- A week after Lupin Ltd. disclosed it had received a Food and Drug Administration warning letter concerning two of its Indian manufacturing facilities, the U.S. agency published the letter in full — and it's stinging.
- At both its Goa and Indore sites, Lupin failed to properly investigate when samples of active pharmaceutical ingredients (API) and finished product were out-of-inspection (OOS), choosing instead to test them repeatedly until they met standards or blame the failures on "laboratory errors." FDA investigators also noted "lengthy" hold times for bulk ingredients the company was using to produce certain drugs.
- "These repeated failures at multiple sites demonstrate that your company's oversight and control over the manufacture of drugs is inadequate," the FDA said in the letter. "You should immediately and comprehensively assess your company’s global manufacturing operations to ensure that systems and processes, and ultimately, the products manufactured, conform to FDA requirements at all your sites."
Lupin's stock tumbled by nearly a fifth last week after the company announced receipt of the FDA's letter. It has since fallen further, trading at 822.65 Indian rupees ($12.62) by close-of-market Wednesday.
While critical, the FDA warning letter isn't exactly surprising. As the FDA noted, Lupin has a history with facilities not meeting current good manufacturing practices. Additionally, drugmakers located in Asia — particularly in China and India — have come under fire for production violations more frequently than those in the U.S. and Europe.
For Lupin, the problems largely stem from its disregard for properly addressing OOS results from tests of its pharmaceutical products. In its inspection of the Goa and Indore plants, for instance, the FDA noted that the company continues to try and remedy its shortcomings through more workplace trainings, rather than adequately investigate the root causes for them.
"It is not appropriate to use an 'outlier test' to invalidate your API assay result," the FDA said in its warning letter, referring to violations at the Goa plant. "Such statistical treatments do not identify the cause of an extreme observation, and are only of informational use in an investigation of chemical testing. Further, in this case, your investigation included multiple retests that were the same or very similar to the original [out-of-inspection] result."