Description
This guidance document provides recommendations on the design and analysis of trials 16 conducted under a master protocol as well as guidance on the submission of documentation to 17 support regulatory review.
Scope & Applicability
Product Classes
5A type of ATMP involving recombinant nucleic acids or viral vectors.
Defined in section 201(g) of the FD&C Act; Articles intended for use in diagnosis, cure, mitigation, treatment, or prevention of disease; Product classification based on chemical action or specific intended uses like altering pH
Regulated under section 351(i) of the PHS Act; Virus, therapeutic serum, toxin, vaccine, or protein applicable to prevention or treatment; Alternative regulation category for products meeting device definition
A clinical investigation using a master protocol should be conducted under the master protocol IND only.
Products requiring demonstration of component contribution per regulations
Stakeholders
10Person or organization who takes responsibility for and initiates the master protocol
Institutional Review Board providing study approvals
Independent Ethics Committee listed in eCTD documentation
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
Governs top dose in clinical studies
Safety oversight body for interpreting adverse events; Safety oversight body for study design
Sponsor responsible for the investigation of an individual drug
Entity responsible for submitting applications under section 524B
Part of the shared oversight infrastructure in a master protocol.
Provides shared oversight for master protocols.
Regulatory Context
Attributes
5The ratio of subjects allocated to control versus drug arms, which may change over time.
1:1 allocation ratio for the pooled placebo arm relative to a given drug
Study-wise control recommended for hypothesis testing in subgroups
Subjects randomized to the control arm during the same time period as the drug arm.
Control data from subjects randomized at a different time than the drug being evaluated.
Related CFR Sections (5)
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR312.32§ 312.32 IND safety reporting.
(a) Definitions. The following definitions of terms apply to this section:Read full regulation →
- 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 →
- 21CFR312.3§ 312.3 Definitions and interpretations.
(a) The definitions and interpretations of terms contained in section 201 of the Act apply to those terms when used in this part:Read full regulation →
- 21CFR300.50§ 300.50 Fixed-combination prescription drugs for humans.
The Food and Drug Administration's policy in administering the new-drug, antibiotic, and other regulatory provisions of the Federal Food, Drug, and Cosmetic Act regarding fixed combination dosage form prescription drugs for humans is as follows:Read full regulation →
Related Warning Letters (3)
- 2021-10-19
Failure to obtain Investigational New Drug Applications
Lauren R. Klein, MD, M.S.
- 2021-10-19
Failure to obtain Investigational New Drug Applications
Jon B. Cole, MD
- 2020-08-19
Unapproved and Misbranded Product Related to Coronavirus Disease 2019 (COVID-19)
Predictive Biotech
See Also (8)
- Guidance for Industry: Providing Regulatory Submissions to CBER in Electronic Format -- Investigational New Drug Applications (INDs) (PDF) (Status: Final)
- INDs for Phase 2 and Phase 3 Studies Chemistry, Manufacturing, and Controls Information: Guidance for Industry (Status: Final)
- Content and Review of Chemistry, Manufacturing, and Control (CMC) Information for Human Somatic Cell Therapy Investigational New Drug Applications (INDs): Guidance for FDA Reviewers and Sponsors (Status: Final)
- Cellular Therapy for Cardiac Disease: Guidance for Industry (Status: Final)
- Codevelopment of Two or More New Investigational Drugs for Use in Combination (Status: Final)
- Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information: Guidance for Industry (Status: Final)
- Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs): Guidance for Industry (Status: Final)
- Psychedelic Drugs: Considerations for Clinical Investigations (Status: Draft)