GPhA Presses Hill on Bioequivalence Study Registration Under FDAAA

September 25, 2008

We previously reported that it has been unclear whether a company submitting an ANDA containing the results of an in vivo bioequivalence study must certify on Form FDA 3674 that new Public Health Service Act (“PHS Act”) § 402(j), as added by Title VIII of the FDA Amendments Act (“FDAAA”), applies and that the studies have been registered at  That is, it has been unclear whether an in vivo bioequivalence study is an “applicable drug clinical trial” subject to the PHS Act § 402(j) databank registration requirements.  New PHS Act § 402(j)(1)(A) defines an “applicable drug clinical trial” to mean “a controlled clinical investigation, other than a phase 1 clinical investigation, of a drug subject to [FDC Act § 505] . . . .” 

Under PHS Act § 402(j), the responsible party of an “applicable drug clinical trial” must submit to the National Institutes of Health certain required information for inclusion in the clinical trial data bank at  Currently, only descriptive information about the trial design and enrollment is required to be registered at; however, certain results of those studies will also be required to be posted within the next few years.  Under FDC Act § 301(jj), as amended by FDAAA, the failure to submit a certification, knowingly submitting a false certification, failing to submit required clinical trial information to, and submitting false or misleading information to is a prohibited act subject to a new civil monetary penalties provision, as well as to other enforcement sanctions under the FDC Act.   

Earlier this month, the Generic Pharmaceutical Association (“GPhA”) sent a letter to Representative John Dingell (D-MI) expressing concern “that FDA will incorrectly interpret the statute to include bioequivalence studies as ‘applicable drug clinical trials,’” and strongly urging that Congress “amend the definition of ‘applicable drug clinical trial’ at PHS Act § 402(j)(1)(A)(iii) to specifically exclude bioequivalence studies.”  According to GPhA:      

Congress passed FDAAA § 801 to give physicians and consumers greater access to the safety and efficacy data generated on drug products.  Indeed, in large part, FDAAA § 801 came about because of the belief that pharmaceutical companies did not always make public all available safety or efficacy data regarding their drug products.  Proponents often cited to Vioxx® as an example of a drug where public access to additional, available safety or efficacy data could have been important to physicians and consumers.  Importantly, bioequivalence studies, which are not studies of safety and effectiveness, were never mentioned during Congress’ consideration of FDAAA § 801, or in any of the predecessor bills to this legislation going back to the 108th Congress.  Instead, the clinical trial registration requirements were explicitly limited to studies of “safety and effectiveness” . . . .  [B]ioequivlence studies do not generate new or additional meaningful safety or effectiveness information about a drug product. Likewise, because bioequivalence studies are usually performed in healthy volunteers rather than in patients with a particular medical condition, enrolling subjects in these studies does not provide patients with opportunities to try new experimental therapies. Hence, there is no public health benefit by publishing bioequivalence study information.

The GPhA letter goes on to note “significant negative consequences on the generic industry and on the public health” that would allegedly result from in vivo bioequivalence study registration, including “[giving] brand companies a significant new ‘heads up’ regarding the existence of a generic filer.”

Earlier this year, we learned that FDA is in the process of drafting a guidance document that will provide the Agency’s interpretation of the scope of the term “applicable drug clinical trial.” Last week at the GPhA Policy Conference in Washington, D.C., FDA’s Chief Counsel, Gerald Masoudi, when questioned about the status of FDA’s decision as to whether or not the Agency will consider in vivo bioequivalence studies to be “applicable drug clinical trials,” said that his office is working on the issue.

By Kurt R. Karst    

Categories: Drug Development