Valsartan Recall: FDA Issues Warning to API Manufacturer

DECEMBER 11, 2018
The FDA has issued a warning letter to the manufacturer of the active pharmaceutical ingredient (API) found in valsartan that is the subject of the agency’s continuing investigation into probable cancer-causing impurities in certain commonly prescribed heart medicines.

The letter to Zhejiang Huahai Pharmaceutical Co Ltd (ZHP), in Linhai, Taizhou Zhejiang, China, outlines several manufacturing violations at the company’s Chuannan facility, including change control, cross contamination from 1 manufacturing process line to another, and impurity control.

The ZHP facility manufactures API including valsartan, a drug in the angiotensin II receptor blocker (ARB) class used to treat heart failure and high blood pressure. The FDA previously put this facility on import alert, which stopped all API made there and finished drug products made using its API from legally entering the United States. The import alert was based, in part, on high levels of impurities found in API manufactured by ZHP.

This week’s warning letter is another step forward in the continuing investigation, according to the FDA.

The agency is still looking into the root cause of the impurity.

“We’re continuing to investigate and take action to protect patient health and safety from products in this angiotensin II receptor blocker class that have been found to have dangerous impurities. As part of that investigation, we’ve uncovered serious manufacturing violations at ZHP, which is one of the manufacturing facilities that has been linked to these products," FDA Commissioner Scott Gottlieb, MD, said in a statement.

"The issues cited in the warning letter are associated with the nitrosamine impurities found in these drugs, and these violations reveal a disturbing lack of oversight at this API manufacturer that puts patients at risk,” he said.

Recalls of products containing valsartan began in July, because of the presence of N-Nitrosodimethylamine (NDMA) in API supplied by ZHP. Subsequent international investigations expanded to include all manufacturers of API and finished drugs in the ARB class and have resulted in additional recalls of valsartan, irbesartan, and losartan-containing products found to contain NDMA and N-Nitrosodiethylamine (NDEA), known animal and suspected human carcinogens. 

Certain ARB products and certain products that contain ARBs and 1 or more other active ingredients in a single dosage form have been recalled.

There may be confusion regarding which products are affected by ARB recalls and which are not, according to the FDA.

The agency’s website provides lists of valsartan products not under recall valsartan products under recall, as well as related irbesartan products under recall for health care providers, patients, and pharmacists to accurately confirm which products are affected.

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The FDA is advising patients taking any recalled ARB to continue taking their medicine until their doctors offer an alternative treatment option or their pharmacists provide a replacement. It also is important to know that not all ARBs contain NDMA or NDEA, so doctors may prescribe a different medication that treats the same condition or pharmacists may be able to provide a refill of medication not affected by the recall.

Health care providers, patients, and pharmacists may contact the FDA’s Division of Drug Information for questions about ARB recalls. Call 855-543-3784, email druginfo@fda.hhs.gov, or visit the FDA’s ARB recall web page, for more information. A question and answer webpage also provides information about these recalls.

Reference

FDA warns API manufacturer involved in valsartan recall, provides information for patients taking these medications [news release]. Silver Spring, MD; December 11, 2018: FDA website. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm628189.htm. Accessed December 2018.

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