The MIT Consortium on Adventitious Agent Contamination in Biomanufacturing aims to: 1) Provide a collaborative environment for companies to share experiences with virus contaminations. 2) Identify and benchmark against best practices to mitigate contamination risks. 3) Sponsor research to better understand contamination and develop detection/prevention methods. The consortium will anonymously collect contamination data from member companies and conduct a risk analysis to guide industry standards that enhance patient safety and regulatory compliance.

1. The MIT Consortium on Adventitious
Agent Contamination in
Biomanufacturing
A Center For Biomedical Innovation Initiative

2. 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 2

3. Consortium Activities
Consortium
Operations & Purposes Participants
Activities
•To evaluate, revise and approve CAACB strategic
Steering Committee Representatives of
plans
Meetings Member Companies
•To identify, recommend and prioritize future projects
•To evaluate and recommend potential future projects
Representatives of
Consortium Task to the Steering Committee
Member Companies
Force Meetings •To assist in analysis of project findings and/or
technology advances in relevant fields
•To learn of advances in selected technology areas
Consortium •To contribute to the understanding of anonymous data Delegates of
Workshops & collected from CAACB projects Member Companies,
Symposia •To exchange ideas, experience and knowhow of Invited MIT faculty
industry practices
•To report progress and future plans of CAACB to
Delegates of Member
Consortium General consortium body
Companies, Invited
Meetings •To highlight technology advances and policy changes
guests
relevant to mission of CAACB
Consortium
•Forum to promote CAACB mission Public
Sponsored Meetings
3

4. Key Components of Consortium
Consortium Operations & Management Fee-based Membership
● MIT CAACB Team ● Full Members
● Program Director: Dr. Stacy Springs
● Manufacture Biologics
● Lead Investigators: Michael Wiebe and James
Leung ● Steering Committee
● MIT Faculty Investigator: Anthony J. Sinskey representation
● MIT Faculty & Staff: As Needed Per Consortium ● Active participants in all
Projects
consortium projects including data
● Steering Committee contribution, results interpretation
● One individual from each member company and report generation
● Advisory Board ● Associate Members
● Kurt Brorson, FDA (CDER) ● Do not manufacture Biologics (e.g.
● Marshall Dinowitz, Consultant Service Providers & Technology
● Jim Gombold, Charles River Laboratories Companies)
● Bill Lucas, WuXi AppTec ● Active participants in projects
● Ray Nims, Consultant focusing on technologies and
● Carol Marcus-Sekura, Consultant methods assessments &
● Anton Steuer, BioReliance development, roles to be defined
● Hannelore Willkommen, Consultant
● Ruth Wolff, Consultant
4

5. Outline
● 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
5

6. Consortium Goals
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.
6

7. Key Components of Consortium
Consortium Operations & Management Fee-based Membership
● MIT CAACB Team ● Full Members
● Program Director: Dr. Stacy Springs
● Manufacture Biologics
● Lead Investigators: Michael Wiebe and James Leung
● MIT Faculty Investigator: Anthony J. Sinskey
● Steering Committee
● MIT Faculty & Staff: As Needed Per Consortium
representation
Projects ● Active participants in all
● Steering Committee consortium projects including data
contribution, results interpretation
● One individual from each member company
and report generation
● Advisory Board
● Associate Members
● Kurt Brorson, FDA (CDER)
● Marshall Dinowitz, Consultant ● Do not manufacture Biologics (e.g.
● Jim Gombold, Charles River Laboratories
Service Providers & Technology
Companies)
● Bill Lucas, WuXi AppTec
● Ray Nims, Consultant ● Active participants in projects
● Carol Marcus-Sekura, Consultant
focusing on technologies and
methods assessments &
● Anton Steuer, BioReliance
development, roles to be defined
● Hannelore Willkommen, Consultant
● Ruth Wolff, Consultant
7

8. Consortium Organization & Deliverables
General
Member
General
(Data Contributor) Steering Advisory
Member Board
General Committee
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
(Data Contributor)
Deliverables Available to
CAACB Members
MIT CBI/CAACB Team
Data Management Anonymous Project Reports:
Project Project Data Data Analysis &
Data Recommendations
Collection Data Analysis: Web Resource
& Coding Trend & Risk Center
CAACB
Analysis, etc. Workshop Technology
Associate Proceedings Research Proposals
Member
Associate
Member
Associate
Member
Associate
Member
Associate
Member
Associate
Member
Public Reports Public Presentations
Summary of Findings Summary of Findings
8

