Context: A biosimilar manufacturer based in the Far East experienced multiple ‘lost batches’ of a CHO cultivation for a monoclonal antibody due to excessive levels of a cytotoxic leachable component derived from single use bioprocess equipment. The indefinite manufacturing delays were a critical concern for the pharmaceutical company, regulators, consumable manufacturers and drug wholesalers, whose product reserves were becoming limited.
Solution: IPAV partnered with a global contract research organisation (CRO) to rapidly and methodically assess the stability of all production cell lines – including master and working cell banks – and upstream single use bioprocess components, under a range of stimulated conditions. This was complemented by a highly focused root cause analysis, utilising design of experiment (DoE) software.
Outcome: After three months of delayed production, within two weeks IPAV and the CRO partner has identified the source of the leachable as cytotoxic compound bis(2,4-di-tert-butylphenyl)phosphate (bDtBPP) leaches out of certain single use cell culture consumables and negatively impacts cell growth. DoE software was then employed to optimise the ‘holding time’ of media components within suspect cell expansion bags, thus limiting leachable accumulation to acceptable levels, allowing production to recommence. IPAV has since partnered with the manufacturer and a global tools and technologies manufacturer to develop consumables with reduced leachable concentrations and improved in-process stability.