Numerous GMP Deviations found at US Manufacturing Site

Recommendation

17-19 September 2024

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GMP Compliance and Technology for the Manufacture of Oral Solid Dosage Forms

Due to the deficiencies discovered during an inspection performed in July 2018, the US FDA has now issued a Warning Letter to a US pharmaceutical manufacturer of homeopathic drug products. Microbiological impurities in the products and the water used to manufacture the medicinal products are an essential aspect of the complaint.

According to the FDA, the company obtained recurring results over the years indicating the microbiological contamination of the water used. Pathogens were also found in some of the manufactured medicinal products. Retention samples and customer complaints reinforce the situation. However, the manufacturing company had not initiated any actions with regard to batches affected and present on the market. Only at the insistence of the FDA, three batches were recalled from the market.

The FDA criticizes the missing investigations of non-conforming products, inappropriate water and the complaint handling. There was neither a search for causes nor measures defined to remedy the deficiencies. In at least one case, the Quality Assurance Manager had recommended a batch recall, but the management had not accepted.

The equipment for the production of Purified Water (PW) has been criticised. According to the FDA, the design, validation and control of the system are inadequate. Some of the water produced and used for manufacturing had  microbial contamination and the bacterial count (CFU/mL) was too high to be determined. For the FDA, the design of the water system is not suitable for producing purified water as biofilm formation in the system is favoured by numerous dead-legs and the ball valves used.

The missing validation of the manufacturing processes was another essential aspect of the complaint. This is particularly worrying, since homeopathic medicinal products are partly derived from very toxic substances (e.g. strychnine). In addition, the FDA found the manufacturing documentation to be insufficient.

Due to the numerous and fundamental GMP deficiencies, the FDA does not consider the Quality Assurance Department (QA) to be sufficiently authorized to ensure a QA Oversight. The QA should be provided with sufficient resources and authorities to perform their function. The FDA also strongly recommends that the company engages a GMP consultant to address the deficiencies and brings the company up to a GMP compliant status.

You can find the Warning Letter to the US homeopathic drugs manufacturer on the FDA website.