New animal drugs for investigational use (21 CFR 511.1-511.3)

82 21 CFR Ch. I (4–1–16 Edition) Pt. 511 EDITORIAL NOTES: 1. For FEDERAL REGISTER citations affecting § 510.600, see the List of CFR Sections Affected, which appears in the Finding Aids section of the printed volume and at www.fdsys.gov. 2. At 72 FR 36595, July 5, 2007, § 510.600, in the table in paragraph (c)(2), was amended by re moving the entry for ‘‘062749’’; however, the amendment could not be incorporated because the entry did not exist. 3. At 77 FR 46613, Aug. 6, 2012, § 510.600 was amended by removing the entry for ‘‘012758’’ in the table in paragraph (c)(2); however, the amendment could not be incorporated because ‘‘012758’’ didn’t exist. PART 511—NEW ANIMAL DRUGS FOR INVESTIGATIONAL USE Sec. 511.1 New animal drugs for investigational use exempt from section 512(a) of the act. 511.3 Definitions. AUTHORITY: 21 U.S.C. 321, 351, 352, 353, 360b, 371. § 511.1 New animal drugs for inves tigational use exempt from section 512(a) of the 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 pur poses shall be exempt from section 512 (a) and (m) of the act if it is labeled as follows: Caution. Contains a new animal drug for investigational use only in laboratory re search animals or for tests in vitro. Not for use in humans. (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 dili gence 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 ani mal drug for introduction into inter state commerce shall maintain ade quate records showing the name and post office address of the expert or ex pert organization to whom the new ani mal drug is shipped and the date, quan tity, 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 author ized 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 anti bacterial sensitivity discs impregnated with any new animal drug or drugs, which discs are intended for use in de termining susceptibility of microorga nisms to the new animal drug or drugs. (b) New animal drugs for clinical inves tigation in animals. A shipment or other delivery of a new animal drug or an animal feed containing a new animal drug intended for clinical investiga tional 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 state ments: Caution. Contains a new animal drug for use only in investigational animals in clin ical 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 Ad ministration or by the U.S. Department of Agriculture. In the case of containers too small or otherwise unable to accommodate a label with sufficient space to bear the caution statements required by para graph (a) or (b) of this section, the statements may be included on the car ton label and other labeling on or with in the package from which the new ani mal drug is to be dispensed. (2) The person or firm distributing or causing the distribution of the new ani mal drug or animal feed containing a new animal drug shall use due dili gence to assure that the new animal drug or animal feed containing a new VerDate Sep<11>2014 10:06 Apr 14, 2016 Jkt 238075 PO 00000 Frm 00092 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 83 Food and Drug Administration, HHS § 511.1 animal drug will actually be used for tests in animals and is not used in hu mans. (3) The person who introduced such shipment or who delivered the new ani mal 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 investi gator 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 ship ment and delivery for a period of 2 years after such shipment and delivery. Upon the request of a properly author ized employee of the Department at reasonable times, such records shall be made available for inspection and copying. (4) Prior to shipment of the new ani mal 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 fol lowing information: (i) The identity of the new animal drug. (ii) All labeling and other pertinent information to be supplied to the inves tigators. When such pertinent informa tion 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 re quirements set forth in part 58 of this chapter, or, if the study was not con ducted in compliance with such regula tions, a brief statement of the reason for the noncompliance. (iii) The name and address of each clinical investigator. (iv) The approximate number of ani mals 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 author ization in accordance with the provi sions prescribed in this section. (b) Approximate dates of the begin ning and end of the experiment or se ries 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 adminis tration, and proposed withdrawal time, if any. (vi) If a sponsor has transferred any obligations for the conduct of any clin ical study to a contract research orga nization, a statement containing the name and address of the contract re search organization, identification of the clinical study, and a listing of the obligations transferred. If all obliga tions governing the conduct of the study have been transferred, a general statement of this transfer—in lieu of a listing of the specific obligations trans ferred—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., chap ter 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 ad vance of identification of the name(s) and address(es) of the clinical investi gator(s) as required by paragraph (b)(4)(iii) of this section. Information required for authorization shall in clude, in addition to all other require ments of this section, the following: (i) Data to show that consumption of food derived from animals treated at the maximum levels with the min imum withdrawal periods, if any, speci fied 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 with drawal periods, if any, specified in ac cordance with paragraph (b)(4)(v)(c) of this section, does not contain drug res idues or metabolites. VerDate Sep<11>2014 10:06 Apr 14, 2016 Jkt 238075 PO 00000 Frm 00093 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 84 21 CFR Ch. I (4–1–16 Edition) § 511.1 (iii) The name and location of the packing plant where the animals will be processed, except that this require ment may be waived, on request, by the terms of the authorization. Authorizations granted under this paragraph do not exempt investiga tional animals and their products from compliance with other applicable in