
[Federal Register Volume 81, Number 181 (Monday, September 19, 2016)]
[Notices]
[Pages 64171-64175]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2016-22442]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-3326]


Biosimilar User Fee Act; Public Meeting

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 Biosimilar User Fee Act (BsUFA) for fiscal years 
(FYs) 2018 through 2022. BsUFA authorizes FDA to collect fees and use 
them for the process for the review of biosimilar biological product 
applications. The current legislative authority for BsUFA expires in 
September 2017. At that time, new legislation will be required for FDA 
to continue collecting biosimilar

[[Page 64172]]

biological product user fees in future fiscal years. Following an 
initial consultation with public stakeholders and discussions with the 
regulated industry, 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 the public views and comments 
and revise the recommendations as necessary.

DATES: The public meeting will be held on October 20, 2016, from 9 a.m. 
to 2 p.m. Please register for the meeting by October 19, 2016, at 
http://bsufapublicmeeting.eventbrite.com. Submit electronic or written 
comments to the public docket by October 19, 2016.

ADDRESSES: The meeting 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, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2015-N-3326 for ``Biosimilar 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/BiosimilarUserFeeActBsUFA/ucm461774.htm.

FOR FURTHER INFORMATION CONTACT: Amanda Roache, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 1176, Silver Spring, MD 20993, 301-796-
4548, FAX: 301-847-8443, amanda.roache@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. Introduction

    FDA is announcing a public meeting to discuss proposed 
recommendations for the reauthorization of BsUFA, the legislation that 
authorizes FDA to collect user fees and use them for the process for 
the review of biosimilar biological product applications. The current 
authorization of the program (BsUFA I) 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 
biosimilar biological product applications. Section 744I(e)(2) of the 
FD&C Act (21 U.S.C. 379j-53(e)(2)) requires that after FDA holds 
negotiations with regulated industry, 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 on the 
recommendations, 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.
    The purpose of the meeting is to hear the public's views on the 
proposed recommendations for the reauthorization of BsUFA II. The 
following information is provided to help potential meeting 
participants

[[Page 64173]]

better understand the history and evolution of the BsUFA program and 
the proposed BsUFA II recommendations.

II. What is BsUFA and what does it do?

    BsUFA is a law that authorizes FDA to collect fees from drug 
companies that submit marketing applications for certain biosimilar 
biological products. BsUFA was originally enacted in 2012 as the 
Biosimilar User Fee Act (Pub. L. 112-144) for a period of 5 years.
    BsUFA's intent is to provide additional revenues so that FDA can 
hire more staff, improve systems, and establish a better-managed 
biosimilar biological product 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 biosimilar biological product 
applications, resubmissions of original applications, and new and 
resubmitted supplements to approved applications. Phased in over the 5 
years of BsUFA I, the goals were to review and act on 90 percent of 
original biosimilar biological product application submissions within 
10 months of receipt and resubmitted original biosimilar biological 
product applications within 6 months of receipt; to review and act on 
90 percent of original supplements with clinical data within 10 months 
of receipt and resubmitted supplements with clinical data within 6 
months of receipt; and review and act on 90 percent of manufacturing 
supplements within 6 months of receipt.

III. Proposed BsUFA II Recommendations

    In preparing the proposed recommendations to Congress for BsUFA 
reauthorization, FDA conducted discussions with the regulated industry 
and consulted with stakeholders, as required by the law. We began the 
BsUFA 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 December 18, 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/BiosimilarUserFeeActBsUFA/ucm461774.htm.
    Following the December 2015 public meeting, FDA conducted 
negotiations with the regulated industry from March 2016 through May 
2016. FDA posted minutes of these meetings on its Web site at http://www.fda.gov/ForIndustry/UserFees/BiosimilarUserFeeActBsUFA/ucm461774.htm.
    The proposed enhancements for BsUFA II 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: Review 
performance, meeting management, guidance development, and 
administrative areas (hiring and financial management). The full text 
of the proposed BsUFA II commitment letter can be found here at http://www.fda.gov/ForIndustry/UserFees/BiosimilarUserFeeActBsUFA/ucm461774.htm. Each significant new or modified enhancement is 
described briefly in sections III.A through III.K.

