FDA expectations for Media Fills

In a recent warning letter, the FDA criticised the lack of media fills. What does the FDA expect from media fills?

Citing 21 CFR 211.113(b), the FDA states, 'Your firm failed to implement and follow appropriate written procedures designed to prevent microbiological contamination of purportedly sterile drug products and that include validation of all aseptic and sterilisation processes'.

The FDA criticised the fact that no media fills were carried out, even though the company exports aseptically filled products to the USA. It considers validation of aseptic filling and sealing to be mandatory. This is followed by a reference to the FDA Guidance ‘Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice’.

The FDA further demands:

• Details of the improvements the company is making to its facility and process to ensure that all units labelled as sterile are manufactured under appropriate aseptic working conditions.
• Suitable specifications for microbiological and chemical quality
• A description of how the equipment used for filling sterile products will be sterilised. This includes the description of a detailed sterilisation method, a list of all equipment sterilised using this method and validation protocols and reports for the processes.
• A summary of the Media Fill programme with corresponding worst case scenarios for routine production. This should include a description of how filled units are analysed for growth and how batch yield is analysed. All relevant SOPs should also be made available to the FDA.

Conclusion: Media fills are a decisive quality assurance ‘pillar’ for demonstrating that a company has its aseptic processes ‘under control’.

You can find the entire Warning Letter on the FDA-Website.