82 FR 42101 - Determination That GYNOREST (Dydrogesterone) Oral Tablets, 5 Milligrams and 10 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 82, Issue 171 (September 6, 2017)

Page Range		42101-42101
FR Document		2017-18816

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(FDA or Agency) has determined that GYNOREST (dydrogesterone) oral tablets, 5 milligrams (mg) and 10 mg, were not withdrawn from sale for reasons of safety or effectiveness.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.

Federal Register, Volume 82 Issue 171 (Wednesday, September 6, 2017)

[Federal Register Volume 82, Number 171 (Wednesday, September 6, 2017)]
[Notices]
[Page 42101]
From the Federal Register Online  [www.thefederalregister.org]
[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Milligrams and 10 Milligrams, Were Not Withdrawn From Sale for Reasons 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(mg) and 10 mg, were not withdrawn from sale for reasons of safety or 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

Federal Register / Vol. 82, No. 171 / Wednesday, September 6, 2017 / Notices 42101

DEPARTMENT OF HEALTH AND for reasons of safety or effectiveness or dydrogesterone and the drug product
HUMAN SERVICES if FDA determines that the listed drug dydrogesterone tablets have a
was withdrawn from sale for reasons of monograph in the current United States
Food and Drug Administration safety or effectiveness (21 CFR 314.162). Pharmacopeia, public information
A person may petition the Agency to indicates that Solvay discontinued the
[Docket No. FDA–2016–P–2675]
determine, or the Agency may product for commercial reasons, there
Determination That GYNOREST determine on its own initiative, whether has been no notice in the Federal
(Dydrogesterone) Oral Tablets, 5 a listed drug was withdrawn from sale Register reflecting an Agency
Milligrams and 10 Milligrams, Were Not for reasons of safety or effectiveness. determination that the product was
Withdrawn From Sale for Reasons of This determination may be made at any withdrawn for reasons of safety or
Safety or Effectiveness time after the drug has been withdrawn effectiveness, and dydrogesterone oral
from sale, but must be made prior to tablets are being sold in many other
AGENCY: Food and Drug Administration, approving an ANDA that refers to the countries.
HHS. listed drug (§ 314.161 (21 CFR 314.161)). We have carefully reviewed our files
ACTION: Notice. FDA may not approve an ANDA that for records concerning the withdrawal
does not refer to a listed drug. of GYNOREST (dydrogesterone) oral
SUMMARY: The Food and Drug GYNOREST (dydrogesterone) oral tablets, 5 mg and 10 mg, from sale. We
Administration (FDA or Agency) has tablets, 5 mg and 10 mg, are the subject have also independently evaluated
determined that GYNOREST of NDA 017388, held by Solvay relevant literature and data for possible
(dydrogesterone) oral tablets, 5 Pharmaceuticals (Solvay), and initially post-marketing adverse events. We have
milligrams (mg) and 10 mg, were not approved on October 31, 1978. found no information that would
withdrawn from sale for reasons of GYNOREST is indicated for amenorrhea indicate that this drug product was
safety or effectiveness. This and abnormal uterine bleeding due to withdrawn from sale for reasons of
determination will allow FDA to hormonal imbalance in the absence of safety or effectiveness.
approve abbreviated new drug organic pathology, such as submucous Accordingly, the Agency will
applications (ANDAs) for GYNOREST fibroids or uterine cancer. continue to list GYNOREST
(dydrogesterone) oral tablets, 5 mg and Solvay never marketed GYNOREST
(dydrogesterone) oral tablets, 5 mg and
10 mg, if all other legal and regulatory (dydrogesterone) oral tablets, 5 mg and
10 mg, in the ‘‘Discontinued Drug
requirements are met. 10 mg, under NDA 017388.1 In previous
Product List’’ section of the Orange
instances (see e.g., 72 FR 9763, March
FOR FURTHER INFORMATION CONTACT: Book. The ‘‘Discontinued Drug Product
5, 2007, and 61 FR 25497, May 21,
Stefanie Kraus, Center for Drug List’’ delineates, among other items,
1996), the Agency has determined that,
Evaluation and Research, Food and drug products that have been
for purposes of §§ 314.61 and 314.162,
Drug Administration, 10903 New discontinued from marketing for reasons
never marketing an approved drug
Hampshire Ave., Bldg. 51, Rm. 6214, other than safety or effectiveness.
product is equivalent to withdrawing
Silver Spring, MD 20993–0002, 301– the drug from sale. In a letter dated June ANDAs that refer to GYNOREST
796–9585. 1, 1992, Solvay requested withdrawal of (dydrogesterone) oral tablets, 5 mg and
SUPPLEMENTARY INFORMATION: In 1984, NDA 017388 for GYNOREST 10 mg, may be approved by the Agency
Congress enacted the Drug Price (dydrogesterone) oral tablets, 5 mg and as long as they meet all other legal and
Competition and Patent Term 10 mg. In the Federal Register of June regulatory requirements for the approval
Restoration Act of 1984 (Pub. L. 98–417) 25, 1993 (58 FR 34466), FDA announced of ANDAs. If FDA determines that
(the 1984 amendments), which that it was withdrawing approval of labeling for this drug product should be
authorized the approval of duplicate NDA 017388, effective July 26, 1993. revised to meet current standards, the
versions of drug products under an Foley and Lardner LLP submitted a Agency will advise ANDA applicants to
ANDA procedure. ANDA applicants citizen petition dated September 7, 2016 submit such labeling.
must, with certain exceptions, show that (Docket No. FDA–2016–P–2675), under Dated: August 28, 2017.
the drug for which they are seeking 21 CFR 10.30, requesting that the Anna K. Abram,
approval contains the same active Agency determine whether GYNOREST Deputy Commissioner for Policy, Planning,
ingredient in the same strength and (dydrogesterone) oral tablets, 5 mg and Legislation, and Analysis.
dosage form as the ‘‘listed drug,’’ which 10 mg, were withdrawn from sale for [FR Doc. 2017–18816 Filed 9–5–17; 8:45 am]
is a version of the drug that was reasons of safety or effectiveness. BILLING CODE 4164–01–P
previously approved. ANDA applicants After considering the citizen petition
do not have to repeat the extensive and reviewing Agency records, and
clinical testing otherwise necessary to based on the information we have at this DEPARTMENT OF HEALTH AND
gain approval of a new drug application time, FDA has determined under HUMAN SERVICES
(NDA). § 314.161 that GYNOREST
The 1984 amendments include what (dydrogesterone) oral tablets, 5 mg and Food and Drug Administration
is now section 505(j)(7) of the Federal 10 mg, were not withdrawn for reasons
Food, Drug, and Cosmetic Act (21 U.S.C. of safety or effectiveness. The petitioner [Docket No. FDA–2015–D–4852]
355(j)(7)), which requires FDA to states that GYNOREST (dydrogesterone)
oral tablets, 5 mg and 10 mg, were not Design Considerations and Premarket
asabaliauskas on DSKBBXCHB2PROD with NOTICES

