[Federal Register Volume 81, Number 138 (Tuesday, July 19, 2016)]
[Notices]
[Pages 46929-46935]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-16916]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-N-1895]


Prescription Drug User Fee Act; Public Meeting; Request for 
Comments

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of public meeting; request for comments.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
a public meeting to discuss proposed recommendations for the 
reauthorization of the Prescription Drug User Fee Act (PDUFA) for 
fiscal years (FYs) 2018 through 2022. PDUFA authorizes FDA to collect 
fees and use them for the process for the review of human drug 
applications. The current legislative authority for PDUFA expires in 
September 2017. At that time, new legislation will be required for FDA 
to continue collecting prescription drug user fees in future fiscal 
years. Following discussions with the regulated industry and periodic 
consultations with public stakeholders, the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) directs FDA to publish the recommendations 
for the reauthorized program in the Federal Register, hold a meeting at 
which the public may present its views on such recommendations, and 
provide for a period of 30 days for the public to provide written 
comments on such recommendations. FDA will then consider such public 
views and comments and revise such recommendations as necessary.

DATES: The public meeting will be held on August 15, 2016, from 9 a.m. 
to 2 p.m. Please register for the meeting by August 8, 2016, at http://pdufareauthorization.eventbrite.com. Submit electronic or written 
comments to the public docket by August 22, 2016.

ADDRESSES: The meeting and workshop will be held at the FDA White Oak 
Campus, 10903 New Hampshire Ave., Bldg. 31 Conference Center, the Great 
Room (Rm. 1503, Section A), Silver Spring, MD 20993-0002. Participants 
must enter through Building 1 and undergo security screening. For more 
information on parking and security procedures, please refer to http://www.fda.gov/AboutFDA/WorkingatFDA/BuildingsandFacilities/WhiteOakCampusInformation/ucm241740.htm.
    You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential,

[[Page 46930]]

if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2016-N-1895 for ``Prescription Drug User Fee Act; Public Meeting.'' 
Received comments will be placed in the docket and, except for those 
submitted as ``Confidential Submissions,'' publicly viewable at http://www.regulations.gov or at the Division of Dockets Management between 9 
a.m. and 4 p.m., Monday through Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. If you do not 
wish your name and contact information to be made publicly available, 
you can provide this information on the cover sheet and not in the body 
of your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    FDA will post the agenda approximately 5 days before the meeting 
at: http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm446608.htm.

FOR FURTHER INFORMATION CONTACT: Graham Thompson, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 1146, Silver Spring, MD 20993, 301-796-
5003, FAX: 301-847-8443, [email protected].

SUPPLEMENTARY INFORMATION: 

I. Introduction

    FDA is announcing a public meeting to discuss proposed 
recommendations for the reauthorization of PDUFA, the legislation that 
authorizes FDA to collect user fees and use them for the process for 
the review of human drug applications. The current authorization of the 
program (PDUFA V) expires in September 2017. Without new legislation, 
FDA will no longer be able to collect user fees for future fiscal years 
to fund the process for the review of human drug applications. Section 
736B(d)(4) of the FD&C Act (21 U.S.C. 379h-2(d)(4)) requires that after 
FDA holds negotiations with regulated industry and periodic 
consultations with stakeholders, we do the following: (1) Present 
recommendations to the relevant Congressional committees, (2) publish 
recommendations in the Federal Register, (3) provide a period of 30 
days for the public to provide written comments on the recommendations, 
(4) hold a meeting at which the public may present its views, and (5) 
after consideration of public views and comments, revise the 
recommendations as necessary.
    This notice, the 30-day comment period, and the public meeting will 
satisfy some of these requirements. After the public meeting, we will 
revise the recommendations as necessary and present our proposed 
recommendations to the Congressional committees.
    The purpose of the meeting is to hear the public's views on the 
proposed recommendations for the reauthorized program (PDUFA VI). The 
following information is provided to help potential meeting 
participants better understand the history and evolution of the PDUFA 
program and the current status of the proposed PDUFA VI 
recommendations.

