Contamination Prompts Voluntary Valsartan Recall

Manufacturing changes at China facility believed to be the source of the NDMA impurity—an issue that could trace back to 2012.

Manufacturing changes at China facility believed to be the source of the NDMA impurity—an issue that could trace back to 2012
Manufacturing changes at China facility believed to be the source of the NDMA impurity—an issue that could trace back to 2012

There’s risk in taking prescription medications. For those prescribed certain drug products containing the active ingredient valsartan, that risk heightened with FDA’s July 13 announcement alerting health care professionals and patients of a voluntary recall of valsartan, which is used to treat high blood pressure and heart failure. The problem: an impurity called N-nitrosodimethylamine, or NDMA, which, the agency says, is classified as a probable human carcinogen.

FDA’s alert noted, “Not all products containing valsartan are being recalled. The presence of NDMA was unexpected and is thought to be related to changes in the way the active substance was manufactured. The FDA’s review is ongoing and has included investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them and what measures can be taken to reduce or eliminate the impurity from future batches produced by the company.”

The agency added, “Its presence in the recalled valsartan drugs may be related to a change in the chemical reactions used during the manufacturing process.”

The agency said the affected companies “are recalling all lots of non-expired products that contain the ingredient valsartan supplied to them by Zhejiang Huahai Pharmaceuticals, in Linhai, China. Not all valsartan-containing medicines distributed in the U.S. have valsartan active pharmaceutical ingredient (API) supplied by this specific company. Zhejiang Huahai has stopped distributing its valsartan API and the FDA is working with the affected companies to reduce or eliminate the valsartan API impurity from future products.”

Recalled products include Valsartan produced by Major Pharmaceuticals, Solco Healthcare and Teva Pharmaceuticals Industries Ltd. Teva and Solco were also recalling Valsartan/Hydrochlorothiazide (HCTZ). However, that list is changing, as noted in a July 24 FDA update on the valsartan recalls, which noted:

• Teval Pharmaceuticals USA is labeled as Major Pharmaceuticals

• Prinston Pharmaceuticals Inc. is labeled as Solco Healthcare LLC

• Teva Pharmaceuticals is labeled as Actavis LLC

“We have carefully assessed the valsartan-containing medications sold in the U.S., and we’ve found that the valsartan sold by these specific companies does not meet our safety standards. This is why we’ve asked these companies to take immediate action to protect patients,” said Janet Woodcock, M.D., Director of the FDA’s Center for Drug Evaluation and Research.

Asked for comment, FDA Center for Drug Evaluation and Research Spokesperson Kristofer Baumgartner said, “The impurity began appearing in the active pharmaceutical ingredient (API) after the manufacturer modified its production process. The amount of the impurity varies in the firm’s API batches. The agency is working with the API manufacturer to further investigate the causes of this impurity and recommends patients talk with their health care provider if they have concerns about their exposure to NDMA.”

The agency encourages patients and health care professionals to report any adverse reaction to FDA’s MedWatch program.

Solco Healthcare response

Prinston Pharmaceutical Inc., dba Solco Healthcare LLC., said, “At present, Prinston is unaware of any evidence that NDMA has resulted in any harm to patients taking the drugs subject to this recall. To date, Prinston Pharmaceutical Inc. has not received any reports of adverse events related to this recall. The products are indicated for the treatment of hypertension. Consumers and patients should contact their pharmacist or physician who can advise them about an alternative treatment prior to returning their medication. Patients who are on valsartan should continue taking their medication, as the risk of harm to a patient's health may be higher if the treatment is stopped immediately without any alternative treatment. The lot number and expiry date information can be found on the manufacturer's unit.”

Alert is “tip of the iceberg”

A July 22 online article in The Epoch Times carried this ominous headline, “Expert: Contamination of China-Made Heart Drug is Just The Tip of the Iceberg.”

Noting that FDA’s recall followed one by the European Medicines Agency (EMA) that affected some 2,300 batches of valsartan sold to 20 European countries, the article says, “Valsartan contamination could have started as early as 2012 according to European regulators, who speculated it was caused by Zhejiang Huahai changing its manufacturing processes at that time.”

The executive summary of a World Health Organization PDF called “Concise International Chemical Assessment Document 38,” provided the following description of NDMA:

“NDMA is the simplest dialkylnitrosamine. It is no longer used industrially or commercially in Canada or the USA but continues to be released as a by-product and contaminant from various industries and from municipal wastewater treatment plants. Major releases of NDMA have been from the manufacture of pesticides, rubber tires, alkylamines, and dyes. NDMA may also form under natural conditions in air, water, and soil as a result of chemical, photochemical, and biological processes and has been detected in drinking-water and in automobile exhaust.”

Founded in 1989, Zhejiang Huahai Pharmaceutical Co., Ltd.’s website says its “workshops of formulation are designed in strict compliance with the international cGMP standard, where the most advanced automatic pharmaceutical production equipment in the world was introduced. We are the first pharmaceutical company in China that has passed USA FDA approval.”

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