Investigational New Drug (IND) Resources

Overview

The following information is provided to guide sponsor-investigators (SI) through the Investigational New Drug (IND) process. The information below is provided only as guidance. Specific questions and inquiries regarding IND Applications should be addressed to the FDA.

An Investigational New Drug (IND) is a drug or biological product that has not been approved for general use by the Food and Drug Administration (FDA). It is used in a clinical trial to investigate its safety and efficacy. The term also includes biological products used in vitro for diagnostic purposes. An IND application is a request for authorization from the FDA to administer an investigational drug or biological product to humans.

The federal regulations for INDs are found at 21 CFR 312.

IND Process Flowchart

All clinical investigations of drugs or biologics, whether or not approved for marketing by the FDA, require IRB review and approval.

Frequently Asked Questions for Early Investigators

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Yes, an IND application is a request to the FDA for authorization to administer an investigational drug (or biologic) to human or a marketed drug in a new indication and/or patient population. However, there are IND Exemptions. Please refer to the section on IND Exemptions for more information.  

A study can be deemed IND Exempt if all of the following criteria are met:

  • If the study is not designed to support approval of a new indication or a change in label;
  • If the study is not intended to support a significant change in the advertising for the product;
  • If the study does not involve a route of administration, dosage level or patient population that significantly increases the risks (or decreases the acceptability of risk) associated with the use of the drug;
  • The study is conducted in compliance with the IRB and Informed Consent regulations; and
  • The study is conducted in compliance with regulations regarding promotion for investigational drugs.

The term includes drugs (including botanicals, biologicals, and gene therapy, and genetically derived products that meet the definition of a “drug”), and medical devices for human use. The FDA has statutory authority to regulate the development and marketing of these products.

An investigational drug is defined as:

  • An article that is not approved (for marketing) in the US as a drug.
  • An approved drug that is not used according to the approved label (or a new combination of approved drugs).

Drug labeling refers to all the printed material that accompanies a drug, including the label, the wrapping, and the package insert.

“Off-label use” is any difference in use, including indication, dose, route of administration, patient populations, and drug formulation from what is approved on the FDA label.

“On-label use” means the drug is being used in the same indication, dose, route of administration, patient populations, and drug formulation. There is no deviation from the approved FDA label. Studies involving the on-label use drug do not require an IND, as long as data will not be used in a marketing application.

An IND is not needed for studies involving marketed drugs such as:

  • Some studies using commercially marketed drugs
  • Some studies using in vitro diagnostic biological products (e.g., blood grouping serum, reagent red blood cells, anti-human globulin)
  • Studies using drugs in vitro or in laboratory research animals

IND Exemptions

Before submitting an IND application, investigators should reference the Guidance for Clinical Investigators, Sponsors, and IRBs: Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND to determine whether their clinical investigations may be conducted without submitting an IND application.

There are 5 types of IND exemptions:   

  1. Drug/Biologic U.S. Product
  2. In Vitro Diagnostic Biological
  3. In Vitro/Animal Lab Research
  4. Placebo
  5. In Vivo Bioavailability or Bioequivalence

To determine if your study qualifies for an IND exemption, please fill out the Appendix for Drugs and submit in eIRB for review. Please reference our Getting Started webpage for more information about submitting an IRB application for review.

IND Exemptions Chart 

Pre-IND Consultation

The FDA’s Center for Drug Evaluation and Research's (CDER) Pre-IND Consultation Program fosters early communications between sponsors and new drug review divisions to provide guidance on the data necessary to warrant IND submission. The review divisions are organized generally along therapeutic class and can each be contacted using the designated CDER Contact Information. See the FDA's guidance on Pre-IND Meetings for more information.

Investigator-Initiated IND Applications

This table provides links to information for investigators about submitting IND applications to the FDA. See Useful Links, Forms, and Templates below for documents needed to submit an IND application to the FDA.

FDA Receipt of IND Application

Upon receipt of the IND application, the FDA assigns an IND number and forwards the application to the appropriate reviewing division. The reviewing division will:

  • Send a letter or email to the SI providing notification of the IND number assigned;
  • Date of receipt of the original application;
  • The address to send future IND submissions; and
  • The name and telephone number of the FDA person to whom questions about the application should be directed.

