[Congressional Record Volume 164, Number 130 (Wednesday, August 1, 2018)]
[Senate]
[Pages S5576-S5577]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




            ANIMAL GENERIC DRUG USER FEE AMENDMENTS OF 2018

  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record the commitment letter for the Animal Generic Drug User 
Fee Agreements of 2018.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

            Animal Generic Drug User Fee Amendments of 2018


 agdufa reauthorization performance goals and procedures for fy's 2019 
                               thru 2023

       The goals and procedures of the Food and Drug 
     Administration (FDA or the Agency) as agreed to under the 
     ``Animal Generic Drug User Fee Amendments of 2018'' are 
     summarized as follows:


                      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) must be created using the eSubmitter tool and 
     submitted to the Agency through the FDA Center for Veterinary 
     Medicine (CVM) Electronic Submission System (ESS).
     1. Original Abbreviated New Animal Drug Applications (ANADAs) 
         and Reactivations
       Review and act on 90 percent of original ANADAs within 240 
     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. If the Agency determines that the 
     deficiencies are not substantial, the Agency will review and 
     act on 90 percent of reactivated applications within 120 days 
     after the reactivated ANADA submission date. This shorter 
     review time for reactivated ANADAs 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. If the Agency determines that the 
     deficiencies are substantial or new substantial information 
     is provided, the Agency will review and act on 90 percent of 
     reactivated applications within 240 days after the 
     reactivated ANADA submission date.
     2. Administrative ANADAs
       Review and act on 90 percent of administrative ANADAs 
     (ANADAs submitted after all scientific decisions have been 
     made in the generic investigational new animal drug (JINAD) 
     process, i.e., prior to the submission of the ANADA) within 
     60 days after the submission date. Paragraph IV certification 
     applications (FD&C Act section 512(n)(1)(H)(iv)) submitted as 
     administrative ANADAs will be excluded from the 
     administrative ANADA cohort.
     3. Prior Approval Manufacturing Supplemental ANADAs and 
         Reactivations
       Review and act on 90 percent of Prior Approval 
     manufacturing supplemental ANADAs within 180 days after the 
     submission date. A Prior Approval manufacturing supplemental 
     ANADA includes: one or more major manufacturing changes 
     according to 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 270 days review 
     goal (see ``Supplement-Changes Being Effected Manufacturing 
     Supplemental ANADAs 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 21CFR 514.8(b)(3)(iv). The Agency 
     will review and act on 90 percent of these reactivated 
     manufacturing supplements within 270 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 180 days after the re-
     submission date of a complete submission.
     4. Supplement--Changes Being Effected Manufacturing 
         Supplemental ANADAs and Reactivations
       Review and act on 90 percent of ``Supplement--Changes Being 
     Effected'' manufacturing supplemental ANADAs 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)(iv), within 270 days 
     after the submission date.
     5. Generic Investigational New Animal Drug (JINAD) Study 
         Submissions
       Review and act on 90 percent of JINAD study submissions 
     within 180 days after the submission date. A submission is 
     incomplete if it would require additional data or information 
     to enable the Agency to complete a comprehensive review of 
     the study submission and reach a decision on the issue(s) 
     presented in the submission. If the Agency determines that 
     the deficiencies are not substantial, the Agency will review 
     and act on 90 percent of resubmitted JINAD study submissions 
     within 60 days after the receipt date of a complete study 
     submission. This shorter review time for resubmitted JINAD 
     study submissions is not intended to prevent the use of minor 
     amendments during Agency review of a study submission. If the 
     Agency determines that the deficiencies are substantial or 
     new substantial information is provided, the Agency will 
     review and act on 90 percent of resubmitted JINAD study 
     submissions within 180 days after the receipt date of a 
     complete study submission.
     6. JINAD Protocols
       Review and act on 90 percent of JINAD submissions 
     consisting of protocols without substantial 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 ANADA or supplemental ANADA, within 75 days after the 
     submission date. Allow comparability protocols as described 
     in 21 CFR 514.8(b)(2)(v) to be submitted as protocols without 
     substantial data in a JINAD file. The Agency will review and 
     act on 90 percent of JINAD submissions consisting of 
     protocols without substantial data within 75 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.
       For the application/submission goals above, the term 
     ``review and act on'' means the issuance of either: (1) a 
     complete action letter that approves an original or 
     supplemental ANADA or notifies a sponsor that a JINAD 
     submission is complete; or (2) an ``incomplete letter'' that 
     sets forth in detail the specific deficiencies in an original 
     or supplemental ANADA or JINAD submission and, where 
     appropriate, the actions necessary to place such an original 
     or supplemental ANADA or JINAD submission in condition for 
     approval. Within 30 days of receipt of the application, FDA 
     shall refuse to file an original or supplemental ANADA, or 
     their reactivation, that 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 receipt of the submission, FDA 
     will refuse to review a JINAD submission that 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.
       FDA may request minor amendments to original or 
     supplemental ANADAs and JINAD 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 JINAD submissions.
       Sponsors are not required to submit study protocols for 
     review. However, for each voluntarily submitted protocol for 
     a 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 original

