[Congressional Record Volume 164, Number 129 (Tuesday, July 31, 2018)]
[Senate]
[Pages S5508-S5511]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




                ANIMAL DRUG USER FEE AMENDMENTS OF 2018

  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record the commitment letter

[[Page S5509]]

for the Animal Drug User Fee Agreements of 2018.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

                Animal Drug User Fee Amendments of 2018


 ADUFA Reauthorization Performance Goals and Procedures--FYs 2019 thru 
                                  2023

       The goals and procedures of the FDA Center for Veterinary 
     Medicine (CVM) as agreed to under the ``Animal Drug User Fee 
     Amendments of 2018'' are summarized as follows:


                             I. Definitions

       1. For the application/submission goals below, the term 
     ``review and act on'' is understood to mean the issuance of a 
     complete action letter after the complete review of an animal 
     drug application, supplemental animal drug application, or 
     investigational animal drug submission which either (1) 
     approves an animal drug application or supplemental 
     application or notifies a sponsor that an investigational 
     animal drug submission is complete or (2) sets forth in 
     detail the specific deficiencies in such animal drug 
     application, supplemental animal drug application, or 
     investigational animal drug submission and, where 
     appropriate, the actions necessary to place such an 
     application, supplemental application, or submission in 
     condition for approval. Within 30 days 17 of submission, FDA 
     shall refuse to file an animal drug application, supplemental 
     animal drug application, or their reactivation, which is 
     determined to be insufficient on its face or otherwise of 
     unacceptable quality for review upon initial inspection as 
     per 21 CFR 514.110. Thus, the Agency will refuse to file an 
     application containing numbers or types of errors, or flaws 
     in the development plan, sufficient to cause the quality of 
     the entire submission to be questioned to the extent that it 
     cannot reasonably be reviewed. Within 60 days of submission, 
     FDA will refuse to review an investigational animal drug 
     submission which is determined to be insufficient on its face 
     or otherwise of unacceptable quality upon initial inspection 
     using criteria and procedures similar to those found in 21 
     CFR 514.110. A decision to refuse to file an application or 
     to refuse to review a submission as described above will 
     result in the application or submission not being entered 
     into the cohort upon which the relevant user fee goal is 
     based. The Agency will keep a record of the numbers and types 
     of such refusals and include them in its annual performance 
     report.
       2. A minor amendment is understood to mean information 
     requested by FDA during the review of the application or 
     investigational submission. FDA may request minor amendments 
     to animal drug applications, supplemental animal drug 
     applications, and investigational animal drug submissions 
     during its review of the application or submission. At its 
     discretion, the Agency may extend an internal due date (but 
     not a user fee goal) to allow for the complete review of an 
     application or submission for which a minor amendment is 
     requested. If a pending application is amended with 
     significant changes, the amended application may be 
     considered resubmitted, thereby effectively resetting the 
     clock to the date FDA received the amendment. The same policy 
     applies for investigational animal drug submissions.
       3. The term ``submission date'' means the date the FDA 
     Center for Veterinary Medicine (CVM) Electronic Submission 
     System (ESS) receives an application or submission. Upon 
     receipt of an application or submission, the CVM ESS creates 
     an electronic receipt that contains the date of receipt and 
     is sent to the submitter.
       4. The term ``labeling supplement'' is understood to mean 
     certain applications as described in 21 CFR 514.8(c)(2)(i)(A) 
     and (D) that require approval of a supplemental application 
     prior to distribution of the drug made using the change.
       5. The term ``presubmission conference'' (PSC) is 
     understood to mean one or more conferences between a 
     potential applicant and FDA as described in 21 CFR 514.5 to 
     reach a binding agreement establishing a submission or 
     investigational requirement.
       6. The term ``dosage characterization'' is understood to 
     mean a justification of the dosage (dose or dose range, 
     dosing frequency, and the dosing duration) and a 
     characterization of the critical aspects of the dose response 
     relationship related to each intended use and associated 
     conditions of use.


