Extractables and Leachables from Single-Use Systems and Their Assessment in Advanced Therapy Medicinal Product (ATMP) Production

The differences between Advanced Therapy Medicinal Products (ATMP) and traditional biopharmaceutical products create new challenges for extractables and leachables (E&L) assessments. These issues are particularly important considering the increasing reliance on single-use systems (SUS). While SUS extractables data can serve as a basis for assessing ATMP applications, there are significant opportunities to improve assessment tools for exposure estimation and toxicological evaluation. In ATMP applications cells or viruses are the therapeutic product and a patient exposure estimation for leachables must consider both the liquid phase and the therapeutic biological material.  

We tested forty-five commonly found extractables and processing aids in a high-throughput screening cell-painting assay using a human cell line. Results showed that most compounds did not create a response in the > 550 cell features analyzed. Only three candidates were found to show an effect in this assay, including the antioxidant degradant bDtBPP, known to be detrimental to cell growth. Further, a concept is developed that allows one to model process equipment-related leachables (PERLs) exposure in an ATMP production environment.  

In summary, cell-based products’ exposure to PERLs is expected to fall far below critical effective concentrations. Nonetheless, avoiding materials of construction containing extractables with a known detrimental effect to cells is advisable.