After triggering a global valsartan recall 3 years ago, Chinese drug manufacturer overcomes FDA warning letter

The Chinese pharma manufacturer that was the first domino to fall in the high-profile scrutiny over possible cancer-causing impurities in heart drugs has overcome an FDA warning letter three years after the regulatory sanction.

The FDA has now closed a warning letter that was slapped on Zhejiang Huahai Pharmaceutical’s Chuannan site in Taizhou, the agency recently disclosed.

The closeout of the warning letter marks a key step in Huahai’s return to the U.S. market and the nearing of the end of a three-year saga battling serious reputation damages not just to the company itself but the overall quality of drug production in China as well.

Though the warning letter is off Huahai’s back, the company can’t yet start selling its products in the U.S. thanks to an import ban that affects 29 products, according to the company. An FDA spokesperson confirmed to Fierce Pharma Manufacturing that the import alert on Huahai remained in place as of Friday, Nov. 12.

Huahai came into the public spotlight in 2018, when high levels of a probable carcinogen called N-nitrosodimethylamine (NDMA) turned up in the active ingredient of the popular heart drug valsartan. Huahai’s finding led to sweeping recalls in the U.S. and the EU, as the company was a major valsartan API supplier with a reported 45% market share in the U.S. and Germany.

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Drug regulators on both sides of the Atlantic started to penalize the company. In the months following a U.S. recall in 2018, the FDA first issued an 11-observation Form 483 in September then added banned imports from the Chuannan site and finally slapped a warning letter that November. The FDA blamed Huahai for not considering the possibilities of potentially cancer-causing impurities when shifting its valsartan API manufacturing process in 2011. Huahai and the FDA identified the technology change as the source of NDMA.

As a result of the incident, Huahai’s estimated losses from the recall, depreciation of existing inventory and compensation for customers amounted to 4.14 billion yuan ($650 million) in 2018, according to its annual report. Its net profit that year dropped 78.4% to 134.9 million yuan.

The recall also flamed distrust in China’s drug manufacturing industry. Before the valsartan debacle, Huahai had been a major drug exporter from China for cardiovascular and central nervous system products; the company boasts that it is the first Chinese drugmaker to have earned the U.S. FDA clearance for a self-developed generic.

The carcinogen problem was, however, soon found to not be restricted to Huahai or valsartan. Later recalls out of carcinogen concerns included losartan by Novartis’ Sandoz and Teva as well as valsartan by Mylan and Aurobindo Pharma, among others. NDMA is also at the center of recent widespread recalls of heartburn drug Zantac since last April.

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In late 2019, European regulators reinstated Huahai’s valsartan certification, but the FDA took longer to come around.

The latest FDA closeout letter followed an FDA inspection at the Chunnan site in July. The API facility came out with flying colors, or, in official FDA language, “no action indicated,” Huahai disclosed (Chinese) in October.

“Based on our evaluation, it appears that you have addressed the deviations contained in this warning letter,” the FDA said in its closeout letter.

Removing the warning letter could help the company overturn the U.S. import ban and improve its sales, Huahai said in a securities filing (PDF) last week. To start the import alert removal process, companies must first submit a petition to the FDA.