Women's Health Initiatives

• Introduction

• Legislation

  • Code of Federal Regulations Final Rules

• General Guidance

  • Guideline for the Study and Evaluation of Gender Differences in Clinical Evaluation of Drugs

  • Women in Clinical Trials

  • Women and Minorities Guidance Requirements

  • Format and Content of the Clinical and Statistical Sections of an Application

  • Population Pharmacokinetics (draft guidance)

  • FDA Commissioner and Society for Women’s Health Research Outline Critical Steps to Improve Women’s Health

• Participation of Women in Clinical Trials  

• Hormone Therapy

  • CDER Information on Conjugated Estrogens

  • FDA Statement on the Results of the Women's Health Initiative

  • Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women

  • Draft Guidance Documents

  • Past Meetings

• Pregnancy Issues

  • Draft Guidance Documents  

  • Dockets

  • Past Meetings

• Past Meetings for Assisted Reproductive Technology

• Additional Women's Health Information  

• Upcoming Meetings

Introduction

The Food and Drug Administration Modernization Act of 1997 (FDAMA) Sec. 115 Clinical Investigations. (b) Women and Minorities. -- Section 505(b)(1) 21 U.S.C. 355 (b)(1) was amended by adding the words in bold:

"The Secretary shall, in consultation with the Director of the National Institutes of Health and the representatives of the drug manufacturing industry, review and develop guidance, as appropriate, on the inclusion of women and minorities in clinical trials required by clause (A).

Historically, women have been neglected in clinical trials for new drugs, devices, and biological products.  To address these and other issues, FDA created the Office of Women's Health.  CDER strongly supports activities on women's health issues through the Women's Health Subcommittee of the CDER Medical Policy Coordinating Committee.

By encouraging diversity at all stages of a drug's development, FDA hopes that drug sponsors will better understand how a drug will affect the different populations once it is marketed. The Agency believes it must identify important information about a drug during the investigational phase, such as dosages for different age groups, genders, and racial subgroups, and to use that information to refine labeling information, patient selection, and dose selection.

This web site bring together regulations, guidance documents, and related information to assist FDA and drug developers in correcting any identified gender disparities in drug, device, and biologics testing and regulation policy.

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Legislation

Code Of Federal Regulations (CFR).  The final regulations published in the Federal Register (daily published record of proposed rules, final rules, meeting notices, etc.) are collected in the CFR.  The CFR is divided into 50 titles which represent broad areas subject to Federal regulations.  The FDA's portion of the CFR interprets the Federal Food, Drug and Cosmetic Act and related statutes.  Section 21 of the CFR contains most regulations pertaining to food and drugs.  The regulations document all actions of all drug sponsors that are required under Federal law. 

Code of Federal Regulations Final Rules:

• 21 CFR Parts 312 and 314 [Docket No. 95N-0010] February 11, 1998.  Investigational New Drug Applications and New Drug Applications.  FDA amended its regulations pertaining to new drug applications (NDA's) to require effectiveness and safety data for important demographic subgroups, specifically gender, age, and racial subgroups.

• 21 CFR Part 314.101.  Applications for FDA Approval to Market a New Drug.  Within 60 days after FDA receives an application, the Agency determines whether the application is complete enough to review. 

• 21 CFR Part 312. [Docket No. 97N-0030].  June 1, 2000.  Final Rule. Investigational New Drug Applications;  Amendment to Clinical Hold Regulations for Products Intended for Life-Threatening Diseases. This final rule amends investigational new drug applications (IND's) to permit FDA to place a clinical hold on one or more studies under an IND involving a drug that is intended to treat a life-threatening disease. The amendment permits the Agency to place a clinical hold if men or women with reproductive potential are excluded from participation in an investigation only because of a risk or potential risk of reproductive or developmental toxicity from use of the investigational drug.

A related FDA Talk Paper entitled FDA Proposes Rule on Women in Clinical Trials provides more background information on this amendment.

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General Guidance

Guidance documents represent the Agency's current thinking on a particular subject. These documents are prepared for FDA review staff and drug sponsors to provide guidelines for the processing, content, and evaluation/approval of applications, and also for the design, production, manufacturing, and testing of regulated products.   They also provide consistency in the Agency's regulation, inspection and enforcement procedures.  Because guidances are not regulations or laws, they are not enforceable.  An alternative approach may be used if it satisfies the requirements of the applicable statute, regulations, or both.

