Labeling Lower-Dose Estrogen-Alone Products for Symptoms of Vulvar and Vaginal Atrophy, 58258-58259 [2015-24509]
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Federal Register / Vol. 80, No. 187 / Monday, September 28, 2015 / Notices
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Dated: September 23, 2015.
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[FR Doc. 2015–24559 Filed 9–25–15; 8:45 am]
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tkelley on DSK3SPTVN1PROD with NOTICES
SUMMARY:
VerDate Sep<11>2014
17:19 Sep 25, 2015
Jkt 235001
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2015–N–3275]
Labeling Lower-Dose Estrogen-Alone
Products for Symptoms of Vulvar and
Vaginal Atrophy
AGENCY:
Food and Drug Administration,
HHS.
Notice of public meeting;
request for comments.
ACTION:
The Food and Drug
Administration (FDA) is announcing a
public meeting and an opportunity for
public comment on the topic of the
labeling for lower-dose estrogen
products delivered vaginally, intended
to treat moderate to severe symptoms of
vulvar and vaginal atrophy (VVA) due
to menopause. Lower-dose estrogen
products means products that contain
less than the 0.625 milligrams (mg) of
conjugated estrogens used in the
Women’s Health Initiative Study, and
estradiol products containing 0.0375 mg
and below. Lower-dose estrogen
products are now approved for the
treatment of moderate to severe
symptoms of VVA due to menopause,
and some in the scientific/medical
community have questioned whether
the current ‘‘Boxed Warnings’’ section
in the labeling is applicable in whole or
in part to these lower-dose estrogen
products. This meeting, a scientific
workshop, will provide an opportunity
for FDA to seek input from experts on
the Boxed Warnings section, estrogen
exposure data, and pharmacokinetic
(PK)/pharmacodynamic (PD)
relationships relative to labeling lowerdose estrogen-alone products intended
SUMMARY:
PO 00000
Frm 00028
Fmt 4703
Sfmt 4703
to treat moderate to severe symptoms of
VVA due to menopause.
DATES: The public meeting will be held
on November 10, 2015, from 8:30 a.m.
to 5 p.m. Registration to attend the
meeting must be received by October 16,
2015, with onsite registration available
between 7 a.m. and 8 a.m. the day of the
meeting. See the SUPPLEMENTARY
INFORMATION section for information on
how to register for this meeting. Submit
either electronic or written comments
by October 16, 2015.
ADDRESSES: The meeting will be held at
the FDA White Oak Campus, 10903
New Hampshire Ave., Bldg. 31
Conference Center, Section A of the
Great Room (Rm. 1503), Silver Spring,
MD 20993. Entrance for the public
meeting participants (non-FDA
employees) is through Building 1, where
routine security check procedures will
be performed. For more information on
parking and security procedures, please
refer to https://www.fda.gov/AboutFDA/
WorkingatFDA/BuildingsandFacilities/
WhiteOakCampusInformation/
ucm241740.htm.
Submit electronic comments to
www.regulations.gov. Submit written
comments to the Division of Dockets
Management (HFA–305), Food and Drug
Administration, 5630 Fishers Lane, Rm.
1061, Rockville, MD 20852. All
comments should be identified with the
docket number found in brackets in the
heading of this document.
FDA will post the agenda
approximately 5 days before the meeting
at https://www.fda.gov/Drugs/
NewsEvents/ucm459690.htm.
FOR FURTHER INFORMATION CONTACT:
Kimberly Shiley, Center for Drug
Evaluation and Research, Food and
Drug Administration, 10903 New
Hampshire Ave. Bldg. 22, Rm. 5377,
Silver Spring, MD 20993, 301–796–
2117, email:
Kimberly.Shiley@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Introduction
The loss of ovarian function with
menopause leads to a drastic reduction
in circulating estrogen concentration,
which in turn leads to physiologic
changes to the vulva, vagina, and lower
urinary tract. Reduced circulating
estrogen concentration results in an
increase in vaginal pH, a thinning and
reduction of the folds of the vaginal
lining, reduction of vaginal secretions,
and loss of elasticity in vaginal tissues.
