[Code of Federal Regulations] [Title 21, Volume 6] [Revised as of January 1, 2003] From the U.S. Government Printing Office via GPO Access [CITE: 21CFR514.80] [Page 73-79] TITLE 21--FOOD AND DRUGS CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PART 514--NEW ANIMAL DRUG APPLICATIONS--Table of Contents Subpart B--Administrative Actions on Applications Sec. 514.80 Records and reports concerning experience with approved new animal drugs. The following table outlines the purpose for each paragraph of this section: ------------------------------------------------------------------------ Purpose 21 CFR Paragraph and Title ------------------------------------------------------------------------ What information must be reported 514.80(a) Applicability. concerning approved NADAs or ANADAs? ------------------------------------------------------------------------ What authority does FDA have for 514.80(a)(1). requesting records and reports? Who is required to establish, maintain, and report required information relating to experiences with a new animal drug? Is information from foreign sources required? ------------------------------------------------------------------------ What records must be established and 514.80(a)(2). maintained and what reports filed with FDA? ------------------------------------------------------------------------ What is FDA's purpose for requiring 514.80(a)(3). reports? ------------------------------------------------------------------------ Do applicants of Type A medicated 514.80(a)(4). articles have to establish, maintain, and report information required under Sec. 514.80? ------------------------------------------------------------------------ How do the requirements under Sec. 514.80(a)(5). 514.80 relate to current good manufacturing practices? ------------------------------------------------------------------------ 514.80(b) Reporting requirements. ------------------------------------------------------------------------ [[Page 74]] What are the requirements for reporting 514.80(b)(1) Three-day NADA/ product/manufacturing defects? ANADA field alert report. ------------------------------------------------------------------------ 514.80(b)(2) Fifteen-day NADA/ ANADA alert report. ------------------------------------------------------------------------ What are the requirements for reporting 514.80(b)(2)(i) Initial serious and unexpected adverse drug report. experiences? ------------------------------------------------------------------------ What are the requirements for followup 514.80(b)(2)(ii) Followup reporting of serious and unexpected report. adverse drug experiences? ------------------------------------------------------------------------ What are the requirements for 514.80(b)(3) Nonapplicant nonapplicants for reporting adverse report. drug experiences? ------------------------------------------------------------------------ What are the general requirements for 514.80(b)(4) Periodic drug submission of periodic drug experience experience report. reports, e.g., forms to be submitted, submission date and frequency, when is it to be submitted, how many copies? How do I petition to change the date of submission or frequency of submissions? ------------------------------------------------------------------------ What must be submitted in the periodic 514.80(b)(4)(i) through drug experience reports? (b)(4)(iv). ------------------------------------------------------------------------ What distribution data must be 514.80(b)(4)(i) Distribution submitted? data. How should the distribution data be submitted? ------------------------------------------------------------------------ What labeling materials should be 514.80(b)(4)(ii) Labeling. submitted? How do I report changes to the labeling materials since the last report? ------------------------------------------------------------------------ 514.80(b)(4)(iii) Nonclinical laboratory studies and clinical data not previously reported. ------------------------------------------------------------------------ What are the requirements for submission 514.80(b)(4)(iii)(A). of nonclinical laboratory studies? ------------------------------------------------------------------------ What are the requirements for submission 514.80(b)(4)(iii)(B). of clinical laboratory data? ------------------------------------------------------------------------ When must results of clinical trials 514.80(b)(4)(iii)(C). conducted by or for the applicant be reported? ------------------------------------------------------------------------ 514.80(b)(4)(iv) Adverse drug experiences. ------------------------------------------------------------------------ How do I report product/manufacturing 514.80(b)(4)(iv)(A). defects and adverse drug experiences not previously reported to FDA? ------------------------------------------------------------------------ What are the requirements for submitting 514.80(b)(4)(iv)(B). adverse drug experiences cited in literature? ------------------------------------------------------------------------ What are the requirements for submitting 514.80(b)(4)(iv)(C). adverse drug experiences in postapproval studies and clinical trials? ------------------------------------------------------------------------ What are the requirements for reporting 514.80(b)(4)(v) Summary report increases in the frequency of serious, of increased frequency of expected, and unexpected adverse drug adverse drug experience. experiences? ------------------------------------------------------------------------ 514.80(b)(5) Other reporting. ------------------------------------------------------------------------ Can FDA request that an applicant submit 514.80(b)(5)(i) Special drug information at different times than experience report. stated specifically in this regulation? ------------------------------------------------------------------------ What are the requirements for submission 514.80(b)(5)(ii) of advertisement and promotional Advertisements and labeling to FDA? promotional labeling. ------------------------------------------------------------------------ What are the requirements for adding a 514.80(b)(5)(iii) new distributor to the approved Distributor's statement. application? ------------------------------------------------------------------------ What labels and how many labels need to 514.80(b)(5)(iii)(A). be submitted for review? ------------------------------------------------------------------------ What changes are required and allowed to 514.80(b)(5)(iii)(A)(1). distributor labeling? ------------------------------------------------------------------------ What are the requirements for making 514.80(b)(5)(iii)(A)(2). other changes to the distributor labeling? ------------------------------------------------------------------------ What information should be included in 514.80(b)(5)(iii)(B)(1) each new distributor's signed through (b)(5)(iii)(B)(5). statement? ------------------------------------------------------------------------ [[Page 75]] What are the conditions for submitting 514.80(c) Multiple information that is common to more than applications. one application? (i.e., can I submit common information to one application?) ------------------------------------------------------------------------ What information has to be submitted to 514.80(c)(1) through (c)(4). the common application and related application? ------------------------------------------------------------------------ What forms do I need? 514.80(d) Reporting forms. What are Forms FDA 1932 and 2301? How can I get them? Can I use computer-generated equivalents? ------------------------------------------------------------------------ How long must I maintain Form FDA 1932 514.80(e) Records to be and records and reports of other maintained. required information, i.e., how long do I need to maintain this information? ------------------------------------------------------------------------ What are the requirements for allowing 514.80(f) Access to records access to these records and reports, and reports. and copying by authorized FDA officer or employee? ------------------------------------------------------------------------ How do I obtain Forms FDA 1932 and 2301? 514.80(g) Mailing addresses. Where do I mail FDA's required forms, records, and reports? ------------------------------------------------------------------------ What happens if the applicant fails to 514.80(h) Withdrawal of establish, maintain, or make the approval. required reports? What happens if the applicant refuses to allow FDA access to, and/or copying and/ or verify records and reports? ------------------------------------------------------------------------ Does an adverse drug experience reflect 514.80(i) Disclaimer. a conclusion that the report or information constitutes an admission that the drug caused an adverse effect? ------------------------------------------------------------------------ (a) Applicability. (1) Each applicant must establish and maintain indexed and complete files containing full records of all information pertinent to safety or effectiveness of a new animal drug that has not been previously submitted as part of the NADA or ANADA. Such records must include information from domestic as well as foreign sources. Each nonapplicant must establish and maintain indexed and complete files containing full records of all information pertinent to safety or effectiveness of a new animal drug that is received or otherwise obtained by the nonapplicant. Such records must include information from domestic as well as foreign sources. (2) Each applicant must submit reports of data, studies, and other information concerning experience with new animal drugs to the Food and Drug Administration (FDA) for each approved NADA and ANADA, as required in this section. A nonapplicant must submit data, studies, and other information concerning experience with new animal drugs to the appropriate applicant, as required in this section. The applicant, in turn, must report the nonapplicant's data, studies, and other information to FDA. Applicants and nonapplicants must submit data, studies, and other information described in this section from domestic, as well as foreign sources. (3) FDA reviews the records and reports required in this section to facilitate a determination under section 512(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b(e)) as to whether there may be grounds for suspending or withdrawing approval of the NADA or ANADA. (4) The requirements of this section also apply to any approved Type A medicated article. In addition, the requirements contained in Sec. 514.80(b)(1), (b)(2), (b)(4)(iv), and (b)(4)(v) apply to any approved Type A medicated article incorporated in animal feeds. (5) The records and reports referred to in this section are in addition to those required by the current good manufacturing practice regulations in parts 211, 225, and 226 of this chapter. (b) Reporting requirements--(1) Three-day NADA/ANADA field alert report. This report provides information pertaining to product and manufacturing defects that may result in serious adverse drug events. The applicant (or nonapplicant through the applicant) [[Page 76]] must submit the report to the appropriate FDA District Office or local FDA resident post within 3 working days of first becoming aware that a defect may exist. The information initially may be provided by telephone or other telecommunication means, with prompt written followup using Form FDA 1932 ``Veterinary Adverse Drug Reaction, Lack of Effectiveness, Product Defect Report.'' The mailing cover for these reports must be plainly marked ``3-Day NADA/ANADA Field Alert Report.'' (2) Fifteen-day NADA/ANADA alert report--(i) Initial report. This report provides information on each serious, unexpected adverse drug event, regardless of the source of the information. The applicant (or nonapplicant through the applicant) must submit the report to FDA within 15 working days of first receiving the information. The report must be submitted on Form FDA 1932, and its mailing cover must be plainly marked ``15-Day NADA/ANADA Alert Report.'' (ii) Followup report. The applicant must promptly investigate all adverse drug events that are the subject of 15-day NADA/ANADA alert reports. If this investigation reveals significant new information, a followup report must be submitted within 15 working days of receiving such information. A followup report must be submitted on Form FDA 1932, and its mailing cover must be plainly