Generic drugs underpin the U.S. prescription drug market, making up 80% of the prescriptions written in the country and saving payers billions of dollars annually. But there have always been questions about whether some generics are as effective as the drugs they copy, and the FDA last year kicked off a program to find out. Up next, extended release versions of a generic blood pressure medicine, mostly copies of AstraZeneca's ($AZN) extended release Toprol XL.
The agency is asking researchers to conduct "pharmacokinetic and pharmacodynamic (PK-PD)" studies of metoprolol succinate, according to an FDA posting. It is a drug that accounts for about 40 million prescriptions a year, according to Bloomberg. Ninety percent of those are generics of Toprol XL, it reports. The generics also have resulted in more than 3,400 adverse reaction reports over effectiveness and side effects, an analysis by the news service found.
Generic metoprolol succinate is sold in the U.S. by Mylan ($MYL), Actavis ($ACT), Dr. Reddy's Laboratories and Wockhardt. Because many of the generics sold in the U.S. come out of Indian plants, the question of generic effectiveness has melded with concerns over the quality standards of some drugmakers. Citing data from investment bank Needham & Co., Bloomberg said that Wockhardt had more than 25% of the market for metoprolol succinate in the U.S. It made the drug in a plant in Chikalthana, India, that the FDA banned in November from shipping to the U.S. In a warning letter, the FDA cited the facility for unsanitary conditions and for manipulating the results of quality tests.The four companies did not comment or could not be reached, Bloomberg said.
Sandy Walsh, a spokeswoman for the FDA, said the agency has already done tests to see if the generics dissolve properly and now wants more extensive studies. She said the FDA also has rethought the criteria that was used for approval of the generics.
|FDA CDER Director Janet Woodcock|
Bloomberg said the FDA started looking into metoprolol succinate after getting complaints from Harry Lever, a cardiologist at the Cleveland Clinic. His issues were based on anecdotal findings that patients don't do as well when switched to generics from branded products. He and some other doctors and researchers have been speaking publicly about their concerns, attracting attention from doctors. They have pointed to a study of generic versions of Pfizer's ($PFE) cholesterol-lowering drug Lipitor, done by Preston Mason at Brigham & Women's Hospital. It found that some of the generics were ineffective because of impurities resulting from the manufacturing. But FDA CDER Director Janet Woodcock has discounted that research, saying it was flawed and the conclusions faulty.
The agency does not have the authority to require generic drugmakers to do postmarketing studies on the equivalency of their copies, so it has taken on the task itself. It was prompted to explore the issue deeper several years ago when questions arose about the effectiveness of a generic made by Teva Pharmaceutical Industries ($TEVA) of Wellbutrin XL, a long-release version of the antidepressant. Teva pulled its copies from the market, although testing of other Wellbutrin XL generics found them to be equivalent. Kathleen Uhl, acting director of the FDA's Office of Generic Drugs, told Bloomberg recently that episode "triggered pretty substantial changes and requests for additional studies."
The agency has generics of 19 products on its list to check, Bloomberg reports. They include immune-suppression medications and inhaled allergy treatments. The agency has indicated that some of the research could be finished as soon as September, while some will take years to conclude.
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