21 CFR 812.46
Monitoring investigations
21 CFR 812.46 is the regulation titled “Monitoring investigations” in 21 CFR Part 812, Investigational Device Exemptions. Since 2021, 2 FDA warning letters have cited it.
- Letters citing it
- 2 since 2021
- Jan 1 to Oct 30, 2026
- 1 against 1 on the same dates in 2025
- Most often cited with
- 21 CFR 812.40, in 2 letters
- Closed out
- 0% of these letters have a published close-out
Letters citing it, by year issued
All are medical device letters. 2026 runs to Oct 30, 2026. Pick a year to see its letters.
What FDA writes when it cites it
The finding headings that cite 21 CFR 812.46 most often, as written in the letters.
- 1 letterFailure to ensure proper monitoring of the investigation and failure to secure clinical investigator’s compliance with investigational plans [21 CFR 812.40, 21 CFR 812.46(a)]
- 1 letterFailure to immediately conduct an evaluation of any unanticipated adverse device effects and failure to report results of such an evaluation to FDA and to all reviewing IRB’s and participating investigators within 10…
- 1 letterFailure to secure clinical investigator’s compliance with the signed agreement, the investigational plan, applicable FDA regulations, and any other conditions of approval imposed by the reviewing IRB or FDA, or if…
The regulation
Read the text of 21 CFR 812.46 (eCFR, as of Sep 1, 2026)
(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 secure compliance, or discontinue shipments of the device to the investigator and terminate the investigator's participation in the investigation. A sponsor shall also require such an investigator to dispose of or return the device, unless this action would jeopardize the rights, safety, or welfare of a subject.
(b) Unanticipated adverse device effects. (1) A sponsor shall immediately conduct an evaluation of any unanticipated adverse device effect.
(2) A sponsor who determines that an unanticipated adverse device effect presents an unreasonable risk to subjects shall terminate all investigations or parts of investigations presenting that risk as soon as possible. Termination shall occur not later than 5 working days after the sponsor makes this determination and not later than 15 working days after the sponsor first received notice of the effect.
(c) Resumption of terminated studies. If the device is a significant risk device, a sponsor may not resume a terminated investigation without IRB and FDA approval. If the device is not a significant risk device, a sponsor may not resume a terminated investigation without IRB approval and, if the investigation was terminated under paragraph (b)(2) of this section, FDA approval.
Text from eCFR as of Sep 1, 2026.
Cited alongside it
Regulations that appear in the same letters as 21 CFR 812.46.
- 21 CFR 812.40General responsibilities of sponsors2 letters cite both
- 21 CFR 807.81When a premarket notification submission is required1 letter cites both
- 21 CFR 812.100General responsibilities of investigators1 letter cites both
- 21 CFR 812.140Records1 letter cites both
- 21 CFR 812.150Reports1 letter cites both
- 21 CFR 812.20Application1 letter cites both
- 21 CFR 812.3Definitions1 letter cites both
- 21 CFR 812.35Supplemental applications1 letter cites both
Latest letters citing it
The 2 letters citing 21 CFR 812.46 that FDA posted most recently.
- DevicesView ExThera Medical CorporationInvestigational blood filters for clinical studiesIssuedFeb 6, 2026PostedFeb 24, 2026
- DevicesView United Health Products, Inc.CelluSTAT Absorbable HemoStatIssuedMar 24, 2025PostedMay 20, 2025
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Counts include every citation in a letter, as the Letters filter does. How this database is built.