[Congressional Record Volume 169, Number 170 (Tuesday, October 17, 2023)]
[Senate]
[Pages S5038-S5044]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]
ANIMAL DRUG AND GENERIC DRUG USER FEE AMENDMENTS OF 2023
Mr. SANDERS. Mr. President, I ask unanimous consent to have printed
in the Record at the appropriate place the commitment letters for the
Animal Drug User Fee Amendments of 2023 and the Animal Generic Drug
User Fee Amendments of 2023.
There being no objection, the material was ordered to be printed in
the Record, as follows:
Animal Drug User Fee Act Reauthorization Performance Goals and
Procedures Fiscal Years 2024 Through 2028
The goals and procedures of the Food and Drug
Administration (FDA or the Agency) as agreed to under the
``Animal Drug User Fee Amendments of 2023'' 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 new animal drug (INAD) submission which
either (1) approves or conditionally approves an animal drug
application or approves a supplemental application or
notifies a sponsor that an INAD submission is complete or (2)
sets forth in detail the specific deficiencies in such animal
drug application, supplemental animal drug application, or
INAD submission and, where appropriate, the actions necessary
to place such an application, supplemental application, or
submission in condition for approval.
Within 30 days of receipt, FDA shall refuse to file an
animal drug application, supplemental new 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 receipt, FDA will refuse to review an
INAD 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 new animal drug
applications, and INAD 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 INAD submissions.
3. The term ``submission date'' or the date of receipt
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'' 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
All applications and submissions under the Federal Food,
Drug, and Cosmetic Act sections 512(b) and 571 must be
created using the CVM eSubmitter tool and submitted to the
Agency through CVM's ESS.
The submissions in this section are sentinel submissions.
CVM's performance toward meeting the associated goals will be
included in the performance reports required by section
740A(a) of the FD&C Act.
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 timeframe
will be reviewed with the highest possible priority among
those pending.
1. Original New Animal Drug Applications (NADAs),
Applications for Conditional Approval (CNADAs), and
Reactivations
Review and act on 90 percent of original NADAs and CNADAs
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 application
submission date if the Agency determines and notifies the
sponsor that the deficiencies are substantial;
ii. Within 135 days after the reactivated application
submission date if the Agency determines and notifies the
sponsor that the deficiencies are not substantial; and the
application 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 after the reactivated application
submission date if the 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 applications 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 and CNADAs
Review and act on 90 percent of administrative NADAs and
CNADAs [(C)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 NADAs
Review and act on 90 percent of non-manufacturing
supplemental NADAs (i.e., supplemental NADAs for which safety
or effectiveness data are required) within 180 days after the
submission date.
A supplemental NADA 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 Animal Drug
Applications and Reactivations
Review and act on 90 percent of Prior Approval
manufacturing supplemental animal drug applications within
120 days after the submission date. A Prior Approval
manufacturing supplemental application 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-
[[Page S5039]]
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 Animal Drug
Applications 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.
1. Supplements--Changes Being Effected Manufacturing
Supplemental Animal Drug Applications and Reactivations
Review and act on 90 percent of ``Supplement- Changes Being
Effected'' manufacturing supplemental applications 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.
2. 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 Study 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 animal drug
application, 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 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 non-concurrence 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. Qualifying 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 labeling 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.
9. Presubmission Conferences
Conduct 90% of qualifying presubmission conferences within
a 60-day timeframe, regardless of forum, 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.
If a sponsor requests a date beyond the 60-day timeframe
for their scheduling purposes or is unable to meet with the
FDA on Agency-available dates within the 60-day timeframe,
the submission will be excluded from the presubmission
conference cohort.
10. 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;
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.
11. Tissue Residue Methods
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.
12. 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)
[[Page S5040]]
ii. The submission meets all of the eligibility criteria
found in section II of P&P 1243.5730, ``Review of 60-Day
Original Animal Drug Availability Act of 1996 (ADAA) Feed Use
Combination New Animal Drug Applications (NADAs).''
