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115. FDA Investigational New Drug Application: Purpose and Withdrawal (IND) (§312.20 - 312.38)

FDA's primary objectives in reviewing an IND are to assure the safety and rights of subjects.

An investigational new drug may be used in a clinical investigation if the sponsor of the investigation submits an IND for the drug to FDA; the IND is in effect; and the sponsor complies with all applicable requirements.

Each participating investigator conducts his or her investigation in compliance with all applicable requirements.

NOTE: An investigator may not administer an investigational new drug to human subjects until the IND has gone into effect.

An IND allows the sponsor to transport or distribute investigational drugs across state lines under one of two categories: commercial and research (non-commercial). The IRB is concerned with research INDs that propose clinical studies to assess the safety and efficacy of an unapproved drug or use of an approved drug for a new population, dosage, or condition.

Information about IND applications and a link to information about investigator-initiated IND applications may be found on the "Investigational New Drug (IND) Application" pages of the FDA website.

Clinical investigation Phases

Phase 1: The initial introduction of an investigational new drug into humans to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and to gain early evidence on effectiveness.

Phase 2: Controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug.

FDA's objective for Phase 2 and 3 investigations is to assure the quality of the scientific evaluation of drugs is adequate to permit an accurate assessment of the drug's effectiveness and safety.

Phase 3: Expanded controlled and uncontrolled trials performed after preliminary evidence suggests effectiveness of the drug has been obtained. Phase 3 studies are intended to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling.

Withdrawal of an IND by a Sponsor

A sponsor may withdraw an effective IND at any time. University and affiliate investigators must notify the Biomedical IRB that the sponsor withdrew the IND along with information about the reason for the withdrawal and specify if stocks of the drugs were returned to the sponsor or disposed of as described in the sponsor protocol or agreement.

116. IND or Sponsor Protocol Amendments (§312.30)

IND or Sponsor Protocol Amendments

FDA categorizes sponsor amendments to an approved IND as follows:

  • Amendments for new protocol: Required when the sponsor intends to conduct a study that is not covered by a protocol already contained in the IND.
  • Amendment for changes to an existing protocol: Required for (1) any changes in a Phase 1 protocol that significantly affect the safety of subjects or (2) any changes in a Phase 2 or 3 protocol that significantly affect the safety of subjects, the scope of the investigation, or the scientific quality of the study.
  • Amendment for new investigator: Required when a new investigator is added to carry out a previously submitted protocol. A protocol amendment is not required when a licensed practitioner is added in the case of a treatment protocol.

Additionally, a sponsor may submit an information amendment to provide the FDA with essential information on the IND that is not within the scope of a protocol amendment, or IND safety or annual report.

Investigator Requirements for Informing the IRB of Sponsor Amendments

University and affiliate investigators must submit all sponsor amendments for IRB review. The submission should include a modification request listing and justifying the amendments, and copies of the relevant sponsor correspondence and the amended materials.

NOTE: If the sponsor requires specific language for IRB approval or authorization letters, investigators are advised to inform the IRB of those requirements.

IRB Review of Sponsor Amendments

Depending on the potential impact of the amendments, the IRB will review and either approve or acknowledge the amendment. Substantive amendments may require review at a convened IRB meeting. Alternatively, the IRB may use expedited procedures to review and acknowledge amendments that are administrative in nature, and neither alter the risk to benefit ratio of the study nor involve changes to study materials.

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