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Article CommentaryCommentary

Biopharmaceutical Industry Approaches to Facility Segregation for Viral Safety: An Effort from the Consortium on Adventitious Agent Contamination in Biomanufacturing

Paul W. Barone, Stephen Avgerinos, Rob Ballard, Audrey Brussel, Philip Clark, Chris Dowd, Lionel Gerentes, Ian Hart, Flora J. Keumurian, Johanna Kindermann, James C. Leung, Nguyen Ly, Sheldon Mink, Stefan Minning, Jürgen Mullberg, Marie Murphy, Kerstin Nöske, Sandi Parriott, Bonnie Shum, Michael E. Wiebe and Stacy L. Springs
PDA Journal of Pharmaceutical Science and Technology March 2019, 73 (2) 191-203; DOI: https://doi.org/10.5731/pdajpst.2018.008862
Paul W. Barone
1Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA, USA;
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  • For correspondence: pbarone@mit.edu
Stephen Avgerinos
2Pfizer, Andover, MA, USA;
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Rob Ballard
3Biogen, Durham, NC, USA;
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Audrey Brussel
4LFB, France;
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Philip Clark
5Amgen, Thousand Oaks, CA, USA;
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Chris Dowd
6Genentech, South San Francisco, CA, USA;
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Lionel Gerentes
7Sanofi, France;
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Ian Hart
8MedImmune, Gaithersburg, MD, USA;
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Flora J. Keumurian
1Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA, USA;
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Johanna Kindermann
9Shire, Vienna, Austria;
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James C. Leung
1Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA, USA;
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Nguyen Ly
10Merck & Co., Inc., Kenilworth, NJ, USA;
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Sheldon Mink
11Regeneron, Rensselaer, NY, USA;
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Stefan Minning
12Boehringer Ingelheim, Germany;
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Jürgen Mullberg
13Bristol-Myers Squibb, Devens, MA, USA;
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Marie Murphy
14Eli Lilly, Dublin, Ireland;
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Kerstin Nöske
15CSL Behring, Marburg, Germany; and
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Sandi Parriott
16BioMarin, San Rafael, CA, USA.
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Bonnie Shum
5Amgen, Thousand Oaks, CA, USA;
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Michael E. Wiebe
1Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA, USA;
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Stacy L. Springs
1Center for Biomedical Innovation, Massachusetts Institute of Technology, Cambridge, MA, USA;
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Abstract

Appropriate segregation within manufacturing facilities is required by regulators and utilized by manufacturers to ensure that the final product has not been contaminated with (a) adventitious viruses, (b) another pre-/postviral clearance fraction of the same product, or (c) another product processed in the same facility. However, there is no consensus on what constitutes appropriate facility segregation to minimize these risks. In part, this is due to the fact that a wide variety of manufacturing facilities and operational practices exist, including single-product and multiproduct manufacturing, using traditional segregation strategies with separate rooms for specific operations that may use stainless steel or disposable equipment to more modern ballroom-style operations that use mostly disposable equipment (i.e., pre- and postviral clearance manufacturing operations are not physically segregated by walls). Further, consensus is lacking around basic definitions and approaches related to facility segregation. For example, given that several unit operations provide assurance of virus clearance during downstream processing, how does one define pre- and postviral clearance and at which point(s) should a viral segregation barrier be introduced? What is a “functionally closed” system? How can interventions be conducted so that the system remains functionally closed? How can functionally closed systems be used to adequately isolate a product stream and ensure its safety? To address these issues, the member companies of the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) have conducted a facility segregation project with the following goals: define “pre- and postviral clearance zones” and “pre- and postviral clearance materials”; define “functionally closed” manufacturing systems; and identify an array of facility segregation approaches that are used for the safe and effective production of recombinant biologics as well as plasma products. This article reflects the current thinking from this collaborative endeavor.

LAY ABSTRACT: Operations in biopharmaceutical manufacturing are segregated to ensure that the final product has not been contaminated with adventitious viruses, another fraction of the same product, or with another product from within the same facility. Yet there is no consensus understanding of what appropriate facility segregation looks like. There are a wide variety of manufacturing facilities and operational practices. There are existing facilities with separate rooms and more modern approaches that use disposable equipment in an open ballroom without walls. There is also no agreement on basic definitions and approaches related to facility segregation approaches. For example, many would like to claim that their manufacturing process is functionally closed, yet exactly how a functionally closed system may be defined is not clear. To address this, the member companies of the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) have conducted a project with the goal of defining important manufacturing terms relevant to designing an appropriately segregated facility and identifying different facility segregation approaches that are used for the safe and effective production of recombinant biologics as well as plasma products.

  • Functionally closed
  • Viral clearance
  • Facility segregation
  • Adventitious agent contamination
  • Physical segregation
  • Open ballroom
  • © PDA, Inc. 2019
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PDA Journal of Pharmaceutical Science and Technology: 73 (2)
PDA Journal of Pharmaceutical Science and Technology
Vol. 73, Issue 2
March/April 2019
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Biopharmaceutical Industry Approaches to Facility Segregation for Viral Safety: An Effort from the Consortium on Adventitious Agent Contamination in Biomanufacturing
Paul W. Barone, Stephen Avgerinos, Rob Ballard, Audrey Brussel, Philip Clark, Chris Dowd, Lionel Gerentes, Ian Hart, Flora J. Keumurian, Johanna Kindermann, James C. Leung, Nguyen Ly, Sheldon Mink, Stefan Minning, Jürgen Mullberg, Marie Murphy, Kerstin Nöske, Sandi Parriott, Bonnie Shum, Michael E. Wiebe, Stacy L. Springs
PDA Journal of Pharmaceutical Science and Technology Mar 2019, 73 (2) 191-203; DOI: 10.5731/pdajpst.2018.008862

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Biopharmaceutical Industry Approaches to Facility Segregation for Viral Safety: An Effort from the Consortium on Adventitious Agent Contamination in Biomanufacturing
Paul W. Barone, Stephen Avgerinos, Rob Ballard, Audrey Brussel, Philip Clark, Chris Dowd, Lionel Gerentes, Ian Hart, Flora J. Keumurian, Johanna Kindermann, James C. Leung, Nguyen Ly, Sheldon Mink, Stefan Minning, Jürgen Mullberg, Marie Murphy, Kerstin Nöske, Sandi Parriott, Bonnie Shum, Michael E. Wiebe, Stacy L. Springs
PDA Journal of Pharmaceutical Science and Technology Mar 2019, 73 (2) 191-203; DOI: 10.5731/pdajpst.2018.008862
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Keywords

  • Functionally closed
  • Viral clearance
  • Facility segregation
  • Adventitious agent contamination
  • Physical segregation
  • Open ballroom

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