LILLY SAYS ITS CEFTAZIDIME IS "DEMONSTRABLY IDENTICAL" TO GLAXO's

LILLY SAYS ITS CEFTAZIDIME IS "DEMONSTRABLY IDENTICAL" TO GLAXO's in Oct. 30 comments to FDA. Lilly's comments were in response to a Glaxo petition filed Oct. 10 seeking a stay of approval for Lilly's pending ceftazidime ANDA ("The Pink Sheet" Nov. 11, T&G-2). Maintaining that Glaxo's petition "conjured up . . . false fears for the safety of Lilly's ceftazidime," Lilly asserted that its product "is demonstrably identical to Glaxo's in every relevant respect." Glaxo maintained in its petition that it had to submit specifications regarding levels of high molecular weight polymer (HMWP) in the drug substance and pyridine in the finished product before the antibiotic could be approved. The firm stated that only its studies established a relationship between pyridine and HMWP levels in the drug product and that "a similar relationship must be shown for any generic versions." Lilly responded that in early 1983 it "determined that ceftazidime, under certain conditions, could degrade to form polymeric impurities" and subsequently shared that data with Glaxo. "During discussions with Glaxo representatives, Lilly also shared information on the methodology, specifically HPLC procedures, for determining polymer levels in ceftazidime," Lilly stated. The company asserted that "tests conducted by Lilly and Glaxo for pyridine and polymer are comparable, and they provide the FDA with adequate evidence of the purity and safety of the respective ceftazidime products." Glaxo also maintained in its petition that Lilly's generic should not be approved until July 19, 1990, five years after Glaxo's Fortaz approval, under marketing exclusivity provisions of the Waxman/Hatch law. Glaxo argued that antibiotics are implicitly covered by Title I of the ANDA/Patent Term Restoration Act because they are exempt from certification and regulated as new drugs. Noting that Fortaz was approved under Section 507 of the FD&C Act (the antibiotic portion of the law) and not Section 505 (the drug portion), Lilly stated that "from the outset, FDA has consistently interpreted the exclusivity provisions of the 1984 amendments as inapplicable to antibiotic drugs." Lilly cited a November 1984 FDA-issued Q-&-A document which stated that Title I "refers to generic versions of those drugs originally approved under Section 505(b). Antibiotics are approved under Section 507 . . . Accordingly, we do not consider these products to be covered by Title I." Lilly also maintained that Glaxo "recognized at the time the 1984 amendments were under consideration that the exclusivity provisions of TitleI would be inapplicable to ceftazidime." Lilly said Glaxo "sought to persuade Sen. East of North Carolina (where its facilities are located) to sponsor an amendment that would add to Section 507 of the act a provision granting three-year exclusivity to every 'third generation cephalosporin . . . approved under Section 507 during the period beginning June 1, 1984, and ending six months after the date of enactment.'" FDA announced in the Nov. 12 Federal Register that a petition had been filed requesting a period of marketing exclusivity for ceftazidime. The agency noted, however, that it has "taken the position that antibiotics are not subject to the provisions of Title I of the Drug Price Competition and Patent Term Restoration Act of 1984." The Patent and Trademark Office also recently issued a letter in response to Glaxo's patent extension application for ceftazidime pentahydrate. The Patent Office questioned whether the patent claimed by Glaxo actually covers the ceftazidime product approved by FDA. "The claims of U.S. patent 4,258,041 are drawn to the compound identified as ceftazidime and the non-toxic salts thereof (claims 1-4) as well as pharmaceutical compositions and the use thereof (claims 5-6)," the Patent Office stated." "However, neither the patent nor applicant's statements have clearly demonstrated that the claims actually include or encompass the pentahydrate as alleged." FDA explained that the question at issue is whether the dry powdered substance approved by FDA (pentahydrate) is closely enough related to the powder in solution (ceftazidime) to be covered under the latter's patent. Regardless of whether or not ceftazidime is entitled to marketing exclusivity, Lilly stated that "Glaxo granted Lilly the right to market cephalosporin products such as ceftazidime in return for similar rights under Lilly cephalosporin patents outside the United States." Glaxo's petition, Lily asserted, "is nothing but a blatantly anticompetitive attempt to obstruct the new antibiotic approval process so as to deny Lilly the fruits of its patent licensing contract with Glaxo." SmithKline also claims to have marketing rights to ceftazidime under cross-licensing agreements entered into in 1969. SmithKline has said it plans to market the drug next year.