GMP Violations at Turkish OTC Manufacturer

Due to some fundamental GMP violations, a pharmaceutical manufacturer for OTC products in Turkey has now received a Warning Letter from the FDA. The inspection had taken place in May 2024.

Insufficient end product testing before batch release

The Turkish manufacturer has not carried out any microbiological tests on its medicinal products. This does not ensure that the products are free from specified (objectionable) microorganisms. In addition, several products showed microbiological contamination, which led to complaints. The FDA is now demanding comprehensive chemical and microbiological testing of the retained samples of all batches released for the US market as well as appropriate measures, such as recalls, in the event of non-compliant test results.

Lack of identity testing of input materials

The manufacturer failed to test input materials, including active ingredients for their identity, and instead relied solely on suppliers' certificates of analysis without verifying their reliability.
The FDA now requires a full review of the material system to ensure that all suppliers are qualified and that incoming materials are tested to specifications. The manufacturer should revise testing methods and specifications to ensure that the identity and quality of all raw materials are verified. If the manufacturer intends to continue to accept test results from supplier COAs, the FDA requires regular verification of the validity of these test results. In addition, the FDA requires the manufacturer to perform at least one specific identity test for each incoming batch in the future.

Lack of validation of production and cleaning processes

The production processes and cleaning procedures have not been validated and there is no evidence that the cleaning for the multipurpose equipment (including equipment for non-drug manufacturing) is adequate.
The FDA now expects a detailed validation programme including qualification of equipment and ongoing monitoring of variation (within and between batches) to ensure continuous control. The cleaning validation programme is also to be revised and so-called "worst case" conditions are to be taken into account. To identify these conditions, the FDA mentions, among other things, medicinal products with higher toxicity, medicinal products with higher concentrations of active ingredients, substances with low solubility, maximum holding times before cleaning.

Due to the nature of the violations, the FDA suggests that the manufacturer hire a GMP consultant who will also conduct a comprehensive six-system audit of the entire facility for CGMP compliance and evaluate the effectiveness of the measure before the manufacturing company contacts the FDA again. 

The original warning letter can be found on the FDA website.