The overwhelming majority of generic drugs are now made abroad. India supplies a large proportion of those formulations. In recent days two large Indian drug companies have received bad news from the U.S. Food and Drug Administration. Dr. Reddy’s Laboratories has drug recalls for certain lots of a heart medication containing amlodipine and atorvastatin as well as the anti-seizure drug divalproex.
Divalproex sodium ER is the generic name for a long-acting epilepsy medicine sold under the brand name Depakote. Apparently the generic formulation from Dr. Reddy is too strong. On the other hand, the heart medicine containing amlodipine and atorvastatin, sold under the brand name Caduet, was not strong enough, hence the drug recalls of this sub-potent combination product.
This is not the first time Dr. Reddy’s manufacturing process has been questioned. Last year the company recalled thousands of bottles of the heart medicine metoprolol succinate, a beta blocker sold under the brand name Toprol XL. That’s because the generic formulation failed dissolution tests. Other problems at Dr. Reddy have included recalls of ranitidine (Zantac) and pantoprazole (Protonix).
The FDA has also banned importation of medications from another Indian drug company this week, Emcure Pharmaceuticals. The plant in Hinjewadi failed to meet quality standards for good manufacturing practices. Trying to find out about such drug recalls is challenging since the FDA does not make that information readily available.
Generic Drug Recalls: Tip of the Iceberg
These latest generic drug recalls are just the most recent of a long list of problems. Last year the FDA sent out 18 warning letters about problems with good manufacturing process. Six went to Indian companies and six went to Chinese companies.
Over a decade ago one of the largest generic drug manufacturers in the world, Ranbaxy of India, was found to have fabricated data at a number of plants. Dozens of drug products had to be pulled from U.S. pharmacy shelves because of the fraud. Eventually, the company paid $500 million in fines and penalties.
Sun Pharma, another Indian generic drug company got into trouble because of disclosure issues and manufacturing problems. Zydus Cadila, Aurobindo, Wockhardt, Amsal Chem, RPG, Kamud Drugs, Posh Chemicals, Yag Mag Labs and Sun Pharmaceutical Industries have all had problems with the FDA.
According to the FDA there are 526 drug manufacturing plants in India making products for the U.S. market. The agency has 10 investigators to cover the entire country, and that is up from past years when there were even fewer FDA feet on the ground. China has 517 drug manufacturing plants making products that will end up in the U.S. market. At last count there were three investigators for the entire country, though that is supposed to eventually increase to 13. Does that give you comfort?
From our perspective the FDA is woefully understaffed abroad, so it is hardly any wonder that there might be problems with generic drugs made in India, China, Slovakia, Brazil, or goodness knows where.
An Even Bigger Generic Drug Disaster
More alarming than the manufacturing mess-ups and drug recalls is the possibility that clinical research organizations (CROs) that conduct generic drug studies may not be meeting quality standards. These are the companies that give generic drugs to dozens of volunteers and then measure their blood levels to determine if the generic drug is getting into the blood stream at the same rate and amount as the brand name drug that is being copied.
The World Health Organization discovered serious problems at one of the largest organizations, GVK Biosciences in India. The European Medicines Agency accused the company of faking data on roughly 700 different generic drugs from dozens of generic drug companies over a five-year period. As a result of the investigation, European regulators disallowed hundreds of generic drugs based on those clinical trials.
We suspect that the FDA has also relied on data supplied by GVK Biosciences. We asked the agency about these problems and have not received an adequate response. The FDA has not been very forthcoming about generic drugs it might have approved based on GVK data. We don’t understand why the FDA hasn’t disallowed most of the generic drugs tested in GVK facilities. If the European regulators doubt the accuracy of the data, shouldn’t we?
Now, a different company, Quest Life Sciences, has also been warned about defective trials. How this might affect generic drugs in the United States is unknown because once again the FDA has not made its investigations public.
The Bottom Line
The FDA is opaque when it comes to revealing generic drug problems. When a company gets busted for fraud or bad manufacturing practices, the U.S. Food and Drug administration often redacts critical information from its official forms. That means the feds black out key data such as which drugs are involved in a recall or what the specific problems were. The agency also hides the bioequivalence data used to support its generic drug approvals. The justification seems to be that the data is “proprietary.”
We do not get that. If there are problems with generic drugs, we should be able to know the details so we can pass them along to you. And we believe that every generic drug the FDA approves should have its bioequivalence curves and data made available for public scrutiny. We also think the country of origin should be listed on every drug product sold in the U.S. If you are informed about where your shirt is made or where the plums you eat are grown, why not the medicine you purchase?
It is time for the FDA and the generic drug industry to make everything transparent so doctors, pharmacists, nurses and patients can see what’s going on for themselves. Until that happens, we fear the American public will have serious doubts about generic drug quality. If you agree, let the leadership of the FDA know. Send a message to the Director of the Office of Generic Drugs, Kathleen Uhl, M.D. Her email address is: firstname.lastname@example.org
If you have ever had problems with a generic drug, please let Dr. Uhl know.