Boston University
Charles River Campus IRB
Policies and Procedures
Title: Research Involving Investigational Drugs
Date: May 31, 2016

Purpose

The purpose of this policy is to outline the requirements for research with human subjects involving investigational drugs, including Institutional Review Board (IRB) review and investigator responsibilities.

Defined Terms

Food and Drug Administration (FDA) Definitions:

Clinical Investigation*: Any experiment that involves a test article and one or more human subjects and that either is subject to requirements for prior submission to the Food and Drug Administration under section 505(i) or 520(g) of the act, or is not subject to requirements for prior submission to the Food and Drug Administration under these sections of the act, but the results of which are intended to be submitted later to, or held for inspection by, the Food and Drug Administration as part of an application for a research or marketing permit

* The terms research, clinical research, clinical study, study, and clinical investigation are deemed to be synonymous for FDA purposes

Human Subject: An individual who is or becomes a participant in research, either as a recipient of the test article or as a control. A subject may be either a healthy individual or a patient.

Investigational New Drug: A new drug or biological drug that is used in a clinical investigation. The term also includes a biological product that is used in vitro for diagnostic purposes. The terms “investigational drug” and “investigational new drug” are deemed to be synonymous for purposes of this part

Investigator: An individual who actually conducts a clinical investigation (i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject) or, in the event of an investigation conducted by a team of individuals, is the responsible leader of that team.

Sponsor*: A person or other entity that initiates a clinical investigation, but that does not actually conduct the investigation, i.e., the test article is administered or dispensed to, or used involving, a subject under the immediate direction of another individual. A person other than an individual (e.g., a corporation or agency) that uses one or more of its own employees to conduct an 2 investigation that it has initiated is considered to be a sponsor (not a sponsor-investigator), and the employees are considered to be investigators.

Sponsor-Investigator: An individual who both initiates and actually conducts, alone or with others, a clinical investigation, i.e., under whose immediate direction the test article is administered or dispensed to, or used involving, a subject. The term does not include any person other than an individual, e.g., it does not include a corporation or agency. The obligations of a sponsorinvestigator under this part include both those of a sponsor and those of an investigator.

Test Article: Any drug for human use, biological product for human use, medical device for human use, human food additive, color additive, electronic product, or any other article subject to regulation under the act or under sections 351 or 354-360F of the Public Health Service Act

*Note: The definition listed here is from the FDA regulations. Please note that this differs from the definition of “Sponsor” from the Office of Sponsored Projects (OSP). For OSP purposes “Sponsor” is the entity awarding the funding to Boston University for the supported activity (e.g. research, training, other sponsored activity). It may be a federal or state agency, private foundation, corporate entity, etc.. More information regarding OSP can be located at: http://www.bu.edu/osp/.

Policy

The Charles River Campus (CRCCharles River Campus) IRB ensures that research involving investigational drugs is conducted in accordance with applicable federal regulations (21 CFR 50, 21 CFR 56, and 21 CFR 312). When a new drug is being tested to determine safety and efficacy an Investigational New Drug Application (IND) must be filed. Research studies involving marketed drugs may also require an IND. The IRB will determine if an IND is required or if the study meets one of the FDA’s criteria for exemption from an IND.

Procedures

The investigator is responsible for submitting sufficient information to the IRB, in order for the IRB to make a determination. Required information may include:

  • Investigator’s brochure
  • Package insert
  • Summary of prior use/investigations
  • FDA correspondence
  • Plan for receipt, storage, control, labeling, and dispensing of drug
  • IRB Drug Form (Appendix B)

If the investigational drug requires an IND, the IRB staff will verify the IND number by requiring the sponsor’s protocol or the FDA correspondence. The IRB will not approve the study until the IRB staff has verified the IND number or verified that it has been 30 days since the investigator submitted the IND to the FDA unless the sponsor receives earlier notice from the FDA. 3 The pharmacist IRB representative will serve as a Reviewer on any study that involves an investigational drug.

FDA Exemptions:

In order to be exempt from IND requirements, the study must fall into one of the following exemption categories. The IRB will determine if the exemption applies:

Exemption 1

  • The drug product is lawfully marketed in the United States.
  • The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug.
  • If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product.
  • The investigation does 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 the risks) associated with the use of the drug product.
  • The investigation is conducted in compliance with 21 CFR 50 and 56.
  • The investigation is conducted in compliance with the requirements of 21 CFR 312.7.

Exemption 2

  • A clinical investigation is for an in vitro diagnostic biological product that involves one or more of the following:
    • Blood grouping serum.
    • Reagent red blood cells.
    • Anti-human globulin.
  • The diagnostic test is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established, diagnostic product or procedure.
  • The diagnostic test is shipped in compliance with 21 CFR 312.160

Exemption 3

  • The drug is intended solely for tests in vitro or in laboratory research animals if shipped in accordance with 21 CFR 312.160.

Exemption 4

  • A clinical investigation involving use of a placebo if the investigation does not otherwise require submission of an IND.

Drug Products NOT Manufactured and/or Compounded by a Licensed Pharmaceutical Company (e.g. Pfizer, Novartis, Genzyme, etc.)