[[Page S5577]]

     or supplemental ANADA, 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 new animal drug. 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 design, execution, or analyses unless 
     the Agency issues a written order that a substantiated 
     scientific requirement essential to the assessment of the 
     study appeared after the Agency's protocol assessment, or 
     public (human or animal) health concerns unrecognized at the 
     time of protocol assessment under this process are evident.
       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.


                      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 will be reviewed with 
     the highest possible priority among those pending.


             amending similar applications and submissions

       The Agency and regulated industry agree that applications 
     and submissions to the Agency will be complete and of 
     sufficient quality to allow the Agency's complete and timely 
     review. The Agency will refuse to file poor quality and 
     incomplete applications and submissions rather than allowing 
     them to serve as ``placeholders'' in the review queue that 
     are subsequently amended to add the missing or inadequate 
     portions.
       The Agency recognizes that there are circumstances in which 
     a controlled amendment process can make the review of 
     similar, pending submissions more efficient without 
     compromising the sponsor's responsibility for high quality 
     submissions. Thus, if the Agency requests an amendment to a 
     non-administrative original ANADA, manufacturing supplemental 
     ANADA, JINAD study submission, or a JINAD protocol submission 
     (a ``CVM-initiated amendment''), or issues an incomplete 
     letter for such an application or submission, a sponsor may 
     request to amend other, similar applications or submissions 
     it has pending with the Agency (``sponsor-initiated 
     amendment(s)'') in accordance with the following criteria:
       1. The amended information for these similar applications 
     or submissions must be the same as in the CVM-initiated 
     amendment or incomplete letter; and
       2. The amended information must not significantly change 
     the similar applications or submissions; and
       3. The amended information for these similar applications 
     or submissions must be submitted no later than:
       a. 120 days after the submission date for the similar 
     original ANADA, manufacturing supplemental ANADA; or
       b. 100 days after the submission date for the similar JINAD 
     study submissions; or
       c. 40 days after the submission date for the similar JINAD 
     protocol submissions.
       If the Agency determines that the above criteria have been 
     met, it will not change the user fee goal for the similar 
     application or submission that has been amended by a sponsor-
     initiated amendment. If the above criteria have not been met, 
     the Agency may consider the similar application or submission 
     resubmitted on the date of the sponsor-initiated amendment, 
     thereby resetting the clock to the date FDA received the 
     amendment.


multiple data submissions to the chemistry, manufacturing, and controls 
                           technical section

       The Agency will continue to allow two-phased Chemistry, 
     Manufacturing, and Controls technical section submissions 
     under the JINAD process. Timely Foreign Pre-Approval 
     Inspections
       1. 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 
     abbreviated application, supplemental abbreviated 
     application, or generic investigational file and may be 
     subject to foreign PAIs for the following fiscal year; and 2) 
     a notification 30 days prior to submitting an abbreviated 
     application, a supplemental abbreviated application, or 
     generic investigational file that informs the Agency that the 
     application 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.
       2. The Agency will keep a record of the number of foreign 
     PAIs conducted for abbreviated 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.


                     timely meetings with industry

       The Agency and the regulated industry agree that the use of 
     both formal meetings (e.g., presubmission conferences, 
     workshops) and informal communication by both parties is 
     critical to ensure high submission quality such that the 
     above performance goals can be achieved.


                          workload adjustment

       The workload adjustment will continue to be calculated per 
     CVM Program Policy and Procedures Manual 1243.3022, page 35, 
     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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