Description
Personalized medicine (also referred to as “precision medicine”) relies on the use of in 17 vitro diagnostic (IVD) devices to detect and measure biomarkers and other individual 18 characteristics of disease or other conditions with the goal of better directing patient 19 treatment. With the continued growth of personalized medicine, an increasing number of 20 clinical investigations of therapeutic products (also referred to here as therapeutic product 21 trials or studies) are using investigational IVDs to guide the management of subjects in 22 such investigations. In some cases this has led to the development of an in vitro 23 companion diagnostic device that is essential to the safe and effective use of the 24 therapeutic product, once approved. The information generated by the use of 25 investigational IVDs in therapeutic product trials may affect important aspects of 26 treatment for the enrolled subjects and, by doing so, directly influence the types of 27 therapeutic products or therapeutic management strategies the subjects may be exposed to 28 during the study. Therefore, use of an investigational IVD in a therapeutic product trial 29 may pose significant risk to subjects. FDA is concerned that sponsors (including sponsor-30 investigators) and IRBs may not understand that many IVDs used as a critical part of 31 therapeutic product trials are investigational. Thisguidance documentis intended to 32 inform stakeholders, including institutional review boards or institutional review 33 committees (referred to hereafter as IRBs) reviewing clinical investigations, and sponsors 34 that therapeutic product4 trials that include investigational IVDs are subject to FDA’s 35 Investigational Device Exemption (IDE) regulation (21 CFR Part 812), regardless of the 36 source or manufacturer of the device, in addition to the Investigational New Drug (IND) 37 regulation (21 CFR Part 312).
Scope & Applicability
Product Classes
6IVD device clinical studies conducted on de-identified specimens
unless the device is a banned device
drug or biological product being studied
Devices requiring full IDE submission
clinical trial involving a human drug and a companion diagnostic
In vitro diagnostic device being evaluated in an oncology trial
Stakeholders
6Bodies responsible for evaluating trial risks and benefits for pregnant participants.; IRBs experienced in this population may advise on compensation.
Governs top dose in clinical studies
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
Individual who both initiates and conducts an investigation.
Institutional Review Board providing study approvals
Regulatory Context
Attributes
3Risk classification for medical device clinical investigations.; A classification for medical device studies.; A risk determination for a clinical study.
The IRB would need to make a SR/NSR determination
Evidence of a new intended use based on communications
Identified Hazards
Hazards
5may misinform patients' healthcare management decisions
risk associated with the investigational therapeutic product
Risk associated with invasive procedures for obtaining samples
Potential for serious risk to health from erroneous IVD data
Procedures like biopsies that may introduce significant risk.
Related CFR Sections (13)
- 21CFR56.108§ 56.108 IRB functions and operations.
In order to fulfill the requirements of these regulations, each IRB shall:Read full regulation →
- 21CFR812.30§ 812.30 FDA action on applications.
(a) Approval or disapproval. FDA will notify the sponsor in writing of the date it receives an application. FDA may approve an investigation as proposed, approve it with modifications, or disapprove it. An investigation may not begin until:Read full regulation →
- 21CFR812.25§ 812.25 Investigational plan.
The investigational plan shall include, in the following order:Read full regulation →
- 21CFR812.35§ 812.35 Supplemental applications.
(a) Changes in investigational plan —Read full regulation →
- 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 →
- 21CFR312.23§ 312.23 IND content and format.
(a) A sponsor who intends to conduct a clinical investigation subject to this part shall submit an “Investigational New Drug Application” (IND) including, in the following order:Read full regulation →
- 21CFR50.25§ 50.25 Elements of informed consent.
(a) Basic elements of informed consent. In seeking informed consent, the following information shall be provided to each subject:Read full regulation →
- 21CFR812.2§ 812.2 Applicability.
(a) General. This part applies to all clinical investigations of devices to determine safety and effectiveness, except as provided in paragraph (c) of this section.Read full regulation →
- 21CFR809.3§ 809.3 Definitions.
(a) In vitro diagnostic products are those reagents, instruments, and systems intended for use in the diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use 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 →
- 21CFR809.10§ 809.10 Labeling for in vitro diagnostic products.
(a) The label for an in vitro diagnostic product shall state the following information, except where such information is not applicable, or as otherwise specified in a standard for a particular product class or as provided in paragraph (e) of this section. Section 201(k) of the act provides that “a 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 →
- 21CFR812.20§ 812.20 Application.
(a) Submission.Read 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 (7)
- CHAPTER 48 - 7348.809 Bioresearch Monitoring (Status: Final)
- Significant Risk and Nonsignificant Risk Medical Device Studies: Guidance For IRBs, Clinical Investigators, and Sponsors (Status: Final)
- Using a Centralized IRB Review Process in Multicenter Clinical Trials: Guidance for Industry (Status: Final)
- IRB Continuing Review After Clinical Investigation Approval: Guidance for IRBs, Clinical Investigators, and Sponsors (Status: Final)
- Changes or Modifications During the Conduct of a Clinical Investigation; Final Guidance for Industry and CDRH Staff (Status: Final)
- Investigational Device Exemptions (IDEs) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies: Guidance for Industry and Food and Drug Administration Staff (Status: Final)
- Questions and Answers Regarding Mandatory Cosmetics Recalls: Guidance for Industry : Draft Guidance for Industry (Status: Draft)