FDA warns Glenmark over GMP, laboratory control issues

Regulatory NewsRegulatory News | 06 December 2022 |  By 

The US Food and Drug Administration (FDA) warned Indian generic drugmaker Glenmark Pharmaceuticals Limited for several good manufacturing practice (GMP) violations observed during an inspection of its Goa, India facility last May.
The warning letter, dated 22 November 2022, cites four violations related to investigating failed batches of drugs, written procedures for production and process control, laboratory controls and incomplete records.
Due to these issues, FDA told the firm that its drug products “are adulterated” under section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act.
According to FDA, the company rejected 15 batches of 0.1mg and 0.2mg strength desmopressin acetate tablets due to out-of-specification (OOS) content uniformity test results. While the company attributed the issue to a lack of defined compression parameters for one batch, FDA said it “failed to test other batches or drug products that used the same [redacted] process and compression equipment.”
Following the inspection, the company acknowledged that it “did not apply the corrective actions for the compression parameters for [its] 0.2mg strength tablets.” The company also identified a batch of the 0.2mg strength tablets with a failing stratified sample assay result and initiated a voluntary recall of those tablets in June.
The agency also dinged the company for failing to adequately validate its manufacturing processes for an unnamed gel product. FDA said that Glenmark’s process validation did not properly evaluate inter-batch and intra-batch variability.
“Your initial process performance qualification for this drug product only tested [redacted] random tube for viscosity taken from tubes collected at the [redacted] of filling for each of the three validation batches. This study did not evaluate variability within the batch, and it is not described in the validation report where the [redacted] tube was collected. This sampling plan for viscosity does not result in statistical confidence in your process performance,” FDA wrote.
The agency noted that a second process performance qualification study used to qualify a “critical excipient used to control viscosity” only included one batch “and therefore inter-batch variability could not be assessed.” The company rejected five batches of the drug from 2020-2021 for viscosity issues.
Additionally, FDA said the company lacked proper procedures for integrating chromatographic peaks, reviewing chromatographic data processing.
“Our investigators identified an example of your firm manually entering timed integration events into the processing methods and reporting passing results without adequate procedural controls or justification. Your analyst manually modified the processing of chromatographic data of [redacted] impurity peak for [redacted] tablets batch [redacted]. 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,” FDA said.
Lastly, FDA said the drugmaker had incomplete batch records and lacked batch-specific data for compression machine reject limits.
“Production operators acknowledged using default pre-set tablet rejection values in the recipes for tablet compression instead of calculating the batch specific rejection limits as required by your procedure. There were two investigations where non-conforming tablets were found and did not meet the hardness specifications. In each of the investigations the impact assessment concluded that since the automatic weight control or compaction force control was turned on, the risk of finding tablets that did not meet specification was low. However, the investigations did not determine if the rejection limits were set appropriately. There was a lack of assurance to ensure the compression machine was correctly rejecting tablets that did not meet specifications,” FDA wrote.
The warning letter calls on the company to address the deficiencies and gives it 15 business days to respond to the agency in writing.
Warning letter


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