On Feb. 2, the Food & Drug Administration issued an alert warning about “Made in India” artificial eye drops that were potentially contaminated with rare drug-resistant bacteria suspected to be the cause of 55 adverse events, including three deaths and several other cases of vision loss from eye infections.
These unfortunate events should not come as a surprise. The FDA frequently announces import alerts for Indian drug manufacturing facilities because of their failure to comply with good manufacturing practices spelled out under U.S. law. As Katherine Eban documents in “Bottle of Lies,” American drug inspectors conducting their annual visits to Indian plants often find violations that range from unhygienic conditions at the manufacturing facilities to brazen data fraud in which companies fabricate quality-testing results for entire batches of drugs intended for the U.S. market.
Given that the United States imports close to $8 billion worth of drugs from India, it was inevitable that a dangerous product from one of these Indian drug manufacturers would slip through the cracks.
Still, the FDA deserves some credit for managing to avoid larger tragedies such as those in Gambia and Uzbekistan, where 90 children died in October and January after taking contaminated cough syrups manufactured in India. Similar scandals in India in the past three years led to the deaths of 12 children due to adulterated cough syrup and six patients who died after receiving an adulterated anesthetic agent. But the real numbers are probably far higher.
These tragedies show that the United States needs to adopt new strategies to complement the annual inspections of overseas facilities. One such strategy could be to force major exporters of pharmaceuticals to improve their drug regulatory frameworks to become more transparent and rigorous like the American system. Countries like India that want to grow their pharmaceutical industry can be quite lackadaisical on drug quality issues. For example, despite the American regulators exposing systemic data fraud and issues with good manufacturing practices compliance in many Indian pharmaceutical companies, we in India are yet to hear a single case of Indian regulators taking action against Indian drug manufacturers red-flagged by U.S. drug inspectors — even though many of these companies likely also cater to the domestic Indian market.
Part of the reason for non-prosecution is the general reluctance of Indian regulators to hold the members of the Indian pharmaceutical industry to account.
The other reason is the admittedly vast difference between Indian and American law on drug regulation. For example, the definition of an adulterated drug in American law includes any drug manufactured in a facility not complying with good manufacturing practices standards in the law. Anybody introducing such adulterated drugs into interstate commerce can be prosecuted in the United States. That’s not the case in India. A manufacturing facility not complying with good manufacturing practices standards in Indian law can at the most have its license revoked. Criminal prosecutions under Indian regulatory law are reserved for pharmaceutical companies whose drugs fail quality testing in random sampling by drug inspectors. In reality, even these prosecutions are rare, since prosecutorial guidelines issued by the government instruct drug inspectors to prosecute only a small sliver of cases where drugs are found to have failed quality testing.
Another major difference is that the FDA is a single regulatory agency, but India has a regulator for each state and union territory whose job it is to regulate manufacturing facilities within its jurisdiction. The quality of regulation and its enforcement varies widely across states, with better-governed states in south India generally doing a better job than those in north India. Thus, for all practical purposes, the FDA is operating not in one country but 37 different jurisdictions when it inspects plants in India.
Simply put, the Indian model of drug regulation is outmoded, opaque, and inefficient. It needs to be reformed, but there is little pressure within the country to do so. Critics like us have been threatened with legal action by the government. Even in the aftermath of heart-breaking tragedies like the one in Gambia, the Indian government has denied responsibility and deflected criticism as a bid to sully India’s reputation as the pharmacy of the world. The Indian government is currently in the process of pushing legislation through the Indian Parliament to completely do away with the current penal provisions in India’s drug regulatory law for manufacturers of sub-standard drugs. These companies can now escape prison time, as long as they pay up monetary fines up to $6,000.
The situation will only improve under international pressure from countries that are importing drugs from India. As paying customers for “Made in India” medicine, countries like the United States are in the position to demand reform of Indian drug regulatory systems and perhaps even propose multilateral treaties to achieve this end.
There are several precedents of international treaties that set regulatory standards from the perspective of safety: the Convention on Nuclear Safety, the Basel Convention on the Control of Transboundary Movements of Hazardous Wastes and their Disposal, and the Stockholm Convention on Persistent Organic Pollutants, to name a few.
Yet remarkably, for drug quality and safety, there is but one resolution of the World Health Assembly, passed in 1969, which created a regulatory mechanism that is self-administered by member countries. For example, member countries participating in this system have to follow WHO-prescribed good manufacturing practices standards for exports — but the WHO cannot examine the extent to which manufacturers in these countries are complying with these standards.
The world needs a new international legal instrument that creates a more robust regulatory framework to govern the manufacturing of pharmaceutical products. The aim of such an instrument should be to force not just India but also countries like China (another big pharmaceutical manufacturer) to execute systemic regulatory reforms if they want to continue exporting drugs to global markets.
At the core of such a legal instrument should be a framework to force greater transparency on national regulators, allow multilateral inspection teams to inspect facilities, create legally binding mechanisms for cross-border information sharing and investigations in cases of public health emergencies involving adulterated or substandard drugs, and, finally, an arbitration framework for compensation to patients who have suffered due to adulterated or substandard drugs, as happened recently in Gambia or Uzbekistan.
Some elements of the aforementioned framework already exist in the form of the WHO’s pre-qualification systems wherein all pharmaceutical companies seeking to sell to programs run by the United Nations and its agencies have to get their facilities qualified by an inspection team from the WHO.
It is time that the world demanded better of the Indian pharmaceutical industry, and it is the United States that should take the lead.
Dinesh S. Thakur was the whistle-blower in the Ranbaxy case. He and Prashant Reddy Thikkavarapu are co-authors of ‘The Truth Pill: The Myth of Drug Regulation in India.”