Ban this carcinogenic ‘heart-burn’ drug

The continued manufacture and sale of Ranitidine, the acid reflux treatment drug, in India must stop; government inaction is jeopardising Indian lives

Last month, the multinational pharmaceutical company, GSK announced a record settlement of $2.2 billion in the United States in order to settle multiple lawsuits regarding one of its best selling drugs to treat “acid reflux”– Zantac ®, containing the active ingredient Ranitidine, after it was revealed that the drug contained high amounts of a cancer causing carcinogen called N-nitrosodimethylamine (NDMA).

According to Valisure, the American pharmacy which first raised the issue, testing of various brands of Ranitidine in its labs found NDMA in excess of 3,000,000 nanograms in some samples; the acceptable limit in the U.S. was 96 nanograms. Like all carcinogens, high exposure to NDMA can cause cancer.

The high amounts of NDMA have been attributed to stability issues with the molecule, which means that it is not a GSK-specific problem. Any company manufacturing Ranitidine will face the same issue; the reason why the United States Food and Drug Administration (USFDA) and the European Medical Agency (EMA) stopped the sale of the various brands of Ranitidine in their jurisdictions as far back as 2020. GSK itself informed stock exchanges in India, in 2020, that it was withdrawing all Ranitidine products in India. Characteristically, India’s Ministry of Health has taken no steps to stop other pharmaceutical companies from continuing to manufacture and sell Ranitidine.

A widely used pharma drug

Back in 2021, after reports in the Indian press pointed out how Ranitidine was still being sold in India, there were some murmurs from the government indicating that it was “looking into” the issue; but there has been no action from the government since then.

There are two questions to ask of the government in this backdrop. The first is, why did the Indian regulatory apparatus never detect/respond to similar levels of impurities in Ranitidine, which is widely consumed in India. The second, why has the government not acted over the last five years in a similar vein as its counterparts in the West to stop the sale of Ranitidine in India, especially when there are enough substitutes in the form of other drugs such as famotidine, cimetidine, esomeprazole, lansoprazole or omeprazole which also treat “gastroesophageal reflux”, the medical phrase for “acidity”.

To answer these questions, it is first important to identify the key institutions within government responsible for different stages of regulating generic drugs.

The chain of standards setting

The task of setting standards, including acceptable limits of impurities and analytical methods for testing generic drugs for such impurities lies with the Indian Pharmacopeia Commission (IPC), an autonomous institution under the Ministry of Health and chaired by the Secretary of Health. In addition to publishing the Indian Pharmacopeia, which lays out standards (including limits for impurities) and testing protocols for different drugs, the IPC is also required to manufacture and supply “reference standards” and “impurity standards” against which drugs such as Ranitidine can be tested in quality control laboratories in the public and private sector.

The task of ensuring that drug manufacturers comply with the quality standards laid down by the IPC lies first, with the State drug controllers responsible for issuing manufacturing licences for such drugs and, second, with drug inspectors of the States and the Centre who randomly draw samples of drugs from the market for testing by analysts in government laboratories against the standards laid down by the IPC. Drugs that fail to comply with the IPC’s standards are deemed to be “not of standard quality”.

With this background, the key questions to ask of the IPC are why did it not detect the NDMA issue with Ranitidine and what exactly has it done since 2020 to lay down permissible standards for NDMA in Ranitidine, along with the testing protocols. We cannot answer these questions because we have no access to copies of the latest version of the Indian Pharmacopeia. It costs ₹50,000 to purchase the most recent version of the Indian Pharmacopeia. Ideally it should be made available for free given that it contains binding legal standards and is very important from a public health perspective. Once the IPC sets the permissible limits for NDMA in Ranitidine, ideally, the manufacturers of Ranitidine who cannot comply with the impurity standards laid down by the IPC either stop manufacturing Ranitidine or drug inspectors prosecute these manufacturers for manufacturing “not of standard quality” drugs.

Separate and apart from the role of the IPC in setting standards, there is the question of who in government is responsible for acting to prohibit a drug from being sold in the market once a public health concern has been flagged anywhere in the world. Under Section 26A of The Drugs and Cosmetics Act, 1940 only the central government, or more precisely, the Drug Regulation Section within the Ministry of Health has the power to prohibit the manufacture and sale of drugs in the country. This section in the Ministry lacks the technical competence to perform its job since it is typically headed by a faceless Joint Secretary from the civil services who knows little about the pharmaceutical industry or pharmacology.

Perhaps it is now time, after a $2.2 billion settlement, for the Ministry of Health to swing into action and issue an order under Section 26A prohibiting with immediate effect, the continued manufacture and sale of Ranitidine in the country.

Dinesh Thakur has authored ‘The Truth Pill: The Myth of Drug Regulation’. Prashant Reddy T. is the co-author of ‘The Truth Pill: The Myth of Drug Regulation’

Published - November 28, 2024 12:36 am IST