Investigational New Drug (IND) Application

Requirements for an IND Application & Process

UTMB as the Sponsor and IND holder is required to submit an Investigational New Drug (IND) application as required by law, policy, and regulations to FDA on behalf of the research faculty member and/or Principal Investigator (PI) who intends to conduct a clinical investigation with an investigational new drug that is subject to 21 CFR 312.2(a). The Office of Research Integrity and Regulatory Affairs represents UTMB as the sponsor administrator.

UTMB can assist in the study planning and protocol development phases to ensure efficient review. We also provide consultation for study and participant documentation practices to assure compliance with UTMB polices and federal standards.

  • submits the application to FDA
  • manages compliance with IND application requirements
  • ensures proper monitoring of the investigation and IRB approval
  • oversees registration on Clinical

Review Time for initial submission of an IND application is 30 days from the date FDA receives the IND. UTMB and the Investigator may proceed with a clinical investigation once UTMB has been notified by FDA that the investigation may proceed or after 30 days if the IND is not placed on Clinical Hold. During this time, FDA has an opportunity to review the IND for safety to assure that research subjects will not be subjected to unreasonable risk.

The IND format set forth in § 312.23 should be followed routinely in the interest of fostering an efficient review of applications. The amount of information included in the IND application helps assist the FDA reviewer weigh the quality of scientific data for the proposed research is adequate to permit an evaluation of the drug’s effectiveness and safety. IND process guide for completion of the IND application including instructions for use and commonly used regulatory affairs forms and templates can be accessed here.

When submitting original applications, UTMB is expected to send the application in triplicate by mail or via electronic submissions depending on current FDA recommendations on receiving IND applications.

Each application should be accompanied with FDA Forms:

IND Submission Process Guide

1. Complete the following FDA required forms:

  1. Form 1571: Investigational New Drug Application
    1. Name of Sponsor and Sponsor Address/Contact information (#’s 1-4)
    2. (Information for #’s 5-9 should be provided by PI)
    3. (#10 should have the serial number of 0000 if this is initial IND application, the next submission as an amendment for an example should be 0001)
    4. (#16 and #17 should provide the person responsible for monitoring and conducting the progress of clinical investigations and review of drug safety moving forward)
  2. Form 1572: Statement of Investigator
    1. (This document should be completed by the Principal Investigator.)
    2. Include copy of all investigators CV’s
    3. Form 3674: Certification of Compliance with Requirements of (Coordinate with Clinical Trials office.)

2. A Cover Letter addressed to the Director of the Review Division is required for triaging an IND application and is expected to include the following:

  1. Submission Identifier: “Initial Investigational New Drug Application”
  2. Brief explanation of the intended investigation (type and title of study)
  3. Investigational new drug product’s name and proposed formulation
  4. Disease or condition under investigation
  5. IND manufacturer’s name and contact information (if applicable)
  6. Reference to an existing IND application (if applicable)

3. A Table of Contents is required with the contents in the application in the following format:

  1. Form FDA 1571 (21 CFR 312.23(a)(1))
  2. Table of Contents (21 CFR 312.23(a)(2))
  3. Investigator’s brochure (21 CFR 312.23(a)(5))
  4. Introductory statement (21 CFR 312.23(a)(3))
  5. General Investigational plan (21 CFR 312.23(a)(3))
  6. Protocol (21 CFR 312.23(a)(6))
    1. Study protocol (21 CFR 312.23(a)(6)) (Form FDA 1572 should substitute b-  d)
    2. Investigator data (21 CFR 312.23(a)(6)(iii)(b)) or completed Form FDA 1572
    3. Facilities data (21 CFR 312.23(a)(6)(iii)(b)) or completed Form FDA 1572
    4. Institutional Review Board data (21 CFR 312.23(a)(6)(iii) (b)) or completed Form FDA 1572
  7. Chemistry, manufacturing, and control data (21 CFR 312.23(a)(7))
    1. Environmental assessment or claim for exclusion (21 CFR 312.23(a)(7)(iv)(e))
  8. Pharmacology and toxicology data (21 CFR 312.23(a)(8))
  9. Previous human experience (21 CFR 312.23(a)(9))
  10. Additional information (21 CFR 312.23(a)(10))
  11. Biosimilar User Fee Cover Sheet (Form FDA 3792, When Applicable)
  12. Clinical Trials Certification of Compliance (Form FDA 3674)

The following contents of the application (#4 – 11) should be retrieved from the PI and/or the Study Team and placed into a Table of Contents as shown in #3 above.