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.
III. ADDITIONAL PERFORMANCE GOALS
Submissions in this section are not sentinel submissions
unless they appear in section II, above.
A. Foreign inspections
1. Pre-Approval Foreign Inspections
a. 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 animal
drug application, a supplemental animal drug application, 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.
b. The Agency will keep a record of the number of foreign
PAIs conducted for 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.
2. Foreign GMP Inspections
The Agency commits to working to implement and maintain the
United States and European Union, and the United States and
United Kingdom, Good Manufacturing Practice mutual
recognition agreements and future mutual recognition
agreements with respect to animal drug products subject to
review.
Beginning in fiscal year (FY) 2024, the Agency will report
quarterly in FDA-TRACK the percentage of pre-approval
inspection risk decisions which relied at least in part on
information from inspections recognized under a mutual
recognition agreement with a foreign regulatory authority.
B. Meetings
1. Presubmission Conferences Held Virtually
Beginning on October 1, 2023, for qualifying presubmission
conferences where the sponsor requests that the conference be
held virtually (not in person), the Agency will provide the
following:
At least 6 days prior to the scheduled presubmission
conference date, written responses to the questions posed by
the sponsor in their meeting request. Responses will be
commensurate to the level of information and complexity of
questions submitted by the sponsor.
Permit the sponsor to cancel the scheduled presubmission
conference should the Agency's written responses provide all
the information they were seeking from the Agency.
Should the presubmission conference be held, provide a
memorandum of conference within 30 days after the
presubmission conference date.
Sponsors may request a virtual presubmission conference and
opt out of the process above. The sponsor will identify their
decision whether to opt out of the above process within the
presubmission conference request. If the sponsor chooses to
opt out, the Agency will not issue any written responses
before the presubmission conference and will provide a
memorandum of conference within 45 days following the
presubmission conference date.
2. Stakeholder Engagement
a. The Agency is committed to engaging with all our
external stakeholders in substantive ways that work for all
parties. Further, the Agency commits to coordinating with AHI
to identify the most appropriate forum based on topic,
timing, and public health safety precautions with the
understanding that it is a priority for AHI to meet in person
when possible.
b. FDA will host triannual meetings (three times a calendar
year) with the Animal Health Institute (AHI) members.
c. During one triannual meeting with AHI per calendar year,
the Agency will dedicate up to 8 hours for an education
session intended for the animal drug industry. These sessions
will be open to the public and hosted in an appropriate
forum. The Agency and AHI will build a plan of educational
topics for the five years of the ADFUA V program period.
Education sessions will be recorded and posted publicly to
the Agency's ``For Industry'' website in a new ``Education
for Industry'' section.
d. The Agency will conduct an industry engagement sub-
meeting during each AHI triannual meeting, that includes CVM
leadership and designated AHI attendees and uses a structured
agenda to provide updates on metrics and performance related
to the ADUFA program and resource utilization (i.e., CVM
staffing).
C. H submissions
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 these data and/
or information in presubmission conferences and/or in an H
submission prior to the presubmission conference; however, a
presubmission conference may be held without such data. By
October 1, 2023, the Agency will publish a Program Policy and
Procedures Manual Guide (P&P) for CVM reviewers who are
advising sponsors on:
information/data included in H submissions related to
presubmission conferences,
timing of the related meeting request submission, and
how CVM should schedule meetings, such that they occur on,
or in close proximity to, the H submission due date.
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.
By October 1, 2023, the Agency will publish a P&P for CVM
reviewers who are advising sponsors regarding the appropriate
timing of a protocol submission in relation to an H
submission containing information to support the protocol.
The P&P will address situations where information was
submitted early in the new animal drug development process,
as described earlier in this section, and situations where
this information was not submitted early in the animal drug
development process. The P&P will provide information to CVM
staff who are advising sponsors about when a protocol may or
may not be submitted after the supporting data has been in
the Agency's queue for at least 50 days.
