Determination That DANOCRINE (Danazol) Capsules, 50 Milligrams, 100 Milligrams, and 200 Milligrams, Were Not Withdrawn From Sale for Reasons of Safety or Effectiveness Except the Indication of Fibrocystic Breast Disease, Which Was Withdrawn From Sale for Reasons of Safety or Effectiveness, 42514-42515 [2018-18081]
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42514
Federal Register / Vol. 83, No. 163 / Wednesday, August 22, 2018 / Notices
ensuring the continued forward progress
of FDA’s Nutrition Innovation Strategy.
FOR FURTHER INFORMATION CONTACT:
Claudine Kavanaugh, Food and Drug
Administration, Office of Foods and
Veterinary Medicine, 10903 New
Hampshire Ave., Bldg. 1, Rm. 3218,
Silver Spring, MD 20993, 301–796–
4647.
[FR Doc. 2018–18072 Filed 8–21–18; 8:45 am]
In the
Federal Register of June 27, 2018 (83 FR
30180), FDA announced that it would
hold a public meeting entitled ‘‘FDA’s
Comprehensive, Multi-Year Nutrition
Innovation Strategy.’’ The public
meeting, which we held on July 26,
2018, was intended to give interested
persons an opportunity to discuss FDA’s
Nutrition Innovation Strategy and to
provide input on ways to modernize
FDA’s approach to better protect public
health while removing barriers to
industry innovation. We stated that the
topics to be addressed at the meeting
would include the following:
• Considering using a standard icon
to denote the claim ‘‘healthy’’ on food
labels.
• Creating a more efficient review
strategy for evaluating qualified health
claims on food labels.
• Discussing new or enhanced
labeling statements or claims that could
facilitate innovation to produce more
healthful foods and more healthful
consumer food choices.
• Modernizing the standards of
identity to provide more flexibility for
the development of healthier products,
while making sure consumers have
accurate information about these food
products.
• Providing opportunities to make
ingredient information more helpful to
consumers.
• FDA’s educational campaign for
consumers about the updated Nutrition
Facts label.
See 83 FR 30180 at 30181 to 30182.
The notice invited interested parties
to provide information on these and
other topics related to FDA’s Nutrition
Innovation Strategy. We asked that
comments be submitted on or before
August 27, 2018.
After the public meeting, we received
several requests to extend the comment
period. The requesters asserted that the
time period of 32 days was insufficient
to respond fully to FDA’s specific
request for comments and to ensure
comprehensive public input and allow
potential respondents to thoroughly
evaluate and address pertinent issues.
We have considered the requests and
are extending the comment period for
another 45 days, until October 11, 2018.
We believe that a 45-day extension
allows adequate time for interested
persons to submit comments while
SUPPLEMENTARY INFORMATION:
amozie on DSK3GDR082PROD with NOTICES1
Dated: August 16, 2018.
Leslie Kux,
Associate Commissioner for Policy.
VerDate Sep<11>2014
16:34 Aug 21, 2018
Jkt 244001
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2018–N–2999]
Determination That DANOCRINE
(Danazol) Capsules, 50 Milligrams, 100
Milligrams, and 200 Milligrams, Were
Not Withdrawn From Sale for Reasons
of Safety or Effectiveness Except the
Indication of Fibrocystic Breast
Disease, Which Was Withdrawn From
Sale for Reasons of Safety or
Effectiveness
AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or Agency) has
determined that DANOCRINE (danazol)
Capsules, 50 milligrams (mg), 100 mg,
and 200 mg, were not withdrawn from
sale for reasons of safety or
effectiveness, except with respect to the
indication of fibrocystic breast disease
that was withdrawn for reasons of safety
or effectiveness. This determination
means that FDA will not begin
procedures to suspend approval of
abbreviated new drug applications
(ANDAs) that refer to this drug product
and have removed the indication for
fibrocystic breast disease. This
determination also will allow FDA to
continue to approve ANDAs that refer to
this drug as long as they meet relevant
legal and regulatory requirements.
However, the Agency will not accept or
approve ANDAs for DANOCRINE
(danazol) Capsules, 50 mg, 100 mg, and
200 mg that include fibrocystic breast
disease as an indication.
FOR FURTHER INFORMATION CONTACT:
Stacy Kane, Center for Drug Evaluation
and Research, Food and Drug
Administration, 10903 New Hampshire
Ave., Bldg. 51, Rm. 6236, Silver Spring,
MD 20993–0002, 301–796–8363.
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
SUMMARY:
PO 00000
Frm 00056
Fmt 4703
Sfmt 4703
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 (§ 314.161 (21 CFR 314.161)).
FDA may not approve an ANDA that
does not refer to a listed drug.
