Risk mitigation and optimization strategies for viral filtration

BIOT 313

Lisa Flansburg, lisa.flansburg@bms.com1, Renyo Forng1, Steven Lee2, and Abhinav A Shukla, abhinav.shukla@bms.com1. (1) Bioprocess Engineering, Bristol-Myers Squibb, PO Box 4755, Syracuse, NY 13221, (2) Technical Operations, Bristol-Myers Squibb, 6000 Thompson Road, East Syracuse, NY 13057
Therapeutic recombinant proteins expressed by mammalian cell lines are susceptible to contamination by retrovirus-like particles. Clearance of viral particles from product streams must be demonstrated in accordance with regulatory requirements for viral safety. Adequate viral safety in manufacturing processes for therapeutic recombinant proteins and plasma-derived biologics can be achieved by the viral filtration step because of its robustness and ease of validation. Viral filters are single use devices employing membranes with tight and narrowly controlled pore structures. Consequently, viral filtration is a costly but necessary unit operation that is commonly employed in many downstream bioprocesses.

Risk mitigation strategies for a viral filter in a commercial bioprocess are identified using an FMEA analysis. A key risk identified was the single sourcing of viral filters. The identification of an alternative viral removal filter for the current bioprocess would mitigate the risk of potential interruptions due to the availability of the single sourced filter used. A strategy using a combination of functional testing studies, economic analysis and viral clearance validation is described for the insertion of a second source of viral filters into a licensed process.

 

Poster Session
5:30 PM-7:30 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007