9. Consortium Information Flow
& Confidentiality Space
General
Consortium Information Domain
Member
General
(Data Contributor) Steering Advisory
Member Board
General Committee
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
(Data Contributor)
Deliverables Available to
CAACB Members
MIT CBI/CAACB Team
Data Management Anonymous Project Reports:
Project Project Data Data Analysis &
Data Recommendations
Collection Data Analysis: Web Resource
& Coding Trend & Risk Center
CAACB
Analysis, etc. Workshop Technology
Associate Proceedings Research Proposals
Member
Associate
Preview, Review
Member
Associate Authorize by Steering
Member
Associate Committee
Member
Associate
Member
Associate
Member
Public Reports Public Presentations
9 Summary of Findings Summary of Findings

10. Company Specific Information:
MIT-Member NDA Confidentiality Space
General
Member
General
(Data Contributor) Steering Advisory
Member Board
General Committee
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
(Data Contributor)
Deliverables Available to
CAACB Members
MIT CBI/CAACB Team
Data Protected by
Project
Data Management Anonymous
Project Data
Project Reports:
Data Analysis &
Individual NDAs between
Data
Collection
Recommendations
Data Analysis: Web Resource
Companies and&MIT
& Coding Trend Risk Center
CAACB
Analysis, etc. Workshop Technology
Associate Proceedings Research Proposals
Member
Associate
Member
Associate
Member
Associate
Member
Associate
Member
Associate
Member
Public Reports Public Presentations
Summary of Findings Summary of Findings
10

11. Company Specific Information:
Confidentiality Protection
General
Member
General
(Data Contributor) Steering Advisory
Member Board
General Committee
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
(Data Contributor)
Deliverables Available to
CAACB Members
MIT CBI/CAACB Team
Data Management Anonymous Project Reports:
Project Project Data Data Analysis &
Data Recommendations
Collection Data Analysis: Web Resource
& Coding Trend & Risk Center
CAACB
Analysis, etc. Workshop Technology
Associate Proceedings Research Proposals
Member
Associate
Member
Associate
Member
Associate Confidentiality
Member
Associate Barrier & Filter
Member
Associate
Member
Public Reports Public Presentations
Summary of Findings Summary of Findings
11

12. Confidential Information Is Protected
General
Consortium Information Domain
Member
General
(Data Contributor) Steering Advisory
Member Board
General Committee
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
General
(Data Contributor)
Member
(Data Contributor)
Deliverables Available to
CAACB Members
MIT CBI/CAACB Team
Data Management Anonymous Project Reports:
Project Project Data Data Analysis &
Data Recommendations
Collection Data Analysis: Web Resource
& Coding Trend & Risk Center
CAACB
Analysis, etc. Workshop Technology
Associate Proceedings Research Proposals
Member
Associate
Preview, Review
Member
Associate Authorize by Steering
Member
Associate Confidentiality Committee
Member
Associate Barrier & Filter
Member
Associate
Member
Public Reports Public Presentations
12 Summary of Findings Summary of Findings

13. Consortium Projects with Confidential Information –
Deliverables and Access by CAACB Participants
Research resource
Research Raw data Full research Research summary
Anonymous with processed data,
tools: e.g. data collected from reports to include reports: major
data pool - interpretation from
collection Participating all methods, data findings and
annotated CAACB forum (MIT
instrument, qu Members & analyses, findings, recommendations
and collated Team & Industry
estionnaire Partners recommendations without data details
Members)
Access Available to:
Full Members Full Members
Full Members Full Members
contributing data participating in project
CAACB Research &
ALL: Internal &
Ops Team with MIT
Associate External of CAACB
Associate NDA coverage ONLY
Members Associate Members Associate Members
Members
contributing data
13

