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SOP on Investigational New Drug (IND) Application and Clinical Investigation Policy

Title: Investigational New Drug (IND) Application and Clinical Investigation Policy

Introduction and Purpose:

The conduct of clinical investigations (clinical trials) under an FDA-Regulated Investigational New Drug (IND) application involves compliance with a complex set of FDA regulations, requirements, and responsibilities. The FDA holds the IND application sponsor accountable for ensuring compliance with these regulations (21 CFR Part 312, Subpart D). While pharmaceutical companies are typical IND sponsors, individuals, governmental agencies, and academic institutions may also serve as sponsors (21 CFR Part 312.3).

This policy serves the following purposes:

  • To assist in determining when an IND is necessary.
  • To provide guidance and resources for individuals conducting clinical investigations, including sponsor-investigators, on obtaining an IND for the investigational drug.
  • To outline the process for compassionate use (expanded access) and emergency use of investigational drugs.

Definitions and Acronyms:

  • Biologic: A product, including vaccines and gene therapies, applicable to the prevention, treatment, or cure of human diseases. Most biologics are considered drugs by the FDA.
  • Botanical: A finished product containing plant matter, which may include plant materials, algae, fungi, or combinations thereof.
  • DEA: Drug Enforcement Administration
  • Drug: A substance recognized by an official pharmacopeia, intended for use in diagnosis, cure, mitigation, treatment, prevention of disease, or affecting the structure/function of the body.
  • Schedule 1 drugs: Substances with no accepted medical use in the United States, often associated with high risk of substance use disorder.
  • Emergency Use: The use of an investigational product under strict criteria on a single subject in a life-threatening situation when no standard treatment is available. It is not considered research.
  • Expanded Access: Also known as compassionate use, it allows a patient to receive an investigational drug outside of a clinical trial when enrollment is not possible.
  • Investigational New Drug (IND): A request submitted to the FDA to administer an investigational drug to humans, necessary before clinical trials.
  • Sponsor-Investigator: An individual initiating and conducting an investigation and directly administering or dispensing the investigational drug.
  • Supplement: A product intended to supplement the diet, including vitamins, minerals, herbs, amino acids, dietary substances, or concentrates.
  • CFR: Code of Federal Regulations
  • CRSO: Contract Research Support Office
  • FDA: United States Food and Drug Administration
  • IRB: Institutional Review Board
  • SOP: Standard Operating Procedure

IND Guidance:

IND Requirements:

  • U.S. regulations mandate an IND before conducting clinical studies of an investigational drug.
  • Investigational use covers unapproved products or approved products used beyond labeled indications.
  • An IND may be required when the primary intent is to develop safety or efficacy information.
  • Schedule 1 drug investigations also require DEA approval.
  • Clinical investigations of marketed drugs may be exempt from IND submission under specific conditions.

Pre-IND Meeting:

  • Sponsor-investigators may request a pre-IND meeting with the FDA.
  • While not obligatory, pre-IND meetings can help confirm IND requirements, ensure study design suitability, minimize clinical hold risks, control costs, and facilitate early FDA interactions.
  • Meetings are typically scheduled within 60 days of request receipt.

Initial IND Submission:

  • The sponsor-investigator is responsible for preparing and submitting the IND application to the FDA.
  • IND content varies but must include a complete protocol, informed consent, and investigational product details.
  • The FDA reviews the submission within 30 days and may request additional information.
  • Clinical study may commence after 30 days, barring FDA notification of clinical hold.

IRB Requirements:

  • The sponsor-investigator ensures IRB review and approval before initiating the study.
  • Proof of IND submission or waivers may be required by the IRB.
  • The Pre-IND Audit must be completed before IRB approval.

IND Amendment Requirements:

  • Protocol, investigator, site changes, and other amendments necessitate IND updates.
  • Informational amendments report non-protocol, non-safety information.
  • IND Safety Reports: Sponsor notifies FDA and investigators of serious, related, unexpected adverse experiences promptly.
  • Follow-up reports may provide additional information.
  • Non-serious adverse events are summarized in Annual Reports.

IND Annual Reports:

  • Due within 60 days of the IND anniversary date.
  • Include study summary and adverse event summaries.
  • Required even if the study has not begun.

IND Final Study Report:

  • Submitted upon study completion for IND closure.

IND Submission Documentation:

  • Maintain complete submission records per Clinical Research SOP, "Study Records Management."
  • FDA submission documents, responses, and correspondence are retained by the CRSO IND Specialist for studies using their services.

References:

  • 21 CFR Part 312: Investigational New Drug Application
  • 21 CFR Part 312, Subpart D: Responsibilities of Sponsors and Investigators
  • 21 CFR Part 312.3: Definitions and Interpretations
  • SOP: Study Records Management

Document Approval

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