                    II. Application/Submission Goals

       Beginning October 1, 2018, all applications and submissions 
     under the Federal Food, Drug, and Cosmetic Act (FD&C Act) 
     section 512(b) and 571 must be created using the eSubmitter 
     tool and submitted to the Agency through CVM's ESS.
     1. Original New Animal Drug Applications (NADAs)
       Review and act on 90 percent of original NADAs within 180 
     days after the submission date.
       An application is incomplete if it would require additional 
     data or information to enable the Agency to complete a 
     comprehensive review of the application and reach a decision 
     on the issue(s) presented in the application.
       The Agency will review and act on 90 percent of reactivated 
     applications:
       i Within 180 days after the reactivated NADA submission 
     date if the Agency determines and notifies the sponsor that 
     the deficiencies are substantial;
       ii Within 135 days after the reactivated NADA submission 
     date if the Agency determines and notifies the sponsor that 
     the deficiencies are not substantial; and the NADA 
     reactivation must be submitted no more than 120 days after 
     the Agency's dated incomplete letter to qualify for the 
     shorter review time; and
       iii Within 180 days alter the reactivated NADA submission 
     date if the NADA reactivation is submitted after 120 days of 
     the Agency's dated incomplete letter or new substantial 
     information is provided in the reactivated application.
       The Agency will generally favor using the shorter 
     reactivation timeframe of 135 days, where possible. The 
     Agency will state in the incomplete letter the appropriate 
     timeframe for review of the reactivation. Sponsors wishing to 
     discuss the selected timeframe should contact the Agency 
     prior to reactivation of the application. The shorter review 
     time of 135 days for reactivated NADAs for which the 
     deficiencies are determined not to be substantial is not 
     intended to prevent the use of minor amendments during Agency 
     review of an application.
     2. Administrative NADAs
       Review and act on 90 percent of administrative NADAs (NADAs 
     filed after all scientific decisions already have been made 
     as part of the investigational new animal drug process) 
     within 60 days after the filing date.
     3. Non-manufacturing Supplemental Animal Drug Applications
       Review and act on 90 percent of non-manufacturing 
     supplemental animal drug applications (i.e. supplemental 
     animal drug applications for which safety or effectiveness 
     data are required) within 180 days after the submission date.
       A supplemental application is incomplete if it would 
     require additional data or information to enable the Agency 
     to complete a comprehensive review of the supplement and 
     reach a decision on the issue (s) presented in the 
     supplement.
       The Agency will review and act on 90 percent of reactivated 
     supplements:
       i Within 180 days after the reactivated supplemental NADA 
     submission date if the Agency determines and notifies the 
     sponsor that the deficiencies are substantial;
       ii Within 135 days after the reactivated supplemental NADA 
     submission date if the Agency determines and notifies the 
     sponsor that the deficiencies are not substantial; and the 
     reactivation to the supplemental application must be 
     submitted no more than 120 days after the Agency's dated 
     incomplete letter to qualify for the shorter review time; and
       iii Within 180 days after the reactivated supplemental NADA 
     submission date if the reactivation to the supplemental 
     application is submitted after 120 days of the Agency's dated 
     incomplete letter or new substantial information is provided 
     in the reactivated supplement.
       The Agency will generally favor using the shorter 
     reactivation timeframe of 135 days, where possible. The 
     Agency will state in the incomplete letter the appropriate 
     timeframe for review of the reactivation. Sponsors wishing to 
     discuss the selected timeframe should contact the Agency 
     prior to the reactivation of the supplement. The shorter 
     review time of 135 days for reactivated supplements for which 
     the deficiencies are determined not to be substantial is not 
     intended to prevent the use of minor amendments during Agency 
     review of a supplemental application.
     4. Prior Approval Manufacturing Supplemental NADAs and 
         Reactivations
       Review and act on 90 percent of Prior Approval 
     manufacturing supplemental NADAs within 120 days after the 
     submission date. A Prior Approval manufacturing supplemental 
     NADA includes: one or more major manufacturing changes as 
     described in 21 CFR 514.8(b)(2)(ii) and in accordance with 
     Guidance for Industry 83 (Chemistry, Manufacturing, and 
     Controls Changes to an Approved NADA or ANADA); and, changes 
     submitted as ``Supplement-Changes Being Effected in 30 Days'' 
     that require prior approval according to 21 CFR 
     514.8(b)(3)(v)(A). If a Prior Approval supplement does not 
     clearly identify any major manufacturing changes, the Prior 
     Approval supplement will be designated by the Agency as a 
     ``Supplement-Changes Being Effected'' with a 180 days review 
     goal (see ``Supplement-Changes Being Effected Manufacturing 
     Supplemental NADAs and Reactivations'' below).
       A submission is incomplete if it requires additional data 
     or information to enable the Agency to complete a 
     comprehensive review of the submission and reach a decision 
     on the issue(s) presented in the submission. If the Agency 
     determines that the deficiencies are not substantial for 
     manufacturing supplements requiring prior approval, the 
     Agency will allow the manufacturing supplements to be 
     resubmitted as ``Supplement Changes Being Effected in 30 
     Days'' as described in 21 CFR 514.8(b)(3) and the drug made 
     with the change can be distributed 30 days after the 
     resubmission according to 21 CFR 514.8(b)(3)(iv). The Agency 
     will review and act on 90 percent of these reactivated 
     manufacturing supplements within 180 days after the 
     resubmission date of a complete submission. If the Agency 
     determines that the deficiencies remain substantial or new 
     substantial information is provided, prior-approval is 
     required according to 21 CFR 514.8(b)(3)(v)(A). The Agency 
     will review and act on 90 percent of these reactivated 
     manufacturing supplements within 120 days after the 
     resubmission date of a complete submission.

