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Pharmacokinetics in Pregnancy — Study Design, Data Analysis, and Impact on Dosing and Labeling

DraftCenter for Drug Evaluation and Research11/01/2004

Description

This guidance describes a basic framework for designing and conducting PK/PD studies in pregnant women. It provides recommendations to sponsors on how to assess the influence of pregnancy on the pharmacokinetics (PK), and where appropriate, the pharmacodynamics (PD) of drugs or biologic products. Additionally, this guidance provides recommendations to primary investigators, clinical researchers, and clinical pharmacologists about issues to consider when designing and conducting PK studies in pregnant women.

Scope & Applicability

Product Classes

3
Biologic products

influence of pregnancy on the PK of drugs or biologic products

Vaccines

Products for which batch/lot information is particularly important

Antihypertensive therapy

Example of therapy where dose modification may be needed during pregnancy

Stakeholders

5
Sponsors

Assist sponsors in the nonclinical evaluation

Investigator

Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining

Sponsor

Entity responsible for submitting applications under section 524B

Clinical researchers

recommendations to primary investigators, clinical researchers, and clinical pharmacologists

Institutional Review Board

Governs top dose in clinical studies

Regulatory Context

Attributes

8
Dosage regimen

safety and efficacy of a drug are established for a particular dosage regimen

Dose adjustment

describing how the dose would be adjusted during pregnancy

Clearance

weight-based changes in clearance

Peak concentration

Standard PK parameter (Cmax)

Area under the plasma concentration curve

Standard PK parameter (AUC)

Plasma protein binding

A key parameter of interest in predicting the risk of drug-drug interactions

Minimal risk

regulatory threshold for involving children in clinical investigations

Narrow therapeutic range

situation where a separate PK study should be considered

Identified Hazards

Hazards

1
Fetal risk

Risk to be minimized in pregnant women volunteering for studies

Related CFR Sections (1)

  • 21CFR312.2§ 312.2 Applicability.

    (a) Applicability. Except as provided in this section, this part applies to all clinical investigations of products that are subject to section 505 of the Federal Food, Drug, and Cosmetic Act or to the licensing provisions of the Public Health Service Act (58 Stat. 632, as amended ( 42 U.S.C. 201 etRead full regulation →

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See Also (4)