BsUFA III Commitment Letter 2023 through 2027

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BIOSIMILAR BIOLOGICAL PRODUCT
REAUTHORIZATION PERFORMANCE GOALS
AND PROCEDURES FISCAL YEARS 2023
THROUGH 2027
I.

ENSURING THE EFFECTIVENESS OF THE BIOSIMILAR BIOLOGICAL
PRODUCT REVIEW PROGRAM

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A. Review Performance Goals

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B. Program for Enhanced Review Transparency and Communication for Original 351(k)
BLAs

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C. Guidance

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D. Review of Proprietary Names to Reduce Medication Errors

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E. Major Dispute Resolution

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F. Clinical Holds

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G. Special Protocol Question Assessment and Agreement

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H. Meeting Management Goals

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II.

ENHANCING BIOSIMILAR AND INTERCHANGEABLE BIOLOGICAL
PRODUCT DEVELOPMENT AND REGULATORY SCIENCE

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A. Promoting Best Practices in Communication between FDA and Sponsors During
Application Review

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B. Inspections and Alternate Tools to Evaluate Facilities

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C. Advancing Development of Biosimilar Biological-Device Combination Products
Regulated by CDER and CBER

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D. Advancing Development of Interchangeable Biosimilar Biological Products

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E. Regulatory Science to Enhance the Development of Biosimilar and Interchangeable
Biological Products

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III.

CONTINUED ENHANCEMENT OF USER FEE RESOURCE MANAGEMENT
A. Resource Capacity Planning

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B. Financial Transparency

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C. Management of Carryover Balance

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IV.

IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF

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A. Set Clear Goals for Biosimilar Biological Product Review Program Hiring

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B. Comprehensive and Continuous Assessment of Hiring and Retention

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V.

INFORMATION TECHNOLOGY GOALS

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A. Develop Data and Technology Modernization Strategy

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B. Monitor and Modernize Electronic Submission Gateway (ESG)

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VI.

DEFINITIONS AND EXPLANATION OF TERMS

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BIOSIMILAR BIOLOGICAL PRODUCT
AUTHORIZATION PERFORMANCE GOALS AND
PROCEDURES FOR FISCAL YEARS 2023
THROUGH 2027
This document contains the performance goals and procedures for the Biosimilar User Fee Act
(BsUFA) reauthorization for fiscal years (FYs) 2023-2027, known as BsUFA III. 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 biosimilar biological product review program that are important for facilitating
timely access to safe and effective biosimilar medicines for patients. FDA is committed to meeting
the performance goals specified in this letter, enhancing management of BsUFA resources, and
ensuring BsUFA user fee resources are administered, allocated, and reported in an efficient and
transparent manner.
Under BsUFA III, FDA is committed to ensuring effective scientific coordination and review
consistency, as well as efficient governance and operations across the biosimilar biological product
review program.
FDA and the regulated industry will periodically and regularly assess the progress of the biosimilar
biological product review program throughout BsUFA III. 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 biosimilar biological product review program.

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I.

ENSURING THE EFFECTIVENESS OF THE BIOSIMILAR BIOLOGICAL
PRODUCT REVIEW PROGRAM
A. REVIEW PERFORMANCE GOALS
1. Original and Resubmitted Biosimilar Biological Product Applications
a. Review and act on 90 percent of original biosimilar biological product
application submissions within 10 months of the 60 day filing date.
b. Review and act on 90 percent of resubmitted original biosimilar biological
product applications within 6 months of receipt.
2. Original and Resubmitted Supplemental Biosimilar Biological Product
Applications
a. Review and act on the following supplements within 3 months of receipt:
i.

Category A: Supplements seeking to update the labeling for a licensed
biosimilar or interchangeable product with regards to safety
information that has been updated in the reference product labeling
and is applicable to one or more indications for which the biosimilar or
interchangeable product is licensed.

b. Review and act on the following supplements within 4 months of receipt:
i.

Category B: Supplements seeking licensure for an additional
indication for a licensed biosimilar or interchangeable product when
the submission does not include new data sets (other than analytical in
vitro data obtained by use of physical, chemical and/or biological
function assays, if needed to support the scientific justification for
extrapolation), provided that:
1) The supplement does not seek a new route of administration,
dosage form, dosage strength, formulation or presentation; and
2) If the supplement is subject to section 505B(a) of the Federal Food,
Drug, and Cosmetic Act (FD&C Act), the supplement contains an
up-to-date agreed initial pediatric study plan (iPSP).

ii.

Category C: Supplements seeking to remove an approved indication
for a licensed biosimilar or interchangeable product.

c. Review and act on the following supplements within 6 months of receipt:
i.

Category D: Supplements seeking licensure for an additional
indication for a licensed biosimilar or interchangeable product when
the submission:
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1) Contains new data sets (other than efficacy data, data to support a
supplement seeking an initial determination of interchangeability,
or only analytical in vitro data obtained by use of physical,
chemical and/or biological function assays); or
2) Does not contain new data sets (other than analytical in vitro data
obtained by use of physical, chemical and/or biological function
assays) but is subject to section 505B(a) of the FD&C Act, and the
supplement does not contain an up-to-date agreed iPSP.
d. Review and act on the following supplements within 10 months of receipt for
the original submissions, and within 6 months of receipt for resubmissions:
i.

Category E: Supplements seeking licensure for an additional
indication for a licensed biosimilar or interchangeable product and
containing efficacy data sets.

ii.

Category F: Supplements seeking an initial determination of
interchangeability.

e. FDA will issue a letter to the applicant for 90% of original Category A
through D supplements within 60 calendar days of receipt. The letter will
acknowledge receipt of the submission and provide the date for FDA to take
action on the supplement.
i.

