Media Fill - What are the FDA's Issues?

In our news about a warning letter sent to an Indian manufacturer, you could read about design deficiencies in filling lines and flow visualisation ('smoke studies'). However, deficiencies were also found in aseptic process simulation (media fill). Reference was made to 21 CFR 211.113(b): Appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to be sterile, shall be established and followed. Such procedures shall include validation of all aseptic and sterilization processes. What were the “findings” of the inspection?

The FDA criticises the fact that the media fills are not representative of the entire commercial manufacturing process. Furthermore, the batch record does not list all personnel involved in the media fill or all procedures performed. Additionally, one employee was found to have exposed skin.

What corrective actions is the FDA requiring?

While the manufacturer acknowledged the identified deficiencies, they did not specify any further corrective actions. This is precisely what the FDA expects, as set out in the FDA Aseptic Guidance:

• An improvement to the batch record to ensure that the type, frequency and duration of interventions are documented during both commercial production and media fills.
• A plan that ensures appropriate aseptic practices and proper cleanroom conduct are followed. It should include steps to provide oversight for all production batches during routine production.
• The designation of the frequency at which Quality Assurance performs its “oversight” during the aseptic process and related activities.
• A detailed assessment and corrective actions to ensure that the quality unit has the necessary resources and authority to effectively fulfill its role.
• A detailed assessment of the staff of the quality assurance unit with regard to their qualifications and duties as they relate to aseptic procedures.

In addition, rust was discovered on the equipment, as well as issues related to data integrity.

Conclusion: As stated in the Aseptic Guidance, a media fill should cover the entire aseptic process, including at least the standard procedures.

You can find the full warning letter on the FDA webseite.