Simulating Extractables and Leachables in Biopharmaceutical Manufacturing to Support Safety Assessment.

The use of single-use systems in the manufacturing of biopharmaceuticals raises concerns about the accumulation of process equipment-related leachables in their production and purification processes. However, this risk is mitigated by effective sinks in the manufacturing processes and dilution of product flow, for example, in tangential-flow-filtration. This paper presents a modeling approach that combines the release and adsorption of compounds with dynamic process conditions of biopharmaceutical processes. These calculations help assess process criticality by identifying sources but also low-risk processes and components regarding extractables and leachables accumulation. This approach can significantly reduce the necessity for resource-intensive practical testing, such as leachable studies, which may be impractical from an analytical perspective due to the complex matrices in biopharmaceutical process streams.