Lupin has indicated it has received another FDA warning letter as regulatory issues continue to pile up for the Indian drugmaker. The most recent letter comes just four months after the agency issued a two-plant warning and told the drugmaker it needs to evaluate its entire manufacturing system because it keeps repeating mistakes.
Lupin disclosed the regulatory whipping in a filing (PDF) with the Bombay Stock Exchange without specifically calling it a warning letter. It said the FDA had sent a letter for its Mandideep Unit 1 indicating official action was indicated (OAI) following a December inspection.
The problems at the API and finished dose plant are extensive according to a highly-redacted, 25-page Form 483 that was posted (PDF) by the FDA when the inspection concluded in December. There were 11 observations for the API portion of the plant and another eight for the finished dose operations.
Problems in API manufacturing ran the gamut from failing to adequately monitor environmental conditions and disinfect during media fills to a general ignorance by both workers and their managers about their day-to-day jobs. Workers couldn’t automatically answer routine questions presented by FDA inspectors, the report said. Managers often had to read directly from manuals to explain their responsibilities.
In the finished dose area, customer complaints into product problems were extensive and the company’s efforts to find their cause too often missed the mark, regulators observed.
It received more than five dozen complaints about a pediatric drug after customers found it 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.
Lupin in its filing said it has no pending drug applications for the Mandideep facility and does not expect the FDA action to impact its revenues or its supplies. It said it continues to communicate with the agency about the steps it is taking to resolve the problems.
This most recent warning, however, is more of the same for the drugmaker. It follows one issued in November that applies both to Lupin’s key finished products plant in Goa and a plant in Indore, India. That letter said Lupin’s efforts to make improvements so far have fallen short and recommended it get a consultant to not only help fix these two plants but to assess its entire manufacturing network.
Despite having been given direction in earlier Form 483s, the FDA said the company keeps repeating its missteps.