14. Consortium Activities
Consortium
Operations & Purposes Participants
Activities
•To evaluate, revise and approve CAACB strategic
Steering Committee Representatives of
plans
Meetings Member Companies
•To identify, recommend and prioritize future projects
•To evaluate and recommend potential future projects
Representatives of
Consortium Task to the Steering Committee
Member Companies
Force Meetings •To assist in analysis of project findings and/or
technology advances in relevant fields
•To learn of advances in selected technology areas
Consortium •To contribute to the understanding of anonymous data Delegates of
Workshops & collected from CAACB projects Member Companies,
Symposia •To exchange ideas, experience and knowhow of Invited MIT faculty
industry practices
•To report progress and future plans of CAACB to
Delegates of Member
Consortium General consortium body
Companies, Invited
Meetings •To highlight technology advances and policy changes
guests
relevant to mission of CAACB
Consortium
•Forum to promote CAACB mission Public
Sponsored Meetings
14

15. Consortium Activities & Participations
MIT External
Associat Non-
Full Faculty/ Experts
Consortium Operations & Activities e member
Members Staff by by
Members Entities
Invitation Invitation
Steering Committee Meetings ✔
Consortium Task Force Meetings ✔ ✔
Consortium Workshops &
Symposia ✔ ✔ ✔
Consortium General Meetings ✔ ✔ ✔ ✔
Consortium Sponsored Meetings ✔ ✔ ✔ ✔ ✔
15

16. 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
16

17. 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.
17

18. Overview of Inaugural Project
Project: The Collection and Analysis of
Virus Contamination Data in
Biomanufacturing
18

19. Premise
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.
19

20. Impact of Virus Contaminations
● Potential Issue For Patient ● Requires Development Of
Safety Comprehensive Plan For
● Production Shutdown Corrective And Preventive
Actions
● Product Stock Out
● Manufacturing Plant
● Lost Product And Lost Sales Decontamination
● Expense Of The ● Encourages The Competition
Comprehensive Investigation
Required ● Complicates Partnerships
And Contractual Agreements
● Delay In Product Approval
● Exposes Company To
● Exposes Company To Intense Lawsuits
Regulatory Scrutiny
● Diverts Focus Of Company
● Changes Public Perception Of Leadership
Product Quality
20

21. Virus Contaminations: An Industry-Wide Issue
Virus Cell Year Company Reported By
EHDV CHO 1988 Bioferon GmbH Bioferon GmbH
MMV CHO 1993 Genentech Genentech
MMV CHO 1994 Genentech Genentech
Reovirus Human 1˚Kidney 1999 Abbott Labs FDA
Reovirus CHO ? ? BioReliance
Cache Valley CHO 1999 Amgen / CMO Amgen
Cache Valley CHO 2000 ? BioReliance
Vesivirus 2117 CHO 2003 Boehringer- Boehringer-
Ingelheim Ingelheim
Cache Valley CHO 2003 ? BioReliance
Cache Valley CHO 2004 ? BioReliance
Hu Adenovirus HEK 293 ? Eli Lilly Eli Lilly
MMV CHO 2006 Amgen Amgen
Vesivirus 2117 CHO 2008 Genzyme, Genzyme
Belgium
Vesivirus 2117 CHO 2008 Genzyme, USA Genzyme
Vesivirus 2117 CHO 2009 Genzyme, USA Genzyme
MMV CHO 2009 Merrimack Merrimack
21

22. Virus Contaminations: Company’s Have Learned
Primarily From Their Contamination Event(s)
● 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
lack of industry wide knowledge
● Companies are only really able to learn from their own contamination
events.
22

23. Potential Value of Industry-wide
“Lessons Learned” Exercise
● 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.
23

24. Initial List of Information to Collect
● Virus Identification
● Method Of Virus Detection And Identification
● Cell Line Contaminated
● Extent Of Contamination
● Source Of Contamination All data will remain
● Process Breach Identification
● Frequency Of Contamination
confidential via
● Raw Material Treatment And Control System NDAs between
● Process Controls companies and MIT
● Methods Of Decontamination
● Corrective Actions
● Preventive Actions
● Lessons Learned
● Success Of Actions Taken
24

25. 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.
25

26. Consortium Member Companies
●Members
●Consortium Pilot Phase
● Developed scope for consortium and inaugural project
● Reviewed and beta-tested survey
26

27. 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
27

28. Contact Us
●Consortium Executive Director
Dr. Stacy Springs
email: ssprings@mit.edu
Tel: 1-617-253-3084
●Lead investigators
Dr. Michael Wiebe Dr. James Leung
email: quantumco@comcast.net email: leungjc@mit.edu
Tel: 1-650-365-7022 Tel: 1-781-333-8822
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