Subpart B - Applications

PDUFA REAUTHORIZATION PERFORMANCE
GOALS AND PROCEDURES FISCAL YEARS 2018
THROUGH 2022
I. ENSURING THE EFFECTIVENESS OF THE HUMAN DRUG REVIEW

PROGRAM
A. Review Performance Goals
B. Program For Enhanced Review Transparency And Communication For NME
NDAs And Original BLAs
C. First Cycle Review Management
D. Review Of Proprietary Names To Reduce Medication Errors
E. Major Dispute Resolution
F. Clinical Holds
G. Special Protocol Question Assessment And Agreement
H. Meeting Management Goals
I. Enhancing Regulatory Science And Expediting Drug Development
J. Enhancing Regulatory Decision Tools To Support Drug Development And
Review
K. Enhancement And Modernization Of The FDA Drug Safety System
II. ENHANCING MANAGEMENT OF USER FEE RESOURCES

A. Resource Capacity Planning And Modernized Time Reporting
B. Financial Transparency And Efficiency
III. IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF

A. Completion Of Modernization Of The Hiring System Infrastructure And
Augmentation Of System Capacity
B. Augmentation Of Hiring Staff Capacity And Capability
C. Complete Establishment Of A Dedicated Function To Ensure Needed Scientific
Staffing For Medical Product Review
D. Set Clear Goals For Drug Review Program Hiring
E. Comprehensive And Continuous Assessment Of Hiring And Retention
IV. INFORMATION TECHNOLOGY GOALS

A. Objective
B. Improve The Predictability And Consistency Of PDUFA Electronic Submission
Processes
C. Enhance Transparency And Accountability Of FDA Electronic Submission And
Data Standards Activities
V. IMPROVING FDA PERFORMANCE MANAGEMENT

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VI. PROGRESS REPORTING FOR PDUFA VI AND CONTINUING PDUFA V
INITIATIVES
VII. DEFINITIONS AND EXPLANATION OF TERMS

2

PDUFA REAUTHORIZATION PERFORMANCE
GOALS AND PROCEDURES FISCAL YEARS 2018
THROUGH 2022
This document contains the performance goals and procedures for the Prescription Drug User
Fee Act (PDUFA) reauthorization for fiscal years (FYs) 2018-2022, known as PDUFA VI. It is
commonly referred to as the “goals letter” or “commitment letter.” The goals letter represents
the product of FDA’s discussions with the regulated industry and public stakeholders, as
mandated by Congress. The performance and procedural goals and other commitments specified
in this letter apply to aspects of the human drug review program that are important for facilitating
timely access to safe, effective, and innovative new medicines for patients. While much of
FDA’s work is associated with formal tracked performance goals, the Agency and industry
mutually agree that it is appropriate to manage some areas of the human drug review program
with internally tracked timeframes. This provides FDA the flexibility needed to respond to a
highly diverse workload, including unanticipated public health needs. FDA is committed to
meeting the performance goals specified in this letter and to continuous improvement of its
performance regarding other important areas specified in relevant published documents 1 that
relate to preapproval drug development and post-approval activities for marketed products. FDA
and the regulated industry will periodically and regularly assess the progress of the human drug
review program throughout PDUFA VI. This will allow FDA and the regulated industry to
identify emerging challenges and develop strategies to address these challenges to ensure the
efficiency and effectiveness of the human drug review program.
Unless otherwise stated, goals apply to cohorts of each fiscal year (FY).

1

Refer to the Good Review Management Principles and Practices for PDUFA Products guidance (hereinafter
referred to as “GRMP guidance”) available at http://www.fda.gov/downloads/Drugs/.../Guidances/ucm079748.pdf
and the Good Review Management Principles and Practices for Effective IND Development and Review MAPP
(hereinafter referred to as “GRMP MAPP”) available at
http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ManualofP
oliciesProcedures/UCM349907.pdf

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I. ENSURING THE EFFECTIVENESS OF THE HUMAN DRUG REVIEW
PROGRAM
A.

REVIEW PERFORMANCE GOALS
1. NDA/BLA Submissions and Resubmissions 2
a. Review and act on 90 percent of standard NME NDA and original BLA
submissions within 10 months of the 60 day filing date.
b. Review and act on 90 percent of priority NME NDA and original BLA
submissions within 6 months of the 60 day filing date.
c. Review and act on 90 percent of standard non-NME original NDA
submissions within 10 months of receipt.
d. Review and act on 90 percent of priority non-NME original NDA
submissions within 6 months of receipt.
e. Review and act on 90 percent of Class 1 resubmitted original
applications within 2 months of receipt.
f. Review and act on 90 percent of Class 2 resubmitted original
applications within 6 months of receipt.
2. Original Efficacy Supplements
a. Review and act on 90 percent of standard efficacy supplements within
10 months of receipt.
b. Review and act on 90 percent of priority efficacy supplement within 6
months of receipt.
3. Resubmitted Efficacy Supplements
a. Review and act on 90 percent of Class 1 resubmitted efficacy
supplements within 2 months of receipt.
b. Review and act on 90 percent of Class 2 resubmitted efficacy
supplements within 6 months of receipt.

2

Refer to Section I.B for a description of the review program for NME NDAs and original BLAs.

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4. Original Manufacturing Supplements
a. Review and act on 90 percent of manufacturing supplements requiring
prior approval within 4 months of receipt
b. Review and act on 90 percent of all other manufacturing supplements
within 6 months of receipt.
5. Review Performance Goal Extensions
a. Major Amendments
i.

A major amendment to an original application, efficacy supplement,
or resubmission of any of these applications, submitted at any time
during the review cycle, may extend the goal date by three months.

ii.

A major amendment may include, for example, a major new clinical
safety/efficacy study report; major re-analysis of previously
submitted study(ies); submission of a Risk Evaluation and
Mitigation Strategy (REMS) with Element to Assure Safe Use
(ETASU) not included in the original application; or significant
amendment to a previously submitted REMS with ETASU.
Generally, changes to REMS that do not include ETASU and minor
changes to REMS with ETASU will not be considered major
amendments.

iii.

A major amendment to a manufacturing supplement submitted at any
time during the review cycle may extend the goal date by two
months.

iv.

Only one extension can be given per review cycle.

v.

Consistent with the underlying principles articulated in the GRMP
guidance, FDA’s decision to extend the review clock should, except
in rare circumstances, be limited to occasions where review of the
new information could address outstanding deficiencies in the
application and lead to approval in the current review cycle.

b. Inspection of Facilities Not Adequately Identified in an Original
Application or Supplement
i.

All original applications, including those in the “Program,” (see
Section I.B.2) and supplements are expected to include a
comprehensive and readily located list of all manufacturing facilities
included or referenced in the application or supplement. This list
provides FDA with information needed to schedule inspections of
manufacturing facilities that may be necessary before approval of the
original application or supplement.

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ii.

If, during FDA’s review of an original application or supplement, the
Agency identifies a manufacturing facility that was not included in the
comprehensive and readily located list, the goal date may be extended.
1) If FDA identifies the need to inspect a manufacturing
facility that is not included as part of the comprehensive
and readily located list in an original application or efficacy
supplement, the goal date may be extended by three
months.
2) If FDA identifies the need to inspect a manufacturing
facility that is not included as part of the comprehensive
and readily located list in a manufacturing supplement, the
goal date may be extended by two months.

6. These review goals are summarized in the following tables:
Table 1: Original and Resubmitted Applications and Supplements:
SUBMISSION COHORT

STANDARD

PRIORITY

NME NDAs and original BLAs

90% in 10 months of the 90% in 6 months of the
60 day filing date
60 day filing date

Non NME NDAs

90% in 10 months of the 90% in 6 months of the
receipt date
receipt date

Class 1 Resubmissions

90% in 2 months of the
receipt date

90% in 2 months of the
receipt date

Class 2 Resubmissions

90% in 6 months of the
receipt date

90% in 6 months of the
receipt date

Original Efficacy Supplements

90% in 10 months of the 90% in 6 months of the
receipt date
receipt date

Class 1 Resubmitted Efficacy
Supplements

90% in 2 months of the
receipt date

90% in 2 months of the
receipt date

Class 2 Resubmitted Efficacy
Supplements

90% in 6 months of the
receipt date

90% in 6 months of the
receipt date

PRIOR APPROVAL

ALL OTHER

90% in 4 months of the
receipt date

90% in 6 months of the
receipt date

Table 2:

Manufacturing Supplements

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B.

PROGRAM FOR ENHANCED REVIEW TRANSPARENCY AND
COMMUNICATION FOR NME NDAs AND ORIGINAL BLAs
To promote transparency and communication between the FDA review team and the
applicant, FDA will apply the following model (“the Program”) to the review of all New
Molecular Entity New Drug Applications (NME NDAs) and original Biologics License
Applications (BLAs), including applications that are resubmitted following a Refuse-toFile decision, received from October 1, 2017, through September 30, 2022. 3 The goal of
the Program is to promote the efficiency and effectiveness of the first cycle review
process and minimize the number of review cycles necessary for approval, ensuring that
patients have timely access to safe, effective, and high quality new drugs and biologics.
Approach to Application Review. The standard approach for the review of NME
NDAs and original BLAs is described in this section. However, the FDA review team
and the applicant may discuss and reach mutual agreement on an alternative approach to
the timing and nature of interactions and information exchange between the applicant and
FDA, i.e., a Formal Communication Plan for the review of the NME NDA or original
BLA. The Formal Communication Plan may include elements of the standard approach
(e.g., a mid-cycle communication or a late-cycle meeting) as well as other interactions
that sometimes occur during the review process (e.g., a meeting during the filing period
to discuss the application, i.e., an “application orientation meeting”). If appropriate, the
Formal Communication Plan should specify those elements of the Program that FDA and
the sponsor agree are unnecessary for the application under review. If the review team
and the applicant anticipate developing a Formal Communication Plan, the elements of
the plan should be discussed and agreed to at the pre-submission meeting (see Section
I.B.1) and reflected in the meeting minutes. The Formal Communication Plan may be
reviewed and amended at any time based on the progress of the review and the mutual
agreement of the review team and the applicant. For example, the review team and the
applicant may mutually agree at any time to cancel future specified interactions in the
Program (e.g., the late-cycle meeting) that become unnecessary (e.g. because previous
communications between the review team and the applicant are sufficient). Any
amendments made to the Formal Communication Plan should be consistent with the goal
of an efficient and timely first cycle review process and not impede the review team’s
ability to conduct its review.
Expedited Reviews. In certain cases, an application reviewed in the Program will be for
a product that the FDA review team identifies as meeting an important public health
need. If the FDA review team determines that a first-cycle approval is likely for such an

3

The decision as to whether the application is included or excluded from the Program is distinct
from FDA's determination as to whether the drug product contains a "new chemical entity," as defined under 21
CFR 314.108(a). Determinations regarding new chemical entity exclusivity are made at the time of approval of an
application.

