[Federal Register Volume 68, Number 21 (Friday, January 31, 2003)]
[Notices]
[Pages 5025-5026]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-2213]


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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Draft Guidance for Industry on Estrogen and Estrogen/Progestin 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availability of a draft guidance for industry entitled ``Estrogen and 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DATES:  Submit written or electronic comments on the draft guidance by 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ADDRESSES:  Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Dockets Management Branch (HFA-305), Food 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section for electronic access to the draft guidance document.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.

    Dated: January 23, 2003.
Margaret M. Dotzel,
Assistant Commissioner for Policy.
[FR Doc. 03-2213 Filed 1-30-03; 8:45 am]
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