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PDA Annual Mtg 2012 - CAACB Talk
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    PDA Annual Mtg 2012 - CAACB Talk PDA Annual Mtg 2012 - CAACB Talk Presentation Transcript

    • The MIT Consortium on Adventitious Agent Contamination in Biomanufacturing Michael E. Wiebe, Ph.D. Quantum Consulting
    • Purpose of the ConsortiumTo combine the knowledge, experience andresources of companies that manufacture, orsupport the manufacture of biopharmaceuticalsor vaccines, to identify best practices andtechnologies that control and mitigate the risk ofcontamination of biomanufacturing processes byadventitious agents. 2
    • Consortium Goals● To provide a collaborative environment for companies to share their experiences● To provide a forum for companies to network, develop collaborations and synergize● To identify best industry practices, and to provide opportunities for companies to benchmark● To sponsor collaborative research activities and initiatives that promote a better understanding of how to address adventitious agent contamination.● To promote the generation and application of new technologies● To make public a summary of consortium findings and recommendations. 3
    • Key Components of ConsortiumConsortium 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 representation ● MIT Faculty Investigator: Anthony J. Sinskey ● MIT Faculty & Staff: As Needed Per Consortium ● Active participants in all Projects consortium projects including data contribution, results interpretation●Steering Committee and report generation ● One individual from each member company●Advisory ● Associate Members Board ● 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
    • Consortium Member Companies 5
    • Consortium ActivitiesConsortium Activities Purposes Participants •To provide company information under NDAs on adventitious agent contamination events, preventive Information Sharing actions and risk mitigation strategies Member Companies Projects •To identify best practices to prevent adventitious agent contamination from the analysis of consolidated industry data •To sponsor targeted research projects that lead to Sponsor Targeted Member Companies better control practices, or new technologies that Research Projects mitigate risk of adventitious agent contamination •To learn of advances in selected technology areas •To contribute to the understanding of anonymous data Delegates of MemberConsortium Workshops collected from CAACB projects Companies, Invited & Symposia •To exchange ideas, experience and knowhow of 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 CAACBConsortium Sponsored •Forum to promote CAACB mission Public Meetings 6
    • Consortium Benefits to Member Companies● Learning from industry-wide experience and solutions, as compared to only learning from your company’s experience● Benchmarking your adventitious agent contamination strategy against best industry practice● Networking and establishing collaborations with individuals in other companies, to address similar adventitious agent issues and solutions● Learning first-hand how others have addressed adventitious agent contaminations, decontaminated facilities and implemented corrective and preventive actions.● 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.● Identification of best strategies to obtain regulatory approval for testing and process changes.● Sharing best approaches to making risk-based management decisions for implementation of improvements (or corrective actions) to mitigate low risk, high impact events.● 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. 7
    • Overview of Inaugural Project The Collection and Analysis of VirusContamination Data in Biomanufacturing 8
    • Virus Safety Record in Biopharmaceutical Manufacturing● No rDNA derived product has been shown to transmit a viral safety problem in 25+ years of biopharmaceutical manufacturing.● This can largely be attributed to lessons learned from the past history of biologics manufacturing, and the implementation of a comprehensive multifaceted approach to prevention and control. ● Master Cell Bank testing ● Raw material testing & source control ● Closed manufacturing systems; Unidirectional flow ● Identification of viruses that replicate in the engineered cell substrate ● Lot by lot virus testing ● Downstream processes for virus clearance; Separation or pre- and post- virus clearance steps● However, we know that adventitious viruses have contaminated cell culture biomanufacturing operations. 9
    • 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 ? ? BioRelianceCache Valley CHO 1999 Amgen / CMO AmgenCache Valley CHO 2000 ? BioRelianceVesivirus 2117 CHO 2003 Boehringer- Boehringer- Ingelheim IngelheimCache Valley CHO 2003 ? BioRelianceCache Valley CHO 2004 ? BioRelianceHu Adenovirus HEK 293 ? Eli Lilly Eli Lilly MMV CHO 2006 Amgen AmgenVesivirus 2117 CHO 2008 Genzyme, Belgium GenzymeVesivirus 2117 CHO 2008 Genzyme, USA GenzymeVesivirus 2117 CHO 2009 Genzyme, USA Genzyme MMV CHO 2009 Merrimack Merrimack PCV-1 Vero 2010 GlaxoSmithKline GlaxoSmithKline 10
    • Premise of Consortium Inaugural ProjectThe confidential collection of industry-wide viral contamination data and asubsequent risk analysis assessment wouldbe a highly valuable “lessons learned”exercise for industry, and could guidecompanies in best practices to mitigate therisks that lead to these events. 11
    • Potential 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 12
    • 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. 13
    • 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. 14
    • Confidential Information Is Protected Consortium Information Domain General Steering Advisory Member General Committee Board (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 Project Data Management Data Collection Data Analysis: & Coding Trend & Risk Analysis, etc. Associate Member Associate Preview, Review Member Associate Authorize by Steering Member Associate Confidentiality Committee Member Associate Barrier & Filter MemberAssociateMember Public Reports Public Presentations Summary of Findings Summary of Findings 15
    • Initial List of Information to Collect● Virus Identification● Method of Virus Detection & Identification● Experience with False Positive Tests● Investigation Organization & Management● Communication with Regulatory Authorities; others● Cell Line Contaminated● Extent of Contamination All data will remain● Source of Contamination confidential via NDAs● Process Breach Identification between companies● Frequency of Contamination● Raw Material Treatment & Control System and MIT● Process Controls● Methods of Decontamination● Corrective Actions; Restart● Preventive Actions● Lessons Learned● Success of Actions Taken 16
    • Project Goals1. Collect and analyze consortium member virus contamination data (if experienced by member)2. Compile processed data into a searchable database with access for members while maintaining confidentiality3. Uncover any new risk factors for contamination4. Determine best industry practice to mitigate risk5. Identify technology gaps for further R&D6. Publish summary of key findings from the project 17
    • Project Stages & Proposed TimelineProject Stage Target CompletionDevelop data collection instrument, questionnaire, and CompleteprocessRaw data collection from participating members & partners In ProgressAnonymous data pooling, annotated and collated 2012Preliminary report to member companies 2012Analysis of processed data; Interpretation from CAACB 2012forum (MIT Team & Industry Member Companies)Full research report to member companies; to include all 2013methods, data analyses, findings, recommendationsPublication of Research Summary Report: Major findings & 2013+recommendationsContinuous Updates & Expansion of Data: Collection & 2013+Analysis 18
    • 2012 Consortium Workshops● Media Treatment Workshop ● Sharing of experience with HTST, UV-C, nanofiltration and other methods of virus inactivation or removal ● Where – MIT, Cambridge, MA ● When – June 21 & 22, 2012 ● Open to Consortium member company participants and invited speakers● Virus Contamination Project Workshop ● Currently in planning phase ● To present early draft of collected data; to solicit input on data interpretation ● When – Q4, 2012 ● Open to Consortium member data contributors 19
    • 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 20
    • 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 21