82 FR 41273 - Determination That CENESTIN (Estrogens, Conjugated Synthetic A) Tablets, 0.3 Milligrams, 0.45 Milligrams, 0.625 Milligrams, 0.9 Milligrams, and 1.25 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness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 167 (August 30, 2017)

Page Range		41273-41274
FR Document		2017-18376

The Food and Drug Administration (FDA or Agency) has determined that CENESTIN (estrogens, conjugated synthetic A) Tablets, 0.3 milligrams (mg), 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg, were not withdrawn from sale for reasons of safety or effectiveness.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 these products, if all other legal and regulatory requirements are met.

Federal Register, Volume 82 Issue 167 (Wednesday, August 30, 2017)

[Federal Register Volume 82, Number 167 (Wednesday, August 30, 2017)]
[Notices]
[Pages 41273-41274]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2017-18376]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2017-P-1461]


Determination That CENESTIN (Estrogens, Conjugated Synthetic A) 
Tablets, 0.3 Milligrams, 0.45 Milligrams, 0.625 Milligrams, 0.9 
Milligrams, and 1.25 Milligrams, Were Not Withdrawn From Sale for 
Reasons of Safety or Effectiveness

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) has 
determined that CENESTIN (estrogens, conjugated synthetic A) Tablets, 
0.3 milligrams (mg), 0.45 mg, 0.625 mg, 0.9

[[Page 41274]]

mg, and 1.25 mg, were not withdrawn from sale for reasons of safety or 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 these products, if all other legal 
and regulatory requirements are met.

FOR FURTHER INFORMATION CONTACT: Bronwen Blass, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave. Bldg. 51, Rm. 6228, Silver Spring, MD 20993-0002, 301-
796-5092.

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.
    CENESTIN (estrogens, conjugated synthetic A) Tablets, 0.3 mg, 0.45 
mg, 0.625 mg, 0.9 mg, and 1.25 mg, is the subject of NDA 020992, held 
by Teva Branded Pharmaceutical Products R&D, Inc. (Teva), and was 
initially approved on March 24, 1999. CENESTIN is indicated for 
treatment of moderate to severe vasomotor symptoms due to menopause and 
treatment of moderate to severe symptoms of vulvar and vaginal atrophy 
due to menopause.
    In 2016, Teva notified FDA that CENESTIN (estrogens, conjugated 
synthetic A) Tablets, 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg, 
were being discontinued, and FDA moved the drug product to the 
``Discontinued Drug Product List'' section of the Orange Book.
    Foley & Lardner submitted a citizen petition dated March 8, 2017 
(Docket No. FDA-2017-P-1461), under 21 CFR 10.30, requesting that the 
Agency determine whether CENESTIN (estrogens, conjugated synthetic A) 
Tablets, 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg, were withdrawn 
from sale for reasons of safety or effectiveness.
    After considering the citizen and reviewing Agency records and 
based on the information we have at this time, FDA has determined under 
Sec.  314.161 that CENESTIN (estrogens, conjugated synthetic A) 
Tablets, 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg, were not 
withdrawn for reasons of safety or effectiveness. The petitioner has 
identified no data or other information suggesting that these products 
were withdrawn for reasons of safety or effectiveness. We have 
carefully reviewed our files for records concerning the withdrawal of 
these products from sale. We have also independently evaluated relevant 
literature and data for possible postmarketing adverse events. We have 
found no information that would indicate that these drug products were 
withdrawn from sale for reasons of safety or effectiveness.
    Accordingly, the Agency will continue to list CENESTIN (estrogens, 
conjugated synthetic A) Tablets, 0.3 mg, 0.45 mg, 0.625 mg, 0.9 mg, and 
1.25 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 
CENESTIN (estrogens, conjugated synthetic A) Tablets, 0.3 mg, 0.45 mg, 
0.625 mg, 0.9 mg, and 1.25 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 24, 2017.
Anna K. Abram,
Deputy Commissioner for Policy, Planning, Legislation, and Analysis.
[FR Doc. 2017-18376 Filed 8-29-17; 8:45 am]
 BILLING CODE 4164-01-P

