Warning Letter following Complaints about Tablets

Back in August 2025, the US FDA inspected an Indian manufacturer of solid dosage forms and identified serious GMP deficiencies. The complaints relate in particular to inadequate investigations of quality defects in tablets, deficiencies in the cleaning of non-dedicated equipment and deficiencies in the cleaning validation programme. Due to these violations, the FDA classifies the manufactured medicinal products as non-GMP-compliant.

Complaint handling / CAPA

One key point of criticism concerns the handling of quality defects in tablets. The FDA objects that customer complaints about tablets with physical defects were not properly investigated. Specifically, there were complaints about tablets from at least two different batches that were described as crumbly and holey, with powder/dust in the container. The deviation investigations carried out by the manufacturer were unable to determine a reliable cause and were concluded with the result 'not confirmed'. In the investigation reports, the manufacturer stated that the occurrence of crumbly/pitted tablets was due to the 'inherent nature' of a raw material used. At the same time, the manufacturer documented that there were further complaints about the same defect pattern from three other batches of the same medicinal product.

Although the manufacturer reopened the deviation investigation after the inspection and has now attributed the cause to the aforementioned raw material, the FDA considers the response to be insufficient. According to the FDA, there is no analytical testing of the retained samples to prove that the affected batches still meet the specifications. Neither a chemical analysis nor a test of dissolution or other quality-related parameters has been documented or promised. In addition, measures to eliminate the identified cause, such as adjustments to the formulation, are lacking. Furthermore, no assessment has been made as to whether other medicinal products containing the same raw material could also be affected by comparable quality defects.

Deficiencies in cleaning and cleaning validation

In addition to deficiencies in complaint/CAPA processing, the FDA identified significant deficiencies in the cleaning and maintenance of non-dedicated equipment. During the inspection, visible contamination was observed in ventilation ducts and residues on a capsule filling machine, even though these systems were documented as having been cleaned and product changes had already been carried out. Analytical investigations of these contaminants revealed the presence of several active ingredients in concentrations above the company's own limits. In the FDA's view, this poses a concrete risk of cross-contamination.

Although the manufacturer carried out investigations and reviewed analytical and stability data for previously manufactured products, it cited gaps in the cleaning instructions as the sole cause. The FDA considers this insufficient, as it has not been proven that products already released are free of cross-contamination. In particular, there is a lack of investigations of retained samples from batches intended for the US market and manufactured on the affected equipment.

In addition, the FDA criticises fundamental deficiencies in the cleaning validation programme. The cleaning validation from 2018 did not take into account the worst-case product identified in each case and is therefore not suitable for ensuring the effectiveness of cleaning in shared facilities, according to the FDA. In addition, the cleaning validation concept was not updated when new products were introduced on the same equipment. There is also no routine cleaning verification.

As a consequence of the deficiencies identified, the manufacturer has agreed to temporarily suspend the manufacture and release of medicinal products at this site. Production for the US market can only be resumed once the deficiencies identified have been completely rectified and the FDA has been informed again.

Please see the FDA website to read the Warning Letter in detail.