Daily Rules, Proposed Rules, and Notices of the Federal Government


Food and Drug Administration

[Docket No. FDA-2012-N-0190]

Determination That ENDURON (methyclothiazide) Tablets and Six Other Drug Products Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
SUMMARY: The Food and Drug Administration (FDA) has determined that the seven drug products listed in this document were not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated new drug applications (ANDAs) that refer to these drug products, and it will allow FDA to continue to approve ANDAs that refer to the products as long as they meet relevant legal and regulatory requirements.
FOR FURTHER INFORMATION CONTACT: Mark Geanacopoulos, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, rm. 6206, Silver Spring, MD 20993-0002, 301-796-6925.

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 sponsors 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. Sponsors of ANDAs 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 (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 generally known as the “Orange Book.” Under FDA regulations, drugs are withdrawn from the list if the Agency withdraws or suspends approval of the drug's NDA or ANDA for reasons of safety or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of safety or effectiveness (21 CFR 314.162).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) (21 CFR 314.161(a)), the Agency must determine whether a listed drug was withdrawn from sale for reasons of safety or effectiveness: (1) Before an ANDA that refers to that listed drug may be approved, (2) whenever a listed drug is voluntarily withdrawn from sale and ANDAs that refer to the listed drug have been approved, and (3) when a person petitions for such a determination under 21 CFR 10.25(a) and 10.30. Section 314.161(d) provides that if FDA determines that a listed drug was removed from sale for safety or effectiveness reasons, the Agency will initiate proceedings that could result in the withdrawal of approval of the ANDAs that refer to the listed drug.

As requested by the applicants, FDA withdrew approval of NDA 012524 for Enduron (methyclothiazide) Tablets and NDA 017577 for Ditropan (oxybutynin chloride) Tablets in theFederal Registerof March 19, 2012 (77 FR 16039). In addition, FDA has become aware that

the other drug products listed in the table in this document are no longer being marketed.

Application No. Drug Applicant NDA 012524 ENDURON (methyclothiazide) Tablets, 2.5 milligrams (mg) and 5 mg Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, IL 60064-3500. NDA 016949 LIMBITROL and LIMBITROL DS (amitriptyline hydrochloride; chlordiazepoxide) Tablets, equivalent to (EQ) 12.5 mg (base), 5 mg, and EQ 25 mg (base), 10 mg Valeant Pharmaceuticals International, Inc., 4787 Levy St., Montreal, Quebec H4R 2P9, Canada. NDA 017577 DITROPAN (oxybutynin chloride) Tablets, 5 mg Janssen Pharmaceuticals, Inc., 1125 Trenton-Harbourton Rd., P.O. Box 200, Titusville, NJ 08560. NDA 017950 WESTCORT (hydrocortisone valerate) Cream, 0.2% Ranbaxy Laboratories, Ltd., 600 College Road East, suite 2100, Princeton, NJ 08540. NDA 018763 TOPICORT (desoximetasone) Ointment, 0.25% Taro Pharmaceuticals, Inc., 3 Skyline Dr., Hawthorne, NY 10532. NDA 020036 AREDIA (pamidronate disodium) Injection, 30 mg/vial Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, NJ 07936-1080. NDA 020038 FLUDARA (fludarabine phosphate) Injection, 50 mg/vial Genzyme Corporation, 1850 K St. NW., suite 650, Washington, DC 20006.

FDA has reviewed its records and, under 314.161, has determined that the drug products listed in this document were not withdrawn from sale for reasons of safety or effectiveness. Accordingly, the Agency will continue to list the drug products listed in this document in the “Discontinued Drug Product List” section of the Orange Book. The “Discontinued Drug Product List” identifies, among other items, drug products that have been discontinued from marketing for reasons other than safety or effectiveness.

Approved ANDAs that refer to the NDAs listed in this document are unaffected by the discontinued marketing of the products subject to those NDAs. Additional ANDAs that refer to these products may also be approved by the Agency if they comply with relevant legal and regulatory requirements. If FDA determines that labeling for these drug products should be revised to meet current standards, the Agency will advise ANDA applicants to submit such labeling.

Dated: September 24, 2012. Leslie Kux, Assistant Commissioner for Policy.