An impurity detected in a stability study...

Full Title: An impurity detected in a stability study: Did we miss anything in our E&L risk assessment? Extractable and leachable (E&L) testing are required to identify substances that can or will migrate into the drug substance or drug product during the manufacturing process, storage and administration to assess the risk for patients being exposed to these substances. Stability testing is required to provide evidence on how the quality of a drug substance or product varies over time. E&L testing and stability testing can be run in parallel, but the conditions and detection techniques used for screening can be different. Although stability testing focuses on the quality of the drug substance or product by investigating the degradation products, it can occur that compounds are detected which are leachables. In this case study an unknown compound was detected during stability studies using LC-UV which could not be linked to a degradation product and was suspected to be a leachable. The question was raised if the unknown compound could be linked to extractables or leachables and if there was a potential risk for patient safety and drug product quality. E&L studies require complementary analytical techniques to screen for a wide range of compounds and the experimental design needs to be considered and stability studies can be set-up differently. This case study shows challenges in identification when using complementary techniques and discusses uncertainty in identification of leachables.