Warning Letter for U.S. Manufacturer due to Defects in Equipment, Stabilities and Complaints

Recommendation

17-19 September 2024

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

In September, a U.S. pharmaceutical manufacturer received a Warning Letter from the FDA due to GMP violations in the areas of equipment cleaning, drug stability and handling complaints.

The FDA criticised the equipment used for repackaging. According to the FDA, the company processes products such as suspensions and products with highly potent active substances (such as atropine) on equipment that is sometimes difficult to clean and not dedicated. The company could not provide cleaning validation reports. Only a cleaning validation plan was available, without any data or evidence to support it. In addition, the FDA complains that no date was given for the completion of the cleaning validation, or measures taken in the meantime to prevent cross-contamination.

According to the FDA, the manufacturer assigned expiration dates of 12 months on repackaged drugs without having any stability data. In a first response, the manufacturer stated that the 12 months were an error and that it should have been 6 months. The batches concerned were withdrawn from the market. The FDA now criticises that no stability data were made available for the 6-month expiration date and now expects the data to be submitted immediately.

The handling of complaints was also criticised. The case of a complaint due to a leaking container was listed as an example, in the course of which neither the batch records, nor the retention samples, nor the packaging process had been evaluated.

The FDA now expects an improvement of the entire CAPA process taking into account atypical events, complaints, OOS results, deviations and their investigations.

All in all, the FDA considers the manufacturer's quality system to be inadequate.

For further information please also see the FDA's Warning Letter to Lohxa LLC.