- The FDA is a very important agency, but it is not omniscient or infallible, and it needs all the help it can get.
- The FDA has a history of dismissing physician complaints about underperforming medicines.
- Knee-jerk attacks by the FDA on American researchers provide cover to India's entrenched industry and its corrupt regulator.
Are American patients taking unsafe medicines from Asia? Even posing that question is leading to unusually public confrontations between scientists and physicians on one side and the Food and Drug Administration on the other.
Six weeks ago I chaired a congressional briefing about the possibility that low-quality drugs are being sold here. There were several topics under discussion that day: corruption at India's drug regulator and the quality problems it ignores; the felonies admitted to by Ranbaxy, one of India's largest exporters to America; and increasing anecdotal evidence that American patients are taking inferior heart medications. But perhaps the most interesting points were covered by Preston Mason, a specialist in cardiological science at Harvard Medical School's Brigham and Women's Hospital. When Mason sampled atorvastatin (generic Lipitor) -- the world's most valuable drug -- from Europe, the U.S., and Asia, he found 36 different versions with impurities that would undermine their clinical efficacy.
Last week, Janet Woodcock -- the FDA's lead drug reviewer -- inexplicably told Bloomberg that Mason's team "didn't use the proper method to extract the active ingredient" from samples "and therefore contaminated it themselves." This is a major charge to level at a senior scientist with decades of research experience at a stellar institution -- and she is wrong. Mason's methods were perfectly sound according to credible independent scientists with whom I've spoken, such as Tadeusz Malinski, a professor of biochemistry at Ohio University in Athens who has been published extensively in the academic literature. Moreover, Mason followed the US Pharmacopeia method, the method any scientist, including those at the FDA, would normally follow.
More bizarrely still, in the Bloomberg piece linked above the FDA effectively defended the entirety of the U.S. supply of atorvastatin by saying samples from one pharmacy it surveyed -- yes, a single pharmacy -- were all fine and hence there is nothing to worry about. A detailed analysis of one pharmacy's atorvastatin is no doubt informative, but to draw policy conclusions we need a bigger sample size.
Had FDA officials bothered to speak to Mason prior to so publicly criticizing his methodology, they would have learned that most of the suspect samples came from Asia, and that all the drugs approved by the FDA for legal sale in the U.S. passed his testing. In fact he stressed many times at the briefing that the U.S.-manufactured samples he tested did not have the impurity in any meaningful volume -- but some foreign versions with impurities, notably from India, did make their way into the U.S. through unauthorized routes. No doubt this fact makes the FDA uncomfortable.
Perhaps even more insulting is the FDA's assertion to Bloomberg that physician concern over poor patient reactions to some generic medicines is all in the minds of the patients and doctors. Harry Lever, a cardiologist at the Cleveland Clinic in Ohio who has raised concerns about medicines made by several Indian producers, has rebuffed the FDA's dismissiveness: "My patient reactions are not all in the mind." After switching from U.S. brand name and generic products to Indian generics, his patients have had dangerous physiological reactions including major elevations of cholesterol levels, rapid weight gain, and blood pressure and heart-rhythm problems. One physician, like one pharmacy, can't provide enough information to drive policy decisions, but it should drive further study.
This isn't the first time the FDA has dismissed physician complaints about underperforming medicines. For five years it ignored increasing evidence that some generic versions of GSK's Wellbutrin, an antidepressant, didn't work. It eventually conducted its own studies and found that, indeed, some generic copies didn't work properly. A year and a half ago the agency issued a recall.
Cavalier and aggressive responses from the FDA are unusual and unexpected. Is the FDA both worried about drug quality, and at the same time trying to shut up any independent voices raising concerns about quality? Is dealing with repeated press inquiries about drug quality getting to the FDA?
Even for those who have considerable faith in the FDA, it should be stressed that it was not the FDA that found out about failing generic Wellbutrin -- and that, while the FDA finds plenty of problems with manufacturing sites, it is independent individuals who provide the evidence to catch the major frauds. FDA investigations did not unearth GSK's problems in Puerto Rico, or Ranbaxy's decade-long string of lies about quality; it was whistleblowers in the companies.
The FDA is ratcheting up its inspection activities overseas, notably in India, because of safety concerns. But knee-jerk attacks by the FDA on independent American researchers provide cover to India's entrenched industry and its incompetent and corrupt regulator. The market certainly interpreted the FDA's remarks as a complete vindication of companies like Ranbaxy.
The FDA is a very important agency, but it is not omniscient or infallible, and it needs all the external help it can get. It is doubtful that independent academics and critics will continue to voice their concerns so willingly if FDA persists in belittling their efforts in public. And while that may be good for the egos of power brokers at the FDA, it is surely not good for American patients, who increasingly depend on India's drug supply.
Roger Bate is the author of Phake: The Deadly World of Falsified and Substandard Medicines and a scholar at the American Enterprise Institute.