[Federal Register Volume 64, Number 75 (Tuesday, April 20, 1999)]
[Notices]
[Pages 19373-19375]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-9770]
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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
Controlled-Release Nitroglycerin; Opportunity for a Hearing
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to
withdraw approval of 23 new drug applications (NDA's) and abbreviated
new drug applications (ANDA's) for certain single-entity coronary
vasodilator drug products containing controlled-release nitroglycerin.
FDA is offering the holders of the applications an opportunity for a
hearing on the proposal. The basis for the proposal is that the
sponsors of these products have failed to submit acceptable data on
bioavailability and bioequivalence.
DATES: Hearing requests are due by May 20, 1999; data and information
in support of hearing requests are due by June 21, 1999.
ADDRESSES: Communications in response to this notice should be
identified with the reference number DESI 1786, and directed to the
attention of the appropriate office named as follows:
A request for a hearing, supporting data, and other comments are
to be identified with Docket No. 77N-0240 and submitted to the Dockets
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852.
A request for applicability of this notice to a specific product
should be 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
[[Page 19374]]
Lane, Rockville, MD 20857, 301-594-2041.
SUPPLEMENTARY INFORMATION:
I. Background
In a notice (DESI 1786) published in the Federal Register of
February 25, 1972 (37 FR 4001), FDA announced its evaluation of reports
received from the National Academy of Sciences/National Research
Council, Drug Efficacy Study group, on certain coronary vasodilator
drugs. FDA classified controlled-release tablets of nitroglycerin as
possibly effective for indications relating to the management,
prophylaxis, or treatment of anginal attacks.
Notices published in the Federal Register of August 26, 1977 (42
FR 43127), October 21, 1977 (42 FR 56156), and September 15, 1978 (43
FR 41282), amended earlier notices (37 FR 26623, December 14, 1972; and
38 FR 18477, July 11, 1973) by temporarily exempting nitroglycerin in
controlled-release forms from the time limits established for the Drug
Efficacy Study Implementation (DESI) program. The notices established
conditions for marketing these products and identical, similar, or
related products Sec. 310.6 (21 CFR 310.6), whether or not they had
been marketed and whether or not they were subjects of approved NDA's.
FDA required distributors and manufacturers to have ANDA's
(conditionally approved, pending the results of ongoing studies) to
market controlled-release nitroglycerin products not the subject of
NDA's. If at least one drug sponsor was conducting clinical studies on
a chemical entity, FDA permitted the marketing of all firms' products
containing the same chemical entity in a similar dosage form, provided
each product met the other conditions estatblished in the notices. Not
all sponsors, therefore, were required to conduct clinical studies.
Because bioavailability is specific for an individual product, however,
FDA required each firm to conduct a bioavailability study on its own
product.
In a notice published in the Federal Register of September 7, 1984
(49 FR 35428), after completing its review of the clinical studies
submitted for single-entity controlled-release nitroglycerin capsules
and tablets, FDA announced that it had concluded that these drugs are
effective for prevention for angina pectoris. The notice set forth the
marketing and labeling conditions for the products. It required
sponsors of these products seeking full approval to submit supplements
providing acceptable in vitro dissolution tests and in vivo
bioavailability/bioequivalence studies. The September 1984 notice
stated that applications not fully approved within 1 year would be
subject to proceedings to withdraw the previous approval and to remove
the products from the market. This deadline was extended to June 26,
1987, in a notice published in the Federal Register of December 26,
1985 (50 FR 52856).
The sponsors of the drug products listed in section II of this
document are not in compliance with the notices of September 7, 1984,
and December 26, 1985, in that they either have not submitted any
bioavailability/bioequivalence data or have not submitted additional
data on incomplete or inadequate studies. Accordingly, this notice
reclassifies these products as lacking substantial evidence of
effectiveness, proposes to withdraw approval of their applications, and
offers an opportunity for a hearing on the proposal.
II. NDA's and ANDA's Known by FDA to be Subject to This Notice
1. NDA 16-447; Nitrospan (controlled-release) Capsules containing
2.5 milligrams (mg) nitroglycerin per capsule; Rhone-Poulenc Rorer
Pharmaceutical, Inc. (formerly held by USV Laboratories), 500 Arcola
Rd., Collegeville, PA 19426-0107.
