EMA/EDQM Find Major Deviations at China Manufacturer Embroiled in Valsartan Contamination
A for-cause inspection conducted by the European Medicines Agency (EMA) and European Directorate for the Quality of Medicines and HealthCare (EDQM) found nine “major” deviations, including “significant flaws” for Zhejiang Huahai Pharmaceutical Co., the company at the center of the valsartan contamination.According to the statement of non-compliance from the Italian Medicines Agency, “The company’s risk assessment performed in the context of the development/implementation of the optimised Valsartan process, conducted in July/August 2018, was not satisfactory; moreover, the company did not identify the need to develop a control strategy to reduce the new risks introduced with the optimised process.”
The statement noted that the changes introduced with this modified process “led to the formation of the NDMA [N-nitrosodimethylamine] impurity,” and, “No recall was formally initiated to manage the actions related to the contaminated Valsartan batches.”
The regulators also found deficiencies with respect to the company’s reprocessing/blending operations including traceability of reprocessed/blended material and data integrity issues.
“Inadequate investigation of unknown peaks detected in GC-MS analysis of batches of Valsartan manufactured with the new process as optimized in July/August 2018,” the report said.
The details of the inspection follow the US Food and Drug Administration’s (FDA) decision to place the company on import alert in late September.
The actions are part of an international effort among regulatory authorities to address the drug safety issue that led to recalls of medicines containing valsartan produced in bulk by Zhejiang Huahai. EMA was the first to initiate a recall of the valsartan products in July over the detected presence of the impurity NDMA, followed by FDA and Health Canada.
Statement of Non-Compliance