Guidance Documents

• Guideline for the Study and Evaluation of Gender Differences in Clinical Evaluation of Drugs. This 1993 guideline provides guidance for the inclusion of women in drug development. The guideline was developed amidst growing concerns that the drug development process did not provide adequate information about the effects of drugs in women.   This guideline has certain implications for the use of institutional review boards as described in the Guidance for Institutional Review Boards and Clinical Investigators.

• FDA Guidelines for Women in Clinical Trials.  This Federal Register notice asks for comments on the 1993 guideline calling for better assessment of possible gender differences in responses to new medications.

• Women and Minorities Guidance Requirements. (Issued 7/20/1998, posted 11/25/1998).  This report from the FDA Modernization Act Women and Minorities Working Group evaluates and summarizes existing guidances.

• Guideline for the Format and Content of the Clinical and Statistical Sections of an Application. (Issued 7/1988, posted 5/21/1997).  This guideline assists an applicant in presenting the clinical and statistical data required as part of an application under 21 CFR 314.50.

• Guidance for Industry:  Population Pharmacokinetics (draft guidance posted 2/10/1999). This guidance makes recommendations on the use of population pharmacokinetics in the drug development process to help identify differences in drug safety and efficacy among population subgroups. It summarizes scientific and regulatory issues that should be addressed using population pharmacokinetics.

FDA News Releases

• FDA Commissioner and Society for Women’s Health Research Outline Critical Steps to Improve Women’s Health. (Posted 10/30/2003)
  

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Participation of Women in Clinical Trials 1995-1999

• Women's Participation in Clinical Trials and Gender-Related Labeling: 
  A Review of New Molecular Entities Approved 1995-1999.  Study results posted June 2001.

• Participation of Women in Clinical Trials 1995-1996. "Special Populations:  Testing and Labeling of New Drugs."  Banks, D.B.; Toigo, T.A.; Carmouse, G.N.  Presented at the FDA Science Forum, February 15, 2000.   The speakers conclude that female volunteers participated in clinical trials for nearly all drugs.

Hormone Therapy

• The CDER Information on Conjugated Estrogens web page explains why FDA has not approved a synthetic generic version of Premarin, the brand name for currently marketed conjugated estrogens in the United States.  Premarin is used to treat symptoms of menopause and to prevent osteoporosis.  
   

• FDA Statement on the Results of the Women’s Health Initiative (8/13/2002) 

  • On July 9, 2002, the National Heart, Lung and Blood Institute (NHLBI) announced that it was stopping the combination conjugated equine estrogen/medroxy progesterone acetate (Prempro) study because the overall health risks of Prempro for invasive breast cancer and coronary heart disease exceded the benefits of the drug, which include a lower risk of fractures and a reduction in the risk of colorectal cancer.
     

• Estrogen and Estrogen with Progestin Therapies for Postmenopausal Women

  • FDA approved new labels for estrogen and estrogen with progestin therapies for postmenopausal women following its review of the results of the Women’s Health Initiative study that raised concerns about risks of using these products.

Draft Guidance Documents

• 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 [Word] or [PDF] (Posted 2/10/2004)
   

• Pharmacokinetics in Pregnancy — Study Design, Data Analysis, and Impact on Dosing and Labeling [HTML] or [Word] or [PDF] (Issued 10/29/2004, Posted 10/29/2004)
   

• 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 [Word] or [PDF] (Posted 2/10/2004)
   

• Estrogen and Estrogen/Progestin Drug Products to Treat Vasomotor Symptoms and Vulvar and Vaginal Atrophy Symptoms — Recommendations for Clinical Evaluation [Word] or [PDF] (Issued 1/2003, Posted 1/30/2003)

Past Meetings

• Endocrinologic and Metabolic Drugs Advisory Committee Meeting.  October 7, 2003.  Discussion of the Women’s Health Initiative Study Results and implications for the use of estrogen/progestin as a second-line therapy for the prevention and treatment of postmenopausal osteoporosis in women. 

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Pregnancy Issues

Draft Guidance Documents:

• Establishing Pregnancy Exposure Registries [Word] or [PDF] (Issued 8/2002, Posted 9/20/2002). This guidance provides sponsors with advice on how to establish pregnancy exposure registries to monitor the outcomes of pregnancies for women who were exposed to specific medical products, including drugs and biological products (including vaccines). The ultimate goal of pregnancy exposure registries is to provide clinically relevant human data that can be used in a product’s labeling to provide medical care providers with useful information for treating or counseling patients who are pregnant or anticipating pregnancy.  

