When drugmakers cut corners on internal manufacturing investigations, they expose themselves to potential recalls and regulatory rebukes—a lesson generics outfit Glenmark Pharmaceuticals is learning the hard way.
On Nov. 22, Glenmark received a warning letter from the FDA outlining a laundry list of problems at its plant in Colvale, Goa in India. The letter covered batch failures, lab controls, record-keeping and more. Glenmark has 15 days to respond to the agency from receiving the letter, which the FDA published online this week.
The FDA’s citation outlined four manufacturing violations, with the first revolving around Glenmark’s failure to properly investigate its operations following rejection of several batches of desmopressin acetate tablets. Desmopressin acetate is used to control the amount of urine a person’s kidneys make by replacing low levels of the hormone vasopressin.
Specifically, Glenmark’s own probe into rejected batches “failed to extend to other batches, dosage strengths and drug products for tablet compression machine settings,” the FDA said.
Between 2018 and 2021, Glenmark threw out 14 batches of 0.1-mg and 0.2-mg desmopressin acetate tablets, thanks in part to content uniformity problems. The company blamed the uniformity failure on poorly defined compression parameters for the drug, though it failed to test other batches or drugs that used that same process and compression equipment, the regulator explained.
Further, Glenmark only took corrective actions on the 0.1-mg tablets, despite rejecting batches of both doses.
After the FDA’s inspection, which took place between May 12 and May 20, 2023, Glenmark ran a retrospective review of its operations and received a subpar sample assay result on one desmopressin acetate 0.2-mg batch, prompting a voluntary recall on June 10.
Glenmark’s written procedures for production and process control are also lacking in Goa, FDA investigators pointed out, and the company failed to follow required laboratory controls and mechanisms there, too. “Your firm failed to have appropriate procedures for the integration of chromatographic peaks and for the review of chromatographic data processing,” the agency wrote.
In fact, investigators witnessed Glenmark workers manually entering timed integration events into the company’s processing methods and reporting passing results “without adequate procedural controls or justification.”
The FDA points out that Glenmark’s chromatographic data integration procedure is “inadequate because it does not indicate when the analyst can manually input timed integration events, how these events should be used or how they should be reviewed.”
Lastly, Glenmark didn’t prepare complete batch production and control records ahead of the FDA’s visit to its plant, omitting batch-specific data for “compression machine reject limits,” according to the FDA.
Glenmark isn’t the only Indian drugmaker to enter FDA investigators’ crosshairs in recent months. In October, manufacturing giant Lupin said on the Bombay Stock Exchange that it had received a Form 483 from the FDA tied to problems at an injectables plant in Nagpur. The announcement marked the third time in the span of five weeks that Lupin revealed a compliance reprimand from the FDA in a regulatory filing.