A. The Review Cycle

    FDA and the regulated industry jointly identified an opportunity to 
reduce multiple review cycles for biosimilar biological products by 
increasing transparency and communication during the review process of 
a 351(k) application. For BsUFA II, it is therefore proposed to 
establish a model for the review of biosimilar biological products 
similar to the Program for Enhanced Review Transparency and 
Communication for New Molecular Entity New Drug Applications and 
original Biologics License Applications (the Program) that was 
established in the fifth authorization of the Prescription Drug User 
Fee Act (PDUFA).
    The Program was first established for PDUFA in 2012. An interim 
assessment of the Program suggested that it 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). Likewise, 
it is anticipated that the review model will promote efficiency and 
effectiveness of the first cycle review process and minimize the number 
of review cycles necessary for approval for 351(k) applications.
    The Program will allow for additional communication between FDA 
review teams and the applicants of biosimilar biological products 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.
    This enhancement is described in section I.B. of the proposed BsUFA 
II commitment letter.

B. Review Goal Extension for Missing Manufacturing Facilities

    When manufacturing facilities are not adequately identified, this 
may result in the need for FDA to conduct inspections late in the 
review process. This can adversely impact FDA's ability to complete 
application review within the performance goal timeframes. Accordingly, 
FDA proposes to extend the goal date for an original application or a 
supplement when FDA 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 BsUFA II commitment letter.

C. Special Protocol Assessment and Agreement

    Further clarity is needed regarding the types of clinical study 
protocols that may qualify for a Special Protocol Assessment and 
Agreement under BsUFA. Pharmacokinetic (PK) and Pharmacodynamic (PD) 
similarity studies should be added to the examples provided in the 
goals letter. It is proposed that the language in the goals is revised 
to include PK and PD similarity studies. This enhancement is described 
in section I.H.1.c of the proposed BsUFA II commitment letter.

D. Prior Approval Manufacturing Supplements

    The review goal date for biosimilar prior approval manufacturing 
supplements is currently 6 months under BsUFA I, compared to 4 months 
for stand-alone biologics under PDUFA. Therefore, to increase 
consistency among user fee programs, it is proposed that prior approval 
manufacturing supplements are reviewed in 4 months, instead of 6 
months, with a phased-in performance goal. The language for prior 
approval supplements is included in section I.A.3 of the proposed BsUFA 
II commitment letter.

E. Meeting Management

    The enhancements in this section focus on FDA's ability to better 
manage meetings with sponsors of 351(k) applications. The details for 
these enhancements can be found in section

[[Page 64174]]

