FDA's Perspective: Media Fill and Smoke Studies

In a recent Warning Letter to Aspen Pharmacare, the FDA highlighted serious deficiencies in aseptic practices, focusing on failed media fills and inadequate smoke studies. Citing 21 CFR 211.113, inspectors observed unhygienic behavior such as employees moving too quickly in ISO 5 zones, contributing to two failed media fills. The company failed to implement corrective hygiene measures. Smoke studies were also flawed—insufficient smoke was used, and essential scenarios like equipment setup and interventions were not tested. Though the company temporarily halted operations and engaged an independent consultant, the FDA criticized the response for lacking specifics on oversight and retrospective risk assessments. The agency now demands detailed corrective actions, including a monitoring plan for aseptic behavior, contamination risk assessments covering human interaction, airflow, and facility layout, and comprehensive, dynamic smoke studies. Ultimately, the FDA emphasizes that both media fills and smoke studies must reliably demonstrate control of aseptic conditions and support product sterility.

13-05-2025