Ranitidine 75 mg applicants not entitled to 180-day exclusivity -- Torpharm petition.

NOVOPHARM 75 MG RANITIDINE INELIGIBLE FOR 180-DAY EXCLUSIVITY, TORPHARM argues in a recent citizen petition to FDA. Neither Novopharm nor any other ANDA applicant for private label versions of Warner-Lambert's Zantac 75 is entitled to 180 days of generic exclusivity because the period already has expired, the petition asserts.

Torpharm asks FDA to rule that "no ANDA applicant for a 75 mg strength ranitidine hydrochloride product is entitled to market exclusivity," or, alternatively, that marketing exclusivity for the OTC dose be considered "expired on or before Feb. 15, 1998."

The petition maintains Novopharm "has publicly stated that it is entitled...to six months of market exclusivity with respect to its 75 mg ranitidine" as the first to file an ANDA for the dosage strength. The petition was submitted on behalf of the Apotex subsidiary by the Chicago-based firm Lord Bissell & Brook.

Zantac 75, marketed by Warner-Lambert under a joint venture agreement with Glaxo Wellcome, loses Waxman/Hatch exclusivity Dec. 19. Torpharm filed an ANDA for the 75 mg strength OTC H2 antagonist stomach remedy on July 10, 1997. Although Glaxo has challenged ANDA applicants for higher Rx ranitidine doses, the Rx ranitidine marketer has not sued any applicants for the 75 mg dose.

The petition suggests any exclusivity that Novopharm may have been entitled to expired by Feb. 15, or "180 days after the first commercial marketing of generic ranitidine hydrochloride, on Aug. 20, 1997."

Torpharm cites FDA's recently released guidance on 180-day exclusivity in support of its argument. The guidance states that marketing exclusivity begins on the date of commercial marketing or the date of a court decision holding the patent to be invalid or infringed, whichever is earlier. The guidance dropped an earlier FDA requirement that a company must have mounted a "successful defense" against a patent infringement suit to qualify for the 180-day exclusivity ("The Tan Sheet" June 29, p. 27).

Emphasizing FDA's language regarding 180-day exclusivity, Torpharm maintains the agency's guidance "speaks to the first commercial marketing of the `drug,' which in this instance is ranitidine." The petition argues that the first commercial marketing of ranitidine occurred with approval of 150 mg and 300 mg strengths of the drug.

"The generic ranitidine hydrochloride that Novopharm seeks to market under expiration of Glaxo's new strength exclusivity is the same drug that it began marketing in August 1997; only the strength differs," the citizen petition asserts.

Torpharm also argues that Novopharm is not entitled to exclusivity because the patents believed to be cited in their paragraph IV certification are the same patents at issue in the previous litigations over Rx ranitidine.

"Novopharm's 75 mg ranitidine hydrochloride ANDA contains the same paragraph IV certification as its 150 mg and 300 mg ranitidine hydrochloride ANDA," which cited Glaxo's 4,521,431 and 4,880,636 patents, the petition states. FDA determined the court decision that held the `431 patent to be invalid was entered on March 3, 1997, upon expiration of Glaxo's right to appeal a decision that Boehringer Ingelheim's generic ranitidine did not infringe its Form 1 ranitidine patent.

FDA also "determined that the 180-day exclusivity period for an ANDA containing a paragraph IV certification with respect to the `431 patent ran from March 3, 1997 to Aug. 19, 1997," which was granted to Genpharm as the first to file paragraph IV certification for a ranitidine product, the petition points out.

"Although Novopharm's ANDA contained a paragraph IV certification with respect to the `636 patent, any exclusivity that Novopharm might have been entitled to expired on or before Feb. 15, 1998, 180 days after the first commercial marketing of generic ranitidine," the petition concludes.

The petition contends "Novopharm risked nothing and invested nothing when it filed its 75 mg ranitidine hydrochloride ANDA," and FDA would violate "both the letter and the spirit" of the Waxman/Hatch Act should the agency award Novopharm exclusivity to market the 75 mg form.

Torpharm requests expedited consideration of the petition because of "Novopharm's ability to enter the market ahead of other generic competitors." A number of private label firms, including Novopharm's subsidiary Granutec, started promoting private label ranitidine to retailers in late 1997 ("The Tan Sheet" Nov. 17, 1997, p. 12). Allegan, Mich.-based Perrigo and Pharmaceutical Formulations, Inc., based in Edison, N.J., also are promoting private label ranitidine to the trade.

Zantac 75 will be the second H2 antagonist to lose exclusivity in 1998 -- SmithKline Beecham's Tagamet HB's three-year exclusivity expired June 19, resulting in the prompt introduction of generic versions by several private label marketers ("The Tan Sheet" June 29, p. 19).