TY - JOUR 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 SP - 115 LP - 132 DO - 10.5731/pdajpst.2021.012691 VL - 77 IS - 2 AU - Andrea L. Koenigsberg AU - Veronica Fowler AU - Reuben Domike AU - Audrey Brussel AU - Paul W. Barone AU - Flora J. Keumurian AU - James Leung AU - Michael E. Wiebe AU - Michael T. Brewer AU - Shawn Chan AU - Nicolas Dumey AU - Anne Fournillier AU - Marcella Goodnight AU - Johanna Kindermann AU - Richard Leavy AU - Buyoung Lee AU - Stefan Minning AU - Marie Murphy AU - Eric Myers AU - Armen Nahabedian AU - Kavita Nanda AU - Sandi Parriott AU - GK Raju AU - Ciaran Scallan AU - Stephanie Schoch AU - Joe Shiminsky AU - Bonnie Shum AU - Sebastian Teitz AU - Bernice Westrek AU - Stacy L. Springs Y1 - 2023/03/01 UR - http://journal.pda.org/content/77/2/115.abstract N2 - 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. ER -