In this post, we outline what University of Minnesota sponsor-investigators need to submit in their initial Investigational New Drug (IND) application to the FDA.
When to submit an IND application
The Food and Drug Administration (FDA) requires an Investigational New Drug (IND) application when an investigator is studying either:
- An unapproved drug/biologic.
- An approved product for a new indication, new route of administration, or in a new patient population.
A study in either of these categories may not proceed without permission from the FDA. In the United States, the use of a drug or biologic in one or more persons other than use of an approved drug in the course of medical practice may require an IND.
Investigational new drug applications are reviewed by the FDA’s Center for Drug Evaluation and Research (CDER), while new biologics applications are reviewed by the FDA’s Center for Biologics Evaluation and Research (CBER).
Note that an IND submission is different from a New Drug Application (NDA), which is submitted to the FDA after clinical trials are completed and when the drug is ready for approval and marketing.
An IND application should be initiated prior to IRB submission to ensure an IND number has been assigned to the project.
Checklist: What’s required for an IND application
FDA form 1571
Regulation: 21 CFR 312.23(a)(1)
This form contains information generally provided in a cover page including the contact information of the IND sponsor, the purpose of the FDA submission, and the serial number assigned to the submission.
FDA form 1572
Regulation: 21 CFR 312.23(a)(6)(iii)(b)
This form lists addresses for clinical, laboratory, and IRB locations, and lists staff who make a significant contribution to the data for the study. Each site in a multi-site study must have its own 1572.
FDA form 3454 or Form 3455
Regulation: 21 CFR 54.4(a)
These are financial disclosure forms. If no investigators have a financial conflict of interest to declare, then checking option 1 in Form 3454 is likely most appropriate.
Any conflicts of interest are disclosed using Form 3455.
FDA form 3674
Regulation: 42 U.S.C. § 282(j)(5)(B)
The purpose of this clinical trials form is to certify compliance with requirements for posting on ClinicalTrials.gov, and to link the ClinicalTrials.gov record for the trial to the IND application.
Our team can help determine if your study is required to be listed on ClinicalTrials.gov and assistance with registration and updates.
Request ClinicalTrials.gov support
Cover letter
The cover letter should include:
- IND number
- Serial number — these begin at 0000, followed by 0001, 0002, etc.
- Contact information
- A brief description of the purpose of the submission
Application packet
The IND application should include:
- Table of contents (21 CFR 312.23(a)(2)).
- Drug name, active ingredients and class, structural formula, formulation of the drug, and route of administration, and objectives and duration of the investigation (21 CFR 312.23(a)(3)(i)).
- Summary of previous human experience (21 CFR 312.23(a)(3)(ii); 21 CFR 312.23(a)(9)).
- Statement of Withdrawal or lack thereof (21 CFR 312.23(a)(3)(iii)).
- Investigational plan, including rationale, indications, approach to trials, estimated enrollment, and anticipated risks (21 CFR 312.23(a)(3)(iv)).
CV for each staff person listed on the 1572(s)
Regulation: 21 CFR 312.23(a)(6)(iii)(b)
There is not a format requirement for CVs.
Protocol
- UMN HRPP protocol template — Most sponsor-investigators use a protocol template from the UMN Human Research Protection Program (HRPP). Need help with your study protocol? The Clinical Research Support Center has protocol experts to guide you.
Consent forms
- Consent forms are not required for an IND submission per FDA regulations, but are often requested by FDA reviewers. It is best to submit a consent with the IND application if possible.
- UMN HRPP consent and HIPAA templates — Most sponsor-investigators at the university use the combined HIPAA and consent form template available from the UMN HRPP.
Package insert or other chemistry, manufacturing, and control (CMC) information
Regulation: 21 CFR 312.23(a)(7)
Currently marketed: If the investigational drug or biologic is marketed already, then providing the publicly available package insert should satisfy the FDA’s requirements for chemistry, manufacturing, and control data.
Not currently marketed: If the investigational product is not currently marketed, then another source of chemistry, manufacturing, and control data is required. The type of data needed to support an IND varies based on the investigational product and the participant population, but this category of data generally includes:
- Description of drug characteristics, manufacturer, preparation, analysis, and stability data
- List of components used in manufacturing
- Description of composition, manufacturing, and control of placebo, if applicable,
- Copy of drug label
- Claim for environmental exclusion
Pharmacology & toxicology information
Regulation: 21 CFR 312.23(a)(8)
Currently marketed: If the investigational drug or biologic is marketed already, then providing the publicly available package insert should satisfy the FDA’s requirements for chemistry, manufacturing, and control data.
Not currently marketed: If the investigational product is not currently marketed, then another source of pharmacology & toxicology data is required. The type of data needed to support an IND varies based on the investigational product and the participant population, but this category of data generally includes:
- Information from animal or in vitro studies showing it is safe to conduct this clinical trial, and where those studies were conducted.
- Pharmacological effects/ mechanisms of the drug and PK information.
- Summary of toxicological effects; include a full table of data for safety-related studies.
- Statement that nonclinical studies were conducted in compliance with GLP regulations Part 58.
Additional relevant information
Examples:
- Drug dependence risk
- Radioactive drug information
- Information relevant to pediatric use
UMN Central File Submission
All FDA communications, including submissions and receipts, must be submitted to the University’s Central File per UMN policy.
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