The US Food and Drug Administration (FDA) earlier this month warned Indian drugmaker Lupin Limited for good manufacturing practice (GMP) deficiencies at its facilities in Goa and Indore, India.
Lupin acknowledged receiving the warning letter in a Bombay Stock Exchange filing on 7 November, saying it had responded to nine observations stemming from FDA's inspections and that it will work to address the concerns raised in the warning letter.
The warning letter says Lupin's responses to the observations did not adequately address the issues raised during the inspection, and notes that some of the observations were similar to observations from earlier inspections in 2015 and 2016.
The company also said that the warning letter would not disrupt the supply of any of the company's existing products, but said "there will likely be a delay of new product approvals from these two facilities."
According to FDA, staff at Lupin's Goa facility frequently invalidated out-of-specification (OOS) test results without adequately investigating the causes of the results by labeling those results as outliers.
"It is not appropriate to use an 'outlier test' to invalidate your [active pharmaceutical ingredient] API assay result. Such statistical treatments do not identify the cause of an extreme observation, and are only of informational use in an investigation of chemical testing," FDA writes.
FDA also says the company tossed out OOS results for content uniformity tests, attributing the results to "probably laboratory error," despite not finding conclusive evidence to indicate that was the case.
Additionally, FDA says the company "failed to establish appropriate time limits for completion of each phase of production," by storing bulk material used to make its drugs for long periods of time without conducting adequate hold time studies.
At the Indore facility, FDA says the company invalidated nearly all (134 out of 139) of the initial OOS results conducted over a two-year period from January 2015 to December 2016.
FDA also says the hold time studies conducted for materials stored at the Indore facility were inadequate "because the holding conditions were not representative of actual operations."
And while Lupin told FDA it would perform "full-scale hold time studies" for certain stages of production, FDA says the company's response is inadequate and that it must conduct a retrospective review of any affected batches shipped to the US.