Warning Letter: fundamental GMP Deficiencies in API Production

Recommendation

23-25 April 2024
Barcelona, Spain

Global Registration and Life Cycle Management for APIs

If a manufacturer violates fundamental GMP rules, it shows in their lax handling of deviations, insufficient monitoring and documentation of critical process steps as well as their ignoring of OOS results in quality control. FDA inspectors were confronted with these violations when they visited the production site of an Indian manufacturer in April this year. The Warning Letter to Vital Laboratories Private Limited issued on October 10 describes in detail the non-GMP compliant procedures of the personnel in several key steps of production and quality assurance:

In-process controls
Despite the in-process controls for active ingredient content included in the batch records, these tests have not been performed for several batches without justification.

Documentation of critical process steps using the dual control principle
Parts of the batch records do not contain signature fields for the documentation of critical process steps by two people. In cases where those fields existed ("done by"; "checked by"), like in weighing operations, for example, the fields had been verified by the same person. Inspectors were told that this was common practice in the production area.

Investigation and documentation of OOS results; CAPA measures
Analytical content determinations provided OOS results which were ignored. Root cause analysis was not performed; rather, the results were used as a basis to assign expiration dates.

Annual product review
The report reviewed by the FDA inspectors contained the same stability data as the one from the year before. Mean values for important quality attributes of APIs such as water content, impurities and optical rotation were wrong insofar as they exceeded the specified maximum values. Furthermore, some mean values reported only referred to a single batch.

The company's responsible persons acknowledged that the errors occurred because the previous year's annual review was used as a template for the new one.

Finally, the Warning Letter stated that similar GMP deficiencies had been found in earlier inspections of other Vital Laboratories sites. The FDA therefore deems the company's quality management over all sites insufficient: "These repeated failures at multiple sites demonstrate that your company's oversight and control over the manufacture of drugs is inadequate."

Source: FDA Warning Letter to Vital Laboratories Private Limited