Investigational New Drug | IND

An academic researcher may be required to submit an IND application to the FDA in order to study a marketed medical product in a new (i.e. unapproved) clinical indication.  An investigator is always required to hold an IND to study an unmarketed (i.e. unapproved) medical product.  In both cases, the products are considered "investigational" by FDA.  The vast majority of INDs on file with the FDA are for noncommercial research.

This table provides links to information about submitting IND applications to the FDA.  The resources apply to IND applications for both clinical research and clinical treatment

IND Applications for Clinical Investigations (Product Development)

IND Application Reporting

IND Application Procedures

 IND Applications for Clinical Treatment (Expanded Access)

Overview Overview  Overview Overview 
Contents & Format  Protocol Amendments  Exemptions Contents & Format 
Regulatory & Administrative Components Information Amendments  Interactions with FDA Treatment of a Single Patient in Emergency Setting
Non-clinical Components   Safety Reports   Clinical Hold Treatment of a Single Patient in Non-emergency Setting
Clinical Components Annual Reports   Investigator's Responsibilities Treatment of a Group of Patients


Please review the latest FDA guidance for determining the need for an IND.   For additional information on submitting INDs for unmarketed medical products please contact the HRPP.


Last updated: 25 Jul 2019

The Pre-IND Process

Review the five requirements below to determine if your study qualifies for exemption from an IND (21 CFR 312.2).

Still not sure? Start with the IND Decision Tool. Pay particular attention to requirement #3. The FDA Draft Guidance Investigational New Drug Applications (INDs) – Determining Whether Human Research Studies Can Be Conducted without an IND provides more detail on a range of issues, including the process for consulting with FDA.

If you think a pre-IND meeting is warranted please contact the HRPP for assistance.  Templates for a meeting request letter and pre-IND briefing packet are provided below.  In addition, please consult with the IRB to determine whether a formal letter from FDA is required to document the waiver.

IND Exemptions 

A drug that is lawfully marketed in the United States is exempt from the requirements for an IND if all of the following apply:

  • The investigation is not intended to be reported to the FDA in support of a new indication for use or any other significant change in the labeling for the drug.

  • The investigation is not intended to support a significant change in the advertising for a prescription drug product.
  • The investigation does not involve a change in route of administration, dosage level, or patient population, or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with use of the drug product.
  • The investigation is conducted in compliance with the requirements for IRB review (21 CFR 56) and informed consent (21 CFR 50).
  • The drug may not be represented as safe or effective for the purposes for which it is under investigation, nor may it be commercially distributed or sold.

For additional information about whether or not an IND is required for a cancer therapy drug you must contact the NCI Regulatory Affairs Branch.

Need assistance or have regulatory questions? Please contact the HRPP.

Last updated: 20 Sep 2019

The IND Study Protocol

A fully developed clinical protocol is the basis for both the IRB Application and the initial IND submission.

Review the IND Protocol Template for required content.  A completed protocol must be included in the IND application.

Start with a Protocol Synopsis (page 7 and 8 of the protocol template). The protocol synopsis will be valuable if you are planning a pre-IND meeting. Compile a reference list - include all published articles and unpublished reports or manuscripts cited.

Collect a copy of each article or report listed. For approved medications, print and read the Prescribing Information.

Product information should be integrated into the protocol. In addition, your safety plan should acknowledge known safety risks from the prescribing information and incorporate relevant safety monitoring into the protocol - or show why it is not relevant to the disease under study.

Need assistance or have regulatory questions? Please contact the HRPP.

Last updated: 7 Feb 2019

Prepare the Initial IND Submission

The IND Sponsor-Investigator compiles information in three broad areas:

  • Animal Pharmacology and Toxicology Studies: Preclinical data used to assess whether the product is reasonably safe for studies in humans. For studies of marketed drugs in new indications, this section might contain data from animal models supporting the utility of the drug in the new indication.

  • Manufacturing Information: The composition, stability, and controls used for manufacturing the drug substance and the drug product.

    • For marketed drugs, the FDA already has this information on file in the manufacturer’s Drug Master File (DMF). For unmarketed drugs, the Investigator-Sponsor can request a Letter of Authorization (LOA) from the manufacturer to cross-reference the Drug Master File or existing IND if there is one. Although it is not required, the LOA is recommended.

