Generics maker Mylan ran afoul of the FDA late last year for lax testing protocols that could have led to active pharmaceutical ingredients (APIs) tainted with a probable carcinogen. Learning its lesson, Mylan battened down operations at another of its Indian API plants—but the FDA still found issues.
The FDA cited Mylan for failing to adequately test recycled solvents at its Sangareddy, India, Unit 7 plant imported from a contract manufacturer the agency previously flagged for nitrosamine contamination, according to a warning letter posted Tuesday.
During an inspection in February, investigators found Mylan failed to maintain cleaning records for bulk storage tanks that contained the manufacturer's recycled solvents and protocols to adequately test solvents before reuse in API production.
In a statement, Mylan said it had submitted a response to the FDA's letter and didn't expect an interruption in supply.
After the FDA flagged another Mylan API plant—Unit 8—in November for nitrosamine contamination, the drugmaker installed new controls to prevent a similar contamination at Unit 7.
Despite using the flagged contract manufacturer's solvents, Mylan said "extensive testing of APIs manufactured and distributed by the site was performed for the presence of nitrosamine impurities and no evidence of cross contamination was identified."
Mylan's Unit 8 in Andhra Pradesh, India, was targeted as part of the fallout from a series of global recalls for "sartan"-based blood pressure medicines found to contain high levels of nitrosamines, particularly the probable human carcinogen N-nitrosodimethylamine (NDMA).
In November, an FDA letter accused Mylan of failing to present written procedures to control the testing and handling of valsartan API at Unit 8 during an inspection the previous May. Mylan's processes were "inadequate" to prevent "contamination and cross-contamination with nitrosamine impurities," including NDMA and N-nitrosodiethylamine, the FDA said.
In August 2019, the agency issued another warning letter to an Indian solvent recovery firm whose products may have contributed to some of the tainted drugs. The letter to Lantech Pharmaceuticals said its processing methods left open the chance for cross-contamination of solvents.
Mylan tied its own contamination back to tainted solvents as well, telling the FDA that contract manufacturers had sent contaminated batches. The FDA still knocked Mylan for not doing enough to adequately track individual batches.
The FDA has implicated NDMA, in particular, for a growing number of recalls, most recently for versions of generic diabetes med metformin found to contain high levels of the compound.
Last month, New Jersey-based Bayshore Pharmaceuticals voluntarily recalled one lot each of its 500- and 750-milligram extended-release metformin after the FDA found high levels of NDMA. The recalled lots were manufactured by Beximco Pharmaceuticals in Dhaka, Bangladesh, in June 2019 for U.S. distribution.
The FDA requested five other drugmakers—Lupin, Apotex, Teva, Amneal, Marksans—pull their versions off shelves after testing. A seventh drugmaker, Granules, also pulled lots of their metformin version off shelves in July.
NDMA was also linked to global recalls for branded and generic heartburn med Zantac, which roped in some of the generics industry's biggest players.