II. What is PDUFA and what does it do?

    PDUFA is a law that authorizes FDA to collect fees from drug 
companies that submit marketing applications for certain human drug and 
biological products. PDUFA was originally enacted in 1992 as the 
Prescription Drug User Fee Act (Pub. L. 102-571) for a period of 5 
years. In 1997, Congress passed the FDA Modernization Act (FDAMA, Pub. 
L. 105-115) that reauthorized the program (PDUFA II) for an additional 
5 years. In 2002, Congress extended PDUFA again through FY 2007 (PDUFA 
III) in the Public Health Security and Bioterrorism Preparedness and 
Response Act (Pub. L. 107-188). In 2007, Title I of the Food and Drug 
Administration Amendments Act of 2007 (FDAAA, Pub. L. 110-85) 
reauthorized PDUFA through FY 2012 (PDUFA IV). Most recently, PDUFA was 
reauthorized through FY 2017 (PDUFA V) as Title I of the Food and Drug 
Administration Safety and Innovation Act (FDASIA, Pub. L. 112-144).
    PDUFA's intent is to provide additional revenues so that FDA can 
hire more staff, improve systems, and establish a better-managed human 
drug review process to make important therapies available to patients 
sooner without compromising review quality or FDA's high standards for 
safety, efficacy, and quality. As part of FDA's agreement with industry 
during each reauthorization, the Agency agrees to certain performance 
goals. These goals apply to the process for the review of new human 
drug and biological product applications, resubmissions of original 
applications, and supplements to approved applications. During the 
first few years of PDUFA I, the additional funding enabled FDA to 
eliminate backlogs of original applications and supplements. Phased in 
over the 5 years of PDUFA I, the goals were to review and act on 90 
percent of priority new drug applications (NDAs), biologics license 
applications (BLAs), and efficacy supplements within 6 months of 
submission of a complete application; to review and act on 90 percent 
of standard original NDAs, BLAs, and efficacy supplements within 12 
months; and to review and act on resubmissions and manufacturing 
supplements within 6 months. Over the course of PDUFA I, FDA exceeded 
all of these performance goals and significantly reduced median review 
times of both priority and standard NDAs and BLAs.
    Under PDUFA II, some of the review performance goals were shortened 
and new procedural goals were added to improve FDA's interactions with 
industry sponsors and to help facilitate the drug development process. 
The procedural goals, for example, articulated timeframes for 
scheduling sponsor-requested meetings intended to address issues or 
questions regarding specific drug development programs, as well as 
timeframes for the timely response to industry-submitted questions on 
special study protocols. FDA met or exceeded nearly all of the review 
and procedural goals under PDUFA II. However, concerns grew that 
overworked review teams often had to return applications as 
``approvable''

[[Page 46931]]

