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Regulatory Focus™ > News Articles > 2019 > 8 > NDEA and NDMA Impurities: Another Indian Manufacturer Receives an FDA Warning Letter

NDEA and NDMA Impurities: Another Indian Manufacturer Receives an FDA Warning Letter

Posted 13 August 2019 | By Zachary Brennan 

NDEA and NDMA Impurities: Another Indian Manufacturer Receives an FDA Warning Letter

The fallout from the N-Nitrosodiethylamine (NDEA) and N-Nitrosodimethylamine (NDMA) impurities fiasco continues as the US Food and Drug Administration (FDA) last week sent a warning letter to India-based Lantech Pharmaceuticals.

Lantech, which was placed on import alert in June and acts as a contract solvent recovery facility for valsartan active pharmaceutical ingredient (API) manufacturers, failed to perform an adequate investigation into a customer’s contaminated valsartan API, FDA said.

Although the investigation focused on NDEA, FDA said Lantech also failed to investigate NDMA samples collected from its equipment. In addition, the Lantech investigation failed to include non-dedicated storage, receiving and charging tanks used in its solvent recovery operations, FDA said.

And although Lantech manufactures angiotensin II receptor blockers (ARBs) including valsartan, telmisartan and olmesartan API and intermediates for countries outside the US, the firm failed to adequately evaluate the potential of these ARBs to form nitrosamines and potentially cross contaminate drugs shipped into the US.

“In your response, you stated that you were unaware of specific aspects of your customer’s valsartan API manufacturing process which were important for predicting nitrosamine formation in the solvent recovery process. Your response is inadequate because it is your responsibility to understand all the potential risks associated with the drug manufacturing processes conducted at your facility,” the warning letter says.

FDA investigators also found “solid and liquid material of unknown origin…pooling at the bottom of a non-dedicated receiving tank.” And FDA said that the company “admitted to routinely deleting recovered solvents gas chromatography (GC) data older than three months permanently, without any backup.”

But this is not the first NDEA- or NMEA-related warning letter, as the agency also sent a warning letter to Indian manufacturer Aurobindo last month, saying the firm failed to adequately investigate the root cause of impurities. China-based Zhejiang Huahai Pharmaceuticals also drew a warning letter last December over failures to conduct investigations into the impurities.

Emtech Pharmaceuticals

In addition to the Lantech warning letter, FDA on Tuesday also released a warning letter for India-based Emtech Pharmaceuticals, which was found to have repeat observations from a previous FDA inspection in 2017.

“FDA cited similar CGMP observations in which you inadequately performed microbiological investigations. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate,” FDA said. The agency also noted that the firm’s sterility failure investigations lacked sufficient data to support its conclusions. 

Lantech Pharmaceuticals Limited

Emcure Pharmaceuticals Limited

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