[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