatory authorities

● Companies that have disclosed rarely describe the event in sufficient detail to be of significant value

● Companies are only really able to learn from their own contamination events.

Virus Contaminations: Company’s Have Learned Primarily From Their Contamination Event(s)

lack of industry wide knowledge

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● Identification Of Industry Risks ● Which viruses have contaminated operations?● What virus sources have been identified?● What are the most likely process breaches?● Which cell lines are most likely to be contaminated?● Do some process designs have higher risk? (batch vs. perfusion)

● Identification of effective barriers● Is there value in raw material testing?● Has the elimination of animal derived raw materials lowered the frequency of virus

contamination?● How effective are procedures used to inactivate virus in cell culture media before

use?● Is there value in using molecular virus detection methods for in-process testing?

● Shared information could save industry millions of dollars and prevent a potential patient safety catastrophe.

Potential Value of Industry-wide “Lessons Learned” Exercise

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● Virus Identification● Method Of Virus Detection And Identification● Cell Line Contaminated● Extent Of Contamination● Source Of Contamination● Process Breach Identification● Frequency Of Contamination● Raw Material Treatment And Control System● Process Controls● Methods Of Decontamination● Corrective Actions● Preventive Actions● Lessons Learned● Success Of Actions Taken

Initial List of Information to Collect

All data will remain confidential via NDAs between companies and MIT

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Project Goals

1. Collect and analyze consortium member virus contamination data (if member has experienced)

2. Compile processed data into a searchable database with access for members while maintaining confidentiality.

3. Uncover any new risk factors for contamination

4. Determine best industry practice to mitigate risk

5. Identify technology gaps for further R&D

6. Publish summary of key learnings from the project.

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Consortium Member Companies

●Members

●Consortium Pilot Phase● Developed scope for consortium and inaugural project● Reviewed and beta-tested survey

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How to Join

●Written information to be sent for review and discussion with colleagues and management

●Teleconference and/or company visit with Consortium Staff

●Consortium agreement and membership fee●Company representatives to steering committee

determined

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●Consortium Executive DirectorDr. Stacy Springs

email: [email protected]

Tel: 1-617-253-3084

●Lead investigators

Dr. Michael Wiebe


Tel: 1-650-365-7022

Contact Us

Dr. James Leung


Tel: 1-781-333-8822

mailto:[email protected]



Pda2012 talk

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