Inadequate Microbiological Testing of Nonsterile Products - FDA Warning Letter

Chapter <61> Microbiological Examination of Nonsterile Products - Microbial Enumeration Test and Chapter <62> Microbiological Examination of Nonsterile Products - Test for Specified Microorganisms go into detail about the requirements for testing applicable pharmaceutical products. Chapter <61> describes the tests for the quantitative enumeration of mesophilic bacteria and fungi that may grow under aerobic conditions. The tests are primarily used to determine whether a substance or preparation meets a defined specification in its microbiological quality. Chapter <62>, on the other hand, deals with specific microorganisms that must not be found in the relevant products, or only in very limited quantities.

The two chapters are among the basic requirements for the US market in terms of ensuring the microbiological quality of pharmaceutical products.

Violations

In a Warning Letter from the US FDA to Marshall's Traditional Healthcare CC dated February 10, 2025, the FDA's first finding is a failure to adequately test the microbiological quality of manufactured products. The FDA states that there was a failure to conduct an adequate laboratory determination of satisfactory compliance with the final drug product specifications, including the identity and strength of each active ingredient, for each batch prior to release. In addition, the batches were not subjected to the required laboratory tests to ensure that the products were free from objectionable microorganisms. The company's response in light of the inspection findings was also deemed insufficient by the FDA, since although the testing had been announced, the FDA states: "Your response is inadequate as you did not provide sufficient details regarding the specific tests to be performed for each batch of finished drug product. You also did not consider a risk assessment or retrospective review of products that have been released without appropriate testing. Without adequate finished product release testing, you do not have scientific evidence that each batch of drug product conforms to appropriate specifications before release."

FDA Requests

The FDA is therefore calling for a comprehensive, independent assessment of laboratory practices, procedures and methods as well as the equipment, documentation and skills of the analysts. As a result of this assessment, a detailed plan for the remediation and evaluation of the effectiveness of the testing and laboratory system is to be submitted.

In addition, the regulatory authority requires a list of the chemical and microbial specifications, including the test methods, used to analyse each batch of medicinal products before a decision on the disposal of the batch is made.

Further information and other deficiencies can be found directly in the FDA's Warning Letter.