TRAVENOL's CISPLATIN ANDA MUST INCLUDE CHEMISTRY, MANUFACTURING

Executive Summary

TRAVENOL's CISPLATIN ANDA MUST INCLUDE CHEMISTRY, MANUFACTURING and controls information, FDA said in response to an ANDA suitability petition filed by Travenol for cisplatin injection, 1 mg/ml in 100 ml and 500 ml pharmacy bulk packages. In an Oct. 6 letter to Baxter International's Travenol subsidiary, FDA requested, in addition to bioequivalence data, that the firm privide stability and sterility information; data on the container/closure system; and in-process and finished product testing results, including formation of impurity limits. In granting approval of Travenol's ANDA suitability petition, FDA also noted that Bristol-Myers' Platinol is still covered by a patent. Bristol-Myers' patent for Platinol is scheduled to expire on Jan. 12, 1999. Travenol filed the ANDA suitability petition for cisplatin in support of the company's business of reconstituting chemotherapeutic and antibiotic injectables for hospital use. Travenol had met with FDA several times prior to the ANDA submission, including a Dec. 5, 1986 meetings, at which FDA told the firm that its reconstituted parenteral products are considered new drugs because they differ from the approved NDA labeling requirements ("The Pink Sheet" Jan. 19, T&G-9). Baring an agreement between Travenol and Bristol-Myers, FDA's requirement of complete chemistry, manufacturing and controls information on reconstituted cisplatin would presumably preclude Travenol's use of the anticancer agent. Travenol indicated that it was still in discussions with FDA, with the goal of avoiding having to submit full ANDAs for all of the company's reconstituted products. Bristol-Myers, in May 14, 1987 comments to FDA, stated that reconstituted cisplatin's potential to interact with pharmacy bulk packages raises questions of safety. Bristol-Myers also reiterated FDA's opinion that Travenol's manipulation of the listed product and its placement in plastic bags makes reconstituted cisplatin a new drug. The altered cisplatin products, Bristol-Myers contended, should therefore be subject to requirements of the FD&C Act including GMPs, FDA pre-clearance before marketing, and the requirement that approved labeling accompany the product. Later in May, FDA seized eight chemotherapeutic and seven antibiotic products from Travenol's Regional Compounding facility in Morton Grove, Illinois. Travenol's chemotherapeutic products include cisplatin, cyclophosphamide, fluorouracil, methotrexate, vinblastine, vincristine, bleomycin, and doxorubicin, and mitomycin ("The Pink Sheet" June 1, T&G-6). FDA has been evaluating the regulatory status of Travenol's reconstituted drug products since June 1985.