because they did not have the resources and sufficient staff time to 
work with the sponsors to resolve issues so that applications could be 
approved in the first review cycle.
    A sound financial footing and support for limited postmarket risk 
management were key themes of PDUFA III. Base user fee resources were 
significantly increased and a mechanism to account for changes in human 
drug review workload was adopted. PDUFA III also expanded the scope of 
user fee activities to include postmarket surveillance of new therapies 
for up to 3 years after marketing approval. FDA committed to the 
development of guidance for industry on risk assessment, risk 
management, and pharmacovigilance as well as guidance to review staff 
and industry on good review management principles and practices 
(GRMPs). Initiatives to improve application submissions and Agency-
sponsored interactions during the drug development and application 
review processes were also adopted.
    With PDUFA's reauthorization under FDAAA Title I (PDUFA IV), FDA 
obtained a significant increase in base fee funding and committed to 
full implementation of GRMPs, which includes providing a planned review 
timeline for premarket review, development of new guidance for industry 
on innovative clinical trials, modernization of postmarket safety, and 
elimination of the 3-year limitation on fee support for postmarket 
surveillance. Additional provisions in FDAAA (Titles IV, V, and IX) 
gave FDA additional statutory authority that increased the pre- and 
postmarket review process requirements, added new deadlines, and 
effectively increased review workload. Specifically, the new provisions 
expanded FDA's drug safety authorities such as the authority to require 
risk evaluation mitigation strategies, order safety labeling changes, 
and require postmarket studies.
    With the current authorization of PDUFA under Title I of FDASIA, 
FDA implemented a new review program (``the Program'') to promote 
greater transparency and increase communication between the FDA review 
team and the applicant on the most innovative products reviewed by the 
Agency. The Program applies to all new molecular entity (NME) NDAs and 
original BLAs received by the Agency from October 1, 2012, through 
September 30, 2017. The Program adds new opportunities for 
communication between the FDA review team and the applicant during 
review of a marketing application, including mid-cycle communications 
and late-cycle meetings, while adding 60 days to the review clock to 
provide for this increased interaction and to address review issues for 
these complex applications. PDUFA V also required two assessments of 
the impact of the Program. The first of these, the interim assessment, 
is available on FDA's Web site at http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM436448.pdf.
    In addition to continued commitment to a significant set of review, 
processing, and procedural goals, PDUFA V also included commitments 
related to enhancing regulatory science and expediting drug 
development, enhancing benefit-risk assessment in regulatory 
decisionmaking, modernizing the FDA drug safety system, and improving 
the efficiency of human drug application review by requiring electronic 
submissions and standardization of electronic drug application data. 
The PDUFA V Commitment Letter requires that FDA report on the progress 
in satisfying these commitments in the annual PDUFA performance report. 
The annual performance reports can be found at http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/UserFeeReports/PerformanceReports/ucm2007449.htm. More information about FDA's implementation of PDUFA V 
can also be found at http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm272170.htm.

III. Proposed PDUFA VI Recommendations

    In preparing the proposed recommendations to Congress for PDUFA 
reauthorization, FDA conducted discussions with the regulated industry 
and consulted with stakeholders, as required by the law. We began the 
PDUFA reauthorization process by publishing a notice in the Federal 
Register requesting public input on the reauthorization and announcing 
a public meeting that was held on July 15, 2015. The meeting included 
presentations by FDA and a series of panels with representatives of 
different stakeholder groups, including patient advocates, consumer 
groups, regulated industry, health professionals, and academic 
researchers. The materials from the meeting, including a transcript and 
Webcast recording, can be found at http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm446608.htm.
    Following the July 2015 public meeting, FDA conducted negotiations 
with the regulated industry and held monthly consultations with 
stakeholders from September 2015 through February 2016. As directed by 
Congress, FDA posted minutes of these meetings on its Web site at 
http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm446608.htm.
    The proposed enhancements for PDUFA VI address many of the top 
priorities identified by public stakeholders, the regulated industry, 
and FDA. While some of the proposed enhancements are new, many either 
build on successful enhancements or refine elements from the existing 
program. The enhancements are proposed in the following areas: 
Premarket review, regulatory decision tools, postmarketing evaluation, 
electronic submissions and data standards, and administrative areas 
(hiring and financial management). The full text of the proposed PDUFA 
VI commitment letter can be found here at http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm446608.htm. Each 
significant new or modified enhancement is described briefly below:

A. Program for Enhanced Review Transparency and Communication for NME 
NDAs and Original BLAs

    The program for enhanced review transparency and communication for 
NME NDAs and original BLAs (the Program), first established in PDUFA V, 
provides for additional communication between FDA review teams and the 
applicants of NME NDAs or original BLAs in the form of pre-submission 
meetings, mid-cycle communications, and late-cycle meetings, while also 
adding 60 days to the review timeframe to accommodate this additional 
interaction. An interim assessment of the Program suggested that the 
Program has created conditions that enhance the ability of applicants 
and FDA reviewers to work toward application approval in the first 
cycle (see http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm327030.htm).
    For PDUFA VI, FDA proposes to maintain the Program with minor 
modifications to reduce administrative burden and increase flexibility 
to the benefit of FDA review teams and applicants. FDA proposes to 
provide an option for the FDA review team and the applicant to agree on 
a formal communication plan to govern interactions during the 
application review. The formal communication plan may or may not 
include Program elements (e.g. mid-cycle communication, late-cycle 
meeting) and may include other interactions that are not part of the 
Program (e.g. application