I.I of the proposed BsUFA II commitment letter.
1. Addition of a Written Response Meeting Format for Biosimilar Initial 
Advisory (BIA) and Biosimilar Program Development (BPD) Type 2 Meetings
    Currently, there is no mechanism to grant a meeting request and 
provide a written response in place of a face-to-face meeting, 
videoconference, or teleconference. From FY 2013 to FY2015, FDA 
provided written responses to sponsors for 16 out of 22 meetings that 
were denied or cancelled due to incomplete, premature, or unnecessary 
requests in order to support biosimilar development programs. Such 
responses are not on a user fee clock and are not tracked work. For 
BsUFA II, it is proposed that for BIA and BPD Type 2 meetings, the 
sponsor may request a written response to questions rather than a face-
to-face meeting, videoconference, or teleconference. If a written 
response is deemed appropriate, FDA will notify the requester of the 
date it intends to send the written response. This date will be 
consistent with the timeframes specified for the specific meeting type.
2. Increase the Scheduling Timeframe for BPD Type 2 Meetings
    The FDA has had challenges scheduling BPD type 2 meetings within 
the 75-day timeframe. Scheduling challenges occur due to an increasing 
number of Type 2 meetings to discuss novel and complex aspects of 
development that require extensive internal discussion. A review 
committee must address many of these aspects to ensure implementation 
of consistent scientific advice and policy concerning biosimilar 
development. Consequently, FDA is unable to answer and provide 
comprehensive responses to such questions at meetings within the 75-day 
timeframe. This results in unresolved issues and additional followup 
questions that ultimately leads to a delay in a sponsor's overall 
development program. To provide the necessary time for FDA discussions 
and to develop comprehensive responses, it is proposed that BPD Type 2 
Meetings occur within 90 calendar days, instead of 75 days, from 
receipt of the meeting request and meeting package with a phased in 
performance goal. Additionally, it is proposed that the Agency will 
send preliminary responses to the sponsor's questions contained in the 
background package no later than five calendar days before the face-to-
face videoconference or teleconference meeting date for BPD Type 2 and 
Type 3 meetings.
3. Reduce the Scheduling Timeframe for Biosimilar Initial Advisory 
(BIA) Meetings
    On average, five BIA meetings were scheduled per fiscal year from 
2013 to 2015. The content of a BIA meeting is limited to a general 
discussion on whether a proposed product could be developed as a 
biosimilar product and to provide high-level advice on the expected 
content of the development program. Targeted advice on the adequacy of 
any comparative data or extensive advice for any aspect of an ongoing 
biosimilar development program is not expected to be provided in a BIA 
meeting. The current 90-day scheduling timeframe may no longer be 
appropriate and should be shortened. Therefore, it is proposed for BIA 
meetings to occur within 75 calendar days, instead of 90 days, from 
receipt of the meeting request and meeting package.

F. Guidance Development

    FDA has received feedback that additional clarity is needed on 
regulatory processes and the scientific criteria for biosimilar 
development and approval to provide certainty to industry and other 
stakeholders related to Agency expectations. Therefore, it is proposed 
that FDA revise its guidance entitled ``Formal Meetings Between the FDA 
and Biosimilar Biological Product Sponsors or Applicants'' and update 
the draft guidance entitled ``Best Practices for Communication Between 
IND Sponsors and FDA During Drug Development'' to include 
communications between IND sponsors and FDA during biosimilar 
biological product development. Additionally, it is proposed that FDA 
publish draft or final guidance on several issues related to biosimilar 
biological product development including considerations in 
demonstrating interchangeability with a reference product; statistical 
considerations for analytic similarity for biosimilar biological 
products; processes and further considerations related to post-approval 
manufacturing changes for biosimilar biological products; clinical 
pharmacology data to support a demonstration of biosimilarity to a 
reference product; nonproprietary naming of biological products; and 
labeling for biosimilar biological products. The proposed goals related 
to guidance development are described in sections I.I.6 and II of the 
proposed BsUFA II commitment letter.

G. Improving FDA Hiring and Retention of Review Staff

    To speed and improve development of safe and effective biosimilar 
biological products for patients, FDA must hire and retain sufficient 
numbers and types of technical and scientific experts to efficiently 
conduct reviews of 351(k) applications. In order to strengthen this 
core function during BsUFA II, FDA proposes to implement a full time 
equivalent staff-based position management system capability and an 
online position classification system. In addition, FDA will complete 
implementation of corporate recruiting practices, augment hiring 
capacity with expert contractor support, establish a dedicated function 
for staffing of the human drug review program, establish clear goals 
for biosimilar review program hiring, and conduct comprehensive and 
continuous assessments of hiring and retention performance. These 
enhancements are described in section V of the proposed BsUFA II 
commitment letter.

