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Investigational New Drug Application (IND) Process Overview

Per the FDA, an IND application 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 would submit an IND to propose a study of an unapproved drug, or a study of an approved product for a new indication or in a new patient population.

Does My Study Need an IND?

When the principal intent of the investigational use of a test article is to develop information about the product's safety or efficacy, submission of an IND may be required. Use this checklist to determine whether your protocol is exempt from IND review and submission. All criteria below must be met to constitute exemption.

  1. The study drug is lawfully marketed in the United States;
  2. The study is not intended to be reported to the FDA as a well-controlled study in support of a new indication or use; or support any significant change in the drug's labeling;
  3. The study is not intended to support a significant change in the advertising for a prescribed drug;
  4. The study does not involve a change in route of administration, dosage level, patient population, or other factors that significantly increases the risks associated with use of the drug product;
  5. The study complies with IRB evaluation and informed consent requirements; and
  6. The study sponsor and/or investigator do not represent in a promotional context that the drug is safe and effective for the purposes in which it is under investigation.

If all of the above criterion are met, your protocol is exempt from IND review and submission.

Note that situations do arise when studies can be exempt from IND submission even though they do not meet all the criteria above. Usually, such exemptions are granted because significant information about these treatments already exists in the literature - e.g., when a drug has been used clinically off-label regularly for the treatment of the studied condition and there is significant information in the literature about this use. In a situation of this kind, only the FDA can determine that the protocol is exempt. If you have doubts about whether your study requires an IND, contact the appropriate department at the FDA.

For guidance in deciding whether a study of marketed drugs or biological products for treating cancer falls within the exemption under 21 CFR 312.2(b)(1) from the general requirement to submit an investigational new drug application, please review the FDA guidance entitled, IND Exemptions for Studies of Study Lawfully Marketed Drug or Biologic Products for the Treatment of Cancer (pdf).

FDA Determination of Exemption

Although 21 CFR 312.2(b)(1) does not require a submission for a determination of exempt status, whenever an IND application is submitted, FDA staff perform an initial limited review of the application to determine whether the study is exempt. The protocol-related criterion used to assess exemption is (#4 above): The investigation must 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 risks) associated with the use of the drug product. If the FDA's initial limited review determines that a study protocol is exempt from the requirement for an IND, no further review of the study is performed. A letter is sent to the sponsor giving notice of the exemption.

The IND Application Process: How to File an IND

The following are the key components of an initial IND application:

Number of copies: Submit the original IND or IDE application and two copies to the FDA; file a copy for yourself in your Regulatory Binder

Where do I send my IND Application?

  • Initial Application
    Food and Drug Administration
    Center for Drug Evaluation and Research
    Central Document Room
    5901-B Ammendale Road
    Beltsville, MD. 20705-1266
  • Subsequent Submissions
    Send all subsequent submissions to your Project Manager using the address given on the IND/IDE 'Letter of Acknowledgement,'

When can I begin my study once I have submitted my IND to the FDA?

You will receive a letter with an IND number and Name of the Project Manager after the FDA receives your initial submission.

The IND/IDE goes into effect 30 days after the FDA has received the application, unless the FDA notifies the sponsor-investigator that the investigation is subject to a clinical hold.

Note: In addition to having your IND go into effect, you must receive formal Dartmouth approval from both the Committee for the Protection of Human Subjects and the Clinical Trials Office before your study may begin.

Maintaining an IND

Once your IND has gone into effect, you are responsible for its maintenance. Maintenance includes:

  1. Protocol Amendments
    • New protocol
    • Significant changes in a protocol, including:
      • Increase in drug dosage or duration of exposure, increase in # of subjects
      • Significant change in design (e.g., addition or dropping of a control group)
      • Addition of new test or procedure; dropping of test intended to monitor safety
    • New Investigator (adding an additional site for the conduct of the study previously approved under the IND)
  2. Information Amendments
    Information Amendments can include new toxicology, new chemistry, or other technical information
  3. IND Safety Reports
    • Required written reports
      For adverse experience associated with the use of the drug that is both serious and unexpected, or any finding from preclinical tests that suggests significant risk for humans:
    • Telephone and facsimile transmission reports
      For unexpected fatal or life-threatening experiences
      • The telephone call or facsimile must be made within 7 calendar days of notification and should be followed with a written report within 8 calendar days
      • Follow-up information should be submitted as soon as the relevant information is available
  4. Annual Report
    The Annual Report should be submitted within 60 days of the anniversary date that the IND went into effect. See IND Annual Report Template (pdf)
    Note: All IND Maintenance documents sent to the FDA should be accompanied by a cover letter and a Form 1571 specifying what updated information is being sent to FDA.

Regulatory Responsibilities of the Sponsor-Investigator

As defined in FDA regulations (21 CFR 312.3 and 812.3[o]), a sponsor-investigator is an individual who both initiates and conducts a clinical investigation, and under whose immediate direction an investigational drug or device is administered, dispensed, or used.

The requirements of a sponsor-investigator include both those applicable to an investigator and those applicable to a sponsor.

The following three documents can be helpful in understanding these obligations.

Additional IND Resources

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