Applicants may include in their cover letter a request that FDA not
approve the supplement before a certain date, as long as that date is not
later than the BsUFA goal date.

f. A filing letter will be issued to the applicant for 90% of original Category E
and F supplements within 74 calendar days of receipt. Consistent with the
underlying principles articulated in the Good Review Management Principles
and Practices (GRMP) guidance, the letter will acknowledge receipt of the
submission and inform the applicant of the planned review timeline and
whether substantive review issues were identified. If no substantive review
issues were identified during the filing review, FDA will so notify the
applicant.
3. 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.
4. Goals Summary Tables

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Table 1: Original and Resubmitted Applications and Category A- F
Supplements
Original Biosimilar Biological Product
Application Submissions

90% in 10 months of the 60 day filing date

Resubmitted Original Biosimilar
Biological Product Applications

90% in 6 months of the receipt date

Category A Supplements
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(original and resubmitted)

Category B and C Supplements
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(original and resubmitted)

Category D Supplements
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(original and resubmitted)

Original Category E and F Supplements

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FY 2023: 70% in 3 months of the receipt date

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FY 2024: 80% in 3 months of the receipt date

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FY 2025: 90% in 3 months of the receipt date

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FY 2026: 90% in 3 months of the receipt date

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FY 2027: 90% in 3 months of the receipt date

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FY 2023: 70% in 4 months of the receipt date

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FY 2024: 80% in 4 months of the receipt date

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FY 2025: 90% in 4 months of the receipt date

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FY 2026: 90% in 4 months of the receipt date

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FY 2027: 90% in 4 months of the receipt date

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FY 2023: 70% in 6 months of the receipt date

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FY 2024: 80% in 6 months of the receipt date

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FY 2025: 90% in 6 months of the receipt date

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FY 2026: 90% in 6 months of the receipt date

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FY 2027: 90% in 6 months of the receipt date

90% in 10 months of the receipt date

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Resubmitted Category E and F
Supplements

90% in 6 months of the receipt date

Table 2: Manufacturing Supplements

Manufacturing
Supplements

PRIOR APPROVAL

ALL OTHER

90% in 4 months of the
receipt date

90% in 6 months of the
receipt date

5. Review Performance Goal Extensions
a. Major Amendments
i.

A major amendment to an original application, supplement with clinical
data, 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
study report; major re-analysis of previously submitted study(ies);
submission of a risk evaluation and mitigation strategy (REMS) with
elements 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 Good
Review Management Principles and Practices (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

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i.

All original applications 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.

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 supplement with clinical data, 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.

B. PROGRAM FOR ENHANCED REVIEW TRANSPARENCY AND
COMMUNICATION FOR ORIGINAL 351(k) 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
original Biologics License Applications (BLAs) submitted under section 351(k) of the
Public Health Service Act (“351(k) BLAs”), including applications that are
resubmitted following a Refuse-to-File decision, received from October 1, 2022,
through September 30, 2027. 1 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 biosimilar and interchangeable biological products.
The standard approach for the review of original 351(k) 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 original 351(k) BLA. The Formal
Communication Plan may include elements of the standard approach (e.g., a midcycle communication or a late-cycle meeting) as well as other interactions that
The “Program for Enhanced Review Transparency and Communication for Original 351(k) BLAs”
(referred to as “the Program” and described in this goals letter) is distinct from the statutory term,
“biosimilar biological product development program,” which is defined in section 744G of the Federal
Food, Drug, and Cosmetic (FD&C Act) as “the program under [the statutory BsUFA fee provisions] for
expediting the process for the review of submissions in connection with biosimilar biological product
development.” Section 744G(6) of the FD&C Act.

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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.
The remainder of this 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
BPD Type 4 (pre-351(k) BLA) meeting. This meeting will be attended by the
FDA review team, including appropriate senior FDA staff.
a. The BPD Type 4 (pre-351(k) 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 regarding the
approach to developing the content for REMS, where applicable, patient
labeling (e.g., Medication Guide and Instructions For Use) and, where
applicable, the development of a Formal Communication Plan. These
discussions will be summarized at the conclusion of the meeting and reflected
in the FDA meeting minutes.
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
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.

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i.

Examples of application components that may be appropriate for
delayed submission include; stability updates, the final audited report
of a preclinical study (e.g., toxicology) where the final draft report is
submitted with the original application, or a limited amount of the data
from an assessment of a single transition from the reference product to
the proposed biosimilar biological product, where applicable.

ii.

Major components of the application (e.g., the complete analytical
similarity assessment, the complete study report of a comparative
clinical study or the full study report of necessary immunogenicity
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 BPD Type 4 (pre351(k) BLA) meeting, at the time of original submission of the application. If the
applicant does not have a BPD Type 4 (pre-351(k) 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.A.1.a.

ii.

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

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.

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iv.

The resubmission goal described in Section I.A.1.b 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 substantive review issues identified during the initial filing
review to the applicant in the “Day 74 letter.” If no substantive review issues
were identified during the filing review, FDA will so notify the applicant. FDA’s
filing review represents a preliminary review of the application and is not
indicative of deficiencies that may be identified later in the review cycle.
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 timeline for review of the application included in the
Day 74 letter for applications in the Program will include:
a. the planned date for the internal mid-cycle review meeting,
b. preliminary plans on whether to hold an Advisory Committee (AC) meeting to
discuss the application,
c. a target date for communication of feedback from the review division to the
applicant regarding proposed labeling and any postmarket requirements or
postmarket commitments the Agency will be requesting.
4. Review performance goals: For original 351(k) BLA submissions that are filed
by FDA under the Program, the BsUFA 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 original 351(k) BLA submissions within 10
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
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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.
The update should include any significant issues identified by the review team to
date, any information requests, and information regarding major concerns with the
following:
a. The analytical similarity data, including the potential relevance of any issues
(e.g. data analysis issues or potential clinical impact of observed analytical
differences), intended to support a demonstration that the proposed biosimilar
biological product is highly similar to the reference product.
b. The data intended to support a demonstration of no clinically meaningful
differences, including discussion of any immunogenicity issues.
c. The data intended to support a demonstration of interchangeability.
d. CMC issues.
In addition, the update should include preliminary review team thinking regarding
the content of the proposed REMS, where applicable, proposed date(s) for the
late-cycle meeting, updates regarding plans for the AC meeting (if an AC meeting
is anticipated), and other projected milestone dates for the remainder of the
review cycle.
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 Advisory Committee (AC)
meeting, the following parameters apply:
i.

