[Federal Register Volume 68, Number 22 (Monday, February 3, 2003)]
[Notices]
[Pages 5300-5301]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-2377]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 98D-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Draft Guidance for Industry on Labeling for Noncontraceptive 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.

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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availability of a draft guidance for industry entitled ``Labeling 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 The draft guidance is intended to assist applicants in 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 for such drug products. 
This is the second draft of the guidance, which initially issued in 
September 1999.

DATES: Submit written or electronic comments on the draft guidance by 
April 4, 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ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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 one 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on the draft guidance to the Dockets Management Branch (HFA-305), Food 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.

[[Page 5301]]

1061, Rockville, MD 20852. Submit electronic comments 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section for electronic access to the draft guidance document.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    FDA is announcing the availability of a draft guidance for industry 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 new drug applications (NDAs). A draft of this guidance was 
first issued in September 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).\1\ This second draft reflects 
the agency's thinking after considering the results of the WHI 
substudy.
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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 second draft of the guidance reflects several changes. For 
example, the draft guidance provides specific labeling recommendations 
for two indications (moderate to severe vasomotor symptoms and moderate 
to severe symptoms of vulvar and vaginal atrophy). It refers sponsors 
to the appropriate review divisions for guidance on labeling products 
to treat other indications. In addition, the guidance recommends that 
the following additions be made to the labeling for noncontraceptive 
estrogen drug products for the treatment of vasomotor symptoms and 
symptoms of vulvar and vaginal atrophy:
    [sbull] New information to the boxed warning;
    [sbull] Information from the WHI, including a statement that, 
although only a single dose and type of estrogen and progestin were 
studied in the WHI, risks for serious adverse events should be assumed 
to be similar for other estrogens and progestins until data show 
otherwise;
    [sbull] A statement recommending that use of estrogens should be at 
the lowest doses and for the shortest duration in hopes of minimizing 
risks;
    [sbull] A revised indication for the treatment of vulvar and 
vaginal atrophy in women who have moderate to severe symptoms so that 
benefits from drug therapy may outweigh risks; and
    [sbull] Information from the WHI on cardiovascular and cancer risks 
as well as other information from the WHI and other studies.
    Finally, the new draft updates other information in the label based 
on current scientific studies.
    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 labeling for 
noncontraceptive estrogen drug products for the treatment of 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 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. 03-2377 Filed 1-31-03; 8:45 am]
BILLING CODE 4160-01-S