[Federal Register: February 17, 2004 (Volume 69, Number 31)]
[Notices]
[Page 7492-7493]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr17fe04-97]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 1998D-0834]
Draft Guidance for Industry on Labeling for Noncontraceptive
Estrogen Drug Products for the Treatment of Vasomotor Symptoms and
Vulvar and Vaginal Atrophy Symptoms--Prescribing Information for Health
Care Providers and Patient Labeling; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
availability of a draft guidance for industry entitled ``Labeling
Guidance for Noncontraceptive Estrogen Drug Products for the Treatment
of Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms--
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 The draft guidance is intended to assist applicants in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 third draft of the guidance, which initially
issued in September 1999.
DATES: Submit written or electronic comments on the draft guidance by
April 19, 2004. 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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug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on the draft guidance to the Division of Dockets Management (HFA-305),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access to the draft guidance document.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 (HFD-580), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-827-4243.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a draft guidance for industry
entitled ``Labeling Guidance for Noncontraceptive Estrogen Drug
Products for the Treatment of Vasomotor Symptoms and Vulvar and Vaginal
Atrophy Symptoms--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
September 27, 1999 (64 FR 52100). However, on September 10, 2002, the
agency withdrew the draft guidance (67 FR 57432), pending consideration
of the results from the National Institutes of Health (NIH) Women's
Health Initiative (WHI). In the Federal Register of February 3, 2003
(68 FR 5300), the agency issued a second draft reflecting the agency's
thinking after considering the results of the WHI substudy concerning
overall risks and benefits of hormone therapy for postmenopausal
symptoms.
The agency is issuing this third draft guidance to address comments
received, to incorporate new study results from the WHI, and to better
inform prescribers and patients regarding the availability of the
lowest effective dose for these drug products. This third draft
supersedes the second draft and reflects the agency's thinking after
considering these issues. Further revisions to the guidance may be
necessary as additional information becomes available.
On May 31, 2002, the WHI study of conjugated estrogens 0.625
milligram (mg)/day (CE) plus medroxyprogesterone acetate 2.5 mg/day
(MPA) in postmenopausal women was stopped after a mean of 5.2 years of
followup because the test statistic 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 through April 30, 2002, regarding increased risks for
invasive breast cancer, heart attacks, strokes, and venous
thromboembolism rates, including pulmonary embolism, became available
July 17, 2002. On March 17, 2003, additional information was published
about health-related quality of life.
The Women's Health Initiative Memory Study (WHIMS), a substudy of
the WHI, was published on May 28, 2003. It concluded that women treated
in the study with conjugated estrogens 0.625 mg combined with
medroxyprogesterone acetate 2.5 mg have a greater risk of developing
probable dementia than those on placebo. Detailed information about
WHIMS is available at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.nih.gov/PHTindex.htm.
This third draft of the guidance retains and updates the labeling
recommendations regarding the results of the WHI study and recommends
adding risk information related to the results of the WHIMS study to
appropriate sections of the labeling, including the boxed warning. It
also adds to the WARNINGS section that use of estrogen-containing
products may increase the risk of mammographic abnormalities. In
addition, because it is unknown whether risks for postmenopausal women
prescribed estrogen-containing products for the treatment of moderate
to severe vasomotor symptoms and moderate to severe symptoms of vulvar
and vaginal atrophy differ depending on the dose prescribed, the
guidance recommends
[[Page 7493]]
that labeling include a statement as to whether or not the lowest
effective dose for the product has been identified.
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.
II. Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding the draft
guidance. Two copies of mailed comments are to be submitted, except
that individuals may submit one 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: February 9, 2004.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 04-3330 Filed 2-11-04; 11:58 am]
BILLING CODE 4160-01-S