Congress Asks FDA for Report on Generic Anti-Epileptic Drugs

November 12, 2009

By Kurt R. Karst –      

Buried in the Conference Report (Report No. 111-279) accompanying the recently-enacted Agriculture, Rural Development, Food and Drug Administration, and Related Agencies Appropriations Act of 2010 (Public Law No. 111-80) is a request that FDA examine and report on “A” rated anti-epileptic drugs (i.e., drug products that FDA considers to be therapeutically equivalent to other pharmaceutically equivalent products).  According to the Conference Report:

The conferees request the FDA report on adverse events and seizures associated with brand and generic anti-epileptic drugs.  Specifically, the agency should examine the pharmacokinetic profiles of “A” rated anti-epileptic drugs from different manufacturers of the same therapeutic agent.  The Committee directs the FDA to submit a report not later than September 30, 2010, detailing whether the agency believes that any changes to the current bioequivalence testing should be recommended.

The request from Congress is presumably related to questions that have been raised over the past several years about generic anti-epileptic drugs, and in particular, whether there is an increased risk of so-called “breakthrough” seizures or toxic side effects when patients are switched from a brand name anti-epileptic to a generic version.  These issues have been the topic of many reports (here and here), including, for example, a 2008 article in the publication NEUROLOGY in which the authors concluded that FDA bioequivalence testing “may not be adequate for [anti-epileptic drugs] and suggests that more clinical evidence is needed.” 

FDA (or at least one FDAer) has stated that it is confident in its generic anti-epileptic drug approvals (a sentiment that has been echoed by the Academy of Managed Care Pharmacy), and the Agency is reportedly in the process of working on studies to address the questions that have been raised about generic anti-epileptic drugs.  Although a citizen petition was submitted to FDA in 2006 requesting that the Agency address the issue of brand name and generic anti-epileptic drug substitution, the Agency has not yet substantively responded to the petition.  Specifically, the petition requests that FDA: (1) require all anti-epileptic drugs to include a warning to exercise extreme caution when switching those products; (2) include a discussion in the Orange Book Preface at § 1 .8 (Description of Special Situations) of the risks associated with switching anti-epileptic drugs; and (3) narrow its bioequivalence range for anti-epileptic drugs to require a showing, at the 90% confidence interval, that the lower limit is at least 90% of its reference listed drug.

FDA’s report to Congress should go a long way to address the long-standing controversy over anti-epileptic drug substitution issues. 

Categories: Hatch-Waxman