RT Journal Article
SR Electronic
T1 MIT CAACB Risk Assessment Case Study: Assessing Virus Cross-Contamination Risk between Two Simultaneous Processes in an Open Biomanufacturing Facility
JF PDA Journal of Pharmaceutical Science and Technology
JO PDA J Pharm Sci Technol
FD Parenteral Drug Association (PDA)
SP 115
OP 132
DO 10.5731/pdajpst.2021.012691
VO 77
IS 2
A1 Koenigsberg, Andrea L.
A1 Fowler, Veronica
A1 Domike, Reuben
A1 Brussel, Audrey
A1 Barone, Paul W.
A1 Keumurian, Flora J.
A1 Leung, James
A1 Wiebe, Michael E.
A1 Brewer, Michael T.
A1 Chan, Shawn
A1 Dumey, Nicolas
A1 Fournillier, Anne
A1 Goodnight, Marcella
A1 Kindermann, Johanna
A1 Leavy, Richard
A1 Lee, Buyoung
A1 Minning, Stefan
A1 Murphy, Marie
A1 Myers, Eric
A1 Nahabedian, Armen
A1 Nanda, Kavita
A1 Parriott, Sandi
A1 Raju, GK
A1 Scallan, Ciaran
A1 Schoch, Stephanie
A1 Shiminsky, Joe
A1 Shum, Bonnie
A1 Teitz, Sebastian
A1 Westrek, Bernice
A1 Springs, Stacy L.
YR 2023
UL http://journal.pda.org/content/77/2/115.abstract
AB Some members of MIT's Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) previously published content on the “Quality Risk Management in the Context of Viral Contamination”, which described tools, procedures, and methodologies for assessing and managing the risk of a potential virus contamination in cell culture processes. To address the growing industry interest in moving manufacturing toward open ballrooms with functionally closed systems and to demonstrate how the ideas of risk management can be leveraged to perform a risk assessment, CAACB conducted a case study exercise of these new manufacturing modalities. In the case study exercise, a cross-functional team composed of personnel from many of CAACB's industry membership collaboratively assessed the risks of viral cross-contamination between a human and non-human host cell system in an open manufacturing facility. This open manufacturing facility had no walls to provide architectural separation of two processes occurring simultaneously, specifically a recombinant protein perfusion cell culture process using the human cell line, HEK-293 (Process 1) and a downstream postviral filtration unit operation (Process 2) of a recombinant protein produced in CHO cells. This viral risk assessment focused on cross-contamination of the Process 2 filtration unit operation after the Process 1 perfusion bioreactor was contaminated with a virus that went undetected. The workflow for quality risk management that is recommended by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) was followed, which included identifying and mapping the manufacturing process, defining the risk question, risk evaluation, and risk control. The case study includes a completed Failure Mode and Effects Analysis (FMEA) to provide descriptions of the specific risks and corresponding recommended risk reduction actions.