Paul Barone, PhD

P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
An Update on the Activities of the
Consortium on Adventitious Agent
Contamination in Biomanufacturing
Paul W. Barone, Ph.D.
Associate Director, BioMAN and CAACB
MIT Center for Biomedical Innovation
PDA/FDA Virus and TSE Safety Conference
Bethesda, MD, 9-11 June 2014
The Mission of the CAACB
To combine the knowledge, experience and
resources of companies that manufacture, or
support the manufacture of biopharmaceuticals or
vaccines, to identify best practices and
technologies that control and mitigate the risk of
contamination of biomanufacturing processes by
adventitious agents.
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
In 25+ years of biopharmaceutical manufacturing
no rDNA derived product has been shown to
transmit a viral safety problem!
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
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Black swan event
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Chronology of Known Contamination Events
Virus /Host Cell
1985‐1989
1990‐1994
1995‐1999
2000‐2004
2005‐2009
2010+
Unknown
Orbivirus /CHO
EHDV /CHO
MMV /CHO
MMV /CHO
Reovirus /Hu 1° Kidney
Vesivirus /CHO
CVV /CHO
CVV /Unknown
CVV /Unknown
Vesivirus /CHO
Vesivirus /CHO
MMV /CHO
CVV /CHO
MMV /CHO
Vesivirus /CHO
MMV /CHO
PCV‐1 /Vero
MMV/BHK‐21
MMV /BHK‐21
Human Adenovirus /HEK293
Reovirus /Unknown
Events
2
2
3
2
6
3
3
21
Total
Events reported to CAACB (may also have been reported publicly)
Events published by non‐member companies
Potential Impact of Virus Contaminations
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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
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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
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Goals of the CAACB
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Provide environment for companies to share experiences
in the control and risk mitigation of adventitious agent
contamination in biomanufacturing
Provide forum for companies to network, develop
collaborations and synergize activities
Identify best industry practices
Provide opportunities to benchmark
Sponsor collaborative research activities
Promote generation & application of new technologies
Provide early access to data and consortium member
participation in analyses prior to sharing summary of
findings with public through publications
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Key Components of Consortium
Fee‐based Membership
Consortium Operations & Mgmt
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MIT CAACB Team
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Steering Committee
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Program Director: Dr. Stacy Springs
Associate Director: Dr. Paul Barone
Lead Investigators: Michael Wiebe and
James Leung
MIT Faculty Investigator: Anthony J.
Sinskey
MIT Faculty & Staff: As Needed Per
Consortium Projects
One individual from each member company
Advisory Board
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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
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Full Members
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Manufacture Biologics
Steering Committee representation
Active participants in all consortium
projects including data contribution,
results interpretation and report
generation
Associate Members
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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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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Consortium Member Companies
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* Founding member
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Key CAACB Activities
CAACB Workshops
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1-2 day small (60 – 75 attendees) interactive meetings
with presentations, case studies and open discussion
CAACB Member Driven Projects
● Collection and Analysis of Virus Contamination
Data in Biomanufacturing
● Evaluation of Media Treatment Options
● Risk Assessment and Risk Control of Virus
Contamination in Biomanufacturing
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
CAACB Inaugural Project
The Collection and Analysis of Virus
Contamination Data in Biomanufacturing
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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.
More to come…
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Evaluation of Media Treatment Options
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Evaluation of Media Treatment Options
1.
2.
3.
Harmonization of HTST inactivation data
Economic analysis of media treatment technologies
Collect and analyze existing inactivation/removal data
(from literature and previously generated member
data) for HTST (and other technologies) using different
model organisms including virus, mycoplasma, and
leptospira
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Published HTST MMV Inactivation Data
Media Treatment Sub‐project 1
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Harmonization of HTST Inactivation Data
(cont.)
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Goal:
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Determine if reported inactivation result differences due to
differences in experimental design or other causative factors.
Reconcile and harmonize available data to generate a
consolidated conclusion on efficacy of HTST inactivation of
MMV.
Deliverables:
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Journal Publication from the CAACB
Conference Presentation(s) (to be determined at a later
date)
Media Treatment Sub‐project 1
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Economic Analysis of Media
Treatment/Inactivation Options
A tool and approach to aid
in estimating media
treatment costs could help
guide business decisions
Media Treatment Sub‐project 2
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Economic Analysis of Media
Treatment/Inactivation Options (cont.)
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Goals:
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Gather data on cost estimation for barrier technology
implementation from consortium members and any open literature
Develop an approach for estimating the costs of implementing
barrier technologies
● Costs including Development costs, Capital costs, Operational
costs, “Lost Opportunity” costs due to decreased productivity
Develop a tool (spreadsheet) for estimating the costs for barrier
technologies
Deliverables:
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Economic analysis tool
White paper including output examples
External publication (e.g. conference presentation)
Media Treatment Sub‐project 2
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Analysis of inactivation/removal data for
different model organisms
The assembly and analysis of existing
inactivation and removal data, both from existing
literature and the confidential collection of member
data, into a single source would be of value to
the industry.
Media Treatment Sub‐project 3
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Analysis of inactivation/removal data for
different model organisms (cont.)
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Goals:
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Collect existing inactivation (UV-C and HTST) and
removal (nanofiltration) data from CAACB members.
Collect and review existing literature data, including
data from other industries.
Analyze compiled inactivation and removal data,
assess gaps in the data with respect to treatment types,
applicability of the data and/or model organisms used.
Deliverables:
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White paper summarizing data
Potential external publications (to be decided later)
Media Treatment Sub‐project 3
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Risk Assessment and Risk Control of
Virus Contamination in Biomanufacturing
A virus contamination risk assessment and risk
control “handbook” establishing industry wide tools
as well as procedures and methodologies for
assessing and managing the risk of potential virus
contamination in cell culture processes would
reduce the resource burden and aid in decision
making.
Yet such a document does not exist.
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Risk Assessment and Risk Control of
Virus Contamination in Biomanufacturing
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Goal:
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Develop a Virus Contamination Risk Assessment and Risk
Control “handbook” to aid companies in their risk
assessment and management process.
Deliverables:
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Virus Contamination Risk Assessment and Risk Control
“handbook”
CAACB workshop to educate membership on project
findings
External publications – determined at a later date
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CAACB Workshops Topics
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Role of testing in the control of virus contamination in
biomanufacturing (July 23-24, 2014).
Adventitious agent control in non-sterile cell culture
operations (December 9-10, 2013).
CAACB virus risk assessment approaches workshop
(June 24-25, 2013)
CAACB virus contamination project workshop
(December 13, 2012).
CAACB media treatment workshop
(June 21-22, 2012)
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P3 - Viral Contamination and Risk Mitigation
By: Paul Barone, PhD
Contact Us
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Consortium Executive Director
Dr. Stacy Springs
email: [email protected]
Tel: 1-617-253-3084
• Associate Director
Dr. Paul Barone
email: [email protected]
Tel: 1-617-253-9604
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Lead investigators
Dr. Michael Wiebe
email: [email protected]
Tel: 1-650-365-7022
Dr. James Leung
email: [email protected]
Tel: 1-781-333-8822
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