FDA intends to convene AC meetings no later than 2 months prior to
the BsUFA goal date. The late-cycle meeting will occur not less than 12
calendar days before the date of the AC meeting.

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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 committee 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 prior to the BsUFA goal
date.
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 before the late-cycle meeting. The package will consist of any
discipline review (DR) letters issues to date, 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 content of proposed
REMS or other risk management actions, where applicable.
e. Late-Cycle Meeting Discussion Topics: Potential topics for discussion at the
late-cycle meeting include:
i.

major deficiencies identified to date;

ii.

analytical similarity data, including the potential relevance of any issues
(e.g. data analysis issues or potential clinical impact of observed
analytical differences), intended to support a demonstration that the
proposed biosimilar biological product is highly similar to the reference
product;

iii.

data intended to support a demonstration of no clinically meaningful
differences, including discussion of any immunogenicity issues;

iv.

data intended to support a demonstration of interchangeability;

v.

CMC issues;

vi.

inspectional findings identified to date;

vii.

issues to be discussed at the AC meeting (if planned);

viii.

current assessment of the content of proposed REMS or other risk
management actions, where applicable;
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ix.

information requests from the review team to the applicant; and
additional data or analyses the applicant may wish to submit.

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 BsUFA goal
date.
7. Inspections: FDA’s goal is to complete all GCP, GLP, and GMP inspections for
applications in the Program within 10 months of the date of original receipt of the
application. This will allow 2 months at the end of the review cycle to attempt to
address any deficiencies identified by the inspections.
C. GUIDANCE
FDA and industry share a commitment to ensuring an efficient and effective review
process for all applications subject to the BsUFA program.
In light of the new, expedited timelines for supplements, FDA will issue guidance
and/or a MAPP on classifying supplements to a licensed 351(k) BLA for purposes of
determining review timelines. FDA will publish a draft guidance for public comment
and/or a MAPP no later than the end of FY 2023. 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.
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 biosimilar biological product proprietary names during the biosimilar biological
product development (BPD) phase and during FDA’s review of a marketing
application:
1. Proprietary Name Review Performance Goals During The BPD Phase
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).

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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 biosimilar biological product proprietary name submissions
filed within 90 days of receipt. Notify sponsor of tentative acceptance/nonacceptance.
b. A supplemental review will be done meeting the above review performance
goals if the proprietary name has been submitted previously (during the BPD
phase) 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
biosimilar biological product applications and supplements (as defined in BsUFA)
that cannot be resolved at the signatory authority 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 responses 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.

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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).
e. In these cases, once the required information is received by the Agency
(including any advice from an advisory committee), the person to whom the
appeal was made, again has 30 calendar days from the receipt of the required
information in which to either deny or grant 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. Note: If the Agency decides to present the issue to an advisory committee and
there are not 30 days before the next scheduled advisory committee, the issue
will be presented at the following scheduled committee meeting to allow
conformance with advisory committee administrative procedures.
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 related 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., are the clinical endpoints adequate to assess

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whether there are clinically meaningful differences between the proposed
biosimilar biological product and the reference product).
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 any necessary clinical study or
studies to prove biosimilarity and/or interchangeability (e.g., protocols for
pharmacokinetics and pharmacodynamics studies, protocols for comparative
clinical studies that will form the primary basis for demonstrating that there
are no clinically meaningful differences between the proposed biosimilar
biological product and the reference product, and protocols for clinical studies
intended to support a demonstration of interchangeability). For such protocols
to qualify for this comprehensive protocol assessment, the sponsor must have
had a BPD Type 2b or 3 Meeting, as defined in section I.I, below, 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. 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 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 protocols assessments and agreement requests
completed and returned to sponsor within 45 days.
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 BsUFA meetings between sponsors and FDA consist of Biosimilar Initial
Advisory and BPD Type 1-4 meetings. These meetings are further described below.
•

A Biosimilar Initial Advisory Meeting is an initial assessment limited to a general
discussion regarding whether licensure under section 351(k) of the Public Health
Service Act may be feasible for a particular product, and, if so, general advice on

17

the expected content of the development program. Such term does not include
any meeting that involves substantive review of summary data or full study
reports. Only one BIA meeting may be granted per program. While preliminary
comparative analytical data from at least one lot of the proposed biosimilar or
interchangeable product compared to the U.S.-licensed reference product is not
required for the meeting request, sufficient information should be provided with
the meeting request to enable FDA to make such a preliminary determination
related to potential licensure under section 351(k) and to provide meaningful
advice. This should include, as appropriate:
•

Identification of reference product.

•

The indications intended to be sought for licensure.

•

A comparative analytical similarity plan, including preliminary
identification of the Critical Quality Attributes and planned
characterization methods.

•

If a sponsor seeks to utilize a non-US-licensed comparator during
development, the proposed bridging strategy for US-licensed reference
product and that comparator should be provided.

•

A conceptual plan for non-clinical studies or rationale and justification of
why such studies may not needed.

•

A conceptual description of the planned clinical pharmacokinetics and/or
pharmacodynamic study(ies), including proposed endpoints.

•

If the sponsor plans to conduct a comparative clinical safety and efficacy
study, a conceptual plan should be provided. This would include the
patient population and proposed endpoints.

•

Any guidance already received from other health authorities on product
development.

•

Identification to the FDA of the regulatory status in other jurisdictions.

•

A BPD Type 1 Meeting is a meeting which is necessary for an otherwise stalled
drug development program to proceed (e.g. meeting to discuss clinical holds,
dispute resolution meeting), a special protocol assessment meeting, or a meeting
to address an important safety issue.

•

A BPD Type 2a Meeting is a meeting focused on a narrow set of issues (e.g.,
often one, but not more than two issues and associated questions), requiring input
from no more than 3 disciplines or review divisions. In order to request a Type 2a
meeting, sponsors must first have had a BIA or other BPD meeting with the
Agency. Requests could include:

18

•

Defined CMC post-approval commitments (e.g., related to analytical
methods) discussing the approach in advance of conducting the study to
ensure the approach is in line with the Agency’s expectations.

•

Immunogenicity testing strategy following prior FDA
recommendations/feedback.

•

Feedback on revised study design when revisions are based on prior FDA
feedback.

