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 U.S. Food and Drug Administration (FDA) regulates drugs, devices, dietary supplements, cosmetics and many other products manufactured and sold in the US.  The Center for Drug Evaluation and Research (CDER) is responsible for regulating manufacturing, testing and importation of pharmaceutical drugs in the US. This includes new drug approvals, abbreviated new drug approvals (generics), over-the-counter drugs, animal drugs and biologics. 

A drug is defined as:

  1. article intended for use in diagnosis, cure, mitigation, treatment, or prevention of the disease;
  2. articles (other than food) intended to affect the structure or any function of the body;
  3. articles intended to be used as components of any of the above.

What is Investigational New Drug Application (IND)?

The IND submission is the first step in the drug review process by the (FDA). An IND application is submitted by the company (sponsor) responsible for developing the drug. The IND is submitted after the sponsor has determined through animal studies that the proposed drug is reasonably safe for initial use in humans, and that it shows sufficient promise as a treatment to justify commercial development. The FDA reviews the IND application and decides whether it is safe for the company to progress to the next stage, i.e. clinical trials, wherein the drug is tested in humans. The sponsor has to wait for 30 calendar days after submitting the IND before commencing any clinical trials. At UC Davis, we typically submit INDs to use an already approved drug in a clinical trials for a new disease indication. 

Determine if your Study is Exempt from IND Requirements

Many academic investigators will want to conduct a clinical study with an already approved drug. This is often done to establish efficacy in a new disease indication. FDA provides provisions for conducting studies of lawfully marketed drugs through the use of an IND exemption. A clinical investigation of a drug is exempt from the IND requirements if all of the criteria for an exemption are met. These criteria are specified in the Codeof Federal Regulation, Chapter 21, Subchapter 312 ( 21 CFR 312.2)

    1. The investigational drug is lawfully marketed in the United States;
    2. The investigation is not intended to be reported to the FDA as a well-controlled study in support of a new indication for use of the drug product;
    3. The investigation is not intended to support a significant change in advertising to an existing lawfully marketed prescription drug product;
    4. The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
    5. The investigation will be conducted in compliance with the requirements for institutional review (IRB)
    6. The investigation will be conducted in compliance with FDA regulations 21 CFR 312.7: Promotion and charging for investigational drugs.

Thorough documentation is required to support this exemption criteria and may include prior publications or other public disclosures. If such evidence cannot be provided, a physician should submit a research IND (limited in scope) to the FDA. The physician who authored the protocol and submitted the IND is considered sponsor-investigator.

An excellent FDA Guidance with examples: Investigational New Drug Applications (INDs)—Determining whether Human Research Studies can be conducted without an IND.

UC Davis IRB could also provide help in determining the IND exemptions.

 

 

Prepare and Submit an IND

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. 

The UC Davis CTO provides step-by-step instructions for preparing and submitting an IND Applications, including templates and examples.

The FDA developed an excellent website to assist sponsor-investigators in IND preparation.

Contact: Kate Marusina, PhD, Director, Clinical Trials Office

Emergency Use/Expanded Access to Investigational Drugs

The terms “expanded access,” “compassionate use,” and “emergency use” are used interchangeably to refer to use of an investigational drug when the primary purpose is to diagnose, monitor, or treat a patient’s disease or condition. The distinction between administering an investigational drug in the setting of a ‘traditional’ clinical trial versus "expanded access" lies in the intention. In a traditional clinical trial the intention is to understand the safety and effectiveness of the investigational drug; in expanded access the intention is treatment.

Emergency use is defined as the use of an investigational drug or biological product with a human subject in a life-threatening situation in which no standard acceptable treatment is available and in which there is no sufficient time to obtain IRB approval. UC Davis IRB provides step-by-step instructions for Emergency Use of an unapproved drug.

General criteria for Emergency use are:

    1. Patients with a serious or immediately life-threatening disease or condition, where there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
    2. No comparable or satisfactory alternative therapy exists.
    3. The potential patient benefit justifies the potential risks of the treatment, and those risks are not unreasonable in the context of the disease or condition being treated.
    4. The expanded use of the investigational drug for the requested treatment will not interfere with the initiation, conduct, or completion of clinical investigations that could support marketing approval of the product.

UC Davis Health Policy 1509 "Emergency or "Compassionate" Use of Unapproved Drugs, Biologics or Devices"  provides important information on the steps that must be taken to ensure appropriate use of investigational products under the Emergency Use.

FDA Expanded Access Contact information is here

Non-Emergency Treatment INDs for Individual patients

In a non-emergency situation, a written request (IND) for individual patient use of an investigational drug must be submitted to the FDA.  The investigational drug may be shipped and treatment of the patient may begin 30 days after the application is received by FDA or earlier - if notified by the FDA that treatment may proceed.  These non-emergency requests are known as individual patient INDs, or single patient expanded access requests.

Here is the FDA instructions on submitting non-Emergency INDs 

Submit:

  • FDA Form 3926 (only opens in Internet Explorer). Instructions to fill out the form are here
  • Principal Investigator CV
  • Sponsor/Manufacturer Letter of Authorization
  • Treatment Protocol
  • Expanded Access Consent (in the UCD IRB template HRP-506)
  • Investigator Brochure

 

FDA Expanded Access Contact information is here

Is IND required for studies with dietary supplements?

Many clinical studies of academic investigators evaluate the effect of dietary supplements on the disease or physiological parameters. Some of these studies may require an IND submission. If the dietary supplements are investigated for diagnosis, cure, mitigation, treatment, or prevention of disease and are used to affect the structure or function of the body, then the dietary supplement will be considered a drug for the purposes of this study.

The study will be subject to the same regulations as any other unapproved drug. Specifically, the FDA will be paying particular attention to the composition of the dietary supplement, its origin and manufacturing processes. When preparing the INDs for dietary supplements, make sure that the supplement manufacturer is willing to provide this information.

An excellent FDA Guidance with examples: Investigational New Drug Applications (INDs)—Determining whether Human Research Studies can be conducted without an IND.

 

Investigational Drug Services at UC Davis 

According to Code of Federal Regulation 21 CFR 312.62(2), an investigator is required to maintain adequate accountability records for the investigational drug or biologic. At UC Davis Health all investigational drugs or biologics (also known as “test articles”) are handled by the Investigational Drug Services (IDS), a Division of the Pharmacy Department. IDS manages the receipt, storage, dispense, return and disposal of study drugs in accordance with Good Clinical Practice Guidelines, the study protocol requirements, and all applicable rules and regulations.  

Contact:  2315 Stockton Blvd, Rm DT 0762, Sacramento, CA 95817  Phone: (916) 703-4093 FAX: (916) 703-7048  email: HS-IDSCC@ucdavis.edu

 

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