FDA Warning Letter to Glenmark due to Laboratory Issues

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter to Glenmark Pharmaceuticals Limited. The document dated November 22, 2022 goes back to an inspection from May 12, 2022 to May 20, 2022 at the company's drug manufacturing facility in Goa, India.

The Warning Letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. These include:

  • Records and reports / Production record review (21 CFR 211.192)
  • Production and process controls (21 CFR 211.100)
  • Laboratory controls (21 CFR 211.160)
  • Batch production and control records (21 CFR 211.188)

Out-of-Specification (OOS) Results

In the Warning Letter, the FDA writes that the company "rejected 14 batches of 0.1mg and 0.2mg strength desmopressin acetate tablets for out-of-specification (OOS) results [...] and content uniformity results" during 2018 to 2021. Glenmark "attributed the content uniformity failure to the lack of defined compression parameters", but "failed to test other batches or drug products that used the same [...] process and compression equipment."

Chromatographic Data Integration Procedure

The FDA criticizes the firm's procedures for the integration of chromatographic peaks and for the review of chromatographic data processing.

In this context, the following observation from the audit is described: An analyst manually modified the processing of chromatographic data of an impurity peak. According to the FDA, "the impurity results would not have met release specification if the automatic integration processing had been applied in the same manner as they were to the standard and other peaks."

The FDA further mentions that the company's chromatographic data integration procedure is inadequate for the following reasons:

  • The procedure does not indicate when the analyst can manually input timed integration events;
  • It is not described how these events should be used;
  • It is unclear how such events should be reviewed;
  • According to the procedure, a supervisory approval for manually entering timed integration events is not mandatory;
  • A review of the original system integrated chromatogram and justification for manually entering the timed events is not required.

In addition, during the audit it came out that "calculations for setting the minimum area for peak integration of related substances are not recorded or reviewed by quality."

Further Observations

For more information and a list of the further observations, please see the complete Warning Letter which can be accessed on the FDA's website.

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