RT Journal Article
SR Electronic
T1 Biopharmaceutical Industry Approaches to Facility Segregation for Viral Safety: An Effort from the Consortium on Adventitious Agent Contamination in Biomanufacturing
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP pdajpst.2018.008862
DO 10.5731/pdajpst.2018.008862
A1 Barone, Paul W
A1 Avgerinos, Stephen
A1 Ballard, Rob
A1 Brussel, Audrey
A1 Clark, Phil
A1 Dowd, Chris
A1 Gerentes, Lionel
A1 Hart, Ian
A1 Keumurian, Flora J.
A1 Kindermann, Johanna
A1 Leung, James C.
A1 Ly, Nguyen
A1 Mink, Sheldon
A1 Minning, Stefan
A1 Mülberg, Jürgen
A1 Murphy, Marie
A1 Nöske, Kerstin
A1 Parriott, Sandra
A1 Shum, Bonnie
A1 Wiebe, Michael E.
A1 Springs, Stacy L.
YR 2018
UL http://journal.pda.org/content/early/2018/11/15/pdajpst.2018.008862.abstract
AB Appropriate segregation within manufacturing facilities is required by regulators and utilized by manufacturers to ensure that the final product has not been contaminated with 1) adventitious viruses, 2) another pre-/ post-viral clearance fraction of the same product, or 3) with another product processed in the same facility. However, there is not 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 and multi-product manufacturing, using traditional segregation strategies with separate rooms for specific operations that may use stainless steel or disposable equipment to more modern ballroom style operation that use mostly disposable equipment (i.e. pre- and post-viral clearance manufacturing operations are not physically segregated by walls). Further, there is a lack of consensus 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 post-viral 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 post-viral clearance zones” and “pre- and post-viral 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.