[Federal Register Volume 64, Number 57 (Thursday, March 25, 1999)]
[Notices]
[Pages 14451-14453]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-7232]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 77N-0240; DESI 1786]
Nitroglycerin Transdermal System; 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 one new drug application (NDA) and five
abbreviated new drug applications (ANDA's) for certain single-entity
coronary vasodilator drug products containing nitroglycerin in a
transdermal system.
[[Page 14452]]
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 April 26, 1999; data and information
in support of hearing requests are due by May 24, 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 below.
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 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 (paragraph XIV, category I
exemption). FDA granted this exemption to allow manufacturers
additional time to study the effectiveness and bioavailability of their
products. FDA also added additional dosage forms of nitroglycerin to
the Drug Efficacy Study and the paragraph XIV, category I exemption.
The exemption notices established conditions for marketing the
single-entity coronary vasodilators 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 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. 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 July 15, 1993 (58
FR 38129), after completing its review of the clinical studies
submitted for the transdermal delivery system of nitroglycerin, FDA
announced its conclusions that this dosage form of nitroglycerin is
effective. The notice set forth the conditions for marketing and
approval of such products. To receive full approval of an application
based on effectiveness, as well as safety, the notice required that
sponsors submit bioavailability/bioequivalence studies within 1 year.
The sponsors of the drug products listed in section II of this
document are not in compliance with the July 15, 1993, notice 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 the products to lacking
substantial evidence of effectiveness, proposes to withdraw approval of
the 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 20-146; Nitrodisc, release rate 0.2 milligrams (mg) of
nitroglycerin per hour (h); G.D. Searle & Co., P.O. Box 5100, Chicago,
IL 60680 (Searle).
Nitrodisc, release rate 0.3 mg of nitroglycerin per h; Searle.
Nitrodisc, release rate 0.4 mg of nitroglycerin per h; Searle.
2. ANDA 88-727; Deponit, release rate 0.2 mg of nitroglycerin per
h; Schwarz Pharma, Inc., 5600 West County Line Rd., Mequon, WI 53092
(Schwarz) (formerly held by Wyeth Laboratories, Inc., P.O. Box 8297
Philadelphia, PA 19101).
3. ANDA 88-782; Nitroglycerin Transdermal System (NTS), release
rate 0.2 mg of nitroglycerin per h; Hercon Pharmaceutical Co., Inc.,
P.O. Box 786, York, PA 17405 (Hercon).
4. ANDA 88-783; NTS, release rate of 0.6 mg of nitroglycerin per h;
Hercon.
5. ANDA 89-022; Deponit, release rate 0.4 mg of nitroglycerin per
h; Schwarz.
6. ANDA 89-516; NTS, release rate of 0.4 mg of nitroglycerin per
h; Hercon.
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 that have been found to be in compliance with the conditions
established for continued marketing.
Therefore, notice is given to the holders of the NDA 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 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
in section II of this document, this notice of opportunity for a
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
[[Page 14453]]
manufacturer or distributor to review this notice of opportunity for a
hearing to determine whether it covers any drug product that they
manufacture or distribute. Such persons may request an opinion on 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. 321(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 (Pub. L. 87-781), or for any other reason.
In accordance with section 505 of the act and 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 a 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 April 26, 1999,
a written notice of appearance and request for hearing; and (2) on or
before May 24, 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. 314.151 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 a
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 products.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 a 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 a 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 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 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 the Federal Food, Drug, and Cosmetic Act (sec. 505 (21
U.S.C. 355)) and under authority delegated to the Director of the
Center for Drug Evaluation and Research (21 CFR 5.82).
Dated: March 3, 1999.
Janet Woodcock,
Director, Center for Drug Evaluation and Research.
[FR Doc. 99-7232 Filed 3-24-99; 8:45 am]
BILLING CODE 4160-01-F
