ViroPharma Sues FDA Over March 2006 Bioequivalence Determination; FOIA Lawsuit a Possible Precursor to Future Litigation

By Kurt R. Karst –

Last week, ViroPharma Inc. announced that the company filed a complaint in the U.S. District Court for the District of Columbia alleging that FDA has “wrongfully withheld agency records requested by [ViroPharma] by failing to comply with the statutory time limit for the processing of [ViroPharma’s] FOIA request, resulting in constructive denial of that request, and by continuing to withhold response records” in connection with the approval requirements for a generic version of the company’s antibiotic drug product VANCOCIN (vancomycin HCl) Capsules.  The lawsuit is the latest salvo in a long-running debate over the approval of generic VANCOCIN Capsules.

On March 17, 2006, ViroPharma submitted a Petition for Stay to FDA requesting that the Agency stay the approval of any ANDA or 505(b)(2) application citing VANCOCIN Capsules as the listed drug until certain requirements are met.  In particular, the petition requested that FDA not approve an application for a generic version of VANCOCIN Capsules based solely on in vitro bioequivalence testing.  According to ViroPharma, prior to March 16, 2006, FDA concluded that “in vivo clinical trials would be the basis for determining bioequivalence for generic vancomycin hydrochloride capsules,” and that on March 16, 2006, it became public knowledge that FDA “was modifying its bioequivalence standard for oral Vancocin capsules and would accept the submission of in vitro dissolution testing data as a surrogate measure of in vivo bioequivalence.”

ViroPharma submitted a FOIA request seeking the administrative record related to FDA’s March 2006 bioequivalence recommendations for generic VANCOCIN.  FDA did not immediately provide records in response to the FOIA request.  According to the ViroPharma complaint, when FDA was threatened with litigation earlier this month, an agency official noted that “FDA would soon be releasing information regarding Vancocin that could ‘vitiate the need’ for filing [a] FOIA action.” 

On December 16, 2008, FDA issued a Federal Register notice announcing the availability of a draft product-specific bioequivalence recommendation – “Bioequivalence Recommendation for Vancomycin HCl.”  Supporting documents for the draft recommendation are available here and here.  According to FDA, the draft recommendation “further clarifies its recommendations on the design of BE studies to support ANDAs for vancomycin HCl capsules.”  Specifically, FDA provides bifurcated bioequivalence testing recommendations based on the formulation of the proposed generic drug product:

If the test product formulations are qualitatively (Q1) (i.e., contain all of the same inactive ingredients) and quantitatively (Q2) the same as the reference listed drug (RLD) with respect to inactive ingredients, bioequivalence (BE) of all capsule strengths may be established based on comparative dissolution. . . .

If the test product formulations are not Q1 and Q2 the same as the RLD with respect to inactive ingredients, BE should be established by conducting an in vivo study with clinical endpoints in patients with Clostridium difficile Associated Diarrhea (CDAD). 

FDA’s bifurcated approach is similar to the approach the Agency announced in May 2008 for generic versions of PRECOSE (acarbose) Tablets.  Comments on FDA’s draft vancomycin HCl bioequivalence recommendations are due by February 17, 2009; however, ViroPharma has requested an extension of the comment period.

FDA’s December 16, 2008 Federal Register notice also alludes to a forthcoming (but don’t expect anything soon) response to ViroPharma’s 2006 petition: 

Comments on this draft guidance will also be considered by FDA as it addresses the complicated issues raised in Viropharma, Inc.’s PSAs.  FDA will carefully consider such comments before responding to the petition and finalizing its BE recommendation for vancomycin HCl.  Because of the lengthy history of FDA’s consideration of bioequivalence methodologies for vancomycin HCl capsules, the pendency of the PSAs, and the complexity of the issues involved, the availability of this draft guidance is being announced in a drug product-specific notice, and the recommendations include a significant amount of background information and explanation of the reasons for the bioequivalence recommendations.

Dissatisfied with FDA’s December 16, 2008 announcement, ViroPharma filed its complaint.  ViroPharma states that “the Draft Guidance does not include the administrative record for FDA’s March 2006 decision to change bioequivalence methods for vancomycin . . . or the data supporting that change,” and “in no way vitiates the need for FDA to respond to ViroPharma’s FOIA request.”  Moreover, ViroPharma alleges that the draft bioequivalence recommendation “confirms that FDA failed to engage in any public process before its 2006 decision . . . .”  ViroPharma alleges that the company has a statutory right to the FDA records it seeks, as well as a statutory right “that FDA not review ANDAs that seek to copy Vancocin based on FDA’s changed interpretation of its bioequivalence regulations. . . .”

Given the importance of VANCOCIN to ViroPharma and the company’s unhappiness with FDA’s December 2008 bioequivalence recommendations, it seems clear that the current FOIA litigation is intended to obtain information that could be used in future litigation in the event FDA denies ViroPharma’s 2006 petition and approves generic versions.  Stay tuned for more as this interesting story develops.