[[Page S5510]]

  

     5. Supplements--Changes Being Effected Manufacturing 
         Supplemental NADAs and Reactivations
       Review and act on 90 percent of ``Supplement--Changes Being 
     Effected'' manufacturing supplemental NADAs and reactivations 
     submitted according to 21 CFR 514.8(b)(3)(vi) and in 
     accordance with Guidance for Industry 83 (Chemistry, 
     Manufacturing, and Controls Changes to an Approved NADA or 
     ANADA), including manufacturing changes not requiring prior 
     approval according to 21 CFR 514.8(b)(3) within 180 days 
     after the submission date.
     6. Investigational New Animal Drug (INAD) Study Submissions
       Review and act on 90 percent of INAD study submissions 
     within 180 days after the submission date.
       An INAD study submission is incomplete if it would require 
     additional data or information to enable the Agency to 
     complete a comprehensive review of the submission and reach a 
     decision on the issue(s) presented in the submission.
       The Agency will review and act on 90 percent of 
     resubmissions:
       i Within 180 days after the resubmitted INAD study 
     submission date if the Agency determines and notifies the 
     sponsor that the deficiencies are substantial;
       ii Within 60 days after the resubmitted INAD study 
     submission date if the Agency determines and notifies the 
     sponsor that the deficiencies are not substantial; and the 
     resubmission must be submitted no more than 120 days after 
     the Agency's dated incomplete letter to qualify for the 
     shorter review time; and
       iii Within 180 days after the resubmitted INAD study 
     submission date if the resubmission is submitted after 120 
     days of the Agency's dated incomplete letter or new 
     substantial information is provided in the resubmission.
       The Agency will generally favor using the shorter 
     resubmission timeframe of 60 days, where possible. The Agency 
     will state in the incomplete letter the appropriate timeframe 
     for review of the resubmission. Sponsors wishing to discuss 
     the selected timeframe should contact the Agency prior to 
     resubmitting the application. The shorter review time of 60 
     days for resubmissions for which the deficiencies are 
     determined not to be substantial is not intended to prevent 
     the use of minor amendments during Agency review of a 
     submission.
       Review and act on 90 percent of microbial food safety 
     hazard characterization submissions within 100 days after the 
     submission date.
     7. INAD Protocols without Data Submissions
       Review and act on 90 percent of INAD submissions consisting 
     of protocols without data, that the Agency and the sponsor 
     consider to be an essential part of the basis for making the 
     decision to approve or not approve an NADA or supplemental 
     NADA, within 50 days after the submission date.
       An INAD protocol without data submission is incomplete if 
     it would require additional information to enable the Agency 
     to complete a comprehensive review of the protocol and reach 
     a decision on the issue(s) presented in the protocol.
       The Agency will review and act on 90 percent of resubmitted 
     INAD protocol without data submissions:
       i Within 50 days after the resubmission date if the Agency 
     determines and notifies the sponsor that the deficiencies are 
     substantial;
       ii Within 20 days after the resubmitted INAD protocol 
     without data submission if the Agency determines and notifies 
     the sponsor that the deficiencies are not substantial; and 
     the resubmission must be submitted no more than 120 days 
     after the Agency's dated nonconcurrence letter to qualify for 
     the shorter review time; and
       iii Within 50 days after the resubmission date if the 
     resubmission is submitted after 120 days of the Agency's 
     dated non-concurrence letter or new substantial information 
     is provided in the resubmission.
       The Agency will generally favor using the shorter 
     resubmission timeframe of 20 days, where possible. The Agency 
     will state in the non-concurrence letter the appropriate 
     timeframe for review of the resubmission. Sponsors wishing to 
     discuss the selected timeframe should contact the Agency 
     prior to resubmission of the protocol without data. The 
     shorter review time of 20 days for resubmitted INAD protocol 
     without data submissions for which the deficiencies are 
     determined not to be substantial is not intended to prevent 
     the use of minor amendments during Agency review of a 
     submission.
       Sponsors are not required to submit study protocols for 
     review. However, for each protocol voluntarily submitted 
     prior to the commencement of the study that the Agency and 
     the sponsor consider to be an essential part of the basis for 
     making the decision to approve or not approve an animal drug 
     application or supplemental animal drug application, the 
     Agency will issue a complete action letter providing comments 
     resulting from a complete review of the protocol. The 
     complete action letter will be as detailed as possible 
     considering the quality and level of detail of the protocol 
     submission; will include a succinct assessment of the 
     protocol; and will state whether the Agency agrees, 
     disagrees, or lacks sufficient information to reach a 
     decision that the protocol design, execution plans, and data 
     analyses are adequate to achieve the objectives of the study.
       If the Agency determines that a protocol is acceptable, 
     this represents an agreement that the data generated by the 
     protocol can be used to support a safety or effectiveness 
     decision regarding the subject animal drug. The fundamental 
     agreement is that having agreed to the design, execution, 
     or analyses proposed in protocols reviewed under this 
     process, the Agency will not later alter its perspectives 
     on the issues of design, execution, or analyses unless the 
     Agency by written order determines that a substantiated 
     scientific requirement essential to the assessment of the 
     study appeared after the Agency's protocol assessment, or 
     public or animal health concerns unrecognized at the time 
     of protocol assessment under this process are evident.
       The Agency will permit comparability protocols as described 
     in 21 CFR 514.8(b)(2)(v) to be submitted as protocols without 
     substantial data in an INAD file. The Agency will review and 
     act on 90 percent of INAD submissions consisting of protocols 
     without substantial data within 50 days after the submission 
     date of the protocol. For potentially more complex 
     comparability protocols, for example sterile process 
     validation protocols, the sponsor should discuss and have 
     Agency concurrence regarding the appropriate filing strategy.
     8. Labeling Supplements
       Review and act on 90 percent of qualifying labeling 
     supplements as described in 21 CFR 514.8(c)(2)(i)(A) and (D) 
     within 60 days after the submission date. Qualifying labeling 
     supplements are defined as those for which the sponsor 
     provides and certifies a complete list of label changes made 
     in the application and that CVM can determine upon initial 
     review do not decrease the safety of drug use.
       The Agency will review and act on 90 percent of non-
     qualifying labeling supplements within 180 days after the 
     submission date.
       Additional Performance Goals
     Work Queue Review Procedures
       The Agency will review all submissions in accordance with 
     procedures for working within a queue. An application/
     submission that is not reviewed within the applicable 
     Application/Submission Goal time frame (noted above) will be 
     reviewed with the highest possible priority among those 
     pending.