•

A BPD Type 2b Meeting is a meeting to discuss a specific issue (e.g., proposed
study design or endpoints) or questions where FDA will provide advice regarding
an ongoing biosimilar biological product development program. This meeting
may include substantive review of summary data, but does not include review of
full study reports.

•

A BPD Type 3 Meeting is an in depth data review and advice meeting regarding
an ongoing biosimilar biological product development program. This meeting
includes substantive review of full study reports, FDA advice regarding the
similarity between the proposed biosimilar biological product and the reference
product, and FDA advice regarding additional studies, including design and
analysis.

•

A BPD Type 4 Meeting is a pre-submission meeting to discuss the format and
content of a complete application for an original biosimilar biological product
application under the Program or supplement submitted under 351(k) of the PHS
Act. The purpose of this meeting is to discuss the format and content of the
planned submission and other items, including identification of those studies that
the sponsor is relying on to support a demonstration of biosimilarity or
interchangeability, discussion of any potential review issues identified based on
the information provided, identification of the status of ongoing or needed studies
to adequately to address the Pediatric Research Equity Act (PREA), acquainting
FDA reviewers with the general information to be submitted in the marketing
application (including technical information), and discussion of the best approach
to the presentation and formatting of data in the marketing application.

1. Response to Meeting Requests
a. Procedure: FDA will notify the sponsor in writing of the date, time, and place
for the meeting, as well as expected Center participants following receipt of a
formal meeting request and background package. Table 1 below indicates the
timeframes for FDA’s response to a meeting request.

19

Table 1:

Meeting Type

Response Time (calendar days)

Biosimilar Initial Advisory

21

BPD Type 1

14

BPD Type 2a, 2b, 3 and 4

21

i.

For Biosimilar Initial Advisory and BPD Type 2a or 2b meetings, the
sponsor may request a written response to its questions, rather than a
face-to-face meeting 2 or teleconference. If a written response is
deemed appropriate, FDA will notify the sponsor of the date it intends
to send the written response. This date will be consistent with the
timeframes specified in Table 2 below for the specific meeting type.

ii.

For the BPD Type 2a meeting, 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 sponsor 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 timeframe for a Type 2a
meeting. If the sponsor believes a face-to-face Type 2a meeting is
valuable and warranted, then the sponsor may provide a rationale in a
follow-up correspondence explaining why a face-to-face meeting is
valuable and warranted, and FDA will reconsider this request. If FDA
agrees to grant the face-to-face format, the Agency will strive to
schedule the meeting to occur within 60 days of FDA’s receipt of the
meeting request.

b. Performance Goal: FDA will respond to meeting requests and provide
notification within the response times noted in Table 1 for 90 percent of each
meeting type.

A “face-to-face” meeting includes both in-person meetings and virtual meetings on IT platforms that
allow for both audio and visual communication.
2

20

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 in Table 2. Table 2 below
indicates the timeframes for FDA to schedule the meeting following receipt of
a formal meeting request and background package, or in the case of a written
response for Biosimilar Initial Advisory and BPD Type 2a and 2b meetings,
the timeframes for the Agency to send the written response. If the requested
date for any meeting type is greater than the specified timeframe, the meeting
date should be within 14 calendar days of the requested date.
Table 2:
Meeting Type

Meeting Scheduling or Written Response Time

Biosimilar Initial
Advisory

75 calendar days from receipt of meeting request and
background package

BPD Type 2a

60 calendar days from receipt of meeting request and
background package

BPD Type 2b

90 calendar days from receipt of meeting request and
background package
Meeting Scheduling Time

BPD Type 1

30 calendar days from receipt of meeting request and
background package

BPD Type 3

120 calendar days from receipt of meeting request and
background package

BPD Type 4

60 calendar days from receipt of meeting request*

*Note the background package for BPD Type 4 meetings must be received
no later than 14 calendar days after FDA receipt of the meeting request.

21

b. Performance goal:
Table 3:
Meeting Type

Goal
FY 2023: 50% of meetings are held or written
responses are sent within the timeframe
FY 2024: 60% of meetings are held or written
responses are sent within the timeframe

BPD Type 2a

FY 2025: 70% of meetings are held or written
responses are sent within the timeframe
FY 2026: 80% of meetings are held or written
responses are sent within the timeframe
FY 2027: 90% of meetings are held or written
responses are sent within the timeframe

Biosimilar Initial
Advisory and BPD
Type 2b

90% of meetings are held or written responses are
sent within the timeframe

BPD Type 1, 3, and 4

90% of meetings are held within the timeframe for
each meeting type

3. Preliminary Responses
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 face-to-face or teleconference meeting date for BPD Type 2b
and Type 3 meetings.

22

b. Performance goal:
Table 4:

Meeting Type

BPD Types 2b and
3

90% of preliminary responses to questions are issued by
FDA no later than five calendar days before the meeting
date

4. Meeting Minutes
a. Procedure: The Agency will prepare minutes which 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 necessary if the Agency transmits a written response
for Biosimilar Initial Advisory, BPD Type 2a, or 2b meetings.
b. Performance Goal: 90% of minutes are issued within 30 calendar days of the
date of the meeting.
5. Conditions: For a meeting to qualify for these performance goals:
a. A written request and supporting documentation (i.e., the background
package) must be submitted to the appropriate review division or office. The
background package must be submitted at the same time as the written request
for Biosimilar Initial Advisory, BPD Type 1, 2a, 2b and 3 meetings. For BPD
Type 4 meetings, the background package must be received no later than 14
calendar days after FDA receipt of the written request.
b. The request must provide:
i.

A brief statement of the purpose of the meeting, the sponsor’s proposal
for the type of meeting, and the sponsor’s proposal for a face-to-face
meeting, teleconference, or for a written response (Biosimilar Initial
Advisory and BPD Type 2a and 2b meetings only);

ii.

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

iii.

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

23

iv.

A list of questions, grouped by discipline (For each question there
should be a brief explanation of the context and purpose of the
question);

v.

A listing of planned external attendees; and

vi.

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

vii.

