Investigation

Bad Medicine

India is flooding the world with tainted drugs -- and getting away with it.

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.

Photo: JEAN-CHRISTOPHE VERHAEGEN/AFP/Getty Images

National Security

No Exit

The Kafka-esque story of the U.S. translators being held against their will in a Kuwaiti hangar.

Faycal Maroufi, a U.S. military translator from Florida, has spent the past three months confined to an American base in the deserts of Kuwait. The local authorities have promised to arrest Maroufi if he leaves the compound, and American officials have so far been powerless to help. Maroufi isn't wanted for a crime or accused of wrongdoing. He, like more than 50 other U.S. citizens, is instead being effectively imprisoned in Kuwait because of a nasty and complicated business dispute between an American contractor and its local partner.

The histories of the Iraq and Afghan wars are littered with cases of low-paid contractors from countries like Nepal, Bangladesh and Pakistan being kept in the war zones against their will by companies that forced them to work seven days a week and sometimes confiscated their passports to ensure that they couldn't return home. The current standoff in Kuwait appears to be the first time that large numbers of American citizens have faced a similar predicament. The contractors are caught in the middle of a fight between two large companies, a battle they didn't choose and don't fully understand. For all intents and purposes they're under house arrest despite not doing anything to deserve it.

Maroufi and his colleagues are currently living in hangars on Camp Arifjan and Camp Buehring, the two main U.S. bases in Kuwait, and using lockers and curtains to carve out small slivers of personal space. Their makeshift barracks are infested with bedbugs, and the nearest bathrooms are in trailers several minutes away. They aren't allowed to access the bases' military hospitals or leave the country for personal emergencies. One employee lost his mother but was blocked from returning to the U.S. for the funeral; another lost his father but was similarly confined to the base by Kuwaiti authorities. Iowa resident Majdi Abdulghani was arrested at the Kuwait City airport as he was preparing to board a flight back to the U.S. to see his ailing mother. He was jailed for a week.

"We are prisoners here," Maroufi said by phone from Kuwait. "We're pawns in a fight between these two companies. I want to go home and be with my family, but instead I'm stuck here, and I don't know when they'll let me leave."

The linguists are now trying to get even. Late last month, Maroufi and 18 colleagues filed a lawsuit against their employer, Global Linguist Solutions, or GLS, a U.S.-based firm that has a piece of a $9.7 billion Pentagon contract to provide translation services to military personnel across the Middle East. GLS is a joint venture between defense contracting giants DynCorp and AECOM, so Maroufi and the other plaintiffs sued them as well. Joe Hennessey, their lawyer, says he plans to ask for damages "in the tens of millions of dollars, if not higher."

GLS and DynCorp declined to comment, citing the litigation, but GLS argues that the Kuwaiti subcontractor, Al Shora General Trading and Contracting Co., bears full responsibility for what has happened to their employees. Al Shora couldn't be reached for comment, either. However, the company's owner, Reham Aljelewi, told Stars and Stripes earlier this year that she no longer wanted to work with GLS and accused it of making false allegations about her firm to various Kuwaiti officials.

American military and civilian officials say they're doing what they can for the contractors, but have gone out of their way to emphasize that the entire crisis boils down to a fight between two private companies.

Ron Young, a spokesperson for the U.S. Army Intelligence and Security Command, which oversees the GLS contract, said the military was working with the State Department to find a way to get the contractors out of Kuwait. But he stressed that the "current situation regarding the American linguists in Kuwait is a legal matter under Kuwaiti law."

A State Department official said the American embassy in Kuwait had "reached out to Kuwaiti government officials at a variety of levels in order to seek clarification and identify a path to allow the citizens to depart Kuwait or otherwise address the matter." The official declined to say whether Ambassador Matthew Tueller had personally lobbied the Kuwaiti government to allow the contractors to return home.

The dispute stems from a Kuwaiti law that requires foreign firms to partner with a Kuwaiti company, or "sponsor," which is responsible for obtaining work visas for individual employees. GLS had initially partnered with Al-Shora, but chose to work with a different Kuwaiti company when it's initial contract ended last year and the firm decided to submit a bid for a new one.

Here's where things get tricky. According to the lawsuit, Al Shora warned GLS that severing the relationship could lead to legal problems for their contractors. GLS, the suit says, "made a conscious business decision" to do so anyway. GLS, for its part, said it had to sever ties with Al Shora because the Kuwaiti firm refused to submit a formal proposal for a share of the new contract. GLS says that Al Shora's managing director, the sister-in-law of the country's prime minister, responded by threatening to "destroy" the American company.

Things soon deteriorated even further. GLS says that Al Shora promised to transfer all of the U.S. contractors to the company's new Kuwaiti sponsor, but never did. Instead, Al Shora told Kuwaiti authorities that Maroufi and the other GLS contractors had failed to show up their jobs, violating the terms of their work visas and putting them in breach of Kuwaiti immigration law. GLS said it tried to negotiate with Al Shora to rescind the allegations, only to have the Kuwaiti company demand $22 million in exchange for doing so. When GLS refused to pay, the Kuwaiti government began arresting individual contractors like Abdulghani, the Iowa resident trying to return home to see his sick mother.

The lawsuit claims that after the arrests of Abdulghani and a pair of other contractors, Maroufi and his remaining colleagues found themselves effectively under house arrest at Buehring and Arifjan.

"They were trapped because they could not venture out beyond the compound for fear of arrest by Kuwait authorities," the lawsuit states. "Moreover, the Kuwait government would not issue exit documents or other papers to such plaintiffs because they were considered to be in the country illegally."

Three months later, the bulk of the contractors remain marooned at the bases. The Army flies aircraft in and out of Arifjan and Buehring every day, and it's not clear why the military doesn't simply take the contractors out of the country on their own. It's also not clear why the U.S. government, which sells large quantities of weapons to Kuwait and once went to war to restore its independence, isn't doing more to pressure the Kuwaiti government to let the contractors leave. For the moment, only a lucky few have managed to do so.

Nada Malek has worked for GLS in both Iraq and Kuwait since the summer of 2010. This past February, her husband developed serious health problems and was put into an intensive care unit, but she was told she couldn't return to her home in Nevada because of the fight between GLS and Al Shora. Malek's husband eventually recovered, but she suffered a bigger blow last month when her son tried to kill himself. Staffers from the office of Senate Majority Leader Harry Reid interceded on her behalf and she was finally allowed out of Kuwait. She returned home last Sunday.

Despite her family problems, Malek is paradoxically one of the lucky ones. The remaining contractors don't have powerful political allies and face the real prospect of being stuck in Kuwait for months as the new lawsuit winds its way through the U.S. legal systems and back channel talks with the Kuwaitis plod forward. This Saturday is Maroufi's birthday, and he will spend it thousands of miles from home.

"I still don't believe that I can sit in my backyard and watch my husband take care of our garden," she said. "I still feel like I'm stuck in Kuwait."

2013.09.20.as.filed.complaint.ocr by Noah Shachtman

courtesy of Joe Hennessy