When its hot-selling antidepressant Wellbutrin XL was facing the prospect of competition from cheaper generics late last year, Biovail Corp. filed a "citizen petition" with the Food and Drug Administration, raising concerns about the safety of its potential rivals.
Impax Laboratories Inc. and several other companies had already gone through much of the FDA application and review process for their generic versions of the drug, and Impax was looking forward to getting a tentative approval that would bring it considerably closer to making and selling its competing drug.
But because of the citizen petition -- a request for agency action that any individual, group or company can file -- the FDA has yet to act, and Biovail still has the market for Wellbutrin XL to itself. Impax is fuming, as are many others in the generic drug industry.
"Biovail's petition is a sham, designed solely to delay the onset of generic competition for its Wellbutrin XL product," Impax told the FDA in a letter. "Biovail has wasted FDA's and Impax's time and resources and has likely cost the American public millions of dollars in taxes and health care expenditures in selfish pursuit of further undeserved windfall profits."
The Wellbutrin XL case has become Exhibit A in the growing debate over citizen petitions, which were created to give groups and individuals a way to bring scientific and safety issues to the FDA's attention. But leaders in the generic drug industry and some at the FDA complain that the petitions are being misused by brand-name drugmakers to stave off generic competition.
The simple act of filing a petition, they say, triggers another round of time-consuming and often redundant reviews by the FDA, and can take months or years.
Statistics collected by the staff of Sen. Debbie Stabenow (D-Mich.), who has introduced legislation with Sen. Trent Lott (R-Miss.) that would rein in industry-filed citizen petitions, show that 20 of the 21 brand-name petitions settled by the FDA since 2003 were ultimately rejected.
"The brand-name drug industry has found a major new loophole," Stabenow said in an interview. "The way things stand now, even if the FDA finds that a petition was frivolous and rejects it, [the drug companies] can get hundreds of millions of dollars of profits from the delay."
In a letter sent last week to FDA Acting Commissioner Andrew von Eschenbach, Stabenow and Lott estimated that the delay in approving a generic version of Wellbutrin XL is costing consumers $37 million a month. Impax already sells a twice-a-day version of Wellbutrin; the once-a-day XL version was approved by the FDA in 2003 as the patent on the shorter-lasting formulations was running out.
Biovail rejects the view that it is trying to block generic competition, and in its petition made the case that generic versions of its product may not be biologically equivalent and could be dangerous. As a result, the company -- which has also filed patent infringement suits against its prospective rivals -- asked the FDA to require substantial additional testing before any generic version of Wellbutrin XL is approved.
Pharmaceutical Research and Manufacturers of America (PhRMA), which represents brand-name drugmakers, supports the citizen petition process and says the dozens of similar petitions pending with the FDA raise legitimate concerns.
‘A vital role’
"Most citizen petitions raise important regulatory, legal or scientific issues," said Caroline Loew, the group's senior vice president. "The fact is, the petitions have played a vital role at the FDA since their adoption almost 30 years ago. They have been responsible for important discussions about health and safety, and have been a catalyst for key agency decisions, such as speeding approval of AIDS medicines and implementing rules to protect children from accidental iron poisoning."
Although citizen petitions have raised many important drug policy issues, the Wellbutrin filing is one of several dozen pending that some call "blocking petitions" because they have the effect of delaying approval of a generic alternative. FDA officials said that about 170 citizen petitions are before the agency -- compared with 90 in 1999 -- and that about 30 percent involve industry challenges to generic applications.
FDA Chief Counsel Sheldon Bradshaw told generic drugmakers at a September conference that the agency has been troubled by the number of such petitions. He said they "appear designed not to raise timely concerns with respect to the legality or scientific soundness of approving a drug application, but rather to delay approval by compelling the agency" to review arguments that could have been made months before.
That response caused PhRMA to write to Bradshaw asking for more information. Scott Lassman, PhRMA's assistant general counsel, said the organization found the comments to be "troubling," especially if they could lead to restrictions on how and when citizen petitions could be filed.
More recently, Scott Gottlieb, FDA deputy commissioner for medical and scientific affairs, said in an interview that the agency has instituted internal reforms that will allow for quicker rulings on citizen petitions, especially if they are filed close to the time when a decision on a new generic is expected. But he said that he did not believe there had been an increase in "what a reasonable person would call a blocking petition."
"It's very hard to decide what's a blocking petition and what has value without taking a serious look," Gottlieb said. "I think citizen petitions are very important and have to be preserved. The last thing we want to do is close off an avenue of discourse with the agency."
By regulation, all generic drugs must be "bioequivalent" to the brand-name drugs they copy and must have the same effects and dependability. Industry-sponsored citizen petitions often challenge the process by which bioequivalence was tested.
Because generics generally cost 25 percent to 75 percent less than brand-name products, the sums of money at stake can be enormous -- for the brand-name company, the generic maker, patients, insurance companies and government programs. Wellbutrin XL (a once-a-day formula of bupropion hydrochloride with fewer side effects than the original) costs $1 to $5 a pill and earns about $800 million a year for Biovail and GlaxoSmithKline PLC, which developed the drug. An Impax spokesman said his company planned to sell its generic version, if approved by the FDA, for "a considerable discount."
Making changes to the citizen petition process is a high priority for the Generic Pharmaceutical Association. Its president, Kathleen Jaeger, said her group considers blocking petitions to be among the greatest obstacles facing the industry.
‘No risk’
"Because of the way the system works now, branded companies have every reason to file citizen petitions," she said. "There's a potentially great benefit, and there's no risk. I can't imagine that this is how the originators of the petitions thought they should work."
This is not the first time that the generic industry has complained about citizen petitions that it believed were unfairly blocking generic applications. The Clinton administration responded to those complaints in 1999 with a proposal that would have changed the way the FDA received and handled citizen petitions. PhRMA strongly opposed the rule, and the Bush administration withdrew it in 2003.
Jaeger said that the generic industry was working hard with Congress at that time to close other loopholes in the patent system that allowed makers of brand-name drugs to extend their time for exclusive sales. "We were working so hard to get that legislation passed that we didn't really focus on what was happening with the citizen petition rule," she said, "so some of what we won in Congress, we lost to the citizen petitions."
Stabenow and Lott, who are trying, in their bill, to reduce the petitions, said in their letter to von Eschenbach that "the Senate Appropriations Committee recognized the unintended effect citizen petitions were having on the approval of [generic drug applications] and directed the FDA to provide a written report explaining the process and suggesting improvements. . . . It is our understanding the FDA has not moved forward with this request."