If the drug product is manufactured and/or compounded by an entity that is not a licensed pharmaceutical company, the IRB will require the following, as applicable:

  • If a compound pharmacy will be used to prepare the drug product, the IRB will require that the pharmacy complete a gap analysis per an Advisory from the Massachusetts Board of Pharmacy:
    • Sterile preparation:
      • http://www.ijpc.com/USP/IJPC%20USP%20797%20GAP%20Analysis.pdf
    • Non-sterile preparation:
      • http://www.ijpc.com/USP/IJPC%20USP%20795%20GAP%20Analysis.pdf
  • Procedures for compounding drugs
  • Procedures for labeling drugs and shipping drugs to the research site
  • Certificate of Analysis (COA)

Control of Investigational Drugs

Investigators are required to have procedures in place to control investigational drugs to ensure that they are used only in approved research protocols and under the direction of approved investigators. The IRB will review the plan for drug accountability, including receipt, control, storage, labeling, dispensing, and recordkeeping to determine that the plan is appropriate and adequate.

Investigator Responsibilities

Investigators must comply with FDA and IRB policies and are responsible for the following:

  • Ensure that the clinical research is conducted according to the approved protocol and applicable regulations.
  • Inform the subjects, or any persons used as controls, that the drugs/biologics are being used for investigational purposes. Include a statement in the consent form.
  • Administer the study drug or biologic only to subjects under the investigator’s personal supervision or the supervision of a qualified co-investigator.
  • Report problems in accordance with IRB policies and applicable regulations.
  • Do not supply the study drug or biologic to any person not authorized to receive it (patient or another investigator).
  • Provide for control of drugs.
  • Maintain adequate records of the disposition of the study drug to include dates, quantity and use by subjects.
  • Return any unused supply of study drug to the sponsor upon completion, suspension, termination or discontinuation of the research study.
  • Permit the FDA to have access to and copy and verify records or reports made during the study

Requirements for Investigators that are also Sponsors

If the investigator is also the sponsor of the drug, the investigator must also comply with the FDA regulations that pertain to Sponsors. Below is an overview of the major responsibilities.

  • Submit IND Application Form 1571 and other required documents to FDA. 21 CFR 312.23
  • Submit annual reports of the progress of the investigation to the FDA 21 CFR 312.56
  • Comply with FDA regulations regarding emergency use. 21 CFR 312.54
  • Review and evaluate the evidence that relates to the safety and effectiveness of the drug as it is obtained from each investigator(s). 21 CFR 312.56
  • Discontinue the study if the investigational drug presents an unreasonable and significant risk to subjects. 21 CFR 312.56
  • Keep investigator(s) informed of the safety and effectiveness of the drug. 21 CFR 312.55
  • Notify the FDA, IRB, and the investigator(s) if the study is discontinued. 21 CFR 312.56
  • Send safety reports to the FDA and investigator(s) 21 CFR 312.32
  • Select qualified investigators based on training and experience. 21 CFR 312.53
  • Obtain FDA Form 1572 from the investigator(s). 21 CFR 312.53
  • Obtain a written statement that the investigator(s) will conduct the study as outlined in the protocol. 21 CFR 312.53
  • Maintain documentation of the financial interests from investigators, for the duration of any covered studies under the IND, plus 1 year following study completion. 21 CFR 312.53
  • Require investigator(s) to meet local IRB requirements. 21 CFR 312.66
  • Terminate investigator'(s) participation when investigator(s) fails to follow protocol. 21 CFR 312.56
  • Select a monitor to oversee the progress of the investigation. 21 CFR 312.53
  • Monitor the progress of all IND investigations. 21 CFR 312.56
  • Label the investigational drug in accordance with FDA regulations. 21 CFR 312.6
  • Promote and distribute the drug in accordance with FDA regulations. 21 CFR 312.7
  • Ship investigational drugs only to investigator(s) participating in the investigation. 21 CFR 312.53
  • Maintain adequate records that show the receipt, shipment, or other disposition of the investigational drug. 21 CFR 312.57
  • Require investigator(s) to store the investigational drug in a secure area. 21 CFR 312.69
  • Require that investigator(s) maintain adequate drug records. 21 CFR 312.62
  • Ensure that investigator(s) return all unused investigational drugs. 21 CFR 312.59
  • Maintain complete and accurate records of payments made to clinical investigator(s). 21 CFR 312.57
  • Require investigator(s) to keep case histories on each individual administered the investigational drug or employed as a control in the investigation. 21 CFR 312.62
  • Collect reports (financial, progress, safety, and final) from investigator(s). 21 CFR 312.64
  • Ensure any electronic data and source documentation for the studies covered under the IND meets the same fundamental elements of data quality expected of paper records. 21 CFR 11

Quality Improvement Review

All studies that involve investigational drugs qualify for review by the Quality Improvement (QI) Program. The QI Program will assist investigators in complying with applicable policies and regulations.

Title: Research Involving Investigational Drugs

Author: Cynthia Monahan

Effective Date: September 5, 2014

Last Review/Update Date: May 31, 2016

Revision #: 2

Approved:
Cynthia Monahan, IRB Director
Kathryn Mellouk, Associate Vice President-Research Compliance

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