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application, the team intends to make every effort to conduct an expedited review 4 and
act early on the application. FDA conducts expedited reviews to promote timely access to
critically needed therapies for patients without compromising FDA’s high standards for
demonstrating the safety, efficacy, and quality of new medicines. Expedited reviews are
typically characterized by frequent contact between the applicant and the FDA review
team throughout the review process. Any parameters of the Program that are intended to
facilitate expedited reviews are noted throughout Section I.B.
If significant application deficiencies are identified by the review team at any time during
an expedited review, FDA intends to revert, for the remainder of the review, to the
standard approach to the review of priority NME NDAs and original BLAs (as described
in this section), and will inform the applicant accordingly.
The remainder of Section I.B describes the parameters that will apply to FDA’s review of
applications in the Program.
1. Pre-submission meeting: The applicant is strongly encouraged to discuss the
planned content of the application with the appropriate FDA review division at a preNDA/BLA meeting. This meeting will be attended by the FDA review team, including
appropriate senior FDA staff.
a. The pre-NDA/BLA meeting should be held sufficiently in advance of the
planned submission of the application to allow for meaningful response to
FDA feedback and should generally occur not less than 2 months prior to the
planned submission of the application.
b. In addition to FDA’s preliminary responses to the applicant’s questions, other
potential discussion topics include preliminary discussions on the need for
REMS or other risk management actions, and, where applicable, the
development of a Formal Communication Plan and a timeline for review
activities associated with a scheduling recommendation under the Controlled
Substances Act for drugs with abuse potential. These discussions will be
summarized at the conclusion of the meeting and reflected in the FDA
meeting minutes.
c. The FDA and the applicant will agree on the content of a complete application
for the proposed indication(s) at the pre-submission meeting. The FDA and
the applicant may also reach agreement on submission of a limited number of
application components not later than 30 calendar days after the submission of
4

The term “expedited review” in this letter refers to FDA’s review of a human drug application that has received
priority review designation where the review team plans to act at least 1 month before the PDUFA goal date
provided that no significant application deficiencies prevent an early action. Expedited review is distinguished from
FDA’s expedited programs: fast track designation, breakthrough therapy designation, accelerated approval, and
priority review. The decision to perform an expedited review of an application is independent of decisions regarding
these expedited programs. Applications that are identified as candidates for expedited review may be reviewed
under any one or more of FDA’s expedited programs.

8

the original application. These submissions must be of a type that would not
be expected to materially impact the ability of the review team to begin its
review. These agreements will be summarized at the conclusion of the
meeting and reflected in the FDA meeting minutes.
i.

Examples of application components that may be appropriate for delayed
submission include updated stability data (e.g., 15-month data to update
12-month data submitted with the original submission) or the final audited
report of a preclinical study (e.g., carcinogenicity) where the final draft
report is submitted with the original application.

ii.

Major components of the application (e.g., the complete study report of a
Phase 3 clinical trial or the full study report of required long-term safety
data) are expected to be submitted with the original application and are not
subject to agreement for late submission.

2. Original application submission: Applications are expected to be complete, as
agreed between the FDA review team and the applicant at the pre-NDA/BLA meeting, at
the time of original submission of the application. If the applicant does not have a preNDA/BLA meeting with FDA, and no agreement exists between FDA and the applicant
on the contents of a complete application or delayed submission of certain components of
the application, the applicant’s submission is expected to be complete at the time of
original submission.
a. All applications are expected to include a comprehensive and readily located
list of all clinical sites and manufacturing facilities included or referenced in
the application.
b. Any components of the application that FDA agreed at the pre-submission
meeting could be submitted after the original application are expected to be
received not later than 30 calendar days after receipt of the original
application.
c. Incomplete applications, including applications with components that are not
received within 30 calendar days after receipt of the original submission, will
be subject to a Refuse-to-File decision.
d. The following parameters will apply to applications that are subject to a
Refuse-to-File decision and are subsequently filed over protest:
i.

The original submission of the application will be subject to the review
performance goal as described in Section I.B.4.

ii.

The application will not be eligible for the other parameters of the
Program (e.g., mid-cycle communication, late-cycle meeting)

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iii.

FDA generally will not review amendments to the application during any
review cycle. FDA also generally will not issue information requests to
the applicant during the agency’s review.

iv.

The resubmission goals described in Section I.A.1.e and I.A.1.f will not
apply to any resubmission of the application following an FDA complete
response action. Any such resubmission will be reviewed as available
resources permit.

e. Since applications are expected to be complete at the time of submission,
unsolicited amendments are expected to be rare and not to contain major new
information or analyses. Review of unsolicited amendments, including those
submitted in response to an FDA communication of deficiencies, will be
handled in accordance with the GRMP guidance. This guidance includes the
underlying principle that FDA will consider the most efficient path toward
completion of a comprehensive review that addresses application deficiencies
and leads toward a first cycle approval when possible.
3. Day 74 Letter: FDA will follow existing procedures regarding identification and
communication of filing review issues in the “Day 74 letter.” For applications subject to
the Program, the timeline for this communication will be within 74 calendar days from
the date of FDA receipt of the original submission. The planned review timeline
included in the Day 74 letter for applications in the Program will include the planned date
for the internal mid-cycle review meeting. The letter will also include preliminary plans
on whether to hold an Advisory Committee (AC) meeting to discuss the application. If
applicable, the Day 74 letter will serve as notification to the applicant that the review
division intends to conduct an expedited review.
4. Review performance goals: For NME NDA and original BLA submissions that are
filed by FDA under the Program, the PDUFA review clock will begin at the conclusion
of the 60 calendar day filing review period that begins on the date of FDA receipt of the
original submission. The review performance goals for these applications are as follows:
a. Review and act on 90 percent of standard NME NDA and original BLA
submissions within 10 months of the 60 day filing date.
b. Review and act on 90 percent of priority NME NDA and original BLA
submissions within 6 months of the 60 day filing date.
5. Mid-Cycle Communication: The FDA Regulatory Project Manager (RPM), and
other appropriate members of the FDA review team (e.g., Cross Discipline Team Leader
(CDTL)), will call the applicant, generally within 2 weeks following the Agency’s
internal mid-cycle review meeting, to provide the applicant with an update on the status
of the review of their application. An agenda will be sent to the applicant prior to the
mid-cycle communication. Scheduling of the internal mid-cycle review meeting will be
handled in accordance with the GRMP guidance. The RPM will coordinate the specific
date and time of the telephone call with the applicant.
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a. The update should include any significant issues identified by the review team
to date, any information requests, information regarding major safety concerns
and preliminary review team thinking regarding risk management, proposed
date(s) for the late-cycle meeting, updates regarding plans for the AC meeting
(if an AC meeting is anticipated), an update regarding FDA’s review activities
associated with a scheduling recommendation under the Controlled
Substances Act (if applicable), and other projected milestone dates for the
remainder of the review cycle.
b. In the case of an expedited review, FDA will communicate the timelines for
the Late-Cycle Meeting and the Late-Cycle Meeting background package (see
Section I.B.6) which may occur earlier with more condensed timeframes
compared to a review that is not expedited.
6. Late-Cycle and Advisory Committee Meetings: A meeting will be held between
the FDA review team and the applicant to discuss the status of the review of the
application late in the review cycle. Late-cycle meetings will generally be face-to-face
meetings; however, the meeting may be held by teleconference if FDA and the applicant
agree. Since the application is expected to be complete at the time of submission, FDA
intends to complete primary and secondary reviews of the application in advance of the
planned late-cycle meeting.
a. FDA representatives at the late-cycle meeting are expected to include the
signatory authority for the application, review team members from appropriate
disciplines, and appropriate team leaders and/or supervisors from disciplines
for which substantive issues have been identified in the review to date.
b. For applications that will be discussed at an AC meeting, the following
parameters apply:
i.

FDA intends to convene AC meetings no later than 2 months (standard
review) or no later than 6 weeks (priority review) prior to the PDUFA goal
date. The late-cycle meeting will occur not less than 12 calendar days
before the date of the AC meeting.

ii.

FDA intends to provide final questions for the AC to the sponsor and the
AC not less than 2 calendar days before the AC meeting.

iii.

Following an AC Meeting, FDA and the applicant may agree on the need
to discuss feedback from the AC for the purpose of facilitating the
remainder of the review. Such a meeting will generally be held by
teleconference without a commitment for formal meeting minutes issued
by the agency.

c. For applications that will not be discussed at an AC meeting, the late-cycle
meeting will generally occur not later than 3 months (standard review) or two
months (priority review) prior to the PDUFA goal date.

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d. Late-Cycle Meeting Background Packages: The Agency background package
for the late-cycle meeting will be sent to the applicant not less than 10
calendar days (or 2 calendar days for an expedited review) before the latecycle meeting. The package will consist of a brief memorandum from the
review team outlining substantive application issues (e.g., deficiencies
identified by primary and secondary reviews), the Agency’s background
package for the AC meeting (incorporated by reference if previously sent to
the applicant), potential questions and/or points for discussion for the AC
meeting (if planned) and the current assessment of the need for REMS or
other risk management actions. If the application is subject to an expedited
review, the background package may be streamlined and brief using a bulleted
list to identify issues to be discussed.
e. Late-Cycle Meeting Discussion Topics: Potential topics for discussion at the
late-cycle meeting include major deficiencies identified to date; issues to be
discussed at the AC meeting (if planned); current assessment of the need for
REMS or other risk management actions; status update of FDA’s review
activities associated with a scheduling recommendation under the Controlled
Substances Act, if applicable; information requests from the review team to
the applicant; and additional data or analyses the applicant may wish to
submit.
i.

With regard to submission of additional data or analyses, the FDA review
team and the applicant will discuss whether such data will be reviewed by
the Agency in the current review cycle and, if so, whether the submission
will be considered a major amendment and trigger an extension of the
PDUFA goal date.

7. Inspections: FDA’s goal is to complete all GCP, GLP, and GMP inspections for
applications in the Program within 6 months of the date of original receipt for priority
applications and within 10 months of the date of original receipt for standard
applications. This will allow 2 months at the end of the review cycle to attempt to
address any deficiencies identified by the inspections.
C.

FIRST CYCLE REVIEW MANAGEMENT

FDA and industry share a commitment to ensuring an efficient and effective first cycle review
process for all applications subject to the PDUFA program. This commitment was first
articulated in the GRMP guidance finalized in 2005. FDA will update this guidance in PDUFA
VI to include review activities (e.g., the NME Program, REMS) that have been added to the
human drug review program since the guidance was finalized, principles regarding notification
to applicants regarding issues identified during FDA’s initial review of the application, principles
regarding FDA’s notification to applicants regarding planned review timelines, and the
importance of internal review timelines that govern aspects of the human drug review program
that are not part of PDUFA performance goals. FDA will publish a revised draft guidance for
public comment no later than the end of FY 2018.

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D.

