The Food and Drug Administration has issued a warning letter to Glenmark Pharmaceuticals following serious manufacturing quality violations at the company's factory in Madhya Pradesh, India, marking an escalation in regulatory action against the generic drugmaker after a ProPublica investigation exposed widespread safety concerns.
Critical Safety Testing Delays
The FDA's July 11 warning letter, made public last week, cited Glenmark's failure to promptly conduct dissolution testing on medications throughout their shelf life as among the most serious violations. The company's backlogged testing "was overdue by 3 months or longer for a large proportion of your samples," according to the FDA letter. This delay in safety testing directly contributed to delayed recalls of defective medications that posed serious risks to patients.
In multiple instances, the FDA found that it took 100 days from the time Glenmark pulled samples of potassium chloride for testing until the company learned the capsules had failed to dissolve correctly. Companies are required to hold samples of pills from batches sold to U.S. customers and test them periodically until they reach their expiration date to ensure proper dissolution, as medicines that don't dissolve properly can cause perilous swings in dosing.
Deadly Medication Recalls
The manufacturing problems led to the recall of more than 50 million potassium chloride extended-release capsules sold in the U.S., which federal regulators determined could be deadly. High potassium levels can stop the heart, according to the June 2024 recall notice. Between July and December 2023, Glenmark reported eight deaths in patients who took the recalled potassium chloride to the FDA, though these adverse event reports don't prove the drug caused the harm.
The recall delays may have contributed to at least one death. A lawsuit alleges that Glenmark's potassium chloride pills were responsible for the death of Mary Louise Cormier, a 91-year-old Maine woman. A letter alerting Cormier that her pills had been recalled arrived three weeks after she died. Glenmark has denied responsibility for her death in court filings and has stopped making the drug for U.S. patients.
Pattern of Manufacturing Violations
The FDA warning letter revealed a troubling pattern of quality control failures across Glenmark's manufacturing network. The director of the FDA's Office of Manufacturing Quality wrote that "these repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate."
Three of the five factories where Glenmark made drugs for the U.S. market in recent years had been in trouble with federal regulators. The company had made similar serious mistakes at three other manufacturing sites, with those factories being the subject of previous warning letters from the agency since 2019. Problems at one facility were so severe that federal regulators blocked drugs made there from being imported to Americans.
Delayed FDA Oversight
Despite Glenmark's troubled track record, FDA inspectors hadn't visited the Madhya Pradesh factory for more than four years before conducting an inspection seven weeks after ProPublica's December investigation was published. The FDA, backlogged from the pandemic, waited five years before sending inspectors back to the plant.
Following the inspection, Glenmark recalled an additional two dozen medicines made at the facility and sold to U.S. patients. The FDA has warned that if Glenmark fails to fix the problems outlined in the warning letter, it may bar drugs made at the factory from entering the U.S.
Inadequate Quality Control Systems
The FDA criticized Glenmark for failing to validate the tests it relies on to prove that its drugs have the required identity, strength, quality and purity. "Without evaluating the validity of methods, you lack the basic assurance that your laboratory data accurately reflects drug product quality," the FDA wrote.
The agency also lambasted Glenmark for failing to thoroughly investigate why pills made at its Madhya Pradesh factory weren't dissolving properly, though many details about potential causes were redacted from the public warning letter to protect trade secrets and confidential business information.
Company Response
A Glenmark spokesperson said in a written statement: "Glenmark is actively engaging with the U.S. FDA and has initiated corrective actions to address the agency's observations. Patient safety, product quality and regulatory compliance are foundational to how we operate." The spokesperson declined to comment further, citing ongoing litigation the company faces.
The FDA has directed Glenmark to "immediately and comprehensively assess your company's global manufacturing operations to ensure that systems, processes, and the products manufactured conform to FDA requirements."