Federal Register / Vol. 82, No. 167 / Wednesday, August 30, 2017 / Notices 41273

approval phase. These periods of time Dated: August 24, 2017. supplement ANDA 078311 in paper
were derived from the following dates: Anna K. Abram, format on August 29, 2013, and in
1. The date an exemption under Deputy Commissioner for Policy, Planning, electronic format on May 9, 2014.
Legislation, and Analysis. On April 14, 2016, FDA informed
section 505(i) of the Federal Food, Drug,
[FR Doc. 2017–18379 Filed 8–29–17; 8:45 am] Upsher-Smith that the applicant’s fed
and Cosmetic Act (the FD&C Act) (21
bioequivalence study failed to meet
U.S.C. 355(i)) became effective: October BILLING CODE 4164–01–P
FDA’s bioequivalence criteria and,
26, 2009. FDA has verified the therefore, requested that Upsher-Smith
applicant’s claim that the date the voluntarily seek withdrawal of ANDA
DEPARTMENT OF HEALTH AND
investigational new drug application 078311 under § 314.150(d) (21 CFR
HUMAN SERVICES
became effective was on October 26, 314.150(d)).
2009. Food and Drug Administration In a letter dated May 13, 2016,
2. The date the application was Upsher-Smith requested that FDA
[Docket No. FDA–2017–N–0002]
initially submitted with respect to the withdraw approval of ANDA 078311 for
human drug product under section Upsher-Smith Laboratories, Inc.; PROPRANOLOL HYDROCHLORIDE
505(b) of the FD&C Act: April 25, 2014. Withdrawal of Approval of an Extended-Release Capsules under
FDA has verified the applicant’s claim Abbreviated New Drug Application for § 314.150(d) because the new
that the new drug application (NDA) for PROPRANOLOL HYDROCHLORIDE bioequivalence data did not
XTORO (NDA 206307) was initially demonstrate therapeutic equivalence of
submitted on April 25, 2014. AGENCY: Food and Drug Administration, its product to the RLD, INDERAL LA. In
HHS. that letter, Upsher-Smith also waived
3. The date the application was any opportunity for a hearing otherwise
ACTION: Notice.
approved: December 17, 2014. FDA has provided under § 314.150(a).
verified the applicant’s claim that NDA SUMMARY: The Food and Drug Therefore, under section 505(e) of the
206307 was approved on December 17, Administration (FDA or the Agency) is Federal Food, Drug, and Cosmetic Act
2014. withdrawing approval of an abbreviated (FD&C Act) (21 U.S.C. 355(e)) and
This determination of the regulatory new drug application (ANDA) for § 314.150(d), and under authority
review period establishes the maximum PROPRANOLOL HYDROCHLORIDE delegated by the Commissioner of Food
potential length of a patent extension. Extended-Release Capsules, held by and Drugs to the Director, Center for
However, the USPTO applies several Upsher-Smith Laboratories, Inc. Drug Evaluation and Research, approval
statutory limitations in its calculations (Upsher-Smith), 6701 Evenstad Dr., of ANDA 078311, and all amendments
of the actual period for patent extension. Maple Grove, MN 55369. Upsher-Smith and supplements thereto, is withdrawn
In its application for patent extension, has voluntarily requested that approval (see DATES). Distribution of this product
this applicant seeks 1,058 days of patent of this application be withdrawn and in interstate commerce without an
term extension. has waived its opportunity for a hearing. approved application is illegal and
DATES: August 30, 2017. subject to regulatory action (see sections
Anyone with knowledge that any of 505(a) and 301(d) of the FD&C Act (21
the dates as published are incorrect may FOR FURTHER INFORMATION CONTACT:
Stefanie Kraus, Center for Drug U.S.C. 355(a) and 331(d)).
submit either electronic or written
Evaluation and Research, Food and Dated: August 24, 2017.
comments and, under 21 CFR 60.24, ask
for a redetermination (see DATES). Drug Administration, 10903 New Anna K. Abram,
Furthermore, as specified in 21 CFR Hampshire Ave., Bldg. 51, Rm. 6215, Deputy Commissioner for Policy, Planning,
60.30, any interested person may Silver Spring, MD 20993–0002, 301– Legislation, and Analysis.
petition FDA for a determination 796–9585. [FR Doc. 2017–18375 Filed 8–29–17; 8:45 am]
regarding whether the applicant for SUPPLEMENTARY INFORMATION: On March BILLING CODE 4164–01–P

