Practical Considerations of FDA’s CLAP List to Support Testing of Extractables for Pharmaceuticals and Medical Devices

The Chemical List for Analytical Performance (CLAP) was developed to support the chemical assessment of medical devices. FDA CDRH published the list, along with supporting data and with the intention that the chemicals in the list could be used to perform non-targeted extractable and simulated use extractable studies for devices. The list can be used to establish relative response factors and understand uncertainty in the context of extractable and simulated use extractable studies and can be used to demonstrate system and method suitability. This study utilizes the CLAP list to emphasize the importance of threshold identification, "semi-quantitative" assessment during the non-targeted analysis process of impurities related to Extractable and Leachable (E&L), and biocompatibility testing to ensure meaningful toxicological risk assessments. The current paper also highlights the complexity of the testing process, which involves the use of multiple analytical techniques, addresses challenges associated with screening methods, response factor databases, and the use of internal standards, and highlights a data set based on a modified CLAP list, focusing on volatiles and semivolatiles analyzed by GC-MS. The authors conclude that the CLAP list is a practical tool for establishing a basic database for GC-MS and system suitability evaluation if it has been evaluated at the AET level of the study. It has a reasonable analyte coverage at the highest studied level of 2.5 μg/mL, and the list can be used for evaluating system performance beyond direct injection of liquid extracts. Practical considerations for database generation and response factor applicability at various matrices and concentrations are discussed, with a conclusion that relative responses are generally constant at levels of 2.5 μg/mL or above and are rapidly changing at trace levels.