The U.S. Food and Drug Administration plans to tighten purview of the way generic-drug manufacturers make extended-release drugs after one failed to perform like its brand-name counterpart.
The failure of 300-milligram bupropion, a generic for the antidepressant Wellbutrin XL, is the first time a generic has been proved less effective. For some, that raises questions about the claim that generics are always as good as name-brand drugs.
Janet Woodcock, director of the agency’s Center for Drug Evaluation and Research, told the Generic Pharmaceutical Association that the FDA was considering tightening standards for how much generics would have to be like the original drugs they sought to duplicate.
Afterwards, she told Bloomberg that "patients and employees of generic-drug makers have told the FDA that some of the medicines don’t work as well as the originals," though she didn't specify which medicines received those complaints. The goal of a review would be to reduce "variability," she said.
Complaints about the generic version of the antidepressant, manufactured by Impax Laboratories and marketed by Teva, began shortly after it was introduced in 2006, according to an article in the New York Times. It said patients who were switched from Wellbutrin to that dose of the generic claimed their depression came back and it noted that Impax no longer sells that particular dose of extended-release generic drug.
"Although regulators have said the episode appears to be limited to one dosage level of a single drug, an FDA official said in October that the agency was now looking more closely at the techniques generic drug makers use to make the extended-release drugs," wrote the Times' Katie Thomas.
A 150-milligram dose of the generic medication is still available and questions have not been raised about its efficacy. And the drug that has been questioned, Budeprion XL 300, is only one generic version of the original. Other generic versions remain available.
Generic drugs are made with the same active ingredient as branded medications, but both the inactive ingredients and the delivery mechanism can vary. The FDA on its generics fact page has stoutly maintained that generics work as well as name-brand drugs. It's a claim that manufacturers of name-brand drugs have sometimes disputed and that insurance companies have embraced, because generics typically cost less than the original medication for which they can be a substitute. The FDA says generics cost 80 to 85 percent less than the original drug after which they're patterned.
Generic drugs have to meet "rigorous standards established by the FDA," the agency says, "with respect to identity, strength, quality, purity and potency. However, some variability can and does occur during manufacturing, for both brand name and generic drugs. When a drug, generic or brand name, is mass-produced, very small variations in purity, size, strength and other parameters are permitted. FDA limits how much variability is acceptable."
A generic must be the bioequivalent of the brand name drug, however, says the FDA, which notes that nearly 80 percent of prescriptions are filled with generic drugs in the United States.
The Washington Post in conjunction with Consumer Reports recently published a question-and-answer explanation of generics and how they can differ from name-brand drugs, featuring Vinod P. Shah, who is a pharmaceutical scientist and consultant for the U.S. Pharmacopeia who worked for decades at the FDA, where he developed guidelines for testing and approving generic drugs.
The New York Times said that patient concerns about that single drug were first brushed off as a likely result of the cyclical nature of depression, but the FDA did ask Teva and Impax to study the 300-milligram version in patients who complained of problems. The companies agreed, but later canceled, citing too-few recruits for the study.
"In 2010, the FDA took the rare step of conducting its own study of the 300-milligram strength," wrote Thomas. "In early October, it announced that the drug did not, in fact, perform as well as the brand."
Some say concerns raised by the FDA's decision to look more closely at drug-making processes are overblown and that the science behind generics is sound. “There are approximately 10,000 FDA-approved interchangeable generics in the U.S. The recall by a single manufacturer of one strength of a generic drug should in no way cast doubt on the impeccable reputation of the generic industry or the FDA,” Ralph Neas, CEO and president of the Generics Pharmaceutical Association, told CBS News.
"David Read, regulatory counsel for the FDA’s office of generic drugs, isn’t concerned," said an article in Forbes on the closer scrutiny. "According to Read, in the last five years the FDA has only had to correct itself on the equivalence of three drugs. Two cases involved drugs from Dr. Reddy’s Laboratories: an antidepressant and an antifungal medication. The third case involved an anti-seizure drug from Upshur-Smith Laboratories."
EMAIL: lois@desnews.com, Twitter: Loisco