• Reviewer Guidance: Evaluation of Human Pregnancy Outcome Data. (6/2/1999)  This guidance provides reviewers with a standard approach to the assessment of potential risks related to exposures of pregnant women to drugs and biological products.  Docket No. 99D-1540, June 4, 1999  requests comments on the draft guidance for reviewers entitled ``Evaluation of Human Pregnancy Outcome Data.''

Dockets

• Docket No. 97N-0289. Content and Format of Labeling for Human Prescription Drugs; Pregnancy Labeling.

• Docket No. 99N-2079.  Assessment of Preclinical Reproductive Toxicity Data.

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Past Meetings

• Clinical Pharmacology During Pregnancy; Public Meeting.   This meeting summarized the state of knowledge on clinical pharmacology in pregnancy, raised awareness among clinician researchers and leaders about the need for clinical research and collaboration in this area, and garnered support for such research from health advocacy groups and others.   Dates: Monday and Tuesday, December 4 and 5, 2000, from 8 a.m. to 5 p.m.

• Dietary Supplement Use During Pregnancy - March 30, 2000.  This web page provides links to the Federal Register announcement of the meeting, questions to be addressed, and an agenda.

• Advisory Committee for Reproductive Health Drugs, Pregnancy Labeling Subcommittee. 

  • September 12, 2000. Discussion of those products for which improved pregnancy labeling is critical for effective prescribing during pregnancy or proper counseling of pregnant women who have been inadvertently exposed. Discussion on drug use during lactation and product labeling on this issue.

  • March 28-29, 2000. Presentations and discussions will include the status of proposed pregnancy labeling changes, the status of activities related to preclinical assessment of reproductive toxicity, the FDA draft guidance entitled, “A Guidance for Industry: Establishing Pregnancy Registries”, and strategies for monitoring drug risks in pregnant women.

  • June 3, 1999. Discussion of possible changes to pregnancy labeling as a result of the September 12, 1997, Part 15 public hearing (see 62 FR 41061).
     

• FDA/Industry Meeting on Preclinical Assessment of Reproductive Toxicity Data, June 24, 1999 (Posted 6/2/1999).  Includes the agenda and paper.

• Subcommittee Meeting of the Advisory Committee for Reproductive Health Drugs. Notice of meeting posted April 30, 1999.

Past Meetings for Assisted Reproductive Technology

• September 29, 2003.  Discussion of clinical trial designs and outcome measures for drug products indicated for ovulation induction and pregnancy in anovulatory, infertile women and development of multiple follicles and pregnancy in ovulating women. 

• September 30, 2003.  Discussion of NDA 21-322, Luveris (lutropin alfa for injection), Serono, Inc., a recombinant human luteinizing hormone drug product, proposed for concomitant administration with recombinant human follicle stimulating hormone for the proposed indication of induction of ovulation in infertile women with severe luteinizing hormone and follicle stimulating hormone deficiency.
  http://www.fda.gov/cder/audiences/acspage/reproductivemeetings1.htm#2003

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Additional Women's Health Information

• New Medicines in Development for Women: 2001 Survey.  Drug development information from PhRMA (Pharmaceutical Research and Manufacturers of America). 

• FDA's Office of Women's Health.

• Information on Food Safety, Nutrition and Cosmetics from FDA's Center for Food Safety and Applied Nutrition.

• Mammography Information from FDA's Center for Devices and Radiological Health.

• National Institutes of Health's Office of Research on Women's Health.

• Department of Health and Human Service's Office on Women's Health.

• Executive Summary of the November, 1995 public workshop "Gender Studies in Product Development: Scientific Issues and Approaches."  This meeting explored the science involved with assessing gender effects during the development of medical products, including drugs, biologics, and medical devices, and identified significant areas for further research and policy development.

• Outreach Notebook for the NIH Guidelines for the Inclusion of Women and Minorities as Subjects in Clinical Research. This publication is intended to help investigators understand and comply with the NIH's inclusion policies.

• Deadly Diseases and People of Color: Are Clinical Trials an Option?

  • Howard University, Washington, DC, October 25, 1996

  • University of Miami, School of Medicine, Miami, FL, May 5, 1997

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FDA/Center for Drug Evaluation and Research
Last Updated:  October 21, 2005
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