spection requirements. Any person who contests a refusal to grant such au thorization shall have an opportunity for a regulatory hearing before FDA pursuant to part 16 of this chapter. (6) On written request of FDA, the sponsor shall submit any additional in formation reported to or otherwise re ceived by him with respect to the in vestigation deemed necessary to facili tate 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 com plete records of the receipt and disposi tion of each shipment or delivery of the new animal drug under investigation. Copies of all records of the investiga tion shall be retained by the investi gator for 2 years after the termination of the investigation or approval of a new animal drug application. (iii) Shall furnish adequate and time ly 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 ap proval of a new animal drug applica tion and make such reports available to a duly authorized employee of the Department for inspection at all rea sonable times. (ii) Shall provide for current moni toring of the investigation by a person qualified by scientific training and ex perience to evaluate information ob tained 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 signifi cant hazards pertinent to the safety of the new animal drug. (iii) Shall not unduly prolong dis tribution 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 informa tion. (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 fol lowing conditions: (i) The importer of all such ship ments or deliveries is an agent of the foreign exporter residing in the United States or the ultimate consignee, which person has, prior to such ship ments and deliveries, informed FDA of his intention to import the new animal drug as sponsor in compliance with the conditions prescribed in this subdivi sion; or (ii) The new animal drug is shipped directly to a scientific institution with adequate facilities and qualified per sonnel to conduct laboratory or clin ical investigations and is intended solely for use in such institutions and which institution has submitted a statement as sponsor of the investiga tion. (10) The sponsor shall submit either a claim for categorical exclusion under § 25.30 or § 25.33 of this chapter or an en vironmental assessment under § 25.40 of this chapter. (c) Disqualification of a clinical investi gator. (1) If FDA has information indi cating that an investigator (including a sponsor-investigator) has repeatedly or deliberately failed to comply with the conditions of these exempting regu lations or has repeatedly or delib erately submitted to FDA or to the VerDate Sep<11>2014 10:06 Apr 14, 2016 Jkt 238075 PO 00000 Frm 00094 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 85 Food and Drug Administration, HHS § 511.1 sponsor false information in any re quired report, the Center for Veteri nary Medicine will furnish the investi gator written notice of the matter complained of and offer the investi gator an opportunity to explain the matter in writing, or, at the option of the investigator, in an informal con ference. 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 oppor tunity 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 any clinical in vestigation that supports an applica tion for a research or marketing per mit for products regulated by FDA. (2) After evaluating all available in formation, including any explanation presented by the investigator, if the Commissioner determines that the in vestigator has repeatedly or delib erately failed to comply with the con ditions 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 in vestigator has been named as a partici pant that the investigator is not eligi ble to receive test articles under this part. The notification to the investi gator and sponsor will provide a state ment of the basis for such determina tion. The notification also will explain that an investigator determined to be ineligible to receive test articles under this part will be ineligible to conduct any clinical investigation that sup ports an application for a research or marketing permit for products regu lated by FDA, including drugs, bio logics, 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. (3) Each application or submission to FDA under the provisions of this chap ter containing data reported by an in vestigator 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 in vestigation or essential to the approval of a marketing application, or essen tial 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 hear ing under part 16 of this chapter. If a danger to the public health exists, how ever, the Commissioner shall termi nate 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 ques tion 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 peti tion submission does not, however, re lieve the sponsor of any obligation under any other applicable regulation to submit to FDA the results of the in vestigation. (5) If the Commissioner determines, after the unreliable data submitted by the investigator are eliminated from consideration, that the continued ap proval of the product for which the data were submitted cannot be justi fied, the Commissioner will proceed to withdraw approval of the product in ac cordance with the applicable provisions of the relevant statutes. (6) An investigator who has been de termined to be ineligible under para graph (c)(2) of this section may be rein stated as eligible when the Commis sioner 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 applica tion for a research or marketing per mit for products regulated by FDA, solely in compliance with the applica ble provisions of this chapter. VerDate Sep<11>2014 10:06 Apr 14, 2016 Jkt 238075 PO 00000 Frm 00095 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 86 21 CFR Ch. I (4–1–16 Edition) § 511.3 (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 estab lished under this section, or (2) The continuance of the investiga tion 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 in vite 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 exemp tion should be terminated. If the ex emption is terminated the sponsor shall recall or have destroyed the un used 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, evalua tion of reports, and preparation of ma terials to be submitted to FDA. (2) A sponsor may transfer responsi bility for any or all of the obligations set forth in this part to a contract re search organization. Any such transfer shall be in writing and, if not all obli gations are transferred, shall describe each of the obligations being assumed by the contract research organization. If all obligations are transferred, a gen eral 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 spon sor shall comply with the specific regu lations in this chapter applicable to this obligation and shall be subject to the same regulatory action as a spon sor for failure to comply with any obli gation assumed under these regula tions. Thus, all references to sponsor in this part apply to a contract research organization to the extent that it as sumes one or more obligations of the sponsor. (g) Index of legally marketed unap proved new animal drugs for minor spe cies. 