Dr. Reddy’s has spent nearly five years trying to get out from under a warning letter for an important API plant in India but has yet to shake off all of the FDA’s concerns. In fact, a new FDA filing raises issues about out-of-spec drugs and cleaning of solvents off equipment at the plant.
The highly redacted, five-observation Form 483 is for Dr. Reddy’s Unit VI API plant in Srikakulam District, Andhra Pradesh, one of three plants cited in a 2015 warning letter. Among other issues, the January inspection was critical of the plant’s investigations of out-of-specification tests. It also said the plant did not even test “for unknown peaks in residual solvents,” in one batch of drugs.
The inspectors' observations about the plant's equipment cleaning focused in part on production of an API that the citation does not publicly name. It said an unsatisfactory cleaning validation might be associated with OSS peaks in it and "unknown peaks in other manufactured APIs … which are pending applications in the United States.” It also faulted the company for not conducting a trend analysis on those peaks.
The inspection report does not name any specific drugs but the discussion of solvents, mentioned six times, underscores the FDA’s focus on them after finding that solvents play a key part in the creation of suspected carcinogens in sartans and ranitidine drugs.
Dr. Reddy’s is among drugmakers that voluntarily recalled ranitidine, generic Zantac, from the market last year after the FDA determined that unacceptable levels of N-nitrosodimethylamine were being created through manufacturing. The company reported the recall of 33 different ranitidine products last fall cost it about $25 million in that quarter.