SUPPLEMENTARY INFORMATION:

Investigational New Drug Application Requirements—21 CFR Part 312

OMB Control Number 0910-0014—Revision

This information collection supports implementation of provisions of section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355) and of the licensing provisions of the Public Health Service Act (42 U.S.C. 201 et seq.) that govern investigational new drugs and investigational new drug applications (INDs). Implementing regulations are found in part 312 (21 CFR part 312), and provide for the issuance of guidance documents (see § 312.145 (21 CFR 312.145)) to assist persons in complying with the applicable requirements. The information collection applies to all clinical investigations subject to section 505 of the FD&C Act and include the following types of INDs:

• An Investigator IND is submitted by a physician who both initiates and investigates, and under whose immediate direction the investigational drug is administered or dispensed. A physician might submit a research IND to propose studying an unapproved drug or an approved product for a new indication or in a new patient population.
• Emergency Use IND allows FDA to authorize use of an experimental drug in an emergency situation that does not allow time for submission of an IND in accordance with § 312.23 or § 312.20 (21 CFR 312.23 or 312.20). It is also used for patients who do not meet the criteria of an existing study protocol or if an approved study protocol does not exist.
• Treatment IND is submitted for experimental drugs showing promise in clinical testing for serious or immediately life-threatening conditions while the final clinical work is conducted and FDA's review takes place.

There are two IND categories: commercial and research (non-commercial).

General IND requirements include submitting an initial application as well as amendments to that application; submitting reports on significant revisions of clinical investigation plans; submitting information to the clinical trials data bank ( clinicaltrials.gov) established by the National Institutes of Health/National Library of Medicine, including expanded information on certain clinical trials and information on the results of these clinical trials; and reporting information on a drug's safety or effectiveness. In addition, sponsors are required to provide to FDA an annual summary of the previous year's clinical experience. The regulations also include recordkeeping requirements regarding the disposition of drugs, records regarding individual case histories, and certain other documentation verifying clinical investigators' fulfillment of responsibilities.

Form FDA 1571 entitled “Investigational New Drug Application (IND)” and Form FDA 1572 entitled “Statement of Investigator,” were developed to assist respondents with the information collection and provide for uniform reporting of required data elements. The information is required to be submitted electronically. Individuals who are interested in receiving printed forms may send an email request to the FDA Forms Manager at formsmanager@OC.FDA.GOV. Fees may apply. Sponsors (including sponsor-investigators) interested in filing or updating a research IND may use a new web-based interface developed for use by mobile device or desktop to help in completing Form FDA 1571. The web-based interface also allows respondents to electronically submit completed Form FDA 1571 and associated files. Form FDA 1571 was recently updated to include the new tracking information for real world evidence and real-world data (RWE/RWD). The new RWE/RWD fields will capture submissions with RWE/RWD based on the requirements set forth in the PDUFA VII commitment letter and the resulting Advancing Real World Evidence Program, so that FDA can track and report on its performance related to these commitments. In addition, collection of this data will support the consistent integration of real-world evidence data into the regulatory review and approval process for new drugs and biologics. Other updates include the addition of fields necessary for ensuring compliance with enhancing security for human biospecimens. For more information regarding Forms FDA 1571 and 1572 visit www.fda.gov/​news-events/​expanded-access/​how-complete-form-fda-1571-and-form-fda-1572. For information regarding updated FDA forms, including Forms FDA 1571 and 1572 visit www.fda.gov/​about-fda/​forms/​new-and-updated-fda-forms.

Human drug, biological product, and device product submissions must be accompanied by Form FDA 3674, as discussed in the guidance document entitled “Form FDA 3674—Certifications To Accompany Drug, Biological Product, and Device Applications/Submissions” (updated November 2017), available from our website at www.fda.gov/​regulatory-information/​search-fda-guidance-documents/​form-fda-3674-certifications-accompany-drug-biological-product-and-device-applicationssubmissions. The guidance document provides procedural instruction on completing and submitting required information to FDA. As communicated in the instructions, the certification must accompany the application or submission and be included at the time of submission to FDA.

Regulations in part 312, subpart B, specify content and format requirements for applications, amendments, annual reporting, and withdrawals, including content and format requirements for protocol and information amendments. The regulations also explain phases of an investigation and set forth principles of IND submissions. To date we have developed and issued the following guidance documents to assist respondents:

• “Establishment and Operation of Clinical Trial Data Monitoring Committees ” guidance (March 2006); and
• “Special Protocol Assessment ” guidance (April 2018).

All Agency guidance documents are issued in accordance with our Good Guidance Practice regulations in 21 CFR 10.115, which provide for public comment at any time. We maintain a searchable guidance database on our ( printed page 53264) website at www.fda.gov/​regulatory-information/​search-fda-guidance-documents that utilizes topic specific search terms.

