An Investigational New Drug is a new drug or biologic used in a clinical investigation.

In general, the submission of an Investigational New Drug (IND) application is required for any clinical research study that proposes the use (e.g., as a research tool to explore a biological phenomenon or disease process) or evaluation (i.e., for safety and/or effectiveness) of an unapproved drug.

Clarifying the "New" in IND

One of the FDA's primary mechanisms for ensuring the safety of research subjects is through Investigational New Drug (IND) filing requirements. The term IND can be misinterpreted, leading researchers to inaccurately conclude that if the drug they are studying is already approved by the FDA, it is not a "new" drug needing a IND application to be filed.

A study that uses a "new" aspect of the drug's use (i.e. different indication, dose, population, etc.) usually requires the filing of an Investigational New Drug Application. An IND application is a request for authorization to administer an investigational drug or biologic to humans or a marketed drug in a new indication and/or patient population.

General Requirements for Submission of IND Applications for Clinical Research Studies involving Drugs (including biologics) NOT Currently Approved for General Marketing by the U.S. Food and Drug Administration (FDA)

Exceptions to the General requirements for an IND submission

• Dietary supplements: Dietary supplements are exempt from FDA regulation as "drugs" provided that they are being evaluated and/or are labeled for intended use in affecting the structure or function of the body (i.e., a structure/function claim). However, the evaluation of a dietary supplement for the diagnosis, prevention, mitigation, treatment or cure of a specific disease or condition (i.e., a disease claim) requires the prior submission of an IND application.
• Human cells, tissues, and cellular and tissue based products (HCT/Ps): Certain HCT/Ps are exempt from FDA regulation as "drugs" and thus their evaluation or use under a clinical research study does not require the prior submission of an IND application.
• Radioactive drugs for research use: Radioactive drugs for certain research uses do not require the submission of an IND application. Please contact Amanda Wood for more information.
• NOTE: The use of new drug combinations not supported by literature are generally NOT exempt. Per FDA guidance: "Unless adequately described in the literature, initial studies involving new drug combinations should be performed under an IND because of the possible occurrence of synergistic toxicity."

Not sure if you need an IND?

If you would like to discuss your research project and the potential need for an IND, or request guidance with an IND application, please contact Amanda Wood. The NC TraCS Regulatory Service is available to assist Sponsor-Investigators with preparing IDE submissions, annual reports, supplements, and other FDA correspondence.

Through our partnership with RTI International, we can also provide pre-clinical guidance for Investigational Drug studies to facilitate thorough pre-clinical testing and trouble-free Pre-IND communications with the FDA.

Preparing an Initial IND Submission: For help, download a detailed IND submission template with instructions. NC TraCS is available to assist investigators through every step of the submission process, through the duration of the investigation, and IND closure.

The "life cycle" of an IND can involve many amendments formal reports over the course of an investigation. To avoid costly delays, submissions should be provided in a timely manner, and correspondence with the FDA initiated early if there are questions.

IND Holder Responsibilities: Once an IND is submitted, the IND Sponsor-Investigator is responsible for:

• Selecting qualified investigators
• Ongoing monitoring of all studies submitted to the IND
• The validity of the data from all sites conducting research under the IND
• Maintaining adequate records of receipt, shipment, and disposition of the investigational drug
• For multi-site studies, ensuring that all sites are kept informed of adverse events and safety updates

The IND holder must notify the FDA of any of the following:

Protocol Amendments

— Any changes to the protocol or any new protocols using the investigational agent
— Any new sub-investigators or changes to investigators (with a revised FDA Form 1572)

Safety Data

— IND Safety Reports
— IND Annual Reports (includes a summary of all study findings and adverse events to date)

Investigational Drug Updates

— Any changes to the chemistry, manufacturing, and controls
— Changes to the Investigational Brochure

Closing Out the IND

Additional guidance on submitting an IND application

• ReGARDD.org: Regulatory Guidance for Academic Research of Drugs and Devices — prepared by a consortium of regulatory specialists from UNC, RTI, Duke, and Wake Forest to assist investigators with regulatory submissions
• FDA.gov: information for sponsor-investigators submitting IND applications
• ClinicalTrials.gov: all applicable clinical trials must be registered on clinicaltrials.gov