Yes, when two things are true: the product is a new animal drug that FDA has not approved, conditionally approved or indexed for the use you are studying, and you are shipping it for a clinical study in client-owned animals. 21 CFR 511.1 exempts that shipment from the approval requirement only if, before the product ships, the sponsor has sent FDA's Center for Veterinary Medicine a Notice of Claimed Investigational Exemption for a New Animal Drug under an INAD file, and meets the rest of the rule's conditions. A study that assigns nothing, or that uses an approved product as its label directs, needs no notice. A "research use only" label on a peptide does not change the answer.
What counts as a new animal drug
FDA's page on unapproved animal drugs says "the intended use of a product determines if it's a drug," and that "if a drug is intended for use in animals, it's almost certain to be a new animal drug." A new animal drug without legal marketing status is an unapproved animal drug, and that includes drugs compounded from bulk drug substances. FDA's page on its regulation of animal drugs calls them "unsafe" and "adulterated" and says marketing them is illegal.
21 CFR 201.128 defines intended use by the objective intent of those responsible for the labelling, shown by labelling, by advertising and by the circumstances in which the product is, with their knowledge, "offered or used for a purpose for which it is neither labeled nor advertised." A vial sold for research and then, with the seller's knowledge, dosed to a dog with a diagnosed condition is a new animal drug.
21 CFR 511.1(a) exempts drugs shipped for in vitro tests or for "laboratory research animals." A client's dog or cat is neither, so a study run in a clinic falls under 511.1(b), the clinical investigation paragraph.
What 21 CFR 511.1(b) asks
The paragraph exempts a shipment "intended for clinical investigational use in animals" if all of its conditions are met. In brief:
- (b)(1) Labelling. Each package carries the caution "Contains a new animal drug for use only in investigational animals in clinical trials. Not for use in humans."
- (b)(3) Shipment records. The sponsor keeps a record of each shipment for two years after it.
- (b)(4) The notice. Filed before the drug ships for clinical tests. Its contents are listed below.
- (b)(7) The investigator. Qualified by scientific training and experience; keeps complete records, including of "the receipt and disposition of each shipment or delivery," for two years after the study ends or an application is approved; reports to the sponsor.
- (b)(8) The sponsor. Provides "current monitoring of the investigation by a person qualified by scientific training and experience"; must "promptly investigate and report to FDA and to all investigators" any findings "that may suggest significant hazards"; must not "represent that the new animal drug is safe or effective for the purposes for which it is under investigation"; must not distribute or test-market it before approval.
- (b)(10) Environment. A claim of categorical exclusion or an environmental assessment.
- (f) Contract research organizations. One that takes on a sponsor's obligations must meet them and is subject to the same regulatory action as a sponsor.
Three things are not in 511.1: an ethics committee, owner consent and an adverse event form. They come from elsewhere.
How the study design changes the answer
| Design | Notice before shipment | What applies instead or as well |
|---|---|---|
| Observational or registry: usual care, nothing assigned | No | Good practice and state records law; a consent form, which draft Guidance #282 recommends for every study in client-owned companion animals |
| Approved product used as its label directs | No | Adverse events go to the product's applicant, who files each serious, unexpected one with FDA within 15 working days under 21 CFR 514.80 |
| Approved product used off label by the study veterinarian | No | 21 CFR Part 530, the extra-label rule for approved drugs used by a licensed veterinarian within a valid veterinarian-client-patient relationship when "the health of an animal is threatened or suffering or death may result from failure to treat" (530.2) |
| Unapproved new animal drug: a peptide, a compounded product, anything with no approval for this use | Yes, under 511.1(b)(4) | Investigational labelling, shipment and disposition records, monitoring, hazard reporting, GL9, Part 11 |
Part 530 reaches only "any approved new animal drug or approved new human drug" (530.1), so it is not a route around the notice for a peptide with no approval at all.
What the notice contains
21 CFR 511.1(b)(4) asks for:
- The identity of the new animal drug.
- All labelling and other pertinent information to be supplied to the investigators.
- The name and address of each clinical investigator.
- The approximate number of animals to be treated, or if that is not known, the amount of drug to be shipped.
- For food-producing animals: commitments about edible products, the dates of the experiment, dose, duration, route and withdrawal time.
- A statement on 21 CFR Part 58 compliance for any nonclinical laboratory studies.
- The name and address of any contract research organization and the obligations transferred to it.
