[Federal Register Volume 70, Number 220 (Wednesday, November 16, 2005)]
[Notices]
[Pages 69578-69579]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-22754]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 1998D-0834 (formerly Docket No. 98D-0834]


Draft Guidance for Industry on Noncontraceptive Estrogen Drug 
Products for the Treatment of Vasomotor Symptoms and Vulvar and Vaginal 
Atrophy Symptoms--Recommended 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availability of a draft guidance for industry entitled 
``Noncontraceptive Estrogen Drug Products for the Treatment of 
Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms--Recommended 
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 The draft guidance is intended to assist applicants in 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 fifth draft of the guidance, which FDA initially 
published for comment in October 1998.

DATES: Submit written or electronic comments on the draft guidance by 
January 17, 2006. 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ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Division of Drug Information (HFD-240), Center for Drug 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on the draft guidance to the Division of Dockets Management (HFA-305), 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access to the draft guidance document.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 (5359), Food and Drug Administration, 10903 New 
Hampshire Ave., bldg. 22, rm. 5376, Silver Spring, MD 20993, 301-796-
0934.

SUPPLEMENTARY INFORMATION:

I. Background

    FDA is announcing the availability of a draft guidance entitled 
``Noncontraceptive Estrogen Drug Products for the Treatment of 
Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms--Recommended 
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 October 15, 1998 (63 
FR 55399). After public review and comment, a second version of this 
draft guidance was issued on September 27, 1999 (64 FR 52100). On May 
31, 2002, the National Institutes of Health Women's Health Initiative 
(WHI) study of oral conjugated estrogens (CE 0.625 milligram (mg)) plus 
medroxyprogesterone acetate (MPA 2.5 mg)/day in postmenopausal women 
was stopped after a mean of 5.2 years of followup because test 
statistics 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 regarding 
increased risks for invasive breast cancer, heart attacks, strokes, and 
venous thromboembolism rates, including pulmonary embolism, became 
available July 17, 2002. Consequently, the agency withdrew the draft 
guidance on September 10, 2002 (67 FR 57432), pending consideration of 
the results from the WHI study. In the Federal Register of February 3, 
2003 (68 FR 5300), the agency issued a third draft reflecting the 
agency's thinking after consideration of the results from the WHI study 
concerning overall risks and benefits of hormone therapy for 
postmenopausal symptoms.
    A fourth draft of this guidance was issued on February 17, 2004 (69 
FR 7492), to address comments received, incorporate new study results 
from the Women's Health Initiative Memory Study (WHIMS), a substudy of 
the WHI study, and better inform prescribers and patients regarding the 
availability of the lowest effective dose for these drug products. (The 
results of the WHIMS substudy were published on May 28, 2003. 
Postmenopausal women, 65 to 79 years of age, during 4 years of 
treatment with CE 0.625 mg plus MPA 2.5 mg/day had a greater risk of 
developing probable dementia than those on placebo.)
    The agency is issuing this fifth draft of the guidance to 
incorporate new study results from the WHI and WHIMS studies. This 
fifth draft supersedes the fourth draft, and retains and updates the 
labeling recommendations regarding the results of the WHI study and the 
WHIMS substudy for postmenopausal women treated with CE 0.625 mg plus 
MPA 2.5 mg/day. It also reflects the agency's thinking after 
consideration of the results published on April 14, 2004, of the WHI 
study, and the results published on June 23/30, 2004, of the WHIMS 
substudy for postmenopausal women with prior hysterectomy treated with 
CE 0.625 mg/day alone. The WHI study of CE 0.625 mg/day alone in 
postmenopausal women with prior hysterectomy was stopped after a mean 
followup of 6.8 years because of an increased risk of stroke. The WHIMS 
substudy of CE 0.625 mg/day alone was stopped after a mean followup of 
5.2 years. Estrogen-alone therapy did not reduce probable dementia or 
cognitive decline incidence and increased the risk for both endpoints 
combined. This fifth draft of the guidance recommends adding risk 
information related to the results of the WHI and WHIMS estrogen-alone 
studies to appropriate sections of labeling including the boxed 
warning. Further revisions to the guidance may be necessary as 
additional information becomes available.
    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.

[[Page 69579]]

II. Comments

    Interested persons may submit to the Division of Dockets Management 
(see ADDRESSES) written or electronic comments regarding this document. 
Submit a single copy of electronic comments or two paper copies of any 
mailed comments, except that individuals may submit one paper 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: November 8, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-22754 Filed 11-15-05; 8:45 am]
BILLING CODE 4160-01-S