Addressing Good Manufacturing Practice Challenges in Hospital Advanced Therapy Medical Product Facilities: A Risk-Based Environmental Microbiological Monitoring Approach

Ensuring GMP compliance for Advanced Therapy Medical Product (ATMP) production within a hospital setting presents significant challenges, particularly in facilities designed for the manufacturing of advanced cellular therapies, including products such as mesenchymal stem cells or CAR-T cells. Maintaining microbiological quality in controlled areas requires a risk-based approach to identify critical points, regardless of ongoing production processes. We implemented a Contamination Control Strategy (CCS) to monitor and maintain the quality of GMP areas, ensuring safe ATMP manufacturing. Annual analysis of environmental trends enhanced our understanding of contamination sources, positively affecting both production and validation processes, including media fill tests, which consistently met regulatory standards. Furthermore, a well-structured environmental monitoring program can support the efficient allocation of monitoring resources according to the validated Clean Holding Time and the actual operational activity. In our experience, post-extraordinary cleaning, the Cleaning Holding Time (CHT) was established at one month. Consequently, periodic monitoring frequencies were adjusted to align with this interval, optimizing resource use and promoting process sustainability. This approach demonstrates that a combination of risk-based environmental monitoring, strategic cleaning, and trend analysis can effectively support GMP compliance in hospital-based ATMP facilities while ensuring safe and sustainable production practices.