[[Page 46932]]

orientation meetings). Additional flexibility is also provided for 
scheduling of advisory committee (AC) meetings and an option for an 
informal teleconference following the AC meeting is provided as well 
for purposes of discussing the committee's input. Review activities 
involving FDA's controlled substance scheduling recommendations are 
also to be discussed at Program meetings, if relevant. Applications 
that receive a refuse-to-file action and are subsequently filed over 
protest are now subject to the Program review performance goals, but do 
not benefit from the Program interactions; additionally any subsequent 
resubmissions for applications filed over protest are not subject to 
any review performance goals.
    This enhancement is described in section I.B. of the proposed PDUFA 
VI commitment letter.

B. Goal Extensions for Missing Manufacturing Facilities

    Inspections late in the review process of inadequately identified 
manufacturing facilities can adversely impact FDA's ability to complete 
application review within the performance goal timeframes. FDA proposes 
to extend the goal date for an original application or an efficacy 
supplement when it identifies a need to inspect a facility that was not 
included in a comprehensive and readily located list of manufacturing 
facilities. This enhancement is described in section I.A.5.b of the 
proposed PDUFA VI commitment letter.

C. Meeting Management

    The number of requests for formal meetings between sponsors and the 
FDA is rapidly increasing; in FY 2015 alone, FDA received over 3,000 
requests for formal PDUFA meetings with sponsors. The background 
packages for these meetings are increasingly complex which creates 
challenges for FDA to review and deliberate internally before providing 
advice to sponsors on complex drug development questions within current 
performance goal timeframes. To help address this issue, FDA proposes 
to create a new Type B End of Phase (EOP) meeting type for certain EOP 
1 and EOP 2/pre-phase 3 meetings. The performance goal timeframes for 
responses to meeting requests, submission of meeting background 
packages, and FDA's issuance of preliminary responses for the Type B 
(EOP) meetings and the Type C meetings would be modified to provide 
adequate time for FDA review and response. Sponsors would receive 
preliminary responses to their questions no later than five calendar 
days before the scheduled meeting, providing the sponsor with time to 
evaluate whether an in-person meeting would still be necessary. 
Sponsors would also be able to request a Written Response Only for any 
meeting type. The language for meeting management is described in 
section I.H of the proposed PDUFA VI commitment letter.

