21 C.F.R. § 511.1 New animal drugs for investigational use exempt from section 512(a) of the Federal Food, Drug, and Cosmetic Act.
(a) New animal drugs for tests in vitro and in laboratory research animals. (1) A shipment or other delivery of a new animal drug or animal feed bearing or containing a new animal drug intended solely for tests in vitro or in animals used only for laboratory research purposes shall be exempt from section 512 (a) and (m) of the act if it is labeled as follows:
(2) The person distributing or causing the distribution of new animal drugs for tests in vitro or in animals used only for laboratory research purposes under this exemption shall use due diligence to assure that the consignee is regularly engaged in conducting such tests and that the shipment of the new animal drug will actually be used for tests in vitro or in animals used only for laboratory research.
(3) The person who introduced such shipment or who delivered the new animal drug for introduction into interstate commerce shall maintain adequate records showing the name and post office address of the expert or expert organization to whom the new animal drug is shipped and the date, quantity, and batch or code mark of each shipment and delivery for a period of 2 years after such shipment and delivery. Upon the request of a properly authorized employee of the Department at reasonable times, he shall make such records available for inspection and copying.
(4) The exemption allowed in this paragraph shall not apply to any new animal drug intended for in vitro use in the regular course of diagnosing or treating disease, including antibacterial sensitivity discs impregnated with any new animal drug or drugs, which discs are intended for use in determining susceptibility of microorganisms to the new animal drug or drugs.
(b) New animal drugs for clinical investigation in animals. A shipment or other delivery of a new animal drug or an animal feed containing a new animal drug intended for clinical investigational use in animals shall be exempt from section 512(a) and (m) of the act if all the following conditions are met:
(1) The label shall bear the statements:
In the case of containers too small or otherwise unable to accommodate a label with sufficient space to bear the caution statements required by paragraph (a) or (b) of this section, the statements may be included on the carton label and other labeling on or within the package from which the new animal drug is to be dispensed.
(2) The person or firm distributing or causing the distribution of the new animal drug or animal feed containing a new animal drug shall use due diligence to assure that the new animal drug or animal feed containing a new animal drug will actually be used for tests in animals and is not used in humans.
(3) The person who introduced such shipment or who delivered the new animal drug or animal feed containing a new animal drug for introduction into interstate commerce shall maintain adequate records showing the name and post office address of the investigator to whom the new animal drug or animal feed containing a new animal drug is shipped and the date, quantity, and batch or code mark of each shipment and delivery for a period of 2 years after such shipment and delivery. Upon the request of a properly authorized employee of the Department at reasonable times, such records shall be made available for inspection and copying.
(4) Prior to shipment of the new animal drug for clinical tests in animals, the sponsor of the investigation shall submit in triplicate to FDA a “Notice of Claimed Investigational Exemption for a New Animal Drug” including a signed statement containing the following information:
(i) The identity of the new animal drug.
(ii) All labeling and other pertinent information to be supplied to the investigators. When such pertinent information includes nonclinical laboratory studies, the information shall include, with respect to each nonclinical study, either a statement that the study was conducted in compliance with the requirements set forth in part 58 of this chapter, or, if the study was not conducted in compliance with such regulations, a brief statement of the reason for the noncompliance.
(iii) The name and address of each clinical investigator.
(iv) The approximate number of animals to be treated (or if not available, the amount of new animal drug to be shipped).
(v) If the new animal drug is given to food-producing animals, the statement shall contain the following additional information:
(a) A commitment that the edible products from such animals shall not be used for food without prior authorization in accordance with the provisions prescribed in this section.
(b) Approximate dates of the beginning and end of the experiment or series of experiments.
(c) The maximum daily dose(s) to be administered to a given species, the size of animal, maximum duration of administration, method(s) of administration, and proposed withdrawal time, if any.
(vi) If a sponsor has transferred any obligations for the conduct of any clinical study to a contract research organization, a statement containing the name and address of the contract research organization, identification of the clinical study, and a listing of the obligations transferred. If all obligations governing the conduct of the study have been transferred, a general statement of this transfer—in lieu of a listing of the specific obligations transferred—may be submitted.