REVIEW OF PROPRIETARY NAMES TO REDUCE MEDICATION ERRORS

To enhance patient safety, FDA is committed to various measures to reduce medication errors
related to look-alike and sound-alike proprietary names and such factors as unclear label
abbreviations, acronyms, dose designations, and error prone label and packaging design. The
following performance goals apply to FDA’s review of drug and biological product proprietary
names during development (as early as end-of-phase 2) and during FDA’s review of a marketing
application:
1. Proprietary Name Review Performance Goals During Drug Development
a. Review 90% of proprietary name submissions filed within 180 days of receipt.
Notify sponsor of tentative acceptance or non-acceptance.
b. If the proprietary name is found to be unacceptable, the sponsor can request
reconsideration by submitting a written rebuttal with supporting data or
request a meeting within 60 days to discuss the initial decision (meeting
package required).
c. If the proprietary name is found to be unacceptable, the above review
performance goals also would apply to the written request for reconsideration
with supporting data or the submission of a new proprietary name.
d. A complete submission is required to begin the review clock.
2. Proprietary Name Review Performance Goals During Application Review
a. Review 90% of NDA/BLA proprietary name submissions filed within 90 days
of receipt. Notify sponsor of tentative acceptance/non-acceptance.
b. A supplemental review will be done meeting the above review performance
goals if the proprietary name has been submitted previously (IND phase after
end-of-phase 2) and has received tentative acceptance.
c. If the proprietary name is found to be unacceptable, the sponsor can request
reconsideration by submitting a written rebuttal with supporting data or
request a meeting within 60 days to discuss the initial decision (meeting
package required).
d. If the proprietary name is found to be unacceptable, the above review
performance goals apply to the written request for reconsideration with
supporting data or the submission of a new proprietary name.
e. A complete submission is required to begin the review clock.
E.

MAJOR DISPUTE RESOLUTION
1. Procedure:
For procedural or scientific matters involving the review of human drug applications and
supplements (as defined in PDUFA) that cannot be resolved at the signatory authority
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level (including a request for reconsideration by the signatory authority after reviewing
any materials that are planned to be forwarded with an appeal to the next level), the
response to appeals of decisions will occur within 30 calendar days of the Center’s
receipt of the written appeal.
2. Performance goal:
90% of such answers are provided within 30 calendar days of the Center’s receipt of the
written appeal.
3. Conditions:
a. Sponsors should first try to resolve the procedural or scientific issue at the
signatory authority level. If it cannot be resolved at that level, it should be
appealed to the next higher organizational level (with a copy to the signatory
authority) and then, if necessary, to the next higher organizational level.
b. Responses should be either verbal (followed by a written confirmation within
14 calendar days of the verbal notification) or written and should ordinarily be
to either grant or deny the appeal.
c. If the decision is to deny the appeal, the response should include reasons for
the denial and any actions the sponsor might take to persuade the Agency to
reverse its decision.
d. In some cases, further data or further input from others might be needed to
reach a decision on the appeal. In these cases, the “response” should be the
plan for obtaining that information (e.g., requesting further information from
the sponsor, scheduling a meeting with the sponsor, scheduling the issue for
discussion at the next scheduled available advisory committee (AC).
e. In these cases, once the required information is received by the Agency
(including any advice from an AC), the person to whom the appeal was made,
again has 30 calendar days from the receipt of the required information in
which to either grant or deny the appeal.
f. Again, if the decision is to deny the appeal, the response should include the
reasons for the denial and any actions the sponsor might take to persuade the
Agency to reverse its decision.
g. N.B. If the Agency decides to present the issue to an AC and there are not 30
days before the next scheduled AC, the issue will be presented at the
following scheduled committee meeting to allow conformance with AC
administrative procedures.

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F.

CLINICAL HOLDS
1. Procedure:
The Center should respond to a sponsor’s complete response to a clinical hold within 30
days of the Agency’s receipt of the submission of such sponsor response.
2. Performance goal:
90% of such responses are provided within 30 calendar days of the Agency’s receipt of
the sponsor’s response.

G.

SPECIAL PROTOCOL QUESTION ASSESSMENT AND AGREEMENT
1. Procedure:
Upon specific request by a sponsor (including specific questions that the sponsor desires
to be answered), the Agency will evaluate certain protocols and issues to assess whether
the design is adequate to meet scientific and regulatory requirements identified by the
sponsor.
a. The sponsor should submit a limited number of specific questions about the
protocol design and scientific and regulatory requirements for which the
sponsor seeks agreement (e.g., is the dose range in the carcinogenicity study
adequate, considering the intended clinical dosage; are the clinical endpoints
adequate to support a specific efficacy claim).
b. Within 45 days of Agency receipt of the protocol and specific questions, the
Agency will provide a written response to the sponsor that includes a succinct
assessment of the protocol and answers to the questions posed by the sponsor.
If the Agency does not agree that the protocol design, execution plans, and
data analyses are adequate to achieve the goals of the sponsor, the reasons for
the disagreement will be explained in the response.
c. Protocols that qualify for this program include: carcinogenicity protocols,
stability protocols, and Phase 3 protocols for clinical trials that will form the
primary basis of an efficacy claim. For such Phase 3 protocols to qualify for
this comprehensive protocol assessment, the sponsor must have had an endof-Phase 2/pre-Phase 3 meeting with the review division so that the division is
aware of the developmental context in which the protocol is being reviewed
and the questions being answered.
d. N.B. For products that will be using Subpart E or Subpart H development
schemes, the Phase 3 protocols mentioned in this paragraph should be
construed to mean those protocols for trials that will form the primary basis of
an efficacy claim no matter what phase of drug development in which they
happen to be conducted.
e. If a protocol is reviewed under the process outlined above and agreement with
the Agency is reached on design, execution, and analyses and if the results of
15

the trial conducted under the protocol substantiate the hypothesis of the
protocol, the Agency agrees that the data from the protocol can be used as part
of the primary basis for approval of the product. The fundamental agreement
here is that having agreed to the design, execution, and analyses proposed in
protocols reviewed under this process, the Agency will not later alter its
perspective on the issues of design, execution, or analyses unless public health
concerns unrecognized at the time of protocol assessment under this process
are evident.
2. Performance goal:
90% of special protocol assessments and agreement requests completed and returned to
sponsor within the timeframe.
3. Reporting:
The Agency will track and report the number of original special protocol assessments and
resubmissions per original special protocol assessment.
H.

MEETING MANAGEMENT GOALS

Formal PDUFA meetings between sponsors and FDA consist of Type A, B, B(EOP), and C
meetings. These meetings are further described below.
•

Type A meetings are those meetings that are necessary for an otherwise stalled drug
development program to proceed (i.e., a “critical path” meeting) or to address an
important safety issue. Post-action meetings requested within three months after an FDA
regulatory action other than approval (i.e., issuance of a complete response letter) will
also generally be considered Type A meetings.

•

Type B meetings include pre-IND meetings and pre-NDA/BLA meetings, while Type
B(EOP) meetings are reserved for certain End-of-Phase 1 meetings (i.e. for 21 CFR Part
312 Subpart E or 21 CFR Part 314 Subpart H or similar products) and End-of-Phase
2/pre-Phase 3 meetings. Meetings regarding REMS or postmarketing requirements that
occur outside the context of the review of a marketing application will also generally be
considered Type B meetings.

•

A Type C meeting is any other type of meeting. 5
1. Responses to Meeting Requests
a. Procedure: FDA will notify the requester in writing of the date, time, and
place for the meeting, as well as expected Center participants following

5

Refer to Section I.I.3 of this document that describes a specific type of Type C meeting pertaining to early
consultations with FDA regarding the use of new surrogate endpoints as the primary basis of product approval in a
proposed context of use.

16

receipt of a formal meeting request. Table 3 below indicates the timeframes
for FDA’s response to a meeting request.
Table 3
Meeting Type

Response Time (calendar days)

A

14

B

21

B(EOP)

14

C

21

i.

For any type of meeting, the sponsor may request a written response to its
questions rather than a face-to-face meeting, videoconference or
teleconference. FDA will review the request and make a determination on
whether a written response is appropriate or whether a face-to-face
meeting, videoconference, or teleconference is necessary. If a written
response is deemed appropriate, FDA will notify the requester of the date
it intends to send the written response in the Agency’s response to the
meeting request. This date will be consistent with the timeframes specified
in Table 4 below for the specific meeting type.

ii.

For pre-IND and Type C meetings, while the sponsor may request a faceto-face meeting, the Agency may determine that a written response to the
sponsor’s questions would be the most appropriate means for providing
feedback and advice to the sponsor. When it is determined that the
meeting request can be appropriately addressed through a written
response, FDA will notify the requester of the date it intends to send the
written response in the Agency’s response to the meeting request. This
date will be consistent with the timeframes specified in Table 4 below for
the specific meeting type.

b. Performance Goal: FDA will respond to meeting requests and provide
notification within the response times noted in Table 3 for 90% of each
meeting type.
2. Scheduling Meetings
a. Procedure: FDA will schedule the meeting on the next available date at
which all applicable Center personnel are available to attend, consistent with
the component’s other business; however, the meeting should be scheduled
consistent with the type of meeting requested. Table 4 below indicates the
timeframes for the scheduled meeting date following receipt of a formal
meeting request, or in the case of a written response, the timeframes for the
Agency to send the written response. If the requested date for any meeting

17

type is greater than the specified timeframe, the meeting date should be within
14 calendar days of the requested date.
Table 4
Meeting Type

Meeting Scheduling or Written Response Time

A

30 calendar days from receipt of meeting request

B

60 calendar days from receipt of meeting request

B(EOP)

70 calendar days from receipt of meeting request

C

75 calendar days from receipt of meeting request

b. Performance goal: 90% of meetings are held within the timeframe for each
meeting type, and 90% of written responses are sent within the timeframe for
each meeting type.
3. Meeting Background Packages
The timing of the Agency’s receipt of the sponsor background package for each meeting
type (including those meetings for which a written response will be provided) is specified
in Table 5 below.
Table 5
Meeting Type

Receipt of Background Package

A

At the time of the meeting request

B

30 calendar days before the date of the meeting or
expected written response

B(EOP)

50 calendar days before the date of the meeting or
expected written response*

C6

47 calendar days before the date of the meeting or
expected written response*

* If the scheduled date of a Type B(EOP) or C meeting is earlier than the timeframes
specified in Table 4, the meeting background package will be due no sooner than 6
calendar days and 7 calendar days following the response time for Type B(EOP) and C
meetings specified in Table 3, respectively.

6 For Type C meetings that are requested as early consultations on the use of a new surrogate endpoint to be used as
the primary basis for product approval in a proposed context of use, the meeting background package is due at the
time of the meeting request. Refer to Section I.I.3 of this document.

18

4. Preliminary Responses to Sponsor Questions
a. Procedure: The Agency will send preliminary responses to the sponsor’s
questions contained in the background package no later than five calendar
days before the meeting date for Type B(EOP) and C meetings.
b. Performance goal: 90% of preliminary responses to questions for Type
B(EOP) meetings are issued by FDA no later than five calendar days before
the meeting date.
5. Sponsor Notification to FDA
Not later than three calendar days following the sponsor’s receipt of FDA’s preliminary
responses for a Type B(EOP) or C meeting, the sponsor will notify FDA of whether the
meeting is still needed, and if it is, the anticipated agenda of the meeting given the
sponsor’s review of the preliminary responses.
6. Meeting Minutes
a. Procedure: The Agency will prepare minutes that will be available to the
sponsor 30 calendar days after the meeting. The minutes will clearly outline
the important agreements, disagreements, issues for further discussion, and
action items from the meeting in bulleted form and need not be in great detail.
Meeting minutes are not required if the Agency transmits a written response
for any meeting type.
b. Performance goal: 90% of minutes are issued within 30 calendar days of the
date of the meeting.
7. Conditions
For a meeting to qualify for these performance goals:
a. A written request must be submitted to the review division.
b. The written request must provide:
i.

