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.