[Federal Register Volume 65, Number 131 (Friday, July 7, 2000)]
[Notices]
[Pages 42018-42019]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-17198]



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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 77N-0240; DESI 1786]


Certain Single-Entity Coronary Vasodilators Containing Isosorbide 
Dinitrate; Withdrawal of Approval of Abbreviated New Drug Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is withdrawing 
conditional approval of 25 abbreviated new drug applications (ANDA's) 
for certain single-entity coronary vasodilator drug products containing 
isosorbide dinitrate. FDA is withdrawing approval because there is a 
lack of substantial evidence that these drugs are effective for their 
labeled indications relating to the treatment and prevention of anginal 
attacks. The sponsors of these conditionally approved products failed 
to provide required adequate bioavailability/bioequivalence data on the 
products to support full approval of the applications.

DATES: Effective August 7, 2000.

ADDRESSES: Requests for an opinion on the applicability of this notice 
to a specific product should be identified with Docket No. 77N-0240 and 
reference number DESI 1786 and directed to the Division of Prescription 
Drug Compliance and Surveillance (HFD-330), Center for Drug Evaluation 
and Research, Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855.

FOR FURTHER INFORMATION CONTACT: Mary E. Catchings, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION: In the Federal Register of March 22, 1999 
(64 FR 13802), FDA published a notice offering an opportunity for a 
hearing (NOOH) on a proposal to withdraw approval of 25 conditionally-
approved ANDA's. The proposal was based on a lack of adequate 
bioavailability/bioequivalence data to support a finding of substantial 
evidence of effectiveness as required by section 505(e) of the Federal 
Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355(e)), 21 CFR 
314.126, and 21 CFR part 320.
    In response to the NOOH, Zeneca Pharmaceuticals requested a hearing 
for Sorbitrate Chewable Tablets (ANDA 86-388) and Sorbitrate Oral 
Tablets (ANDA 88-074). Zeneca later withdrew its hearing request for 
these products. No other sponsor of the products listed in the March 
22, 1999, NOOH requested a hearing. As stated in the NOOH, the failure 
of an applicant or any other person subject to the notice to request a 
hearing constitutes an election by that person not to use the 
opportunity for a hearing and a waiver of any contentions concerning 
the legal status of that person's drug product(s). Accordingly, this 
notice withdraws conditional approval of the following ANDA's:
    1. ANDA 85-783; Isordil Chewable Tablets containing 10 milligrams 
(mg) of isosorbide dinitrate per tablet; Wyeth-Ayerst Laboratories, 
(formerly held by Ives Laboratories, Inc.), P.O. Box 8299, 
Philadelphia, PA 19101.
    2. ANDA 86-045; Isosorbide Dinitrate Tablets containing 5 mg of the 
drug per tablet; Bolar Pharmaceutical Co., Inc., 130 Lincoln St., 
Copiague, NY 11726.
    3. ANDA 86-186; Isosorbide Dinitrate (controlled release, colored) 
Capsules containing 40 mg of the drug per capsule; Eon Labs 
Manufacturing, Inc. (formerly held by The Vitarine Co., Inc.), 227-15 
North Conduit Ave., Laurelton, NY 11413.
    4. ANDA 86-191; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Bolar.