Regulations in part 312, subpart C, describe administrative actions pertaining to respondents' requests for and responses to clinical holds, terminations, and inactive IND status determinations, as well as various types of meetings (for example, End-of-Phase 2 and Pre-new drug application (NDA) meetings).

Regulations in part 312, subpart D, set forth sponsor and investigator responsibilities, including general responsibilities; transfer of obligations to a contract research organization; recordkeeping and record retention controls; reporting responsibilities; and responsibility for disposition of unused supply of investigational drug. The regulations also provide for investigator controls including review of ongoing investigations; compliance with requirements regarding the protection of human subjects and institutional review board assurance; and disqualification of clinical investigators.

Regulations in part 312, subpart E, sets forth requirements applicable to drugs intended to treat life-threatening and severely debilitating illnesses. The regulations establish procedures to reflect that physicians and patients accept greater risk or side effects from products that treat life-threatening and severely debilitating illnesses than they would accept from products that treat less serious illnesses. The procedures also reflect the recognition that the benefits of the drug need to be evaluated in light of the severity of the disease being treated.

Regulations in part 312, subpart F, include provisions pertaining to import and export requirements; foreign clinical studies not conducted under an IND; the disclosure of data and information in an IND; and the issuance of guidance documents. To date we have developed and issued the following guidance documents to assist respondents:

• “Oversight of Clinical Investigations” guidance (August 2013);
• “Pharmacogenomic Data Submissions” guidance (March 2005);
• “Adaptive Designs for Clinical Trials of Drugs and Biologics” guidance (December 2019); and
• “E6(R2) Good Clinical Practice: Integrated Addendum to ICH E6(R1)” guidance (March 2018).

All Agency guidance documents are issued in accordance with our Good Guidance Practice regulations in 21 CFR 10.115, which provide for public comment at any time. We maintain a searchable guidance database on our website at www.fda.gov/​regulatory-information/​search-fda-guidance-documents that utilizes topic specific search terms.

Regulations in part 312, subpart G, provide for drugs for investigational use in laboratory research animals or in vitro tests.

Finally, 21 CFR 300.200 requires the submission of an annual report by sponsors and manufacturers who provide an “ eligible investigational drug” under the Right to Try Act. The regulation also establishes content and format elements and requires that information be submitted to FDA no later than March 31 of each year, including data for the preceding calendar year. Respondents use Form FDA 5023 entitled “ Right to Try Reporting Requirement: Annual Summary,” currently available for download from our website at www.fda.gov/​patients/​learn-about-expanded-access-and-other-treatment-options/​right-try-annual-reporting-summary. As required by the applicable statute, section 561B of the FD&C Act (21 U.S.C. 360bbb-0a), the information is submitted to an FDA-designated point of contact, and in accordance with instructions to be posted at: www.fda.gov/​patients/​learn-about-expanded-access-and-other-treatment-options/​right-try.

In the Federal Register of March 13, 2026 (91 FR 12422) we published a 60-day notice requesting public comment on the proposed collection of information. Three comments were received all offering general support for the information collection. Two comments pertained to FDA rulemaking (RIN 0910-AH07, Docket No. FDA-2019-N-2650) proposing to amend regulations on investigational new drug applications (INDs) to exempt from the IND requirements certain clinical investigations of lawfully marketed foods for human consumption (including both conventional foods and dietary supplements) and cosmetics when the product is to be studied to evaluate its use as a drug. While the comments fall beyond the scope of the information collection topics solicited in our 60-day notice in accordance with 5 CFR 1320.8(d)(1), we have added the comments to the respective rulemaking docket for Agency consideration.

A third comment suggested FDA increase its estimate for effort attributable to reporting elements under 21 CFR parts 312.23 and 312.33, explaining that certain first time applicants may incur more burden that our figures suggest. We acknowledge that individual respondents may incur greater than or less than the estimate proffered, however, consistent with 5 CFR 1320.5(a)(1)(iv), figures are cumulative and averaged among respondents. The comment also recommended specific automated improvements that might facilitate the submission of IND applications. As announced in the Federal Register of June 24, 2026 (91 FR 37996; Docket No. 2026-N-4699), FDA is inviting comment on a proposed IND pilot program. At the conclusion of the pilot, we intend to identify potential refinements to the IND review process targeting those we can address with our limited resources.

FDA greatly appreciates the comments it received, however we have made no changes to our estimates, which are as follows:

( printed page 53266)

While we have corrected an inadvertent calculation error pertaining to 21 CFR 300.200, we have otherwise retained the currently approved estimates attributable to IND requirements. We also note that reporting activities applicable to the “Right to Try” provisions began in 2020 and we continue to monitor the information collection activity.

91 FR 53262