D. Enhancing Regulatory Science and Expediting Drug Development

    The enhancements under this section focus on enhancing regulatory 
science and expediting drug development. Regulatory science, in this 
context, is the science of developing and applying new tools, 
standards, and approaches to assess the safety, effectiveness, quality, 
and performance of FDA-regulated drug products. The details of these 
enhancements can be found in section I.I of the proposed PDUFA VI 
commitment letter.
1. FDA-Sponsor Communication During Drug Development
    FDA recognizes that timely interactive communication with sponsors 
can help foster efficient and effective drug development. Under 
commitments in PDUFA V, FDA focused on improving communication between 
FDA and sponsors during drug development by establishing a dedicated 
drug development communications and training staff in the Center for 
Drug Evaluation and Research (CDER) and augmenting existing 
communications staff in the Center for Biologics Evaluation and 
Research (CBER). Under PDUFA VI, FDA proposes to build on this 
enhancement by conducting a third-party evaluation of current 
communication practices between FDA and sponsors during drug 
development, to convene a public workshop to discuss results of this 
evaluation, and then to update the guidance on ``Best Practices for 
Communication Between IND Sponsors and FDA During Drug Development,'' 
if necessary (available here: http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm475586.pdf).
2. Breakthrough Therapies
    FDASIA established a new designation, breakthrough therapy, for 
drugs intended to treat a serious or life threatening disease or 
condition where preliminary clinical evidence indicates that the drug 
may demonstrate substantial improvement over existing therapies on one 
or more clinically significant endpoints. Utilization of the 
breakthrough therapy program has been higher than anticipated with over 
300 requests for designation received, and over 100 granted (as of 
March 2016). Additional resources will enable the FDA to continue to 
work closely with sponsors throughout the development and review of 
breakthrough therapies. Both the FDA and the regulated industry are 
committed to ensuring the expedited development and review of 
innovative therapies for serious or life-threatening diseases by 
investing additional resources in the breakthrough therapy program 
during PDUFA VI.
3. Early Consultation on New Surrogate Endpoints
    FDA recognizes that early consultation can be important to an 
efficient development program when a sponsor intends to use a biomarker 
as a new surrogate endpoint that has never been used as the primary 
basis for product approval in the proposed context of use. Early 
consultation enables the FDA review team to consult with senior 
management to evaluate the sponsor's proposal before providing advice 
to the sponsor on a critical aspect of their development program. FDA 
proposes that these requests for early consultation in PDUFA VI be 
considered as Type C meeting requests. The purpose of the meeting will 
be to discuss the feasibility of the surrogate as a primary endpoint, 
any knowledge gaps, and how these gaps should be addressed before the 
surrogate endpoint could be used as the primary basis for approval. To 
qualify for this consultation, the meeting background package will be 
due at the time of the meeting request and must include preliminary 
human data indicating the impact of the drug on the biomarker.
4. Rare Disease Drug Development
    In PDUFA VI, FDA proposes to build on the success of the Rare 
Disease Program (RDP) by continuing to advance and facilitate the 
development and timely approval of drugs and biologics for rare 
diseases, including diseases in children. In addition to providing 
training for review staff related to development and review of drugs 
for rare diseases and engaging in outreach to external stakeholders, 
the RDP staff in CDER will be integrated into review teams for rare 
disease development programs and application review, while the RDP 
Staff in CBER will ensure that CBER's review offices consider flexible 
and feasible approaches in review. The RDP will also continue to foster 
collaborations in the development of tools to support rare disease drug 
development and facilitate interactions

[[Page 46933]]

