Document ID: FDA-2016-P-2675-0005
Agency: fda
Document Type: Notice
Title: Determination That GYNOREST (Dydrogesterone) Oral Tablets, 5  Milligrams and 10 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness
Posted Date: 2017-09-06T04:00Z

[Federal Register Volume 82, Number 171 (Wednesday, September 6, 2017)]
[Notices]
[Page 42101]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2017-18816]

[[Page 42101]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-P-2675]

Determination That GYNOREST (Dydrogesterone) Oral Tablets, 5 
Milligrams and 10 Milligrams, Were Not Withdrawn From Sale for Reasons 
of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) has 
determined that GYNOREST (dydrogesterone) oral tablets, 5 milligrams 
(mg) and 10 mg, were not withdrawn from sale for reasons of safety or 
effectiveness. This determination will allow FDA to approve abbreviated 
new drug applications (ANDAs) for GYNOREST (dydrogesterone) oral 
tablets, 5 mg and 10 mg, if all other legal and regulatory requirements 
are met.

FOR FURTHER INFORMATION CONTACT: Stefanie Kraus, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 6214, Silver Spring, MD 20993-0002, 301-
796-9585.

SUPPLEMENTARY INFORMATION: 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 under an ANDA procedure. ANDA applicants 
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. ANDA applicants do not have to 
repeat the extensive clinical testing otherwise necessary to gain 
approval of a new drug application (NDA).
    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 known generally as the ``Orange 
Book.'' Under FDA regulations, drugs are removed 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).
    A person may petition the Agency to determine, or the Agency may 
determine on its own initiative, whether a listed drug was withdrawn 
from sale for reasons of safety or effectiveness. This determination 
may be made at any time after the drug has been withdrawn from sale, 
but must be made prior to approving an ANDA that refers to the listed 
drug (Sec.  314.161 (21 CFR 314.161)). FDA may not approve an ANDA that 
does not refer to a listed drug.
    GYNOREST (dydrogesterone) oral tablets, 5 mg and 10 mg, are the 
subject of NDA 017388, held by Solvay Pharmaceuticals (Solvay), and 
initially approved on October 31, 1978. GYNOREST is indicated for 
amenorrhea and abnormal uterine bleeding due to hormonal imbalance in 
the absence of organic pathology, such as submucous fibroids or uterine 
cancer.
    Solvay never marketed GYNOREST (dydrogesterone) oral tablets, 5 mg 
and 10 mg, under NDA 017388.\1\ In previous instances (see e.g., 72 FR 
9763, March 5, 2007, and 61 FR 25497, May 21, 1996), the Agency has 
determined that, for purposes of Sec. Sec.  314.61 and 314.162, never 
marketing an approved drug product is equivalent to withdrawing the 
drug from sale. In a letter dated June 1, 1992, Solvay requested 
withdrawal of NDA 017388 for GYNOREST (dydrogesterone) oral tablets, 5 
mg and 10 mg. In the Federal Register of June 25, 1993 (58 FR 34466), 
FDA announced that it was withdrawing approval of NDA 017388, effective 
July 26, 1993.
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    \1\ GYNOREST was marketed in the United States under a 
supplement to NDA 012985 for DUPHASTON (dydrogesterone, oral 
tablets). Distribution of GYNOREST under the DUPHASTON NDA 
discontinued around 1981.
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    Foley and Lardner LLP submitted a citizen petition dated September 
7, 2016 (Docket No. FDA-2016-P-2675), under 21 CFR 10.30, requesting 
that the Agency determine whether GYNOREST (dydrogesterone) oral 
tablets, 5 mg and 10 mg, were withdrawn from sale for reasons of safety 
or effectiveness.
    After considering the citizen petition and reviewing Agency 
records, and based on the information we have at this time, FDA has 
determined under Sec.  314.161 that GYNOREST (dydrogesterone) oral 
tablets, 5 mg and 10 mg, were not withdrawn for reasons of safety or 
effectiveness. The petitioner states that GYNOREST (dydrogesterone) 
oral tablets, 5 mg and 10 mg, were not withdrawn for reasons of safety 
and effectiveness because the active pharmaceutical ingredient 
dydrogesterone and the drug product dydrogesterone tablets have a 
monograph in the current United States Pharmacopeia, public information 
indicates that Solvay discontinued the product for commercial reasons, 
there has been no notice in the Federal Register reflecting an Agency 
determination that the product was withdrawn for reasons of safety or 
effectiveness, and dydrogesterone oral tablets are being sold in many 
other countries.
    We have carefully reviewed our files for records concerning the 
withdrawal of GYNOREST (dydrogesterone) oral tablets, 5 mg and 10 mg, 
from sale. We have also independently evaluated relevant literature and 
data for possible post-marketing adverse events. We have found no 
information that would indicate that this drug product was withdrawn 
from sale for reasons of safety or effectiveness.
    Accordingly, the Agency will continue to list GYNOREST 
(dydrogesterone) oral tablets, 5 mg and 10 mg, in the ``Discontinued 
Drug Product List'' section of the Orange Book. The ``Discontinued Drug 
Product List'' delineates, among other items, drug products that have 
been discontinued from marketing for reasons other than safety or 
effectiveness. ANDAs that refer to GYNOREST (dydrogesterone) oral 
tablets, 5 mg and 10 mg, may be approved by the Agency as long as they 
meet all other legal and regulatory requirements for the approval of 
ANDAs. If FDA determines that labeling for this drug product should be 
revised to meet current standards, the Agency will advise ANDA 
applicants to submit such labeling.

    Dated: August 28, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-18816 Filed 9-5-17; 8:45 am]
 BILLING CODE 4164-01-P