KARACHI - The Provincial Pharmacovigilance Centre Punjab issued an alert asking manufacturers to review their sources of raw materials of valsartan (a formula used in the making of hypertension medicines).

As a result, the Drug Regulatory Authority of Pakistan (Drap) triggered a recall of all valsartan containing medicines having made using same source of active substance. The active ingredient is set to have a cancer-causing impurity called Nitrosodimethylamine (NDMA) also known as dimethylnitrosamine (DMN).

NDMA is a yellow oily liquid with a faint characteristic odor and a sweet taste. It is an industrial by-product or waste product of several industrial processes, such as treatment of water via chlorination for use in manufacturing various products including processed foods and medicines.

While lower levels or traces of NDMA can transfer to finished products (food and medicines) these would be considered harmless. However, improper manufacturing processes and monitoring can lead to higher levels of NDMA in the final product leading to toxicity damaging liver, heart and kidneys.

Intake of higher levels of NDMA can be carcinogenic to humans. The recent detection of higher levels of NDMA in raw materials imported from a particular supplier in China (Zheijhiang Huahai Pharmaceuticals Linhai China) indicates improper processes and poor monitoring at the suppliers facility.

Manufacturing companies in Pakistan who are importing raw materials from this Chinese company to produce medicines for sale in Pakistan are advised by the authorities to immediately stop using materials imported from this Chinese company and to recall the finished products containing material contaminated with NDMA.

This incident raises serious questions regarding the quality methods employed by the Pakistan Pharmaceutical Manufacturing Industry (PPMI). As a matter of routine, all raw materials used in pharmaceutical manufacturing are required to undergo rigorous testing before being released for commercial production, however in Pakistan it appears that the pharmaceutical industry relies solely on the supplier’s Certificate of Analysis and does not conduct any additional testing at their own facility.

This puts unsuspecting patients’ lives at serious risk and it is surprising that it has gone undetected by the regulatory authorities until a voluntary disclosure was made to the European Medicines Agency (EMA). The EMA subsequently issued an alert for recall of the finished drugs containing Valsartan manufactured by the Zheijhiang Huahai Pharmaceuticals Linhai China and contaminated with NDMA.

On July 12, 2018, the Drug Regulatory Authority of Pakistan (DRAP) issued a recall alert to twelve local pharmaceutical manufacturing companies advising them to recall all finished products containing the contaminated substance.

A similar recall notification issued by the Provincial Pharmacovigilance Centre of Punjab on July 16, 2018, named a number of local pharmaceutical companies who are allegedly importing the contaminated raw material from China. It is surprising that even after several weeks of the EMA alert, physical recall of the products containing the contaminated raw material from China is yet to be initiated and the same continues to be sold and prescribed by doctors in Pakistan.

It is strictly advised that only those pharmaceuticals/medicines declared “safe to use” by the competent authorities such as DRAP and Punjab Drug Control Unit should be prescribed.