Under § 314.161(a)(2), the Agency
must also determine whether a listed
drug was withdrawn from sale for
reasons of safety or effectiveness if
ANDAs that referred to the listed drug
have already been approved prior to its
market withdrawal. If the Agency
determines that a listed drug was
withdrawn from sale for reasons of
safety or effectiveness, and there are
approved ANDAs that reference that
listed drug, FDA will initiate a
proceeding to determine whether the
suspension of the ANDAs is also
required (§ 314.161(d)).
DANOCRINE (danazol) Capsules, 50
mg, 100 mg, and 200 mg, is the subject
of NDA 017557 held by Sanofi-Aventis,
and initially approved on June 21, 1976.
DANOCRINE is indicated for the
treatment of endometriosis amenable to
hormonal management, prevention of
attacks of angioedema of all types
(cutaneous, abdominal, and laryngeal)
in males and females, and fibrocystic
breast disease. Specifically, with respect
to fibrocystic breast disease, the labeling
states ‘‘Most cases of fibrocystic breast
disease may be treated by simple
E:\FR\FM\22AUN1.SGM
22AUN1
amozie on DSK3GDR082PROD with NOTICES1
Federal Register / Vol. 83, No. 163 / Wednesday, August 22, 2018 / Notices
measures (e.g., padded brassieres and
analgesics). In infrequent patients,
symptoms of pain and tenderness may
be severe enough to warrant treatment
by suppression of ovarian function.
DANOCRINE is usually effective in
decreasing nodularity, pain, and
tenderness. It should be stressed to the
patient that this treatment is not
innocuous in that it involves
considerable alterations of hormone
levels and that recurrence of symptoms
is very common after cessation of
therapy.’’
DANOCRINE (danazol) Capsules, 50
mg, 100 mg, and 200 mg, were
discontinued from sale in December
2004. FDA moved the product to the
‘‘Discontinued Drug Product List’’
section of the Orange Book at that time.
In a letter dated October 17, 2011,
Sanofi-Aventis requested the
withdrawal of the DANOCRINE
application. On July 19, 2013, the
Agency issued a Federal Register notice
withdrawing NDA 017557, the
application for DANOCRINE, effective
August 19, 2013.
After reviewing our records and based
on the information we have at this time,
FDA has determined that under
§ 314.161 DANOCRINE (danazol)
Capsules, 50 mg, 100 mg, and 200 mg,
were not withdrawn from sale for
reasons of safety or effectiveness, except
with respect to the indication for
fibrocystic breast disease. Fibrocystic
breast disease refers to mastalgia or
breast pain caused by benign
proliferative breast tissue. The term
fibrocystic breast disease is no longer
used, in part because it is not accurate
to describe the condition as a disease
when it is in fact the result of normal
physiologic changes.
DANOCRINE (danazol) has been
associated with two serious adverse
reactions: hepatocellular injury (i.e.,
hepatocellular injury, hepatocellular
jaundice, and hepatic failure) and an
increased risk of rhabdomyolysis in
patients taking danazol and statins.
These two adverse reactions were not
yet recognized when DANOCRINE
(danazol) was originally approved for
fibrocystic breast disease in 1980. Both
of these adverse reactions were added to
the safety labeling for the product
several years after the product was
initially approved. In addition,
androgenic adverse effects and a
contraindication for use in women who
are pregnant or attempting to become
pregnant limit the utility of
DANOCRINE (danazol) for the
fibrocystic breast disease indication.
The Agency conducted a review of the
benefit-risk profile for each indication of
DANOCRINE (danazol). For the
VerDate Sep<11>2014
16:34 Aug 21, 2018
Jkt 244001
treatment of fibrocystic breast disease,
the Agency concluded that the benefitrisk profile of the product is unfavorable
given the risk of potentially serious
adverse reactions and that the condition
is a benign, non-disease state. In
addition, many other treatment options
exist for this condition, including
dietary measures, use of supportive
undergarments and pain relievers such
as acetaminophen or non-steroidal antiinflammatory drug products. Many of
these treatment options present a very
low risk of adverse reactions. For the
indications of treatment of
endometriosis amenable to hormone
management and prevention of attacks
of angioedema of all types (cutaneous,
abdominal, and laryngeal) in males and
females, the Agency has determined that
DANOCRINE (danazol) continues to
have a favorable benefit-risk profile.
Accordingly, the Agency will
continue to list DANOCRINE (danazol)
Capsules, 50 mg, 100 mg, and 200 mg,
in the ‘‘Discontinued Drug Product List’’
section of the Orange Book. All
approved ANDAs have removed the
fibrocystic breast disease indication
from their labeling. In addition, FDA
will continue to approve ANDAs that
refer to DANOCRINE (danazol) Capsules
as long as they meet relevant legal and
regulatory requirements, but FDA will
not accept or approve ANDAs that refer
to this drug product and propose to
include the fibrocystic breast disease
indication.
