MMD PETITION, RESPONSE TO BIOAVAIL SUIT QUESTIONS FDA AUTHORITY

MMD PETITION, RESPONSE TO BIOAVAIL SUIT QUESTIONS FDA AUTHORITY to "permit 505(b)(2) applications at all for non- bioequivalent versions of ANDA eligible drugs," Peter Safir of Kleinfeld, Kaplan and Becker told the Food & Drug Law Institute annual conference in Washington, D.C. Dec. 13. Safir is counsel for Marion Merrell Dow in its legal wrangles with Hoechst and Bioavail over sustained-release diltiazem.

Safir said MMD's petition to FDA also raises "issues of the scope of patent certification for 505Co)(2) applications," or "paper NDAs." MMD filed a patent infringement suit in November 1993 in Newark, N.J. federal court over the 505(b)(2) application filed by Hoechst for a once-daily diltiazem with a different release profile from MMD's sustained-release diltiazem product, Cardizem CD. In response, Bioavail, which licensed the formulation to Hoechst, filed an antitrust suit Oct. 19 in San Juan, P.R. federal court alleging that MMD was manipulating administrative regulations to discourage competition and evergreen its product ("The Pink Sheet" Nov. 28, T&G-12).

Safir's speech to FDLI was elaborated in MMD's reply comments, co-authored by Safir and Millicent Yim, filed with FDA Dec. 6. The comments discuss the issues raised by the Hoechst and Bioavail lawsuits and MMD's own citizen's petition requesting a stay on sustained-release diltiazem filed Sept. 19. The comments state that "since ANDAs may be filed for duplicates of Cardizem CD, non- bioequivalent versions of once-a-day diltiazem should not be permitted under Section 505(b)(2) at all."

MMD maintains that a "full NDA under Section 505(b)(1) is the appropriate mechanism for the approval of non-bioequivalent forms of sustained-release diltiazem which seek approval through the submission of clinical data supporting safety and efficacy without patent certification." Patent certification is required in "paper NDAs" so that "pioneer companies are afforded the opportunity to protect their patents," the comments say.

Since Hoechst relied upon toxicology investigations of MMD's diltiazem in its 505(b)(2), the submission falls under the scope of 21 CFR 314(i)(1)(i)(A), the comments state. That regulation requires "a 505(b)(2) applicant...to certify not only with respect to each patent that claims a drug product, but any patent claiming a 'drug substance' on which investigations relied upon by the 505(b)(2) applicant were conducted," according to the petition.

In MMD's reading of the regs, even though the mechanism of action in the Hoechst/Bioavail product is different from that of Cardizem CD -- and the new product is thus not subject to regulations covering "drug products" -- the drug substance in question is diltiazem, and therefore requires patent certification.

The comments further claim that the patent infringement issue "is a matter of patent law, not FDA law, and is exactly the type of dispute that FDA is least equipped to decide."

The issue of pioneer company abuse of drug protection raised by the Bioavail suit is getting attention from yet another federal agency. At the FDLI conference, Mark Whitener, the acting director of the Federal Trade Commission Bureau of Competition, said an "area that has been and is a topic of investigation of generic competition involves the abuse of either the judicial or regulatory process that are designed not to achieve a legitimate outcome on the merits but to impede competition." He previously indicated such investigations were being undertaken by FTC at a Senate Aging Committee hearing in November 1993 ("The Pink Sheet" Nov. 22, 1993, p. 3). Whitener illustrated his comment by referring to "the possible sham use of state formulary processes to block approval of competing drugs" and "sham petitioning before the FDA."