Inadequate CAPAs lead to FDA Warning Letter

Deviations and CAPA are still hotly debated topics in GMP inspections. This is shown once again by a recent Warning Letter issued by the U.S. Food and Drug Administration (FDA).

In this Warning Letter, the FDA tells the Indian company Jubilant Life Sciences that it failed to investigate "unexplained discrepancy or failure". In particular, the authority mentions the management of deviations and CAPA:

The FDA found that investigations (root cause analysis) for the deviations and complaints were insufficient. In particular, the causes described were not adequately substantiated and investigations were not extended to other potentially affected batches. In addition, corrective and preventive actions (CAPA) were not implemented as planned and their effectiveness was not sufficiently assessed.

This is described with two examples:

After a problem with the particle size of an excipient used, a wrong inner label on a drum was determined as the reason. A total of four drums were delivered in one consignment. However, the company had already discarded the three other drums from this consignment by the time of the investigation. It was therefore assumed that only this one drum was incorrectly labelled. The FDA could not comprehend this. In addition, only two batches of the 12 batches of tablets made from excipients in question were recalled.

There were also complaints about "peeling, rippled, wet, discolored, and sticking tablets" for several batches of Pantoprazole tablets. Irregularities were also found in retention samples examined. However, the company then only tested samples with minor defects (discolorations). Further tests on tablets with damage to the functional coating were missed. This meant that the full scope of the problem could not be recorded at all. A recall was initiated when further batches with defective coatings were discovered after the investigations had been completed.
The FDA now expects a "comprehensive, independent assessment of your overall system for investigations of deviations, atypical events, complaints, out-of-specification results, and failures", including an assessment of CAPA effectiveness.

For the Pantoprazole tablets, a "summary of all atypical or failing dissolution test results […] including, but not limited to, those related to complaints, stability, and release in the last four years" is required.

In general, an independent, retrospective review of all complaints and related investigations for batches within the expiration period is expected.

Go back


Stay informed with the GMP Newsletters from ECA

GMP Newsletter

The ECA offers various free of charge GMP newsletters for which you can subscribe to according to your needs.

To subscribe, please click here.