Symptoms of decreased circulating
estrogen include vaginal and vulvar
itching and/or irritation, vaginal dryness
and vaginal pain (dyspareunia), and/or
bleeding with intercourse. Not all
E:\FR\FM\28SEN1.SGM
28SEN1
Federal Register / Vol. 80, No. 187 / Monday, September 28, 2015 / Notices
tkelley on DSK3SPTVN1PROD with NOTICES
postmenopausal women have symptoms
of VVA that require treatment, but some
women (particularly those 5 to10 years
postmenopausal), when asked, will
report one or more of the above
symptoms, which they deem to be
bothersome and self-categorize as
moderate to severe in intensity. To date,
the Agency has approved estrogen
products (both estrogen-alone and
estrogen plus progestin) for the
indications of ‘‘treatment of moderate to
severe vaginal dryness, a symptom of
vulvar and vaginal atrophy due to
menopause’’ and ‘‘treatment of
moderate to severe dyspareunia, a
symptom of vulvar and vaginal atrophy
due to menopause.’’
Estrogen-alone products have Boxed
Warnings stating:
(1) There is an increased risk of
endometrial cancer in a woman with a
uterus who uses unopposed estrogen;
(2) estrogen-alone therapy should not
be used for the prevention of
cardiovascular disease or dementia;
(3) an increased risk of stroke and
deep vein thrombosis was reported in
the Women’s Health Initiative (WHI)
estrogen-alone substudy; and
(4) an increased risk of probable
dementia in postmenopausal women 65
years of age and older was reported in
WHI Memory Study (WHIMS) estrogenalone ancillary study.
The WHI estrogen-alone studies
evaluated only a single estrogen dose
consisting of 0.625 mg of conjugated
estrogen. As lower-dose estrogen
products are now approved for the
treatment of moderate to severe
symptoms of VVA due to menopause,
some in the scientific/medical
community have questioned whether
these statements in the Boxed Warning
section are applicable in whole or in
part to the lower-dose estrogen
products.
II. Discussion Topics
The scientific workshop on November
10th will include discussions of
scientific challenges related to the
following topics:
• The relevance to lower-dose
estrogen products of the Boxed
Warnings related to the WHI findings
that: (1) Estrogens should not be used
for the prevention of cardiovascular
disease or dementia, (2) there is an
increased risk of stroke and deep vein
thrombosis in women treated with
estrogen-alone, and (3) there is an
increased risk of probable dementia in
postmenopausal women 65 years of age
and older treated with estrogen-alone.
• How to educate prescribers on the
interpretation of estrogen exposure data
across various estrogen dosage forms
VerDate Sep<11>2014
17:19 Sep 25, 2015
Jkt 235001
indicated for treatment of moderate to
severe symptoms of vulvar and vaginal
atrophy due to menopause. Presentation
of basic PK and clinical pharmacology
data concepts and an informed
framework for comparing various
estrogen products for prescribing
purposes.
• Discuss the level of available data
supporting that a given estrogen serum
concentration is or is not related to
adverse outcomes (for example,
pulmonary emboli, deep venous
thrombosis, and myocardial infarction).
• Presentation and discussion of PD
biomarkers for thrombosis. Presentation
of a comparison of metabolic profiles
from various products, key clotting
factors responsible for thrombosis, and
PK/PD relationships.
III. Meeting Attendance and
Participation
If you wish to attend this meeting,
email FDAVVAworkshop@fda.hhs.gov.
Please register by October 16, 2015.
Those who are unable to attend the
meeting in person can register to view
a live Webcast of the meeting. You will
be asked to indicate in your registration
whether you plan to attend in person or
via the Webcast. Your registration
should also contain your complete
contact information, including name,
title, affiliation, address, email address,
and telephone number.
Seating will be limited, so early
registration is recommended.
Registration is free and will be on a firstcome, first-served basis. However, FDA
may limit the number of participants
from each organization based on space
limitations. Registrants will receive
confirmation once they have been
accepted. Onsite registration on the day
of the meeting will be based on space
availability. If you need special
accommodations because of disability,
please contact Kimberly Shiley (see FOR
FURTHER INFORMATION CONTACT) at least 7
days before the meeting.
FDA will hold an open public
comment session during the November
10th public meeting to give the public
an opportunity to comment. Register for
this session at
FDAVVAworkshop@fda.hhs.gov by
October 16, 2015. Additional
registration will occur at the registration
desk on the day of the meeting on a
first-come, first-served basis if there is
still time available during this session.
Docket Comments: Regardless of
attendance at the meeting, you can
submit electronic or written comments,
including responses to the public docket
(see ADDRESSES), by October 16, 2015.
Received comments may be seen in the
Division of Dockets Management
PO 00000
Frm 00029
Fmt 4703
Sfmt 4703
58259
between 9 a.m. and 4 p.m., Monday
through Friday, and will be posted to
the docket at https://
www.regulations.gov.
Transcripts: Transcripts for the
November 10th meeting will be posted,
when available, at https://www.fda.gov/
Drugs/NewsEvents/ucm401167.htm.
