Sterile means Sterile

In a recent Warning Letter to a Chinese manufacturer of over-the-counter medicines that are also marketed in the USA, the FDA clarifies what it understands by "sterile".

Citing 21 CFR 211.113, the FDA criticises failures in implementing requirements for preventing microbial contamination in products declared as sterile. What does this mean in this case?

It criticises the fact that the manufacturer's products are labelled as sterile even though they were not sterilised. The manufacturer argued that it works under "controlled conditions" in order to meet the microbiological limits stated in the certificate of analysis. However, the certificate of analysis does not list the product as sterile either. The FDA makes it very clear that sterile medicinal products must be manufactured in such a way that controls are in place to ensure sterility. Furthermore, the manufacturer did not carry out sterility testing as part of batch release.

From the FDA's point of view, the microbiological specifications and test methods in line with the Chinese Pharmacopoeia were also unacceptable, particularly as aerobic microorganisms were found in one batch.

The FDA summarises its requirements in one sentence: medicinal products labelled as sterile must comply with the CGMP regulations (21 CFR 211), including ensuring sterility.

In response to the Warning Letter, the FDA expects an action plan covering the products marketed in the USA that are labelled as sterile, with regard to their risks to product quality or patient safety. This should include possible customer notifications, recalls and the withdrawal of marketing authorisations.

Conclusion: sterility is of very high importance to the FDA.

Please see the FDA website for the full Warning Letter.