marked ``15-Day NADA/ANADA Alert Report Followup.'' The followup report must state the date of the initial report and provide the additional information. If additional information is sought but not obtained within 3 months of the initial report, a followup report is required describing the steps taken and why additional information was not obtained. (3) Nonapplicant report. Nonapplicants must forward reports of adverse drug experiences to the applicant within 3 working days of first receiving the information. The applicant must then submit the report(s) to FDA as required in this section. The nonapplicant must maintain records of all nonapplicant reports, including the date the nonapplicant received the information concerning adverse drug experiences, the name and address of the applicant, and a copy of the adverse drug experience report including the date such report was submitted to the applicant. If the nonapplicant elects to also report directly to FDA, the nonapplicant should submit the report on Form FDA 1932 within 15 working days of first receiving the information. (4) Periodic drug experience report. This report must be accompanied by a completed Form FDA 2301 ``Transmittal of Periodic Reports and Promotional Materials for New Animal Drugs.'' It must be submitted every 6 months for the first 2 years following approval of an NADA or ANADA and yearly thereafter. Reports required by this section must contain data and information for the full reporting period. The 6-month periodic drug experience reports must be submitted within 30 days following the end of the 6-month reporting period. The yearly periodic drug experience reports must be submitted within 60 days of the anniversary date of the approval of the NADA or ANADA. Any previously submitted information contained in the report must be identified as such. For yearly (annual) periodic drug experience reports, the applicant may petition FDA to change the date of submission or frequency of reporting, and after approval of such petition, file such reports on the new filing date or at the new reporting frequency. Also, FDA may require a report at different times or more frequently. The periodic drug experience report must contain the following: (i) Distribution data. Information about the distribution of each new animal drug product, including information on any distributor- labeled product. This information must include the total number of distributed units of each size, strength, or potency (e.g., 100,000 bottles of 100 5-milligram tablets; 50,000 10-milliliter vials of 5- percent solution). This information must be presented in two categories: Quantities distributed domestically and quantities exported. (ii) Labeling. Applicant and distributor current package labeling, including package inserts (if any). For large-size package labeling or large shipping cartons, a representative copy must be submitted (e.g., a photocopy of [[Page 77]] pertinent areas of large feed bags). A summary of any changes in labeling made since the last report (listed by date of implementation) must be included with the labeling or if there have been no changes, a statement of such fact must be included with the labeling. (iii) Nonclinical laboratory studies and clinical data not previously reported. (A) Copies of in vitro studies (e.g., mutagenicity) and other nonclinical laboratory studies conducted by or otherwise obtained by the applicant. (B) Copies of published clinical trials of the new animal drug (or abstracts of them) including clinical trials on safety and effectiveness, clinical trials on new uses, and reports of clinical experience pertinent to safety conducted by or otherwise obtained by the applicant. Review articles, papers, and abstracts in which the drug is used as a research tool, promotional articles, press clippings, and papers that do not contain tabulations or summaries of original data are not required to be reported. (C) Descriptions of completed clinical trials conducted by or for the applicant must be submitted no later than 1 year after completion of research. Supporting information is not to be reported. (iv) Adverse drug experiences. (A) Product/manufacturing defects and adverse drug experiences not previously reported under Sec. 514.80(b)(1) and (b)(2) must be reported individually on Form FDA 1932. (B) Reports of adverse drug experiences in the literature must be noted in the periodic drug experience report. A bibliography of pertinent references must be included with the report. Upon FDA's request, the applicant must provide a full text copy of these publications. (C) Reports of previously not reported adverse drug experiences that occur in postapproval studies must be reported separately from other experiences in the periodic drug experience report and clearly marked or highlighted. (v) Summary report of increased frequency of adverse drug experience. The applicant must periodically review the incidence of reports of adverse drug experiences to determine if there has been an increased frequency of serious (expected and unexpected) adverse drug events. The applicant must evaluate the increased frequency of serious (expected or unexpected) adverse drug events at least as often as reporting of periodic drug experience reports. The applicant must report the increased frequency of serious (expected and unexpected) adverse drug events in the periodic drug experience report. Summaries of reports of increased frequency of adverse drug events must be submitted in narrative form. The summaries must state the time period on which the increased frequency is based, time period comparisons in determining increased frequency, references to any previously submitted Form FDA 1932, the method of analysis, and the interpretation of the results. The summaries must be submitted in a separate section within the periodic drug experience report. (5) Other reporting--(i) Special drug experience report. Upon written request, FDA may require that the applicant submit a report required under Sec. 514.80 at different times or more frequently than the timeframes stated in Sec. 514.80. (ii) Advertisements and promotional labeling. The applicant must submit at the time of initial dissemination one set of specimens of mailing pieces