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Washington State University

HRPP policies & procedures manual

1104: Food and Drug Administration

1. Purpose

The purpose of this policy is to define the procedures as they apply to human research that is funded by the Food and Drug Administration (FDA). Research supported by the FDA requires compliance with additional federal regulations, directives and instructions.

2. Policy

2.1 Additional informed consent elements for FDA-regulated clinical investigations

FDA personnel may review any and all documents related to the research, including subject medical records, in either a directed or routine audit of the investigator, the institution, or the IRB.

Under new 21 CFR 50.25(c), the following statement must be reproduced word-for-word in informed consent documents for applicable clinical trials:

“A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time.”

2.2 Reporting requirements for FDA-regulated clinical investigations

*Taken in portion from the FDA’s Guidance for Clinical Investigators, Sponsors, and IRBs.  Adverse Event Reporting to IRBs—Improving Human Subject Protection. (pdf)

For clinical investigations of drug and biological products conducted under an investigational new drug (IND) application, information about adverse events must be communicated among investigators, sponsors, and IRBs as follows:

  • Investigators are required to report promptly “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 shall report the adverse effect immediately” (21 CFR § 312.64(b)).
  • Sponsors are specifically required to notify all participating investigators (and FDA) in a written IND safety report of “any adverse experience associated with the use of the drug that is both serious and unexpected” and “any finding from tests in laboratory animals that suggests a significant risk for human subjects” (§ 312.32(c)(1)(i)(A),(B)). And, more generally, sponsors are required to “keep each participating investigator informed of new observations discovered by or reported to the sponsor on the drug, particularly with respect to adverse effects and safe use” (§ 312.55(b)).
  • Investigators are required to report promptly “to the IRB… all unanticipated problems involving risks to human subjects or others,” including adverse events that should be considered unanticipated problems (§§ 56.108(b)(1), 312.53(c)(1)(vii), and 312.66).
  • For clinical investigations of drug and biological products conducted under an investigational new drug (IND) application, information about adverse events must be communicated among investigators, sponsors, and IRBs as follows:
  • Investigators are required to report promptly “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 shall report the adverse effect immediately” (§ 312.64(b)).
  • Sponsors are specifically required to notify all participating investigators (and FDA) in a written IND safety report of “any adverse experience associated with the use of the drug that is both serious and unexpected” and “any finding from tests in laboratory animals that suggests a significant risk for human subjects” (§ 312.32(c)(1)(i)(A),(B)). And, more generally, sponsors are required to “keep each participating investigator informed of new observations discovered by or reported to the sponsor on the drug, particularly with respect to adverse effects and safe use” (§ 312.55(b)).
  • Investigators are required to report promptly “to the IRB… all unanticipated problems involving risks to human subjects or others,” including adverse events that should be considered unanticipated problems (§§ 56.108(b)(1), 312.53(c)(1)(vii), and 312.66).
2.2.1 Defining unanticipated problems

In general, an adverse event observed during the conduct of a study should be considered an unanticipated problem involving risk to human subjects, and reported to the IRB, only if it were unexpected, serious, and would have implications for the conduct of the study (e.g., requiring a significant, and usually safety-related, change in the protocol such as revising inclusion/exclusion criteria or including a new monitoring requirement, informed consent, or investigator’s brochure).

2.2.2 Reporting adverse events to IRBs in clinical trials of devices under the IDE regulations

The investigational device exemption (IDE) regulations define an unanticipated adverse device effect (UADE) as “any serious adverse effect on health or safety or any life-threatening problem or death caused by, or associated with, a device, if that effect, problem, or death was not previously identified in nature, severity, or degree of incidence in the investigational plan or application (including a supplementary plan or application), or any other unanticipated serious problem associated with a device that relates to the rights, safety, or welfare of subjects” (21 CFR 812.3(s)). UADEs must be reported by the clinical investigator to the sponsor and the reviewing IRB, as described below:

  • For device studies, investigators are required to submit a report of a UADE to the sponsor and the reviewing IRB as soon as possible, but in no event later than 10 working days after the investigator first learns of the event (§ 812.150(a)(1)).
  • Sponsors must immediately conduct an evaluation of a UADE and must report the results of the evaluation to FDA, all reviewing IRBs, and participating investigators within 10 working days after the sponsor first receives notice of the effect (§§ 812.46(b), 812.150(b)(1)).

The IDE regulations, therefore, require sponsors to submit reports to IRBs in a manner consistent with the recommendations made above for the reporting of unanticipated problems under the IND regulations.

2.3 Reporting requirements for serious non-compliance, suspension or termination of IRB approval

Under 21 CFR 56.113, an IRB shall have the authority to suspend or terminate approval of research that is not being conducted in accordance with the IRB’s requirements or that has been associated with unexpected serious harm to subjects. Any suspension or termination of approval shall include a statement of the reasons for the IRB’s action and shall be reported promptly to the investigator, appropriate institutional officials, and the Food and Drug Administration.

21 CFR 56.108(b) requires that the IRB follow written procedures for ensuring prompt reporting to the IRB, appropriate institutional officials, and the Food and Drug Administration of:

  1. Any unanticipated problems involving risks to human subjects or others;
  2. Any instance of serious or continuing noncompliance with these regulations or the requirements or determinations of the IRB; or any suspension or termination of IRB approval.

When reporting suspensions or terminations of IRB approval, please include the Investigational New Drug (IND) or Device Exemption (IDE) number, the full name of the research protocol, the name(s) of the clinical investigators, and the reason(s) for the suspension or termination. These reports may be submitted via e-mai: irb@wsu.edu

3. Applicable regulations and guidelines

4. Forms

FDA Guidance: IRB Continuing Review After Clinical Investigation Approval (pdf)

FDA Guidance for Clinical Investigators, Sponsors, and IRBs. Adverse Event Reporting to IRBs—Improving Human Subject Protection. (pdf)

5. Procedures employed to implement this policy & assignment of responsibility

WhoTask
Principal investigator Determine if an IND or IDE is required. If so, follow the process to procure one from the FDA before submitting IRB application.
IRB membersReview the need for an IND or IDE, and require that the principal investigator obtains one before approving the protocol.