H. Enhancing Capacity for Biosimilar Guidance Development, Reviewer 
Training, and Timely Communication

    In order to accelerate patient access to safe and effective 
biosimilar biological products and ensure accuracy, consistency, and 
timeliness FDA needs a more focused and better resourced capacity to 
coordinate key legal, scientific, review, and outreach functions in 
FDA's development phase advice and premarket review. It is proposed 
that FDA strengthen its staff capacity to: (1) Develop new regulations 
and guidance to clarify scientific criteria for biosimilar development 
and approval, and to provide certainty to industry and other 
stakeholders on key regulatory issues including the scope of eligible 
biosimilar biological products; (2) develop or revise manuals of policy 
and procedures, standard operating procedures, and review templates to 
facilitate rapid update and application of new policies and guidance by 
review staff, and to develop and deliver timely, comprehensive training 
to all Center for Drug Evaluation and Research and Center for Biologics 
Evaluation and Research review staff and special government employees 
involved in the review of 351(k) BLAs; (3) deliver timely information 
to the public to improve public understanding of biosimilarity and 
interchangeability; and (4) deliver information concerning the date of 
first licensure and the reference product exclusivity expiry date, to 
be included in the Purple

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Book.\1\ The language for enhanced capacity is included in section III 
of the proposed BsUFA II commitment letter.
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    \1\ The ``Purple Book'' lists biological products, including any 
interchangeable biological products, licensed by FDA under the 
Public Health Service Act.
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I. Enhancing Management of User Fee Resources

    FDA is committed to enhancing management of BsUFA resources and 
ensuring BsUFA user fee resources are administered, allocated, and 
reported in an efficient and transparent manner. In BsUFA II, 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 BsUFA program resource management, to publish a 5-year 
BsUFA 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. FDA also 
proposes to reduce the carryover balance to no greater than 21 weeks of 
the FY 2022 target revenue by the end of FY 2022. These enhancements 
are described in section IV of the proposed BsUFA II commitment letter.

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

    The current BsUFA fee structure references PDUFA fees each fiscal 
year and calculates biosimilar biological product development program 
(BPD) fees based on the PDUFA application fee. FDA and industry agreed 
that the BsUFA II 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. To address these issues, FDA proposes to 
discontinue the reduction of the biosimilar biological product 
application fee by the cumulative BPD fees paid by sponsors, to 
discontinue the establishment and supplement fees, to rename the 
product fee as the BsUFA Program fee, to modify the Program fee billing 
date to minimize the need for multiple billing cycles, and to add a 
limitation that a sponsor shall not be assessed more than five BsUFA 
Program fees for a fiscal year for products identified in each distinct 
approved biosimilar biological product application held by that 
sponsor.

K. Enhancements to User Fee Revenue Amounts and Adjustments

    FDA and industry agreed that the BsUFA II user fee revenue amounts 
and fee amounts should be independent of PDUFA and based on BsUFA 
program costs. FDA proposes to establish fees to generate a total of 
$45 million in user fee revenue for FY 2018. However, FDA also proposes 
that it can adjust this amount when setting the user fee amounts 
published in the FY 2018 Federal Register notice to reflect an updated 
assessment of the BsUFA workload, with the limitation that this 
adjustment cannot increase user fee revenue by more than $9 million 
(i.e. relative to the $45 million specified for FY 2018 user fee 
revenue). To enhance the predictability of user fee amounts, FDA 
proposes that the amount for each BsUFA fee cannot increase more than 
25 percent from the respective FY2018 fee amount until the capacity 
planning adjustment is effective and that FDA can otherwise modify the 
amount of the user fee revenue generated from each fee type each fiscal 
year. FDA proposes to adjust the annual user fee revenue amount for 
inflation, to develop a robust methodology for adjusting fees based on 
the capacity needs of the program, and to introduce an annual operating 
reserve adjustment to provide for adequate carryover resources.

IV. Purpose and Scope of the Meeting

    If you wish to attend this meeting, visit http://bsufapublicmeeting.eventbrite.com. Please register by October 19, 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 Amanda 
Roache (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/BiosimilarUserFeeActBsUFA/ucm461774.htm.

    Dated: September 13, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-22442 Filed 9-16-16; 8:45 am]
 BILLING CODE 4164-01-P