A brief statement of the purpose of the meeting and the sponsor’s proposal
for either a face-to-face meeting or a written response from the Agency;

ii.

A listing of the specific objectives/outcomes the requester expects from
the meeting;

iii.

A proposed agenda, including estimated times needed for each agenda
item;

iv.

A listing of planned external attendees;

19

v.

A listing of requested participants/disciplines representative(s) from the
Center with an explanation for the request as appropriate; and

vi.

The date that the meeting background package will be sent to the Center.
Refer to Table 5 for timeframes for the Agency’s receipt of background
packages.

c. The Agency concurs that the meeting will serve a useful purpose (i.e., it is not
premature or clearly unnecessary). However, requests for a Type B or B(EOP)
meeting will be honored except in the most unusual circumstances.
8. Guidance
FDA will publish revised draft guidance on formal meetings between FDA and sponsors
no later than September 30, 2018.
I.

ENHANCING REGULATORY SCIENCE AND EXPEDITING DRUG
DEVELOPMENT

To ensure that new and innovative products are developed and available to patients in a timely
manner, FDA will build on the success of the FDA’s regulatory science program that included
advancing the science of meta-analysis methodologies, advancing the use of biomarkers and
pharmacogenomics, enhancing communications between FDA and sponsors during drug
development, and advancing the development of drugs for rare diseases. The extension and
continuation of this work will encompass further evaluation and enhancement of FDA-sponsor
communications, ensuring the sustained success of the breakthrough therapy program,
establishing early consultations between FDA and sponsors on the use of new surrogate
endpoints as the primary basis for product approval, advancing rare disease drug development,
advancing the development of combination products, and exploring the use of real world
evidence for use in regulatory decision-making.
1. Promoting Innovation Through Enhanced Communication Between FDA and
Sponsors During Drug Development
FDA’s philosophy is that timely interactive communication with sponsors during drug
development is a core Agency activity to help achieve the Agency’s mission to facilitate
the conduct of efficient and effective drug development programs, which can enhance
public health by making new safe and effective drugs available to the American public in
a timely manner. Accordingly, FDA will maintain dedicated drug development
communication and training staffs in CDER and CBER, focused on enhancing
communication between FDA and sponsors during drug development.
One function of the staff is to serve as a liaison that will facilitate general and, in some
cases, specific interactions between sponsors and each Center. The liaison will serve as a
point of contact for sponsors who have general questions about drug development or who
need clarification on which review division to contact with their questions. The liaison
will also serve as a secondary point of contact in each Center for sponsors who are

20

encountering challenges in communication with the review team for their IND (e.g., in
instances when they have not received a response from the review team to a simple or
clarifying question or referral to the formal meeting process within 30 days of the
sponsor’s initial request). In such cases, the liaison will work with the review team and
the sponsor to facilitate resolution of the issue.
The second function of the staff is to provide ongoing training to the review organizations
on best practices in communication with sponsors. The content of training includes, but
is not limited to, FDA’s philosophy regarding timely interactive communication with
sponsors during drug development as a core Agency activity, best practices for
addressing sponsor requests for advice and timely communication of responses through
appropriate mechanisms (e.g., teleconferences, secure email, or when questions are best
addressed through the formal meetings process), and the role of the liaison staff in each
Center in facilitating communication between the review staff and sponsor community,
including the staff’s role in facilitating resolution of individual communication requests.
The staff will also collaborate with sponsor stakeholders (e.g., through participation in
workshops, webinars, and other meetings) to communicate FDA’s philosophy and best
practices regarding communication with sponsors during drug development.
To continue to enhance timely interactive communication with sponsors during drug
development in PDUFA VI, FDA will do the following:
a. Independent Assessment. FDA will contract with an independent third party
to assess current practices of FDA and sponsors in communicating during
drug development. The statement of work for this effort will be published for
public comment prior to beginning the assessment. The third party will be
expected to separately engage both FDA staff and individual sponsors through
contractor-led interviews as part of the assessment. Due to the significant
volume of FDA-sponsor interactions in a given year, the assessment will be
based on a random subset of drug development programs identified by IND
number. The third party will identify best practices and areas for
improvement in communication by FDA review staff and sponsors. FDA will
publish the final report of the assessment on FDA’s website no later than the
end of FY 2020.
b. Public Workshop. FDA will convene a public workshop by the end of
March 2021 to discuss the findings of the independent assessment, including
anonymized, aggregated feedback from sponsors and FDA review teams
resulting from the contractor interviews.
c. Guidance. FDA will consider the third party’s recommendations for best
practices in communication and update the current draft or final guidance on
“Best Practices for Communication Between IND Sponsors and FDA During
Drug Development” if appropriate. If FDA determines that the guidance
should be updated, based on the recommendations of the third party and the
feedback received from the public workshop, FDA will update the guidance
no later than one year following the public workshop.

21

2. Ensuring Sustained Success of Breakthrough Therapy Program
Breakthrough therapy designation is intended to expedite the development and review of
drug and biological products, alone or in combination, for serious or life-threatening
diseases or conditions when preliminary clinical evidence indicates that the drug may
demonstrate substantial improvement over existing therapies. 7 A breakthrough therapy
designation includes the features of the fast track program, intensive FDA guidance on an
efficient drug development program, and an organizational commitment by FDA
involving senior managers. 8 Additional resources will enable the Agency to continue to
work closely with sponsors throughout the breakthrough therapy designation,
development, and review processes. Both FDA and the regulated industry are committed
to ensuring the expedited development and review of innovative therapies for serious or
life-threatening diseases or conditions by investing additional resources into the
breakthrough therapy program.
3. Early Consultation on the Use of New Surrogate Endpoints
FDA and industry believe that early consultation between review teams and sponsors is
important for development programs where the sponsor intends to use a biomarker as a
new surrogate endpoint that has never been previously used as the primary basis for
product approval in the proposed context of use. Early consultation in the drug
development program allows the review team to consult with FDA senior management to
evaluate the sponsor’s proposal before providing advice regarding the proposed
biomarker as a new surrogate endpoint to support accelerated or traditional approval.
Requests to engage with FDA on this topic will be considered a Type C meeting request.
The purpose of this meeting is to discuss the feasibility of the surrogate as a primary
endpoint, and identify any gaps in knowledge and how they might be addressed. The
outcome of this meeting may require further investigation by the sponsor and discussion
and agreement with the agency before the surrogate endpoint could be used as the
primary basis for product approval. To qualify for this consultation, these Type C
meeting requests must be accompanied by the complete meeting background package at
the time the request is made that includes preliminary human data indicating impact of
the drug on the biomarker at a dose that appears to be generally tolerable. 9 The
remaining meeting procedures as described in Section I.H of this document will apply.
4. Advancing Development of Drugs for Rare Diseases
7

See Section 506(a) of the Federal Food, Drug, and Cosmetic (FD&C) Act, 21 U.S.C. § 356(a).
See FDA Guidance for Industry entitled “Expedited Programs for Serious Conditions – Drugs and Biologics,” May
2014. A drug designated as a breakthrough therapy may also qualify for one or more of the other expedited
programs as described in this guidance.
9
Refer to Table 5 in Section I.H of this document.
8

22

FDA will build on the success of the Rare Disease Program (RDP) in CDER and CBER
by continuing to advance and facilitate the development and timely approval of drugs and
biologics for rare diseases, including rare diseases in children. The Rare Disease
Program staff in CDER will be integrated into review teams for rare disease development
programs and application review to provide their unique expertise on flexible and feasible
approaches to studying and reviewing such drugs to include, for example, innovative use
of biomarkers, consideration of non-traditional clinical development programs, use of
adaptive study designs, evaluation of novel endpoints, application of new approaches to
statistical analysis, and appropriate use of FDA’s expedited development and review
programs (i.e., Fast Track, Breakthrough, Priority Review, and Accelerated Approval).
CBER, through its Rare Disease Program Staff, will also ensure that its review offices
consider such flexible and feasible approaches in review.
The RDP staff will also continue to provide training to all CDER and CBER review staff
related to development, review, and approval of drugs for rare diseases as part of the
reviewer training core curriculum. The objective of the training will be to familiarize
review staff with the challenges associated with rare disease applications and strategies to
address these challenges; to promote best practices for review and regulation of rare
disease applications; and to encourage flexibility and scientific judgment among
reviewers in the review and regulation of rare disease drug development and application
review. The training will also emphasize the important role of the RDP staff as members
of the core review team to help ensure consistency of scientific and regulatory
approaches across applications and review teams.
RDP staff will continue to engage in outreach to industry, patient groups, and other
stakeholders to provide training on FDA’s RDP. The staff will continue to foster
collaborations in the development of tools (e.g., patient reported outcome measures) and
data (e.g., natural history studies) to support development of drugs for rare diseases. In
addition, the staff will also facilitate interactions between stakeholders and FDA review
divisions to increase awareness of FDA regulatory programs and engagement of patients
in FDA’s regulatory decision-making.
FDA will include updates on the activities and success of the RDP in the PDUFA annual
performance report to include, for example, the number of training courses offered and
staff trained, the number of review programs where RDP staff participated as core team
members, and metrics related to engagement with external stakeholders. FDA will also
continue to include information on rare disease approvals in its annual reports on
innovative drug approvals, including utilization of expedited programs and regulatory
flexibility and appropriate comparative metrics to non-rare disease innovative approvals.
5. Advancing Development of Drug-Device and Biologic-Device Combination
Products Regulated by CBER and CDER
a. FDA will develop staff capacity and capability across the medical product
centers and the Office of Combination Products (OCP) to more efficiently,
effectively, and consistently review and respond to submissions that include

23

combination products. These staff will advance the development of
combination products by providing combination product expertise as part of
the core review team as applicable, and through promoting best practices for
review of combination products. The additional capacity will include staff
who will focus on review of cGMP, engineering aspects, human factors and
bridging study protocols and study reports, and labeling, to include
instructions-for-use materials.
b. FDA will streamline the process for combination product review and improve
the Agency’s ability to assess workload and allocate resources to the review of
combination products.
i.

By no later than December 31, 2017, FDA will complete a lean process
mapping for combination product review in order to inform changes to
review work flow to improve the inter-center consultation process.

ii.

By no later than December 31, 2017, FDA will begin tracking workload
and timelines for cross-center consultations to enable appropriate
allocation of resources and regularly assess the progress of combination
product review throughout PDUFA VI.

iii.