After review, the FDA may:

  • Grant the IND
  • Grant an IND Exemption
    • The FDA can exempt a clinical investigation of a drug product that is lawfully marketed in the US from the requirements for an IND if it meets certain criteria. The IRB can also make this exemption determination.
  • Place the IND Application on a Complete or Partial Clinical Hold
    • Holds may require modifications to and resubmission of the protocol to the FDA. If approved, the modifications should be submitted to the IRB.
    • When a proposed study has been placed on hold, the investigational drug may not be administered to research subjects.

The FDA is required to respond to an IND sponsor within thirty (30) calendar days of receipt of a complete IND application. An IND goes into effect thirty (30) days after the FDA receives the application. The SI may begin the study thirty (30) days after the FDA receives the IND application.

If the IRB determines that an IND is required, but the FDA disagrees, the investigator must attach documentation of the FDA’s determination to the IRB application. This documentation can be an email or letter from the FDA and should be clearly labeled as such. See the FDA’s Information for Sponsor-Investigators.

IND Sponsor-Investigator Responsibilities Checklist

An individual may function as an investigator, sponsor, or sponsor-investigator of a clinical investigation. A sponsor-investigator assumes the responsibilities of, and must comply with, FDA regulations applicable to both a sponsor and an investigator. These responsibilities include the submission and maintenance of an IND.

IND Sponsor-Investigator Responsibilities Checklist

Maintaining the IND

To maintain an IND, the Sponsor-Investigator has reporting responsibilities:

  • Each type of report is time-sensitive and has a specific structure.
  • Protocol Amendments and Safety Reports are submitted when needed to report updated or unforeseen circumstances.
  • 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 from the FDA in response to the initial submission.

IND Protocol Amendments

Once an IND application is in effect, the sponsor may amend the application as needed to ensure that the clinical investigations are conducted according to protocols included in the IND application. A sponsor of an IND application is expected to submit a protocol amendment to the IND when:

  • There is a new study using the same drug/biologic, which is not covered by the current protocol.
  • There are changes in the existing protocol that significantly affect safety of subjects, scope of the investigation, or scientific quality of the study.
  • There is a new investigator.

Safety Reports

The IND regulations require that, for serious adverse events (SAE):

  • Investigators: Except for study endpoints, the investigator must immediately report to the sponsor all SAEs, regardless of whether the investigator believes that they are drug-related or anticipated. Investigator must include an assessment of causality.
  • Sponsors: Within fifteen (15) days of becoming aware, the sponsor must notify the FDA and all participating investigators via IND Safety Reports of events that are unexpected, caused by the study drug, and meet the FDA definition of “serious.”

For nonserious adverse events, the FDA requires that the investigator report to the sponsor in accordance with sponsor and protocol requirements, generally on case report forms.

The IRB requires that the investigator report all unanticipated problems (UP) involving risk to participants or others to the IRB promptly (UA IRB defines “prompt” as 10 calendar days once the UP is discovered). UPs are unexpected, caused by the study intervention, and suggest risk to subjects or others.

Annual Reports

IND application sponsors are expected to submit brief reports of the progress of the investigations conducted under their respective IND application within sixty (60) days of the anniversary date that the IND application went into effect. Such reports are submitted annually.

Definitions

The following definitions appear in the Investigational New Drug Application regulations 21 CFR 312.3:

Any experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of this part, an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice.

Food and Drug Administration.

Investigational New Drug Application.

An individual who actually conducts a clinical investigation (i.e., under whose immediate direction the drug is administered or dispensed to a subject). In the event an investigation is conducted by a team of individuals, the investigator is the responsible leader of the team. "Sub investigator" includes any other individual member of that team.

A person who takes responsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic institution, private organization, or other organization. The sponsor does not actually conduct the investigation unless the sponsor is a sponsor-investigator. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has initiated is a sponsor, not a sponsor-investigator, and the employees are investigators.

An individual who both initiates and conducts an investigation, and under whose immediate direction the investigational drug is administered or dispensed. The term does not include any person other than an individual. The requirements applicable to a sponsor-investigator under this part include both those applicable to an investigator and a sponsor.

A human who participates in an investigation, either as a recipient of the investigational new drug or as a control. A subject may be a healthy human or a patient with a disease.

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