Abstract
CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1–3, 2010
Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA)
The December 2010 workshop on detection and mitigation strategies for adventitious viruses in biologics was organized by the PDA and FDA in response to recent viral contamination events to encourage modernization in industry with respect to viral detection and control measures for enhancing product safety. Such a strategy would further assure continued use of vaccines for public health and avoid costly interruptions in the manufacture of medically necessary biological drugs and the associated shortages that affect seriously ill patients.
The meeting was opened by welcoming remarks from Patricia Hughes (CDER, FDA).
Session 1 was moderated by Arifa Khan (CBER, FDA), who introduced the keynote speaker Dr. Anthony Lubiniecki from Johnson & Johnson and his talk on Evolution of Approaches to Viral Safety Issues for Biological Products. This talk led us through the history of adventitious agent issues in early vaccines, plasma derivatives, and early modern biopharmaceuticals. It also included issues related to animal-derived raw materials with a discussion of viral control approaches, and concluded with lessons learned and future expectations.
The following session 2 was moderated by Christopher Joneckis (CBER, FDA) and Johannes Blümel (PEI) and included talks on Current Regulatory Approaches for Control of Viral Contamination from Philip Krause (CBER, FDA), Amy Rosenberg (CDER, FDA), and Johannes Blümel (PEI). This session described the FDA and European regulatory expectations for control of adventitious viruses in a variety of biological products and included discussion of strategies for prevention, detection, and elimination of viral contaminants with consideration of the evolving risks, challenges, and new technologies.
Sessions 3 and 4 were moderated by Barry Cherney (CDER, FDA) and Michael Wiebe (Quantum Consulting, LLC) and included a Review of Viral Contamination and Case Studies with talks from Nathan Jones (Genzyme), James Skrine (Amgen), Mark Moody (Merrimack Pharmaceuticals), Dominick Vacante for Linda Hendricks (Johnson & Johnson), Isabelle Pierard (GlaxoSmithKline Biologicals), and Colette Ranucci (Merck and Co). The talks highlighted recent cases of viral contamination with discussion of virus identification, root cause analysis, extent of contamination, facility decontamination, and corrective and preventative actions. This plenary session was associated with Breakout Session E, which was moderated by Anthony Lubiniecki and Kurt Brorson, and included talks on Case Studies of Viral Contaminations with focus on root cause determinations and evaluation of mitigations. Speakers included Dominick Vacante (Johnson & Johnson), Keith Peden (CBER, FDA), and Lowell Jackson (Amgen) followed by a panel discussion with the session speakers and the audience. Additionally, discussions on Facility and Equipment Decontamination Strategies were continued in Breakout Session F, which was moderated by Laurie Norwood (CBER, FDA) and Kalavati Suvarna (CDER, FDA). Speakers included Eric Mundhenke (Amgen), Mark Lutgen (Amgen), and John Mason (The Sabre Companies) followed by a discussion with the audience on decontamination plans and implementation strategies.
Session 5 on Viral Testing: Existing Assays and Emerging Technologies was moderated by Arifa Khan (CBER, FDA) and Ranga Sampath (Ibis/Abbott Molecular). This session discussed the current virus testing methods with focus on identifying gaps in testing strategies and the use of existing or emerging technologies to fill the gaps. Speakers included Arifa Khan (CBER, FDA), Jens-Peter Gregersen (Novartis), Ivar Kljavin (Genentech/Roche), and David Onions (BioReliance Corp). The topic of Current Virus Detection Methods was further discussed in Breakout Session C, which was moderated by Andrew Byrnes (CBER, FDA) and Hannelore Willkommen (Regulatory Affairs & Biological Safety Consulting), and included talks by Paul Duncan (Merck & Co), Garry Takle (WuXi AppTec), Andrew Byrnes (CBER, FDA), Hannelore Willkommen (Regulatory Affairs & Biological Safety Consulting), and Kathleen Clouse (CDER, FDA) followed by a panel discussion of the advantages and limitations of the various in vitro and in vivo current testing methods for adventitious agents in biologic and cell substrates. Additionally, Emerging Technologies for Virus Detection were further discussed in Breakout Session D moderated by Arifa Khan (CBER, FDA), John Kolman (BioReliance), and Crystal Jaing (Lawrence Livermore National Labs). Speakers on new virus detection methods and their applications included John Kolman (BioReliance), Rangarajan Sampath (Ibis/Abbott Molecular), Crystal Jaing (Lawrence Livermore National Labs), David Munroe (SAIC-Frederick, NCI), C. Richard Ill (Amgen), Mike Morrow (Nanostring Technologies), Christine Uhlenhaut (CBER, FDA), and Hailun Ma (CBER, FDA). Kathryn King (CDER, FDA) presented a progress report on the PDA Cell Substrate Task Force emerging technologies technical document.