between stakeholders to increase awareness of FDA regulatory programs 
and engagement of patients in FDA's regulatory decisionmaking.
5. Advancing Development of Drug-Device and Biologic-Device Combination 
Products Regulated by CBER and CDER
    Under PDUFA VI FDA will pursue the opportunity to improve inter-
center and intra-center combination review coordination and 
transparency for PDUFA-led products. FDA proposes to enhance staff 
capacity and capability across the relevant medical product centers and 
the Office of Combination Products to more efficiently, effectively, 
and consistently review drug and device-led combination products. FDA 
also proposes to streamline the process for combination product review 
and to improve the Agency's ability to track drug and device-led 
combination product review workload, including a third party assessment 
of current practices for combination drug product review.
    Under this enhancement FDA will also establish new performance 
goals and submission procedures for the review of human factors 
protocols for PDUFA combination products. These goals will be to 
provide the sponsor with written comments on these protocols within 60 
days of receipt. The goals to provide written comments within 60 days 
will begin at the 50 percent level in FY 2019, and increase to 90 
percent by FY 2021.
    In addition, FDA proposes to publish draft guidance or update 
previously published guidance on bridging studies and patient-oriented 
labeling.
6. Enhancing Use of Real World Evidence for Use in Regulatory 
Decisionmaking
    FDA recognizes the potential value of utilizing ``real-world'' 
evidence in evaluating not only the safety of medications but also 
their effectiveness. To better understand how real-world evidence can 
be generated and used appropriately in product evaluation, FDA proposes 
to conduct one or more public workshops, as well as other appropriate 
activities (e.g. pilot studies or methodology development projects). 
Considering the available input, FDA will then publish draft guidance 
on how real-world evidence can contribute to the assessment of safety 
and effectiveness in regulatory submissions.
7. Enhancing Regulatory Decision Tools to Support Drug Development and 
Review
    The enhancements under this section focus on enhancing regulatory 
decision tools to support drug development and review. The details of 
these enhancements can be found in section I.J of the proposed PDUFA VI 
commitment letter.
8. Enhancing the Incorporation of the Patient's Voice in Drug 
Development and Decisionmaking
    In PDUFA V, FDA conducted a series of Patient-Focused Drug 
Development (PFDD) meetings with the aim to more systematically gather 
patients' perspectives on their condition and available therapies to 
treat their condition. Under PDUFA VI, FDA proposes to build on these 
efforts to bridge from PFDD meetings to fit-for-purpose tools to 
collect meaningful patient input that can be incorporated into 
regulatory review. FDA proposes to develop a series of guidance 
documents to advance the collection of meaningful patient input. The 
publication of each draft guidance will be preceded by a public 
workshop conducted by FDA to gather stakeholder input relevant to the 
topics that will be the focus of that guidance. FDA also proposes to 
publish a repository of publicly available tools on FDA's Web site as a 
resource for stakeholders, to update internal policies and procedures, 
as appropriate, to incorporate an increased focus on patient input, and 
to enhance staff capacity to facilitate development and use of patient-
focused methods to inform drug development and regulatory decisions.
9. Enhancing Benefit-Risk Assessment in Regulatory Decisionmaking
    Ensuring the safety, effectiveness, and quality of drug products is 
an increasingly complicated regulatory task, requiring FDA's expert 
consideration of a multitude of complex factors. During PDUFA V, FDA 
implemented an enhanced structured approach to benefit-risk assessment 
in regulatory decisionmaking for drug products. In PDUFA VI, FDA 
proposes to publish an update to its benefit-risk framework 
implementation plan, to conduct an evaluation of the implementation of 
the benefit-risk framework, to develop guidance on benefit-risk 
assessments for new drugs and biologics, and to revise relevant 
policies and procedures to include new approaches that incorporate the 
benefit-risk framework into the human drug review program.
10. Advancing Model-Informed Drug Development
    The development and application of exposure-based, biological, and 
statistical models derived from preclinical and clinical data sources 
can be used to inform regulatory decision-making, for example, in 
determining patient selection in clinical trials, individualized dosing 
for specific populations, or the need for post-marketing studies. To 
facilitate the development and application of these approaches during 
PDUFA VI, FDA proposes to convene a series of workshops to identify 
best practices for model-informed drug development (MIDD), to conduct a 
pilot program, to develop guidance on MIDD, and to update policies and 
procedures, as appropriate, to incorporate guidelines for the 
evaluation of MIDD approaches.
11. Enhancing Capacity To Review Complex Innovative Designs
    To facilitate the advancement and use of complex adaptive, 
Bayesian, and other novel clinical trial designs during PDUFA VI, FDA 
proposes to convene a public workshop on complex innovative trial 
designs, publish guidance on complex innovative trial designs, to 
conduct a pilot program, and to update policies and procedures as 
appropriate to incorporate guidelines on evaluating complex innovative 
trial designs.
12. Enhancing Capacity To Support Analysis Data Standards for Product 
Development and Review
    As regulatory submissions are increasingly submitted in fully 
standard electronic format, it becomes increasingly important to ensure 
that analysis datasets are structured according to the standards to 
facilitate acceptance and analysis of the datasets. To support the 
enhancement of analysis data standards for product development and 
review in PDUFA VI, FDA proposes to enhance staff capacity to develop 
and update relevant standards, to support the efficient submission and 
review of analysis datasets, to convene a public workshop to advance 
the development and application of analysis data standards, to 
collaborate with external stakeholders on development of data 
standards, and to update, as appropriate, internal policies and 
procedures associated with the submission and utilization of 
standardized analysis datasets.
13. Enhancing Drug Development Tools Qualification Pathway for 
Biomarkers
    The Biomarker Qualification Program was established to support 
FDA's work with external partners to develop

[[Page 46934]]

biomarkers that aid in the drug development process. To facilitate the 
enhancement of the drug development tools qualification pathway for 
biomarkers in PDUFA VI, FDA proposes to convene a public meeting to 
discuss taxonomy and a framework with standards for biomarkers used in 
drug development, to develop guidance on biomarker taxonomy, contexts 
of uses, and general evidentiary standards, and to maintain a public 
Web site to communicate a list of biomarker qualification submissions 
in the qualification process.

