Description
This guidance is intended to provide you, sponsors, with recommendations for the conduct of developmental toxicity2studies for investigational preventive and therapeutic vaccines for infectious disease indications. The recommendations set forth in this document pertain to the assessment of the developmental toxicity potential of preventive and therapeutic vaccines for infectious diseases indicated for females of childbearing potential and pregnant individuals.3This guidance applies prospectively to investigational vaccines, i.e., vaccines under investigational new drug applications (IND) and vaccines the subject of a new biologics licenseapplication (BLA). These recommendations do not apply retrospectively to already licensed vaccines except those the subject of additional INDs. This guidance document finalizes the draft guidance entitled “Guidance for Industry: Considerations for Reproductive Toxicity Studies for Preventive Vaccines for Infectious Disease Indications” dated August 2000 (65 FR 54534; September 8, 2000).
Key Topics
Terms and concepts identified from this document
Scope & Applicability
Product Classes
4animal models used to demonstrate prevention of disease
Vaccines intended for the treatment of infectious diseases
Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Primary focus of the guidance for infectious disease indications; Subject of the developmental toxicity study guidance
Stakeholders
5Entity responsible for submitting applications under section 524B
Offspring evaluated for normal growth and development
Animal models used in the toxicity study
Target population for vaccines who may become pregnant
Scientific and ethical considerations for inclusion in clinical trials
Regulatory Context
Regulatory Activities
2Investigational New Drug submissions
Biologics License Application
Attributes
5Assessment required for immunization programs
Distinguishing feature of vaccines compared to other pharmaceuticals
Endpoint for natural delivery group
Endpoint for natural delivery group
Endpoint for natural delivery group
Technical Details
Substances
8Samples used to assess placental transfer of maternal antibodies
CQAs should be evaluated during vaccine stability studies
Exception excipient for parenteral, ophthalmic, or otic use.
Constituent of the vaccine product
Type of vaccine derived from polynucleotides
Component of the vaccine formulation
Assessment of excipient differences
Example of a permissible inactive ingredient
Testing Methods
6Routine uterine and fetal examinations at the end of pregnancy
Used to obtain information about onset and duration of antibody response
Method for terminal examination of maternal animals and fetuses
necropsy results including gross pathology
Microscopic examination of tissues with macroscopic findings
Tests to screen for normal neuro-development in F1 generation
Processes
2Products specifically intended for use in pregnant women
Non-clinical studies to evaluate effects on pregnancy and offspring
Clinical Concepts
5Indications for which the vaccines are developed
Example of a condition to be captured in the medical history section.
detecting malformed offspring or reduced birth weight
Evaluation of risks to the fetus during animal studies
Critical phase of pregnancy from implantation to closure of the hard palate
Identified Hazards
Hazards
4Potential risks caused by vaccine biological activity
Potential direct effects of vaccine components on the embryo
Potential cause of adverse effects on pregnancy status
Potential risks to offspring screened in animal models
Standards & References
Specifications
1Assessment to verify exposure of the embryo/fetus to maternal antibody
ICH References (1)
Detection of Toxicity to Reproduction for Medicinal Products
Related CFR Sections (2)
- 21CFR201.57§ 201.57 Specific requirements on content and format of labeling for human prescription drug and biological products described in § 201.56(b)(1) .
The requirements in this section apply only to prescription drug products described in § 201.56(b)(1) and must be implemented according to the schedule specified in § 201.56(c) , except for the requirement in paragraph (c)(18) of this section to reprint any FDA-approved patient labeling at the end oRead full regulation →
- 21CFR601.2§ 601.2 Applications for biologics licenses; procedures for filing.
(a) General. To obtain a biologics license under section 351 of the Public Health Service Act for any biological product, the manufacturer shall submit an application to the Director, Center for Biologics Evaluation and Research or the Director, Center for Drug Evaluation and Research (see mailing aRead full regulation →
Enforcement Impact
Deficiencies cited in Warning Letters referencing the same regulations
Recent Cases
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Mid-Link Testing Company, Ltd
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Sanitation & Environmental Technology Institute dba SDWH
- 2023-10-31
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Samm Solutions, Inc., d.b.a. BTS Research
Related Warning Letters (9)
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
CCIC Huatongwei International Inspection Co., Ltd.
- 2025-08-26
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Jiangsu Kerbio Medical Technology Group Co.
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Mid-Link Testing Company, Ltd
- 2024-09-11
Investigational Device Exemptions (IDE)/Premarket Approval Application (PMA)
Sanitation & Environmental Technology Institute dba SDWH
- 2023-10-31
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Samm Solutions, Inc., d.b.a. BTS Research
- 2022-08-09
Bioresearch Monitoring Program
Valley Biosystems
- 2022-02-22
Good Laboratory Practice (GLP)
Toxikon Corporation/Labcorp Bedford LLC
- 2020-05-05
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
University of Kentucky
- 2020-04-07
Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies
Steiner Biotechnology, LLC
Related MFDS Guidelines
Korean regulatory guidelines covering similar topics
See Also (8)
- Advanced Manufacturing Technologies Designation Program (Status: Final)
- Environmental Assessment of Human Drug and Biologics Applications: Guidance for Industry (Status: Final)
- Content and Format of Chemistry, Manufacturing and Controls Information and Establishment Description Information for a Vaccine or Related Product: Guidance for Industry (Status: Final)
- Providing Regulatory Submissions to the Center for Biologics Evaluation and Research (CBER) in Electronic Format - Biologics Marketing Applications: Guidance for Industry (Status: Final)
- Submission of Abbreviated Reports and Synopses in Support of Marketing Applications. (Status: Final)
- Use of Sterile Connecting Devices in Blood Bank Practices: Guidance for Industry (Status: Final)
- Submitting Marketing Applications According to the ICH/CTD Format: General Considerations (Status: Draft)
- Pharmacogenomic Data Submissions; Examples of Voluntary Submissions or Submissions Required Under 21 CFR 312, 314, or 601 (Status: Final)