@article {Koenigsberg115, author = {Andrea L. Koenigsberg and Veronica Fowler and Reuben Domike and Audrey Brussel and Paul W. Barone and Flora J. Keumurian and James Leung and Michael E. Wiebe and Michael T. Brewer and Shawn Chan and Nicolas Dumey and Anne Fournillier and Marcella Goodnight and Johanna Kindermann and Richard Leavy and Buyoung Lee and Stefan Minning and Marie Murphy and Eric Myers and Armen Nahabedian and Kavita Nanda and Sandi Parriott and GK Raju and Ciaran Scallan and Stephanie Schoch and Joe Shiminsky and Bonnie Shum and Sebastian Teitz and Bernice Westrek and Stacy L. Springs}, title = {MIT CAACB Risk Assessment Case Study: Assessing Virus Cross-Contamination Risk between Two Simultaneous Processes in an Open Biomanufacturing Facility}, volume = {77}, number = {2}, pages = {115--132}, year = {2023}, doi = {10.5731/pdajpst.2021.012691}, publisher = {Parenteral Drug Association (PDA)}, abstract = {Some members of MIT{\textquoteright}s Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) previously published content on the {\textquotedblleft}Quality Risk Management in the Context of Viral Contamination{\textquotedblright}, 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{\textquoteright}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.}, issn = {1079-7440}, URL = {https://journal.pda.org/content/77/2/115}, eprint = {https://journal.pda.org/content/77/2/115.full.pdf}, journal = {PDA Journal of Pharmaceutical Science and Technology} }