Session 6 on Facility Control and GMP Expectations was moderated by Patricia Hughes (CDER, FDA) and Norbert Hentschel (BI Pharma). This session included talks on the GMP requirements and enforcement actions available to the Agency designed to ensure that manufacturing standards for the control of adventitious viruses are met at the time of approval and over a product's life cycle. The speakers were John Eltermann (CBER, FDA), Rick Friedman (CDER, FDA), and Ronald Taticek (Genentech). The discussions on Regulatory Expectations for CGMP were continued in Breakout Session B, which was moderated by Robert Sausville (CBER, FDA) and Chantal Cazeault (Health Canada). Talks on the approaches that can be followed to ensure that a facility is in control and that CGMP expectations are met were given by David Jarowski (CDER, FDA), Robert McElwain (CBER, FDA), and Anissa Cheung (CBER, FDA) followed by a panel discussion of issues of concerns regarding regulations and CGMP requirements for the control of adventitious agents.
Session 7 on Process Design Strategies for Prevention of Viral Contaminations was moderated by Patrick Swann (CDER, FDA) and Robert Kozak (Bayer) focused on Quality by Design (QBD as described in ICH Q8r2) and Quality Risk Management (QRM as defined by ICH Q9) as well as discussions of a Pharmaceutical Quality System (as defined by ICH Q10). The speakers were Mahmood Farshid (CBER, FDA), Barry Cherney (CDER, FDA), Robert Kiss (Genentech), and Sridhar Pennathur (MedImmune).
Additionally, Breakout Session A, moderated by Roman Drews (CBER, FDA) and Robert Kiss (Genentech) focused on Elimination or Treatment of High-Risk Raw Materials. The session discussed assessment and different mitigation strategies for reducing the risk of viral contamination that may be introduced by a raw material. Presentations on different approaches to raw material risk reduction were given by Robert Baffi (BioMarin Pharmaceuticals), Mike Brewer (Invitrogen), Michael Mercaldi (MedImmune), and Ruth Cordoba-Rodriguez (CDER, FDA) followed by a panel discussion, which also included Weichang Zhou (Genzyme).
Session 8 on Moving Forward: Best Practices To Mitigate the Risk of Virus Contamination of Parenteral Products was moderated by Rich Levy (PDA) and included a talk by G. K. Raju (Light Pharma; MIT) on Risk, Detection, and Mitigation: Lessons Learned During This Workshop.
Session 9 was a Wrap-Up Session moderated by Arifa Khan (CBER, FDA) in which the moderators of the breakout sessions summarized and presented the highlights of their sessions.
The final Session 10, moderated by Patricia Hughes (CDER, FDA), was an Expert Panel Discussion, which included panelists Chantal Cazeault (Health Canada), Philip Krause (CBER, FDA), David Jaworski (CBER, FDA), Anthony Lubiniecki (Johnson & Johnson), David Onions (BioReliance), G. K. Raju (Light Pharma; MIT), and Amy Rosenberg (CDER, FDA). The panel discussed issues raised in the sessions as well as questions from the audience with particular focus on recent contamination events and use of emerging methods for virus detection. The need for further discussions on the applications of new methodologies for viral safety at a future meeting was indicated.
The meeting was closed by Michael Wiebe (Quantum Consulting) with recognition that the Workshop provided a unique opportunity to examine adventitious virus contamination in biomanufacturing by sharing industry experiences, regulatory insights, and the applications of new technologies. Hopefully, this exchange of knowledge and lessons learned from this Workshop, along with the enthusiastic interactive discussions during the question and answer periods after each plenary session and throughout the breakout sessions, will be of significant value to industry for detection of adventitious viruses and risk mitigation strategies. This edition of the PDA Journal of Pharmaceutical Science and Technology contains papers and abstracts based upon the talks given in the plenary sessions in the meeting. Additionally, for the breakout sessions, there are papers or summaries based upon the session format.
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