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Investigational Drugs or Biologics - Investigational New Drug (IND)

Form FDA 1572

Principal Investigators on treatment protocols that involve an Investigational New Drug (IND) must complete Form FDA 1572, which the sponsor then submits to FDA.

Form FDA 1572 is the contract between the clinical investigator and the federal government assuring that he or she will comply with the FDA regulations 21 CFR 312.53. In signing Form FDA 1572, the investigator assumes full responsibility for the study. The Principal Investigator may delegate some of the work of the study (subinvestigators listed on Form FDA 1572), but the responsibility remains with the Principal Investigator.

Protocols that involve an IND must be submitted for convened IRB review, and the Principal Investigator must include a copy of the most recent version of Form FDA 1572 along with the application.

If the Principal Investigator's Form FDA 1572 is changed in any way, a copy of the revised form should be submitted to the IRB along with a Project Revision/Amendment Form. If the revision includes any change in Subinvestigator(s), the Principal Investigator must submit a memorandum signed by any person(s) being added to document that they have read the protocol and agree to be a subinvestigator. If there is a change in Principal Investigator, the outgoing PI submits the Project Revision/Amendment Form and has the incoming PI sign also, indicating their agreement to transfer PI responsibilities. (See "Change in Principal Investigator" under Project Revisions & Amendments.)

IND Investigator Responsibilities

Performance of FDA-regulated studies using investigational drugs or biologics (i.e., agents that require an IND application/number for human use) creates important responsibilities for research investigators. See 21 CFR parts 11, 54, 210, 211, 312; the FDA Center for Drug Evaluation and Research; and UAB HRPP PRO121 Procedure to Ensure Handling of Investigational or Unlicensed Test Articles Meets Organizational Standards Relating to Pharmacy, Inventory Control, and Documentation.

In this circumstance the investigator is responsible for the following:

  • Ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations;
  • Protecting the rights, safety, and welfare of subjects under the investigator’s care;
  • and
  • Controlling the drugs under investigation.
  • Obtaining the informed consent of each human subject to whom the drug is administered, unless there is a specific exception under the FDA regulations (21 CFR §312.60).

The investigator statement (Form FDA 1572), once signed, contains a number of commitments by the investigator that generate specific investigator responsibilities. Under these commitments the investigator: Will conduct a study under the relevant current protocol and will only make changes in a protocol after notifying the sponsor, except, when necessary to protect the safety, the rights, or welfare of subjects;

  • Will comply with all the investigator obligations and pertinent requirements in the FDA regulations pertaining to investigational drugs;
  • Will personally conduct or supervise the described investigation;
  • Will inform any potential subjects that the drugs are being used for investigational purposes;
  • Will ensure that the requirements under FDA regulations for obtaining informed consent and IRB review and approval are met;
  • Will report to the sponsor adverse experiences that occur during the course of an investigation in accordance with FDA regulations;
  • Has read and understands the information in the investigator’s brochure, including the potential risks and side effects of the drug; and
  • Will assure that all associates, colleagues, and employees assisting in the conduct of the study are informed about their obligations in meeting the above commitments.

In addition, the investigator statement expressly commits the investigator to have an IRB that is constituted in accordance with FDA regulations perform the initial and continuing reviews and approvals for any investigation which requires IRB review. This commitment requires the investigator to promptly report to the IRB all changes in the research activity and all unanticipated problems involving risks to human subjects or others, and not to make changes in the research without IRB approval, except when necessary to eliminate apparent immediate hazards to the human subjects (21 CFR §312.53(c)(1); 21 CFR §312.66).

All clinical investigators subject to the IND regulations must provide the sponsor of the study with sufficient accurate information to allow the sponsor to file accurate financial statements with the FDA. There are two types of financial statements: a financial disclosure statement listing prescribed categories of financial interests that could potentially bias a clinical study and a certification stating no such financial interests exist. The investigator must promptly update this information if any relevant changes occur in the course of the investigation or for 1 year following completion of the study. The categories of financial interests requiring disclosure include:

  1. Any financial arrangement between the sponsor and investigator whereby the outcome of the study affects the amount of compensation to the investigator,
  2. Any proprietary interest in the tested product held by any investigator involved in a study,
  3. Any significant equity interest in the sponsor of the study held by any clinical investigator involved in the study,
  4. Any significant payments of other sorts from the sponsor of the study.

A significant equity interest generally means any equity interest (e.g., stock, stock options) for non-publicly traded companies and an equity value greater than $50,000 for publicly traded companies. Significant payments of other sorts means payments by the sponsor made to the investigator or institution to support the activities of the investigator that have a monetary value of more than $25,000, exclusive of the costs of conducting the clinical study or other clinical studies (e.g., grants, equipment, retainers, or honoraria) during the time the clinical investigator is carrying out the study and for 1 year after completion of the study. Residual credit balances in grant accounts that meet this definition may constitute significant payments of other sorts if these credit balances are available to support the activities of the investigator (21 CFR §§54.1-54.4).

The investigator must maintain control of an investigational study drug. An investigational drug may only be administered to subjects under the personal supervision of the investigator or a designated subinvestigator. An investigator must not supply the drug to anyone not authorized under FDA regulations to receive it (21 CFR §312.61). It is generally and highly preferable to meet this responsibility by arranging for a central pharmacy to receive, store, distribute, and keep proper documentation according to a predefined protocol for investigational drugs.