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 are
integral to the review of a protocol, the Agency and the
regulated industry agree that these 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. Raw Data Submission Expectations
By October 1, 2024, the Agency will publish a draft
Guidance for Industry on raw data submission expectations for
non-clinical studies conducted under Good Laboratory Practice
requirements and clinical studies conducted under Good
Clinical Practice requirements.
By October 1, 2023, the Agency will publish a P&P for CVM
reviewers reviewing H submissions in which the sponsor is
seeking agreement on a proposed list of copies of raw data
and documents related to their submission of a target animal
safety (TAS) protocol without data submission. After
publication of the P&P, CVM will permit the submission of H
submissions containing a proposed list of copies of raw data
and documents supporting a TAS protocol.
4. eSubmitter and H Submissions for Raw Data
By October 1, 2023, FDA will launch a new or updated
eSubmitter template for TAS protocols, to facilitate
efficient review of the H submissions containing proposed raw
data to be included in TAS study reports, provided that
industry stakeholders that use the eSubmitter tool have
provided timely feedback to further the Agency's work. FDA
will continue to accept stakeholder feedback on the
eSubmitter template for these H submissions during ADUFA V.
The Agency and industry stakeholders will assess the
benefits of the eSubmitter template for H submissions for TAS
protocols before the Agency develops a template for H
submissions for effectiveness protocols. If the Agency
proceeds with the template for H submissions for
effectiveness protocols, industry stakeholders that use the
eSubmitter
[[Page S5041]]
tool will be invited to provide timely feedback to advance
the Agency's work.
D. Exploration with Industry
1. Animal Drug Availability Act (ADAA) Combination Medicated Feeds
The Agency agrees to explore, in concert with affected
parties including the animal health industry, CVM P&P
1243.5730, ``Review of 60-day original Animal Drug
Availability Act of 1996 (ADAA) feed use combination new
animal drug applications (NADAs)'', to determine why the
process is not being utilized and to understand how to
increase utilization of the process, thereby reducing the
review time for eligible ADAA combinations drug applications
following the approval of a new Type A medicated article. The
exploration phase will be completed by October 1, 2025. The
Agency may revise P&P 1243.5730 based on the outcome of the
exploration phase.
2. Residue Method Trial
The Agency agrees to explore, in concert with affected
parties including the animal health industry, the drug
residue analytical method trial process and its requirements
as they relate to the approval of new animal drugs intended
for food producing animals. If implementation of
recommendations is possible, it may include modification of
current processes. Implementation also may include
procedural, policy, and/or guidance revisions. The
exploration phase will be completed by October 1, 2025.
Implementation of actionable recommendations will be
completed during ADUFA V.
3. Sentinel Submission Clock Stop
Beginning on October 1, 2023, the Agency agrees to explore,
in concert with industry, the feasibility of using additional
review tools to enhance the efficiency of the animal drug
review process, such as implementing a ``clock stop'' during
the review of sentinel submissions. A working group will
develop a written analysis and recommendations for the tools
identified by September 30, 2025.
4. Feedback on Product Development Plans
The Agency agrees to explore, in concert with affected
parties including the animal health industry, means for the
Agency to provide feedback on a sponsor's animal drug
development plan more efficiently and effectively for both
industry and the Agency. By October 1, 2025, a working group
will develop a report outlining suggestions for providing
feedback.
E. Other
1. Chemistry, Manufacturing, and Controls
By September 30, 2024, the Agency will publish a P&P for
Chemistry, Manufacturing, and Controls (CMC) reviewers to
clarify when reviewers should request amendments, use
shortened review time, or classify submissions as incomplete.
In addition, this P&P will describe what administrative
actions are appropriate when GMP status (or pending PAI) is
the only comment remaining for a CMC technical section.
