21 CFR 312.2
Applicability
21 CFR 312.2 is the regulation titled “Applicability” in 21 CFR Part 312, Investigational New Drug Application. Since 2021, 23 FDA warning letters have cited it.
- Letters citing it
- 23 since 2021
- Jan 1 to Oct 30, 2026
- 2 against 3 on the same dates in 2025
- Most often cited with
- 21 CFR 312.20, in 18 letters
- Closed out
- 0% of these letters have a published close-out
Letters citing it, by year issued
All are drug 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 312.2 most often, as written in the letters.
- 5 lettersYou failed to submit an Investigational New Drug application (IND) for the conduct of a clinical investigation with an investigational new drug that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a), 312.20(b), and…
- 2 lettersFailure to submit INDs for the conduct of clinical investigations with investigational new drugs subject to 21 CFR 312.2(a) [21 CFR 312.20 and 312.40(a)]
- 2 lettersYou failed to submit an Investigational New Drug application (IND) for the conduct of a clinical investigation with investigational new drugs that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a), 312.20(b), and…
The regulation
Read the text of 21 CFR 312.2 (eCFR, as of Sep 1, 2026)
(a) Applicability. Except as provided in this section, this part applies to all clinical investigations of products that are subject to section 505 of the Federal Food, Drug, and Cosmetic Act or to the licensing provisions of the Public Health Service Act (58 Stat. 632, as amended (42 U.S.C. 201 et seq.)).
(b) Exemptions. (1) The clinical investigation of a drug product that is lawfully marketed in the United States is exempt from the requirements of this part if all the following apply:
(i) The investigation is not intended to be reported to FDA as a well-controlled study in support of a new indication for use nor intended to be used to support any other significant change in the labeling for the drug;
(ii) If the drug that is undergoing investigation is lawfully marketed as a prescription drug product, the investigation is not intended to support a significant change in the advertising for the product;
(iii) The investigation does not involve a route of administration or dosage level or use in a patient population or other factor that significantly increases the risks (or decreases the acceptability of the risks) associated with the use of the drug product;
(iv) The investigation is conducted in compliance with the requirements for institutional review set forth in part 56 and with the requirements for informed consent set forth in part 50; and
(v) The investigation is conducted in compliance with the requirements of § 312.7.
(2)(i) A clinical investigation involving an in vitro diagnostic biological product listed in paragraph (b)(2)(ii) of this section is exempt from the requirements of this part if (a) it is intended to be used in a diagnostic procedure that confirms the diagnosis made by another, medically established, diagnostic product or procedure and (b) it is shipped in compliance with § 312.160.
(ii) In accordance with paragraph (b)(2)(i) of this section, the following products are exempt from the requirements of this part: (a) blood grouping serum; (b) reagent red blood cells; and (c) anti-human globulin.
(3) A drug intended solely for tests in vitro or in laboratory research animals is exempt from the requirements of this part if shipped in accordance with § 312.160.
(4) FDA will not accept an application for an investigation that is exempt under the provisions of paragraph (b)(1) of this section.
(5) A clinical investigation involving use of a placebo is exempt from the requirements of this part if the investigation does not otherwise require submission of an IND.
(6) A clinical investigation involving an exception from informed consent under § 50.24 of this chapter is not exempt from the requirements of this part.
(c) Bioavailability studies. The applicability of this part to in vivo bioavailability studies in humans is subject to the provisions of § 320.31.
(d) Unlabeled indication. This part does not apply to the use in the practice of medicine for an unlabeled indication of a new drug product approved under part 314 or of a licensed biological product.
(e) Guidance. FDA may, on its own initiative, issue guidance on the applicability of this part to particular investigational uses of drugs. On request, FDA will advise on the applicability of this part to a planned clinical investigation.
[52 FR 8831, Mar. 19, 1987, as amended at 61 FR 51529, Oct. 2, 1996; 64 FR 401, Jan. 5, 1999]
Text from eCFR as of Sep 1, 2026.
Cited alongside it
Regulations that appear in the same letters as 21 CFR 312.2.
- 21 CFR 312.20Requirement for an IND18 letters cite both
- 21 CFR 312.40General requirements for use of an investigational new drug in a clinical investigation10 letters cite both
- 21 CFR 201.5Drugs; adequate directions for use4 letters cite both
- 21 CFR 312.3Definitions and interpretations4 letters cite both
- 21 CFR 312.7Promotion of investigational drugs4 letters cite both
- 21 CFR 201.100Prescription drugs for human use3 letters cite both
- 21 CFR 312.60General responsibilities of investigators3 letters cite both
- 21 CFR 50.27Documentation of informed consent3 letters cite both
Latest letters citing it
The 3 letters citing 21 CFR 312.2 that FDA posted most recently.
- DrugsView Center For Immunology Science, LLCheat-killed Mycobacteria smegmatisIssuedJan 13, 2026PostedJan 27, 2026
- DrugsView Prodrome Sciences USA, LLCProdromeNeuro™ OilIssuedJan 8, 2026PostedJan 20, 2026
- DrugsView Verdure Sciences, Inc.Maplifa®IssuedNov 10, 2025PostedNov 18, 2025
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Counts include every citation in a letter, as the Letters filter does. How this database is built.