and other labeling for prescription and over-the-counter new animal drugs. For prescription new animal drugs, the applicant must also submit one set of specimens of any advertisement at the time of initial publication or broadcast. Mailing pieces and labeling designed to contain product samples must be complete except that product samples may be omitted. Each submission of promotional labeling or advertisements must be accompanied by a completed Form FDA 2301. (iii) Distributor's statement. At the time of initial distribution of a new animal drug product by a distributor, the applicant must submit a special drug experience report accompanied by a completed Form FDA 2301 containing the following: (A) The distributor's current product labeling. (1) The distributor's labeling must be identical to that in the approved [[Page 78]] NADA/ANADA except for a different and suitable proprietary name (if used) and the name and address of the distributor. The name and address of the distributor must be preceded by an appropriate qualifying phrase as permitted by the regulations such as ``manufactured for'' or ``distributed by.'' (2) Other labeling changes must be the subject of a supplemental NADA or ANADA as described under Sec. 514.8. (B) A signed statement by the distributor stating: (1) The category of the distributor's operations (e.g., wholesale or retail), (2) That the distributor will distribute the new animal drug only under the approved labeling, (3) That the distributor will promote the product only for use under the conditions stated in the approved labeling, (4) That the distributor will adhere to the records and reports requirements of this section, and (5) That the distributor is regularly and lawfully engaged in the distribution or dispensing of prescription products if the product is a prescription new animal drug. (c) Multiple applications. Whenever an applicant is required to submit a periodic drug experience report under the provisions of Sec. 514.80(b)(4) with respect to more than one approved NADA or ANADA for preparations containing the same new animal drug so that the same information is required to be reported for more than one application, the applicant may elect to submit as a part of the report for one such application (the primary application) all the information common to such applications in lieu of reporting separately and repetitively on each. If the applicant elects to do this, the applicant must do the following: (1) State when a report applies to multiple applications and identify all related applications for which the report is submitted by NADA or ANADA number. (2) Ensure that the primary application contains a list of the NADA or ANADA numbers of all related applications. (3) Submit a completed Form FDA 2301 to the primary application and each related application with reference to the primary application by NADA/ANADA number and submission date for the complete report of the common information. (4) All other information specific to a particular NADA/ANADA must be included in the report for that particular NADA/ANADA. (d) Reporting forms. Applicant must report adverse drug experiences and product/manufacturing defects on Form FDA 1932, ``Veterinary Adverse Drug Reaction, Lack of Effectiveness, Product Defect Report.'' Periodic drug experience reports and special drug experience reports must be accompanied by a completed Form FDA 2301 ``Transmittal of Periodic Reports and Promotional Material for New Animal Drugs,'' in accordance with directions provided on the forms. Computer-generated equivalents of Form FDA 1932 or Form FDA 2301, approved by FDA before use, may be used. Form FDA 1932 and Form FDA 2301 may be obtained on the Internet at http://www.fda.gov/cvm/forms/forms.html, by telephoning the Division of Surveillance (HFV-210), or by submitting a written request to the following address: Food and Drug Administration, Center for Veterinary Medicine, Division of Surveillance (HFV-210), 7500 Standish Pl., Rockville, MD 20855-2764. (e) Records to be maintained. The applicants and nonapplicants must maintain records and reports of all information required by this section for a period of 5 years after the date of submission. (f) Access to records and reports. The applicant and nonapplicant must, upon request from any authorized FDA officer or employee, at all reasonable times, permit such officer or employee to have access to copy and to verify all such required records and reports. (g) Mailing addresses. Completed 15-day alert reports, periodic drug experience reports, and special drug experience reports must be submitted to the following address: Food and Drug Administration, Center for Veterinary Medicine, Document Control Unit (HFV-199), 7500 Standish Pl., Rockville, MD 20855-2764. Three-day alert reports must be submitted to the appropriate FDA district office or local FDA resident post. Addresses for district offices [[Page 79]] and resident posts may be obtained from the Internet at http:// www.fda.gov (click on ``Contact FDA,'' then ``FDA Field Offices''). (h) Withdrawal of approval. If FDA finds that the applicant has failed to establish the required records, or has failed to maintain those records, or failed to make the required reports, or has refused access to an authorized FDA officer or employee to copy or to verify such records or reports, FDA may withdraw approval of the application to which such records or reports relate. If FDA determines that withdrawal of the approval is necessary, the agency shall give the applicant notice and opportunity for hearing, as provided in Sec. 514.200, on the question of whether to withdraw approval of the application. (i) Disclaimer. Any report or information submitted under this section and any release of that report or information by FDA will be without prejudice and does not necessarily reflect a conclusion that the report or information constitutes an admission that the drug caused or contributed to an adverse event. A person need not admit, and may deny, that the report or information constitutes an admission that a drug caused or contributed to an adverse event. [68 FR 15365, Mar. 31, 2003] Effective Date Note: At 68 FR 15365, Mar. 31, 2003, Sec. 514.80 was added, effective June 30, 2003.