By September 30, 2024, the Agency will revise Guidance for
Industry 227 ``Two-Phased Chemistry, Manufacturing, and
Controls (CMC) Technical Sections'' to define situations for
which parallel submission of phased data submissions would be
allowed.
IV. REPORTING METRICS
A. Sentinel Submissions Filed/Submitted at Division Level
Beginning in FY 2024, as part of the annual ADUFA V
performance report, FDA will report the number of certain
filed/submitted sentinel submissions by review division.
Performance will be reported at the program level. The
sentinel submissions are:
1. Original NADAs, CNADAs and reactivations
2. Administrative NADAs and CNADAs
3. Non-manufacturing supplemental NADAs and reactivations
4. INAD study submissions
5. INAD study protocols without data submissions
6. Qualifying labeling supplements
7. Presubmission conferences
B. Time in Agency/Time in Industry
Beginning in FY 2024, in concert with industry, explore
potential Agency-reported metrics regarding review time of
investigational submissions that lead to approvals by the
Agency and response time by industry. The exploration may
include discussions on which metrics to report, what
processes currently exist to calculate and report these
metrics, which systems might need to be developed to
facilitate reporting the metrics, what the results of the
metrics mean, and how best to report the metrics.
Following publication of the third-party assessment in
2025, industry and the Agency will initiate a follow up
effort, which may include a pilot period, to inform how these
metrics might be collected and reported.
C. Favorable Outcomes
Beginning in the second quarter (Q2) of FY 2024, FDA will
report quarterly in FDA-TRACK, for INAD protocols without
data and for INAD study submissions, the number of the
following outcomes: (1) favorable, (2) non-concurrence/non-
accepted but shortened review offered, and (3) non-
concurrence/non-accepted and shortened review not offered.
FDA and industry will work together to identify a process
to annually report the cycle number for all for INAD
protocols without data and INAD study submissions with
favorable outcomes and whether the favorable outcomes were
first, second, or third+ submissions.
FDA and industry will work together to make sustained,
substantial, and incremental improvements in the annual
percentage of favorable outcomes for the CMC INAD study
submissions and/or to improve utilization of the shortened
review process.
D. INAD H Submissions Submitted at Division Level
Beginning in Q2 of FY 2024, FDA will report quarterly in
FDA-TRACK the number of H submissions submitted to ONADE by
division.
E. Average Review Times in Hours
Beginning in FY 2024, FDA will report in the ADUFA
performance report the average review times, in hours, for
protocols without data and INAD study submissions (broken
down by technical section) by fiscal year.
V. ENHANCING MANAGEMENT OF USER FEE RESOURCES
FDA is committed to enhancing management of ADUFA resources
and ensuring ADUFA user fee resources are administered,
allocated, and reported in an efficient and transparent
manner.
A. Third-Party Assessment
The Agency will engage an independent, third-party to
conduct a comprehensive assessment of the process for the
review of animal drug applications. The assessment will
include consultation with both the Agency and industry. The
assessment will include first cycle reviews as they pertain
to the ADUFA program's objective of expediting the animal
drug development process and the review of new and
supplemental animal drug applications and investigational
animal drug submissions.
The assessment will examine past and current utilization
and effectiveness of the review process, available resources
[e.g., full-time equivalents (FTEs)], and tools used by the
Agency and industry, as established through previous ADUFA
authorizations to foster favorable first cycle review
outcomes for sentinel submissions. The scope of this
assessment will include the analysis of submissions (starting
from the request to establish an INAD file and ending with
approval) and include all technical section submissions (both
sentinel and non-sentinel) to INAD files, NADAs, and
conditional approval application files. It will also evaluate
the impact of specific user fee-based enhancements from prior
reauthorizations on approved original NADAs and applications
for conditional approval.
