[Federal Register: January 31, 2003 (Volume 68, Number 21)]
[Notices]
[Page 5025-5026]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr31ja03-89]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 03D-0007]
Draft Guidance for Industry on Estrogen and Estrogen/Progestin
Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal
Atrophy Symptoms--Recommendations for Clinical Evaluation; 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availability of a draft guidance for industry entitled ``Estrogen and
Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar
and Vaginal Atrophy Symptoms--Recommendations for Clinical
Evaluation.'' The agency is revising its guidance for industry entitled
``Guidance for Clinical Evaluation of Combination Estrogen/Progestin-
Containing Drug Products Used for Hormone Replacement Therapy of
Postmenopausal Women,'' which was issued in March 1995 (the 1995
guidance). Once finalized, this guidance will replace the 1995
guidance.
DATES: Submit written or electronic comments on the draft guidance by
April 1, 2003. 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ADDRESSES: Submit written requests for single copies of the draft
guidance to the Division of Drug Information (HFD-240), Center for Drug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 on self-addressed adhesive label to
assist that office in processing your requests. Submit written comments
on the draft guidance to the Dockets Management Branch (HFA-305), Food
and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD
20852. Submit electronic comments to http://
[[Page 5026]]
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section for electronic access to the draft guidance document.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
In March 1995, the agency issued a guidance entitled ``Guidance for
Clinical Evaluation of Combination Estrogen/Progestin-Containing Drug
Products Used for Hormone Replacement Therapy of Postmenopausal
Women''. The agency was revising the 1995 guidance when the results of
a substudy of the National Institutes of Health (NIH) Women's Health
Initiative (WHI) trial were made available to the public.\1\ In light
of the interim results of the WHI substudy, on September 10, 2002 (67
FR 57432), the agency withdrew the 1995 guidance. Once finalized, this
guidance will replace the 1995 guidance.
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\1\ The results of the NIH Women's Health Initiative trial were
reported in the Journal of the American Medical Association, 288:
321-333, 2002.
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In the WHI substudy, postmenopausal women who took conjugated
estrogen 0.625 milligram (mg) combined with medroxyprogesterone acetate
2.5 mg had higher risks of several serious adverse events relative to
those women who took placebo. Conjugated estrogens alone also increased
the rates of cardiovascular disease compared to placebo. Other doses of
conjugated estrogens and medroxyprogesterone acetate and other
combinations of estrogens and progestins were not studied in the WHI.
However, in the absence of comparable data, the risks of serious
adverse events should be assumed to be similar because other studies
show that estrogens and progestins are associated with these types of
events.
This draft guidance revises the 1995 guidance in several ways. For
example, the draft guidance no longer uses the phrase ``hormone
replacement'' because neither estrogen alone nor estrogen/progestin
treatments for symptoms of menopause should be considered replacement
hormones. The guidance only addresses two indications (moderate to
severe vasomotor symptoms and moderate to severe vulvar and vaginal
atrophy symptoms) and explains under what conditions both indications
can be studied concurrently in a single trial. For other indications,
such as the prevention of osteoporosis, sponsors are asked to direct
inquiries to the appropriate review division in the Center for Drug
Evaluation and Research. A section entitled Primary Endpoints has been
added for each indication, and the Study Analysis section has been
modified to clarify analyses of the primary endpoints. The Monitoring
section for drug products containing estrogen plus progestin has been
expanded. The additions to this section were made to address diagnostic
ambiguities in the efficacy evaluation for protection of the
endometrium.
This level 1 draft guidance is being issued consistent with FDA's
good guidance practices regulation (21 CFR 10.115). The draft guidance
represents the agency's current thinking on recommendations for
clinical evaluation of estrogen and estrogen/progestin drug products to
treat vasomotor symptoms and 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 Dockets Management Branch (see
ADDRESSES) written or electronic comments regarding the draft guidance.
Submit a single copy of electronic comments to http://www.fda.gov/dockets/ecomments
or two hard copies of any written comments, except
that individuals may submit one hard 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 Dockets Management Branch between 9 a.m. and 4 p.m., Monday through
Friday.
III. Electronic Access
Persons with access to the Internet may obtain the draft document
at either http://www.fda.gov/cder/guidance/index.htm or http://www
.fda.gov/ohrms/dockets/default.htm.
www.fda.gov/ohrms/dockets/default.htm.
Dated: January 23, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-2213 Filed 1-30-03; 8:45 am]
BILLING CODE 4160-01-S