By no later than September 30, 2018, for each component within FDA that
is consulted to participate in review of combination products, FDA will
outline in appropriate internal documents the Agency’s process for
resolving internally any scientific or regulatory issues that arise, as well as
a commitment for the medical product centers and OCP to coordinate and
complete reviews and related activities when consulted in timelines set
forth by PDUFA and other published documents (e.g., the GRMP
guidance and GRMP MAPP).

c. FDA will establish Manuals of Policies and Procedures (MAPPs) and
Standard Operating Policy and Procedures (SOPPs) to promote efficient,
effective, and consistent combination product development and review. The
documents will describe processes and procedures for conducting review of
combination products, including the expectations for consultation of internal
experts outside the reviewing Center. FDA will describe the responsibilities
of staff in each Center and Office, expectations for core review team members
and for other consultant staff in activities and meetings related to the
combination product development program and application review. FDA will
define the key terms to be used by staff in review of combination products to
foster clear communication within FDA and to regulated industry. The topic
areas and expected completion dates of these documents are specified below:
i.

Human Factors Assessments (March 31, 2019)

ii.

Quality assessment of combination products, including coordination of
facility inspections (September 30, 2019)

24

iii.

Patient-oriented labeling, including instructions-for-use materials for those
drug-device and biologic-device combination products regulated by CBER
and CDER (September 30, 2019)

d. By no later than December 31, 2018, FDA will make available on FDA’s
website key points of contact in OCP and the medical product centers for
combination product review. FDA agrees to maintain and update this
information periodically.
e. FDA will establish submission procedures for Human Factors protocols no
later than September 30, 2018. Beginning in FY 2019, FDA will establish
timelines to review and provide comment on the protocols for Human Factors
studies of combination drug-device and biologic-device products within 60
days.
i.

Procedure for review of human factors protocols for combination
products: Upon specific request by a sponsor (including specific questions
that the sponsor desires to be answered) consistent with the steps below,
the Agency will evaluate human factors protocols and issues to assess
whether the design is adequate to meet scientific and regulatory
requirements identified by the sponsor.
(1) The sponsor should submit a limited number of specific questions
about the human factors protocol design and scientific and
regulatory requirements for which the sponsor seeks agreement
(e.g., are the study participant groups appropriate to represent
intended users, is the study endpoint adequate, are the critical tasks
that should be evaluated appropriately identified).
(2) Within 60 days of Agency receipt of the protocol and specific
questions, the Agency will provide a written response to the
sponsor that includes a succinct assessment of the protocol and
answers to the questions posed by the sponsor. If the Agency does
not agree that the protocol design, execution plans, and data
analyses are adequate to achieve the goals of the sponsor, the
reasons for the disagreement will be explained in the response.
(3) Performance goals for FDA will be phased in, starting in FY 2019
as follows:
a. By FY 2019, review 50% of human factors protocol submissions
within 60 days and provide sponsor with written comments.
b. By FY 2020, review 70% of human factors protocol submissions
within 60 days and provide sponsor with written comments.
c. By FY 2021, review 90% of human factors protocol submissions
within 60 days and provide sponsor with written comments.

25

f. By no later than December 31, 2018, FDA will begin staff training related to
development, review, and approval of drug-device and biologic-device
combination products reviewed in CDER and CBER. The training will be
provided to all CDER, CBER, Center for Devices and Radiological Health
(CDRH), and Office of Combination Products (OCP) staff, and will be part of
the reviewer training core curriculum. The key purposes of this training
include familiarizing review staff with the regulatory requirements and
challenges associated with combination product applications and strategies to
address these challenges; promoting best practices for review and regulation
of combination products regulated by CDER and CBER, and helping ensure
coordination and consistent approaches within the Centers in the review and
regulation of combination product applications. The training will also
emphasize the role of various experts in the Centers as members of the review
team and OCP’s roles and responsibilities in order to help ensure consistency
of scientific and regulatory approaches across applications and review teams.
g. FDA will contract with an independent third party to assess current practices
for combination drug product review. This study will focus on areas where the
needs for inter-center coordination and consistent approaches are greatest,
including such areas as the Request-for-Designation, cGMPs/facilities topics,
human factors and bridging studies, and labeling. The contractor will be
expected to engage both FDA staff and individual sponsors as part of the
assessment. The assessment will be based on a randomly selected subset of
combination products in various phases of development. The assessment will
identify best practices and areas for improvement by FDA review staff and
sponsors in the submission and review of combination products for
consideration by both FDA and sponsors. FDA will publish the final report of
the assessment on FDA’s website no later than the end of FY 2020. FDA will
consider the assessment findings regarding best practices on the part of FDA
review staff and sponsors in any updates to relevant documents such as
MAPPs, SOPPs, and submission procedures for human factors protocols, and
in the review and submission of Combination Product applications.
h. By the end of FY 2019, FDA will publish draft guidance or update previously
published guidance issued by the medical product centers and OCP for review
staff and industry describing considerations related to drug-device and
biologic-device combination product on the topics noted below. The draft
guidance(s) will be finalized by the end of FY 2022.
i.

Bridging studies, including the bridging of data from combination
products that employ different device components for the same drug or
biologic and the same device component across different drugs and
biologics.

ii.

Patient-oriented labeling (e.g., instructions-for-use).

6. Enhancing Use of Real World Evidence for Use in Regulatory Decision-Making

26

As we participate in the current data revolution, it is important that FDA consider the
possibilities of using so-called “real world” data as an important tool in evaluating not
only the safety of medications but also their effectiveness. To accomplish this will
require an understanding of what questions to ask, including how such data can be
generated and used appropriately in product evaluation, what the challenges are to
appropriate generation and use of these data, and how to address such challenges.
Towards this end, FDA will do the following:
a. By no later than the end of FY 2018, FDA will complete one or more public
workshop(s) with key stakeholders, including patients, biopharmaceutical
companies, and academia, to gather input into issues related to Real World
Evidence (RWE) use in regulatory decision-making. The workshop(s) should
address, among other things, the following topics:
•

Benefits to patients, regulators, and biopharmaceutical companies of RWE
in regulatory decision making;

•

RWE availability, quality, and access challenges, and approaches to
mitigate these;

•

Methodological approaches for the collection, analysis, and
communication of RWE; and

•

Appropriate contexts of use of RWE in regulatory decision-making
regarding effectiveness.

b. By no later than the end of FY 2019, FDA will initiate (or fund by contract),
appropriate activities (e.g., pilot studies or methodology development
projects) aimed at addressing key outstanding concerns and considerations in
the use of RWE for regulatory decision making.
c. By no later than the end of FY 2021, considering available input, such as from
activities noted above, FDA will publish draft guidance on how RWE can
contribute to the assessment of safety and effectiveness in regulatory
submissions, for example in the approval of new supplemental indications and
for the fulfillment of postmarketing commitments and requirements. FDA will
work toward the goal of publishing a revised draft or final guidance within 18
months after the close of the public comment period.
J.

ENHANCING REGULATORY DECISION TOOLS TO SUPPORT DRUG
DEVELOPMENT AND REVIEW
1. Enhancing the Incorporation of the Patient’s Voice in Drug Development and
Decision-Making
To facilitate the advancement and use of systematic approaches to collect and utilize
robust and meaningful patient and caregiver input that can more consistently inform drug
development and, as appropriate, regulatory decision making, FDA will conduct the
following activities during PDUFA VI:

27

a. FDA will strengthen the staff capacity to facilitate development and use of
patient-focused methods to inform drug development and regulatory
decisions. This staff, composed primarily of clinical, statistical, psychometric,
and health outcomes research expertise, will be integrated into review teams
as core members of the team during drug development and application review
where the sponsor intends to use patient input or clinical outcome assessment
(COAs) such as patient-reported outcomes (PROs) as part of the development
program. A core responsibility of the staff will be to engage patient
stakeholders and provide timely development-phase consultations to sponsors
developing new tools to collect patient and caregiver input. This additional
capacity is expected to advance the science of COA development and
analysis, and the staff will also support the public qualification activities for
COAs.
b. FDA will develop a series of guidance documents to focus on approaches and
methods to bridge from initial patient-focused drug development meetings,
like those piloted under PDUFA V, to fit-for-purpose tools to collect
meaningful patient and caregiver input for ultimate use in regulatory decision
making. Prior to the issuance of each guidance, as part of the development,
FDA will conduct a public workshop to gather input from the wider
community of patients, patient advocates, academic researchers, expert
practitioners, industry, and other stakeholders.
i.

By the end of FY 2018, FDA will publish a draft guidance describing
approaches to collecting comprehensive and representative patient and
caregiver input on burden of disease and current therapy. The guidance
will address topics including: standardized nomenclature and
terminologies, methods to collect meaningful patient input throughout the
drug development process, and methodological considerations for data
collection, reporting, management, and analysis.

ii.

By the end of FY 2019, FDA will publish a draft guidance describing
processes and methodological approaches to development of holistic sets
of impacts that are most important to patients. The guidance will address
topics including: methods for sponsors, patient organizations, academic
researchers, and expert practitioners to develop and identify what are most
important to patients in terms of burden of disease, burden of treatment,
and other critical aspects. The guidance will address how patient input can
inform drug development and review processes, and, as appropriate,
regulatory decision making.

iii.

By the end of FY 2020, FDA will publish a draft guidance describing
approaches to identifying and developing measures for an identified set of
impacts (e.g., burden of disease and treatment), which may facilitate
collection of meaningful patient input in clinical trials. The guidance will
address methods to measure impacts in a meaningful way, and identify an
appropriate set of measure(s) that matter most to patients.

28

iv.

By the end of FY 2021, FDA will publish a draft guidance on clinical
outcome assessments, which, when final, will, as appropriate, revise or
supplement the 2009 Guidance to Industry on Patient-Reported Outcome
Measures. The draft guidance will also address technologies that may be
used for the collection, capture, storage, and analysis of patient
perspective information. The guidance will also address methods to better
incorporate clinical outcome assessments into endpoints that are
considered significantly robust for regulatory decision-making.

v.

For each of the above, FDA will work toward the goal of publishing a
revised draft or final guidance within 18 months after the close of the
public comment period on the draft guidance.

c. FDA will create and maintain a repository of publicly available tools on
FDA’s website as a resource for stakeholders. The repository will also include
FDA’s clinical outcome assessment compendium, patient-focused drug
development meeting resources, and ongoing efforts on patient-focused drug
development.
d. As appropriate, FDA will revise existing MAPPs and SOPPs to include
suggested approaches for incorporating an increased patient focus in other ongoing or planned FDA public meetings (e.g., FDA scientific workshops). In
addition, as appropriate, FDA will develop and implement staff training
related to processes, tools, and methodologies described in this section.
e. By the end of FY 2019, FDA will conduct a public workshop, through a
qualified third party, with the primary purpose of gathering ideas and
experiences of the patient and caregiver community and their
recommendations on approaches and best practices that would enhance patient
engagement in clinical trials. The meeting may also gather input from
sponsors, academic researchers, and expert practitioners. The meeting will
result in a published report on proceedings and recommendations from
discussions at the meeting.
2. Enhancing Benefit-Risk Assessment in Regulatory Decision-Making
FDA will further the agency’s implementation of structured benefit-risk assessment,
including the incorporation of the patient’s voice in drug development and decisionmaking, in the human drug review program through the following commitments to be
accomplished during PDUFA VI:
a. By March 31, 2018, FDA will publish an update to the implementation plan
titled “Structured Approach to Benefit-Risk Assessment in Drug Regulatory
Decision-Making.” The update will include a report on the progress made
during PDUFA V and a plan for continued implementation during FYs 20182022.
b. By the end of FY 2019, FDA will convene and/or participate in, at least one
meeting, conducted through a qualified third party, to gather industry, patient,

29

researcher, and other stakeholder input on key topics. This would include
applying the benefit-risk framework throughout the human drug lifecycle,
including best approaches to communicating FDA’s benefit-risk assessment.
c. By the end of FY 2020, FDA will publish a draft guidance on benefit-risk
assessments for new drugs and biologics. This guidance will:
i.