The assessment will include evaluation of a random set of
applications approved from FY 2009 through FY 2022. The
samples will include representation from new chemical
entities, multiple animal drug sponsors, all major
species, and multiple different dosage form. The
evaluation will include the proposal and evaluation of the
optimal process to provide data on how resources are
utilized (i.e., user fee funds; headcount and process FTEs
with ADUFA allowable activities by office and division)
and of applicable metrics (e.g., time to approval, divided
between time in agency and time with industry, for
technical sections to INADs and NADAs; and favorable first
cycle outcomes) that evaluate progress towards the ADUFA
program's objective mentioned above.
The Agency will obtain the services of a contractor to
complete this assessment. After the final assessment report
is accepted by the responsible Agency official, it will be
posted on FDA.gov. When publishing the final assessment
report on the FDA website, the Agency will comply with
requirements to protect confidential commercial information
and other information exempt from disclosure.
FDA will convene a public workshop approximately three
months after accepting the final assessment report to present
the findings of the independent assessment, including the
third-party's report of anonymized, aggregated feedback
resulting from its interviews of animal drug sponsors and
Agency personnel. The assessment report and the public
meeting will be completed by December 31, 2025.
Following the completion of the assessment and public
meeting, the Agency and industry will analyze the
recommendations for improvement opportunities identified in
the assessment. FDA, with input from stakeholders, will
incorporate findings and recommendations, as it determines to
be possible and appropriate, into its management of the
process for the review of animal drug applications and
Industry will incorporate findings and recommendations, as
appropriate, into their filing and submission processes.
B. Financial Transparency
1. FDA will publish an ADUFA 5-year financial plan no later
than the end of the second quarter of FY 2024 that aligns
with the plans published for GDUFA II, PDUFA VI and BsUFA II.
2. FDA will publish updates to the 5-year plan no later
than the end of the second quarter of each subsequent fiscal
year.
VI. Statutory Adjustments
A. Workload Adjustment
For the purposes of calculating the workload adjustment,
the base years will be a rolling average comprising the five
most recently completed fiscal years. For example, beginning
October 1, 2024 (FY 2025), the base will comprise FY 2019
through FY 2023. At the start of each fiscal year thereafter,
the base will be adjusted upward by one year on the upper and
lower ends of the range. There will be no workload adjustment
for FY 2024.
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Workload adjustments are one-time adjustments and are
calculated annually. The weighting factor is the percent of
direct review time spent on each of the five component
submission types over the most recent five-year period.
As stated in the Federal Food, Drug, and Cosmetic (FD&C)
Act, the workload adjustment ``shall be made for each fiscal
year that the adjustment determined by the Secretary is
greater than 3 percent, except for the first fiscal year that
the adjustment is greater than 3 percent, except for the
first fiscal year that the adjustment is greater than 3
percent.'' See section 740(c)(3) of the FD&C Act [21 U.S.C.
379j-12(c)(3)] for the full text of the workload adjustment.
B. Operating Reserve Adjustment
The operating reserve of carryover user fees for the
process for the review of animal drug applications will be
used to fund the third-party assessment described in section
V.A. and any ADUFA V negotiated, one-time IT enhancements.
Additionally, as stated in the FD&C Act, fee revenue
amounts will be adjusted to provide an operating reserve of
carryover user fees for the process of the review of animal
drug applications of not less than 12 weeks and not more than
16 weeks. The reduction of the operating reserve to the 16-
week maximum will be phased in over the 5-year lifecycle of
ADUFA V. Section 740(c)(4) of the FD&C Act [21 U.S.C. 379j-
12(c)(4)] contains the text of the operating reserve
adjustment, as follows:
``(4) OPERATING RESERVE ADJUSTMENT.--
``(A) IN GENERAL.--For fiscal year 2025 and each subsequent
fiscal year, after the fee revenue amount established under
subsection (b) is adjusted in accordance with paragraphs (2)
and (3), the Secretary shall--
(i) increase the fee revenue amount for such fiscal year,
if necessary to provide an operating reserve of not less than
12 weeks; or
(ii) if the Secretary has an operating reserve in excess of
the number of weeks specified in subparagraph (C) for that
fiscal year, the Secretary shall decrease the fee revenue
amount to provide not more than the number of weeks specified
in subparagraph (C) for that fiscal year.