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. [40 FR 13823, Mar. 27, 1975, as amended at 41 FR 48268, Nov. 2, 1976; 42 FR 15675, Mar. 22, 1977; 50 FR 7517, Feb. 22, 1985; 50 FR 16668, Apr. 26, 1985; 52 FR 8847, Mar. 19, 1987; 54 FR 18280, Apr. 28, 1989; 57 FR 6475, Feb. 25, 1992; 62 FR 40599, July 29, 1997; 72 FR 69121, Dec. 6, 2007; 77 FR 25359, Apr. 30, 2012] § 511.3 Definitions. As used in this part: 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, evalua tion of reports, and preparation of ma terials to be submitted to the Food and Drug Administration. Investigator means an individual who actually conducts a clinical investiga tion (i.e., under whose immediate di rection the drug is administered or dis pensed to a subject). In the event an in vestigation is conducted by a team of individuals, the investigator is the re sponsible leader of the team. ‘‘Sub investigator’’ includes any other indi vidual member of that team. Sponsor means a person who takes re sponsibility for and initiates a clinical investigation. The sponsor may be an individual or pharmaceutical company, governmental agency, academic insti tution, private organization, or other organization. The sponsor does not ac tually conduct the investigation unless the sponsor is a sponsor-investigator. A person other than an individual that uses one or more of its own employees to conduct an investigation that it has VerDate Sep<11>2014 10:06 Apr 14, 2016 Jkt 238075 PO 00000 Frm 00096 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B 87 Food and Drug Administration, HHS § 514.1 initiated is a sponsor, not a sponsor-in vestigator, and the employees are in vestigators. Sponsor-Investigator means an indi vidual who both initiates and conducts an investigation, and under whose im mediate direction the investigational drug is administered or dispensed. The term does not include any person other than an individual. The requirements applicable to a sponsor-investigator under this part include both those ap plicable to an investigator and a spon sor. [77 FR 25359, Apr. 30, 2012] PART 514—NEW ANIMAL DRUG APPLICATIONS Subpart A—General Provisions Sec. 514.1 Applications. 514.3 Definitions. 514.4 Substantial evidence. 514.5 Presubmission conferences. 514.6 Amended applications. 514.7 Withdrawal of applications without prejudice. 514.8 Supplements and other changes to an approved application. 514.11 Confidentiality of data and informa tion in a new animal drug application file. 514.12 Confidentiality of data and informa tion in an investigational new animal drug notice. 514.15 Untrue statements in applications. Subpart B—Administrative Actions on Applications 514.80 Records and reports concerning expe rience with approved new animal drugs. 514.100 Evaluation and comment on applica tions. 514.105 Approval of applications. 514.106 Approval of supplemental applica tions. 514.110 Reasons for refusing to file applica tions. 514.111 Refusal to approve an application. 514.115 Withdrawal of approval of applica tions. 514.116 Notice of withdrawal of approval of application. 514.117 Adequate and well-controlled stud ies. 514.120 Revocation of order refusing to ap prove an application or suspending or withdrawing approval of an application. 514.121 Service of notices and orders. Subpart C—Hearing Procedures 514.200 Contents of notice of opportunity for a hearing. 514.201 Procedures for hearings. Subparts D–E [Reserved] Subpart F—Judicial Review 514.235 Judicial review. AUTHORITY: 21 U.S.C. 321, 331, 351, 352, 354, 356a, 360b, 371, 379e, 381. SOURCE: 40 FR 13825, Mar. 27, 1975, unless otherwise noted. Subpart A—General Provisions § 514.1 Applications. (a) Applications to be filed under sec tion 512(b) of the act shall be submitted in the form and contain the informa tion described in paragraph (b) of this section, as appropriate to support the particular submission. If any part of the application is in a foreign lan guage, an accurate and complete English translation shall be appended to such part. Translations of literature printed in a foreign language shall be accompanied by copies of the original publication. The application must be signed by the applicant or by an au thorized attorney, agent, or official. If the applicant or such authorized rep resentative does not reside or have a place of business within the United States, the application must also fur nish the name and post office address of, and must be countersigned by, an authorized attorney, agent, or official residing or maintaining a place of busi ness within the United States. Perti nent information may be incorporated in, and will be considered as part of, an application on the basis of specific ref erence to such information, including information submitted under the provi sions of § 511.1 of this chapter, in the files of the Food and Drug Administra tion; however, the reference must be specific in identifying the information. Any reference to information furnished by a person other than the applicant may not be considered unless its use is authorized in a written statement signed by the person who submitted it. (b) Applications for new animal drugs shall be submitted in triplicate and as sembled in the manner prescribed by VerDate Sep<11>2014 10:06 Apr 14, 2016 Jkt 238075 PO 00000 Frm 00097 Fmt 8010 Sfmt 8010 Q:\21\21V6.TXT 31lp o w e ll o n D S K 5 4 D X V N 1 O F R w ith $ $ JO B