extension acted with due diligence 6, 2009, FDA approved abbreviated new
during the regulatory review period. To drug application (ANDA) 078311 for
PROPRANOLOL HYDROCHLORIDE DEPARTMENT OF HEALTH AND
meet its burden, the petition must HUMAN SERVICES
comply with all the requirements of 21 Extended-Release Capsules, USP, 60
CFR 60.30, including but not limited to: milligrams (mg), 80 mg, 120 mg, and
Food and Drug Administration
Must be timely (see DATES), must be 160 mg. In a letter dated August 9, 2011,
filed in accordance with 21 CFR 10.20, FDA informed Upsher-Smith that it had [Docket No. FDA–2017–P–1461]
must contain sufficient facts to merit an concerns about the validity of
bioequivalence data submitted with Determination That CENESTIN
FDA investigation, and must certify that (Estrogens, Conjugated Synthetic A)
a true and complete copy of the petition ANDA 078311 from studies conducted
by a certain contract research Tablets, 0.3 Milligrams, 0.45 Milligrams,
has been served upon the patent 0.625 Milligrams, 0.9 Milligrams, and
organization, establishing
applicant. (See H. Rept. 857, part 1, 98th 1.25 Milligrams, Were Not Withdrawn
bioequivalence of Upsher-Smith’s
Cong., 2d sess., pp. 41–42, 1984.) From Sale for Reasons of Safety or
product to the reference listed drug
Petitions should be in the format Effectiveness
(RLD), INDERAL LA (propranolol
specified in 21 CFR 10.30.
hydrochloride) Extended Release AGENCY: Food and Drug Administration,
Submit petitions electronically to Capsules, 60 mg, 80 mg, 120 mg, and
mstockstill on DSK30JT082PROD with NOTICES

HHS.
https://www.regulations.gov at Docket 160 mg. In that letter, FDA directed ACTION: Notice.
No. FDA–2013–S–0610. Submit written Upsher-Smith to supplement its ANDA
petitions (two copies are required) to the with either: (1) New bioequivalence SUMMARY: The Food and Drug
Dockets Management Staff (HFA–305), studies or (2) re-assays of the samples Administration (FDA or Agency) has
Food and Drug Administration, 5630 from the original bioequivalence determined that CENESTIN (estrogens,
Fishers Lane, Rm. 1061, Rockville, MD studies. Upsher-Smith submitted new conjugated synthetic A) Tablets, 0.3
20852. fasted and fed bioequivalence studies to milligrams (mg), 0.45 mg, 0.625 mg, 0.9

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41274 Federal Register / Vol. 82, No. 167 / Wednesday, August 30, 2017 / Notices