    5. ANDA 86-224; Isosorbide Dinitrate (controlled release) Tablets 
containing 40 mg of the drug per tablet; Geneva Pharmaceuticals, Inc. 
(formerly held by Cord Laboratories, Inc.), 2555 West Midway Blvd., 
P.O. Box 446, Broomfield, CO 80038-0446.
    6. ANDA 86-362; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Bolar.
    7. ANDA 86-388; Sorbitrate (chewable) Tablets containing 10 mg of 
isosorbide dinitrate per tablet; Zeneca Pharmaceuticals (formerly held 
by Stuart Pharmaceuticals), 1800 Concord Pike, Wilmington, DE 19897.
    8. ANDA 86-788; Isosorbide Dinitrate (controlled release, green) 
Tablets containing 40 mg of the drug per tablet; Forest Laboratories, 
Inc., 919 Third Ave., New York, NY 10022.
    9. ANDA 86-790; Isosorbide Dinitrate (controlled release, yellow) 
Tablets containing 40 mg of the drug per tablet; Forest.
    10. ANDA 87-314; Isosorbide Dinitrate (chewable) Tablets containing 
10 mg of the drug per tablet; D. M. Graham Laboratories, Inc., 58 Pearl 
St., P.O. Box P, Hobart, NY 13788.
    11. ANDA 87-414; Isosorbide Dinitrate (controlled release, scarlet/
clear) Capsules containing 40 mg of the drug per capsule; Eon Labs.
    12. ANDA 87-461; Isosorbide Dinitrate (controlled release orange/
clear) Capsules containing 40 mg of the drug per capsule; Eon Labs.
    13. ANDA 87-477; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Ascot Hospital 
Pharmaceuticals, Inc., 8055 North Ridgeway Ave., Skokie, IL 60076.
    14. ANDA 87-482; Isosorbide Dinitrate (controlled release) Tablets 
containing 40 mg of the drug per tablet; Ascot.
    15. ANDA 87-507; Isosorbide Dinitrate (controlled release, white/
amethyst) Capsules containing 40 mg of the drug per capsule; Eon Labs.
    16. ANDA 87-558; Isosorbide Dinitrate (controlled release) Tablets 
containing 40 mg of the drug per tablet; Par Pharmaceutical, Inc., One 
Ram Ridge Rd., Spring Valley, NY 10977.
    17. ANDA 87-680; Isosorbide Dinitrate (controlled release, white/
clear) Capsules containing 40 mg of the drug; Eon Labs.
    18. ANDA 87-694; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Vangard Labs, Inc., P.O. Box 
1268, Glasgow, KY 42142-1268.
    19. ANDA 87-700; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Vangard.
    20. ANDA 88-074; Sorbitrate Tablets containing 20 mg of isosorbide 
dinitrate per tablet; Zeneca.
    21. ANDA 88-428; Isosorbide Dinitrate (controlled release) Tablets 
containing 20 mg of the drug per tablet; Forest.
    22. ANDA 88-589; Isosorbide Dinitrate Tablets containing 5 mg of 
the drug per tablet; Barr Laboratories, Inc., Two Quaker Rd., P.O. Box 
2900, Pomona, NY 10970-0519.
    23. ANDA 88-590; Isosorbide Dinitrate Tablets containing 5 mg of 
the drug per tablet; Barr.
    24. ANDA 88-591; Isosorbide Dinitrate Tablets containing 20 mg of 
the drug per tablet; Barr.
    25. ANDA 88-592; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Barr.
    The effectiveness conclusions and conditions for marketing 
described in a notice published in the Federal Register of August 3, 
1984 (49 FR 31151), also applied to the drug products described below. 
Although approval of these products was withdrawn previously based on 
the written requests of the applicants, who no longer market the 
products, this notice constitutes FDA's final conclusions on the 
effectiveness of these products.