publish a list of all approved drugs.
FDA publishes this list as part of the withdrawn for reasons of safety and Submission Recommendations for
‘‘Approved Drug Products With effectiveness because the active Interoperable Medical Devices;
Therapeutic Equivalence Evaluations,’’ pharmaceutical ingredient Guidance for Industry and Food and
which is known generally as the Drug Administration Staff; Availability
1 GYNOREST was marketed in the United States
‘‘Orange Book.’’ Under FDA regulations, AGENCY: Food and Drug Administration,
under a supplement to NDA 012985 for
drugs are removed from the list if the DUPHASTON (dydrogesterone, oral tablets). HHS.
Agency withdraws or suspends Distribution of GYNOREST under the ACTION: Notice.
approval of the drug’s NDA or ANDA DUPHASTON NDA discontinued around 1981.

VerDate Sep<11>2014 17:37 Sep 05, 2017 Jkt 241001 PO 00000 Frm 00046 Fmt 4703 Sfmt 4703 E:\FR\FM\06SEN1.SGM 06SEN1

Document Created: 2017-09-06 00:56:57
Document Modified: 2017-09-06 00:56:57

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Notices
Action		Notice.
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.
FR Citation		82 FR 42101

82 FR 42101 - Determination That GYNOREST (Dydrogesterone) Oral Tablets, 5 Milligrams and 10 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 82, Issue 171 (September 6, 2017)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration