[Federal Register Volume 69, Number 31 (Tuesday, February 17, 2004)]
[Notices]
[Pages 7492-7493]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-3330]


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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Draft Guidance for Industry on Labeling for Noncontraceptive 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.

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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availability of a draft guidance for industry entitled ``Labeling 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 The draft guidance is intended to assist applicants in 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 (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DATES: Submit written or electronic comments on the draft guidance by 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ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Division of Dockets Management (HFA-305), 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://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access to the draft guidance document.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    FDA is announcing the availability of a draft guidance for industry 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://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://www.fda.gov/cder/guidance/index.htm or 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