2. NDA 16-518; Nitro-Bid (controlled-release) Capsules containing
2.5 mg nitroglycerin per capsule; Hoechst Marion Roussel (formerly held
by Marion Laboratories, Inc.), 10236 Marion Park Dr., Kansas City, MO
64137.
3. NDA 16-975; Nitro-Bid (controlled-release) Capsules containing
6.5 mg nitroglycerin per capsule; Hoechst Marion Roussel.
4. NDA 17-384; Nitrong (controlled-release) Tablets containing 2.6
mg nitroglycerin per tablet; Wharton Laboratories, Inc., Division of
U.S. Ethicals, Inc., 37-02 48th Ave., Long Island City, NY 11101.
5. ANDA 86-126; Nitrong (controlled-release) Tablets containing
6.5 mg nitroglycerin per tablet; Wharton Laboratories.
6. ANDA 86-138; Nitrong (controlled-release) Tablets containing
2.6 mg nitroglycerin per tablet; Wharton Laboratories.
7. ANDA 86-214; Nitrospan (controlled-release) Capsules containing
2.5 mg nitroglycerin per capsule; Rhone-Poulenc Rorer.
8. ANDA 86-426; Nitro-Bid (controlled-release) Capsules containing
13 mg nitroglycerin per capsule; Hoechst Marion Roussel.
9. ANDA 86-537; Nitroglycerin Controlled-Release Capsules
containing 6.5 mg of the drug per capsule; KV Pharmaceutical Co., 2503
South Hanley Rd., St. Louis, MO 63144-2555.
10. ANDA 86-787; Sustac (controlled-release) Tablets containing 10
mg nitroglycerin per tablet; Forest Laboratories, 909 Third Ave., New
York, NY 10022-4731.
11. ANDA 86-869; Nitrospan (controlled-release) Capsules
containing 6.5 mg of nitroglycerin per capsule; Rhone-Poulenc Rorer.
12. ANDA 87-229; Nitrobon (controlled-release) Capsules containing
2.5 mg nitroglycerin per capsule; Inwood Laboratories, Inc., Division
of Forest Laboratories, Inc., 909 Third Ave., New York, NY 10022-4731.
13. ANDA 87-544; Nitrobon (controlled-release) Capsules containing
6.5 mg nitroglycerin per capsule; Inwood Laboratories (formerly held by
Ascot Hospital Pharmaceuticals, Inc.).
14. ANDA 87-715; Nitrong (controlled-release) Tablets containing 9
mg nitroglycerin per tablet; Wharton Laboratories.
15. ANDA 87-814; Nitro-Time (controlled-release) Capsules
containing 2.5 mg nitroglycerin per capsule; Time-Cap Laboratories, 7
Michael Ave., Farmingdale, NY 11735.
16. ANDA 87-815; Nitro-Time (controlled-release) Capsules
containing 6.5 mg nitroglycerin per capsule; Time-Cap Laboratories.
17. ANDA 87-816; Nitro-Time (controlled-release) Capsules
containing 9 mg nitroglycerin per capsule; Time-Cap Laboratories.
18. ANDA 87-975; Nitroglycerin Controlled-Release Capsules
containing 2.5 mg of the drug per capsule; Eon Labs Manufacturing, Inc.
(formerly held by The Vitarine Co.), 227-15 North Conduit Ave.,
Laurelton, NY 11413.
19. ANDA 87-976; Nitroglycerin Controlled-Release Capsules
containing 6.5 mg of the drug per capsule; Eon Labs Manufacturing.
20. ANDA 88-435; Nitrocardin Sustained Action Capsules containing
2.5 mg nitroglycerin per capsule; Sidmak Laboratories, Inc., P.O. Box
371, East Hanover, NJ 07936.
21. ANDA 88-436; Nitrocardin Sustained Action Capsules containing
6.5 mg nitroglycerin per capsule; Sidmak Laboratories.
22. ANDA 88-437; Nitrocardin Sustained Action Capsules containing
9 mg nitroglycerin per capsule; Sidmak Laboratories.
23. ANDA 88-509; Nitroglycerin Controlled-Release Capsules
containing 9 mg of the drug per capsule; Eon Labs Manufacturing
(formerly held by Phoenix Pharmaceutical, Inc.).
[[Page 19375]]
III. Notice of Opportunity for a Hearing
On the basis of all the data and information available to her, the
Director of the Center for Drug Evaluation and Research is unaware of
any adequate and well-controlled clinical investigation, conducted by
experts who are qualified by scientific training and experience,
meeting the requirements of section 505 of the Federal Food, Drug, and
Cosmetic Act (the act) (21 U.S.C. 355), 21 CFR 314.126, and 21 CFR part
320 that demonstrates effectiveness (i.e., bioavailability/
bioequivalence) of the drugs listed in section II of this document and
that is in compliance with the conditions established in the September
7, 1984, and December 26, 1985, notices for continued marketing.
Therefore, notice is given to the holders of the NDA's and ANDA's
listed in section II of this document and to all other interested
persons that the Director of the Center for Drug Evaluation and
Research proposes to issue an order under section 505(e) of the act
withdrawing approval of the applications and all amendments and
supplements thereto on the ground that new information before her with
respect to the drug products, evaluated together with the evidence
available to her when the applications were approved, shows there is a
lack of substantial evidence that the drug products will have the
effect they purport or are represented to have under the conditions of
use prescribed, recommended, or suggested in the labeling.
In addition to the holders of the applications specifically named
previously, this notice of opportunity for hearing applies to all
persons who manufacture or distribute a drug product, not the subject
of an approved application, that is identical, related, or similar to a
drug product named in section II of this document, as defined in
Sec. 310.6. It is the responsibility of every drug manufacturer or
distributor to review this notice of opportunity for hearing to
determine whether it covers any drug product that they manufacture or
distribute. Such manufacturers or distributors may request an opinion
of the applicability of this notice to a specific drug product by
writing to the Division of Prescription Drug Compliance and
Surveillance (address above).
This notice of opportunity for a hearing encompasses all issues
relating to the legal status of the drug products subject to it
(including identical, related, or similar drug products as defined in
Sec. 310.6), e.g., any contention that any such product is not a new
drug because it is generally recognized as safe and effective within
the meaning of section 201(p) of the act (21 U.S.C. 3241(p)) or because
it is exempt from part or all of the new drug provisions of the act
under the exemption for products marketed before June 25, 1938, in
section 201(p) of the act, or under section 107(c) of the Drug
Amendments of 1962, or for any other reason.
In accordance with section 505 of the act and the regulations
issued under it (parts 310 and 314 (21 CFR parts 310 and 314)), an
applicant and all other persons subject to this notice are hereby given
an opportunity for hearing to show why approval of the applications
should not be withdrawn.
An applicant or any other person subject to this notice who
decides to seek a hearing shall file: (1) On or before May 20, 1999, a
written notice of appearance and request for hearing, and (2) on or
before June 21, 1999, the data, information, and analyses relied on to
demonstrate that there is a genuine issue of material fact to justify a
hearing, as specified in Sec. 314.200. Any other interested person may
also submit comments on this notice. The procedures and requirements
governing this notice of opportunity for a hearing, a notice of
appearance and request for a hearing, information and analyses to
justify a hearing, other comments, and a grant or denial of a hearing
are contained in Secs. 314.150, 314.151, and 314.200 and in 21 CFR part
12.
The failure of an applicant or any other person subject to this
notice to file a timely written notice of appearance and request for
hearing, as required by Sec. 314.200, constitutes an election by that
person not to use the opportunity for a hearing concerning the action
proposed and a waiver of any contentions concerning the legal status of
that person's drug product(s). Any new drug product marketed without an
approved new drug application is subject to regulatory action at any
time.
A request for a hearing may not rest upon mere allegations or
denials, but must present specific facts showing that there is a
genuine and substantial issue of fact that requires a hearing. If it
conclusively appears from the face of the data, information, and
factual analyses in the request for hearing that there is no genuine
and substantial issue of fact which precludes the withdrawal of
approval of the application, or when a request for hearing is not made
in the required format or with the required analyses, the Commissioner
of Food and Drugs will enter summary judgment against the person(s) who
requests the hearing, making findings and conclusions, and denying a
hearing.
All submissions under this notice of opportunity for a hearing are
to be filed in four copies. Except for data and information prohibited
from public disclosure under section 301 of the act (21 U.S.C. 331(j))
or 18 U.S.C. 1905, the submissions may be seen in the Dockets
Management Branch (address above) between 9 a.m. and 4 p.m., Monday
through Friday.
This notice is issued under section 505 of the act and under
authority delegated to the Director of the Center for Drug Evaluation
and Research (21 CFR 5.82).
Dated: April 13, 1999.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 99-9770 Filed 4-19-99; 8:45 am]
BILLING CODE 4160-01-F
