Intellectual Property Advisory - New Requirements for Submission of Bioequivalence Data for Generic Drug Applications

On Friday, January 16, 2009, the US Food and Drug Administration (“FDA”) issued a final rule requiring abbreviated new drug application (“ANDA”) filers to submit all available bioequivalence (“BE”) studies rather than only the studies relied upon by the applicant.  74 Fed. Reg. 2849-2862 (Jan. 16, 2009) (to be codified at 21 C.F.R. §§ 314.94(a)(7), 314.96(a)(1), 320.1(g), and 320.21(b)(1)).  By requiring submission of all BE studies, ANDA filers will be required to submit the results of nonpassing BE studies to the FDA after the effective date of the rule.  The rule brings a measure of consistency between NDA ("new drug application") and ANDA submission requirements.  The effective date of the new rule is July 15, 2009.

After July 15, 2009, ANDA filers submitting applications, amendments or supplements containing BE studies will be required to submit all BE studies conducted on the same drug product formulation, even those studies on which the ANDA filer does not rely.  An ANDA filer will also need to submit all eligible studies it conducts or has conducted by a third party, including those made before the current ANDA filer purchased the ANDA.  Id. at 2854-55.  For approved ANDAs, the filers will also have to submit the results of any BE study conducted within an annual reporting period with any annual reports submitted after the effective date.  This last requirement includes “reports of all BE studies on the approved drug product, both passing and nonpassing, conducted or obtained by the applicant during the annual reporting period, including those studies conducted before the effective date but within the applicant’s annual reporting period.”  Id. at 2858 (emphasis added).

All BE studies conducted on the same drug product formulation fall under the new rule.  The FDA defined the “same drug product formulation” to mean “the formulation of the drug product submitted for approval and any formulations that have minor differences in composition or method of manufacture from the formulation submitted for approval, but are similar enough to be relevant to the agency’s determination of equivalence.”  Id. at 2861-62.  Following this definition, the FDA explained that BE studies on drug formulations that differ in particle size and morphic form, which are differences not in chemical structure but only internal solid-state structure, would need to be submitted to the FDA.  Id. at 2854.

The new submission requirement does not apply to all types of studies.  For example, animal studies are not required to be submitted.  Id. at 2853.  In vitro studies, however, will need to be submitted when the in vitro testing is conducted to demonstrate bioequivalence.  Id.  The data from in vitro dissolution studies conducted for purposes other than BE need not be submitted under the rule, but they may be required by other regulations, e.g., 21 C.F.R. § 314.94(a)(9).

If you have any questions about the new rule, please contact Harold H. Fox (202.429.6284) or Timothy C. Bickham (202.429.5517).