The Use of Clinical Holds Following Clinical Investigator Misconduct: Guidance for Industry and Clinical Investigators | Guideline Explorer

Description

This guidance provides information on one use by the Food and Drug Administration (FDA) of its authority to impose a clinical hold on a study or study site if FDA finds that human subjects are or would be exposed to an unreasonable and significant risk of illness or injury. Specifically, this guidance describes circumstances in which FDA may impose a clinical hold based on credible evidence that a clinical investigator conducting the study has committed serious violations of FDA regulations on clinical trials of human drugs and biologics, including 21 CFR Parts 312, 50, and 56, or has submitted false information to FDA or the sponsor in any required report. FDA may consider imposing a clinical hold in these situations where necessary to protect human subjects in the study from an unreasonable and significant risk of illness or injury. Such a clinical hold may be imposed on the study in which the misconduct occurred or on other studies of drugs or biological products in which the clinical investigator is directly involved or proposed to be involved. Although FDA has authority to take various enforcement actions against a clinical investigator who commits serious violations of FDA regulations, these actions may not be completed swiftly enough to protect human subjects who may be at risk in ongoing studies conducted by the investigator. Where the investigator's misconduct appears to pose an ongoing threat to the safety and welfare of such subjects, imposition of a full or partial clinical hold on ongoing or proposed studies of human drugs or biological products may be appropriate. See 21 CFR 312.42(b)(1)(i), 312.42(b)(2)(i), 312.42(b)(3)(iii), and 312.42(b)(4)(i). This guidance does not address other circumstances in which FDA may impose a clinical hold if FDA finds that human subjects are or would be exposed to an unreasonable and significant risk of illness or injury, including when there is no evidence of clinical investigator misconduct or a serious regulatory viol

Scope & Applicability

Stakeholders

5

Clinical Investigator

Veterinarian responsible for selecting anesthetic regimens and conducting field studies

Institutional Review Board

Governs top dose in clinical studies

Sponsor

Entity responsible for submitting applications under section 524B

IRB

Institutional Review Board providing study approvals

sponsor-investigator

individual who both initiates and conducts a clinical investigation

Identified Hazards

Hazards

1

Unreasonable and significant risk of illness or injury

Criteria for imposing a clinical hold; Primary criteria for imposing a clinical hold; criteria for maintaining or lifting a clinical hold

Related CFR Sections (8)

21CFR312.42§ 312.42 Clinical holds and requests for modification.
(a) General. A clinical hold is an order issued by FDA to the sponsor to delay a proposed clinical investigation or to suspend an ongoing investigation. The clinical hold order may apply to one or more of the investigations covered by an IND. When a proposed study is placed on clinical hold, subjectRead full regulation →
21CFR312.60§ 312.60 General responsibilities of investigators.
An investigator is responsible for ensuring that an investigation is conducted according to the signed investigator statement, the investigational plan, and applicable regulations; for protecting the rights, safety, and welfare of subjects under the investigator's care; and for the control of drugs Read full regulation →
21CFR312.66§ 312.66 Assurance of IRB review.
An investigator shall assure that an IRB that complies with the requirements set forth in part 56 will be responsible for the initial and continuing review and approval of the proposed clinical study. The investigator shall also assure that he or she will promptly report to the IRB all changes in thRead full regulation →
21CFR312.53§ 312.53 Selecting investigators and monitors.
(a) Selecting investigators. A sponsor shall select only investigators qualified by training and experience as appropriate experts to investigate the drug.Read full regulation →
21CFR312.61§ 312.61 Control of the investigational drug.
An investigator shall administer the drug only to subjects under the investigator's personal supervision or under the supervision of a subinvestigator responsible to the investigator. The investigator shall not supply the investigational drug to any person not authorized under this part to receive iRead full regulation →
21CFR312.62§ 312.62 Investigator recordkeeping and record retention.
(a) Disposition of drug. An investigator is required to maintain adequate records of the disposition of the drug, including dates, quantity, and use by subjects. If the investigation is terminated, suspended, discontinued, or completed, the investigator shall return the unused supplies of the drug tRead full regulation →
21CFR312.64§ 312.64 Investigator reports.
(a) Progress reports. The investigator shall furnish all reports to the sponsor of the drug who is responsible for collecting and evaluating the results obtained. The sponsor is required under § 312.33 to submit annual reports to FDA on the progress of the clinical investigations.Read full regulation →
21CFR312.70§ 312.70 Disqualification of a clinical investigator.
(a) If FDA has information indicating that an investigator (including a sponsor-investigator) has repeatedly or deliberately failed to comply with the requirements of this part, part 50 or part 56 of this chapter , or has repeatedly or deliberately submitted to FDA or to the sponsor false informatioRead full regulation →

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