0032 supporting statement final 5-14-2019

U.S. Food and Drug Administration

Reporting Associated with New Animal Drug Applications

and Veterinary Master Files

OMB Control No. 0910-0032

SUPPORTING STATEMENT

Terms of Clearance: None.

A. Justification

1. Circumstances Making the Collection of Information Necessary

Under section 512(b)(1) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360b(b)(1)), any person may file a new animal drug application (NADA) seeking our approval to legally market a new animal drug. Section 512(b)(1) sets forth the information required to be submitted in a NADA. Sections 514.1, 514.4, 514.6, 514.8, and 514.11 of our regulations (21 CFR 514.1, 514.4, 514.6, 514.8, and 514.11) further specify the information that the NADA must contain. The application must include safety and effectiveness data, proposed labeling, product manufacturing information, and where necessary, complete information on food safety (including microbial food safety) and any methods used to determine residues of drug in edible tissue from food producing animals. FDA Guidance #152 outlines a risk assessment approach for evaluating the microbial food safety of antimicrobial new animal drugs. We request that applicants utilize Form FDA 356V, as appropriate, to ensure efficient and accurate processing of information to support new animal drug approval.

Under section 512(b)(3) of the FD&C Act, any person intending to file a NADA or supplemental NADA or a request for an investigational exemption under section 512(j) of the FD&C Act is entitled to one or more conferences with us prior to making a submission. Section 514.5 of our regulations (21 CFR 514.5) describes the procedures for requesting, conducting, and documenting pre-submission conferences. We have found that these meetings have increased the efficiency of the drug development and drug review processes. We encourage sponsors to submit data for review at the most appropriate and productive times in the drug development process. Rather than submitting all data for review as part of a complete application, we have found that the submission of data supporting discrete technical sections during the investigational phase of the new animal drug is the most appropriate and productive. This “phased review” of data submissions has created efficiencies for both us and the animal pharmaceutical industry.

Additionally, we have found that various uses of veterinary master files have increased the efficiency of the drug development and drug review processes for both us and the animal pharmaceutical industry. A veterinary master file is a repository for submission to FDA’s Center for Veterinary Medicine of confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of one or more veterinary drugs. The benefits of veterinary master files include confidential exchange of information with FDA, a process for reporting information outside of a NADA or an investigational new animal drug (INAD) file, as well as an opportunity for increased communication with FDA during early stages of product development. Respondents may choose to use veterinary master files to provide and organize confidential detailed information to the Agency. A holder of a veterinary master file may also authorize other parties to reference information in the veterinary master file without disclosing information in the file to those parties. Veterinary master files can be used as repositories for information that can be referenced in multiple submissions to the Agency, thus minimizing paperwork burden. Veterinary master files are already used by the animal pharmaceutical industry in support of information being submitted for NADAs, abbreviated new animal drug applications (ANADAs), INAD files, and generic investigational new animal drug (JINAD) files. In previous information collection requests, we have included the time necessary to compile and submit such information to veterinary master files within the burden estimates provided for applications and amended applications (for NADAs and INAD files) and abbreviated applications and amended abbreviated applications (for ANADAs and JINAD files), respectively. We are now combining the time necessary to compile and submit such information to veterinary master files within the burden estimates provided in this collection of information.

We are also developing new approaches to permit more complex uses of veterinary master files to facilitate the development of animal drug products. We expect respondents will want to use veterinary master files to submit information to us for review and consultation during all phases of animal drug product development (including product development that precedes the establishment of an INAD file or the submission of a NADA). This information could include information about processes, facilities, or articles used in the manufacturing, processing, packaging, and storing of veterinary drugs and drug substances. Information submitted to FDA through a veterinary master file could also include drug characterization, methods, protocols, or other relevant information. In this request for OMB review, we seek approval of an increased use of veterinary master files by respondents to submit additional information to us for review and consultation during all phases of animal drug product development (including product development that precedes the establishment of an INAD file or the submission of a NADA). To account for an expected increase in reporting burden hours associated with the increased use of veterinary master files by respondents, we are separately estimating in table 1, row 10, the burden of the use of veterinary master files during all phases of product development (including product development that precedes the establishment of an INAD file or the submission of a NADA).

Finally, § 558.5(i) of our regulations (21 CFR 558.5(i)) describes the procedure for requesting a waiver of the labeling requirements of § 558.5(h) in the event that there is evidence to indicate that it is unlikely a new animal drug would be used in the manufacture of a liquid medicated feed.

We request extension of OMB approval of the information collection requirements in the following citations; in Form FDA 356V, New Animal Drug Application; and in Guidance #152. We also request OMB approval of the proposed increased use of veterinary master files to submit information to us.

21 CFR 514.1 and 514.6 - Reporting

This section specifies content and format of the New Animal Drug Application and amendment of a pending application.

21 CFR 514.1(b)(8) and 514.8(c)(1) and Guidance #152 – Reporting

This section specifies information for NADAs and supplements for antimicrobial animal drugs. Guidance #152 provides sponsors with a recommended approach to assessing antimicrobial concerns as part of the overall pre-approval safety evaluation.