Articulate FDA’s decision-making context and framework for benefit-risk
assessment, illustrating the application of the benefit-risk framework
throughout the human drug lifecycle, using a case study approach, if
appropriate.

ii.

Discuss appropriate interactions between a sponsor and FDA during drug
development to understand the therapeutic context (i.e., the severity of
disease that represents the targeted indication and the extent of unmet
medical need in the target population) regarding regulatory decisions for
the product at the various stages of drug development and evaluation.

iii.

Discuss appropriate approaches to communicate to the public FDA’s
thinking on a product’s benefit-risk assessment, such as through productspecific discussions using the benefit-risk framework at AC meetings.

d. Beginning in FY 2021, FDA will conduct an evaluation of the implementation
of the benefit-risk framework in the human drug review program. This
evaluation will assess how reviewers across the organization apply the
benefit-risk framework and identify best practices in use of the benefit-risk
framework. The evaluation of the benefit-risk framework implementation
conducted in PDUFA V will serve as a baseline for this PDUFA VI
assessment.
e. As appropriate, FDA will revise relevant MAPPs and SOPPs to include new
approaches that incorporate FDA’s benefit-risk framework into the human
drug review program.
3. Advancing Model-Informed Drug Development
To facilitate the development and application of exposure-based, biological, and
statistical models derived from preclinical and clinical data sources, herein referred to as
“model-informed drug development” (MIDD) approaches, FDA will conduct the
following activities during PDUFA VI:
a. FDA will develop its regulatory science and review expertise and capacity in
MIDD approaches. This staff will support the highly-specialized evaluation of
model-based strategies and development efforts.
b. FDA will convene a series of workshops to identify best practices for MIDD.
Topics will include: (1) physiologically-based pharmacokinetic modeling; (2)
design analysis and inferences from dose-exposure-response studies; (3)
disease progression model development, including natural history and trial
simulation; and (4) immunogenicity and correlates of protection for evaluating
30

biological products, including vaccines and blood products. Each workshop
will focus on current and emerging scientific approaches, including
methodological limitations. FDA will produce a written summary of the topics
discussed in each workshop.
c. Starting in FY 2018, FDA will conduct a pilot program for MIDD approaches.
For sponsors participating in the pilot program, FDA will grant a pair of
meetings specifically designed for this pilot program, consisting of an initial
and a follow-up meeting on the same drug development issues, to occur
within a span of approximately 120 days. These meetings will be led by the
clinical pharmacology or biostatistical review components within CDER or
CBER.
i.

FDA will publish a Federal Register Notice announcing the pilot program
and outlining the eligibility criteria and process for submitting to FDA
requests to participate in the pilot program.

ii.

FDA will select 2-4 proposals (e.g., 1-2 per Center) quarterly each year.
FDA will convene an internal review group to review proposals on a
quarterly basis and provide recommendations on prioritization and
selection of proposals and share knowledge and experience. Program
selection will take into account development programs where clinical data
are limited such that integration across non-traditional sources may be
needed, and for which MIDD can assess uncertainties about issues such as
dosing, duration, and patient selection in a way that can inform regulatory
decision-making.

iii.

Sponsors who do not participate in the pilot will have an opportunity to
interact with the Agency through traditional channels.

d. By end of FY 2019, FDA will publish draft guidance, or revise relevant
existing guidance, on model-informed drug development.
e. By end of FY 2021, FDA will develop or revise, as appropriate, relevant
MAPPs or SOPPs, and/or review templates and training, to incorporate
guidelines for the evaluation of MIDD approaches.
4. Enhancing Capacity to Review Complex Innovative Designs
To facilitate the advancement and use of complex adaptive, Bayesian, and other novel
clinical trial designs, FDA will conduct the following activities during PDUFA VI:
a. FDA will develop the staff capacity to enable processes to facilitate
appropriate use of these types of methods. This staff will support the
computationally intensive review work necessary to evaluate complex
adaptive, Bayesian, and other novel clinical trial designs, with a particular
focus on clinical trial designs for which simulations are necessary to evaluate
the operating characteristics.

31

b. Starting in FY 2018, FDA will conduct a pilot program for highly innovative
trial designs for which analytically derived properties (e.g., Type I error) may
not be feasible, and simulations are necessary to determine trial operating
characteristics. For INDs in the pilot program, FDA will grant a pair of
meetings specifically designed for this pilot program, consisting of an initial
and follow-up meeting on the same design, to occur within a span of
approximately 120 days. These meetings will be led by the biostatistical
review components within CDER or CBER. The opportunity for increased
interaction with the agency will provide better understanding of the agency’s
requirements for trial simulations involved in the use of the pilot study design
and allow for iteration of design modifications, if needed. In return, FDA’s
ability to publicly discuss example designs will provide better clarity on the
acceptance of different types of trial designs that should facilitate their use in
future development programs.
i.

FDA will publish a Federal Register Notice announcing the pilot program,
clarifying pilot program eligibility, and describing the proposal
submission and selection process.

ii.

FDA will select up to 2 proposals (e.g., 1 per Center) quarterly each year.
FDA will convene an internal review group to review proposals on a
quarterly basis and provide recommendations on prioritization and
selection of proposals and share knowledge and experience. Program
selection will be prioritized based on trial design features and therapeutic
areas of high unmet need.

iii.

To promote innovation in this area, trial designs developed through the
pilot program may be presented by FDA (e.g., in a guidance or public
workshop) as case studies, including while the drug studied in the trial has
not yet been approved by FDA. Before FDA grants the initial meeting,
FDA and the sponsor will agree on the information that FDA may share
publicly in these case studies. Participation in the pilot program, including
such agreement on information disclosure, will be voluntary and at the
discretion of the sponsor.

iv.

FDA may periodically review the progress of the pilot program and
determine whether it is appropriate to adjust any aspects of the program.

v.

Sponsors who do not participate in the pilot will have an opportunity to
interact with the Agency through traditional channels. The pilot program
will not affect FDA’s existing procedures for providing advice on trial
designs.

c. By end of 2nd Quarter FY 2018, FDA will convene a public workshop to
discuss various complex adaptive, Bayesian, and other novel clinical trial
designs, with a particular focus on clinical trial designs for which simulations
are necessary to evaluate the operating characteristics, and the acceptability of
those designs in regulatory decision-making.

32

d. By end of FY 2018, FDA will publish draft guidance on complex adaptive
(including Bayesian adaptive) trial designs.
e. By end of FY 2020, FDA will develop or revise, as appropriate, relevant
MAPPs, SOPPs and/or review templates and training to incorporate
guidelines on evaluating complex clinical trial designs that rely on computer
simulations to determine operating characteristics.
5. Enhancing Capacity to Support Analysis Data Standards for Product
Development and Review
To support the enhancement of analysis data standards for product development and
review in the human drug review program, FDA will conduct the following activities
during PDUFA VI:
a. FDA will develop the staff capacity to efficiently review and provide
feedback to sponsors on the readiness of submitted analysis data sets and
programs for statistical review. This staff will support pre- and postsubmission discussion of standardized datasets and programs, and maintain
the knowledge of and engage in collaborations about standards models used in
the design, analysis and review of clinical and non-clinical studies. Examples
of these standards models could include the Standard for Exchange of
Nonclinical Data (SEND), Clinical Data Acquisition Standards Harmonization
(CDASH), Study Data Tabulation Model (SDTM), and Analysis Data Model
(ADaM).
b. In parallel, FDA will improve staff capacity to assist with FDA development
and updating of therapeutic area user guides (TAUGs) to include the
appropriate content for the analysis data standards used in submission and
review.
c. By end of FY 2019, FDA will convene a public workshop to advance the
development and application of analysis data standards.
d. FDA will collaborate with external stakeholders and participate in public
workshops held by third parties such as standards development organizations,
on development of data standards, processes, documentation and continuous
improvement of clinical trials and regulatory science.
e. By end of FY 2020, FDA will develop or revise, as appropriate, relevant
guidance, MAPPs, SOPPs and training associated with submission and
utilization of standardized analysis datasets and programs used in review, and
on the processes, procedures, and responsibilities related to the receipt,
handling, and documentation of submitted analysis data and programs.
6.

Enhancing Drug Development Tools Qualification Pathway for Biomarkers

To facilitate the enhancement of the drug development tools qualification pathway for
biomarkers, FDA will conduct the following activities during PDUFA VI:

33

a. FDA will develop the staff capacity to enhance biomarker qualification review
by increasing base capacity. FDA will also pilot processes to engage external
experts to support review of biomarker qualification submissions.
b. By the end of FY 2018, FDA will convene a public meeting to discuss 1)
taxonomy for biomarkers used in drug development, and 2) a framework with
appropriate standards and scientific approaches to support biomarkers under
the taxonomy, including scientific criteria to determine acceptance of a
biomarker qualification submission and essential elements of a formal
biomarker qualification plan.
c. By the end of FY 2018, FDA will publish draft guidance on proposed
taxonomy of biomarker usage and related contexts of use.
d. By the end of FY 2020, FDA will publish draft guidance on general
evidentiary standards for biomarker qualification to be supplemented with
focused guidance on specific biomarker uses and contexts.
e. FDA will develop or revise, as appropriate and necessary, relevant MAPPs
and SOPPs on the biomarker qualification process.
f. FDA will list biomarker qualification submissions that are in the qualification
process on a public website, to be updated quarterly. Inclusion of a
submission on this list will be based on the consent of the submitter for FDA
to publish information about the submission, including stage and current
status of qualification and the proposed use of the biomarker. Following
qualification of a biomarker FDA will post reviews and summary documents
that outline the qualification program and data supporting a qualification
decision.
g. Sponsors who do not use this qualification pathway will have an opportunity
to interact with the Agency through traditional channels.

K.

