A top U.S. regulator is discrediting research published a year ago that found impurities in dozens of generic heart drugs made overseas, saying the investigators contaminated the samples during their testing.
The study by Preston Mason, a researcher at the Harvard-affiliated Brigham & Women’s Hospital in Boston, was one of the first independent probes into generic heart drugs. Outlined by Mason at a congressional briefing last month, it has been at the center of a growing debate over the quality of copycat drugs as insurers increasingly demand their use to trim medical costs.
Janet Woodcock, the Food and Drug Administration’s lead drug reviewer, said Mason’s team “didn’t use the proper method to extract the active ingredient” from samples “and therefore contaminated it themselves.” Mason defended his work, saying he used the same method on all of the drugs, and only the foreign-made ones had high levels of contaminants. Tests on Pfizer Inc. (PFE:US)’s Lipitor found very low levels, he said.
“A tiny bit is fine, but a larger amount is a problem” that can change a drug’s effectiveness, Mason said in a telephone interview.
Woodcock said a soon-to-be-published study by the agency on generic heart medicines uses a different testing approach. It failed to find contaminants in samples from the U.S., Canada, India and Slovenia obtained from a retail pharmacy.
More than 67 million prescriptions were written in the past year for Lipitor and its generic copies, according to data compiled by Bloomberg. Ranbaxy Laboratories Ltd. (RBXY), based in Gurgaon, India, generated $1.3 billion from U.S. sales of its copies in 2012, according to data from IMS Health.
Woodcock also dismissed complaints by doctors that patients sometimes do better when switched off certain generic drugs, saying they may be based more on psychological factors than physical ones. When people know they’re taking something different than the branded medicine, it may affect how they feel, according to the FDA official.
“There’s been a huge amount of study about the psychological effects about feeling better and not feeling better, and your doctor’s attitude toward things,” Woodcock said.
Those comments drew a swift response from Harry Lever, a cardiologist at the Cleveland Clinic in Ohio who testified at the congressional briefing. The responses he has seen from patients have nothing to do with psychology, he said.
“When I see that the blood pressure isn’t under control, the heart rate isn’t under control, the symptoms aren’t getting better, all I do is switch them,” Lever said in a telephone interview. “Patients don’t even know there’s a generic issue. We desperately need more studies.”
Concerns that generic drugs made overseas may be unsafe have risen in the past year as the FDA has beefed up its inspection system. Over the last 10 months, the agency has banned five factories in India from exporting drugs to the U.S. because of manufacturing deficiencies, and it has promised to add inspectors to ensure better compliance with U.S. rules.
Generic drugs, which make up 84 percent of the medicines used in the U.S., helped Americans save $217 billion in 2012 as health-care costs rise and insurers force more consumers to use them. At the same time, some doctors at last month’s congressional briefing called for a more aggressive stance by federal officials and the agency, citing differences in patient reactions to copycat drugs.
While the FDA rarely tests drugs to confirm their quality, the Mason study, published in the June issue of the Journal of Clinical Lipidology, raised concerns among health professionals and politicians.
In his research, Mason said he used a methanol to extract atorvastatin, the primary ingredient in the heart drugs, exposing the generics to the solvent for a few days at most. The FDA claims the methanol contaminated the drugs. Mason disputes this because he says he left Lipitor in methanol for 10 weeks and was still was unable to replicate the high levels of impurities in the brand-name version that he found in generics.
The FDA is finalizing results of its test of generic heart drugs and intends to publish a paper soon, said Sandy Walsh, an agency spokeswoman. The FDA study includes all generic Lipitor pills approved by the FDA and sold in the U.S., she said.
Walsh declined to comment on Mason’s statement about his testing of Lipitor. “We cannot comment on what the researcher said about testing Lipitor for 10 weeks because we do not have any details about that study,” she said.
The FDA announced it was reviewing Mason’s research just prior to the congressional briefing. After the briefing, Kathleen Uhl, acting director of the FDA Office of Generic Drugs, said the agency would be more transparent on how they regulate the $30 billion generic-drug industry so U.S. consumers were aware of safeguards in place.
The FDA doesn’t regularly test drugs on the market to ensure effectiveness and safety, Woodcock said. Instead, she said, the agency prefers to focus on helping companies maintain high manufacturing standards.
“Generally speaking, for quality management and producing a high-quality product, testing is useful but it cannot be relied upon to produce a quality product,” she said. “You can’t test for everything that might have gone wrong.”
The FDA began a $20 million research program last year that will examine the effect of factors such as inactive ingredients and packaging on generic-drug effectiveness. The agency investigates specific complaints, Walsh said, and responded about 10 times last year.
Judi Spann, a spokeswoman for the Journal of Clinical Lipidology, said the journal took no responsibility for Mason’s research, which was released in conjunction with the National Lipid Association’s meeting.
Mason’s research was “reviewed and accepted by a committee appointed by the National Lipid Association” in the same manner as other abstracts submitted for release at the meeting, Spann said in an e-mail.
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