21 CFR 514.4 – Reporting

This section specifies definition of substantial evidence of effectiveness. (No burden hours associated with this definition).

21 CFR 514.5(b), (d) and (f) – Reporting

This section specifies paperwork needed to request a presubmission conference, provide the advanced materials, and comment on the memorandum of conference.

21 CFR 514.8(b) – Reporting

This section specifies required information for supplements requesting approval of changes to manufacturing for an approved new animal drug.

21 CFR 514.8(c)(1) – Reporting

This section specifies the information that must be provided to FDA to support a supplemental application, which describes each change in each condition established in an approved application.

21 CFR 514.8(c)(2) and (c)(3) – Reporting

This section specifies paperwork an applicant submits to support supplemental applications seeking changes to approved labeling.

21 CFR 514.11 – Reporting

This section specifies requirements for freedom of information summaries of information and data for an NADA. FDA generally takes responsibility for preparing the FOI Summary.

21 CFR 558.5(i) – Reporting

This section specifies requirements for obtaining a waiver (filing a petition) from labeling requirements for certain drugs intended for use in animal feed or drinking water.

2. Purpose and Use of the Information Collection

The reporting associated with NADAs and related submissions is necessary to ensure that new animal drugs are in compliance with section 512(b)(1) of the FD&C Act. We use the information collected to review the data, labeling and manufacturing controls and procedures to evaluate the safety and effectiveness of the proposed new animal drug.

Description of Respondents: Respondents include persons developing, manufacturing, and/or researching new animal drugs, such as animal drug manufacturers (sponsors). Respondents include individuals and the private sector (for-profit businesses).

3. Use of Improved Information Technology and Burden Reduction

Submissions related to the new animal drug approval process contain summaries of data and narrative text. The animal health industry may use the free FDA eSubmitter software to prepare all submissions related to the new animal drug approval process. CVM’s eSubmitter program is an electronic, question-based tool for submitting information electronically through the FDA Electronic Submission Gateway (ESG) and CVM Electronic Submission System (ESS). CVM is moving to 100% electronic submission as required by the Animal Drug and Animal Generic Drug User Fee Amendments of 2018, signed into law on August 14, 2018. We estimate that 100% of the NADA submissions will be submitted electronically in the next three years.

4. Efforts to Identify Duplication and Use of Similar Information

The information provided in an application for approval of a new animal drug is unique to the particular product covered by the application. This information is not collected by any other Agency in the Government. The information collection required as a result of the statute does not duplicate any other information collection. There are no other regulations that require the submission of this same information. The information is generally not available from any recognized scientific sources, unless the information has been made public by the NADA applicant.

5. Impact on Small Businesses or Other Small Entities

This collection carries the same burden for small or large firms. The FD&C Act and our regulations require all respondents to submit the same information. There is no exemption from the requirements of the regulation for small businesses. We estimate that approximately 50% of the estimated 182 respondents reported in table 1, or approximately 91 firms, are small businesses. FDA aids small businesses in complying with its requirements through the Agency’s Regional Small Business Representatives and through the scientific and administrative staffs within the Agency. FDA also provides a Small Business Guide on the Agency’s website at http://www.fda.gov/oc/industry/.

6. Consequences of Collecting the Information Less Frequently

Data collection occurs occasionally. There are no specific regulatory time frames imposed on an applicant for the collection or recording of information. Original NADAs are submitted only once and therefore cannot be collected less frequently.

7. Special Circumstances Relating to the Guidelines of 5 CFR 1320.5

There are no special circumstances associated with this collection of information.

8. Comments in Response to the Federal Register Notice and Efforts to Consult Outside the Agency

In accordance with 5 CFR 1320.8(d), FDA published a 60-day notice for public comment in the Federal Register of February 15, 2019 (84 FR 4479). No comments were received.

9. Explanation of Any Payment or Gift to Respondents

We do not provide any payments or gifts to respondents.

10. Assurance of Confidentiality Provided to Respondents

This information collection request (ICR) is collecting personally identifiable information (PII). PII is collected in the context of the individuals’ professional capacity. The PII submitted for FDA Form 356V (Application for Approval of a New Animal Drug or submission to support new animal drug approval) is name, address, telephone number, fax number, and email address. This ICR involves the submission to FDA of applications for approval to legally market a new animal drug. The FD&C Act and FDA’s regulations specify the information that must be submitted to FDA by persons developing, manufacturing, and/or researching new animal drugs.

FDA further determined that although PII is collected the collection is not subject to the Privacy Act of 1974 and the particular notice and other requirements of the Act do not apply. Specifically, FDA does not use name or any other personal identifier to routinely retrieve records from the information collected. FDA also minimized the PII to be collected to protect the privacy of the individuals.

In preparing this Supporting Statement, FDA staff consulted with the FDA Privacy Office to ensure appropriate handling of information collected.

We expect that an application for approval of a new animal drug will contain trade secret and commercial confidential information. As a result, all files are maintained in a secured area. Confidentiality of the information submitted under these reporting requirements is protected under 21 CFR 514.11. Only information that is releasable under the agency’s regulations in 21 CFR part 20 would be released to the public. This information is also safeguarded by section 301(j) of the FD&C Act and would be protected from disclosure under the Freedom of Information Act (FOIA) under sections 552(a) and (b) (5 U.S.C. 552(a) and (b)).