Dated: September 22, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015–24509 Filed 9–25–15; 8:45 am]
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DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA–2015–N–3326]
Biosimilar User Fee Act; Public
Meeting
AGENCY:
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HHS.
Notice of public meeting;
request for comments.
ACTION:
The Food and Drug
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announcing a public meeting on the
reauthorization of the Biosimilar User
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FDA to collect user fees for the process
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September 2017. At that time, new
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and Cosmetic Act (the FD&C Act)
requires that FDA begin the BsUFA
reauthorization process by publishing a
notice in the Federal Register
requesting public input and holding a
public meeting where the public may
present its views on the reauthorization.
FDA invites public comment on the
BsUFA performance goals as the Agency
begins the process to reauthorize the
program in FYs 2018–2022.
DATES: The public meeting will be held
on December 18, 2015, from 9 a.m. to 2
p.m. Registration to attend the meeting
must be received by November 18, 2015.
See section III of this document for
information on how to register for the
meeting. Submit written or electronic
comments by January 19, 2016.
ADDRESSES: The meeting will be held at
the FDA White Oak Campus, 10903
New Hampshire Ave., Bldg. 31
Conference Center, in section B and C
of the Great Room (Rm. 1503), Silver
Spring, MD 20993. Participants must
SUMMARY:
E:\FR\FM\28SEN1.SGM
28SEN1
]]>Agencies
[Federal Register Volume 80, Number 187 (Monday, September 28, 2015)]
[Notices]
[Pages 58258-58259]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-24509]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2015-N-3275]
Labeling Lower-Dose Estrogen-Alone Products for Symptoms of
Vulvar and Vaginal Atrophy
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public meeting; request for comments.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing a public
meeting and an opportunity for public comment on the topic of the
labeling for lower-dose estrogen products delivered vaginally, intended
to treat moderate to severe symptoms of vulvar and vaginal atrophy
(VVA) due to menopause. Lower-dose estrogen products means products
that contain less than the 0.625 milligrams (mg) of conjugated
estrogens used in the Women's Health Initiative Study, and estradiol
products containing 0.0375 mg and below. Lower-dose estrogen products
are now approved for the treatment of moderate to severe symptoms of
VVA due to menopause, and some in the scientific/medical community have
questioned whether the current ``Boxed Warnings'' section in the
labeling is applicable in whole or in part to these lower-dose estrogen
products. This meeting, a scientific workshop, will provide an
opportunity for FDA to seek input from experts on the Boxed Warnings
section, estrogen exposure data, and pharmacokinetic (PK)/
pharmacodynamic (PD) relationships relative to labeling lower-dose
estrogen-alone products intended to treat moderate to severe symptoms
of VVA due to menopause.
DATES: The public meeting will be held on November 10, 2015, from 8:30
a.m. to 5 p.m. Registration to attend the meeting must be received by
October 16, 2015, with onsite registration available between 7 a.m. and
8 a.m. the day of the meeting. See the SUPPLEMENTARY INFORMATION
section for information on how to register for this meeting. Submit
either electronic or written comments by October 16, 2015.
ADDRESSES: The meeting will be held at the FDA White Oak Campus, 10903
New Hampshire Ave., Bldg. 31 Conference Center, Section A of the Great
Room (Rm. 1503), Silver Spring, MD 20993. Entrance for the public
meeting participants (non-FDA employees) is through Building 1, where
routine security check procedures will be performed. For more
information on parking and security procedures, please refer to https://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
Submit electronic comments to www.regulations.gov. Submit written
comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. All
comments should be identified with the docket number found in brackets
in the heading of this document.
FDA will post the agenda approximately 5 days before the meeting at
https://www.fda.gov/Drugs/NewsEvents/ucm459690.htm.
FOR FURTHER INFORMATION CONTACT: Kimberly Shiley, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave. Bldg. 22, Rm. 5377, Silver Spring, MD 20993, 301-796-
2117, email: Kimberly.Shiley@fda.hhs.gov.
SUPPLEMENTARY INFORMATION:
I. Introduction
The loss of ovarian function with menopause leads to a drastic
reduction in circulating estrogen concentration, which in turn leads to
physiologic changes to the vulva, vagina, and lower urinary tract.