Suggested dates and times (e.g., morning or afternoon) for the meeting
that are within or beyond the appropriate time frame of the meeting type
being requested.

c. The Agency concurs that the meeting will serve a useful purpose (i.e., it is not
premature or clearly unnecessary). However, requests for BPD Type 2b, 3,
and 4 Meetings will be honored except in the most unusual circumstances.
The Center may determine that a different type of meeting (i.e., Biosimilar
Initial Advisory, or BPD Type 1-4) is more appropriate and it may grant a
meeting of a different type than requested, which may require the payment of a
biosimilar biological product development fee as described in section 744H of
the Federal Food, Drug, and Cosmetic Act before the meeting will be provided.
If a biosimilar biological product development fee is required under section
744H, and the sponsor does not pay the fee within the time frame required under
section 744H, the meeting will be cancelled. If the sponsor pays the biosimilar
biological product development fee after the meeting has been cancelled due to
non-payment, the time frame described in section I.I.1.a will be calculated from
the date on which FDA received the payment, not the date on which the sponsor
originally submitted the meeting request.
Sponsors are encouraged to consult available FDA guidance to obtain further
information on recommended meeting procedures.
6. Guidance, Clarity, and Transparency
a. Guidance: By September 30, 2023, FDA will issue a revised draft of the
existing draft guidance on “Formal Meetings Between the FDA and Sponsors
or Applicants of BsUFA Products” with information pertaining to BIA, Type
2a, and Type 4 meetings, as well as the follow-up opportunity described
below. In addition, FDA will update relevant MAPPs and SOPPs.
b. Follow-up opportunity: For all meeting types, to ensure the sponsor’s
understanding of FDA feedback from meeting discussions or a WRO,
sponsors may submit clarifying questions to the agency. Only questions of a
clarifying nature will be permitted, i.e., to confirm something in minutes or a
WRO issued by FDA, rather than raising new issues or new proposals. FDA
will develop criteria and parameters for permissible requests, and FDA may
exercise discretion about whether requests are in-scope. The clarifying
24

questions should be sent in writing as a “Request for Clarification” to the
FDA within 20 calendar days following receipt of meeting minutes or a WRO.
For questions that meet the criteria, FDA will issue a response in writing
within 20 calendar days of receipt of the clarifying questions. FDA’s response
will reference the original meeting minutes or WRO.
c. Transparency: On or before March 31st, 2025, FDA will publish on its public
webpage certain metrics regarding the new Type 2a meeting and sponsor
requests for face-to-face meetings for year 1 and year 2 of BsUFA III.

II.

ENHANCING BIOSIMILAR AND INTERCHANGEABLE BIOLOGICAL
PRODUCT DEVELOPMENT AND REGULATORY SCIENCE
To facilitate the timely development of biosimilar and interchangeable biological
products and their availability to patients, FDA will focus on enhancing communications
during application review, including inspection communications, and advancing the
development of combination and interchangeable products. FDA will also pilot a
regulatory science program focused on enhancing regulatory decision-making and
facilitating science-based recommendations in areas foundational to biosimilar and
interchangeable biological development.
A. PROMOTING BEST PRACTICES IN COMMUNICATION BETWEEN FDA
AND SPONSORS DURING APPLICATION REVIEW
The utilization of best practices in communication during application review are the
responsibility of both industry and FDA. Efforts from both industry and FDA are
needed in order to continue advancement, improvement, and updating of best
practices.
To continue to enhance communication with sponsors during biosimilar application
review in BsUFA III, FDA will update relevant guidances, MAPPs and SOPPs, as
appropriate, on or before December 31st, 2023 regarding best practices in
communication. FDA will utilize input from the BsUFA II final assessment of the
Program, FDA experiences, and discussion from a meeting with industry on best
practices in FY 2022 to update the above documents, as appropriate.
B. INSPECTIONS AND ALTERNATIVE TOOLS TO EVALUATE FACILITIES
1. Enhancing Inspection Communication for Applications, not Including
Supplements
FDA and industry believe enhanced communication between review teams and
industry on certain pre-license inspections can facilitate an efficient application
review process.

25

When FDA determines for an application, not including supplements, that it is
necessary to conduct a pre-license inspection at a time when the product identified
in the application is being manufactured, FDA’s goal is to communicate its intent
to inspect a manufacturing facility at least 60 days in advance of the pre-license
inspection and no later than mid-cycle. FDA reserves the right to conduct
manufacturing facility inspections at any time during the review cycle, whether or
not FDA has communicated to the facility the intent to inspect.
2. Alternative Tools to Assess Manufacturing Facilities Named in Pending
Applications
During the COVID-19 public health emergency, the FDA expanded its use of
alternate tools for assessing facilities named in applications, including exercising
its authority to request records and other information in advance of or in lieu of an
inspection, granted per section 704(a)(4) of the Federal Food, Drug, and Cosmetic
Act (FD&C Act) (21 U.S.C. 374(a)). Where appropriate, the Agency also
increased the use of information, including inspection reports, shared by trusted
foreign regulatory partners through mutual recognition agreements and other
confidentiality agreements. As FDA continues to gain experience and lessons
learned from the use of these tools, FDA will communicate its thinking on the use
of such methods beyond the pandemic.
On or before September 30, 2023, FDA will issue draft guidance on the use of
alternative tools to assess manufacturing facilities named in pending applications
(e.g., requesting existing inspection reports from other trusted foreign regulatory
partners through mutual recognition and confidentiality agreements, requesting
information from applicants, requesting records and other information directly
from facilities and other inspected entities, and, as appropriate, utilizing new or
existing technology platforms to assess manufacturing facilities). The guidance
will incorporate best practices, including those in existing published documents,
from the use of such tools during the COVID-19 pandemic. FDA will work
towards the goal of publishing final guidance within 18 months after the close of
the public comment period on the draft guidance. If, after receiving comments on
the draft guidance, FDA determines that the guidance requires substantive
changes on which further public comments are warranted, FDA will issue a
revised draft guidance within those 18 months instead. It then will work towards
publishing a final guidance within 18 months after the close of the public
comment period on the revised draft guidance.
C. ADVANCING THE DEVELOPMENT OF BIOSIMILAR BIOLOGICALDEVICE COMBINATION PRODUCTS REGULATED BY CDER AND CBER
1. Use-Related Risk Analysis (URRA)
Sponsors employ URRA to identify the need for risk mitigation strategies and to
design a human factors (HF) validation study. Based on a URRA, a sponsor may
propose that a HF validation study is not needed to be submitted to support the