E. Enhancement and Modernization of the FDA Drug Safety System

    The drug safety enhancements in PDUFA VI focus on expansion of the 
Sentinel System and enhancements to support the review, oversight, 
tracking, and communication of postmarketing drug safety issues. The 
enhancements are described in I.K of the proposed PDUFA VI commitment 
letter.
1. Advancing Postmarketing Drug Safety Evaluation Through Expansion of 
the Sentinel System and Integration into FDA Pharmacovigilance 
Activities
    FDA's Sentinel Initiative is a long-term program designed to build 
and implement a national electronic system for monitoring the safety of 
FDA-approved medical products. FDA recently transitioned from the Mini-
Sentinel pilot to the Sentinel System, but full utilization of the 
Sentinel System remains a work in progress. Continued development and 
integration of the Sentinel System is needed to realize the system's 
full value to the postmarketing safety review process. To help realize 
the full value of the Sentinel System during PDUFA VI, FDA proposes to 
continue to expand the systems' data sources and core capabilities, to 
systematically integrate Sentinel into postmarketing review activities, 
to enhance Sentinel communication practices with sponsors and the 
public, and to conduct an analysis of the impact of Sentinel expansion 
and integration for regulatory purposes.
2. Timely and Effective Evaluation and Communication of Postmarketing 
Safety Findings Related to New Drugs
    During PDUFA VI, FDA proposes to continue to support the review, 
oversight, tracking, and communication of postmarketing drug safety 
issues. FDA proposes to make improvements to its current processes and 
information technology systems to enhance the management and oversight 
of postmarketing drug safety issues, to update policies and procedures 
to provide timely notification to a sponsor, to the extent practicable, 
when a serious safety signal is identified, and to conduct an 
assessment of how its data systems and processes support review, 
oversight, and communication of postmarketing drug safety issues.

F. Electronic Submissions and Data Standards Activities

    FDA is committed to achieving the long-term goal of improving the 
predictability and consistency of the electronic submission process and 
enhancing transparency and accountability of FDA information technology 
related activities. During PDUFA VI, FDA proposes to publish submission 
documentation, metrics, submission status, and system and process 
changes, to hold quarterly meetings to share performance updates 
between FDA and the regulated industry, to hold annual public meetings 
to gather stakeholder input to inform the FDA information technology 
strategic plan, and to collaborate with standards development 
organizations and stakeholders to ensure the long-term sustainability 
of supported data standards. These enhancements are described in 
section IV of the proposed PDUFA VI commitment letter.

G. Improving FDA Hiring and Retention of Review Staff

    To speed and improve development of safe and effective new 
therapies for patients requires 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 during PDUFA VI, FDA proposes to commit to completing 
implementation of an full time equivalent staff (FTE)-based position 
management system capability, to complete implementation of an online 
position classification system, to complete implementation of corporate 
recruiting practices, to augment hiring capacity with expert contractor 
support, to complete establishment of a dedicated function to ensure 
needed scientific staffing for the human drug review program, to 
establish clear goals for human drug review program hiring, and to 
conduct a comprehensive and continuous assessment of hiring and 
retention performance. These enhancements are described in section III 
of the proposed PDUFA VI commitment letter.

H. Enhancing Management of User Fee Resources

    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. In PDUFA VI, FDA 
proposes to establish a resource capacity planning function to improve 
its ability to analyze current resource needs and project future 
resource needs, to modernize its time reporting approach, to conduct an 
evaluation of PDUFA program resource management, to publish a 5-year 
PDUFA financial plan with annual updates, and to convene an annual 
public meeting, beginning in FY 2019, to discuss the financial plan and 
progress towards the financial management enhancements. These 
enhancements are described in section II of the proposed PDUFA VI 
commitment letter.