The notice goes under an INAD file, which FDA's page on the approval journey says the sponsor opens by contacting CVM's Office of New Animal Product Evaluation and "then uses the file as a way to correspond with CVM throughout the journey." CVM's eSubmitter tool carries the notice in a notice of shipment template.
After the notice: conduct, records and events
A study meant to support approval also meets 21 CFR 514.117(b)(2): an appropriate standard of conduct for study conduct, personnel, facilities and documentation, and a protocol that "contains a statement acknowledging the applicability of, and intention to follow, a standard of conduct acceptable to FDA." That standard is Guidance #85, VICH GL9, final since May 2001, which FDA says "should be followed when developing clinical study data that are intended to be submitted to regulatory authorities."
Owner consent comes from guidance, not from 511.1. Draft Guidance #282, September 2023, says "CVM recommends all studies conducted with client-owned companion animals use an ICF and be conducted in accordance with Good Clinical Practice guidelines," and defines informed consent as a documented process by which an owner or owner's agent voluntarily confirms their willingness to let the animal take part. It is a draft: CVM's current thinking, not a requirement.
Electronic records in an INAD study fall under 21 CFR Part 11, because 11.1(b) applies to records kept "under any records requirements set forth in agency regulations," and 511.1(b)(7) and (b)(8) are such requirements. There is more in 21 CFR Part 11 for veterinary studies.
Part 511 has no adverse event form; the duty is the sponsor's prompt report of significant hazards under (b)(8). FDA's reporting page says Form FDA 1932a can be used "to report adverse events for any animal drug (FDA-approved or unapproved) or animal device," including compounded drugs.
Whose job each part is
The sponsor opens the INAD file, files the notice before each shipment, labels the product, keeps the shipment records, monitors, reports significant hazards to FDA and every investigator, and makes no claim that the product is safe or effective. The investigator keeps the receipt, disposition and study records for two years, reports to the sponsor, and obtains and keeps the owner's consent. The protocol, the ethics review where an institution or funder requires one, and the consent text are theirs, not a vendor's.
Signalment is a data system. It holds the protocol and consent versions, the case report forms, an adverse event form with the seriousness criteria of 21 CFR 514.3, the audit trail and the exports a monitor or reviewer asks for; the sponsor page at signalment.app/sponsors shows them. It does not open an INAD file, file a notice, label a shipment or report to FDA. It has an administration log per subject, but a shipment and reconciliation ledger is not built yet, and neither are VeDDRA coding or a Form FDA 1932a export; until then those records live elsewhere.
Sources
- 21 CFR 511.1, new animal drugs for investigational use: https://www.ecfr.gov/current/title-21/section-511.1
- 21 CFR 201.128, meaning of intended uses: https://www.ecfr.gov/current/title-21/section-201.128
- 21 CFR 530.1, scope of the extra-label rules: https://www.ecfr.gov/current/title-21/section-530.1
- 21 CFR 530.2, purpose of the extra-label rules: https://www.ecfr.gov/current/title-21/section-530.2
- 21 CFR 514.117, adequate and well-controlled studies: https://www.ecfr.gov/current/title-21/section-514.117
- 21 CFR 514.80, reports on approved new animal drugs: https://www.ecfr.gov/current/title-21/section-514.80
- 21 CFR 514.3, definitions: https://www.ecfr.gov/current/title-21/section-514.3
- 21 CFR 11.1, scope of Part 11: https://www.ecfr.gov/current/title-21/section-11.1
- FDA, Unapproved Animal Drugs: https://www.fda.gov/animal-veterinary/compliance-enforcement/unapproved-animal-drugs
- FDA, FDA Regulation of Animal Drugs: https://www.fda.gov/animal-veterinary/resources-you/fda-regulation-animal-drugs
- FDA, From an Idea to the Marketplace: https://www.fda.gov/animal-veterinary/animal-health-literacy/idea-marketplace-journey-animal-drug-through-approval-process
- FDA, CVM GFI #85 (VICH GL9) Good Clinical Practice: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-85-vich-gl9-good-clinical-practice
- FDA, CVM GFI #282 Informed Consent Forms for Studies that Enroll Client-Owned Companion Animals, draft: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-282-informed-consent-forms-studies-enroll-client-owned-companion-animals
- FDA, How to Report Animal Drug and Device Side Effects and Product Problems: https://www.fda.gov/animal-veterinary/report-problem/how-report-animal-drug-and-device-side-effects-and-product-problems
- FDA, 2020 CVM eSubmitter Application History: https://www.fda.gov/industry/fda-esubmitter/2020-cvm-esubmitter-application-history