FULL TITLE: A Comprehensive Approach to Assess the Impact of Microbial Impurities on Patient Safety and Product Quality of Biologics
Presented by Dr Friedrich von Wintzingerode, QC Lead iNeST Project (individualized Neoantigen Specific Therapy) at Roche
Large-scale Production of Biologics is susceptible to microbial contamination because many manufacturing steps occur under non-sterile conditions in aqueous systems at ambient temperature or 2-8 °C under substantially neutral pH conditions. Regardless of where in the Drug Substance (DS) manufacture (manufacture of the Active Pharmaceutical Ingredient), or Drug Product (DP) manufacture (manufacture of the Final Drug, e.g. formulated mAbs filled in vials or syringes) they occur, microbial contaminations can have a significant impact on product quality and patient safety. Even after bioburden removal by 0.2 µm filtration subcellular microbial components like toxins, lipopeptide/lipoproteins, flagellin, bacterial and fungal DNA, cell wall polysaccharides, extracellular proteases or endoglycosidases remain in the product. Those microbial components potentially lead to toxic, allergic or inflammatory responses in humans or product degradation or modification. The Case-by-Case Assessment of Bioburden (CCAB) approach described here enables a comprehensive assessment of these risks.