SUPPLEMENTARY INFORMATION:

In 1984, Congress enacted the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98-417) (the 1984 amendments), which authorized the approval of duplicate versions of drug products approved under an ANDA procedure. ANDA applicants must, with certain exceptions, show that the drug for which they are seeking approval contains the same active ingredient in the same strength and dosage form as the “listed drug,” which is a version of the drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing otherwise necessary to gain approval of a new drug application (NDA). The only clinical data required in an ANDA are data to show that the drug that is the subject of the ANDA is bioequivalent to the listed drug.

The 1984 amendments include what is now section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(j)(7)), which requires FDA to publish a list of all approved drugs. FDA publishes this list as part of the “Approved Drug Products With Therapeutic Equivalence Evaluations,” which is known generally as the “Orange Book.” Under FDA regulations, drugs are removed from the list if the Agency withdraws or suspends approval of the drug's NDA or ( printed page 3144) ANDA for reasons of safety or effectiveness or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162). Under § 314.161(a)(1) (21 CFR 314.161(a)(1)), the Agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness before an ANDA that refers to that listed drug may be approved. FDA may not approve an ANDA that does not refer to a listed drug.

ALBAMYCIN (novobiocin sodium) capsule, 250 mg, is the subject of NDA 50-339, held by Pfizer, Inc. (Pfizer), and initially approved on September 4, 1964. ALBAMYCIN is indicated for the treatment of serious infections due to susceptible strains of Staphylococcus aureus when other less toxic antibiotics such as the penicillins, cephalosporins, vancomycin, lincomycin, erythromycin, and the tetracyclines cannot be used.

Novobiocin antibiotic drug products were reviewed for efficacy under the Drug Efficacy Study Implementation (DESI) program. Under this program, implemented in response to the 1962 amendments to the FD&C Act requiring demonstration of effectiveness (The Kefauver-Harris Amendments, Public Law 87-781 (1962)), the National Academy of Sciences-National Research Council (NAS-NRC) undertook a study of some 4,000 drug formulations to assess the efficacy of the products. Upon consideration of the findings and recommendations of the NAS-NRC, FDA set forth in the Federal Register its conclusions and assessment of whether and under what circumstances the reviewed drug products are considered “effective” for use as required by the FD&C Act.

In the Federal Register of May 2, 1969 (34 FR 7252), FDA announced its conclusions following consideration of the findings and recommendations of the NAS-NRC regarding oral and parenteral forms of novobiocin including ALBAMYCIN (novobiocin sodium) capsule, 250 mg. The announcement stated that FDA had concluded that novobiocin is effective for certain indications and provided labeling guidelines in accordance with this conclusion. We note, however, that the initial panel review of a syrup form of novobiocin raised questions, even at that time, concerning the safety and effectiveness of this antibiotic. The panel report included the following statement: “The development of safer and more effective drugs has virtually eliminated the need for novobiocin. The majority of the Panel believes that orally administered novobiocin should be taken off the market.” Report of the Anti-Infectives Panel, National Academy of Sciences-National Research Council, Albamycin Syrup.

In an annual report received on June 9, 1999, Pharmacia & Upjohn (now Pfizer, Inc.) notified FDA that ALBAMYCIN (novobiocin sodium) capsule, 250 mg, was no longer being manufactured. In a letter dated June 27, 2007, Pfizer, then the current holder of NDA 50-339, notified FDA that ALBAMYCIN (novobiocin sodium) capsule, 250 mg, had been discontinued. In the Federal Register of February 11, 2009 (74 FR 6896), FDA announced that it was withdrawing approval of NDA 50-339 in response to Pfizer's withdrawal request. As a result, ALBAMYCIN (novobiocin sodium) capsule, 250 mg, was moved to the “Discontinued Drug Product List” section of the Orange Book.

Crixmore LLC submitted a citizen petition dated July 9, 2008 (Docket No. FDA-2008-P-0431), under 21 CFR 10.30, requesting that the Agency determine whether ALBAMYCIN (novobiocin sodium) capsule, 250 mg, was withdrawn from sale for reasons of safety or effectiveness.

After considering the citizen petition and reviewing Agency records, FDA has determined under § 314.161 that ALBAMYCIN (novobiocin sodium) capsule, 250 mg, was withdrawn for reasons of safety or effectiveness. The petitioner stated that it had identified no data or other information suggesting that ALBAMYCIN (novobiocin sodium) capsule, 250 mg, was withdrawn for reasons of safety or effectiveness and speculated that the discontinuation of this product was an economic/strategic decision totally unrelated to safety and/or efficacy. We have carefully reviewed our files for records concerning the withdrawal of ALBAMYCIN (novobiocin sodium) capsule, 250 mg, from sale. We have also independently evaluated relevant literature and data for possible postmarketing adverse events. The literature and adverse event reports reveal several significant safety concerns. Reported adverse reactions include relatively common skin reactions, jaundice, hepatic failure, and blood dyscrasias (neutropenia, anemia, and thrombocytopenia). The literature also reveals concern about the development of novobiocin-resistant Staphylococci during treatment, and a potential for drug interactions. In light of the significant safety concerns with this product, we conclude that the withdrawal of this product from the market was on the basis of safety or effectiveness.

Accordingly, the Agency will remove ALBAMYCIN (novobiocin sodium) capsule, 250 mg, from the list of drug products published in the Orange Book. FDA will not accept or approve ANDAs that refer to this drug product.