    • For legally marketed drugs, the information in the product label or package insert might suffice for the manufacturing information.

  • Clinical Protocols and Investigator Brochures: A detailed clinical study protocol, and Investigator Brochure are required sections of an IND application. The Investigator Brochure is primarily needed for multi-center studies and is a summary of information needed by participating investigators to assess the safety of the investigational product. For approved medications, a copy of the Prescribing Information may be used in place of an Investigator Brochure.

The IND Sponsor-Investigator writes the IND in the format of IND Application Template. The initial IND submission should be accompanied by a cover letter, an IND Application Form - FDA 1571 (see instructions) and a ClinicalTrials.Gov Certification of Compliance - FDA 3674. (All forms optimized for Safari)

The IND Sponsor-Investigator must also submit a Statement of Investigator - FDA Form FDA 1572 (see instructions). This form is a formal contract with FDA to adhere to Informed Consent, IRB review, and general IND regulations.


Preparing the IND application package per FDA filing requirements (number of copies, cover colors, etc):

Last updated: 25 Jul 2019

File the Initial IND and Receive an IND Number

  1. The initial IND submission should be accompanied by a cover letter, a Form FDA 1571 (see instructions) and a ClinicalTrials.Gov Certification of Compliance - FDA 3674. (All forms optimized for Safari)
  2. All must be submitted in triplicate (an original and two photocopies):
  3. The IND Sponsor-Investigator completes, signs, and dates the Form FDA 1571.
  4. The IND Sponsor-Investigator assembles the signed submission and makes three photocopies and one PDF of the original documents.

*Please Note:  Academic Institutions are not required to submit electronically. However, if you would like to submit electronically, please see the following contacts and guidance.

For an initial submission, the IND Sponsor-Investigator sends the original and two photocopies to the appropriate address via overnight courier.  Keep one copy of the submission packet as well as a photocopy of the courier airbill.

For a Drug:

Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
5901-B Ammendale Rd.
Beltsville, MD. 20705-1266

For a Therapeutic Biological Product:
Food and Drug Administration
Center for Drug Evaluation and Research
Therapeutic Biological Products Document Room
5901-B Ammendale Rd.
Beltsville, MD. 20705-1266

On the delivery date, track the shipment on the courier website for confirmation of delivery.  Print the delivery confirmation and file it with the copy of the submission packet, which is kept in an IND Binder.

The FDA responds to the initial submission of a new IND with a letter, acknowledging receipt of the submission and assigning the IND number. The sponsor must wait 30 calendar days before initiating any clinical trials.  During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk. If there are no issues, the IND generally goes into effect 30 days after the Date of Receipt shown in this letter. It is advised that you obtain written confirmation (email or fax) that the FDA review has been completed and that the study May Proceed.

The IND Acknowledgement letter also provides the mailing address for all subsequent submissions to the IND.

Last updated: 23 Sep 2019

Maintain the IND

To maintain an IND, the Sponsor-Investigator has three reporting responsibilities.  Each type of report is time-sensitive and has a specific structure.  The first two, Protocol Amendments and Safety Reports, are submitted when needed to report updated or unforeseen circumstances. The third type, the Annual Report, is submitted every year, even when no studies are in progress under the IND.  Send all submissions to the address provided in the IND Acknowledgement letter received in response to the initial submission.

IND Protocol Amendments 

Once an IND is in effect, the IND Sponsor-Investigator is responsible to amend it as needed to ensure that the clinical investigations are conducted according to protocols included in the application.  An IND Protocol Amendment should have a cover letter and is a submission to an existing IND notifying the FDA of one or more of the following:

IND Annual Reports

An IND Annual Report requires a cover letter and is a brief report of the progress of studies conducted under an IND, due annually to the FDA within 60 days of the anniversary of the date that the IND went into effect.

IND Safety Reports

An IND Safety Report is expedited, written notification to the FDA of an adverse experience associated with the use of a study drug that is both serious and unexpected. “Associated with the use of the drug” is a Code of Federal Regulations term meaning “There is a reasonable possibility that the experience may have been caused by the drug.”  An IND Safety Report  consists of a MedWatch Form and a cover letter.  It is due to the FDA within 15 calendar days of initial receipt of the SAE Report.

Last updated: 30 Apr 2021
Last updated: 20 Mar 2019