Title 21

SECTION 514.80

514.80 Records and reports concerning experience with approved new animal drugs.

§ 514.80 Records and reports concerning experience with approved new animal drugs.

The following table outlines the purpose for each paragraph of this section:

(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 § 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) 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.” If the applicant elects to also report directly to the FDA's Center for Veterinary Medicine (CVM), the applicant must submit the report to CVM in electronic format as described in paragraph (d)(1) of this section, unless the applicant obtains a waiver under paragraph (d)(2) of this section or FDA requests the report in an alternate format.

(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 to FDA in electronic format as described in paragraph (d)(1) of this section, unless the applicant obtains a waiver under paragraph (d)(2) of this section or FDA requests the report in an alternate format.

(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 to FDA in electronic format as described in paragraph (d)(1) of this section, unless the applicant obtains a waiver under paragraph (d)(2) of this section or FDA requests the report in an alternate format. 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 must submit the report to FDA in electronic format as described in paragraph (d)(1) of this section, unless the nonapplicant obtains a waiver under paragraph (d)(2) of this section or FDA requests the report in an alternate format.

(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 90 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. (A) 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.

(B) Applicants submitting annual sales and distribution reports for antimicrobial new animal drug products under § 514.87 have the option not to report distribution data under paragraph (b)(4)(i)(A) of this section for the approved applications that include these same products, but only provided each of the following conditions are met:

(1) Applicants must have submitted complete periodic drug experience reports under this section for such applications for at least 2 full years after the date of their initial approval.

(2) Applicants must ensure that the beginning of the reporting period for the annual periodic drug experience reports for such applications is January 1. For applications that currently have a reporting period that begins on a date other than January 1, applicants must request a change in reporting submission date such that the reporting period begins on January 1 and ends on December 31, as described in paragraph (b)(4) of this section.

(3) Applicants that change their reporting submission date must also submit a special drug experience report, as described in paragraph (b)(5)(i) of this section, that addresses any gaps in distribution data caused by the change in date of submission.

(4) Applicants who choose not to report under paragraph (b)(4)(i)(A) of this section must ensure that full sales and distribution data for each product approved under such applications are alternatively reported under § 514.87, including products that are labeled for use only in nonfood-producing animals.

(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 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 paragraphs (b)(1) and (2) of this section must be reported individually to FDA in electronic format as described in paragraph (d)(1) of this section, unless the applicant obtains a waiver under paragraph (d)(2) of this section or FDA requests the report in an alternate format.

(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 individually to FDA in electronic format as described in paragraph (d)(1) of this section, unless the applicant obtains a waiver under paragraph (d)(2) of this section or FDA requests the report in an alternate format.

(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 reports previously submitted under paragraphs (b)(1), (2), and (3) and (b)(4)(iv)(A) and (C) of this section, 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 § 514.80 at different times or more frequently than the timeframes stated in § 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 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 § 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 § 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) Format for submissions - (1) Electronic submissions. Except as provided in paragraph (d)(2) of this section, reports submitted to FDA under paragraphs (b)(2)(i) and (ii), (b)(3), and (b)(4)(iv)(A) and (C) of this section and reports submitted to CVM under paragraph (b)(1) of this section must be submitted in an electronic format that FDA can process, review, and archive. Data provided in electronic submissions must be in conformance with the data elements in Form FDA 1932 and FDA technical documents describing transmission. As necessary, FDA will issue updated technical documents on how to provide the electronic submission (e.g., method of transmission and processing, media, file formats, preparation, and organization of files). Unless requested by FDA, paper copies of reports submitted electronically should not be submitted to FDA.

(2) Waivers. An applicant or nonapplicant may request, in writing, a temporary waiver of the electronic submission requirements in paragraph (d)(1) of this section. The initial request may be by telephone or email to CVM's Division of Veterinary Product Safety, with prompt written followup submitted as a letter to the application(s). FDA will grant waivers on a limited basis for good cause shown. If FDA grants a waiver, the applicant or nonapplicant must comply with the conditions for reporting specified by FDA upon granting the waiver.

(3) Paper forms. If approved by FDA before use, a computer-generated equivalent of Form FDA 1932 may be used for reports submitted to the appropriate FDA District Office or local FDA resident post under paragraph (b)(1) of this section and to FDA under paragraph (d)(2) of this section, and a computer-generated equivalent of Form FDA 2301 may be used for reports submitted to FDA under paragraph (b)(4) of this section. Form FDA 1932 may be obtained on the FDA website, by telephoning CVM's Division of Veterinary Product Safety, or by submitting a written request to the following address: Food and Drug Administration, Center for Veterinary Medicine, Division of Veterinary Product Safety (HFV-240), 7500 Standish Pl., Rockville, MD 20855-2764. Form FDA 2301 may be obtained on the FDA website, by telephoning CVM's 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. Three-day alert reports must be submitted to the appropriate FDA District Office or local FDA resident post. Addresses for District Offices and resident posts may be obtained on the FDA website. Other reports not required to be submitted to FDA in electronic format 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.

(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 § 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, as amended at 81 FR 29141, May 11, 2016; 85 FR 45512, July 29, 2020]

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