                 iii. pre-approval foreign inspections

       The Agency and regulated industry are committed to 
     improving the review and business processes that will 
     facilitate the timely scheduling and conducting of pre-
     approval inspections (PAIs). To improve the timeliness and 
     predictability of foreign PAIs, sponsors may voluntarily 
     submit 1) at the beginning of the calendar year, a list of 
     foreign manufacturing facilities that are specified in an 
     animal drug application, supplemental animal drug 
     application, or investigational animal drug submission and 
     may be subject to foreign PAIs for the following fiscal year; 
     and 2) a notification 30 days prior to submitting an NADA, a 
     supplemental NADA, or INAD submission that informs the Agency 
     that the application/submission includes a foreign 
     manufacturing facility. Should any changes to the annual list 
     occur after its submission to the Agency, the sponsor may 
     provide the updated information to the Agency.
       The Agency will keep a record of the number of foreign PAIs 
     conducted for new animal drug applications, along with the 
     average time for completing the PAIs, and include this 
     information in its annual performance report. The time for 
     completing the PAI is understood to mean the time from the 
     inspection scheduling request through notification to the 
     Center of inspectional findings.


                      iv. foreign gmp inspections

       The Agency commits to working to implement the US-EU GMP 
     Inspection Mutual Recognition Agreement starting in FY 2019 
     for establishments manufacturing animal/veterinary drugs. The 
     Agency will provide annual progress updates to the industry.
     1. Supporting Information for Presubmission Conferences and 
         INAD Protocols without Data Submissions
       The Agency and the regulated industry agree that data and/
     or information which uniquely describes the general 
     attributes of the new animal drug (e.g. the known 
     characteristics of the drug that can impact safety, 
     effectiveness and/or quality) needs to be submitted early in 
     the new animal drug development process in order to enable 
     the parties to reach agreement at a presubmission conference 
     or to begin review of a protocol. The intent of this 
     provision is to avoid the submission of data or information 
     between the presubmission conference and the submission of a 
     protocol. Eligibility both for short justifications in 
     protocols and for concurrent supporting data and protocol 
     review described below is predicated on the sponsor 
     submitting information early in the new animal drug 
     development process.
       The Agency will allow for the inclusion of this data and/or 
     information in presubmission conferences; however it would 
     not preclude holding a presubmission conference without such 
     data.
       The Agency will allow short justifications within INAD 
     protocols without data submissions that are limited in scope 
     (e.g., no more than ten pages or no more than two (peer-
     reviewed) journal articles).
       The Agency will allow for the concurrent submission of 
     supporting data (INAD H submissions) and protocols (INAD E 
     submissions) provided that the protocol is not submitted 
     until the supporting data has been in the Agency's queue for 
     at least 50 days.