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    1. NDA 17-226; Sorbitrate (controlled release) Tablets containing 
40 mg isosorbide dinitrate per tablet; Zeneca.
    2. ANDA 84-473; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Zenith Goldline 
Pharmaceuticals, 140 Legrand Ave., Northvale, NJ 07647.
    3. ANDA 84-474; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Zenith Goldline.
    4. ANDA 86-035; Isosorbide Dinitrate Tablets containing 10 mg of 
the drug per tablet; Zenith Goldline.
    5. ANDA 86-044; Isosorbide Dinitrate Tablets, containing 10 mg of 
the drug per tablet; Circa Pharmaceuticals (formerly held by Bolar 
Pharmaceutical Co., Inc.), 15 Grand Park Blvd., Athens, OH 45701.
    6. ANDA 86-048; Isosorbide Dinitrate Tablets containing 20 mg of 
the drug per tablet; Bolar.
    7. ANDA 86-051; Isosorbide Dinitrate (controlled release) Tablets 
containing 40 mg of the drug per tablet; Bolar.
    8. ANDA 86-071; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Chelsea Laboratories, Inc., 896 
Orlando Ave., West Hempstead, NY 11552.
    9. ANDA 86-072; Isosorbide Dinitrate Tablets containing 5 mg of the 
drug per tablet; Chelsea.
    10. ANDA 86-073; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Chelsea.
    11. ANDA 86-078; Isosorbide Dinitrate Tablets containing 10 mg of 
the drug per tablet; Chelsea.
    12. ANDA 86-302; Isosorbide Dinitrate Tablets containing 10 mg of 
the drug per tablet; Purepac Pharmaceutical Co., 200 Elmora Ave., 
Elizabeth, NJ 07207.
    13. ANDA 86-304; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Purepac.
    14. ANDA 86-855; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Lederle Laboratories, North 
Middletown Rd., Pearl River, NY 10965.
    15. ANDA 86-858; Isosorbide Dinitrate Tablets containing 5 mg of 
the drug per tablet; Lederle.
    16. ANDA 86-861; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Lederle.
    17. ANDA 86-862; Isosorbide Dinitrate Tablets containing 10 mg of 
the drug per tablet; Lederle.
    18. ANDA 86-922; Isosorbide Dinitrate (sublingual) Tablet 
containing 5 mg of the drug per tablet; Par.
    19. ANDA 86-924; Isosorbide Dinitrate (sublingual) Tablets 
containing 2.5 mg of the drug per tablet; Par.
    20. ANDA 87-163; Isosorbide Dinitrate (chewable) Tablets containing 
5 mg of the drug per tablet; D. M. Graham.
    21. ANDA 87-344; Isosorbide Dinitrate (controlled release) Capsules 
containing 40 mg of the drug per capsule; Inwood Laboratories, Inc., 
909 Third Ave., New York, NY 10022-4731.
    22. ANDA 87-415; Isosorbide Dinitrate (controlled release, green/
clear) Capsules containing 40 mg of the drug per capsule; Eon.
    23. ANDA 87-469; Isosorbide Dinitrate (sublingual) Tablets 
containing 10 mg of the drug per tablet; Chelsea.
    24. ANDA 87-474; Isosorbide Dinitrate Tablets containing 5 mg of 
the drug per tablet; Ascot.
    25. ANDA 87-475; Isosorbide Dinitrate Tablets containing 10 mg of 
the drug per tablet; Ascot.
    26. ANDA 87-476; Isosorbide Dinitrate Tablets containing 20 mg of 
the drug per tablet; Ascot.
    27. ANDA 87-478; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Ascot.
    28. ANDA 87-486; Isosorbide Dinitrate (controlled release) Capsules 
containing 40 mg of the drug per capsule; Ascot.
    29. ANDA 87-490; Isosorbide Dinitrate Tablets containing 20 mg of 
the drug per tablet; Chelsea.
    30. ANDA 87-491; Isosorbide Dinitrate Tablets containing 30 mg of 
the drug per tablet; Chelsea.
    31. ANDA 87-618; Isosorbide Dinitrate Tablets containing 10 mg of 
the drug per tablets; Vangard.
    32. ANDA 87-673; Isosorbide Dinitrate Tablets containing 5 mg of 
the drug per tablet; Vangard.
    33. ANDA 87-933; Isosorbide Dinitrate (sublingual) Tablets 
containing 10 mg of the drug per tablet; Par.
    34. ANDA 88-005; Isosorbide Dinitrate (sublingual) Tablets 
containing 5 mg of the drug per tablet; Unit Dose Laboratories, 1718 
Northrock Court, Rockford, IL 61103.
    35. ANDA 88-006; Isosorbide Dinitrate (sublingual) Tablets 
containing 10 mg of the drug per tablet; Unit Dose Labs.
    36. ANDA 88-123; Sorbitrate (sublingual) Tablets containing 10 mg 
of isosorbide dinitrate per tablet; Zeneca.
    Any drug product that is identical, related, or similar to the drug 
products named above and is not the subject of an approved new drug 
application (NDA) is covered by the applications listed above and is 
subject to this notice (21 CFR 310.6). Any person who wishes to 
determine whether a specific product is covered by this notice should 
write to the Division of Prescription Drug Compliance and Surveillance 
(address above).
    The Director of the Center for Drug Evaluation and Research, under 
the act (section 505) and under authority delegated to her (21 CFR 
5.82), finds that, on the basis of new information on the drugs and the 
evidence available when the applications were approved, there is a lack 
of substantial evidence that the products named above will have the 
effects they purport or are represented to have under the conditions of 
use prescribed, recommended, or suggested in their labeling.
    Therefore, based on the foregoing finding, approval of the 
applications listed above and all their amendments and supplements is 
withdrawn effective August 7, 2000. Shipment in interstate commerce of 
these products or of any identical, related, or similar product that is 
not the subject of a fully approved NDA will then be unlawful.

    Dated: June 20, 2000.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 00-17198 Filed 7-6-00; 8:45 am]
BILLING CODE 4160-01-F