26

safe and effective use of a biosimilar biologic-device combination product. FDA
will establish the following procedures for review of URRAs for combination
products:
The sponsor should submit a request for review of their URRA to their IND.
The submission should include specific questions, justification that a HF
validation study is not needed to be submitted including any supporting
information, and scientific and regulatory requirements for which the sponsor
seeks agreement.
Within 60 days of Agency receipt of the URRA and specific questions, the
Agency will provide a written response to the sponsor that includes a succinct
assessment of the URRA and answers to the questions posed by the sponsor.
If the Agency does not agree that either the URRA or the sponsor’s
justification are adequate to support the absence of a HF validation study, the
reasons for the disagreement will be explained in the response.
URRA submission: performance goals for FDA will be phased in, starting FY
2024 as follows:
i.

By FY 2024, review and notify sponsor of agreement or nonagreement with comments for 50% of filed submissions, within 60
days of receipt of submission.

ii.

By FY 2025, review and notify sponsor of agreement or nonagreement with comments for 70% of filed submissions, within 60
days of receipt of submission.

iii.

By FY 2026, review and notify sponsor of agreement or nonagreement with comments for 90% of filed submissions, within 60
days of receipt of submission.

iv.

By FY 2027, review and notify sponsor of agreement or nonagreement with comments for 90% of filed submissions, within 60
days of receipt of submission.

On or before the end of FY 2024, FDA will publish new draft or revised
guidance for review staff and industry describing considerations related to
biosimilar biologic-device combination products on the topics noted below.
Guidance will convey FDA’s current thinking regarding how a URRA along
with other information can be used to inform when the results from an HF
validation study may need to be submitted to a marketing application. The
guidance will provide a comprehensive, systematic and stepwise approach
with examples, when applicable, to illustrate how to make this determination.

27

Sponsors may still elect to submit a URRA with a HF validation protocol and
will only be subject to timelines in Section II.C.2., For Human Factor
Validation Study Protocols.
2. Human Factor Validation Study Protocols
Human factors studies are conducted to evaluate the user interface of a biosimilar
biologic-device combination product to eliminate or mitigate use-related hazards
that may affect the safe and effective use of the combination product. Over the
past decade, more combination products have been developed to deliver
therapeutics via different routes of administration (e.g., parenteral, inhalation)
with complex engineering designs. HF validation protocols are reviewed during
the IND stage with the goal towards developing a final finished combination
product that supports the marketing application. To achieve this objective, FDA
will establish the following procedures for review of HF validation study
protocols:
The sponsor should submit a human factors protocol to the IND with specific
questions, including 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).
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.
Performance goals for FDA will be as follows:
Beginning in FY 2023, review and provide sponsor with written comments for
90% of human factors validation protocol submissions within 60 days of
receipt of protocol submission.
D. ADVANCING DEVELOPMENT OF INTERCHANGEABLE BIOSIMILAR
BIOLOGICAL PRODUCTS
FDA is committed to a focused effort to further advance the development of safe and
effective interchangeable biosimilar biological products. The effort will address
current needs, prospectively identify future needs and incorporate the following
components:
1. Research: FDA will leverage the BsUFA III Regulatory Science Program to
advance product development, assist regulatory decision-making, and support
guidance development for interchangeable biosimilar products.

28

2. Foundational guidance development: FDA will develop foundational guidances
for the development of interchangeable biosimilar biological products:
a. On or before September 30, 2025, FDA will publish a draft guidance
describing considerations for developing presentations, container closure
systems and device constituent parts for proposed interchangeable biosimilar
biological products. FDA will work towards the goal of publishing final
guidance within 18 months after the close of the public comment period on
the draft guidance. If, after receiving comments on the draft guidance, FDA
determines that the guidance requires substantive changes on which further
public comments are warranted, FDA will issue a revised draft guidance
within those 18 months instead. It will then work towards publishing a final
guidance within 18 months after the close of the public comment period on
the revised draft guidance.
b. On or before September 30, 2023, FDA will publish draft guidance on
labeling for interchangeable biosimilar biological products. FDA will work
towards the goal of publishing final guidance within 18 months after the close
of the public comment period on the draft guidance. If, after receiving
comments on the draft guidance, FDA determines that the guidance requires
substantive changes on which further public comments are warranted, FDA
will issue a revised draft guidance within those 18 months instead. It will then
work towards publishing a final guidance within 18 months after the close of
the public comment period on the revised draft guidance.
c. On or before September 30, 2024, FDA will publish a draft guidance on
promotional labeling and advertising considerations for interchangeable
biosimilar biological products. FDA will work towards the goal of publishing
final guidance within 18 months after the close of the public comment period
on the draft guidance. If, after receiving comments on the draft guidance,
FDA determines that the guidance requires substantive changes on which
further public comments are warranted, FDA will issue a revised draft
guidance within those 18 months instead. It will then work towards publishing
a final guidance within 18 months after the close of the public comment
period on the revised draft guidance.
d. On or before September 30, 2024, FDA will publish a draft guidance on the
nature and type of information, for different reporting categories, a sponsor
should provide to support post-approval manufacturing changes to approved
biosimilar and interchangeable biosimilar biological products. FDA will work
towards the goal of publishing final guidance within 18 months after the close
of the public comment period on the draft guidance. If, after receiving
comments on the draft guidance, FDA determines that the guidance requires
substantive changes on which further public comments are warranted, FDA
will issue a revised draft guidance within those 18 months instead. It then will
work towards publishing a final guidance within 18 months after the close of
the public comment period on the revised draft guidance.
29

