FDA Warning Letter: Inadequate Investigation of Humidity Excursions

The U.S. Food and Drug Administration (FDA) has published a new Warning Letter. The document dated 20 July 2023, goes back to an inspection conducted in January 2023 at a manufacturer of numerous over-the-counter (OTC) drug products located in India.

During this inspection, the FDA investigators observed several GMP violations.

Investigation of Humidity Excursions

One of the key aspects described in the Warning letter is that the company did not adequately investigate several humidity excursions during the production as well as in the stability chambers. To make matters worse, a subsequent investigation was made difficult by the fact that the raw data were not backed up and deleted every month.

In this context, the authority points out that high levels of humidity can impact product quality and make it vulnerable to undesirable microbiological contamination. For this reason, the FDA requested the company to provide, among other things, the microbiological test results for drug products currently on the U.S. market.

OOS Invalidation

Another topic mentioned in the Warning Letter is that the company invalidated out-of-specification (OOS) results without adequate scientific justification.

The firm hypothesized that the probable root cause for the OOS results was an error in sample preparation and retested and released the batches in question. The FDA has now asked the company to provide a retrospective, independent review of all invalidated OOS, a summary of potential manufacturing root causes for each investigation, and a CAPA plan.

Quality Unit

The FDA believes that the firm’s quality unit (QU) failed to exercise its responsibility. The QU "did not provide adequate oversight and control over your drug manufacturing operations"  for example, by not ensuring controlled access to master batch records and appropriate data integrity controls.

So far, the company has not yet answered the question of how the QU will be able to oversee the implementation of the CAPAs and check their effectiveness in the future.

Identity Testing of Incoming Components

The company did not perform adequate testing on each component lot used to manufacture the drug products. As already documented in several other Warning Letters addressed to other companies, the component identity testing did not include a limit test for diethylene glycol (DEG) and ethylene glycol (EG) on all lots of high-risk drug components such as glycerin, propylene glycol, and sorbitol solution before use in the manufacture or preparation of your drug products.

For further information, please see the complete Warning Letter to Medgel Private Limited on the FDA website.