Microbial Impact Assessment of In-Process Bioburden Limit Excursions

Biologic manufacturing processes are vulnerable to microbial growth, requiring strong contamination controls and in-process bioburden monitoring. Bioburden in-process limit excursions should be rare but when they occur, the impact from microbial impurities can be unclear. Filtration alone does not remove them and unlike endotoxin, there is no reliable way to detect the full range of microbial by-products, e.g. exotoxins, PAMPs, and proteases. From a patient safety and product quality perspective, the potential impact of microbial contamination must be assessed as part of the investigation. The biologics industry has not harmonized on a method for conducting microbial impact assessments. This leads to inconsistency in how firms respond to in-process bioburden excursions, particularly when deciding whether to release or to discard the resulting batch. This presentation will highlight the specific challenges and best practices for assessing the potential product quality impact of an in-process bioburden contamination, including two distinct approaches: a quantitative method built on extensive studies of Roche/Genentech, and a qualitative approach focused on process vulnerability from PDA TR. 90.