Months after the FDA demanded Lupin act on failures at its Mandideep, India finished dose plant, the Indian drugmaker was waiting for the other shoe to fall. It fell in a form of a warning letter.
Lupin was hit with the warning letter after an “earlier intimation” from the FDA in March requiring Lupin to address a smorgasbord of manufacturing and data safety concerns, the company said in a regulatory filing (PDF) with the Bombay Stock Exchange.
The drugmaker said its Mandideep facility had no outstanding drug applications and did not expect that the letter would “have an impact on disruption of supplies or the existing revenues from operations of this facility.”
The newest knock from the FDA followed a December investigation and damning Form 483. In that report, the agency cited a raft of failures at the Mandideep Unit 1 facility, including 11 observations in the API portion of the plant and another eight in finished dose operations.
The plant’s many API problems included failing to adequately monitor environmental conditions and disinfect during media fills, to a general lack of knowledge among workers on what their day-to-day tasks were. Investigators said workers couldn’t automatically answer routine questions presented by FDA inspectors, and managers often had to read directly from manuals to explain their responsibilities.
In finished dose operations, Lupin received a swath of customer complaints, including a pediatric drug that customers found was thickening, making it difficult to dose. Some complaints said vials were short of the dose. The FDA said the plant’s quality control people didn’t put two-and-two together to investigate whether the thickening was the reason vials were short.
Of course, Lupin isn’t a first-time offender in the FDA’s eyes.
In November 2017, Lupin received a warning letter after the FDA found issues with key finished products plant in Goa and a plant in Indore, India. That letter said Lupin’s efforts to make improvements had fallen short and recommended it get a consultant to not only help fix those plants but to assess its entire manufacturing network.
The major concerns at that time focused on product testing. The FDA ordered Lupin to retest batches of drugs that the company had released for sale in the U.S. even though repeated testing found they failed to meet spec. At Lupin’s plant in Indore, analysts ignored nearly all of the initial out-of-spec testing results, 134 of 139 in a two-year period, the FDA said.