3. Stakeholder Engagement: FDA will hold a scientific workshop on the
development of interchangeable products to help identify future needs (e.g.,
guidance, research) on or before October 31, 2025. Within 12 months following
the public workshop, FDA will issue a draft strategy document for public
comment that outlines the specific actions the agency will take to facilitate the
development of interchangeable biosimilar biological products. The strategy
document may identify activities and deliverables including updating or creating
new procedures, MAPPs, SOPPs, guidances, and other changes to FDA’s
scientific and other programs related to the topics discussed in the workshop. The
strategy document will also include proposed timeframes for the specific actions
outlined in the document. FDA will consider public input and will publish a final
strategy document within 9 months after the close of the public comment period
on the draft strategy document.
E. REGULATORY SCIENCE TO ENHANCE THE DEVELOPMENT OF
BIOSIMILAR AND INTERCHANGEABLE BIOLOGICAL PRODUCTS
FDA is committed to enhancing regulatory decision-making and facilitating sciencebased recommendations in areas foundational to biosimilar development. Starting in
FY 2023, FDA will pilot a regulatory science program broadly applicable to
facilitating biosimilar and interchangeable biological product development. Project
goals should not be specific to a product or product class 3. The pilot program will
focus on two demonstration projects: (1) advancing the development of
interchangeable products, and (2) improving the efficiency of biosimilar product
development.
1. Advancing Development of Interchangeable Products
This demonstration project will be focused on progressing research to advance the
development of interchangeable products. Specifically, this demonstration project
will:
a. Investigate and evaluate the data and information (including Real World
Evidence) needed to meet the safety standards for determining
interchangeability under section 351(k)(4) of the PHS Act, including:
i.

Investigate and evaluate informative, scientifically appropriate
methodologies to assess the potential impact of differences between
proposed interchangeable biosimilar and reference product
presentations and container closure systems.

ii.

Investigate and evaluate informative, scientifically appropriate
methodologies to predict immunogenicity by advancing the knowledge
of analytical (including physical, chemical and biological function

See Guidance for Industry: Questions and Answers on Biosimilar Development and the BPCI Act,
December 2018 Biosimilars, Revision 1, Q&A II.2.

3

30

assays), pharmacological and clinical correlations as relates to
interchangeability.
2. Improving the Efficiency of Biosimilar Product Development
This demonstration project will be focused on progressing research to advance the
efficiency of biosimilar product development, enhance regulatory decisionmaking based on the latest scientific knowledge, and advance the use of
innovative scientific methodologies and experience with biosimilars. Specifically,
this demonstration project will:
a. Review and evaluate opportunities for streamlining and targeting biosimilar
product development in consideration of scientific advancements in analytical
(including physical, chemical and biological function assays), and
pharmacological assessments and experience with prior biosimilar product
development and marketed biosimilar products.
b. Investigate and evaluate informative, scientifically appropriate methodologies
to predict immunogenicity by advancing the knowledge of analytical
(including physical, chemical and biological function assays),
pharmacological and clinical correlations as it relates to biosimilarity.
3. Stakeholder Engagement: On or before October 31, 2025, FDA will hold a
public meeting to review the progress of the demonstration projects and solicit
input on future priorities. An interim report will be posted on FDA’s website in
advance of the public meeting. On or before September 30, 2027, a final summary
report of outcomes from the pilot program will be posted on FDA’s website.
4. Deliverables: Within 12 months of the completion of the demonstration projects,
FDA will use the learnings from the demonstration projects to publish a
comprehensive strategy document outlining specific actions the agency will take
to facilitate the development of biosimilar and interchangeable biological
products. The comprehensive strategy document may include updating or creating
new procedures, MAPPs, SOPPs, and guidances and will also include proposed
timeframes for the specific actions outlined in the document. The comprehensive
strategy document will be distinct from the final summary report of the pilot
program.

III.

CONTINUED ENHANCEMENT OF USER FEE RESOURCE MANAGEMENT
FDA is committed to ensuring the sustainability of BsUFA program resources and to
enhancing the operational agility of the BsUFA program. FDA will build on the financial
enhancements included in BsUFA II and continue activities in BsUFA III to ensure
optimal use of user fee resources and the alignment of staff to workload through the
continued maturation and assessment of the Agency’s resource capacity planning

31

capability. FDA will also continue activities to promote transparency of the use of
financial resources in support of the BsUFA program.
A. RESOURCE CAPACITY PLANNING
FDA will continue activities to mature the Agency’s resource capacity planning
function, including utilization of modernized time reporting, to support enhanced
management of BsUFA resources in BsUFA III and help ensure alignment of user fee
resources to staff workload.
1. Resource Capacity Planning Implementation
a. On or before the end of the 2nd quarter of FY 2023, FDA will publish an
implementation plan that will describe how resource capacity planning and
time reporting will continue to be implemented during BsUFA III. This
implementation plan will address topics relevant to the maturation of resource
capacity planning, including, but not limited to, detailing FDA’s approach to:
The continued implementation of the Agency’s resource capacity
planning capability, including:
1) The continual improvement of the Capacity Planning Adjustment
(CPA); and
2) The continual improvement of time reporting and its utilization in
the CPA.
The integration of resource capacity planning analyses in the Agency’s
resource and operational decision-making processes.
b. FDA will provide annual updates on the FDA website on the Agency’s
progress relative to activities detailed in this implementation plan on or before
the end of the 2nd quarter of each subsequent fiscal year.
c. FDA will document in the annual BsUFA Financial Report how the CPA fee
revenues are being utilized.
2. Resource Capacity Planning Assessment
On or before the end of FY 2025, an independent contractor will complete and
publish an evaluation of the resource capacity planning capability. This will
include an assessment of the following topics:
The ability of the CPA to forecast resource needs for the BsUFA program,
including an assessment of the scope of the workload drivers in the CPA and
their ability to represent the overall workload of the BsUFA program;

