Objectionable Microorganisms – Inadequate Testing and Other Deficiencies Identified During an FDA Inspection

Particularly in the case of non-sterile medicinal products, but also in cosmetics and certain foodstuffs that may contain a certain level of microbial contamination, it is especially important to prevent the presence of high-risk microorganisms and to demonstrate their absence. These are often referred to as ‘undesirable’ or ‘specified’ microorganisms ('Objectionable Microorganisms’). As a rule, such tests are based on the relevant chapters of pharmacopoeias such as Ph.Eur. 5.1.4, 2.6.12 and 2.6.13 or the corresponding USP chapters >1111>, <61> and <62>.

In September 2025, the FDA conducted an unannounced inspection at A. Nelson & Co., Ltd. (London). A number of deficiencies classified as serious were identified, including, for example, those relating to the testing of such “Objectionable Microorganisms”. Subsequently, the FDA issued a Warning Letter to Nelson at the end of February. Below is a brief summary of the most significant deficiencies:

1. Critical deficiency: Inadequate testing for objectionable microorganisms

First and foremost, the FDA states that the company did not carry out sufficient microbiological testing on every batch of its homeopathic medicines, which were marketed for children aged two years and over. In particular, the company failed to test:

• Total Microbial Count 
• Absence of objectionable microorganisms

In some cases, tests were carried out only on a random basis, and some batches were released without testing. Furthermore, the following points were set out in this section of the warning letter:

• One product was rejected at the US border because FDA tests detected microbial contamination
• Extensions of shelf life without sufficient stability data
• Failure to retest previously released batches (no retain sample tests undertaken)

Consequently, the FDA requires:

• Full specifications (chemical & microbiological)
• Re-testing of all retain samples
• Risk assessment and, where necessary, recalls

2. Deficiencies in quality management (Quality Unit, QU)

In general, the company’s quality management is accused of failing to exercise adequate supervision and control over the manufactured medicinal products and the collected data. This is substantiated by the following deficiencies:

• Inadequate monitoring of product quality
• Faulty documentation and archiving
• Important CGMP documents were disposed of
• Critical deviations (e.g. ‘out-of-trend’) were not documented or investigated

This results in a lack of control over: :

• Issuing and tracking of documents
• Handling of incorrect analytical results

This gives rise to significant data integrity risks  and doubts regarding the reliability of all quality data. As the company’s response regarding measures to rectify the deficiencies was, in the FDA’s view, inadequate, and as the measures taken did not resolve either the insufficient capacity in QM or the data integrity issues, a Warning Letter followed in February. This also requires:

• A comprehensive improvement plan for the Quality Unit
• Clear responsibilities and a comprehensive batch release review

5. Notes on API manufacturing

Nelson also manufactures active pharmaceutical ingredients (APIs) for its own products. In this regard, the FDA  also draws particular attention once again to the  ICH Q7 guideline ‘Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients’ regarding GMP requirements for active ingredients.

Further information can be found directly in the Warning Letter of the FDA.