India is flooding the world with tainted drugs -- and getting away with it.
- By Roger BateRoger Bate is a resident scholar at the American Enterprise Institute specializing in international health policy.
ACCRA, Ghana — Each time we take medicine, we assume that the manufacturer did its best to produce a quality product. Evidence is mounting, however, that some pharmaceutical manufacturers in countries like India cut corners and send low-quality products to major, developed markets. Worse still, they may have separate production lines for drugs they sell in developing markets like Africa, where poor quality is more likely to go unnoticed.
In mid-2013, India’s largest drugmaker, Ranbaxy, pleaded guilty in a U.S. court to several criminal offenses relating to the fraudulent manufacture and sale of adulterated drugs. (The United States is the biggest importer of generic Indian drugs.) Among other revelations, Ranbaxy’s executives acknowledged that "more than 200 products in more than 40 countries" are affected by "elements of data that were fabricated to support [Ranbaxy’s] business needs." In other words, Ranbaxy made up facts and figures to demonstrate product safety for myriad drugs, including critical HIV medicines paid for by U.S. tax dollars and destined for the poor in Africa. As a consequence, the company was fined $500 million.
The Indian government, protective of its country’s $20 billion pharmaceutical industry, quickly responded by claiming that Indian drugs are in fact safe. But in September, the U.S. Food and Drug Administration banned imports of drugs from another Ranbaxy plant that had not been implicated in the recent settlement.
Frighteningly, the problems with Ranbaxy are not isolated incidents. Over the past six years, my research group has sampled thousands of medicines used to treat tuberculosis, malaria, and major bacterial infections in emerging markets. Of these medicines, 3,695 were allegedly made by Indian companies. We tested them for quality and published the results in peer-reviewed publications. In short, the results were not good.
Pulling all the data together, I wanted to see whether the problems occurring at Ranbaxy were repeated by other Indian producers. After removing falsified samples, which were obviously counterfeited (they had no active ingredients, and the packaging was flawed), just over 5 percent of products failed quality-control tests. There is no evidence to suggest these samples were not made in India by the supposedly reputable firms identified on the labels. (More detailed data analysis can be found here.)
To put this finding in human terms: Given that probably over 100 million people around the world take Indian drugs every week, if one in 20 of those drugs doesn’t work, millions of patients are not taking the medicines they need.
This is a shocking thought — but in many ways, it shouldn’t surprise. There is a long-standing concern that the Indian drug regulator, the Central Drugs Standard Control Organization (CDSCO), cannot be fully trusted to ensure that drugs coming out of India meet internationally agreed-upon quality standards. The CDSCO has received repeated criticism in recent years from the Indian Parliament for colluding with local companies and not testing approved products. This May, the Indian Parliamentary Standing Committee on Health and Family Welfare published a report acknowledging that at least 7 percent of medicines in India are substandard and that some "can harm patients."
In addition to Ranbaxy, other prominent manufacturers — including several whose products are approved by respected regulatory agencies and the World Health Organization (WHO) — are among those producing apparently substandard products. But critically, the data we’ve collected indicate that smaller Indian companies that are not major sellers to markets like the United States cause most of the problems. Indeed, some lesser-known Indian pharmaceutical companies seem to be willfully producing low-quality products for poor markets — and getting away with it.
Consider the case of Ghana. This February, the country’s Food and Drugs Authority (GFDA) and the United States Pharmacopeial Convention (USP), supported by the United States Agency for International Development, published a study on maternal-health products sold in Ghana. The GFDA and USP procured samples of oxytocin and ergometrine, used to treat potentially lethal postpartum hemorrhage. While Western hospitals routinely use such products to lower the risk of hemorrhage, Anna Adjoa, an obstetric nurse in Accra, explains that she uses them "mainly in emergency situations." She says that when these drugs don’t work, the chances are "far higher" that a new mother will bleed out during delivery.
The GFDA study found that of 303 samples, 220 (or 73 percent) were not registered in Ghana — and all of those that were not registered failed basic quality tests, making them unfit for patients. Moreover, roughly 95 percent of the 80 samples that were subjected to all methods of quality and sterility testing failed. The companies that registered the products they sold (a legal requirement fulfilled by only three of the 16 companies examined) performed somewhat better, but most of their products failed too. For example, Ciron, an Indian generics firm, registered its product Ergogen, but half its samples failed.
To quickly dispel other possible hypotheses about the test results: Degradation during storage is unlikely to have created poor quality. The samples made by a Swiss manufacturer all passed tests, and the conditions I have seen in major clinics are reasonable for storing the medicines in question. In other words, Ghanaians were not to blame. And though some products may have been intentionally falsified — that is, made by criminal outfits pretending their products were those of legitimate companies — USP, which has a history of conducting thorough product analysis, suggested only a few of the samples were fake. Subsequent investigations by the GFDA identified three Ghanaian companies (Lymens Medical Supplies, Osons Chemists, and Sarkuff Pharmacy) as importing most of these suspect products. Some of them may have come from bogus companies in China. Yikang Pharma, Nantong Jinghua Pharmaceutical, and Jiangsu Huayang, for instance, appear not to have real addresses. But the majority of the products that failed quality testing were made by the legitimate companies that appeared on the packaging.
And eight of these companies, responsible for 109 of the samples, are in India. None are large producers like Ranbaxy, but at least three claim to have WHO Good Manufacturing Practices certificates, and at least one certificate is verifiable from publicly available WHO data. Stephen Opuni, chief executive of the GFDA in Accra, told me that some of the companies also registered the products with his agency — providing the dossiers for their medicines, along with samples to test. "[But] eventually, after they got their marketing authorization from the Food and Drugs Authority, they intentionally put substandard and, some of them, fake medicines on our market," Opuni says.
Broadening the investigation, in Ghana, other African countries, Thailand, and Brazil, my team found both good- and poor-quality samples of antibiotics and antimalarials made by some of the same companies named in the USP-GFDA report. The sample size from just these producers is too small to provide reliable results. But, in examining test results across all our samples produced by smaller Indian companies similar to those implicated in wrongdoing by the Ghanaian study, we found striking results: When they were sold in India or in other wealthier emerging markets, five of 54 samples (9 percent) failed quality-control tests. But when the same products were sold by the same companies in Africa, 13 of 37 samples (35 percent) failed.
Put simply, these companies, including ones certified by the WHO, are capable of making good products, at least most of the time. Yet the products they send to Africa are up to four times more likely to fail basic quality tests, putting the lives of patients across the continent at risk. The only conclusion one can draw is that the companies are deliberately making bad drugs and sending them to markets where they are unlikely to be identified or, if they are identified, where they are unlikely to land the companies in court, paying fines and suffering international reputational damage in the way Ranbaxy has.
To Opuni’s credit, his agency responded to the USP-GFDA report by recalling the dangerous products and asking the police to pursue those companies thought to be "involved in criminal acts." Other African countries, namely Rwanda, have also taken steps to limit imports of critical drugs (for HIV, tuberculosis, and malaria) to suppliers approved by the WHO or another stringent regulatory authority, and to coordinate quality-control efforts among customs, health, and legal agencies.
But with insufficient resources to combat substandard drug manufacturing and little regulatory harmonization across borders, Africa and other developing regions will continue to be receptive markets to suspect products manufactured in India and elsewhere. In other words, companies will continue to sell bad drugs to the countries and their people who are most in need of cheap, good medicine — and most vulnerable when poor substitutes fail them.