11. Justification for Sensitive Questions

This information collection does not involve questions that are of a personally sensitive nature.

12. Estimates of Annualized Burden Hours and Costs

12a. Annualized Hour Burden Estimate

We estimate the burden of this collection of information as follows:

Table 1.--Estimated Annual Reporting Burden
21 CFR Section; Activity	No. of Respondents	No. of Responses per Respondent	Total Annual Responses	Average Burden per Response	Total Hours
514.1 and 514.6; applications and amended applications	182	0.05	9	212	1,908
514.1(b)(8) and 514.8(c)(1)1; evidence to establish safety and effectiveness	182	0.10	18	90	1,620
514.5(b), (d), (f); requesting presubmission conferences	182	0.49	89	50	4,450
514.8(b); manufacturing changes to an approved application	182	1.40	255	35	8,925
514.8(c)(1); labeling and other changes to an approved application	182	0.05	9	71	639
514.8(c)(2) and (3); labeling and other changes to an approved application	182	0.43	78	20	1,560
514.11; submission of data, studies, and other information	182	0.09	16	1	16
558.5(i); requirements for liquid medicated feed	182	0.01	2	5	10
Form FDA 356V	182	2.92	531	5	2,655
Use of veterinary master files during all phases of product development (including product development that precedes the establishment of an INAD file or the submission of a NADA)	15	1	15	20	300
Total			1,022		22,083

¹NADAs and supplements regarding antimicrobial animal drugs that use a recommended approach to assessing antimicrobial concerns as part of the overall preapproval safety evaluation.

We base our estimate of the number of respondents on the number of sponsors subject to animal drug user fees. We base our estimates of the average burden per response and total annual responses on our experience with NADAs and related submissions. Based on a review of the information collection since our last request for OMB approval, we have made no adjustments to our previous estimates. However, as discussed, we have separately estimated the burden of the “Use of veterinary master files during all phases of product development (including product development that precedes the establishment of an INAD file or the submission of an NADA)” in table 1, row 10. We base our estimate of the total annual responses for the use of veterinary master files on such uses initiated during calendar year 2018. We base our estimate of the hours per response upon our experience with the respondents’ use of veterinary master files. We estimate that the time it takes to compile information and submit it to a veterinary master file will vary from 1 to 50 hours, depending on the complexity of the information; therefore, we are estimating on average the burden per response to be 20 hours. Accordingly, we report an additional 300 burden hours and 15 total annual responses in row 10.

12b. Annualized Cost Burden Estimate

We estimate that the average hourly wage for respondents is equivalent to a GS-11-7 level in the locality pay area of Washington-Baltimore in 2019, approximately $40.01/hour. Increasing this wage by 30% to account for overhead costs ($12.00), FDA estimates the average hourly cost to respondents to be $52.01/hour. The overall estimated cost incurred by the respondents is $1,148,537 (22,083 burden hours x $52.01/hr = $1,148,536.80).

13. Estimates of Other Total Annual Cost Burden to Respondents and Recordkeepers

There are no capital, start-up, operating, or maintenance costs associated with this collection.

14. Annualized Cost to the Federal Government

We estimate the annualized cost to the Federal government for the review and evaluation of submissions to be $10,315,360. These figures are only an analysis of pioneer animal drug review work (NADAs) and do not include review hours and FTEs for generic animal drug review work (ANADA). We estimate that we expend approximately 176,000 person hours annually in review, support and supervisory support of the review of submissions. We estimate the average hourly wage for personnel to review and evaluate a submission to be at the GS-13-8 level in the locality pay area of Washington-Baltimore in 2019, approximately $58.61/hour. The estimated annualized cost to the Federal government is $10,315,360 (176,000 hours x $58.61/hr = $10,315,360).

15. Explanation for Program Changes or Adjustments

Based on a review of the information collection since our last request for OMB approval, we have made the following adjustments:

In previous submissions of this ICR we included the time necessary to compile and submit information to veterinary master files within the burden estimates provided for applications and amended applications (for NADAs and INAD files). In this request for OMB extension of approval, we anticipate respondents’ need for increased use of veterinary master files and therefore seek approval for such increase. We have separately estimated the burden of the “Use of veterinary master files during all phases of product development (including product development that precedes the establishment of an INAD file or the submission of an NADA)” in table 1, row 10. 

We report an additional 300 burden hours and 15 total annual responses in row 10, representing such increased use of veterinary master files.  In addition, we are also correcting several rounding errors that were made in our last request for OMB approval. Thus, our estimated burden for the information collection reflects a net overall increase of 124 hours and a corresponding increase of 14 responses.

16. Plans for Tabulation and Publication and Project Time Schedule

We have no plans to tabulate and publish information from this information collection.

17. Reasons Display of OMB Expiration Date is Inappropriate

FDA will display the OMB expiration date as required by 5 CFR 1320.5.

18. Exceptions to Certification for Paperwork Reduction Act Submissions

There are no exceptions to the certification.

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