ENHANCEMENT AND MODERNIZATION OF THE FDA DRUG SAFETY
SYSTEM

FDA will continue to use user fees to enhance and modernize the current U.S. drug safety
system, including adoption of new scientific approaches, improving the utility of existing tools
for the detection, evaluation, prevention, and mitigation of adverse events, standardization and
integration of REMS into the healthcare system, enhancing communication and coordination
between postmarketing and pre-market review staff, and improving tracking, communication and
oversight of postmarketing safety issues. Enhancements to the drug safety system will improve
public health by increasing patient protection while continuing to enable access to needed
medical products.
User fees will provide support for A) advancing postmarketing drug safety evaluation through
expansion of the Sentinel System and integration into FDA pharmacovigilance activities, and B)

34

timely and effective evaluation and communication of postmarketing safety findings related to
human drugs.
1. Advancing Postmarketing Drug Safety Evaluation Through Expansion of the
Sentinel System and Integration into FDA Pharmacovigilance Activities
FDA will use user fee funds to conduct a series of activities to systematically implement
and integrate Sentinel in FDA pharmacovigilance practices. These activities will involve
augmenting the quality and quantity of data available through the Sentinel System,
improving methods for determining when and how that data is utilized, and
comprehensive training of review staff on the use of Sentinel.
a. FDA will work toward expanding the Sentinel System’s sources of data and
enhancing the system’s core capabilities.
b. FDA will enhance its communication with sponsors and the public regarding
general methodologies for Sentinel queries, including what the Agency has
learned regarding the most appropriate ways to query and use Sentinel data.
This can be done through enhancement of existing mechanisms and/or greater
frequency of such mechanisms.
c. FDA will evaluate additional ways to facilitate public and sponsor access to
Sentinel’s distributed data network to conduct safety surveillance.
d. By the end of FY 2019, FDA will hold or support a public meeting engaging
stakeholders to discuss current and emerging Sentinel projects and seek
stakeholder feedback and input regarding gaps in the current system to
facilitate the further development of Sentinel and its system of Active Risk
Identification and Analysis (ARIA).
e. By the end of FY 2020, FDA will establish policies and procedures (MAPPs
and SOPPs) to facilitate informing sponsors about the planned use of Sentinel
to evaluate a safety signal involving their respective products. These MAPPs
and SOPPs will address what types of evaluations and what information about
the evaluations will be shared with sponsors, and the timing of such
communications.
f. By the end of FY 2020, FDA will facilitate integration of Sentinel into the
human drug review program in a systematic, efficient, and consistent way
through staff development and by updating existing SOPPs and MAPPs, as
needed.
g. By the end of FY 2020, FDA will develop a comprehensive training program
for review staff (e.g., epidemiologists, statisticians, medical officers, clinical
analysts, project managers, and other review team members) to ensure that
staff have a working knowledge of Sentinel, can identify when Sentinel can
inform important regulatory questions, and are able to consistently participate
in use of Sentinel to evaluate safety issues.

35

h. By the end of FY 2022, FDA will analyze, and report on the impact of the
Sentinel expansion and integration on FDA’s use of Sentinel for regulatory
purposes, e.g., in the contexts of labeling changes, PMRs, or PMCs.
2. Timely and Effective Evaluation and Communication of Postmarketing Safety
Findings Related to Human Drugs
FDA will use user fee funds to continue to support the review, oversight, tracking, and
communication of postmarketing drug safety issues.
a. FDA will make improvements to its current processes that capture and track
information, including enhancements to its information technology systems,
as needed, in order to support the management and oversight of postmarketing
drug safety issues.
b. By the end of FY 2019, FDA will update existing policies and procedures
(MAPPs and SOPPs) concerning tracking postmarketing safety signals to
include consistent and timely notification to a sponsor (1) when a serious
safety signal involving a product is identified and (2) to the extent practicable,
not less than 72 hours before public posting of a safety notice under section
921 of the Food and Drug Administration Amendments Act of 2007. 10
c. By the end of FY 2022, FDA will conduct, or fund by contract, an assessment
of how its data systems and processes, as described in MAPPs and SOPPs,
support review, oversight, and communication of postmarketing drug safety
issues.

10

FD&C Act § 505(k)(5), 21 U.S.C. 355(k)(5).

36

II. ENHANCING MANAGEMENT OF USER FEE RESOURCES
FDA will modernize the user fee structure to improve the predictability of FDA funding and
sponsor invoices, improve efficiency by simplifying the administration of user fees, and enhance
flexibility of financial mechanisms to improve management of PDUFA program funding. FDA is
committed to enhancing management of PDUFA resources and ensuring PDUFA user fee
resources are administered, allocated, and reported in an efficient and transparent manner. FDA
will conduct a series of resource capacity planning and financial transparency activities to
enhance management of PDUFA resources in PDUFA VI.
A.

RESOURCE CAPACITY PLANNING AND MODERNIZED TIME REPORTING

FDA is committed to enhancing management of PDUFA resources in PDUFA VI. FDA will
conduct activities to develop a resource capacity planning function and modernized time
reporting approach in PDUFA VI.
1. FDA will publish a PDUFA program resource capacity planning and modernized
time reporting implementation plan no later than the 2nd quarter of FY 2018. FDA will
continue to utilize information and recommendations from a third party assessment of
resource capacity planning, financial analytics, and modernized time reporting for
PDUFA as part of the implementation plan.
2. FDA will staff a resource capacity planning team that will implement and manage a
capacity planning system across the PDUFA program in PDUFA VI.
3. FDA will obtain through a contract with an independent accounting or consulting
firm an evaluation of options and recommendations for a new methodology to accurately
assess changes in the resource and capacity needs of the human drug review program.
The report will be published no later than end of FY 2020 for public comment. Upon
review of the report and comments, FDA will implement robust methodologies for
assessing resource needs of the program. This will include the adoption of a new resource
capacity adjustment methodology, in place of the current PDUFA workload adjuster, that
accounts for sustained increases in PDUFA workload.
4. FDA recognizes that revenue generated by the workload adjuster and the resource
capacity adjustment will be allocated to and used by organizational review components
engaged in direct review work to enhance resources and expand staff capacity and
capability. FDA will document in the annual financial report how the workload adjuster
and resource capacity adjustment fee revenues are being utilized.
B.

FINANCIAL TRANSPARENCY AND EFFICIENCY

FDA is committed to ensuring PDUFA user fee resources are administered, allocated, and
reported in an efficient and transparent manner. FDA will conduct activities to evaluate the
37

financial administration of the PDUFA program to help identify areas to enhance efficiency.
FDA will also conduct activities to enhance transparency of PDUFA program resources.
1. FDA will contract with an independent third party to conduct an evaluation of
PDUFA program resource management during FY 2018 to ensure that PDUFA user fee
resources are administered, allocated, and reported in an efficient and transparent manner
in PDUFA VI. The study will include, but is not limited, to the following areas:
a. Evaluate all components of the PDUFA program resource planning, request,
and allocation process from when FDA receives the user fee funds through
when funds are spent. The contractor will recommend options to improve the
process and data needed to enhance resource management decisions.
b. Assess how FDA administers PDUFA user fees organizationally, including,
but not limited to, billing, user fee collection, and execution. The contractor
will recommend options to enhance the efficiency of user fee administration.
c. Evaluate FDA’s existing PDUFA program financial and administrative
oversight and governance functions. Assess alternative governance models
including roles and responsibilities, organizational location, and personnel
skill sets required. The contractor will recommend options on the most
effective governance model to support the human drug review program.
d. Assess FDA’s technical capabilities to conduct effective financial
management and planning in the context of generally accepted government
resource management and planning practices. The contractor will recommend
options for the technical capabilities needed by financial personnel involved in
PDUFA resource management to enhance financial management and
planning.
e. Evaluate how FDA estimates fee paying units for annual fee setting. The
contractor will recommend options to enhance the accuracy of FDA’s PDUFA
user fee estimation methods.
2. FDA will publish a PDUFA 5-year financial plan no later than the 2nd quarter of FY
2018. FDA will publish updates to the 5-year plan no later than the 2nd quarter of each
subsequent fiscal year.
3. FDA will convene a public meeting no later than the third quarter of each fiscal year
starting in FY 2019 to discuss the PDUFA 5-year financial plan, along with the Agency’s
progress in implementing modernized time reporting, resource capacity planning, and the
modernized user fee structure.

38

III. IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF
To speed and improve development of safe and effective new therapies for patients,
enhancements to the human drug review program require that FDA hire and retain sufficient
numbers and types of technical and scientific experts to efficiently conduct reviews of human
drug applications. In order to strengthen this core function and increase the public health impact
of new therapies, the FDA will commit to do the following:
A.

COMPLETION OF MODERNIZATION OF THE HIRING SYSTEM
INFRASTRUCTURE AND AUGMENTATION OF SYSTEM CAPACITY:
1. Complete implementation of FTE-based position management system capability.
a. FDA will complete development of Position Management baseline accounting
of all current positions and FTE counts engaged in the human drug review
program for each applicable Center and Office including filled and vacant
positions, a governance structure for on-going position management that will
be accountable to FDA senior management, and Position Management policy
and guidance ratified by FDA senior management, outlining processes for
adding new positions, deleting positions, and changing established positions.
b. FDA will complete implementation of the new Position-Based Management
System.
2. Complete implementation of an online position classification system
a. FDA will finalize the establishment of an online Position Description (PD)
library. The library will include all current well-classified PDs and current
standardized PDs. Once operational, any new PDs classified using the on-line
classification tools, and any newly created standardized PDs, will be stored
and accessible within FDA’s PD library and available for FDA-wide use as
appropriate.
3. Complete implementation of corporate recruiting
a. For key scientific and technical disciplines commonly needed across offices
engaged in the human drug review program, FDA will complete the transition
from the use of individual vacancy announcements for individual offices to
expanded use of a common vacancy announcement and certificate of eligible
job applicants that can be used by multiple offices. As a part of this effort,
FDA will complete the transition from use of individual announcements that
are posted for a limited period to common vacancy announcements with open
continuous posting to maximize the opportunity for qualified applicants to
apply for these positions.

B.

AUGMENTATION OF HIRING STAFF CAPACITY AND CAPABILITY

39

In recognition of the chronic and continuing difficulties of recruiting and retaining
sufficient numbers of qualified Human Resources (HR) staff, FDA will engage a
qualified contractor to provide continuous support throughout PDUFA VI to augment the
existing FDA HR staff capacity and capabilities. The utilization of a qualified contractor
will assist FDA in successfully accomplishing PDUFA goals for recruitment and
retention of human drug review program staff.
C.

COMPLETE ESTABLISHMENT OF A DEDICATED FUNCTION TO ENSURE
NEEDED SCIENTIFIC STAFFING FOR HUMAN DRUG REVIEW PROGRAM
1. Rapid advances in the science and technology of human drug development and
manufacturing require FDA’s human drug review program staff to keep pace with
science and learn innovative methods and techniques for review of new therapies. FDA
will complete the establishment of a new dedicated unit within the Office of Medical
Products and Tobacco charged with the continuous recruiting, staffing, and retention of
scientific, technical and professional staff for the process for the review of human drug
applications.
a. The unit will continuously develop and implement scientific staff hiring
strategies and plans, working closely with the center review offices and the
FDA HR office, to meet discipline-specific hiring commitments and other
targeted staffing needs. It will function as a scientific-focused recruiter
conducting ongoing proactive outreach to source qualified candidates, and
conducting competitive recruiting to fill vacancies that require top scientific,
technical and professional talent.
b. The unit will conduct analyses, no less than annually, of compensation and
other factors affecting retention of key staff in targeted disciplines, providing
leadership and support for agency compensation oversight boards that
currently exist or may be established as needed to ensure retention of key
scientific, technical and professional staff.

