An impurity detected in a stability study: Did we miss anything in our E&L risk assessment?



15th March 2022 | 10:00am EST / 2:00pm GMT / 3:00pm CET | Petra Booij, Investigator bij GlaxoSmithKline and Ward D’Autry, PhD Study Director at Nelson Labs Europe |WATCH FOR FREE

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.
Presented by Petra Booij, Investigator bij GlaxoSmithKline

Petra obtained a PhD in analytical chemistry from the VU University in Amsterdam, The Netherlands. She is currently working in GSKs Trace Analysis Extractables & Leachables team based in Stevenage, United Kingdom. Her work focusses on extractable and leachable studies and risk assessments to support regulatory submissions within biopharma and cell and gene therapy. She is an active member of the ELSIE consortium and involved in harmonising approaches for extractable and leachable testing.

Oh no, an unknown! What now? On how mass spectrometry can give you very good ID’s

Impurities in drug substances (DS) and drug products (DP) must be continuously controlled and monitored in order to safeguard the quality and safety for the patient. Reporting, identification and qualification thresholds for impurities and setting acceptance criteria are available in regulatory guidances. When during routine quality control a new or previously unidentified impurity suddenly emerges above the identification or qualification threshold, the impurity needs to be identified, often under time pressure. One of the common analytical strategies and unquestionably a powerful tool for the identification of impurities is high resolution accurate mass spectrometry (HRAM MS) in combination with tandem mass spectrometry (MS/MS) for structural elucidation. However, not all compounds that are responsive to LC/UV are equally responsive to LC/MS, especially in the case of leachable impurities. Hence the analytical toolbox for impurity identification should not be limited to LC/MS alone. In this presentation this will be demonstrated with case studies where unexpected impurities in drug products were eventually identified as leachables using an expanded mass spectrometry toolbox.
Presented by Ward D’Autry, PhD Study Director at Nelson Labs Europe

Ward D’Autry is study director structural elucidation at Nelson Labs, where he manages projects related to the identification of unknowns using high-end mass spectrometry platforms. Mr. D’Autry received his Ph.D. from the Laboratory for Pharmaceutical Analysis, Faculty of Pharmaceutical Sciences of the University of Leuven (Belgium) in 2010. From 2010 to 2017 he worked for DSM and SABIC in Geleen, The Netherlands, where he worked as R&D scientist developing and optimizing chromatography & mass spectrometry based analytical methods for improved analysis of (complex) petrochemical samples or polymeric systems. Often the work included de novo interpretation of mass spectral data.
From 2017 onwards, Mr. D’Autry works for Nelson Labs Europe as study director extractables & leachables. Until recently, he managed extractables & leachables studies with focus on manufacturing components. In 2021 he transitioned to his current role as study director structural elucidation.
Sponsored by Nelson Labs

Nelson Labs, A Sotera Health company, is the leading, global provider of lab testing and expert consulting services. We perform microbiological and analytical laboratory tests across the medical device, pharmaceutical, and tissue industries. The company is regarded as a best-in-class partner with a strong track record of collaborating with customers to solve complex problems. We have over 700 scientists, technicians, and service specialists who diligently perform more than 700 rigorous tests in 13 global laboratory locations.
Based in Belgium, Nelson Labs Europe specializes in providing premium Extractables & Leachables testing services to the pharmaceutical and medical device industries. We also support pharmaceutical companies across the globe in developing worldwide compliance testing strategies to qualify container/closure applications and pharmaceutical production equipment from an Extractables & Leachables perspective.


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