This guidance is intended to help researchers in meeting the FDA requirements when investigating new drugs, biologics or dietary supplements in clinical research. Federal regulation 21 CFR 312 defines the requirements for clinical investigations of investigational drugs.
In This Section
- What is the Requirement?
- How Do I Comply With the Requirement?
- Ethical Considerations
[21CFR312.60] General responsibilities of investigators:
An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects under the investigator’s care; and for the control of drugs under investigation. An investigator shall, in accordance with the provisions of part 50 of this chapter, obtain the informed consent of each human subject to whom the drug is administered, except as provided in 50.23 or 50.24 of this chapter. Additional specific responsibilities of clinical investigators are set forth in this part and in parts 50 and 56 of this chapter.
In addition to the responsibilities of an investigator, if you hold an Investigator IND you will also assume the responsibilities of the Sponsor as laid out in 21 CFR 312.50:
Sponsors are responsible for selecting qualified investigators, providing them with the information they need to conduct an investigation properly, ensuring proper monitoring of the investigation, ensuring that the investigation is conducted in accordance with the general investigational plan and protocols contained in the IND, maintaining an effective IND with respect to the investigations, and ensuring that FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug.
Initial Review Application
On the ”Drugs and Biologics” page you will find the following information and question:
The risks of all drugs specified by the protocol must be described in the consent document. This includes investigational drugs and other drugs required for participation in this research. You must submit a package insert for all drugs required by the protocol with this application.
A drug is defined as:
- A substance recognized by an official pharmacopoeia or formulary.
- A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease.
- A substance (other than food) intended to affect the structure or any function of the body.
- A substance intended for use as a component of a medicine but not a device or a component, part or accessory of a device.
Biological products are included within this definition and are generally covered by the same laws and regulations, but differences exist regarding their manufacturing processes (chemical process versus biological process.)
From FDA glossary of terms.
Are investigational drugs, biologics or dietary supplements being studied in this project?
Mark “Yes” only if the research involves a drug that is not FDA-approved or is being used outside of its approved labeling; this is an investigational drug.
On the “Drugs and Biologics” page you will provide the following details:
- Drug, Biologic, or Dietary Supplement Name:
- Generic Name:
- Is this approved by the FDA?
- If it is approved by the FDA, will the results of this study be reported to the FDA to support a new indication or labeling change?
- If approved by the FDA, will the results of this study be used to support a significant change in advertising?
- If approved by the FDA, does this study involve a route of administration, dosage level, or use in a population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the drug?
- If approved by the FDA, are you monitoring for long term safety and efficacy of the approved drug with the intention of submitting the data to the FDA?
- Do you have an IND?
- What is the IND number?
- Who is the holder of the IND?
Investigator’s Brochure (IB)
Submit a copy of the current IB with your application for initial review.
Proof of IND
Proof of an IND can either be the letter received from the FDA acknowledging receipt of the submitted IND application (common for investigator-initiated research requiring an IND) or having the IND number imprinted on the study protocol (common for Sponsored research).
UC Davis IRB approval is required prior to initiation of any drug study. The IRB will review the research to ensure there are adequate protections for the human subjects and compliance with applicable regulations and policies. UC Davis IRB WORKSHEET: Drugs HRP-306 outlines the determinations the IRB must make when reviewing a clinical investigation involving medical drugs.
A Clinical Investigation is an experiment in which a drug is administered or dispensed to, or used involving, one or more human subjects. For the purposes of the IND regulations, an experiment is any use of a drug (whether approved or unapproved) except for the use of a marketed drug in the course of medical practice.
For example, a randomized trial evaluating an unapproved use of a lawfully marketed drug is a clinical investigation and may require an IND. In contrast, use of a lawfully marketed drug for an unapproved use in the course of medical practice is not a clinical investigation and does not require an IND because it involves the use in an individual patient where the primary intent is to treat the patient.
Emergency Use IND
An Emergency Use IND allows the 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 21CFR , Sec. 312.23 or Sec. 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.
IND (Investigational New Drug)
An IND means a new drug or biologic that is used in a clinical investigation. The term “IND” may also be used to describe the IND application required to be submitted to and approved by the FDA prior to beginning a clinical investigation of an unapproved drug or, in some cases, an approved drug used in a clinical investigation to test its safety and efficacy in an unapproved indication.
An Investigator IND is submitted by a physician who both initiates and conducts an investigation, 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.
A 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 the FDA review takes place.