Dated: August 16, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018–18081 Filed 8–21–18; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Meeting of the Advisory Committee on
Training in Primary Care Medicine and
Dentistry
Health Resources and Service
Administration (HRSA), Department of
Health and Human Services (HHS).
ACTION: Notice of meeting.
AGENCY:
In accordance with the
Federal Advisory Committee Act, this
notice announces that the Advisory
Committee on Training in Primary Care
Medicine and Dentistry (ACTPCMD)
will hold a public meeting. Information
about ACTPCMD and the agenda for this
meeting can be found on the ACTPCMD
website at: https://www.hrsa.gov/
advisory-committees/primarycaredentist/.
SUMMARY:
PO 00000
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Fmt 4703
Sfmt 4703
42515
September 10, 2018, 9:00 a.m.–
5:00 p.m. ET, and September 11, 2018,
8:30 a.m.–2:30 p.m. ET.
ADDRESSES: This meeting will be held in
person and offer virtual access through
teleconference and webinar. The
address for the meeting is 5600 Fishers
Lane, Rockville, Maryland 20857.
• Conference call-in number: 1–800–
238–9007; Passcode: 532320.
• Webinar link: https://
hrsa.connectsolutions.com/actpcmd.
FOR FURTHER INFORMATION CONTACT: Dr.
Kennita Carter, Designated Federal
Official (DFO), Division of Medicine
and Dentistry, Bureau of Health
Workforce, HRSA, 5600 Fishers Lane,
15N–116, Rockville, Maryland 20857;
301–945–3505; or KCarter@hrsa.gov.
SUPPLEMENTARY INFORMATION:
ACTPCMD provides advice and
recommendations to the Secretary of
HHS (Secretary) on policy, program
development, and other matters of
significance concerning the activities
under section 747 of Title VII of the
Public Health Service (PHS) Act, as it
existed upon the enactment of Section
749 of the PHS Act in 1998. ACTPCMD
prepares an annual report describing the
activities of the Committee, including
findings and recommendations made by
the Committee concerning the activities
under section 747, as well as training
programs in oral health and dentistry.
The annual report is submitted to the
Secretary and Chairman and ranking
members of the Senate Committee on
Health, Education, Labor and Pensions,
and the House of Representatives
Committee on Energy and Commerce.
The Committee also develops,
publishes, and implements performance
measures and guidelines for
longitudinal evaluations of programs
authorized under Title VII, Part C, of the
PHS Act, and recommends
appropriation levels for programs under
this Part.
During the September 10–11, 2018,
meeting, ACTPCMD will have follow-up
discussions on PHS Act section 747 and
oral health training programs, and
finalize its recommendations on funding
and appropriation levels to be included
in its 16th report. In addition, the
Committee will complete the 16th
report and a pending report on
promoting clinical trainee and faculty
well-being and mitigating burnout.
Agenda items are subject to change as
priorities dictate.
Members of the public will have the
opportunity to provide comments.
Public participants may submit written
statements in advance of the scheduled
meeting. Oral comments will be
honored in the order they are requested
DATES:
E:\FR\FM\22AUN1.SGM
22AUN1
]]>Agencies
[Federal Register Volume 83, Number 163 (Wednesday, August 22, 2018)]
[Notices]
[Pages 42514-42515]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-18081]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-N-2999]
Determination That DANOCRINE (Danazol) Capsules, 50 Milligrams,
100 Milligrams, and 200 Milligrams, Were Not Withdrawn From Sale for
Reasons of Safety or Effectiveness Except the Indication of Fibrocystic
Breast Disease, Which Was 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 DANOCRINE (danazol) Capsules, 50 milligrams (mg), 100
mg, and 200 mg, were not withdrawn from sale for reasons of safety or
effectiveness, except with respect to the indication of fibrocystic
breast disease that was withdrawn for reasons of safety or
effectiveness. This determination means that FDA will not begin
procedures to suspend approval of abbreviated new drug applications
(ANDAs) that refer to this drug product and have removed the indication
for fibrocystic breast disease. This determination also will allow FDA
to continue to approve ANDAs that refer to this drug as long as they
meet relevant legal and regulatory requirements. However, the Agency
will not accept or approve ANDAs for DANOCRINE (danazol) Capsules, 50
mg, 100 mg, and 200 mg that include fibrocystic breast disease as an
indication.
FOR FURTHER INFORMATION CONTACT: Stacy Kane, Center for Drug Evaluation
and Research, Food and Drug Administration, 10903 New Hampshire Ave.,
Bldg. 51, Rm. 6236, Silver Spring, MD 20993-0002, 301-796-8363.
