21-23 September 2021
A manufacturer of homeopathic drugs and hormone preparations in the USA has received a Warning Letter from the FDA due to several GMP violations. The manufacturer's portfolio includes both hormone-containing topical OTC products and homeopathic drugs.
In its letter, which was issued following an inspection of the manufacturer in December 2019, the FDA criticises, among other things, the insufficient testing of batches of over-the-counter (OTC) products before release. Batches were released to the market without testing for identity, strength, content uniformity and by-products - including drugs containing the hormone progesterone. In its response, the pharmaceutical manufacturer had stated that it would no longer manufacture the OTC products and would establish a stability programme for the products that had been released by monitoring odour and appearance. The FDA now rightly complains that no stability determination can be made on the basis of these parameters. In addition, there is no assessment of the possible risks from the batches that have been released using these parameters.
The FDA also considers the controls of incoming components used for both OTC products and homeopathic medicines to be insufficient. For example, components from unqualified suppliers were used without conducting testing to determine their identity, strength, purity or quality, but solely relying on their certificates of analysis (CoA) from the supplier. In its response, the manufacturer said that it would carry out a physical audit of one of the suppliers and that the components mentioned had been tested for identity by an external laboratory. The FDA states that all suppliers must be qualified and that even then, an identity check and periodic review of the supplier's analytical results must be performed.
The production of products containing hormones and homeopathic drug products on the same equipment is also critical. The FDA criticizes the lack of cleaning validation, which is intended to ensure that no other products can be contaminated with the highly active hormone progesterone. In its response, the manufacturer stated that it no longer produces the hormone OTC products and that it would establish a cleaning validation. The FDA lacks an assessment of the extent to which batches already produced could be contaminated with the hormone. Furthermore, the planned cleaning "validation" of the manufacturer only considers the removal a detergent but not the removal of product residues or the prevention of cross-contamination.
Finally, the US-American manufacturer also lacks a validation for its OTC products or a validation programme in general. In its response, the manufacturer reiterates that it no longer produces the OTC products. The FDA also lacks a retrospective evaluation of the batches that have already been released for the US-American market. The FDA also requires a detailed validation programme from the manufacturer with a timeline of when these will be completed for the marketed products.
You can find the original FDA Warning Letter to Homeocare on the FDA website.