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     2. Dosage Characterization
       The Agency and the regulated industry agree that dosage 
     characterization is part of the effectiveness technical 
     section of an investigational new animal drug file. In 
     instances where data and/or information about the dosage is 
     integral to the review of a protocol, the Agency and the 
     regulated industry agree that this data and/or information 
     should be submitted as supporting data (INAD H submission) 
     well in advance of the protocol submission. Such information 
     may be needed to ensure selection of optimal study time 
     points and would be particularly important for novel drugs 
     and drugs with modified-release characteristics.
     3. Animal Drug Availability Act (ADAA) Combination Medicated 
         Feeds Applications
       Review and act on 90 percent of qualifying ADAA Combination 
     Medicated Feeds Applications within 60 days after the 
     submission date. An ADAA combination application will qualify 
     for the 60 day review timeframe only if the following 
     criteria are met:
       i. The regulatory requirements for an ADAA combination 
     application have been met as outlined in 21 CFR 
     514.4(c)(2)(ii)
       ii. A presubmission conference has been conducted and 
     either
       a. No data are needed (i.e., no tissue residue non-
     interference study is required) and this is documented in the 
     memorandum of conference for the presubmission conference; or
       b. A justification for not conducting a tissue residue 
     noninterference study has been submitted, reviewed and found 
     acceptable under an INAD, prior to the submission of the ADAA 
     combination application; or
       c. A tissue residue non-interference study has been 
     submitted, reviewed and found acceptable under an INAD, prior 
     to the submission of the ADAA combination application.
       iii. No effectiveness or target animal safety data are 
     required.
       iv. No manufacturing data requirements- sponsor can address 
     in meeting assay non-interference, but data submission is not 
     required.
       v. All other information is referenced to previous drug 
     experience reports.
       vi. Sponsor makes submission and it includes: Bluebird 
     labeling, Veterinary Feed Directive (if applicable).
       vii. Includes a request for categorical exclusion from the 
     need to prepare an environmental assessment (EA); i.e., no EA 
     required.
       viii. Reference to presubmission conference.
       ix. Right of reference (if applicable) to NADA(s) not owned 
     by the filing sponsor of the ADAA combination application has 
     been received by the Agency.
       Review and act on 90 percent of ADAA combination 
     applications within 100 days for those applications initially 
     accepted for the 60-day timeframe but subsequently determined 
     to need minor amendments.
       If any of the above conditions cannot be met, the ADAA 
     combination application will be given a 180-day review 
     timeframe and placed in the original NADA application cohort.
     4. Categorical Exclusions
       Review and act on 90 percent of resubmissions of a 
     previously completed Environmental Impact technical section 
     within 60 days after the resubmission date where:
       i. A Categorical Exclusion was issued; and
       ii. All other technical sections have been submitted; and
       iii. Information contained in the other technical sections 
     reveals a change in the conditions of use of the drug that 
     may affect the previous determination of categorical 
     exclusion.
     5. Presubmission Conferences
       Conduct 90% of qualifying presubmission conferences within 
     a 60-day timeframe when all of the following conditions are 
     met:
       i. All background materials, including presentations, have 
     been submitted, and
       ii. A complete agenda has been agreed upon by the Agency 
     and the sponsor
       A sponsor and the Agency can mutually agree to exclude a 
     particular presubmission conference from this performance 
     goal. If a sponsor accepts a date beyond the 60-day timeframe 
     for their scheduling purposes or is unable to meet with the 
     Agency on Agency available dates, the submission will be 
     excluded from the presubmission conference cohort.
     6. Tissue Residue Method
       Commence 90% of tissue residue method demonstrations within 
     120 days of completion of the ``3-hour meeting'' process or 
     equivalent process milestone where there is a single 
     laboratory validation tissue residue method demonstration.


                         V. Workload Adjustment

       The workload adjustment will continue to be calculated per 
     CVM Program Policy and Procedures Manual 1243.3022, except 
     that, for purposes of calculating the workload adjustment, it 
     has been agreed to reset the base years to FY 2014-FY 2018. 
     There will be no workload adjustment for FY 2019. Workload 
     adjustments are one-time adjustments, and are calculated 
     annually.

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