(5) Authorization for use of edible products derived from a treated food-producing animal may be granted under the provisions of this section and when the following specified conditions are met, except that in the case of an animal administered any unlicensed experimental veterinary biological product regulated under the viruses, serums, toxins statute (21 U.S.C., chapter V, sec. 151 et seq. ) the product shall be exempt from the requirements of this section when U.S. Department of Agriculture approval has been obtained as provided in 9 CFR 103.2. Conditional authorization may be granted in advance of identification of the name(s) and address(es) of the clinical investigator(s) as required by paragraph (b)(4)(iii) of this section. Information required for authorization shall include, in addition to all other requirements of this section, the following:
(i) Data to show that consumption of food derived from animals treated at the maximum levels with the minimum withdrawal periods, if any, specified in accordance with paragraph (b)(4)(v)(c) of this section, will not be inconsistent with the public health; or
(ii) Data to show that food derived from animals treated at the maximum levels and with the minimum withdrawal periods, if any, specified in accordance with paragraph (b)(4)(v)(c) of this section, does not contain drug residues or metabolites.
(iii) The name and location of the packing plant where the animals will be processed, except that this requirement may be waived, on request, by the terms of the authorization.
(6) On written request of FDA, the sponsor shall submit any additional information reported to or otherwise received by him with respect to the investigation deemed necessary to facilitate a determination whether there are grounds in the interest of public health for terminating the exemption.
(7) The sponsor shall assure himself that the new animal drug is shipped only to investigators who:
(i) Are qualified by scientific training and/experience to evaluate the safety and/or effectiveness of the new animal drug.
(ii) Shall maintain complete records of the investigations, including complete records of the receipt and disposition of each shipment or delivery of the new animal drug under investigation. Copies of all records of the investigation shall be retained by the investigator for 2 years after the termination of the investigation or approval of a new animal drug application.
(iii) Shall furnish adequate and timely reports of the investigation to the sponsor.
(8) The sponsor:
(i) Shall retain all reports received from investigators for 2 years after the termination of the investigation or approval of a new animal drug application and make such reports available to a duly authorized employee of the Department for inspection at all reasonable times.
(ii) Shall provide for current monitoring of the investigation by a person qualified by scientific training and experience to evaluate information obtained from the investigation, and shall promptly investigate and report to FDA and to all investigators any findings associated with use of the new animal drug that may suggest significant hazards pertinent to the safety of the new animal drug.
(iii) Shall not unduly prolong distribution of the new animal drug for investigational use.
(iv) Shall not, nor shall any person acting for or on behalf of the sponsor, represent that the new animal drug is safe or effective for the purposes for which it is under investigation. This requirement is not intended to restrict the full exchange of scientific information.
(v) Shall not commercially distribute nor test-market the new animal drug until a new animal drug application is approved pursuant to section 512(c) of the act.
(9) If the shipment or other delivery of the new animal drug is imported or offered for importation into the United States for clinical investigational use in animals, it shall also meet the following conditions:
(i) The importer of all such shipments or deliveries is an agent of the foreign exporter residing in the United States or the ultimate consignee, which person has, prior to such shipments and deliveries, informed FDA of his intention to import the new animal drug as sponsor in compliance with the conditions prescribed in this subdivision; or
(ii) The new animal drug is shipped directly to a scientific institution with adequate facilities and qualified personnel to conduct laboratory or clinical investigations and is intended solely for use in such institutions and which institution has submitted a statement as sponsor of the investigation.
(10) The sponsor shall submit either a claim for categorical exclusion under § 25.30 or § 25.33 of this chapter or an environmental assessment under § 25.40 of this chapter.
(c) Disqualification of a clinical investigator. (1) If FDA has information indicating that an investigator (including a sponsor-investigator) has repeatedly or deliberately failed to comply with the conditions of these exempting regulations or has repeatedly or deliberately submitted to FDA or to the sponsor false information in any required report, the Center for Veterinary Medicine will furnish the investigator written notice of the matter complained of and offer the investigator an opportunity to explain the matter in writing, or, at the option of the investigator, in an informal conference. If an explanation is offered and accepted by the Center for Veterinary Medicine, the Center will discontinue the disqualification proceeding. If an explanation is offered but not accepted by the Center for Veterinary Medicine, the investigator will be given an opportunity for a regulatory hearing under part 16 of this chapter on the question of whether the investigator is eligible to receive test articles under this part and eligible to conduct:
(i) Any clinical investigation that supports an application for a research or marketing permit for products regulated by FDA; and
(ii) Any nonclinical laboratory study intended to support an application for a research or marketing permit for a new animal drug.