I. Enhancements to Fee Structure and Related Mechanisms for Increased 
Predictability, Stability, and Efficiency

    The current overall PDUFA fee structure and the fee setting process 
were established in 1993 for PDUFA I and have generally remained in 
place through four reauthorizations of PDUFA. Over the years, FDA and 
industry agreed that some elements of the fee structure and the fee 
setting process could be updated to enhance the predictability and 
stability of fee amounts and revenues in a manner to improve FDA's 
ability to engage in long-term financial planning. Additionally, some 
elements of the fee structure reduce the efficiency of administrative 
work without a corresponding benefit to the public or to the regulated 
industry. To address these issues, FDA proposes to shift a greater 
proportion of the target revenue allocation to more predictable fee-
paying types (20 percent to applications; 80 percent to Program fees), 
to discontinue the establishment and supplement fees, to rename the 
product fee as the PDUFA Program fee, to modify the Program fee billing 
date to minimize the need for multiple billing cycles, to add a 
limitation that a sponsor shall not be assessed more than five PDUFA 
Program fees for a fiscal year for products identified in each distinct 
approved human drug application held by that sponsor, and to 
discontinue the Fees-Exceed-the-Costs waiver. FDA also proposes during 
PDUFA VI to replace the workload adjuster with a robust methodology for 
adjusting fees based on the capacity needs of the program, and to 
replace the fifth year offset provision and final year

[[Page 46935]]

adjustment provisions with an annual operating reserve adjustment to 
provide for adequate carryover resources.

J. Impact of PDUFA VI Enhancements on User Fee Revenue

    To implement the proposed enhancements for PDUFA VI, funding for a 
cumulative total of 230 FTE staff is proposed to be phased in over the 
course of PDUFA VI. The new funding will be phased in as follows:

 $20,077,793 for FY 2018
 $21,317,472 for FY 2019
 $16,953,329 for FY 2020
 $5,426,896 for FY 2021
 $2,769,609 for FY 2022
    In addition, $8.73 million will be added in FY 2018 to provide for 
other additional direct costs associated with the PDUFA VI 
enhancements. This amount will be included for FYs 2019 through 2022 
after being adjusted for inflation.

IV. Purpose and Scope of the Meeting

    If you wish to attend this meeting, visit http://pdufareauthorization.eventbrite.com. Please register by August 8, 2016. 
If you are unable to attend the meeting in person, you can register to 
view a live Webcast of the meeting. You will be asked to indicate in 
your registration if you plan to attend in person or via the Webcast. 
Seating will be limited, so early registration is recommended. 
Registration is free and will be on a first-come, first-served basis. 
However, FDA may limit the number of participants from each 
organization based on space limitations. Registrants will receive 
confirmation once they have been accepted. Onsite registration on the 
day of the meeting will be based on space availability. If you need 
special accommodations because of a disability, please contact Graham 
Thompson (see FOR FURTHER INFORMATION CONTACT) at least 7 days before 
the meeting.
    The meeting will include a presentation by FDA and a series of 
invited panels representing different stakeholder groups identified in 
the statute (such as patient advocacy groups, consumer advocacy groups, 
health professionals, and regulated industry). We will also provide an 
opportunity for other organizations and individuals to make 
presentations at the meeting or to submit written comments to the 
docket before the meeting.
    FDA will also hold an open public comment period at the meeting to 
give the public an opportunity to present their comments. Registration 
for open public comment will occur at the registration desk on the day 
of the meeting and workshop on a first-come, first-served basis.
    Transcripts: As soon as a transcript is available, FDA will post it 
at http://www.fda.gov/ForIndustry/UserFees/PrescriptionDrugUserFee/ucm446608.htm.

    Dated: July 13, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-16916 Filed 7-15-16; 4:15 pm]
 BILLING CODE 4164-01-P