[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.
[[Page S5511]]
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.
____________________