Advanced Extractables and Leachables Assessment of Microcarriers Used for Adherent Cell Cultures.

The study outlines principles and workflows for a comprehensive extractables and leachables qualification trial of microcarriers for use in a cell therapy application. Styrene-based MCs were qualitatively and quantitatively analyzed in accordance with USP 〈665〉, followed by a kinetic investigation. Extractables data were fitted to an algorithm to enable reconstructive modeling of dynamic experimental data for both stable and degradable extractables. In a subsequent step, the temporal exposure to process equipment-related leachables (PERLs) was modeled for MCs used in a hypothetical cell therapy application with partial and continuous medium exchange. The results demonstrated that, in a dynamic environment, the release of PERLs from MCs in a perfused system does not influence product quality at levels that would pose a patient safety risk. Furthermore, process concentrations remain significantly below exposure levels that could have detrimental effects on therapeutic human cells. This demonstrates the benefits of perfused systems, or systems with partial medium exchange, as the washout effect dominates PERL release rates. PERL concentrations in such dynamic systems will always be significantly lower than PERL equilibrium concentrations under static, stagnant conditions.