(2) After evaluating all available information, including any explanation presented by the investigator, if the Commissioner determines that the investigator has repeatedly or deliberately failed to comply with the conditions of the exempting regulations in this subchapter, or has repeatedly or deliberately submitted to FDA or to the sponsor false information in any required report, the Commissioner will notify the investigator and the sponsor of any investigation in which the investigator has been named as a participant that the investigator is not eligible to receive test articles under this part. The notification to the investigator and sponsor will provide a statement of the basis for such determination. The notification also will explain that an investigator determined to be ineligible to receive test articles under this part will be ineligible to conduct:
(i) Any clinical investigation that supports an application for a research or marketing permit for products regulated by FDA, including drugs, biologics, devices, new animal drugs, foods, including dietary supplements, that bear a nutrient content claim or a health claim, infant formulas, food and color additives, and tobacco products; and
(ii) Any nonclinical laboratory study intended to support an application for a research or marketing permit for a new animal drug.
(3) Each application or submission to FDA under the provisions of this chapter containing data reported by an investigator who has been determined to be ineligible to receive FDA-regulated test articles is subject to examination to determine whether the investigator has submitted unreliable data that are essential to the continuation of an investigation or essential to the approval of a marketing application, or essential to the continued marketing of an FDA-regulated product.
(4) If the Commissioner determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the data remaining are inadequate to support a conclusion that it is reasonably safe to continue the investigation, the Commissioner will notify the sponsor, who shall have an opportunity for a regulatory hearing under part 16 of this chapter. If a danger to the public health exists, however, the Commissioner shall terminate the exemption immediately and notify the sponsor of the termination. In such case, the sponsor shall have an opportunity for a regulatory hearing before FDA under part 16 on the question of whether the exemption should be reinstated. The determination that an investigation may not be considered in support of a research or marketing application or a notification or petition submission does not, however, relieve the sponsor of any obligation under any other applicable regulation to submit to FDA the results of the investigation.
(5) If the Commissioner determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the continued approval of the product for which the data were submitted cannot be justified, the Commissioner will proceed to withdraw approval of the product in accordance with the applicable provisions of the relevant statutes.
(6) An investigator who has been determined to be ineligible under paragraph (c)(2) of this section may be reinstated as eligible when the Commissioner determines that the investigator has presented adequate assurances that the investigator will employ all test articles, and will conduct any clinical investigation that supports an application for a research or marketing permit for products regulated by FDA and any nonclinical laboratory study intended to support an application for a research or marketing permit for a new animal drug, solely in compliance with the applicable provisions of this chapter.
(d) Termination of exemption. If the Commissioner finds that:
(1) The sponsor of the investigation has failed to comply with any of the conditions for the exemption established under this section, or
(2) The continuance of the investigation is unsafe or otherwise contrary to the public interest or the drug is being or has been used for purposes other than bona fide scientific investigation, he shall first notify the sponsor and invite his immediate correction. If the conditions of the exemption are not immediately met, the sponsor shall have an opportunity for a regulatory hearing before FDA pursuant of part 16 of this chapter on whether the exemption should be terminated. If the exemption is terminated the sponsor shall recall or have destroyed the unused supplies of the new animal drug.
(e) Statements and requests. “Notice(s) of Claimed Investigational Exemption for a New Animal Drug” and requests for authorization to use investigational animals and their products for food should be addressed to the Department of Health and Human Services, Food and Drug Administration, Center for Veterinary Medicine, 7500 Standish Pl., Rockville, MD 20855.
(f) Contract research organizations. (1) For purposes of this part and part 514, contract research organization means a person that assumes, as an independent contractor with the sponsor, one or more of the obligations of a sponsor, e.g., design of a protocol, selection or monitoring of investigations, evaluation of reports, and preparation of materials to be submitted to FDA.
(2) A sponsor may transfer responsibility for any or all of the obligations set forth in this part to a contract research organization. Any such transfer shall be in writing and, if not all obligations are transferred, shall describe each of the obligations being assumed by the contract research organization. If all obligations are transferred, a general statement that all obligations have been transferred is acceptable. Any obligation not covered by the written description shall be deemed not to have been transferred.
(3) A contract research organization that assumes any obligation of a sponsor shall comply with the specific regulations in this chapter applicable to this obligation and shall be subject to the same regulatory action as a sponsor for failure to comply with any obligation assumed under these regulations. Thus, all references to sponsor in this part apply to a contract research organization to the extent that it assumes one or more obligations of the sponsor.
(g) Index of legally marketed unapproved new animal drugs for minor species. All provisions of part 511 apply to new animal drugs for investigational use in support of indexing, as described in section 572 of the act, subject to the provisions of § 516.125 of this chapter.
Caution. Contains a new animal drug for investigational use only in laboratory research animals or for tests in vitro. Not for use in humans.
Caution. Contains a new animal drug for use only in investigational animals in clinical trials. Not for use in humans. Edible products of investigational animals are not to be used for food unless authorization has been granted by the U.S. Food and Drug Administration or by the U.S. Department of Agriculture.