How do you develop a comprehensive adventitious agent testing strategy?

Adventitious agent testing strategy ensures biopharmaceutical safety from viral and other contamination. Framework includes: raw material testing (bovine-derived components for BSE and viruses, human-derived for bloodborne pathogens), cell bank testing (species-specific viruses, retroviruses for rodent cells, mycoplasma, sterility), in-process testing (bulk harvest for viruses, mycoplasma at defined stages), and lot release testing. Testing methods: in vitro assays (broad-spectrum detection using indicator cell lines), in vivo assays (embryonated eggs, animal inoculation), PCR panels for specific agents, transmission electron microscopy, and retrovirus assays (PERT, infectivity). ICH Q5A provides guidance. Strategy considers: cell substrate origin and history, raw material risks, and process capability for clearance. Validation demonstrates detection sensitivity and specificity. Novel methods (NGS for unknown viruses) are emerging.