International drug monitoring efforts have largely focused on catching drugs made by counterfeiters, which infringe on pharmaceutical companies' intellectual property. But for all the talk about fakes, there's another problem with drug integrity that's discussed much less frequently: medicines made and marketed by legitimate drug companies that contain compromised levels of active ingredient.

As opposed to a fake pill that sometimes contains harmful ingredients, a substandard drug simply does not produce the desired medical benefit. It effectively gets passed “through your stomach like a little pebble,” says Andreas Seiter, who develops pharmaceutical policy for the World Bank in Washington, DC.

Around 10% of India's total pharmaceutical market is substandard or illegal, according to government figures; World Health Organization estimates are even higher. But the problem is not ubiquitous. “Some states' political actors have good oversight of drug production and not obviously corrupt policing; others have woeful enforcement,” says Bate. Here, we show the extent of substandard antimalarial, antibiotic and antimycobacterial drugs sampled randomly from pharmacies in and around three major Indian cities. Source: PLoS One 4, e6003 (2009); Roger Bate.

Regulators have had a tougher time cracking down on the production of substandard drugs compared to straightforward counterfeiting—a crime with clear legal ramifications. Some countries, for example, need to institute better quality standards, whereas others have strong rules on paper but require better enforcement or monitoring. “There's still a big gap in conceptualizing the problem” of substandard drugs, says Meir Pugatch, director of research at the Stockholm Network, a pan-European think tank based in London, who published a report in February calling on policymakers to address the issue and critiquing drug regulations in China, India, Brazil, Argentina and Turkey.

Although counterfeiting is the major concern in the West, “if you're talking about the poorest cities, the problem is quality,” says Roger Bate, an economic health policy scholar at the American Enterprise Institute, a conservative think tank in Washington, DC. And, as more medicines are being exported from developing nations, the reach of the substandard medicines problem is rapidly growing.

Last year, Bate led a pilot study on drug quality in India that showed regional differences in the prevalence of substandard drugs (see map). A similar study in six African countries found that 35% of sampled medicines tested failed quality control—many of which were substandard rather than fake (PLoS One 3, e2132, 2008).