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Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy Guidance for Industry

DraftCenter for Drug Evaluation and Research07/12/2019

Description

This guidance provides recommendations for clinical trials designed to establish clinical effectiveness and safety for hormonal drug products intended to prevent pregnancy . Drug product development in hormonal contraception has evolved over the years, especially with the development of lower-dose hormonal drug products and longer-acting reversible contraceptives. Changes in patient demographics, pregnancy testing, determinations of conception date, and dosing directions have also occurred. This guidance reflects these developments and is generally consistent with advice we have been providing to individual sponsors developing hormonal drug products.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

4
Novel contraceptive drug product

Two phase 3 trials may be recommended.

Combined estrogen and progestin products

May conduct a single phase 3 trial for these products.

Long-acting reversible contraceptives

evolution of drug product development in hormonal contraception; Trials of longer duration recommended for these systems.

Hormonal Drug Products

intended to prevent pregnancy

Stakeholders

2
Sponsor

Entity responsible for submitting applications under section 524B

Sponsors

Assist sponsors in the nonclinical evaluation

Regulatory Context

Regulatory Activities

2
Postmarketing evaluation

May be required for risks like venous thromboembolism.

Clinical trials

Development program for drugs intended for sGERD treatment

Document Types

2
Daily diary

Subjects should complete to capture vaginal intercourse and contraceptive use.

Labeling

Cybersecurity information should be included in device labeling

Attributes

3
BMI

Body Mass Index used for weight classification and estimating adiposity

BMI of at least 30 kg/m2

definition of obese women for trial population

Body mass index

effectiveness of some contraceptives may be reduced with increasing body weight

Technical Details

Substances

2
Medroxyprogesterone acetate

Example of long-acting injectable contraceptive.

New molecular entity

Drug type that may alter the minimum acceptable size of the safety database

Testing Methods

6
Life table analysis

Supportive analysis to provide monthly and cumulative failure rates.

Ultrasonography

Performed for dating if pregnancy is confirmed.

Serum testing

Used to confirm positive urine pregnancy tests.

Urine pregnancy tests

Performed regularly at clinic visits.

Single-arm, open-label, historically controlled trials

generally sufficient to establish efficacy

Subgroup efficacy analysis

prespecified analysis in the obese population

Processes

2
Lactation studies

Sponsors encouraged to conduct for new drug products.

Pregnancy testing

developments in drug product development

Clinical Concepts

7
On-treatment pregnancy

Defined as pregnancy occurring during use or within specific timeframe after last use.

Invasive cervical cancer

screening criteria for enrollment

Dysplasia

screening criteria for enrollment

Postmenarchal adolescents

subjects likely to use the drug product

Obese women

defined as BMI of at least 30 kg/m2

Premenopausal women

recommended enrollment criteria for clinical trials

Pregnancy

Example of a condition to be captured in the medical history section.

Identified Hazards

Hazards

1
Venous thromboembolism

Infrequent but well-known risk of hormonal contraceptives.

Standards & References

Specifications

2
95% confidence interval

the lower bound of the one-sided 95% confidence interval (CI) must be above 0 ms.; statistical metric for demonstrating independence of QTc to RR

Pearl Index

Primary efficacy endpoint defined as number of pregnancies per 100 woman-years.

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Establishing Effectiveness and Safety for Hormonal Drug Products Intended to Prevent Pregnancy Guidance for Industry | Guideline Explorer | BioRegHub