Warning Letter: Lack of Repairs at US-American Manufacturer

Recommendation

17-19 September 2024

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

A US-American pharmaceutical manufacturer of OTC solutions and suppositories has received a Warning Letter from the US-American FDA due to non-executed repairs and deficiencies in cleaning and laboratory testing.

During the inspection and an ongoing production of suppositories, missing ceiling tiles were noticed directly above the mixing tank and the open hopper and filling machine. In its response to this deficiency, the manufacturer had indicated that the ceiling tiles would be fixed and a checklist for cleanliness for completion implemented. This answer was inadequate for the FDA who would have expected evidence that the repairs had actually been carried out, such as photographs. In addition, there was a lack of a systematic definition of measures to keep the facility in good condition (CAPA). The manufacturer should now provide a plan to ensure in future that necessary repairs are quickly identified and carried out and that preventive maintenance intervals are observed.

During the inspection, however, further deficiencies were discovered in the cleaning and maintenance of production equipment. For example, non-dedicated production equipment covered with residue was found. For dedicated equipment, the manufacturer was unable to provide evidence of the validated cleaning procedures. Besides, a different cleaning agent was used than the one specified in the cleaning instructions.
In another case, for the production of suppositories, the filling temperature should be kept at 4 °C. According to the FDA, the manufacturer cannot prove that the filling equipment is capable of achieving or maintaining a temperature of 4 °C.

The FDA also found cause for complaint in the laboratory. A Certificate of Analysis (CoA) of suppositories listed microbiological test results as "conform" and the batches were released. However, the manufacturer was unable to provide any test results to prove compliance with the requirements. During the inspection it could also not be clarified whether the samples had been tested by a third-party laboratory and whether this would support the result on the CoA.

The FDA expects a comprehensive list of all chemical and microbial test methods and specifications. In addition, an independent assessment of laboratory methods and equipment as well as the documentation and competence of laboratory staff is required.

The manufacturer was already known to the FDA. Similar GMP violations had already been detected during an inspection in 2017. However, the Warning Letter has been issued only now.

The detailed Warning Letter for the OTC pharmaceutical manufacturer can be found on the FDA website.