29 September - 1 October 2020
Prague, Czech Republic
Due to fundamental GMP deficiencies, the FDA has issued a Warning letter to a US manufacturer of homeopathic drugs for human and veterinary use.
As one such deficiency, the FDA listed a missing CAPA system. The manufacturer had received out-of-specification results, e.g. for water and finished products, by a contract laboratory multiple times. However, instead of investigating the root causes and assessing possible effects on patient safety, the manufacturer simply sent new samples to the laboratory. According to FDA, there had also been several instances in which batches were released before their compliance with the release specifications had been confirmed.
Another fundamental deficiency was that manufacturing processes had not been validated. Numerous batches had been released into the market without process validation. The FDA criticised this because many of the homeopathic drugs produced are extracted from highly toxic substances such as belladonna or strychnine. Without a completed process validation, the FDA says, there is no guarantee that the finished products are no longer toxic. Interestingly enough, the non-existent process validation had already been criticised during inspections by the FDA in 2012 and 2017.
The cleaning of process equipment is another GMP deficiency listed in the warning letter. Products were manufactured in non-dedicated systems. Samples taken during the cleaning process frequently showed the non-compliance with microbiological and Total Organic Carbon limits [e.g. > 300 CFU/mL; TOC > 896 000 ppb]. To the FDA, this means a risk of cross contamination as well as contamination of the drug product with microorganisms or cleaning agents.
Furthermore, the FDA criticised that there was no Annual Product Review (APR). This was a recurring inspection finding (2006 and 2008), as well.
In a closing statement, the FDA made it clear that homeopathic medicinal products are subject to the same requirements as other drug products [201(g)(1), FD&C Act (21 U.S.C. 321(g)(1)]. The FDA suggests the manufacturer hire an independent GMP consultant in order to get a grip on the present GMP deficiencies.
The original warning letter to the homeopathic manufacturer can be found on the FDA website.