Description
This guidance provides information on risk-based approaches to monitoring the conduct of clinical investigations of human drug and biological products, medical devices, and combination products. Clinical investigation monitoring is a quality control tool for determining whether investigation activities are being carried out as planned. This guidance contains recommendations on planning a monitoring approach, developing the content of a monitoring plan, and addressing and communicating monitoring results. This guidance expands on the guidancefor industryOversight of Clinical Investigations – A Risk-Based Approach to Monitoring(August 2013) by providing additional information to facilitate sponsors’ implementation of risk-based monitoring.
Scope & Applicability
Product Classes
1Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.
Stakeholders
5Bodies responsible for evaluating trial risks and benefits for pregnant participants.; IRBs experienced in this population may advise on compensation.
Entity responsible for submitting applications under section 524B
Responsible for qualifications, training, and trial conduct; Individual responsible for trial conduct and data governance at a site.; May delegate tasks but retains overall responsibility; Person responsible for the conduct of the clinical trial at a trial site; Responsible for trial conduct and participant safety; Responsible for trial conduct, data integrity, and investigational product management.; Individual responsible for trial conduct at a site and informing the institution.; maintaining
Veterinarian responsible for selecting anesthetic regimens and conducting field studies
May access unblinded data as described in the DMC Charter.
Regulatory Context
Attributes
1whether blinding to treatment assignment was maintained
Identified Hazards
Hazards
1Issues suggesting a problem with the protocol or investigational plans.
Related CFR Sections (8)
- 21CFR50.3§ 50.3 Definitions.
As used in this part:Read full regulation →
- 21CFR56.102§ 56.102 Definitions.
As used in this part:Read full regulation →
- 21CFR312.3§ 312.3 Definitions and interpretations.
(a) The definitions and interpretations of terms contained in section 201 of the Act apply to those terms when used in this part:Read full regulation →
- 21CFR812.3§ 812.3 Definitions.
(a) Act means the Federal Food, Drug, and Cosmetic Act (sections 201-901, 52 Stat. 1040 et seq., as amended ( 21 U.S.C. 301-392 )).Read full regulation →
- 21CFR3.2§ 3.2 Definitions.
For the purpose of this part:Read full regulation →
- 21CFR312.50§ 312.50 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators, providing them with the information they need to conduct an investigation properly, ensuring proper monitoring of the investigation(s), ensuring that the investigation(s) is conducted in accordance with the general investigational plan Read full regulation →
- 21CFR812.40§ 812.40 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators and providing them with the information they need to conduct the investigation properly, ensuring proper monitoring of the investigation, ensuring that IRB review and approval are obtained, submitting an IDE application to FDA, and ensurRead full regulation →
- 21CFR812.46§ 812.46 Monitoring investigations.
(a) Securing compliance. A sponsor who discovers that an investigator is not complying with the signed agreement, the investigational plan, the requirements of this part or other applicable FDA regulations, or any conditions of approval imposed by the reviewing IRB or FDA shall promptly either securRead full regulation →
Related Warning Letters (10)
- 2025-12-23
In Vivo Bioavailability-Bioequivalence Studies – Clinical
Maria A. Carballosa, M.D.
- 2025-12-09
Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)
Celularity, Inc
- 2025-11-18
Sponsor/Investigator
Verdure Sciences, Inc.
- 2025-09-30
Clinical Investigator (Sponsor)
Pamela K. Den Besten, DDS, MS
- 2025-09-23
Clinical Investigator/Sponsor
Ralph A. DeFronzo, M.D.
- 2025-09-09
Clinical Investigator
Shirish M. Gadgeel, M.D.
- 2025-07-15
Clinical Investigator
Mark J. Savant, M.D
- 2025-07-01
Clinical Investigator
Peter Michael, M.D.
- 2025-06-10
Clinical Investigator (Sponsor)
American Behavioral Research Institute, LLC
- 2025-06-03
Bioresearch Monitoring Program
Amy Lightner, MD
See Also (8)
- Use of Electronic Health Record Data in Clinical Investigations Guidance for Industry (Status: Final)
- Research Involving Children as Subjects and Not Otherwise Approvable by an Institutional Review Board: Process for Referrals to Food and Drug Administration and Office for Human Research Protections: Draft Guidance for Institutional Review Boards, Investigators, and Sponsors (Status: Draft)
- Informed Consent: Guidance for IRBs, Clinical Investigators, and Sponsors (Status: Final)
- Digital Health Technologies for Remote Data Acquisition in Clinical Investigations (Status: Final)
- Electronic Systems, Electronic Records, and Electronic Signatures in Clinical Investigations: Questions and Answers (Status: Final)
- Expanded Access to Investigational Drugs for Treatment Use: Questions and Answers (Status: Final)
- Safety Reporting Requirements for INDs (Investigational New Drug Applications) and BA/BE (Bioavailability/Bioequivalence) Studies: Guidance for Industry and Investigators (Status: Final)
- PHS Guideline on Infectious Disease Issues in Xenotransplantation: PHS Guideline (Status: Final)