FDA Spotted Quality Defects at Valsartan Manufacturer Almost Two Years Before Recall
In a sign that quality defects were known well before the recent valsartan recalls, the US Food and Drug Administration (FDA) late Thursday released two Form 483s sent to China-based Zhejiang Huahai Pharmaceuticals in November 2016 and May 2017.Zhejiang Huahai is the manufacturer at the center of the EU and US recalls of valsartan due to the presence of an N-nitrosodimethylamine (NDMA) impurity—classified as a probable human carcinogen—in the company’s high blood pressure and heart drugs.
According to the Form 483 from 2016, Zhejiang Huahai was cited for four observations, including a failure to use written procedures to prevent contamination, deficient systems for cleaning and disinfecting equipment and data that are “not recorded contemporaneously.”
The integrity of the company’s analytical testing was questioned in the other Form 483 from 2017.
“Facilities and equipment are not maintained to ensure quality attributes of drug product,” the heavily redacted Form 483 from 2017 said.
The report also revealed what has been seen in other China-based active pharmaceutical ingredient (API) manufacturers: repeat testing of the same API batch without investigating initial test results.
The release of the Form 483s follows FDA’s updating of the list of valsartan products under recall and the list of valsartan products not under recall to incorporate recalls of valsartan-containing products manufactured by Hetero Labs Limited, in India, labeled as Camber Pharmaceuticals Inc.
The European Medicines Agency (EMA) also said Friday that it has learnt that low levels of NDMA have been detected in the valsartan active substance manufactured by a second company, Zhejiang Tianyu.
Zhejiang Huahai Pharmaceutical Co. Ltd., Taizhou, China 11.18.16 Form 483
Zhejiang Huahai Pharmaceutical Co. Ltd., Duqiao, China 5.19.17 Form 483