Ensuring Quality

Generic-brand market competition also affects FDA regulatory programs. Agency officials maintain that its test procedures and standards ensure that an approved generic drug will yield the same clinical results and safety features of the reference product. Such assurance, however, requires clear documentation that generic drugs meet manufacturing standards and comply with regulatory requirements.

Here, generics makers could do more, according to FDA officials. At GPhA's October technical conference, Helen Winkle, director of the Office of Pharmaceutical Science in FDA's Center for Drug Evaluation and Research (CDER), urged manufacturers to be more vigilant in monitoring manufacturing processes and supply chains. A number of product recalls and FDA warnings have tarnished the industry and aggravated public concerns. Last year FDA banned the import of Ranbaxy products from two plants in India. In recent months, FDA hit KV Pharmaceuticals and Caraco Pharmaceutical Laboratories with consent decrees, launched an extensive recall of products from Actavis' New Jersey plant, and banned imports from Canada's Apotex.

As the demand grows for more affordable generic drugs, Buehler noted, it's important for the public to have confidence in these treatments. "Many Americans are waiting for our products," he said, "but we want them to be the products they are waiting for."

At the September GPhA meeting, FDA deputy commissioner Joshua Sharfstein called on generics industry leaders to assume more responsibility for informing doctors and patients about how to use drugs safely, and urged greater industry collaboration on such important public health issues as those described in FDA's Safe Use initiative.

Anteing Up

Sharfstein also responded to manufacturer complaints that it still takes almost two years to gain approval of a generic drug application, and that backlogs in pending applications are growing. He said that reducing the generic application backlog is a top priority for FDA leadership, but that a user fee program was needed to achieve this goal. At that meeting, both Sen. Orrin Hatch (R-UT) and Rep. Henry Waxman (D-CA) agreed on the need for increased funding for OGD and for generic drug user fees. This would expedite the review process for generics, said Hatch, and speed consumer access to medicines. Waxman noted that a user fee program should come with "real accountability" on review processes and regulatory transparency.

OGD currently receives more than 800 abbreviated new drug applications each year (up from about 350 in 2002) and approves about 600; the result is more than 1,600 pending applications. Congress earmarked an extra $10 million for OGD in its 2010 budget, but the office needs more to make a real dent in the backlog, Buehler acknowledged.

Earlier this year, the Obama administration proposed a $36 million fee program for generics, (more than double previous levels), but industry opposed the plan and Congress dropped it. Now industry leaders say they're willing to reopen fee negotiations in what they see as a more congenial environment at FDA. Manufacturers are encouraged by the agency's progress in responding to citizen petitions within a new six-month time frame and in dealing more efficiently with 30-month stays. Such gains could lead to performance metrics that could form the basis of a fee program, such as consults on complex drug development, and timely plant inspections and specific application approval limits. "But we want some value for what we're paying," said Teva's Marth.

More Support for Science

One way to address generic drug quality and safety concerns, says OPS director Helen Winkle, is for "the generics industry to step up to the plate" and support efforts to "strengthen the science underpinning FDA regulatory decisions." FDA researchers are examining the effects of excipients on bioavailability and new sequential designs for bioequivalent studies on highly variable drugs, but many other topics require collaboration and support from manufacturers. Outside research organizations also are examining generic drug safety and efficacy. The National Institute on Neurological Disorders and Stroke at the National Institutes of Health, for example, is studying pharmacokinetic results of patients who have reported problems with generic epilepsy treatments to assess whether generic anticonvulsants do pose safety problems for some patients.

And payers and PBMs want information to support prescribing decisions when new generics come to market. In anticipation of generic versions of the anti-clotting drug Plavix (clopidogrel), Medco has launched a large study comparing deaths and heart problems of patients prescribed the blockbuster Plavix to those using the newer brand Effient (prasugrel). The study will identify patients who are able to metabolize Plavix normally through pharmacogenetic assessments with an eye to determining that certain patient populations could fare well on low-cost generic clopidogrel when it appears in two years, while a smaller group that does poorly on clopidogrel should be allowed to stay with the more expensive brand prasugrel.

Jill Wechsler is Pharmaceutical Executive's Washington correspondent. She can be reached at jwechsler@advanstar.com