Valsartan Disaster Highlights Importance Of Clean Room Standards

clean room standards

Laboratories across the world work tirelessly to develop new medicines, manufacture current medications, and further our understanding of science. When medicine is involved, clean room standards must be upheld. This involves maintaining and monitoring the lab's humidity (electronic sensing devices now ensure a plus or minus 1% accuracy), air purity, and ensuring that no cross-contamination occurs.

Unfortunately, human beings are fallible creatures. The most recent instance of failed clean room standards involved global recalls of valsartan, irbesartan, and losartan -- all common drugs used to lower blood pressure. In the summer of 2018, the FDA learned of the potential nitrosamine impurities (also known as NDMA) -- which are considered probable carcinogens -- present in the medicines.

The original active pharmaceutical ingredient (API) impurity was manufactured by Zhejiang Huahai Pharmaceutical (ZHP) in China. When it was discovered, it had already been circulating in the U.S. market for an estimated four years. The contamination is thought to have occurred when the manufacturing process of the API was altered, though the FDA does not know exactly how.

"Our ongoing effort has determined that the impurities may be generated when specific chemicals and reaction conditions are present in the manufacturing process of the drug's API, and may also result from the reuse of materials, such as solvents."

At the same time, systemic problems of supervision at ZHP were revealed by the government agency. This example shows what a large impact a small lapse in judgment can have; in the development and production of medicines, mistakes like this can take lives and leave lasting effects in their wake. Even in clinical drug trials, the manufacture of radiolabeled compounds (like C14 radiolabeling) must be held to strict clean room standards.

Fortunately in this case, the FDA doesn't believe that the risk to patients is significant enough to warrant concern, though the drugs have since been recalled.

"Overall, the risk to individual patients remains very small, although this doesn't diminish the significance of this episode or our concerns. FDA scientists estimate that if 8,000 people took the highest daily valsartan dose (320 mg) that contained NDMA, for four years, there may be one additional case of cancer beyond the average cancer rate among those 8,000 Americans."

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