Reduced circulating estrogen concentration results in an increase in
vaginal pH, a thinning and reduction of the folds of the vaginal
lining, reduction of vaginal secretions, and loss of elasticity in
vaginal tissues. Symptoms of decreased circulating estrogen include
vaginal and vulvar itching and/or irritation, vaginal dryness and
vaginal pain (dyspareunia), and/or bleeding with intercourse. Not all
[[Page 58259]]
postmenopausal women have symptoms of VVA that require treatment, but
some women (particularly those 5 to10 years postmenopausal), when
asked, will report one or more of the above symptoms, which they deem
to be bothersome and self-categorize as moderate to severe in
intensity. To date, the Agency has approved estrogen products (both
estrogen-alone and estrogen plus progestin) for the indications of
``treatment of moderate to severe vaginal dryness, a symptom of vulvar
and vaginal atrophy due to menopause'' and ``treatment of moderate to
severe dyspareunia, a symptom of vulvar and vaginal atrophy due to
menopause.''
Estrogen-alone products have Boxed Warnings stating:
(1) There is an increased risk of endometrial cancer in a woman
with a uterus who uses unopposed estrogen;
(2) estrogen-alone therapy should not be used for the prevention of
cardiovascular disease or dementia;
(3) an increased risk of stroke and deep vein thrombosis was
reported in the Women's Health Initiative (WHI) estrogen-alone
substudy; and
(4) an increased risk of probable dementia in postmenopausal women
65 years of age and older was reported in WHI Memory Study (WHIMS)
estrogen-alone ancillary study.
The WHI estrogen-alone studies evaluated only a single estrogen
dose consisting of 0.625 mg of conjugated estrogen. As lower-dose
estrogen products are now approved for the treatment of moderate to
severe symptoms of VVA due to menopause, some in the scientific/medical
community have questioned whether these statements in the Boxed Warning
section are applicable in whole or in part to the lower-dose estrogen
products.
II. Discussion Topics
The scientific workshop on November 10th will include discussions
of scientific challenges related to the following topics:
The relevance to lower-dose estrogen products of the Boxed
Warnings related to the WHI findings that: (1) Estrogens should not be
used for the prevention of cardiovascular disease or dementia, (2)
there is an increased risk of stroke and deep vein thrombosis in women
treated with estrogen-alone, and (3) there is an increased risk of
probable dementia in postmenopausal women 65 years of age and older
treated with estrogen-alone.
How to educate prescribers on the interpretation of
estrogen exposure data across various estrogen dosage forms indicated
for treatment of moderate to severe symptoms of vulvar and vaginal
atrophy due to menopause. Presentation of basic PK and clinical
pharmacology data concepts and an informed framework for comparing
various estrogen products for prescribing purposes.
Discuss the level of available data supporting that a
given estrogen serum concentration is or is not related to adverse
outcomes (for example, pulmonary emboli, deep venous thrombosis, and
myocardial infarction).
Presentation and discussion of PD biomarkers for
thrombosis. Presentation of a comparison of metabolic profiles from
various products, key clotting factors responsible for thrombosis, and
PK/PD relationships.
III. Meeting Attendance and Participation
If you wish to attend this meeting, email
FDAVVAworkshop@fda.hhs.gov. Please register by October 16, 2015. Those
who are unable to attend the meeting in person can register to view a
live Webcast of the meeting. You will be asked to indicate in your
registration whether you plan to attend in person or via the Webcast.
Your registration should also contain your complete contact
information, including name, title, affiliation, address, email
address, and telephone number.
Seating will be limited, so early registration is recommended.
Registration is free and will be on a first-come, first-served basis.
However, FDA may limit the number of participants from each
organization based on space limitations. Registrants will receive
confirmation once they have been accepted. Onsite registration on the
day of the meeting will be based on space availability. If you need
special accommodations because of disability, please contact Kimberly
Shiley (see FOR FURTHER INFORMATION CONTACT) at least 7 days before the
meeting.
FDA will hold an open public comment session during the November
10th public meeting to give the public an opportunity to comment.
Register for this session at FDAVVAworkshop@fda.hhs.gov by October 16,
2015. Additional registration will occur at the registration desk on
the day of the meeting on a first-come, first-served basis if there is
still time available during this session.
Docket Comments: Regardless of attendance at the meeting, you can
submit electronic or written comments, including responses to the
public docket (see ADDRESSES), by October 16, 2015. Received comments
may be seen in the Division of Dockets Management between 9 a.m. and 4
p.m., Monday through Friday, and will be posted to the docket at https://www.regulations.gov.
Transcripts: Transcripts for the November 10th meeting will be
posted, when available, at https://www.fda.gov/Drugs/NewsEvents/ucm401167.htm.
Dated: September 22, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-24509 Filed 9-25-15; 8:45 am]
BILLING CODE 4164-01-P
