[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]
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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.
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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 http://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
http://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: [email protected].
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
[email protected]. 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 [email protected] 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 http://www.regulations.gov.
Transcripts: Transcripts for the November 10th meeting will be
posted, when available, at http://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