Other responsibilities under FDA regulations on investigational drugs include the following:

  • Keep, maintain, and retain records;
  • Supply reports;
  • Comply with inspections; and
  • Secure controlled substances.

Records

Investigators must prepare, maintain, and retain records of the investigation. Adequate records are required for drug disposition including dates, times, and amounts administered to subjects. Any unused supplies of drug must go back to the sponsor or be disposed of at the sponsor´s direction in accordance with regulation. Again, record requirements for drug disposition are accomplished best by using a central pharmacy to handle the drug.

Also, an investigator must prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the study for each individual receiving an investigational drug or serving as a control. Case histories consist of case report forms and supporting documentation such as copies of progress notes, radiographic interpretations, and laboratory reports. All case histories must document that informed consent was obtained prior to participation in the study or a regulatory exception applied. Under the FDA regulations, records must be retained for at least 2 years following the date of marketing approval of the drug or 2 years after an investigation is completed and FDA notified. In most instances this time period will exceed the 3-year retention requirement under DHHS regulations.

Reports

Besides supplying information for financial statements (see above), an investigator has responsibility to furnish information for or prepare the following:

  • Progress reports,
  • Safety reports, and
  • Final reports.

An investigator must furnish to the sponsor all reports required for submission of the annual progress report to the FDA. Also, the investigator must promptly report to the sponsor any adverse effect that may reasonably be regarded as caused by, or probably caused by, the drug. If the adverse effect is alarming, the investigator must report it immediately. Shortly after completion of an investigator’s participation in the study, (s)he must provide a final report to the sponsor (21 CFR §312.64).

Inspections

An investigator must permit, at reasonable times, an authorized FDA official or employee to have access to, and copy, and verify any records or reports made by the investigator pertaining to case histories and drug disposition. The names of the subjects do not have to be divulged unless the records of particular individuals require more detailed study or unless there is reason to believe the records do not represent actual case histories or actual results obtained (21 CFR §312.68).

Controlled Substances

An investigator must take adequate precautions to prevent theft or illegal diversion of investigational drugs that are controlled substances. Such precautions include maintaining security of the drugs with controlled access and a locked sturdy repository when such drugs are maintained for some reason outside a central pharmacy (21 CFR §312.69).

IND Sponsor Responsibilities

If you are the sponsor and the investigator for the drug, you must meet the requirements for the sponsor and the investigator. This is an overview of the Food and Drug Administration (FDA) sponsor requirements contained in 21 CFR 312 for research with Investigational New Drugs (INDs). Other FDA regulations for sponsors include, but are not limited to, 21 CFR Parts 11, 54, 210, and 211. Please review the federal regulations before performing any sponsor’s duties.

Major Responsibilities of Sponsors with IND Studies
  • Submits an IND application form 1571 and other required documents to FDA. (21 CFR 312.23)
  • Labels the investigational drug in accordance with FDA regulations. (21 CFR 312.6)
  • Promotes and distributes the drug in accordance with FDA regulations. (21 CFR 312.7)

21 CFR 312.53-55

  • Selects qualified investigators based on training and experience.
  • Ships investigational drugs only to investigator(s) participating in the investigation.
  • Obtains FDA Form 1572 from the investigator(s).
  • Obtains a written statement that the investigator(s) will conduct the study as outlined in the protocol.
  • Obtains relevant financial information from the investigator(s). (21 CFR 312.54)
  • Selects a qualified monitor to oversee the progress of the investigation.
  • Complies with FDA regulations regarding emergency use. (21 CFR 312.54)
  • Keeps investigator(s) informed on the safety and effectiveness of the drug. (21 CFR 312.55)

21 CFR 312.56

  • Monitors the progress of all IND investigations.
  • Terminates investigator(s) participation when investigator(s) fails to follow protocol.
  • Reviews and evaluates the evidence relating to the safety and effectiveness of the drug as it is obtained from each investigator(s).
  • Discontinues the study if the investigational drug presents an unreasonable and significant risk to subjects.
  • Notifies the FDA, IRB, and the investigator(s) if the study is discontinued.
  • Sends safety reports to FDA. (21 CFR 312.32)

21 CFR 312.57

  • Maintains adequate records showing the receipt, shipment, or other disposition of the investigational drug.
  • Maintains complete and accurate records of payments made to clinical investigator(s).
  • Assures that investigator(s) return all unused investigational drugs. (21 CFR 312.59)

21 CFR 312.62

  • Requires investigator(s) to maintain adequate drug records.
  • Requires investigator(s) to keep case histories on each individual administered the investigational drug or employed as a control in the investigation.
  • Requires investigator(s) to meet local IRB requirements. (21 CFR 312.66)
  • Collects reports (financial, progress, safety, and final report) from investigator(s). (21 CFR 312.64)
  • Requires investigator(s) to store the investigational drug in a secure area. (21 CFR 312.69).

There are other sponsor responsibilities beyond the scope of this summary (e.g., good manufacturing practices (21 CFR 210)). If you have questions, contact UAB Office of Counsel.