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.
Under Sec. 314.161(a)(2), the Agency must also determine whether a
listed drug was withdrawn from sale for reasons of safety or
effectiveness if ANDAs that referred to the listed drug have already
been approved prior to its market withdrawal. If the Agency determines
that a listed drug was withdrawn from sale for reasons of safety or
effectiveness, and there are approved ANDAs that reference that listed
drug, FDA will initiate a proceeding to determine whether the
suspension of the ANDAs is also required (Sec. 314.161(d)).
DANOCRINE (danazol) Capsules, 50 mg, 100 mg, and 200 mg, is the
subject of NDA 017557 held by Sanofi-Aventis, and initially approved on
June 21, 1976. DANOCRINE is indicated for the treatment of
endometriosis amenable to hormonal management, prevention of attacks of
angioedema of all types (cutaneous, abdominal, and laryngeal) in males
and females, and fibrocystic breast disease. Specifically, with respect
to fibrocystic breast disease, the labeling states ``Most cases of
fibrocystic breast disease may be treated by simple
[[Page 42515]]
measures (e.g., padded brassieres and analgesics). In infrequent
patients, symptoms of pain and tenderness may be severe enough to
warrant treatment by suppression of ovarian function. DANOCRINE is
usually effective in decreasing nodularity, pain, and tenderness. It
should be stressed to the patient that this treatment is not innocuous
in that it involves considerable alterations of hormone levels and that
recurrence of symptoms is very common after cessation of therapy.''
DANOCRINE (danazol) Capsules, 50 mg, 100 mg, and 200 mg, were
discontinued from sale in December 2004. FDA moved the product to the
``Discontinued Drug Product List'' section of the Orange Book at that
time. In a letter dated October 17, 2011, Sanofi-Aventis requested the
withdrawal of the DANOCRINE application. On July 19, 2013, the Agency
issued a Federal Register notice withdrawing NDA 017557, the
application for DANOCRINE, effective August 19, 2013.
After reviewing our records and based on the information we have at
this time, FDA has determined that under Sec. 314.161 DANOCRINE
(danazol) Capsules, 50 mg, 100 mg, and 200 mg, were not withdrawn from
sale for reasons of safety or effectiveness, except with respect to the
indication for fibrocystic breast disease. Fibrocystic breast disease
refers to mastalgia or breast pain caused by benign proliferative
breast tissue. The term fibrocystic breast disease is no longer used,
in part because it is not accurate to describe the condition as a
disease when it is in fact the result of normal physiologic changes.
DANOCRINE (danazol) has been associated with two serious adverse
reactions: hepatocellular injury (i.e., hepatocellular injury,
hepatocellular jaundice, and hepatic failure) and an increased risk of
rhabdomyolysis in patients taking danazol and statins. These two
adverse reactions were not yet recognized when DANOCRINE (danazol) was
originally approved for fibrocystic breast disease in 1980. Both of
these adverse reactions were added to the safety labeling for the
product several years after the product was initially approved. In
addition, androgenic adverse effects and a contraindication for use in
women who are pregnant or attempting to become pregnant limit the
utility of DANOCRINE (danazol) for the fibrocystic breast disease
indication.
The Agency conducted a review of the benefit-risk profile for each
indication of DANOCRINE (danazol). For the treatment of fibrocystic
breast disease, the Agency concluded that the benefit-risk profile of
the product is unfavorable given the risk of potentially serious
adverse reactions and that the condition is a benign, non-disease
state. In addition, many other treatment options exist for this
condition, including dietary measures, use of supportive undergarments
and pain relievers such as acetaminophen or non-steroidal anti-
inflammatory drug products. Many of these treatment options present a
very low risk of adverse reactions. For the indications of treatment of
endometriosis amenable to hormone management and prevention of attacks
of angioedema of all types (cutaneous, abdominal, and laryngeal) in
males and females, the Agency has determined that DANOCRINE (danazol)
continues to have a favorable benefit-risk profile.
Accordingly, the Agency will continue to list DANOCRINE (danazol)
Capsules, 50 mg, 100 mg, and 200 mg, in the ``Discontinued Drug Product
List'' section of the Orange Book. All approved ANDAs have removed the
fibrocystic breast disease indication from their labeling. In addition,
FDA will continue to approve ANDAs that refer to DANOCRINE (danazol)
Capsules as long as they meet relevant legal and regulatory
requirements, but FDA will not accept or approve ANDAs that refer to
this drug product and propose to include the fibrocystic breast disease
indication.
Dated: August 16, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-18081 Filed 8-21-18; 8:45 am]
BILLING CODE 4164-01-P