D.

SET CLEAR GOALS FOR HUMAN DRUG REVIEW PROGRAM HIRING
1. FDA will establish priorities for management of the metric goals for targeted hires
within the human drug review program staff for the years of PDUFA VI. These goals for
targeted hires are summarized in the Table 6 below:
Table 6
FY 2018

FY 2019

FY 2020

FY 2021

FY 2022

CDER

43

57

45

17

9

CBER

16

8

7

1

0

Other FDA

12

9

6

0

0

Total FTE

71

74

58

18

9

40

2. FDA will confirm progress in the hiring of PDUFA V FTEs. FDA will report on
progress against the hiring goals for FY 2018-2022 on a quarterly basis posting updates
to the FDA website PDUFA Performance webpage.
E.

COMPREHENSIVE AND CONTINUOUS ASSESSMENT OF HIRING AND
RETENTION
FDA hiring and retention of staff for the human drug review program will be evaluated
by a qualified, independent contractor with expertise in assessing HR operations and
transformation. This will include continuous assessments throughout the course of
implementation of the performance initiatives identified in sections III.A-D, and metrics
including, but not limited to, those related to recruiting and retention in the human drug
review program including, but not limited to, specifically targeted scientific disciplines
and levels of experience. The contractor will conduct a comprehensive review of current
hiring processes and hiring staff capacity and capabilities that contribute to achievement
of successes, potential problems, or delays in human drug review program staff hiring.
This includes the entire hiring function and related capabilities. FDA and regulated
industry leadership will periodically and regularly assess the progress of hiring and
retention throughout PDUFA VI.
1. Initial Assessment: The assessment will include an initial baseline assessment to be
conducted and completed no later than December 31, 2017. The initial baseline study
will include an evaluation of the current state and provide recommended options to
address any identified gaps or areas identified as priorities for improvement, and a study
report to be published no later than December 31, 2017. FDA will hold a public meeting
no later than December 31, 2017, to present and discuss report findings, and present its
specific plans, including agency senior management oversight, and timeline for
implementing recommended enhancements to be fully operational by no later than
December 31, 2018.
2. Interim Assessment: An interim assessment will be published by March 31, 2020, for
public comment. By June 30, 2020, FDA will hold a public meeting during which the
public may present their views. FDA will discuss the findings of the interim assessment,
including progress relative to program milestones and metrics, and other aggregated
feedback from internal customers and participants in HR services that may be included in
the continuous assessment. FDA will also address any issues identified to date including
actions proposed to improve the likelihood of success of the program.
3. Final Assessment: A final assessment will be published by December 31, 2021, for
public comment. FDA will hold a public meeting by no later than March 30, 2022,
during which the public may present their views. FDA will discuss the findings of the
final assessment, including progress relative to program milestones and metrics, and
other aggregated feedback from internal customers and participants in HR services that
may be included in the continuous assessment. FDA will also address any issues
identified and plans for addressing these issues.

41

IV. INFORMATION TECHNOLOGY GOALS
A.

OBJECTIVE
FDA is committed to achieve the long-term goal of improving the predictability and
consistency of the electronic submission process (Section IV.B), and enhancing
transparency and accountability of FDA information technology related activities
(Section IV.C). FDA is pursuing these objectives through IT investments that support the
PDUFA program.

B.

IMPROVE THE PREDICTABILITY AND CONSISTENCY OF PDUFA
ELECTRONIC SUBMISSION PROCESSES
1. Electronic Submission Documentation:
By December 31, 2017, FDA will publish and maintain up-to-date documentation for the
following:
a. The electronic submission process, including key electronic submission
milestones and associated sponsor notifications. The description should cover
the complete process undergone by a submission from the completion of its
upload to the Electronic System Gateway (ESG) through the time the
submission is made available to the review team.
b. The rejection process for electronic submissions.
c. The electronic submission validation criteria.
d. Software names and versions for Electronic Common Technical Document
(eCTD) validation and data validation tools.
2. Electronic Submission and System Status:
By September 30, 2018, FDA will:
a. Publish targets for and measure ESG availability overall (including scheduled
downtime) and during business hours (8am to 8pm Eastern Time). ESG
availability is defined for the purposes of this commitment letter as the ability
for an external user to complete a submission from each entry point to its
delivery to the appropriate FDA Center.
b. Post current ESG operational status on its public website.
c. Publish submission instructions to use in the event of an ESG service
disruption.
3. By December 31, 2017, FDA will publish target time frames for the 1) expected
submission upload duration(s) and 2) timeframe between key milestones and notifications
as defined in 1(a).
42

4. By September 30, 2018, FDA will implement the ability to communicate electronic
submission milestone notifications, including final submission upload status (e.g.,
successfully processed or rejected), to sender/designated contact.
5. FDA will provide expert technical support for electronic submissions to FDA review
staff for submission navigation and troubleshooting.
6. For those systems that sponsors interact with directly, FDA will invite industry to
provide feedback and/or participate in user acceptance testing in advance of
implementing significant changes that impact industry's interaction with the system.
7. By December 31, 2017, FDA will document and implement a process to provide
ample advance notification of systems and process changes commensurate with the
complexity of the change and the impact to sponsors for ESG scheduled unavailability
and user interface changes.
C.

ENHANCE TRANSPARENCY AND ACCOUNTABILITY OF FDA ELECTRONIC
SUBMISSION AND DATA STANDARDS ACTIVITIES
1. FDA staff and industry will jointly plan and hold quarterly meetings and will share
performance updates prior to each meeting. The meeting will address current challenges
and emerging needs.
2. Beginning no later than September 30, 2018, FDA will hold annual public meetings
to seek stakeholder input related to electronic submission system past performance, future
targets, emerging industry needs and technology initiatives to inform the FDA IT
Strategic Plan and published targets.
3. By December 31, 2017, FDA will post, at least annually, historic and current metrics
on ESG performance in relation to published targets, characterizations and volume of
submissions, and standards adoption and conformance.
4. By December 31, 2017, FDA will incorporate strategic initiatives in support of
PDUFA goals into the FDA IT Strategic Plan. Milestones and metrics for PDUFA
initiatives will be included in the plan. The plan will be updated and discussed annually
during a meeting described in Section IV.C.1..
5. FDA will:
a. Collaborate with Standards Development Organizations and stakeholders to
ensure long-term sustainability of supported data standards.
b. Publish a data standards action plan updated at least quarterly.
c. Publish and maintain a current FDA Data Standards Catalog.

43

V. IMPROVING FDA PERFORMANCE MANAGEMENT
A.

THE STUDIES CONDUCTED UNDER THIS INITIATIVE ARE INTENDED TO
FOSTER:
1. Development of programs to improve access to internal and external expertise
2. Reviewer development programs, particularly as they relate to the human drug review
program
3. Advancing science and use of information management tools
4. Improving both inter- and intra-Center consistency, efficiency, and effectiveness
5. Improved reporting of management objectives
6. Increased accountability for use of user fee revenues
7. Focused investments on improvements in the process for the review of human drug
applications
8. Improved communication between the FDA and industry

B.

STUDIES WILL INCLUDE:
1. Assessment of current practices of FDA and sponsors in communicating during drug
development as described in Section I.I.1.
2. Assessment of the current practices for combination drug product review as described
in Section I.I.5.
3. Evaluation of how reviewers across the organization apply the benefit-risk framework
and identify best practices in use of the benefit-risk framework as described in Section
I.J.2.
4. Analysis of the impact of the Sentinel expansion and use for regulatory purposes as
described in Section I.K.1.
5. Assessment of how FDA data systems and processes, as described in MAPPs and
SOPPs, support review, oversight, and communication of postmarketing drug safety
issues, as described in Section I.K.2.
6. Evaluation of options and recommendations for a new methodology to accurately
assess changes in the resource and capacity needs of the human drug review program as
described in Section II.A.3.

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7. Evaluation of PDUFA program resource management to ensure that PDUFA user fee
resources are administered, allocated, and reported in an efficient and transparent manner
in PDUFA VI as described in Section II.B.1.
8. Comprehensive and continuous assessment of hiring and retention as described in
Section III.E.

VI. PROGRESS REPORTING FOR PDUFA VI AND CONTINUING PDUFA V
INITIATIVES
A. FDA will include in the annual PDUFA Performance Report information on the
Agency’s progress in meeting the specific commitments identified in Sections I.I-K of
this document.
B. FDA will include in the annual PDUFA Financial Report information on the Agency’s
progress in the hiring of new staff used to support the new initiatives as identified in
Section III.

VII.

DEFINITIONS AND EXPLANATION OF TERMS

1. “Human drug applications” refers to new drug applications submitted under section
505(b) of the Federal Food, Drug, and Cosmetic Act and biologics license applications
submitted under section 351(a) of the Public Health Service Act, as defined in the
Prescription Drug User Fee Act. 11
2. “Human drug review program” refers to the activities to conduct “the process for the
review of human drug applications,” as defined in the Prescription Drug User Fee Act. 12
3. The term “review and act on” means the issuance of a complete action letter after the
complete review of a filed complete application. The action letter, if it is not an approval,
will set forth in detail the specific deficiencies and, where appropriate, the actions
necessary to place the application in condition for approval.
4. A resubmitted original application is a complete response to an action letter
addressing all identified deficiencies.
5. Class 1 resubmitted applications are applications resubmitted after a complete
response letter (or a not approvable or approvable letter) that include the following items
only (or combinations of these items):
a. Final printed labeling
11
12

FD&C Act § 735(1), 21 U.S.C. § 379g(1).
FD&C Act § 735(6), 21 U.S.C. § 379g(6).

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b. Draft labeling
c. Safety updates submitted in the same format, including tabulations, as the
original safety submission with new data and changes highlighted (except
when large amounts of new information including important new adverse
experiences not previously reported with the product are presented in the
resubmission)
d. Stability updates to support provisional or final dating periods
e. Commitments to perform Phase 4 studies, including proposals for such studies
f. Assay validation data
g. Final release testing on the last 1-2 lots used to support approval
h. A minor reanalysis of data previously submitted to the application
i. Other minor clarifying information (determined by the Agency as fitting the
Class 1 category)
j. Other specific items may be added later as the Agency gains experience with
the scheme and will be communicated via guidance documents to industry
6. Class 2 resubmissions are resubmissions that include any other items, including any
items that would require presentation to an advisory committee.
7. The performance goals and procedures also apply to original applications and
supplements for human drugs initially marketed on an over-the-counter (OTC) basis
through an NDA or switched from prescription to OTC status through an NDA or
supplement.
8. As used in this commitment letter, “regulatory decision making” may include, for
example, FDA’s process for making a regulatory decision regarding a drug or biological
product throughout the product lifecycle, such as during drug development, following
FDA’s review of a marketing application, including review of proposed labeling for the
product, or in the post-approval period (e.g., FDA’s decision regarding a supplement to
an approved application).

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