Beginner’s Guide to Investigational New Drug and Investigational Device Exemption

Meghan Hosely
May 5th, 2020

When a trial originates within a research site, an investigator begins what is known as an investigator-initiated trial (IIT). When conducting an IIT, oftentimes, an investigational new drug (IND) or investigational device exemption (IDE) application is necessary.

To review, an IND is a request for authorization from the Food & Drug Administration (FDA) to administer an investigational drug or biologic to humans. An IDE allows an investigational device to be used in a clinical study to collect safety and effectiveness data that’s required to support premarket approval application or a premarket notification submission to the FDA.

Requirements for an IND or IDE Application

When working with the FDA for an IND or IDE, a site must submit an application prior to proceeding. The initial application includes a variety of information pertaining to the sponsor-investigator and information on the study.

To show they’re qualified, the sponsor-investigator’s CV is required in the application, along with the Form FDA 1572, which proves they’re qualified to work on the IND or IDE. The complete protocol and any protocol amendments must also be attached to the application, along with the investigator brochure. The investigator brochure must contain information on drug dosage, risks to taking the drug, as well as storage, handling, and procurement of the drug. If at any point there are changes to the brochure, the FDA needs to know so the brochure is kept as accurate as possible. Lastly, the application must include information about the Institutional Review Board (IRB) the site is working with to conduct the IND or IDE.

Once the FDA receives the application, a site can move forward with their IND or IDE 30 calendar days after initial submission. The FDA won’t notify the investigator of approval – if the 30 days have passed and there isn’t notification from the FDA, it’s considered safe to proceed with the IND or IDE.

Safety Reporting for an IND and IDE

As with other trials, sites working with an IND or IDE will run into adverse events (AEs) and, occasionally, serious adverse events (SAEs). When working on an IIT, the responsibility falls on the investigator to determine if the event is serious enough to report to the FDA. Determining if an event needs to be reported is challenging since it will largely be determined by the investigator’s experience to decide if it’s serious. When in doubt, it’s best practice to report to the FDA.

If there is an SAE or an unexpected AE that was likely to be related to the IDE or IND, the investigator needs to report it to the FDA within 15 days. Any unexpected fatal or life-threatening SAEs must be reported within seven days. Investigators can report SAEs or unexpected AEs on via the MedWatch form.

Since it’s up to the discretion of the investigator to define an AE or SAE, coordinators have the advantage of sitting down with their investigator to lay out the entire protocol. Defining an AE or SAE will help mitigate confusion, and everyone on protocol will see and understand what must be reported right away.

IND and IDE Annual Report Requirements

Reporting to the FDA doesn’t stop once the application is submitted, approved and the study team begins work on the protocol. Submit the annual report within 60 days of the first anniversary of the date the IND went into effect, and every subsequent year. The annual report will need to include documentation summaries such as:

  • Each study in progress or completed
  • Most frequent and most serious AE
  • General investigational plan for the upcoming year

An annual report should also include a list of any participant deaths, including the cause of death, in order to give a comprehensive view of any patterns. In addition to the AE summary, provide a list of subjects who withdrew from the study due to AEs. Documenting these requirements as they happen in real time will help the research team immensely when gathering information to submit to the FDA.

IND and IDE Exemption

Not all IITs will require an IND or IDE – there are exceptions. The FDA may determine a trial is exempt from IND and IDE requirements if the following criteria are met:

  • The drug or device is lawfully marketed in the U.S.,
  • The study isn’t intended to result in a new indication or significant change in labeling of the drug or device,
  • The investigation isn’t intended to support a significant change in advertising for the prescription drug,
  • The investigation doesn’t increase the risk associated with the drug or device,
  • The investigation is overseen by an IRB, and
  • The investigation is not intended to promote or commercialize the drug or device

As if your site was handling an IND or IDE, if you are unsure if your IIT requires one, it never hurts to reach out to the FDA to determine if an application is needed. Ensuring your trial is or is not exempt will save your research team time in the end, enabling everyone to focus more on conducting the trial.

To learn more about IITs, including funding sources and challenges, read Advarra’s article “The Noble Pursuit of Investigator-Initiated Research.”

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