4. An Introductory Statement:

  1. Introductory statement must include investigational drug’s name and all of its active ingredients, pharmacologic class, structural formula (if known), formulation of the dosage form to be used, the route of administration, and the broad objectives of the proposed clinical trial.
  2. There also must be a brief summary of previous human experience with the investigational drug including any marketing experience in other countries

5. General Investigational Plan:

  1. Discuss the research rationale for the use of the study agent and the specific study, the indications to be studied, the overall objectives and general approach to be followed in evaluating the drug
  2. An overview of the study proposed for the first year of investigation
    1. Summary includes study design, estimated enrollment, total number of subjects exposed to study drug, endpoints, and treatment plan. Include any anticipated risks from the study drug based on pre-clinical and clinical experience with the drug

6. Include Investigator’s Brochure (“IB”)

  1. The IB will be useful to both the sponsor-investigator and the FDA review team.

7. Include the Study Protocol

  1. IND regulations allow a protocol outline, rather than a complete protocol to be submitted for Phase 1 trials with the following information:
    1. Estimate of number of subjects involved
    2. Description of safety exclusions (and inclusion criteria)
    3. Description of dosing plan including the duration, dose, dose escalation, schedule or method to be used in determining dose
    4. All details that describe those elements of the trial that are critical to safety (necessary monitoring of vital signs and blood chemistries)

  2. For Phase 2 and 3 trials, the following must be provided in detailed protocols
    1. Statement of the objectives and purpose of trial
    2. For a sponsor-investigator, the sponsor-investigator’s name, address, and statement of qualifications and the name of each sub investigator
    3. Subject Inclusion and exclusion criteria
    4. Description of the trial design including type of control group used if any
    5. Method for determining the doses to be administered. Maximum dosage and duration of subject exposure to investigational drug
    6. Description of observations and measurements to be made to fulfill trial objectives
    7. Description of clinical procedures, laboratory tests, and other measures taken to monitor the effects of the investigational drug in human subjects to minimize risk
  3. Informed Consent forms are frequently included with protocols and are encouraged to be submitted with the protocol

8. Include Chemistry, Manufacturing and Control Information

  1. An IND must include sufficient CMC information to ensure the proper identity, strength, quality, and purity of the investigational drug.
    1. The label for the immediate packaging of the investigational drug must contain “Caution: New Drug – Limited by Federal (or United States) law to investigational use”
    2. An environmental assessment under 21 CFR 25.40 or a statement requesting a categorical exclusion from an environmental assessment under provisions for in 21 CFR 25.31

9. Include Pharmacology and Toxicology Information

  1. Information regarding any pharmacological and toxicological studies of the investigational drug involving lab animals or in vitro support that is reasonably safe to conduct the proposed clinical trial

10.     Include Previous Human Experience with the Investigational Drug

  1. If there has been previous human experience with the investigational drug, the sponsor-investigator is required to provide a summary of this information

11.     Additional Information

  1. If the drug has evidence of dependence, abuse potential or is a radioactive drug, this information must be included
  2. If a device is to be used in conjunction with the investigational drug, the FDA may require more information on the manufacturer and model of the device

Once items #4-11 are collected, submission can commence by the compliance or regulatory office.

12.     Submit Application & Documents to the FDA

  1. The initial IND submission and each subsequent submission to the IND should be accompanied by a Form FDA 1571 and must be submitted in triplicate (the original and two photocopies are acceptable)

  2. Mailing Address for a Drug:
    Food and Drug Administration
    Center for Drug Evaluation and Research
    Central Document Room
    5901-B Ammendale Rd.
    Beltsville, Md. 20705-1266

  3. Mailing Address for a Therapeutic Biological Product:
    Food and Drug Administration
    Center for Drug Evaluation and Research
    Therapeutic Biological Products Document Room
    5901-B Ammendale Road
    Beltsville, MD 20705-1266