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Opportunities for the enhancement of time reporting toward informing
resource needs; and
The integration and utilization of resource capacity planning information
within resource and operational decision-making processes of the BsUFA
program.
The contractor will provide options and recommendations in the evaluation
regarding the continued enhancement of the above topics as warranted. The
evaluation findings and any related recommendations will be discussed at the FY
2026 BsUFA 5-year financial plan public meeting. After review of the findings
and recommendations of the evaluation, FDA will, as appropriate, continue
improving the resource capacity planning capability and the CPA.
B. FINANCIAL TRANSPARENCY
1. FDA will publish a BsUFA 5-year financial plan on or before the end of the 2nd
quarter of FY 2023. The plan shall recognize that the retention of the strategic
hiring and retention adjustment required by section 744H(b)(1)(C) of the FD&C
Act is subject to renegotiation under a subsequent reauthorization of BsUFA.
FDA will publish updates to the 5-year plan on or before the end of the 2nd
quarter of each subsequent fiscal year. The annual updates will include the
following topics:
a. The changes in the personnel compensation and benefit costs for the process
for the review of biosimilar biological product applications that exceed the
amounts provided by the personnel compensation and benefit costs portion of
the inflation adjustment; and
b. FDA’s plan for managing costs related to strategic hiring and retention after
the adjustment required by section 744H(b)(1)(C) of the FD&C Act expires at
the end of fiscal year 2027, given this adjustment is not intended to be
reauthorized in a subsequent reauthorization of BsUFA.
2. FDA will convene a public meeting on or before the end of the 3rd quarter of each
fiscal year to discuss the BsUFA 5-year financial plan and the Agency’s progress
in implementing resource capacity planning, including the continual improvement
of the CPA and time reporting, and the integration of resource capacity planning
in resource and operational decision-making processes.
C. MANAGEMENT OF CARRYOVER BALANCE
FDA is committed to reducing the carryover balance to no greater than 21 weeks of
the target revenue by the end of FY 2025.
In the annual updates to the BsUFA five-year financial plan, FDA will provide
updates on its progress towards implementing its plan to reduce the carryover balance
as outlined in the FY 2022 BsUFA financial report and the five-year financial plan.
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IV.

IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF
Enhancements to the biosimilar biological product review program require that FDA hire
and retain sufficient numbers and types of technical and scientific experts to efficiently
conduct reviews of 351(k) applications. During BsUFA III, the FDA will commit to do
the following:
A. SET CLEAR GOALS FOR BIOSIMILAR BIOLOGICAL PRODUCT
REVIEW PROGRAM HIRING
1. The BsUFA III agreement provides FDA additional user fee funding to hire
additional staff for the biosimilar biological product review program in BsUFA
III. FDA will set clear goals to hire the new staff outlined in Table 1.
Table 1

CDER

FY 2023

FY 2024

FY 2025

FY 2026

FY 2027

14

1

0

0

0

2. FDA will report on progress against the hiring goal for BsUFA III on a quarterly
basis posting updates to the FDA BsUFA Performance webpage.
B. COMPREHENSIVE AND CONTINUOUS ASSESSMENT OF HIRING AND
RETENTION
The Directors of CDER and CBER will utilize a qualified, independent contractor
with expertise in assessing HR operations to conduct a targeted assessment of the
hiring and retention of staff for the biosimilar biological product review program. The
BsUFA III assessment will be conducted under the same contract and by the same
independent contractor that will conduct the assessment related to hiring and retention
of staff for the human drug review program in PDUFA VII. The contractor will assess
the factors that contribute to HR successes and challenges, including factors outside
of FDA’s control. The assessment will build upon the findings of previous
evaluations conducted under BsUFA II and PDUFA VI with a focus on the changes
and adjustments that have improved FDA’s hiring and retention outcomes and which
challenges remain. In addition to evaluating the outcomes of various hiring changes,
the assessment will include metrics related to recruiting and retention in the
biosimilar biological product review program, including, but not limited to, specific
targeted scientific disciplines, attrition, and utilization of pay authorities. The report
will include the contractor’s findings and recommendations on further enhancements
to hiring and retention of staff for the biosimilar biological product review program, if
warranted.
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The assessment will be published on FDA’s website on or before June 30th, 2025 for
public comment. FDA will also hold a public meeting on or before September 30th,
2025 to discuss the report, its findings, and the Agency’s specific plans to address the
report recommendations.
V.

INFORMATION TECHNOLOGY GOALS
Under BsUFA III, FDA will:
A. DEVELOP DATA AND TECHNOLOGY MODERNIZATION STRATEGY
FDA will progress a Data and Technology Modernization Strategy (“Strategy”) that
provides FDA’s strategic direction for current and future state data-driven regulatory
initiatives.
1. No later than Q4 FY 2023, FDA will establish a Data and Technology
Modernization Strategy that reflects the vision in FDA’s Technology and Data
Modernization Action Plans, including:
outlining key areas of focus and approach including leveraging cloud
technologies to support Applicant-FDA regulatory interaction;
articulating enterprise-wide approaches for both technology and data
governance; and
aligning strategic initiatives in support of BsUFA review goals, drawing a line
of sight between initiatives and the enterprise strategy (i.e. the agency-wide
strategy also supporting components outside BsUFA).
2. The Strategy will be shared and annually updated to reflect progress and any
needed adjustments. Milestones and metrics for BsUFA initiatives will be
included in the updates.
B. MONITOR AND MODERNIZE ELECTRONIC SUBMISSION GATEWAY
(ESG)
FDA will continue to ensure the usability and improvement of the ESG.
1. Annually, FDA will provide on the ESG website historic and current metrics on
ESG performance in relation to published targets, characterizations and volume of
submissions, and standards adoption and conformance.
FDA will advance the ESG cloud-based modernization with an improved architecture
that supports greatly expanding data submission bandwidth and storage, while
continuing to ensure its stable operation.

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2. Annually, FDA will provide on the ESG website historic and current metrics on
ESG performance in relation to published targets, characterizations and volume of
submissions, and standards adoption and conformance.
3. By the end of FY 2025, FDA will complete ESG transition to the cloud, including
set-up and integration of an enterprise Identity and Access Management solution
that will streamline applicant access to FDA resources.
4. Annually, FDA will share progress against the implementation project plan.
5. FDA will engage industry to provide feedback and/or participate in pilot testing in
advance of implementing significant changes that impact industry's interaction
with the enterprise-wide systems.

VI.

DEFINITIONS AND EXPLANATION OF TERMS
A. 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.
B. A resubmitted original application is a complete response to an action letter
addressing all identified deficiencies.

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