[Federal Register: November 16, 2005 (Volume 70, Number 220)]
[Notices]
[Page 69578-69579]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr16no05-85]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 1998D-0834 (formerly Docket No. 98D-0834]
Draft Guidance for Industry on Noncontraceptive Estrogen Drug
Products for the Treatment of Vasomotor Symptoms and Vulvar and Vaginal
Atrophy Symptoms--Recommended Prescribing Information for Health Care
Providers and Patient Labeling; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled
``Noncontraceptive Estrogen Drug Products for the Treatment of
Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms--Recommended
Prescribing Information for Health Care Providers and Patient
Labeling.'' The draft guidance is intended to assist applicants in
developing labeling for new drug applications (NDAs) for such drug
products. This is the fifth draft of the guidance, which FDA initially
published for comment in October 1998.
DATES: Submit written or electronic comments on the draft guidance by
January 17, 2006. General comments on agency guidance documents are
welcome at any time.
ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug
Evaluation and Research, Food and Drug Administration, 5600 Fishers
Lane, Rockville, MD 20857. Send one self-addressed adhesive label to
assist that office in processing your requests. Submit written comments
on the draft guidance to the Division of Dockets Management (HFA-305),
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville,
MD 20852. Submit electronic comments to http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/dockets/ecomments.
See the SUPPLEMENTARY INFORMATION section for electronic
access to the draft guidance document.
FOR FURTHER INFORMATION CONTACT: Margaret Kober, Center for Drug
Evaluation and Research (5359), Food and Drug Administration, 10903 New
Hampshire Ave., bldg. 22, rm. 5376, Silver Spring, MD 20993, 301-796-
0934.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance entitled
``Noncontraceptive Estrogen Drug Products for the Treatment of
Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms--Recommended
Prescribing Information for Health Care Providers and Patient
Labeling.'' The draft guidance describes the recommended labeling for
health care providers and patient instructions for inclusion in NDAs.
A draft of this guidance was first issued on October 15, 1998 (63
FR 55399). After public review and comment, a second version of this
draft guidance was issued on September 27, 1999 (64 FR 52100). On May
31, 2002, the National Institutes of Health Women's Health Initiative
(WHI) study of oral conjugated estrogens (CE 0.625 milligram (mg)) plus
medroxyprogesterone acetate (MPA 2.5 mg)/day in postmenopausal women
was stopped after a mean of 5.2 years of followup because test
statistics for invasive breast cancer exceeded the stopping boundary
for this adverse effect and the global index statistic supported risks
exceeding benefits. Data on the major clinical outcomes regarding
increased risks for invasive breast cancer, heart attacks, strokes, and
venous thromboembolism rates, including pulmonary embolism, became
available July 17, 2002. Consequently, the agency withdrew the draft
guidance on September 10, 2002 (67 FR 57432), pending consideration of
the results from the WHI study. In the Federal Register of February 3,
2003 (68 FR 5300), the agency issued a third draft reflecting the
agency's thinking after consideration of the results from the WHI study
concerning overall risks and benefits of hormone therapy for
postmenopausal symptoms.
A fourth draft of this guidance was issued on February 17, 2004 (69
FR 7492), to address comments received, incorporate new study results
from the Women's Health Initiative Memory Study (WHIMS), a substudy of
the WHI study, and better inform prescribers and patients regarding the
availability of the lowest effective dose for these drug products. (The
results of the WHIMS substudy were published on May 28, 2003.
Postmenopausal women, 65 to 79 years of age, during 4 years of
treatment with CE 0.625 mg plus MPA 2.5 mg/day had a greater risk of
developing probable dementia than those on placebo.)
The agency is issuing this fifth draft of the guidance to
incorporate new study results from the WHI and WHIMS studies. This
fifth draft supersedes the fourth draft, and retains and updates the
labeling recommendations regarding the results of the WHI study and the
WHIMS substudy for postmenopausal women treated with CE 0.625 mg plus
MPA 2.5 mg/day. It also reflects the agency's thinking after
consideration of the results published on April 14, 2004, of the WHI
study, and the results published on June 23/30, 2004, of the WHIMS
substudy for postmenopausal women with prior hysterectomy treated with
CE 0.625 mg/day alone. The WHI study of CE 0.625 mg/day alone in
postmenopausal women with prior hysterectomy was stopped after a mean
followup of 6.8 years because of an increased risk of stroke. The WHIMS
substudy of CE 0.625 mg/day alone was stopped after a mean followup of
5.2 years. Estrogen-alone therapy did not reduce probable dementia or
cognitive decline incidence and increased the risk for both endpoints
combined. This fifth draft of the guidance recommends adding risk
information related to the results of the WHI and WHIMS estrogen-alone
studies to appropriate sections of labeling including the boxed
warning. Further revisions to the guidance may be necessary as
additional information becomes available.
This level 1 draft guidance is being issued consistent with FDA's
good guidance practices regulation (21 CFR 10.115). The draft guidance,
when finalized, will represent the agency's current thinking on
labeling for noncontraceptive estrogen drug products for the treatment
of moderate to severe vasomotor symptoms and moderate to severe vulvar
and vaginal atrophy symptoms. It does not create or confer any rights
for or on any person and does not operate to bind FDA or the public. An
alternative approach may be used if such approach satisfies the
requirements of the applicable statutes and regulations.
[[Page 69579]]
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document.
Submit a single copy of electronic comments or two paper copies of any
mailed comments, except that individuals may submit one paper copy.
Comments are to be identified with the docket number found in brackets
in the heading of this document. The draft guidance and received
comments may be seen in the Division of Dockets Management between 9
a.m. and 4 p.m., Monday through Friday.
III. Electronic Access
Persons with access to the Internet may obtain the document at
either http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/cder/guidance/index.htm or http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www
.fda.gov/ohrms/dockets/default.htm.
Dated: November 8, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-22754 Filed 11-15-05; 8:45 am]
BILLING CODE 4160-01-S