(B) CARRYOVER USER FEES.--For purposes of this paragraph,
the operating reserve of carryover user fees for the process
for the review of animal drug applications does not include
carryover user fees that have not been appropriated.
(C) NUMBER OF WEEKS OF OPERATING RESERVES.--The number of
weeks of operating reserves specified in this subparagraph
is--
``(i) 22 weeks for fiscal year 2025;
``(ii) 20 weeks for fiscal year 2026;
``(iii) 18 weeks for fiscal year 2027; and
``(iv) 16 weeks for fiscal year 2028.
Animal Generic Drug User Fee Act Reauthorization Performance Goals and
Procedures--Fiscal Years 2024 Through 2028
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 2023 are
summarized as follows:
Application/Submission Goals
Beginning October 1, 2023, 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
Reactivation
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 21 CFR 514.8(b)(3)(iv). The Agency
will review and act on 90 percent of these reactivated
manufacturing supplements within 270 days after the re-
submission 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
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.
7. Request to Establish a JINAD File
Review and act on 90 percent of original submissions
requesting establishment of a JINAD file, within 100 days
after the submission date.
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 that a JINAD file has been
established; 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, filing, or complete submission. 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.
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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 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.
Foreign GMP Inspections
The Agency commits to exploration and implementation of the
United States and European Union and the United States and
United Kingdom Good Manufacturing Practice Mutual Inspection
Agreement and future Mutual Recognition Agreements, with
respect to generic new animal drug products subject to
review, starting in FY 2024 for establishments manufacturing
animal/veterinary drugs. The Agency will provide annual
progress updates to the industry.
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.
Transparency in the Review Process
Bioequivalence Technical Section meeting process
The Agency will enhance transparency by establishing the
Bioequivalence Technical Section (BETS) meeting process. The
term ``Bioequivalence Technical Section (BETS) meeting''
means an optional meeting for a sponsor seeking further
discussion with the Agency after their receipt of CVM's
response to their submission of bioequivalence study data in
support of their ANADA.
The formalized process is the following: Once CVM receives
a bioequivalence technical section with study data for
review, CVM will schedule the BETS meeting for a date
approximately one month after the date CVM's review of the
technical section is due. The sponsor is expected to submit a
detailed list of questions to CVM by email no later than two
weeks prior to the BETS meeting date to facilitate
preparation for the discussion. The BETS meeting will be a
virtual meeting and will include the CVM scientific reviewer
and CVM team leader to whom the submission has been assigned
for review. CVM will not generate any formal documents after
a BETS meeting (e.g., a memorandum of conference).
Response to request to establish a JINAD file
When a sponsor submits a request to establish a JINAD file,
the Agency will include in its response information
describing its current thinking regarding specific elements
for inclusion in the Chemistry, Manufacturing, and Controls
technical section for the dosage form proposed. The response
will list relevant guidance, regulations, and compendial
expectations relevant to that dosage form.
Workload Adjustment
For purposes of calculating the workload adjustment, it has
been agreed to reset the base years to a rolling average
comprising the most recent 5-year completed fiscal years. For
example, beginning October 1, 2024 (FY 2025), the base will
comprise Fiscal Years 2019 through 2023. At the start of each
fiscal year thereafter, the base will be adjusted upward by
one year on the upper and lower ends of the range. There will
be no workload adjustment for FY 2024. Workload adjustments
are one-time adjustments, and are calculated annually. The
percent increase in fees will be made if the amount of the
workload adjuster is equal to or greater than one percent
(1%). The weighting factor is the percent of direct review
time spent on each of the six component submission types over
the most recent five-year period.
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