mg, and 1.25 mg, were not withdrawn on March 24, 1999. CENESTIN is Dated: August 24, 2017.
from sale for reasons of safety or indicated for treatment of moderate to Anna K. Abram,
effectiveness. This determination will severe vasomotor symptoms due to Deputy Commissioner for Policy, Planning,
allow FDA to approve abbreviated new menopause and treatment of moderate Legislation, and Analysis.
drug applications (ANDAs) for these to severe symptoms of vulvar and [FR Doc. 2017–18376 Filed 8–29–17; 8:45 am]
products, if all other legal and vaginal atrophy due to menopause. BILLING CODE 4164–01–P
regulatory requirements are met. In 2016, Teva notified FDA that
FOR FURTHER INFORMATION CONTACT: CENESTIN (estrogens, conjugated
Bronwen Blass, Center for Drug synthetic A) Tablets, 0.3 mg, 0.45 mg, DEPARTMENT OF HEALTH AND
Evaluation and Research, Food and 0.625 mg, 0.9 mg, and 1.25 mg, were HUMAN SERVICES
Drug Administration, 10903 New being discontinued, and FDA moved the
Hampshire Ave. Bldg. 51, Rm. 6228, drug product to the ‘‘Discontinued Drug Food and Drug Administration
Silver Spring, MD 20993–0002, 301– Product List’’ section of the Orange [Docket Nos. FDA–2016–E–1283; FDA–
796–5092. Book. 2016–E–1291]
Foley & Lardner submitted a citizen
SUPPLEMENTARY INFORMATION: In 1984,
petition dated March 8, 2017 (Docket Determination of Regulatory Review
Congress enacted the Drug Price No. FDA–2017–P–1461), under 21 CFR Period for Purposes of Patent
Competition and Patent Term 10.30, requesting that the Agency Extension; KENGREAL
Restoration Act of 1984 (Pub. L. 98–417) determine whether CENESTIN
(the 1984 amendments), which (estrogens, conjugated synthetic A) AGENCY: Food and Drug Administration,
authorized the approval of duplicate Tablets, 0.3 mg, 0.45 mg, 0.625 mg, 0.9 HHS.
versions of drug products under an mg, and 1.25 mg, were withdrawn from ACTION: Notice.
ANDA procedure. ANDA applicants sale for reasons of safety or
must, with certain exceptions, show that SUMMARY: The Food and Drug
effectiveness. Administration (FDA or the Agency) has
the drug for which they are seeking After considering the citizen and
approval contains the same active determined the regulatory review period
reviewing Agency records and based on
ingredient in the same strength and for KENGREAL and is publishing this
the information we have at this time,
dosage form as the ‘‘listed drug,’’ which notice of that determination as required
FDA has determined under § 314.161
is a version of the drug that was by law. FDA has made the
that CENESTIN (estrogens, conjugated
previously approved. ANDA applicants determination because of the
synthetic A) Tablets, 0.3 mg, 0.45 mg,
do not have to repeat the extensive submission of applications to the
0.625 mg, 0.9 mg, and 1.25 mg, were not
clinical testing otherwise necessary to Director of the U.S. Patent and
withdrawn for reasons of safety or
gain approval of a new drug application Trademark Office (USPTO), Department
effectiveness. The petitioner has
(NDA). of Commerce, for the extension of a
identified no data or other information
The 1984 amendments include what patent which claims that human drug
suggesting that these products were
is now section 505(j)(7) of the Federal product.
withdrawn for reasons of safety or
Food, Drug, and Cosmetic Act (21 U.S.C. effectiveness. We have carefully DATES: Anyone with knowledge that any
355(j)(7)), which requires FDA to reviewed our files for records of the dates as published (in the
publish a list of all approved drugs. concerning the withdrawal of these SUPPLEMENTARY INFORMATION section) are
FDA publishes this list as part of the products from sale. We have also incorrect may submit either electronic
‘‘Approved Drug Products With independently evaluated relevant or written comments and ask for a
Therapeutic Equivalence Evaluations,’’ literature and data for possible redetermination by October 30, 2017.
which is known generally as the postmarketing adverse events. We have Furthermore, any interested person may
‘‘Orange Book.’’ Under FDA regulations, found no information that would petition FDA for a determination
drugs are removed from the list if the indicate that these drug products were regarding whether the applicant for
Agency withdraws or suspends withdrawn from sale for reasons of extension acted with due diligence
approval of the drug’s NDA or ANDA safety or effectiveness. during the regulatory review period by
for reasons of safety or effectiveness or Accordingly, the Agency will February 26, 2018. See ‘‘Petitions’’ in
if FDA determines that the listed drug continue to list CENESTIN (estrogens, the SUPPLEMENTARY INFORMATION section
was withdrawn from sale for reasons of conjugated synthetic A) Tablets, 0.3 mg, for more information.
safety or effectiveness (21 CFR 314.162). 0.45 mg, 0.625 mg, 0.9 mg, and 1.25 mg, ADDRESSES: You may submit comments
A person may petition the Agency to in the ‘‘Discontinued Drug Product List’’ as follows. Please note that late,
determine, or the Agency may section of the Orange Book. The untimely filed comments will not be
determine on its own initiative, whether ‘‘Discontinued Drug Product List’’ considered. Electronic comments must
a listed drug was withdrawn from sale delineates, among other items, drug be submitted on or before October 30,
for reasons of safety or effectiveness. products that have been discontinued 2017. The https://www.regulations.gov
This determination may be made at any from marketing for reasons other than electronic filing system will accept
time after the drug has been withdrawn safety or effectiveness. ANDAs that refer comments until midnight Eastern Time
from sale, but must be made prior to to CENESTIN (estrogens, conjugated at the end of October 30, 2017.
approving an ANDA that refers to the synthetic A) Tablets, 0.3 mg, 0.45 mg, Comments received by mail/hand
listed drug (§ 314.161 (21 CFR 314.161)). 0.625 mg, 0.9 mg, and 1.25 mg, may be delivery/courier (for written/paper
FDA may not approve an ANDA that approved by the Agency as long as they submissions) will be considered timely
mstockstill on DSK30JT082PROD with NOTICES

does not refer to a listed drug. meet all other legal and regulatory if they are postmarked or the delivery
CENESTIN (estrogens, conjugated requirements for the approval of service acceptance receipt is on or
synthetic A) Tablets, 0.3 mg, 0.45 mg, ANDAs. If FDA determines that labeling before that date.
0.625 mg, 0.9 mg, and 1.25 mg, is the for this drug product should be revised
subject of NDA 020992, held by Teva to meet current standards, the Agency Electronic Submissions
Branded Pharmaceutical Products R&D, will advise ANDA applicants to submit Submit electronic comments in the
Inc. (Teva), and was initially approved such labeling. following way:

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Document Created: 2017-08-30 04:08:38
Document Modified: 2017-08-30 04:08:38

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		Bronwen Blass, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave. Bldg. 51, Rm. 6228, Silver Spring, MD 20993-0002, 301- 796-5092.
FR Citation		82 FR 41273

82 FR 41273 - Determination That CENESTIN (Estrogens, Conjugated Synthetic A) Tablets, 0.3 Milligrams, 0.45 Milligrams, 0.625 Milligrams, 0.9 Milligrams, and 1.25 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 167 (August 30, 2017)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration