[Congressional Record Volume 168, Number 157 (Wednesday, September 28, 2022)]
[Senate]
[Pages S5171-S5220]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]
FOOD AND DRUG ADMINISTRATION USER FEE REAUTHORIZATION
Mrs. MURRAY. Mr. President, I ask unanimous consent to have printed
in the Record a copy of the transmittal and commitment letters from the
Secretary of Health and Human Services to the chair and ranking member
of the Committee on Health, Education, Labor, and Pensions of the
Senate and the chair and ranking member of the Committee on Energy and
Commerce of the House of Representatives regarding reauthorization of
the Prescription Drug User Fee Act, Medical Device User Fee Amendments,
Generic Drug User Fee Amendments, and Biosimilar User Fee Act.
There being no objection, the material was ordered to be printed in
the Record, as follows:
The Secretary of Health
and Human Services,
Washington, DC, January 12, 2022.
Hon. Patty Murray,
Chair, Committee on Health, Education, Labor and Pensions,
U.S. Senate, Washington, DC.
Dear Chair Murray: The Prescription Drug User Fee Act
[PDUFA] as reauthorized by the Food and Drug Administration
Reauthorization Act [FDARA P.L. 115-52], expires at the end
of Fiscal Year 2022. With this letter the Administration is
providing our recommendations for the reauthorization of
PDUFA for the Fiscal Years 2023-2027 [PDUFA VII].
Under PDUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to expedite the
process for the review of new prescription drugs and to
support and augment regulatory science and drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
PDUFA VII will average approximately $1.4 billion per year.
PDUFA has proven to be an extremely effective program that
has transformed the U.S. drug review to be the fastest in the
world, while setting the global gold standard for quality,
efficacy, and safety.
Throughout this process, the FDA has solicited input and
worked with various stakeholders, including representatives
from consumer and patient advocates, academic research, and
health provider groups, and negotiated with the
pharmaceutical and biotechnology industries, to develop
reauthorization recommendations for PDUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of existing
programs and performance goals with improvements and
expansions to address areas of emerging regulatory science
and drug development. For example, this includes, but is not
limited to:
Investing critical resources in the Center for Biologics
Evaluation and Research to support development, review, and
approval of cell and gene therapy products;
Introducing new pilot programs to expedite patient access
to novel uses for existing therapies, advance rare diseases
development through efficacy endpoint development, and
improve the quality and acceptability of real-world evidence;
Enhancing the drug safety system through optimizing the
Sentinel Initiative capabilities and improving Risk
Evaluation and Mitigation Strategy (REMS) assessments;
Introducing new enhancements related to product quality
reviews, chemistry, manufacturing, and control approaches,
and advancing the utilization of innovative manufacturing
technologies;
Enhancing the use of digital health technologies to support
drug development and review, along with leveraging modem
technology to accelerate FDA's data and technology
modernization;
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuing activities to enhance financial transparency.
The following five enclosures are provided for your
consideration: The proposed PDUFA VII statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization of PDUFA in Fiscal
Years 2023 through 2027; the PDUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration's program.
Sincerely,
Xavier Becerra.
[[Page S5172]]
____
The Secretary of Health
and Human Services
Washington, DC., January 12, 2022.
Hon. Richard Burr,
Raking Member, Committee on Health, Education, Labor and
Pensions, U.S. Senate, Washington, DC.
Dear Senator Burr: The Prescription Drug User Fee Act
[PDUFA] as reauthorized by the Food and Drug Administration
Reauthorization Act [FD ARA P. L. 115-52], expires at the end
of Fiscal Year 2022. With this letter the Administration is
providing our recommendations for the reauthorization of
PDUFA for the Fiscal Years 2023-2027 [PDUFA VII].
Under PDUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to expedite the
process for the review of new prescription drugs and to
support and augment regulatory science and drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
PDUFA VII will average approximately $1.4 billion per year.
PDUFA has proven to be an extremely effective program that
has transformed the U.S. drug review to be the fastest in the
world, while setting the global gold standard for quality,
efficacy, and safety.
Throughout this process, the FDA has solicited input and
worked with various stakeholders, including representatives
from consumer and patient advocates, academic research, and
health provider groups, and negotiated with the
pharmaceutical and biotechnology industries, to develop
reauthorization recommendations for PDUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of existing
programs and performance goals with improvements and
expansions to address areas of emerging regulatory science
and drug development. For example, this includes, but is not
limited to:
Investing critical resources in the Center for Biologics
Evaluation and Research to support development, review, and
approval of cell and gene therapy products;
Introducing new pilot programs to expedite patient access
to novel uses for existing therapies, advance rare diseases
development through efficacy endpoint development, and
improve the quality and acceptability of real-world evidence;
Enhancing the drug safety system through optimizing the
Sentinel Initiative capabilities and improving Risk
Evaluation and Mitigation Strategy (REMS) assessments;
Introducing new enhancements related to product quality
reviews, chemistry, manufacturing, and control approaches,
and advancing the utilization of innovative manufacturing
technologies;
Enhancing the use of digital health technologies to support
drug development and review, along with leveraging modern
technology to accelerate FDA's data and technology
modernization;
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuing activities to enhance financial transparency.
The following five enclosures are provided for your
consideration: The proposed PDUFA VII statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization of PDUFA in Fiscal
Years 2023 through 2027; the PDUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health
and Human Services,
Washington, DC, January 12, 2022.
Hon. Frank Pallone, Jr.,
Chairman, Committee on Energy and Commerce, House of
Representatives, Washington, DC.
Dear Chair Pallone: The Prescription Drug User Fee Act
[PDUFA] as reauthorized by the Food and Drug Administration
Reauthorization Act [FDARA P. L. 115-52], expires at the end
of Fiscal Year 2022. With this letter the Administration is
providing our recommendations for the reauthorization of
PDUFA for the Fiscal Years 2023-2027 [PDUFA VII].
Under PDUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to expedite the
process for the review of new prescription drugs and to
support and augment regulatory science and drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
PDUFA VII will average approximately $1.4 billion per year.
PDUFA has proven to be an extremely effective program that
has transformed the U.S. drug review to be the fastest in the
world, while setting the global gold standard for quality,
efficacy, and safety.
Throughout this process, the FDA has solicited input and
worked with various stakeholders, including representatives
from consumer and patient advocates, academic research, and
health provider groups, and negotiated with the
pharmaceutical and biotechnology industries, to develop
reauthorization recommendations for PDUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of existing
programs and performance goals with improvements and
expansions to address areas of emerging regulatory science
and drug development. For example, this includes, but is not
limited to:
Investing critical resources in the Center for Biologics
Evaluation and Research to support development, review, and
approval of cell and gene therapy products;
Introducing new pilot programs to expedite patient access
to novel uses for existing therapies, advance rare diseases
development through efficacy endpoint development, and
improve the quality and acceptability of real-world evidence;
Enhancing the drug safety system through optimizing the
Sentinel Initiative capabilities and improving Risk
Evaluation and Mitigation Strategy (REMS) assessments;
Introducing new enhancements related to product quality
reviews, chemistry, manufacturing, and control approaches,
and advancing the utilization of innovative manufacturing
technologies;
Enhancing the use of digital health technologies to support
drug development and review, along with leveraging modem
technology to accelerate FDA's data and technology
modernization;
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuing activities to enhance financial transparency.
The following five enclosures are provided for your
consideration: The proposed PDUFA VII statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization of PDUFA in Fiscal
Years 2023 through 2027; the PDUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health
and Human Services,
Washington, DC, January 12, 2022.
Hon. Cathy McMorris Rodgers,
Ranking Member, Committee on Energy and Commerce,
House of Representatives, Washington, DC.
Dear Representative McMorris Rodgers: The Prescription Drug
User Fee Act [PDUFA] as reauthorized by the Food and Drug
Administration Reauthorization Act [FDARA P.L. 115-52],
expires at the end of Fiscal Year 2022. With this letter the
Administration is providing our recommendations for the
reauthorization of PDUFA for the Fiscal Years 2023-2027
[PDUFA VII].
Under PDUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to expedite the
process for the review of new prescription drugs and to
support and augment regulatory science and drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
PDUFA VII will average approximately $1.4 billion per year.
PDUFA has proven to be an extremely effective program that
has transformed the U.S. drug review to be the fastest in the
world, while setting the global gold standard for quality,
efficacy, and safety.
Throughout this process, the FDA has solicited input and
worked with various stakeholders, including representatives
from consumer and patient advocates, academic research, and
health provider groups, and negotiated with the
pharmaceutical and biotechnology industries, to develop
reauthorization recommendations for PDUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of existing
programs and performance goals with improvements and
expansions to address areas of emerging regulatory science
and drug development. For example, this includes, but is not
limited to:
[[Page S5173]]
Investing critical resources in the Center for Biologics
Evaluation and Research to support development, review, and
approval of cell and gene therapy products;
Introducing new pilot programs to expedite patient access
to novel uses for existing therapies, advance rare diseases
development through efficacy endpoint development, and
improve the quality and acceptability of real-world evidence;
Enhancing the drug safety system through optimizing the
Sentinel Initiative capabilities and improving Risk
Evaluation and Mitigation Strategy (REMS) assessments;
Introducing new enhancements related to product quality
reviews, chemistry, manufacturing, and control approaches,
and advancing the utilization of innovative manufacturing
technologies;
Enhancing the use of digital health technologies to support
drug development and review, along with leveraging modern
technology to accelerate FDA's data and technology
modernization;
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuing activities to enhance financial transparency.
The following five enclosures are provided for your
consideration: The proposed PDUFA VII statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization of PDUFA in Fiscal
Years 2023 through 2027; the PDUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health
and Human Services,
Washington, DC, May 10, 2022.
Hon. Patty Murray,
Chair, Committee on Health, Education, Labor and Pensions,
U.S. Senate,
Washington, DC.
Dear Chair Murray: The Medical Device User Fee Amendments
of 2017 (MDUFA IV), as reauthorized by the Food and Drug
Administration Reauthorization Act (P.L. 115-52), expires at
the end of Fiscal Year (FY) 2022. With this letter, the
Administration is providing our recommendations for the
reauthorization of MDUFA for FY 2023-2027 (MDUFA V).
Under MDUFA, the revenues generated from fees paid by the
medical device industry have been used to expedite the
process for the review of device applications and to support
and augment regulatory science and medical device
development. The expenditure of these funds is in accordance
with the statute and provides resources to meet the
performance goals and procedures that were developed by the
U.S. Food and Drug Administration (FDA) in consultation with
representatives of regulated industry.
FDA estimates that the fees negotiated in MDUFA V provide
for the following five-year total revenue, prior to
adjustments for inflation. They provide a minimum total
revenue of approximately $1.784 billion. In addition, if
specific performance goals are met in FY 2023-2025, FDA may
collect up to an additional total of approximately $116
million in FY 2025-2027, for a maximum potential total of
approximately $1.9 billion.
The MDUFA V package also reflects use of an additional $118
million in funding from the current MDUFA IV carryover
balance to support MDUFA V activities.
Throughout this process, FDA negotiated with the regulated
industry and has solicited input and worked with various
stakeholders, including representatives from patient,
consumer, academic research, and health provider groups, to
develop reauthorization recommendations for MDUFA that would
build upon and enhance the success of the program. In
addition, FDA complied with the statutory requirements to
solicit public comments on the draft recommendations, and the
summary of public comments is posted on the agency web site.
Now pending its fourth reauthorization, MDUFA has proven to
be a highly effective program for supporting the device
review process. The program is designed to help ensure
patient access to safe, effective, and high-quality medical
devices. During the current reauthorization cycle,
negotiations with industry primarily focused on: enhancements
to certain performance goals; filling funding needs that had
not been adequately addressed in MDUFA IV; the launch of a
pilot program designed to speed patient access to certain
innovative medical devices; programs to advance the
development of regulatory science and to advance
opportunities for patient input and collaboration in the
device development process; and proposals to enhance FDA's
accountability and transparency in its use of fees.
The following enclosures are provided for your
consideration: the MDUFA Reauthorization Performance Goals
and Procedures--Fiscal Years 2023 through 2027 (the MDUFA V
Commitment Letter); a redline showing the proposed MDUFA V
statutory changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of MDUFA in FY 2023-2027; and the summary of
public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and
Human Services,
Washington, DC, May 10, 2022.
Hon. Richard Burr,
Ranking Member, Committee on Health, Education, Labor and
Pensions, U.S. Senate, Washington, DC.
Dear Senator Burr: The Medical Device User Fee Amendments
of 2017 (MDUFA IV), as reauthorized by the Food and Drug
Administration Reauthorization Act (P.L. 115-52), expires at
the end of Fiscal Year (FY) 2022. With this letter, the
Administration is providing our recommendations for the
reauthorization of MDUFA for FY 2023-2027 (MDUFA V).
Under MDUFA, the revenues generated from fees paid by the
medical device industry have been used to expedite the
process for the review of device applications and to support
and augment regulatory science and medical device
development. The expenditure of these funds is in accordance
with the statute and provides resources to meet the
performance goals and procedures that were developed by the
U.S. Food and Drug Administration (FDA) in consultation with
representatives of regulated industry.
FDA estimates that the fees negotiated in MDUFA V provide
for the following five-year total revenue, prior to
adjustments for inflation. They provide a minimum total
revenue of approximately $1.784 billion. In addition, if
specific performance goals are met in FY 2023-2025, FDA may
collect up to an additional total of approximately $116
million in FY 2025-2027, for a maximum potential total of
approximately $1.9 billion.
The MDUFA V package also reflects use of an additional $118
million in funding from the current MDUFA IV carryover
balance to support MDUFA V activities.
Throughout this process, FDA negotiated with the regulated
industry and has solicited input and worked with various
stakeholders, including representatives from patient,
consumer, academic research, and health provider groups, to
develop reauthorization recommendations for MDUFA that would
build upon and enhance the success of the program. In
addition, FDA complied with the statutory requirements to
solicit public comments on the draft recommendations, and the
summary of public comments is posted on the agency web site.
Now pending its fourth reauthorization, MDUFA has proven to
be a highly effective program for supporting the device
review process. The program is designed to help ensure
patient access to safe, effective, and high-quality medical
devices. During the current reauthorization cycle,
negotiations with industry primarily focused on: enhancements
to certain performance goals; filling funding needs that had
not been adequately addressed in MDUFA IV; the launch of a
pilot program designed to speed patient access to certain
innovative medical devices; programs to advance the
development of regulatory science and to advance
opportunities for patient input and collaboration in the
device development process; and proposals to enhance FDA's
accountability and transparency in its use of fees.
The following enclosures are provided for your
consideration: the MDUFA Reauthorization Performance Goals
and Procedures--Fiscal Years 2023 through 2027 (the MDUFA V
Commitment Letter); a redline showing the proposed MDUFA V
statutory changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of MDUFA in FY 2023-2027; and the summary of
public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and
Human Services,
Washington, DC, May 10, 2022.
Hon. Frank Pallone, Jr.
Chairman, Committee on Energy and Commerce,
House of Representatives, Washington, DC.
Dear Chair Pallone: The Medical Device User Fee Amendments
of 2017 (MDUFA IV), as reauthorized by the Food and Drug
Administration Reauthorization Act (P.L. 115-52), expires at
the end of Fiscal Year (FY) 2022. With this letter, the
Administration is providing our recommendations for the
reauthorization of MDUFA for FY 2023-2027 (MDUFA V).
Under MDUFA, the revenues generated from fees paid by the
medical device industry have been used to expedite the
process for the review of device applications and to support
and augment regulatory science and medical device
development. The expenditure of these funds is in accordance
with the
[[Page S5174]]
statute and provides resources to meet the performance goals
and procedures that were developed by the U.S. Food and Drug
Administration (FDA) in consultation with representatives of
regulated industry.
FDA estimates that the fees negotiated in MDUFA V provide
for the following five-year total revenue, prior to
adjustments for inflation. They provide a minimum total
revenue of approximately $1.784 billion. In addition, if
specific performance goals are met in FY 2023-2025, FDA may
collect up to an additional total of approximately $116
million in FY 2025-2027, for a maximum potential total of
approximately $1.9 billion.
The MDUFA V package also reflects use of an additional $118
million in funding from the current MDUFA IV carryover
balance to support MDUFA V activities.
Throughout this process, FDA negotiated with the regulated
industry and has solicited input and worked with various
stakeholders, including representatives from patient,
consumer, academic research, and health provider groups, to
develop reauthorization recommendations for MDUFA that would
build upon and enhance the success of the program. In
addition, FDA complied with the statutory requirements to
solicit public comments on the draft recommendations, and the
summary of public comments is posted on the agency web site.
Now pending its fourth reauthorization, MDUFA has proven to
be a highly effective program for supporting the device
review process. The program is designed to help ensure
patient access to safe, effective, and high-quality medical
devices. During the current reauthorization cycle,
negotiations with industry primarily focused on: enhancements
to certain performance goals; filling funding needs that had
not been adequately addressed in MDUFA IV; the launch of a
pilot program designed to speed patient access to certain
innovative medical devices; programs to advance the
development of regulatory science and to advance
opportunities for patient input and collaboration in the
device development process; and proposals to enhance FDA's
accountability and transparency in its use of fees.
The following enclosures are provided for your
consideration: the MDUFA Reauthorization Performance Goals
and Procedures--Fiscal Years 2023 through 2027 (the MDUFA V
Commitment Letter); a redline showing the proposed MDUFA V
statutory changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of MDUFA in FY 2023-2027; and the summary of
public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
Hon. Cathy McMorris Rodgers,
Ranking Member, Committee on Energy and Commerce, House of
Representatives, Washington, DC.
Dear Representative McMorris Rodgers: The Medical Device
User Fee Amendments of 2017 (MDUFA IV), as reauthorized by
the Food and Drug Administration Reauthorization Act (P.L.
115-52), expires at the end of Fiscal Year (FY) 2022. With
this letter, the Administration is providing our
recommendations for the reauthorization of MDUFA for FY 2023-
2027 (MDUFA V).
Under MDUFA, the revenues generated from fees paid by the
medical device industry have been used to expedite the
process for the review of device applications and to support
and augment regulatory science and medical device
development. The expenditure of these funds is in accordance
with the statute and provides resources to meet the
performance goals and procedures that were developed by the
U.S. Food and Drug Administration (FDA) in consultation with
representatives of regulated industry.
FDA estimates that the fees negotiated in MDUFA V provide
for the following five-year total revenue, prior to
adjustments for inflation. They provide a minimum total
revenue of approximately $1.784 billion. In addition, if
specific performance goals are met in FY 2023-2025, FDA may
collect up to an additional total of approximately $116
million in FY 2025-2027, for a maximum potential total of
approximately $1.9 billion.
The MDUFA V package also reflects use of an additional $118
million in funding from the current MDUFA IV carryover
balance to support MDUFA V activities.
Throughout this process, FDA negotiated with the regulated
industry and has solicited input and worked with various
stakeholders, including representatives from patient,
consumer, academic research, and health provider groups, to
develop reauthorization recommendations for MDUFA that would
build upon and enhance the success of the program. In
addition, FDA complied with the statutory requirements to
solicit public comments on the draft recommendations, and the
summary of public comments is posted on the agency web site.
Now pending its fourth reauthorization, MDUFA has proven to
be a highly effective program for supporting the device
review process. The program is designed to help ensure
patient access to safe, effective, and high-quality medical
devices. During the current reauthorization cycle,
negotiations with industry primarily focused on: enhancements
to certain performance goals; filling funding needs that had
not been adequately addressed in MDUFA IV; the launch of a
pilot program designed to speed patient access to certain
innovative medical devices; programs to advance the
development of regulatory science and to advance
opportunities for patient input and collaboration in the
device development process; and proposals to enhance FDA's
accountability and transparency in its use of fees.
The following enclosures are provided for your
consideration: the MDUFA Reauthorization Performance Goals
and Procedures--Fiscal Years 2023 through 2027 (the MDUFA V
Commitment Letter); a redline showing the proposed MDUFA V
statutory changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of MDUFA in FY 2023-2027; and the summary of
public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and
Human Services,
Washington, DC, January 12, 2022.
Hon. Patty Murray,
Chair, Committee on Health, Education, Labor and Pensions,
U.S. Senate, Washington, DC.
Dear Chair Murray: The Generic Drug User Fee Amendments of
2017 [GDUFA II], as reauthorized by the Food and Drug
Administration Reauthorization Act [FDARA P. L. 115-52],
expires at the end of Fiscal Year 2022. With this letter, the
Administration is providing our recommendations for the
reauthorization of GDUFA for the Fiscal Years 2023-2027
[GDUFA III].
Under GDUFA, the revenues generated from fees paid by the
generic pharmaceutical industry have been used to expedite
the process for the review of generic drugs and to support
and augment regulatory science and generic drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
GDUFA III will be over $600 million per year, adjusted
annually for inflation.
Throughout this process, FDA has solicited input and worked
with various stakeholders, including representatives from
consumer, patient, academic research, and health provider
groups, and negotiated with the regulated industry, to
develop reauthorization recommendations for GDUFA that would
build upon and enhance the success of the program. In
addition, we have complied with the statutory requirements to
solicit public comments on our recommendations, and the
summary of public comments is posted on the agency web site.
Our recommendations build upon the successes of existing
programs and performance goals with enhancements to advance
approvals in fewer review cycles, proposals to enhance
regulatory science and expedite complex generic drug
development, and financial proposals to support the generic
drug program as it evolves. For example, minimizing the
issuance of complete response letters through the use of
``imminent actions'' to approve an application within 60 days
after the goal date will reduce the number of review cycles.
The pre-ANDA program, which was initiated as part of GDUFA
II, has several enhancements, including new goal dates for
Product-Specific Guidances [PSGs] that expedite complex
generic drug development. The proposals also include
improvements for FDA to enhance the operational agility of
the GDUFA program through maturation of the Resource Capacity
Planning (RCP) capability and the proposed implementation of
a Capacity Planning Adjustment (CPA) in fee-setting to
generally allow for up to a three percent increase in
inflation-adjusted target revenue for the upcoming fiscal
year if sustained increases in the workload are predicted,
using a methodology developed and evaluated during GDUFA II.
The following five enclosures are provided for your
consideration: the proposed GDUFA III statutory language; a
redline of these changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of GDUFA in Fiscal Years 2023 through 2027;
the GDUFA Reauthorization Performance Goals and Procedures--
Fiscal Years 2023 through 2027 [the GDUFA III Commitment
Letter]; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely
[[Page S5175]]
with Congress to reauthorize the program in a timely manner.
The Office of Management and Budget has advised that the bill
and the enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and
Human Services,
Washington, DC, January 12, 2022.
Hon. Richard Burr,
Ranking Member, Committee on Health, Education, Labor and
Pensions,
U.S. Senate, Washington, DC.
Dear Senator Burr: The Generic Drug User Fee Amendments of
2017 [GDUFA II], as reauthorized by the Food and Drug
Administration Reauthorization Act [FDARA P.L. 115-52],
expires at the end of Fiscal Year 2022. With this letter, the
Administration is providing our recommendations for the
reauthorization of GDUFA for the Fiscal Years 2023-2027
[GDUFA III].
Under GDUFA, the revenues generated from fees paid by the
generic pharmaceutical industry have been used to expedite
the process for the review of generic drugs and to support
and augment regulatory science and generic drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
GDUFA III will be over $600 million per year, adjusted
annually for inflation.
Throughout this process, FDA has solicited input and worked
with various stakeholders, including representatives from
consumer, patient, academic research, and health provider
groups, and negotiated with the regulated industry, to
develop reauthorization recommendations for GDUFA that would
build upon and enhance the success of the program. In
addition, we have complied with the statutory requirements to
solicit public comments on our recommendations, and the
summary of public comments is posted on the agency web site.
Our recommendations build upon the successes of existing
programs and performance goals with enhancements to advance
approvals in fewer review cycles, proposals to enhance
regulatory science and expedite complex generic drug
development, and financial proposals to support the generic
drug program as it evolves. For example, minimizing the
issuance of complete response letters through the use of
``imminent actions'' to approve an application within 60 days
after the goal date will reduce the number of review cycles.
The pre-ANDA program, which was initiated as part of GDUFA
II, has several enhancements, including new goal dates for
Product-Specific Guidances [PSGs] that expedite complex
generic drug development. The proposals also include
improvements for FDA to enhance the operational agility of
the GDUFA program through maturation of the Resource Capacity
Planning (RCP) capability and the proposed implementation of
a Capacity Planning Adjustment (CPA) in fee-setting to
generally allow for up to a three percent increase in
inflation-adjusted target revenue for the upcoming fiscal
year if sustained increases in the workload are predicted,
using a methodology developed and evaluated during GDUFA II.
The following five enclosures are provided for your
consideration: the proposed GDUFA III statutory language; a
redline of these changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of GDUFA in Fiscal Years 2023 through 2027;
the GDUFA Reauthorization Performance Goals and Procedures--
Fiscal Years 2023 through 2027 [the GDUFA III Commitment
Letter]; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
Secretary of Health and
Human Services,
Washington, DC, January 12, 2022.
Hon. Frank Pallone, Jr.,
Chairman, Committee on Energy and Commerce,
House of Representatives, Washington, DC.
Dear Chair Pallone: The Generic Drug User Fee Amendments of
2017 [GDUFA II], as reauthorized by the Food and Drug
Administration Reauthorization Act [FDARA P.L. 115-52],
expires at the end of Fiscal Year 2022. With this letter, the
Administration is providing our recommendations for the
reauthorization of GDUFA for the Fiscal Years 2023-2027
[GDUFA III].
Under GDUFA, the revenues generated from fees paid by the
generic pharmaceutical industry have been used to expedite
the process for the review of generic drugs and to support
and augment regulatory science and generic drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
GDUFA III will be over $600 million per year, adjusted
annually for inflation.
Throughout this process, FDA has solicited input and worked
with various stakeholders, including representatives from
consumer, patient, academic research, and health provider
groups, and negotiated with the regulated industry, to
develop reauthorization recommendations for GDUFA that would
build upon and enhance the success of the program. In
addition, we have complied with the statutory requirements to
solicit public comments on our recommendations, and the
summary of public comments is posted on the agency web site.
Our recommendations build upon the successes of existing
programs and performance goals with enhancements to advance
approvals in fewer review cycles, proposals to enhance
regulatory science and expedite complex generic drug
development, and financial proposals to support the generic
drug program as it evolves. For example, minimizing the
issuance of complete response letters through the use of
``imminent actions'' to approve an application within 60 days
after the goal date will reduce the number of review cycles.
The pre-ANDA program, which was initiated as part of GDUFA
II, has several enhancements, including new goal dates for
Product-Specific Guidances [PSGs] that expedite complex
generic drug development. The proposals also include
improvements for FDA to enhance the operational agility of
the GDUFA program through maturation of the Resource Capacity
Planning (RCP) capability and the proposed implementation of
a Capacity Planning Adjustment (CPA) in fee-setting to
generally allow for up to a three percent increase in
inflation-adjusted target revenue for the upcoming fiscal
year if sustained increases in the workload are predicted,
using a methodology developed and evaluated during GDUFA II.
The following five enclosures are provided for your
consideration: the proposed GDUFA III statutory language; a
redline of these changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of GDUFA in Fiscal Years 2023 through 2027;
the GDUFA Reauthorization Performance Goals and Procedures--
Fiscal Years 2023 through 2027 [the GDUFA III Commitment
Letter]; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and
Human Services,
Washington, DC, January 12, 2022.
Hon. Cathy McMorris Rodgers,
Ranking Member, Committee on Energy and Commerce,
House of Representatives, Washington, DC.
Dear Representative McMorris Rodgers: The Generic Drug User
Fee Amendments of 2017 [GDUFA II], as reauthorized by the
Food and Drug Administration Reauthorization Act [FDARA P.L.
115-52], expires at the end of Fiscal Year 2022. With this
letter, the Administration is providing our recommendations
for the reauthorization of GDUFA for the Fiscal Years 2023-
2027 [GDUFA III].
Under GDUFA, the revenues generated from fees paid by the
generic pharmaceutical industry have been used to expedite
the process for the review of generic drugs and to support
and augment regulatory science and generic drug development.
The expenditure of these funds is in accordance with the
statute and provides resources to meet the performance goals
and procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
GDUFA III will be over $600 million per year, adjusted
annually for inflation.
Throughout this process, FDA has solicited input and worked
with various stakeholders, including representatives from
consumer, patient, academic research, and health provider
groups, and negotiated with the regulated industry, to
develop reauthorization recommendations for GDUFA that would
build upon and enhance the success of the program. In
addition, we have complied with the statutory requirements to
solicit public comments on our recommendations, and the
summary of public comments is posted on the agency web site.
Our recommendations build upon the successes of existing
programs and performance goals with enhancements to advance
approvals in fewer review cycles, proposals to enhance
regulatory science and expedite complex generic drug
development, and financial proposals to support the generic
drug program as it evolves. For example, minimizing the
issuance of complete response letters through the use of
''imminent actions'' to approve an application within 60 days
after the goal date will reduce the number of review cycles.
The pre-ANDA program, which was initiated as part of GDUFA
II, has several enhancements, including new goal dates for
Product-Specific Guidances [PSGs] that expedite complex
generic drug development. The proposals also include
improvements for FDA to enhance the operational agility of
[[Page S5176]]
the GDUFA program through maturation of the Resource Capacity
Planning (RCP) capability and the proposed implementation of
a Capacity Planning Adjustment (CPA) in fee-setting to
generally allow for up to a three percent increase in
inflation-adjusted target revenue for the upcoming fiscal
year if sustained increases in the workload are predicted,
using a methodology developed and evaluated during GDUFA II.
The following five enclosures are provided for your
consideration: the proposed GDUFA III statutory language; a
redline of these changes compared to the current law; the
Justifications of Proposed Statutory Changes for
reauthorization of GDUFA in Fiscal Years 2023 through 2027;
the GDUFA Reauthorization Performance Goals and Procedures--
Fiscal Years 2023 through 2027 [the GDUFA III Commitment
Letter]; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We were
pleased to brief your staff on the details of the Commitment
Letter and hope to continue working closely with Congress to
reauthorize the program in a timely manner. The Office of
Management and Budget has advised that the bill and the
enclosed performance goals are in accordance with the
Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health
and Human Services,
Washington, DC, January 12, 2022.
Hon. Patty Murray,
Chair, Committee on Health, Education, Labor and Pensions,
U.S. Senate, Washington, DC.
Dear Chair Murray: The Biosimilar User Fee Act [BsUFA] as
reauthorized by the FDA Reauthorization Act of 2017 [Pub. L.
115-52], expires at the end of Fiscal Year 2022. With this
letter the Administration is providing our recommendations
for the reauthorization of BsUFA for the Fiscal Years 2023-
2027 [BsUFA III].
Under BsUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to support the process
for the review of biosimilar biological products. The
expenditure of these funds is in accordance with the statute
and provides resources to meet the performance goals and
procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
BsUFA III will average approximately $51 million per year.
As part this process, the FDA has negotiated with the
pharmaceutical and biotechnology industries to develop
reauthorization recommendations for BsUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of the BsUFA
program by refining elements of the existing program and
including new enhancements where appropriate. For example,
these recommendations include, but are not limited to:
Introducing new supplement categories, review timelines,
and performance goals to expedite the review of certain
supplements, including safety labeling updates
Advancing the development of safe and effective
interchangeable biosimilar biological products through
foundational guidance development, stakeholder engagement,
and other activities
Piloting a regulatory science program focused on enhancing
regulatory decision-making and facilitating science-based
recommendations in areas foundational to biosimilar and
interchangeable biological product development
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuation of activities to enhance financial transparency
The following five enclosures are provided for your
consideration: The proposed BsUFA III statutory language; a
redline of current law; the Justifications ofProposed
Statutory Changes for Reauthorization of BsUFA in Fiscal
Years 2023 through 2027; the BsUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office ofManagement and Budget has advised
that the bill and the enclosed performance goals are in
accord with the Administration 's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health
and Human Services,
Washington, DC, January 12, 2022.
Hon. Richard Burr,
Ranking Member, Committee on Health, Education, Labor and
Pensions,
U.S. Senate, Washington, DC.
Dear Senator Burr:
The Biosimilar User Fee Act [BsUFA] as reauthorized by the
FDA Reauthorization Act of 2017 [Pub. L. 115-52], expires at
the end ofFiscal Year 2022. With this letter the
Administration is providing our recommendations for the
reauthorization ofBsUFA for the Fiscal Years 2023-2027 [BsUFA
III].
Under BsUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to support the process
for the review of biosimilar biological products. The
expenditure of these funds is in accordance with the statute
and provides resources to meet the performance goals and
procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
BsUFA III will average approximately $51 million per year.
As part this process, the FDA has negotiated with the
pharmaceutical and biotechnology industries to develop
reauthorization recommendations for BsUF A that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of the BsUF A
program by refining elements of the existing program and
including new enhancements where appropriate. For example,
these recommendations include, but are not limited to:
Introducing new supplement categories, review timelines,
and performance goals to expedite the review of certain
supplements, including safety labeling updates
Advancing the development of safe and effective
interchangeable biosimilar biological products through
foundational guidance development, stakeholder engagement,
and other activities
Piloting a regulatory science program focused on enhancing
regulatory decision-making and facilitating science-based
recommendations in areas foundational to biosimilar and
interchangeable biological product development
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuation of activities to enhance financial transparency
The following five enclosures are provided for your
consideration: The proposed BsUFA III statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization ofBsUFA in Fiscal Years
2023 through 2027; the BsUFA Reauthorization Performance
Goals and Procedures in Fiscal Years 2023 through 2027; and
the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and Human Services,
Washington, DC, January 12, 2022.
Hon. Frank Pallone Jr.,
Chairman, Committee on Energy and Commerce,
House of Representatives,
Washington, DC.
Dear Chair Pallone: The Biosimilar User Fee Act [BsUFA] as
reauthorized by the FDA Reauthorization Act of 2017 [Pub. L.
115-52], expires at the end of Fiscal Year 2022. With this
letter the Administration is providing our recommendations
for the reauthorization of BsUFA for the Fiscal Years 2023-
2027 [BsUFA III].
Under BsUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to support the process
for the review of biosimilar biological products. The
expenditure of these funds is in accordance with the statute
and provides resources to meet the performance goals and
procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
BsUFA III will average approximately $51 million per year.
As part this process, the FDA has negotiated with the
pharmaceutical and biotechnology industries to develop
reauthorization recommendations for BsUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of the BsUFA
program by refining elements of the existing program and
including new enhancements where appropriate. For example,
these recommendations include, but are not limited to:
Introducing new supplement categories, review timelines,
and performance goals to expedite the review of certain
supplements, including safety labeling updates
Advancing the development of safe and effective
interchangeable biosimilar biological products through
foundational guidance development, stakeholder engagement,
and other activities
Piloting a regulatory science program focused on enhancing
regulatory decision-making and facilitating science-based
recommendations in areas foundational to biosimilar and
interchangeable biological product development
[[Page S5177]]
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuation of activities to enhance financial transparency
The following five enclosures are provided for your
consideration: The proposed BsUFA III statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization of BsUFA in Fiscal
Years 2023 through 2027; the BsUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration 's program.
Sincerely,
Xavier Becerra.
____
The Secretary of Health and Human Services,
Washington, DC, January 12, 2022.
Hon. Cathy McMorris Rodgers,
Ranking Member, Committee on Energy and Commerce,
House of Representatives,
Washington, DC.
Dear Representative McMorris Rodgers: The Biosimilar User
Fee Act [BsUFA] as reauthorized by the FDA Reauthorization
Act of 2017 [Pub. L. 115-52], expires at the end of Fiscal
Year 2022. With this letter the Administration is providing
our recommendations for the reauthorization of BsUFA for the
Fiscal Years 2023-2027 [BsUFA III].
Under BsUFA, the revenues generated from fees paid by the
pharmaceutical industry have been used to support the process
for the review of biosimilar biological products. The
expenditure of these funds is in accordance with the statute
and provides resources to meet the performance goals and
procedures that were developed by the Food and Drug
Administration [FDA] in consultation with representatives of
regulated industry. FDA estimates that the fees negotiated in
BsUFA III will average approximately $51 million per year.
As part this process, the FDA has negotiated with the
pharmaceutical and biotechnology industries to develop
reauthorization recommendations for BsUFA that would build
upon and enhance the success of the program. In addition, we
have complied with the statutory requirements to solicit
public comments on our recommendations, and the summary of
public comments is posted on the agency web site and enclosed
with this letter.
Our recommendations build upon the successes of the BsUFA
program by refining elements of the existing program and
including new enhancements where appropriate. For example,
these recommendations include, but are not limited to:
Introducing new supplement categories, review timelines,
and performance goals to expedite the review of certain
supplements, including safety labeling updates
Advancing the development of safe and effective
interchangeable biosimilar biological products through
foundational guidance development, stakeholder engagement,
and other activities
Piloting a regulatory science program focused on enhancing
regulatory decision-making and facilitating science-based
recommendations in areas foundational to biosimilar and
interchangeable biological product development
Improving management of user fee resources through
advancing FDA's Resource Capacity Planning function and
continuation of activities to enhance financial transparency
The following five enclosures are provided for your
consideration: The proposed BsUFA III statutory language; a
redline of current law; the Justifications of Proposed
Statutory Changes for Reauthorization of BsUFA in Fiscal
Years 2023 through 2027; the BsUFA Reauthorization
Performance Goals and Procedures in Fiscal Years 2023 through
2027; and the summary of public comments.
Thank you for the opportunity to present our
recommendations to reauthorize this vital program. We would
be pleased to brief your staff on the details and want to
work closely with Congress to reauthorize the program in a
timely manner. The Office of Management and Budget has
advised that the bill and the enclosed performance goals are
in accord with the Administration 's program.
Sincerely,
Xavier Becerra.
____
PDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROCEDURES FISCAL YEARS
2023 THROUGH 2027
I. Ensuring the Effectiveness of the Human Drug Review
Program
A. Review Performance Goals
B. Program for Enhanced Review Transparency and
Communication for NME NDAs and Original BLAs
C. New Molecular Entity (NME) Milestones and Postmarketing
Requirements (PMRs)
D. Split Real Time Application Review (STAR) Pilot Program
E. Expedited Reviews
F. Review of Proprietary Names to Reduce Medication Errors
G. Major Dispute Resolution
H. Clinical Holds
I. Special Protocol Question Assessment and Agreement
J. Meeting Management Goals
K. Enhancing Regulatory Science and Expediting Drug
Development
L. Enhancing Regulatory Decision Tools to Support Drug
Development and Review
M. Enhancement and Modernization of the FDA Drug Safety
System
N. Enhancements Related to Product Quality Reviews,
Chemistry, Manufacturing, and Controls Approaches, and
Advancing the Utilization of Innovative Manufacturing
Technologies
O. Enhancing CBER's Capacity to Support Development,
Review, and Approval of Cell and Gene Therapy Products
P. Supporting Review of New Allergenic Extract Products
II. Continued Enhancement of User Fee Resource Management
A. Resource Capacity Planning
B. Financial Transparency
III. Improving FDA Hiring and Retention of Review Staff
A. Set Clear Goals for Human Drug Review Program Hiring
B. Assessment of Hiring and Retention
IV. Information Technology and Bioinformatics Goals
A. Enhancing Transparency and Leveraging Modern Technology
B. Expanding and Enhancing Bioinformatics Support
C. Enhancing Use of Digital Health Technologies to Support
Drug Development and Review
V. Improving FDA Performance Management
A. Studies will include:
VI. Progress Reporting for PDUFA VII and Continuing PDUFA
VI Initiatives
Appendix. Definitions and Explanation of Terms
PDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROCEDURES FISCAL YEARS
2023 THROUGH 2027
This document contains the performance goals and procedures
for the Prescription Drug User Fee Act (PDUFA)
reauthorization for fiscal years (FYs) 2023-2027, known as
PDUFA VII. It is commonly referred to as the ``goals letter''
or ``commitment letter.'' The goals letter represents the
product of FDA's discussions with the regulated industry and
public stakeholders, as mandated by Congress. The performance
and procedural goals and other commitments specified in this
letter apply to aspects of the human drug review program that
are important for facilitating timely access to safe,
effective, and innovative new medicines for patients. While
much of FDA's work is associated with formal tracked
performance goals, the Agency and industry mutually agree
that it is appropriate to manage some areas of the human drug
review program with internally tracked timeframes. This
provides FDA the flexibility needed to respond to a highly
diverse workload, including unanticipated public health
needs. FDA is committed to meeting the performance goals
specified in this letter and to continuous improvement of its
performance regarding other important areas specified in
relevant published documents that relate to preapproval drug
development and post-approval activities for marketed
products. FDA and the regulated industry will periodically
and regularly assess the progress of the human drug review
program throughout PDUFA VII. This will allow FDA and the
regulated industry to identify emerging challenges and
develop strategies to address these challenges to ensure the
efficiency and effectiveness of the human drug review
program.
Unless otherwise stated, goals apply to cohorts of each
fiscal year (FY).
I. ENSURING THE EFFECTIVENESS OF THE HUMAN DRUG REVIEW PROGRAM
A. REVIEW PERFORMANCE GOALS
1. NDA/BLA Submissions and Resubmissions
a. Review and act on 90 percent of standard NME NDA and
original BLA submissions within 10 months of the 60-day
filing date.
b. Review and act on 90 percent of priority NME NDA and
original BLA submissions within 6 months of the 60-day filing
date.
c. Review and act on 90 percent of standard non-NME
original NDA submissions within 10 months of receipt.
d. Review and act on 90 percent of priority non-NME
original NDA submissions within 6 months of receipt.
e. Review and act on 90 percent of Class 1 resubmitted
original applications within 2 months of receipt.
f. Review and act on 90 percent of Class 2 resubmitted
original applications within 6 months of receipt.
2. Original Efficacy Supplements
a. Review and act on 90 percent of standard efficacy
supplements within 10 months of receipt.
b. Review and act on 90 percent of priority efficacy
supplements within 6 months of receipt.
3. Resubmitted Efficacy Supplements
a. Review and act on 90 percent of Class 1 resubmitted
efficacy supplements within 2 months of receipt.
b. Review and act on 90 percent of Class 2 resubmitted
efficacy supplements within 6 months of receipt.
4. Original Manufacturing Supplements
a. Review and act on 90 percent of manufacturing
supplements requiring prior approval within 4 months of
receipt.
b. Review and act on 90 percent of all other manufacturing
supplements within 6 months of receipt.
5. Review Performance Goal Extensions
a. Major Amendments
i. A major amendment to an original application, efficacy
supplement, or resubmission
[[Page S5178]]
of any of these applications, submitted at any time during
the review cycle, may extend the goal date by three months.
ii. A major amendment may include, for example, a major new
clinical safety/efficacy study report; major re-analysis of
previously submitted study(ies); submission of a Risk
Evaluation and Mitigation Strategy (REMS) with Element to
Assure Safe Use (ETASU) not included in the original
application; or significant amendment to a previously
submitted REMS with ETASU. Generally, changes to REMS that do
not include ETASU and minor changes to REMS with ETASU will
not be considered major amendments.
iii. A major amendment to a manufacturing supplement
submitted at any time during the review cycle may extend the
goal date by two months.
iv. Only one extension can be given per review cycle.
v. Consistent with the underlying principles articulated in
the GRMP guidance, FDA's decision to extend the review clock
should, except in rare circumstances, be limited to occasions
where review of the new information could address outstanding
deficiencies in the application and lead to approval in the
current review cycle.
b. Inspection of Facilities Not Adequately Identified in an
Original Application or Supplement
i. All original applications, including those in the
``Program,'' (see Section I.B.2) and supplements are expected
to include a comprehensive and readily located list of all
manufacturing facilities included or referenced in the
application or supplement. This list provides FDA with
information needed to schedule inspections of manufacturing
facilities that may be necessary before approval of the
original application or supplement.
ii. If, during FDA's review of an original application or
supplement, the Agency identifies a manufacturing facility
that was not included in the comprehensive and readily
located list, the goal date may be extended.
1) If FDA identifies the need to inspect a manufacturing
facility that is not included as part of the comprehensive
and readily located list in an original application or
efficacy supplement, the goal date may be extended by three
months.
2) If FDA identifies the need to inspect a manufacturing
facility that is not included as part of the comprehensive
and readily located list in a manufacturing supplement, the
goal date may be extended by two months.
6. These review goals are summarized in the following
tables:
TABLE 1
------------------------------------------------------------------------
Submission Cohort Standard Priority
------------------------------------------------------------------------
NME NDAs and original BLAs...... 90% in 10 months 90% in 6 months of
of the 60-day the 60-day filing
filing date. date
Non NME NDAs.................... 90% in 10 months 90% in 6 months of
of the receipt the receipt date
date.
Class 1 Resubmissions........... 90% in 2 months of 90% in 2 months of
the receipt date. the receipt date
Class 2 Resubmissions........... 90% in 6 months of 90% in 6 months of
the receipt date. the receipt date
Original Efficacy Supplements... 90% in 10 months 90% in 6 months of
of the receipt the receipt date
date.
Class 1 Resubmitted Efficacy 90% in 2 months of 90% in 2 months of
Supplements. the receipt date. the receipt date
Class 2 Resubmitted Efficacy 90% in 6 months of 90% in 6 months of
Supplements. the receipt date. the receipt date
------------------------------------------------------------------------
TABLE 2
------------------------------------------------------------------------
Prior Approval All Other
------------------------------------------------------------------------
Manufacturing Supplements....... 90% in 4 months of 90% in 6 months of
the receipt date. the receipt date
------------------------------------------------------------------------
B. Program for Enhanced Review Transparency and Communication
for NME NDAs and Original BLAs
To promote transparency and communication between the FDA
review team and the applicant, FDA will apply the following
model (``the Program'') to the review of all New Molecular
Entity New Drug Applications (NME NDAs) and original
Biologics License Applications (BLAs), including applications
that are resubmitted following a Refuse-to-File decision,
received from October 1, 2022, through September 30, 2027.
The goal of the Program is to promote the efficiency and
effectiveness of the first cycle review process and minimize
the number of review cycles necessary for approval, ensuring
that patients have timely access to safe, effective, and high
quality new drugs and biologics.
Approach to Application Review. The standard approach for
the review of NME NDAs and original BLAs is described in this
section. However, the FDA review team and the applicant may
discuss and reach mutual agreement on an alternative approach
to the timing and nature of interactions and information
exchange between the applicant and FDA, i.e., a Formal
Communication Plan for the review of the NME NDA or original
BLA. The Formal Communication Plan may include elements of
the standard approach (e.g., a mid-cycle communication or a
late-cycle meeting) as well as other interactions that
sometimes occur during the review process (e.g., a meeting
during the filing period to discuss the application, i.e., an
``application orientation meeting''). If appropriate, the
Formal Communication Plan should specify those elements of
the Program that FDA and the applicant 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 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 pre-NDA/BLA
meeting. This meeting will be attended by the FDA review
team, including appropriate senior FDA staff.
a. The pre-NDA/BLA meeting should be held sufficiently in
advance of the planned submission of the application to allow
for meaningful response to FDA feedback and should generally
occur not less than 2 months prior to the planned submission
of the application.
b. In addition to FDA's preliminary responses to the
applicant's questions, other potential discussion topics
include preliminary discussions on the need for REMS or other
risk management actions, and, where applicable, the
development of a Formal Communication Plan and a timeline for
review activities associated with a scheduling recommendation
under the Controlled Substances Act for drugs with abuse
potential. These discussions will be summarized at the
conclusion of the meeting and reflected in the FDA meeting
minutes.
c. The FDA and the applicant will agree on the content of a
complete application for the proposed indication(s) at the
pre-submission meeting. The FDA and the applicant may also
reach agreement on submission of a limited number of
application components not later than 30 calendar days after
the submission of the original application. These submissions
must be of a type that would not be expected to materially
impact the ability of the review team to begin its review.
These agreements will be summarized at the conclusion of the
meeting and reflected in the FDA meeting minutes.
i. Examples of application components that may be
appropriate for delayed submission include updated stability
data (e.g., 15-month data to update 12-month data submitted
with the original submission) or the final audited report of
a preclinical study (e.g., carcinogenicity) where the final
draft report is submitted with the original application.
ii. Major components of the application (e.g., the complete
study report of a Phase 3 clinical trial or the full study
report of required long-term safety data) are expected to be
submitted with the original application and are not subject
to agreement for late submission.
2. Original application submission: Applications are
expected to be complete, as agreed between the FDA review
team and the applicant at the pre-NDA/BLA meeting, at the
time of original submission of the application. If the
applicant does not have a pre-NDA/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.
[[Page S5179]]
c. Incomplete applications, including applications with
components that are not received within 30 calendar days
after receipt of the original submission, will be subject to
a Refuse-to-File decision.
d. The following parameters will apply to applications that
are subject to a Refuse-to-File decision and are subsequently
filed over protest:
i. The original submission of the application will be
subject to the review performance goal as described in
Section I.B.4.
ii. The application will not be eligible for the other
parameters of the Program (e.g., mid-cycle communication,
late-cycle meeting).
iii. FDA generally will not review amendments to the
application during any review cycle. FDA also generally will
not issue information requests to the applicant during the
agency's review.
iv. The resubmission goals described in Sections I.A.1.e
and I.A.1.f will not apply to any resubmission of the
application following an FDA complete response action. Any
such resubmission will be reviewed as available resources
permit.
e. Since applications are expected to be complete at the
time of submission, unsolicited amendments are expected to be
rare and not to contain major new information or analyses.
Review of unsolicited amendments, including those submitted
in response to an FDA communication of deficiencies, will be
handled in accordance with the GRMP guidance. This guidance
includes the underlying principle that FDA will consider the
most efficient path toward completion of a comprehensive
review that addresses application deficiencies and leads
toward a first cycle approval when possible.
3. Day 74 Letter: FDA will follow existing procedures
regarding identification and communication of filing review
issues in the ``Day 74 letter.'' For applications subject to
the Program, the timeline for this communication will be
within 74 calendar days from the date of FDA receipt of the
original submission. The planned review timeline included in
the Day 74 letter for applications in the Program will
include the planned date for the internal mid-cycle review
meeting. The letter will also include preliminary plans on
whether to hold an Advisory Committee (AC) meeting to discuss
the application. If applicable, the Day 74 letter will serve
as notification to the applicant that the review division
intends to conduct an expedited review (See Section I.E).
4. Review performance goals: For NME NDA and original BLA
submissions that are filed by FDA under the Program, the
PDUFA review clock will begin at the conclusion of the 60-day
filing review period that begins on the date of FDA receipt
of the original submission. The review performance goals for
these applications are as follows:
a. Review and act on 90 percent of standard NME NDA and
original BLA submissions within 10 months of the 60-day
filing date.
b. Review and act on 90 percent of priority NME NDA and
original BLA submissions within 6 months of the 60-day filing
date.
5. Mid-Cycle Communication: The FDA Regulatory Project
Manager (RPM), and other appropriate members of the FDA
review team (e.g., Cross Discipline Team Leader (CDTL)), will
call the applicant, generally within 2 weeks following the
Agency's internal mid-cycle review meeting, to provide the
applicant with an update on the status of the review of their
application. An agenda will be sent to the applicant prior to
the mid-cycle communication. Scheduling of the internal mid-
cycle review meeting will be handled in accordance with the
GRMP guidance. The RPM will coordinate the specific date and
time of the telephone call with the applicant.
a. The update should include any significant issues
identified by the review team to date, any information
requests, information regarding major safety concerns and
preliminary review team thinking and rationale regarding:
1. risk management,
2. the potential need for any post-marketing requirement(s)
(PMRs), and
3. the ability of adverse event reporting and FDA's Active
Risk Identification and Analysis (ARIA) system under the
Sentinel Initiative to provide sufficient information about
product risk.
b. The update should also include proposed date(s) for the
late-cycle meeting, updates regarding plans for the AC
meeting (if an AC meeting is anticipated), an update
regarding FDA's review activities associated with a
scheduling recommendation under the Controlled Substances Act
(if applicable), and other projected milestone dates for the
remainder of the review cycle.
c. In the case of an expedited review, FDA will communicate
the timelines for the Late-Cycle Meeting and the Late-Cycle
Meeting background package (see Section I.B.6) which may
occur earlier with more condensed timeframes compared to a
review that is not expedited.
6. Late-Cycle and Advisory Committee Meetings: A meeting
will be held between the FDA review team and the applicant to
discuss the status of the review of the application late in
the review cycle. Late-cycle meetings will generally be face-
to-face meetings; however, the meeting may be held by
teleconference if FDA and the applicant agree. Since the
application is expected to be complete at the time of
submission, FDA intends to complete primary and secondary
reviews of the application in advance of the planned late-
cycle meeting.
a. FDA representatives at the late-cycle meeting are
expected to include the signatory authority for the
application, review team members from appropriate
disciplines, and appropriate team leaders and/or supervisors
from disciplines for which substantive issues have been
identified in the review to date.
b. For applications that will be discussed at an AC
meeting, the following parameters apply:
1. FDA intends to convene AC meetings no later than 2
months (standard review) or no later than 6 weeks (priority
review) prior to the PDUFA goal date. The late-cycle meeting
will occur not less than 12 calendar days before the date of
the AC meeting.
2. FDA intends to provide final questions for the AC to the
applicant and the AC not less than 2 calendar days before the
AC meeting.
3. Following an AC Meeting, FDA and the applicant may agree
on the need to discuss feedback from the AC for the purpose
of facilitating the remainder of the review. Such a meeting
will generally be held by teleconference without a commitment
for formal meeting minutes issued by the agency.
c. For applications that will not be discussed at an AC
meeting, the late-cycle meeting will generally occur not
later than 3 months (standard review) or two months (priority
review) prior to the PDUFA goal date.
d. Late-Cycle Meeting Background Packages: The Agency
background package for the late-cycle meeting will be sent to
the applicant not less than 10 calendar days (or 2 calendar
days for an expedited review) before the late-cycle meeting.
The package will consist of a brief memorandum from the
review team outlining substantive application issues (e.g.,
deficiencies identified by primary and secondary reviews),
the Agency's background package for the AC meeting
(incorporated by reference if previously sent to the
applicant), potential questions and/or points for discussion
for the AC meeting (if planned) and the current assessment of
the need for REMS or other risk management actions. If the
application is subject to an expedited review, the background
package may be streamlined using a bulleted list to identify
issues to be discussed.
e. Late-Cycle Meeting Discussion Topics: Potential topics
for discussion at the late-cycle meeting include major
deficiencies identified to date; issues to be discussed at
the AC meeting (if planned); current assessment of the need
for REMS and current assessment of the sufficiency of adverse
event reporting and the ARIA system to provide information on
product risk and the rationale for potential need for a PMR
to characterize product risk or other risk management
actions; status update of FDA's review activities associated
with a scheduling recommendation under the Controlled
Substances Act, if applicable; information requests from the
review team to the applicant; and additional data or analyses
the applicant may wish to submit.
i. With regard to submission of additional data or
analyses, the FDA review team and the applicant will discuss
whether such data will be reviewed by the Agency in the
current review cycle and, if so, whether the submission will
be considered a major amendment and trigger an extension of
the PDUFA goal date.
7. Inspections: FDA's goal is to complete all GCP, GLP, and
GMP inspections for applications in the Program within 6
months of the date of original receipt for priority
applications and within 10 months of the date of original
receipt for standard applications. This will allow 2 months
at the end of the review cycle to attempt to address any
deficiencies identified by the inspections.
C. New Molecular Entity (NME) Milestones and Postmarketing
Requirements (PMRs)
FDA will continue to review, oversee, track, and
communicate postmarketing drug safety issues.
1. Pre-approval review of PMRs: The Agency recognizes the
importance of PMRs to ensure the timely availability of
information on the safety and efficacy of therapies to the
United States public. Therefore, FDA will establish processes
to support consistency and predictability for both the Agency
and applicants throughout the identification, determination,
and evaluation of postmarketing studies.
FDA will establish the following pre-approval process
enhancements and guidelines in PDUFA VII:
a. For standard NME NDAs and original BLAs, FDA will
communicate details on anticipated PMRs required under
Section 505(o)(3), PREA, Accelerated Approval, and the Animal
Rule to the applicant no later than 8 weeks prior to the
PDUFA action goal date.
b. For priority NME NDAs and original BLAs, FDA will
communicate details on anticipated PMRs required under
Section 505(o)(3), PREA, Accelerated Approval, and the Animal
Rule to the applicant no later than 6 weeks prior to the
PDUFA action goal date.
c. The communications described above in clauses (a) and
(b) will summarize FDA's preliminary evaluation of required
postmarketing studies, including the study purpose, critical
study design elements including type of study and study
population, timelines for discussions and engagement on the
PMR for the remainder of the review cycle, and for 505(o)(3)
PMRs the specific serious risk.
d. If a major safety issue which requires a PMR is
identified based on data submitted
[[Page S5180]]
subsequent to submission of the application these timelines
may not apply.
FDA's performance goals for standard NME NDAs and original
BLAs will be phased in, starting in FY 2023 as follows:
a. In FY 2023, communicate anticipated PMRs to the
applicant no later than 8 weeks prior to the PDUFA action
goal date for 60% of standard NME NDAs and original BLAs.
b. In FY 2024, communicate anticipated PMRs to the
applicant no later than 8 weeks prior to the PDUFA action
goal date for 70% of standard NME NDAs and original BLAs.
c. In FY 2025, communicate anticipated PMRs to the
applicant no later than 8 weeks prior to the PDUFA action
goal date for 80% of standard NME NDAs and original BLAs.
d. In FY 2026, communicate anticipated PMRs to the
applicant no later than 8 weeks prior to the PDUFA action
goal date for 80% of standard NME NDAs and original BLAs.
e. In FY 2027, communicate anticipated PMRs to the
applicant no later than 8 weeks prior to the PDUFA action
goal date for 80% of standard NME NDAs and original BLAs.
FDA's performance goals for priority NME NDAs and original
BLAs will be phased in, starting in FY 2023 as follows:
a. In FY 2023, communicate anticipated PMRs to the
applicant no later than 6 weeks prior to the PDUFA action
goal date for 60% of priority NME NDAs and original BLAs.
b. In FY 2024, communicate anticipated PMRs to the
applicant no later than 6 weeks prior to the PDUFA action
goal date for 70% of priority NME NDAs and original BLAs.
c. In FY 2025, communicate anticipated PMRs to the
applicant no later than 6 weeks prior to the PDUFA action
goal date for 80% of priority NME NDAs and original BLAs.
d. In FY 2026, communicate anticipated PMRs to the
applicant no later than 6 weeks prior to the PDUFA action
goal date for 80% of priority NME NDAs and original BLAs.
e. In FY 2027, communicate anticipated PMRs to the
applicant no later than 6 weeks prior to the PDUFA action
goal date for 80% of priority NME NDAs and original BLAs.
For the purposes of tracking and reporting metrics on all
PMR goals described above, FDA will calculate metrics based
on all NME and original BLA applications with issued PMRs,
including Section 505(o)(3), PREA, Accelerated Approval, and
the Animal Rule.
In addition, FDA will enhance clarity and transparency for
the NME Review Program by updating all relevant Manuals of
Policies and Procedures (MAPPs), Standard Operating
Procedures and Policies (SOPPs), and guidances regarding the
pre-approval processes for establishing PMRs beginning FY
2023 and finalizing by the end of FY 2027. The Agency will
also conduct training for all relevant review and program
support staff on updated processes related to postmarketing
studies beginning FY 2023, including:
a. Preliminary communication with applicants at mid-cycle
for PMRs, PMCs, and REMS.
b. Processes and procedures for ARIA sufficiency
determination.
2. Post-approval review of existing PMRs: In addition to
mechanisms currently in place for FDA to review existing PMRs
(e.g., Annual Status Reports (ASRs), protocol submissions),
applicants may also request review of existing PMRs for
release. FDA will establish an additional process for
reviewing sponsor-initiated requests as summarized below:
a. The applicant will submit a request summarizing their
rationale for why an existing PMR is no longer needed,
including all necessary supporting data and information.
b. The relevant FDA review division/office and discipline
will initiate review of the request. FDA will notify the
applicant of any additional information considered necessary
to evaluate the request within 45 days of receipt.
c. FDA will respond to the applicant with a decision within
60 days of receipt of the original request or within 60 days
of receipt of the additional information requested by FDA
described in the previous step, whichever is later. FDA's
response can be an agreement letter or a non-agreement
letter. In a case of a non-agreement letter, the FDA will
provide a rationale for their decision.
d. If FDA's response is a non-agreement letter, the
applicant may submit a request to the review division for
reconsideration by the appropriate committee(s) described in
(e) below with justification, and any additional information,
and/or data if appropriate.
e. Upon receipt of a reconsideration request, the review
division/office will discuss with the appropriate internal
committee that includes senior Agency leadership (e.g.,
Medical Policy and Program Review Committee, Medical Policy
Coordinating Committee, and Pediatric Review Committee).
f. The review division/office will issue a written response
within 45 days of receipt of the reconsideration request.
FDA's response can be an agreement letter or a non-agreement
letter. In a case of a non-agreement letter, the FDA will
provide a rationale for their decision.
The process and timelines described above will be
incorporated into all relevant MAPPs, SOPPs, and guidances
beginning FY 2023 and finalizing by the end of FY 2027 and
will not be PDUFA-tracked metrics or subject to performance
goals.
D. Split Real Time Application Review (STAR) Pilot Program
FDA will establish a STAR pilot program, which has the goal
of shortening the time from the date of complete submission
to the action date, in order to allow earlier patient access
to therapies that address an unmet medical need. The STAR
pilot program will apply to efficacy supplements across all
therapeutic areas and review disciplines that meet specific
criteria. Accepted STAR applications will be submitted in a
``split'' fashion, specifically in two parts (with the
components submitted approximately 2 months apart).
1. Scope: The STAR program will seek to expedite patient
access to novel uses for existing therapies by supporting
initiation of review earlier than would otherwise occur and
therefore allowing earlier approval for qualified efficacy
supplements. This program will apply across all therapeutic
areas and review disciplines for applications that meet
specific criteria. An application will be considered eligible
for STAR if each of the following criteria are met:
a. Clinical evidence from adequate and well-controlled
investigation(s) indicates that the drug may demonstrate
substantial improvement on a clinically relevant endpoint(s)
over available therapies.
i. Breakthrough Therapy Designation (BTD) or Regenerative
Medicine Advanced Therapy Designation (RMAT) is not required,
but above criteria must be met.
b. The application is for a drug intended to treat a
serious condition with an unmet medical need.
c. No aspect of the submission is likely to require a
longer review time (e.g., requirement for new REMS, etc.).
d. There is no chemistry, manufacturing, or control
information that would require a foreign manufacturing site
inspection (i.e., domestic site inspections may be allowed if
it does not affect the expedited timeframe).
2. Process and Timeline: The following steps summarize the
process for applying to and participating in the STAR
program:
a. An applicant who believes an efficacy supplement
qualifies for review under the STAR program will request an
informal pre-submission teleconference with FDA and provide
FDA with topline trial results and proposed labeling.
i. Alternatively, the preliminary discussion may take place
as part of a pre-sNDA/sBLA meeting.
b. If FDA agrees that the pre-submission request meets the
STAR program eligibility criteria, the application will be
accepted into the STAR program, and the applicant will agree
to provide the complete application in two parts (these two
parts are described in the Split Submission Components
section below or as agreed to with the Review Division).
c. FDA will initiate review of the data upon receipt of the
Part 1 submission.
d. The PDUFA timeline will begin upon receipt of the Part 2
submission (which completes the application). FDA intends to
follow the expedited review timelines (as described in
Section I.E below). These timelines target taking an action
at least 1 month earlier than the applicable PDUFA goal date.
e. The filing meeting will be scheduled within 30 days of
FDA's receipt of the Part 2 submission. During the filing
meeting, FDA will determine an action date at least 1 month
in advance of the priority 6-month PDUFA goal date.
i. FDA will notify the applicant of the intended action
date in the filing letter. The PDUFA goal date will remain
unchanged.
3. Split Submission Components: Applications reviewed under
the STAR program will comprise two separate submissions.
a. The Part 1 submission initiates FDA's review and will
contain:
i. All components of the NDA/BLA efficacy supplement (e.g.,
complete datasets, proposed labeling, clinical protocols and
amendments, topline efficacy and safety results), except for
final clinical study reports for the adequate and well-
controlled investigation(s) supporting the proposed claim and
the eCTD module 2 clinical summaries, and
ii. A document providing topline results for each of the
adequate and well-controlled investigations will also be
provided in the Part 1 submission.
Any modifications to submission content are at the
discretion of the OND/CDER clinical division or CBER review
office and must be agreed to in advance.
b. The Part 2 submission initiates the PDUFA timeline and
will contain:
i. The clinical study reports for the adequate and well-
controlled investigation(s) (e.g., Phase 3 studies) intended
to support the proposed indication, and
ii. The eCTD module 2 clinical summaries not included in
the Part 1 submission.
Part 1 will be submitted approximately 2 months, and not
longer than 3 months, in advance of Part 2. If the Part 1
submission is incomplete (i.e., it does not include every
component described in Section D.3.a. above, except for
easily correctable minor deficiencies of components not
essential to initiating review, as determined by the OND/CDER
division or CBER review office), the review will not be
initiated until the application is complete and the
application will no longer be considered within the STAR
program.
4. Transparency: The Agency will develop a public-facing
webpage outlining detailed criteria for potential acceptance
and participation in the STAR program by October 1, 2022. FDA
will conduct an interim assessment that includes internal
activities related to STAR by the end of FY 2025. FDA will
also conduct a public workshop by the end of Q2 in FY 2026 to
discuss the potential value and feasibility of expanding the
pilot program to select NME NDAs and BLAs and solicit
feedback on experiences with the pilot program
[[Page S5181]]
from industry stakeholders. Outputs from the assessment and
workshop will be published in a publicly available report
summarizing both overall metrics for the pilot program and
external stakeholder feedback, including the percentage of
applications accepted into the program based on the number of
requests and the percentage of applications that had an
action date at least 1 month in advance of the priority 6-
month PDUFA goal date. FDA will also commit to training
review staff on STAR processes and providing a publicly
available report summarizing training activities conducted.
5. Implementation: The STAR program will be available to
applicants beginning in FY 2023. Expediting reviews will be
fully implemented by FY 2024 to allow time for FDA to hire
necessary staff to support the expedited timeline.
E. Expedited Reviews
The term ``expedited review'' in this letter refers to
FDA's review of either 1) a human drug application in the
Program that has received priority review designation and the
FDA review team identifies as meeting an important public
health need, or 2) an efficacy supplement in the STAR pilot
program, where the review team plans to act at least 1 month
before the PDUFA goal date provided that no significant
application deficiencies prevent an early action. In such
cases the FDA review team intends to make every effort to
conduct an expedited review and act early on the application.
FDA conducts expedited reviews to promote timely access to
critically needed therapies for patients without compromising
FDA's high standards for demonstrating the safety, efficacy,
and quality of new medicines. If significant application
deficiencies are identified by the review team at any time
during an expedited review, FDA intends to revert, for the
remainder of the review, to the normal priority review
approach, and will inform the applicant accordingly.
F. Review of Proprietary Names to Reduce Medication Errors
To enhance patient safety, FDA is committed to various
measures to reduce medication errors related to look-alike
and sound-alike proprietary names and such factors as unclear
label abbreviations, acronyms, dose designations, and error-
prone label and packaging design. The following performance
goals apply to FDA's review of drug and biological product
proprietary names during development (as early as end-of-
phase 2) and during FDA's review of a marketing application:
1. Proprietary Name Review Performance Goals During Drug
Development
a. Review 90% of proprietary name submissions filed within
180 days of receipt. Notify sponsor of tentative acceptance
or non-acceptance.
b. In the proprietary name is found to be unacceptable, the
sponsor can request reconsideration by submitting a written
rebuttal with supporting data or request a meeting within 60
days to discuss the initial decision (meeting package
required).
c. In the proprietary name is found to be unacceptable, the
above review performance goals also would apply to the
written request for reconsideration with supporting data or
the submission of a new proprietary name.
d. A complete submission is required to begin the review
clock.
2. Proprietary Name Review Performance Goals During
Application Review
a. Review 90% of NDA/BLA proprietary name submissions filed
within 90 days of receipt. Notify applicant of tentative
acceptance/non-acceptance.
b. A supplemental review will be done meeting the above
review performance goals if the proprietary name has been
submitted previously (investigational new drug (IND) phase
after end-of-phase 2) and has received tentative acceptance.
c. In the proprietary name is found to be unacceptable, the
applicant 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. In 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.
G. Major Dispute Resolution
1. Procedure:
For procedural or scientific matters involving the review
of human drug applications and supplements (as defined in
PDUFA) that cannot be resolved at the signatory authority
level (including a request for reconsideration by the
signatory authority after reviewing any materials that are
planned to be forwarded with an appeal to the next level),
the response to appeals of decisions will occur within 30
calendar days of the Center's receipt of the written appeal.
2. Performance goal:
90% of such answers are provided within 30 calendar days of
the Center's receipt of the written appeal.
3. Conditions:
a. Sponsors should first try to resolve the procedural or
scientific issue at the signatory authority level. If it
cannot be resolved at that level, it should be appealed to
the next higher organizational level (with a copy to the
signatory authority) and then, if necessary, to the next
higher organizational level.
b. Responses should be either verbal (followed by a written
confirmation within 14 calendar days of the verbal
notification) or written and should ordinarily be to either
grant or deny the appeal.
c. If the decision is to deny the appeal, the response
should include reasons for the denial and any actions the
sponsor might take to persuade the Agency to reverse its
decision.
d. In some cases, further data or further input from others
might be needed to reach a decision on the appeal. In these
cases, the ``response'' should be the plan for obtaining that
information (e.g., requesting further information from the
sponsor, scheduling a meeting with the sponsor, scheduling
the issue for discussion at the next scheduled available
advisory committee (AC)).
e. In these cases, once the required information is
received by the Agency (including any advice from an AC), the
person to whom the appeal was made again has 30 calendar days
from the receipt of the required information in which to
either grant or deny the appeal.
f. Again, if the decision is to deny the appeal, the
response should include the reasons for the denial and any
actions the sponsor might take to persuade the Agency to
reverse its decision.
g. N.B. If the Agency decides to present the issue to an AC
and there are not 30 days before the next scheduled AC, the
issue will be presented at the following scheduled committee
meeting to allow conformance with AC administrative
procedures.
H. 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.
I. Special Protocol Question Assessment and Agreement
1. Procedure:
Upon specific request by a sponsor (including specific
questions that the sponsor desires to be answered), the
Agency will evaluate certain protocols and issues to assess
whether the design is adequate to meet scientific and
regulatory requirements identified by the sponsor.
a. The sponsor should submit a limited number of specific
questions about the protocol design and scientific and
regulatory requirements for which the sponsor seeks agreement
(e.g., is the dose range in the carcinogenicity study
adequate, considering the intended clinical dosage; are the
clinical endpoints adequate to support a specific efficacy
claim).
b. Within 45 days of Agency receipt of the protocol and
specific questions, the Agency will provide a written
response to the sponsor that includes a succinct assessment
of the protocol and answers to the questions posed by the
sponsor. If the Agency does not agree that the protocol
design, execution plans, and data analyses are adequate to
achieve the goals of the sponsor, the reasons for the
disagreement will be explained in the response.
c. Protocols that qualify for this program include:
carcinogenicity protocols, stability protocols, and Phase 3
protocols for clinical trials that will form the primary
basis of an efficacy claim. For such Phase 3 protocols to
qualify for this comprehensive protocol assessment, the
sponsor must have had an end-of-Phase 2/pre-Phase 3 meeting
with the review division so that the division is aware of the
developmental context in which the protocol is being reviewed
and the questions being answered.
d. N.B. For products that will be using Subpart E or
Subpart H development schemes, the Phase 3 protocols
mentioned in this paragraph should be construed to mean those
protocols for trials that will form the primary basis of an
efficacy claim no matter what phase of drug development in
which they happen to be conducted.
e. If a protocol is reviewed under the process outlined
above and agreement with the Agency is reached on design,
execution, and analyses and if the results of the trial
conducted under the protocol substantiate the hypothesis of
the protocol, the Agency agrees that the data from the
protocol can be used as part of the primary basis for
approval of the product. The fundamental agreement here is
that having agreed to the design, execution, and analyses
proposed in protocols reviewed under this process, the Agency
will not later alter its perspective on the issues of design,
execution, or analyses unless public health concerns
unrecognized at the time of protocol assessment under this
process are evident.
2. Performance goal:
90% of special protocol assessments and agreement requests
completed and returned to sponsor within the timeframe.
3. Reporting:
The Agency will track and report the number of original
special protocol assessments and resubmissions per original
special protocol assessment.
J. Meeting Management Goals
Formal PDUFA meetings between sponsors and FDA consist of
Type A, B, B(EOP), C, Type D and INTERACT meetings. FDA plays
an active role during drug development by providing advice
and feedback to sponsors on the overall drug development
programs during meetings conducted between sponsors
[[Page S5182]]
and FDA. In general, FDA's guidance provided at these
meetings describe the Agency's current thinking on a topic
and should be viewed only as recommendations, unless specific
regulatory or statutory requirements are cited. These
meetings are further described below.
Type A meetings are those meetings that are necessary for
an otherwise stalled drug development program to proceed
(i.e., a ``critical path'' meeting) or to address an
important safety issue. Post-action meetings requested within
three months after an FDA regulatory action other than
approval (i.e., issuance of a complete response letter) will
also generally be considered Type A meetings.
Type B meetings include pre-IND meetings and pre-NDA/BLA
meetings, while Type B(EOP) meetings are reserved for certain
End-of-Phase 1 meetings (i.e., for 21 CFR Part 312 Subpart E
or 21 CFR Part 314 Subpart H or similar products) and End-of-
Phase 2/pre-Phase 3 meetings. Meetings regarding REMS or
postmarketing requirements that occur outside the context of
the review of a marketing application will also generally be
considered Type B meetings.
A Type C meeting is any type of meeting other than Type A,
B, B(EOP), D, or INTERACT.
A Type D meeting is focused on a narrow set of issues
(e.g., often one, but typically not more than two issues and
associated questions). Requests could include:
A follow-up question that raises a new issue after a formal
meeting (i.e., more than just a clarifying question about an
FDA response from a prior meeting);
A narrow issue on which the sponsor is seeking Agency input
with only a few associated questions; or
A general question about an innovative development approach
that does not require extensive, detailed advice.
Type D meetings should be limited to no more than 2 focused
topics. If the sponsor has several issues or a complex single
issue with multiple questions, a Type C meeting should be
requested rather than requesting several Type D meetings. In
addition, the issue should not require input from more than 3
disciplines or Divisions. If the scope of the meeting is
broad or includes complex questions/issues that require input
from more than 3 disciplines or Divisions, then FDA will
inform the sponsor that the Agency will be converting the
meeting to the appropriate meeting type (Type B or C) and the
sponsor can either withdraw their request or accept the FDA's
meeting-type conversion without re-submitting a new meeting
request.
1. INitial Targeted Engagement for Regulatory Advice on
CBER/CDER ProducTs (INTERACT) meetings are intended for novel
questions and unique challenges in early development (i.e.,
prior to filing of an IND). The issues typically relate to
IND requirements for example: questions regarding design of
IND-enabling toxicity studies (e.g., species, endpoints),
complex manufacturing technologies or processes, development
of innovative devices used with a drug or biologic, or the
use of cuttingedge testing methodologies. INTERACT meetings
are intended to facilitate IND-enabling efforts where the
sponsor is facing a novel, challenging issue that might
otherwise delay progress of the product towards entry into
the clinic in the absence of this early FDA input. Typically,
the issue is early in a development program--prior to when a
pre-IND meeting might be requested--and the issue may delay
initiation of, or progress of, IND-enabling studies. The
sponsor needs to have selected a specific investigational
product or a product-derivation strategy to evaluate in a
clinical study before requesting an INTERACT meeting.
a. Questions and topics within the scope of an INTERACT
meeting include:
i. Novel questions for all CDER and CBER products (i.e.,
questions where there is no existing guidance or other
information in writing the company could reference from FDA).
ii. These meetings are intended to provide FDA input on
issues that a sponsor needs to address prior to a pre-IND
meeting, including issues such as:
1) Choice of appropriate preclinical models or necessary
toxicology studies for novel drug platforms or drug
candidates;
2) CMC issues or testing strategies aimed to demonstrate
product safety, adequate to support first-in-human study;
3) Overall advice related to the design of proof-of-concept
or other pilot safety/biodistribution studies necessary to
support administration of an investigational product in a
first-in-human clinical trial;
4) General recommendations regarding a future first-in-
human trial in a target clinical population where the
population is novel and there is no prior precedent or
guidance;
5) Recommendations on approach for further development of
an early-stage product with limited CMC, pharmacology/
toxicology, and/or clinical data that were collected outside
of a US IND; and
6) Other topics that would be agreed upon by FDA.
2. Responses to Meeting Requests
a. Procedure: FDA will notify the requester in writing of
the date, time, and place for the meeting, as well as
expected Center participants following receipt of a formal
meeting request. Table 3 below indicates the timeframes for
FDA's response to a meeting request.
TABLE 3
------------------------------------------------------------------------
Response
Time
Meeting Type (calendar
days)
------------------------------------------------------------------------
A.......................................................... 14
B.......................................................... 21
B(EOP)..................................................... 14
C.......................................................... 21
D.......................................................... 14
INTERACT................................................... 21
------------------------------------------------------------------------
i. For any type of meeting, the sponsor may request a
written response to its questions rather than a face-to-face
or teleconference meeting. FDA will review the request and
make a determination on whether a written response is
appropriate or whether a face-to-face or teleconference
meeting is necessary. If a written response is deemed
appropriate, FDA will notify the requester of the date it
intends to send the written response in the Agency's response
to the meeting request. This date will be consistent with the
timeframes specified in Table 4 below for the specific
meeting type.
ii. For pre-IND, Type C, Type D, and INTERACT meetings,
while the sponsor may request a face-to-face meeting, the
Agency may determine that a written response to the sponsor's
questions would be the most appropriate means for providing
feedback and advice to the sponsor. When it is determined
that the meeting request can be appropriately addressed
through a written response, FDA will notify the requester of
the date it intends to send the written response in the
Agency's response to the meeting request. This date will be
consistent with the timeframes specified in Table 4 below for
the specific meeting type. If the sponsor believes a face-to-
face Pre-IND 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 convert where possible WRO to a face-
to-face meeting for requests that includes novel approaches
to clinical development and/or where precedents are not well
established.
b. Performance Goal: FDA will respond to meeting requests
and provide notification within the response times noted in
Table 3 for 90% of each meeting type.
3. Scheduling Meetings
a. Procedure: FDA will schedule the meeting on the next
available date at which all applicable Center personnel are
available to attend, consistent with the component's other
business; however, the meeting should be scheduled consistent
with the type of meeting requested. Table 4 below indicates
the timeframes for the scheduled meeting date following
receipt of a formal meeting request, or in the case of a
written response, the timeframes for the Agency to send the
written response. If the requested date for any meeting type
is greater than the specified timeframe, the meeting date
should be within 14 calendar days of the requested date.
Table 4
------------------------------------------------------------------------
Meeting Scheduling or
Meeting Type Written Response Time
------------------------------------------------------------------------
A......................................... 30 calendar days from
receipt of meeting request
B......................................... 60 calendar days from
receipt of meeting request
B(EOP).................................... 70 calendar days from
receipt of meeting request
C......................................... 75 calendar days from
receipt of meeting request
D......................................... 50 calendar days from
receipt of meeting request
INTERACT.................................. 75 calendar days from
receipt of meeting request
------------------------------------------------------------------------
b. Performance goal:
i. Type A, B, B(EOP) and C meetings: 90% of meetings are
held within the timeframe for each meeting type, and 90% of
written responses are sent within the timeframe for each
meeting type.
ii. Type D meeting: performance goals for FDA will be
phased in, starting in FY 2023 as follows:
1) By FY 2023, hold 50% of Type D meetings, or send written
response, within 50 calendar days from receipt of meeting
request.
2) By FY 2024, hold 60% of Type D meetings, or send written
response, within 50 calendar days from receipt of meeting
request.
3) By FY 2025, hold 70% of Type D meetings, or send written
response, within 50 calendar days from receipt of meeting
request.
4) By FY 2026, hold 80% of Type D meetings, or send written
response, within 50 calendar days from receipt of meeting
request.
5) By FY 2027, hold 90% of Type D meetings, or send written
response, within 50 calendar days from receipt of meeting
request.
INTERACT meeting: performance goals for FDA will be phased
in, starting in FY 2023 as follows:
1) By FY 2023, hold 50% of INTERACT meetings, or send
written response, within 75 calendar days from receipt of
meeting request.
2) By FY 2024, hold 60% of INTERACT meetings, or send
written response, within 75 calendar days from receipt of
meeting request.
3) By FY 2025, hold 70% of INTERACT meetings, or send
written response, within 75 calendar days from receipt of
meeting request.
4) By FY 2026, hold 80% of INTERACT meetings, or send
written response, within 75 calendar days from receipt of
meeting request.
5) By FY 2027, hold 90% of INTERACT meetings, or send
written response, within 75 calendar days from receipt of
meeting request.
4. Meeting Background Packages
The timing of the Agency's receipt of the sponsor
background package for each meeting type (including those
meetings for which a written response will be provided) is
specified in Table 5 below.
[[Page S5183]]
TABLE 5
------------------------------------------------------------------------
Receipt of Background
Meeting Type Package
------------------------------------------------------------------------
A......................................... At the time of the meeting
request
B......................................... 30 calendar days before the
date of the meeting or
expected written response
B(EOP).................................... 50 calendar days before the
date of the meeting or
expected written response*
C......................................... 47 calendar days before the
date of the meeting or
expected written response*
D......................................... At the time of the meeting
request
INTERACT.................................. At the time of the meeting
request
------------------------------------------------------------------------
* If the scheduled date of a Type B(EOP) or C meeting is earlier than
the timeframes specified in Table 4, the meeting background package
will be due no sooner than 6 calendar days and 7 calendar days
following the response time for Type B(EOP) and C meetings specified
in Table 3, respectively.
5. Preliminary Responses to Sponsor Questions
a. Procedure: The Agency will send preliminary responses to
the sponsor's questions contained in the background package
no later than five calendar days before the meeting date for
Type B(EOP), C, D, and INTERACT meetings. For all other
meeting types, the FDA intends to send the requester its
preliminary responses no later than 2 calendar days before
the meeting.
b. Performance goal: 90% of preliminary responses to
questions for Type B(EOP), D, and INTERACT meetings are
issued by FDA no later than five calendar days before the
meeting date.
6. Sponsor Notification to FDA
Not later than three calendar days following the sponsor's
receipt of FDA's preliminary responses for a Type B(EOP), D,
INTERACT, or C meeting, the sponsor will notify FDA of
whether the meeting is still needed, and if it is, the
anticipated agenda of the meeting given the sponsor's review
of the preliminary responses.
7. Meeting Minutes
a. Procedure: The Agency will prepare minutes that will be
available to the sponsor 30 calendar days after the meeting
for Type A, B, B(EOP), C, and D. The minutes will clearly
outline the important agreements, disagreements, issues for
further discussion, and action items from the meeting in
bulleted form and need not be in great detail. Meeting
minutes are not required if the Agency transmits a written
response for any meeting type. For INTERACT meetings,
preliminary responses will be annotated and resent within 30
calendar days if advice provided changes as a result of the
meeting. In cases of a WRO, the WRO will serve as meeting
minutes from FDA.
b. Performance goal: 90% of minutes are issued within 30
calendar days of the date of the meeting.
8. Conditions
For a meeting to qualify for these performance goals:a.
A written request must be submitted to the review division.
b. The written request must provide:
i. A brief statement of the purpose of the meeting and the
sponsor's proposal for either a face-to-face/virtual/
teleconference meeting or a written response from the Agency;
ii. A listing of the specific objectives/outcomes the
requester expects from the meeting;
iii. A proposed agenda, including estimated times needed
for each agenda item;
iv. A listing of planned external attendees;
v. A listing of requested participants/disciplines
representative(s) from the Center with an explanation for the
request as appropriate; and
vi. The date that the meeting background package will be
sent to the Center. Refer to Table 5 for timeframes for the
Agency's receipt of background packages.
c. The Agency concurs that the meeting will serve a useful
purpose (i.e., it is not premature or clearly unnecessary).
However, requests for a Type B or B(EOP) meeting will be
honored except in the most unusual circumstances.
9. Guidance, Clarity, and Transparency
a. 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 PDUFA Products'' with
information pertaining to INTERACT, Type D meetings, and 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 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. Training: FDA will conduct external training to ensure
the best practices outlined in the draft guidances are
communicated to Industry.
K. Enhancing Regulatory Science and Expediting Drug
Development
To ensure that new and innovative products are developed
and available to patients in a timely manner, FDA will
continue to advance the use of biomarkers and
pharmacogenomics, enhancing communications between FDA and
sponsors during drug development, and advancing the
development of drugs for rare diseases. The extension and
continuation of this work will encompass further evaluation
and enhancement of FDA-sponsor communications, ensuring the
sustained success of the breakthrough therapy program,
continuing early consultations between FDA and sponsors on
the use of new surrogate endpoints as the primary basis for
product approval, advancing rare disease drug development,
advancing the development of combination products, and
exploring the use of real world evidence for use in
regulatory decision-making.
1. Promoting Innovation Through Enhanced Communication
Between FDA and Sponsors During Drug Development
FDA's philosophy is that timely interactive communication
with sponsors during drug development is a core Agency
activity to help achieve the Agency's mission to facilitate
the conduct of efficient and effective drug development
programs, which can enhance public health by making new safe
and effective drugs available to the American public in a
timely manner. Accordingly, FDA will maintain dedicated drug
development communication and training staffs in CDER and
CBER, focused on enhancing communication between FDA and
sponsors during drug development.
One function of the staff is to serve as a liaison that
will facilitate general and, in some cases, specific
interactions between sponsors and each Center. The liaison
will serve as a point of contact for sponsors who have
general questions about drug development or who need
clarification on which review division to contact with their
questions. The liaison will also serve as a secondary point
of contact in each Center for sponsors who are encountering
challenges in communication with the review team for their
IND (e.g., in instances when they have not received a
response from the review team to a simple or clarifying
question or referral to the formal meeting process within
30 days of the sponsor's initial request). In such cases,
the liaison will work with the review team and the sponsor
to facilitate resolution of the issue.
The second function of the staff is to provide ongoing
training to the review organizations on best practices in
communication with sponsors. The content of training
includes, but is not limited to, FDA's philosophy regarding
timely interactive communication with sponsors during drug
development as a core Agency activity, best practices for
addressing sponsor requests for advice and timely
communication of responses through appropriate mechanisms
(e.g., teleconferences, secure email, or when questions are
best addressed through the formal meetings process), and the
role of the liaison staff in each Center in facilitating
communication between the review staff and sponsor community,
including the staff's role in facilitating resolution of
individual communication requests. The staff will also
collaborate with sponsor stakeholders (e.g., through
participation in workshops, webinars, and other meetings) to
communicate FDA's philosophy and best practices regarding
communication with sponsors during drug development.
Best Practices for meetings 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 timely
interactive communication with sponsors during drug
development in PDUFA VII, FDA will do the following:
a. Public Workshop. FDA will hold a public meeting to
discuss best practices for meeting management by July 30,
2024, including issues related to submission of meeting
requests, efficient time management, coordinating meeting
agenda, development and submission of meeting background
packages and lessons learned from the Coronavirus Disease
2019 (``COVID-19'') pandemic including virtual meeting
platforms. Learnings from the public meeting could inform
FDA's internal process improvement efforts and, as
appropriate, be reflected in updating guidances, as noted
below. This public workshop will also discuss and share
experience and metrics related to all PDUFA meeting
activities, including Type D and INTERACT meetings. FDA will
discuss the number of meeting requests granted and denied for
INTERACT meetings, including a summary of rationales for
denied meeting requests. Reported metrics will include the
number of requests granted and denied for in-person pre-IND,
Type C, Type D, and INTERACT meetings. FDA and Industry will
agree on the information that FDA may share publicly in this
meeting.
b. Guidance. Based on the discussion at the public meeting
mentioned above in paragraph (a), and FDA's experience with
conducting meetings effectively, FDA will update public
documents, as appropriate, including publishing revised draft
or final version of the Best Practices for Communication
Between IND Sponsors and FDA During Drug Development guidance
mentioned below, 18 months after the public meeting is held.
c. Training. FDA will conduct external training to ensure
the best practices outlined in the guidances are communicated
to Industry.
2. Ensuring Sustained Success of Breakthrough Therapy
Program
[[Page S5184]]
Breakthrough therapy designation is intended to expedite
the development and review of drug and biological products,
alone or in combination, for serious or life-threatening
diseases or conditions when preliminary clinical evidence
indicates that the drug may demonstrate substantial
improvement over existing therapies. A breakthrough therapy
designation includes the features of the fast track program,
intensive FDA guidance on an efficient drug development
program, and an organizational commitment by FDA involving
senior managers. FDA will continue to retain current
resources to enable the Agency to continue to work closely
with sponsors throughout the breakthrough therapy
designation, development, and review processes. Both FDA and
the regulated industry are committed to ensuring the
expedited development and review of innovative therapies for
serious or life-threatening diseases or conditions by
investing additional resources into the breakthrough therapy
program.
3. Early Consultation on the Use of New Surrogate Endpoints
FDA and industry believe that early consultation between
review teams and sponsors is important for development
programs where the sponsor intends to use a biomarker as a
new surrogate endpoint that has never been previously used as
the primary basis for product approval in the proposed
context of use. Early consultation in the drug development
program allows the review team to consult with FDA senior
management to evaluate the sponsor's proposal before
providing advice regarding the proposed biomarker as a new
surrogate endpoint to support accelerated or traditional
approval. Requests to engage with FDA on this topic will be
considered a Type C meeting request. The purpose of this
meeting is to discuss the feasibility of the surrogate as a
primary endpoint and identify any gaps in knowledge and how
they might be addressed. The outcome of this meeting may
require further investigation by the sponsor and discussion
and agreement with the agency before the surrogate endpoint
could be used as the primary basis for product approval. To
qualify for this consultation, these Type C meeting requests
must be accompanied by the complete meeting background
package at the time the request is made that includes
preliminary human data indicating impact of the drug on the
biomarker at a dose that appears to be generally tolerable.
The remaining meeting procedures as described in Section I.J
of this document will apply.
4. Advancing Development of Drugs for Rare Diseases
FDA will build on the success of rare disease programs in
CDER and CBER by continuing to advance and facilitate the
development and timely approval of drugs and biologics for
rare diseases, including rare diseases in children. The Rare
Diseases Team staff in CDER will continue to be integrated
into review teams for rare disease development programs and
application review to provide their unique expertise on
flexible and feasible approaches to studying and reviewing
such drugs to include, for example, innovative use of
biomarkers, consideration of non-traditional clinical
development programs, use of adaptive study designs,
evaluation of novel endpoints, application of new approaches
to statistical analysis, and appropriate use of FDA's
expedited development and review programs (i.e., Fast Track,
Breakthrough, Priority Review, and Accelerated Approval).
CBER, through its Rare Disease Program Staff, will also
ensure that its review offices consider such flexible and
feasible approaches in review.
The rare disease staff will also continue to provide
training to all CDER and CBER review staff related to
development, review, and approval of drugs for rare diseases
as part of the reviewer training core curriculum. The
objective of the training will be to familiarize review staff
with the challenges associated with rare disease applications
and strategies to address these challenges; to promote best
practices for review and regulation of rare disease
applications; and to encourage flexibility and scientific
judgment among reviewers in the review and regulation of rare
disease drug development and application review. The training
will also emphasize the important role of the rare disease
staff as members of the core review team to help ensure
consistency of scientific and regulatory approaches across
applications and review teams.
Rare disease staff will continue to engage in outreach to
industry, patient groups, and other stakeholders to provide
training on FDA's rare disease programs. The staff will
continue to foster collaborations in the development of tools
(e.g., patient reported outcome measures) and data (e.g.,
natural history studies) to support development of drugs for
rare diseases. In addition, the staff will also facilitate
interactions between stakeholders and FDA review divisions to
increase awareness of FDA regulatory programs and engagement
of patients in FDA's regulatory decision-making.
FDA will include updates on the activities and success of
the rare disease programs in the PDUFA annual performance
report to include, for example, the number of training
courses offered and staff trained, the number of review
programs where rare disease staff participated as core team
members, and metrics related to engagement with external
stakeholders. FDA will also continue to include information
on rare disease approvals in its annual reports on innovative
drug approvals, including utilization of expedited programs
and regulatory flexibility and appropriate comparative
metrics to non-rare disease innovative approvals.
a. Rare Disease Endpoint Advancement (RDEA) Pilot Program
The lack of regulatory precedent, small trial populations,
and/or limited understanding of disease natural history
associated with rare diseases creates unique challenges when
determining the appropriate efficacy endpoint(s) for clinical
trials intended to evaluate the effectiveness of rare disease
therapies.
Though difficult to establish, well-developed efficacy
endpoints, especially those that could apply to other rare
diseases with similar manifestations, drive the general
advancement of rare disease drug development. In addition to
challenges associated with developing endpoints that
appropriately capture key signs and symptoms of a rare
disease and directly measure how patients feel, function,
or survive, surrogate endpoint development is also
challenging in diseases with slow progression, small
patient populations, or other challenges commonly
associated with drug development in rare diseases.
Current mechanisms for sponsors of rare disease drug
development programs to collaborate with FDA are not
structured to provide repeated, intensive interactions with
the Agency. To support the advancement of rare disease
treatments, FDA will establish a pilot program for supporting
efficacy endpoint development for drugs that treat rare
diseases by offering additional engagement opportunities with
the Agency to sponsors of development programs that meet
specific criteria. In addition, FDA will develop the staff
capacity to enable and facilitate appropriate development and
use of these types of novel endpoints. This staff will
support the complex and intensive review work necessary to
evaluate novel endpoint development with a focus on the
challenges of trial designs utilizing small populations.
Scope. The RDEA pilot program will seek to advance rare
disease drug development programs by providing a mechanism
for sponsors to collaborate with FDA throughout the efficacy
endpoint development process. An endpoint, or endpoints, will
be considered eligible for proposal submission to RDEA if
each of the following criteria are met:
(1) The associated development program should be active and
address a rare disease, with an active IND or pre-IND for the
rare disease.
(a) Sponsors who do not yet have an active development
program but have, or are initiating, a natural history study
where the proposed endpoint is intended to be studied are
also eligible to apply.
(b) The FDA may also consider accepting a proposal for a
development program for a common disease that includes
innovative or novel endpoint elements, including the specific
endpoint and/or the methodology being developed, if there is
sufficient justification that the proposal could be
applicable to a rare disease.
(2) The proposed endpoint is a novel efficacy endpoint
intended to establish substantial evidence of effectiveness
for a rare disease treatment.
(a) An endpoint is considered novel if it has never been
used to support drug approval or if it has been substantially
modified from previous use to support drug approval.
(b) Preference will be given to proposals that have the
potential to impact drug development more broadly, such as
one that uses a novel approach to develop an efficacy
endpoint or an endpoint that could potentially be relevant to
other diseases. Preference will also be given to accepting
proposals that reflect a range of different types of
endpoints.
(c) For surrogate endpoint proposals, preference will be
given to those with novel approaches for collecting
additional clinical data in the pre-market stage to advance
the validation of these endpoints. If the sponsor is
proposing to develop a surrogate endpoint as part of a rare
disease application, participation in a prior Type C
Surrogate Endpoint meeting is encouraged.
(3) FDA will select a limited number of qualified proposals
for admission into RDEA that increases after the first year
of PDUFA VII:
(a) FY 2023: Sponsors may submit proposals beginning in Q4,
and FDA will accept a maximum of 1 proposal.
(b) FY 2024-FY 2027: FDA will accept up to 1 proposal per
quarter with a maximum of 3 proposals per year.
(c) Expansion of the program may be dependent on FDA
staffing.
Process and Timeline. The following steps summarize the
process for applying to and participating in the RDEA pilot
program:
(1) A sponsor who believes a development program qualifies
for participation in RDEA will submit a proposal to FDA that
includes a justification addressing each of the criteria
described above, including scientific justification for why
the endpoint is being explored to measure meaningful clinical
benefit in the disease/condition, relevant summaries of
pertinent information related to the endpoint from prior
studies, as well as a statement indicating if the company is
willing to allow disclosure of information for broader
development and educational purposes.
(2) FDA will confirm receipt of the sponsor's proposal
within 14 days of receipt.
(3) FDA will notify the sponsor with a final selection
decision no later than 60 days following the end of the FY
quarter during which it is submitted.
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(4) Before FDA grants the initial meeting, FDA and the
sponsor will agree on the information that FDA may share
publicly. When feasible, FDA will notify a sponsor in advance
when the sponsor's program is the planned focus of a public
discussion. Participation in the pilot program, including
such agreement on information disclosure, will be voluntary
and at the discretion of the sponsor. If FDA and the sponsor
of an accepted proposal are unable to reach agreement on
elements for public disclosure, however, that proposal will
no longer be part of the RDEA pilot program and the Agency
will proceed with an alternate submission.
(5) Sponsors admitted to the RDEA pilot may participate in
up to 4 focused meetings with relevant FDA staff to discuss
endpoint development.
(a) The sponsor will provide a briefing document upon
submission of each meeting request.
(b) Each meeting will be scheduled within 45 days following
FDA's receipt of the sponsor's meeting request and complete
briefing document.
(c) The scheduling timeline may be shortened for meeting
requests to discuss narrow issues and/or questions at FDA's
discretion.
(d) The timing between each meeting is flexible and depends
on how much time the sponsor needs to identify new issues
and/or questions and prepare required materials for the next
meeting.
(6) Sponsors who have completed the maximum of 4 RDEA
meetings or do not have additional endpoint-focused questions
or issues to discuss with FDA may proceed with the standard
regulatory submission process.
(a) FDA's advice provided during and between RDEA meetings
does not constitute a regulatory decision and is considered
non-binding. Completing the 4 RDEA meetings does not
guarantee approval for a regulatory submission that includes
efficacy endpoints discussed during RDEA meetings.
(b) After completion of 4 RDEA meetings, the sponsor can
request additional input from FDA, as needed, through other
formal meeting mechanisms, such as Type B, Type C, Type C
Surrogate Endpoint, or Type D meetings.
(7) Sponsors who do not participate in the pilot will have
an opportunity to interact with the Agency through
traditional channels.
iii. Transparency and Endpoint Advancement. As part of
RDEA, FDA will conduct up to 3 public workshops by the end of
FY 2027 to discuss various topics relevant to endpoint
development for rare diseases, such as the use of multidomain
analysis methods. To promote innovation and evolving science,
novel endpoints developed through RDEA may be presented by
FDA, such as in guidance documents, on a public-facing
website, or at public workshops as case studies, including
prior to FDA's approval for the drug studied in the trial.
However, as noted above, before FDA grants the initial RDEA
meeting the Agency and the sponsor will agree on the
information that FDA may share publicly in these case
studies. When feasible, FDA will notify a sponsor in
advance when the sponsor's program is the planned focus of
a public discussion.
5. Advancing Development of Drug-Device and Biologic-Device
Combination Products Regulated by CBER and CDER
a. For 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 safe and effective use of a drug-device or
biologic-device combination product. FDA will establish the
following procedures for review of URRAs for combination
products:
i. 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.
ii. 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.
iii. URRA submission: performance goals for FDA will be
phased in, starting FY 2024 as follows:
1) By FY 2024, review and notify sponsor of agreement or
non-agreement with comments for 50% of filed submissions,
within 60 days of receipt of submission.
2) By FY 2025, review and notify sponsor of agreement or
non-agreement with comments for 70% of filed submissions,
within 60 days of receipt of submission.
3) By FY 2026, review and notify sponsor of agreement or
non-agreement with comments for 90% of filed submissions,
within 60 days of receipt of submission.
4) By FY 2027, review and notify sponsor of agreement or
non-agreement with comments for 90% of filed submissions,
within 60 days of receipt of submission.
iv. By the end of FY 2024, FDA will publish new draft or
revised guidance for review staff and industry describing
considerations related to drug-device and biologic-device
combination products on the topics noted below.
Guidance that 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.
v. Sponsors may still elect to submit a URRA with a HF
validation protocol and will only be subject to timelines in
Section I.K.5.b, For Human Factor Validation Study Protocols.
b. For Human Factor Validation Study Protocols
Human factors studies are conducted to evaluate the user
interface of a drug-device or 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:
i. 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).
ii. 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:
i. 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.
6. Advancing Real-World Evidence for Use in Regulatory
Decision-Making
In accordance with Section 3022 of the 21st Century Cures
Act, and by providing earlier and increased Agency advice,
the Advancing RWE Program seeks to improve the quality and
acceptability of RWE-based approaches in support of new
intended labeling claims, including approval of new
indications of approved medical products or to satisfy post-
approval study requirements. Specifically, FDA will do the
following:
a. By no later than December 31, 2022, FDA will establish
and communicate publicly a pilot Advancing RWE Program
intended to:
i. Identify approaches for generating RWE that meet
regulatory requirements in support of labeling for
effectiveness (e.g., new indications, populations, dosing
information) or for meeting post-approval study requirements;
ii. Develop agency processes that promote consistent
decision-making and shared learning regarding RWE;
iii. Promote awareness of characteristics of RWE that can
support regulatory decisions by allowing FDA to discuss study
designs considered in the Advancing RWE Program in a public
forum.
b. The Advancing RWE Program will include but not be
limited to the following activities and components:
i. FDA will solicit applications for the Advancing RWE
Program twice (i.e., two cycles) each year, asking sponsors
to describe--before protocol development or study
initiation--the regulatory question(s) they seek to address
with RWE, the proposed RWE study design, and the potential
real-world data (RWD) source(s) to support that design;
ii. FDA will use a structured review process to evaluate
and rank applications, based on the information they present
that the data may be fit-for-use, the study design will be
adequate, and the proposed study conduct can be anticipated
to meet regulatory requirements. Consideration will be given
to promoting diversity of data sources, study designs,
analytical methodologies and regulatory indications, as well
as to diversity of diseases under study and FDA Centers and
Offices involved;
iii. FDA will accept one to two eligible and appropriate
proposals each cycle in the first and second year (FY 2023-
2024) of the Advancing RWE Program and one to four eligible
and appropriate proposals each cycle thereafter (FY 2025-
2027);
iv. FDA will notify sponsors regarding acceptance or non-
acceptance of their submission within 45 days of the
application deadline;
v. FDA will convene the first of up to four dedicated
Advancing RWE Program meetings within 75 days of the
application deadline, with subsequent meetings to be
scheduled within 45 days after receiving a request for such
meetings from the sponsor;
vi. The Advancing RWE Program represents an optional
pathway for sponsors
[[Page S5186]]
submitting RWE proposals to an IND with CDER or CBER.
Regardless of whether an Advancing RWE application is
accepted, not accepted, or was never submitted to the
Advancing RWE Program, established procedures (e.g., formal
PDUFA meetings with the review division) will continue to be
available;
vii. Before FDA grants the initial meeting, FDA and the
sponsor will agree on the information that FDA may share
publicly. When feasible, FDA will notify a sponsor in advance
when the sponsor's program is the planned focus of a public
discussion. Participation in the pilot program, including
such agreement on information disclosure, will be voluntary
and at the discretion of the sponsor;
viii. If FDA and the sponsor of an accepted proposal are
unable to reach agreement on elements for public disclosure,
however, that proposal will no longer be part of the
Advancing RWE Program and the Agency will proceed with an
alternate submission (The timelines for meetings described
above would shift based on the dates of accepting alternate
submissions, if applicable.);
ix. Discussions at Advancing RWE program-related meetings
will focus on data, design, and regulatory issues that have
the potential to generate RWE in support of a proposed
regulatory decision;
x. FDA participation in the Advancing RWE Program,
including the selection process and program-related meetings,
will include representatives from relevant review divisions,
other offices with RWE expertise, and senior leadership with
expertise in RWE;
xi. Sponsors and FDA can decide that four meetings may not
be necessary if an agreed-upon protocol is identified.
Conversely, if FDA determines that key data- or design-
related problems make the protocol unlikely to support the
intended regulatory decision, then subsequent meetings within
the Advancing RWE Program may not be conducted;
xii. FDA and sponsors agree that the goal of the Advancing
RWE Program is general agreement on key design elements. The
acceptability of evidence generated from any completed study
is a subsequent review issue;
xiii. Sponsors who do not participate in the pilot will
have an opportunity to interact with the Agency through
traditional channels.
c. By no later than June 30, 2024, FDA will report
aggregate and anonymized information, on at least an annual
basis and based on available sources (e.g., information
provided by review divisions), describing RWE submissions to
CDER and CBER. The reports will describe application type
(e.g., primary focus on safety or effectiveness), data
sources used (e.g., medical claims, electronic health
records, registries, digital health technologies), study
design employed (e.g., randomized trial, externally
controlled trial, observational study), and regulatory
request (e.g., new indication, population, dosing
information, post-approval study requirement for a marketed
product). This reporting will include but not be limited to
protocols emerging from the Advancing RWE Program.
d. By no later than December 31, 2025, FDA will convene a
public workshop or meeting to discuss RWE case studies with a
particular focus on approaches for generating RWE that can
potentially meet regulatory requirements in support of
labeling for effectiveness (e.g., new indications,
populations, dosing information) or for meeting post-approval
study requirements.
e. By no later than December 31, 2026, experience gained
with the Advancing RWE Program, as well as CDER's and CBER's
RWE program in general, will be used to update existing RWE-
related guidance documents or generate new draft guidance, as
appropriate.
L. Enhancing Regulatory Decision Tools to Support Drug
Development and Review
Delivering new medicines to patients through biomedical
innovation requires advances in regulatory decision tools to
support drug development and review. FDA will build on the
successes of its efforts on Patient Focused Drug Development
(PFDD), benefit-risk assessment in regulatory decision-
making, and the drug development tools qualification pathway
for biomarkers. FDA will also continue to advance modern
approaches to enhance the efficiency of the drug development
and review processes, such as complex adaptive, Bayesian, and
other novel clinical trial designs and model-informed drug
development (MIDD).
1. Enhancing the Incorporation of the Patient's Voice in
Drug Development and Decision-Making
To facilitate the advancement and use of systematic
approaches to collect and utilize robust and meaningful
patient and caregiver input that can more consistently inform
drug development and, as appropriate, regulatory decision
making, FDA will conduct the following activities during
PDUFA VII:
a. FDA will continue to strengthen capacity to facilitate
development and use of Patient-Focused methods to inform drug
development and regulatory decisions. This includes expanded
internal staff training and external outreach to industry
sponsors and other involved stakeholders with emphasis on
patient-focused drug development (PFDD) methods and tools-
related guidance and practice to achieve broad acceptance and
integration into regulatory decision making across review
divisions and industry development programs. FDA will also
engage external experts, through a mechanism called the
Intergovernmental Personnel Act, to support the review of
patient experience data. These external methodological
experts will possess extensive knowledge in methods and
approaches related to patient experience data and will
augment existing internal expertise.
i. FDA will undertake a broad-based effort to conduct
outreach and training across review divisions, with follow-up
consultation as these methods gain broad acceptance and
integration, including development of methodology training
courses for review staff that will be conducted at least two
times per year.
ii. FDA will conduct targeted outreach to industry and
methodological consulting organizations to provide
presentations, sessions, and resources to increase
understanding, acceptance, and integration into development
programs.
b. FDA will issue a Request for Information (RFI) to elicit
public input on methodological issues, including the
submission and evaluation of patient experience data in the
context of the benefit-risk assessment and product labeling,
and other areas of greatest interest or concern to public
stakeholders. This RFI will be issued by no later than the
end of June 2023.
i. FDA will issue a Federal Register Notice summarizing the
input to the RFI by no later than the end of December 2023
and, based on the input received in response to the RFI, FDA
will plan to conduct at least 2 public workshops focused on
methodological issues.
ii. The first workshop will be held no later than the end
of FY 2024.
iii. The second workshop will be held no later than the end
of FY 2025.
iv. Based on the RFI and the learnings from the workshops,
FDA will produce a written summary with identified priorities
for future work no later than the end of FY 2026.
c. FDA will continue to work to develop a virtual catalog
of standard core sets of Clinical Outcome Assessments (COAs)
and Related Endpoints, pursuing non-user fee funding for the
work to develop standard core sets, which will be available
for public use. FDA will also work to enhance understanding
of how patient preference informs meaningful benefit or
benefit-risk tradeoffs in therapeutic areas.
d. A public input process through either the Federal
Register or Public Meetings will allow FDA to understand
stakeholder's perspectives on diseases and domains of
greatest need or highest priority for development of Standard
Core COAs and Endpoints as well as priority areas where
decisions are preference-sensitive and patient preference
information (PPI) data can inform regulatory decision-making.
e. By September 30, 2026, FDA will publish draft guidance
on use and submission of patient preference information to
support regulatory decision making. 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.
2. Benefit-Risk Assessment in Regulatory Decision-Making
Benefit-risk assessment is a foundation of FDA's regulatory
review of marketing applications for new human drugs and
biologics. FDA currently includes the Benefit-Risk Framework
in its NDA and BLA review training, processes, and templates
to support the conduct and communication of its benefit-risk
assessment. CBER incorporates benefit-risk assessment through
interdisciplinary review and has integrated the Benefit-Risk
Framework into its clinical review template for its new BLA
and supplement assessments. CDER has similarly integrated the
Benefit-Risk Framework into its clinical review and
decisional memo templates.
FDA is committed to continuing its implementation and
application of structured benefit-risk assessment in its
regulatory review processes and documentation. FDA will
continue to explore additional opportunities to enhance its
use and communication of its benefit-risk assessments for new
drug and biological review.
3. Advancing Model-Informed Drug Development
FDA will build on the success of the ``model-informed drug
development'' (MIDD) approaches by continuing to advance and
integrate the development and application of exposure-based,
biological, and statistical models derived from preclinical
and clinical data sources in drug development and regulatory
review. FDA will conduct the following activities during
PDUFA VII:
a. By no later than the end of 1st Quarter of FY 2023, FDA
will publish a Federal Register Notice announcing the
continuation of the MIDD paired meeting program, outlining
program eligibility, and describing the proposal submission
and selection process.
b. For sponsors participating in the MIDD paired meeting
program, FDA will grant a pair of meetings specifically
designed for this program, consisting of an initial and a
follow-up meeting on the same drug development issues. The
second meeting will occur within approximately 60 days of
receiving the briefing materials. These meetings will be led
by the clinical pharmacology or biostatistical review
components within CDER
[[Page S5187]]
or CBER in partnership with clinical staff at the relevant
center to ensure alignment with decision makers.
c. Starting in FY 2023, FDA will select 1-2 eligible and
appropriate proposals per quarter each year (i.e. up to 8 per
year). Additional proposals that meet the eligibility
criteria may be selected depending upon the availability of
resources. The internal review group instituted by FDA will
continue to review proposals on a quarterly basis and provide
recommendations on prioritization and selection of proposals
and share knowledge and experience.
d. Sponsors who do not participate in the MIDD paired
meeting program will have an opportunity to interact with the
Agency through traditional channels.
e. FDA will issue a Request for Information (RFI) to elicit
public input for identifying priority focus areas for future
policy or guidance development and stakeholder engagement.
This RFI will be issued by no later than the end of FY 2024.
4. Enhancing Capacity to Review Complex Innovative Designs
To facilitate the advancement and use of complex adaptive,
Bayesian, and other novel clinical trial designs, FDA will
conduct the following activities during PDUFA VII:
a. FDA will continue to develop CDER and CBER staff
capacity to enable processes to facilitate appropriate use of
these types of methods. This staff will support the
computationally intensive review work necessary to evaluate
complex adaptive, Bayesian, and other novel clinical trial
designs, with a particular focus on clinical trial designs
for which simulations are necessary to evaluate the operating
characteristics. FDA will also engage external experts
through existing FDA mechanisms (e.g., Intergovernmental
Personnel Act assignment) to support the review of complex
innovative designs. These methodological experts will possess
extensive knowledge in the aforementioned topics and will
augment existing internal expertise.
b. FDA will maintain the paired meeting program, selecting
1-2 eligible and appropriate proposals per quarter each year
(i.e. up to 8 per year) for highly innovative trial designs
for which analytically derived properties (e.g., Type I
error) may not be feasible, and simulations are necessary to
determine trial operating characteristics. Additional
proposals that meet the eligibility criteria may be selected
depending upon the availability of resources. For INDs in the
program, FDA will grant a pair of meetings, consisting of an
initial and follow-up meeting on the same design. The second
meeting will occur within approximately 90 days of receiving
the briefing materials. Management of the overall program as
well as specific meetings to discuss innovative designs will
be led by the biostatistical review components within CDER or
CBER in partnership with clinical staff at each center. The
opportunity for increased interaction with the agency will
provide better understanding of the agency's requirements for
trial simulations involved in the use of the pilot study
design and allow for iteration of design modifications, if
needed. In return, FDA's ability to publicly discuss example
designs as agreed upon with participating sponsors will
provide better clarity on the acceptance of different types
of trial designs that should facilitate their use in future
development programs.
i. By no later than the end of 1st Quarter of FY 2023, FDA
will publish a Federal Register Notice announcing the
continuation of the paired meeting program, outlining program
eligibility, and describing the proposal submission,
selection process, and example topics that will advance the
use of complex innovative designs and inform the development
of a guidance document.
ii. FDA will select up to 8 proposals each year from
proposals submitted to either CDER or CBER. The selections
are expected to be made on a quarterly basis. Program
selection will be prioritized based on trial design features
and therapeutic areas of high unmet need.
iii. To promote innovation in this area, trial designs
developed through the paired meeting program may be presented
by FDA (e.g., in a guidance, at public workshops and
conferences, on the Complex Innovative Design website) as
case studies, including while the drug studied in the trial
has not yet been approved by FDA. Before FDA grants the
initial meeting, FDA and the sponsor will agree on the
information that FDA may share publicly in these case
studies. When feasible, FDA will notify a sponsor in advance
when the sponsor's program is the planned focus of a public
discussion. Participation in the paired meeting program,
including such agreement on information disclosure, will be
voluntary and at the discretion of the sponsor.
c. In order to encourage increased submissions by CBER-
regulated sponsors to the complex innovative design (CID)
paired meeting program, CBER staff will continue to engage in
outreach to industry and other stakeholders. Such outreach
will include providing information on the paired meeting
program and its benefits, such as enhanced attention
regarding CID proposals and advancing the leveraging and
sharing of knowledge to support efficient product
development; clarifying policies and procedures for
submitting CID proposals for review; and presenting FDA's
current thinking on CID-related technical topics.
d. Sponsors who do not participate in this paired meeting
program will have an opportunity to interact with the Agency
through traditional channels. This program will not affect
FDA's existing procedures for providing advice on trial
designs.
e. By the end of 2nd Quarter FY 2024, FDA will convene a
public workshop to discuss aspects of complex adaptive,
Bayesian, and other novel clinical trial designs. Discussion
topics will include considerations for external data sources,
Bayesian statistical methods, simulations, and clinical trial
implementation (e.g. examples of defining and mitigating bias
when using select trial design methods) and will be based on
FDA accumulated experience both within and outside of the
paired meeting program.
f. By the end of FY 2025, FDA will publish draft guidance
on the Use of Bayesian Methodology in Clinical Trials of
Drugs and Biologics. 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.
5. Enhancing Drug Development Tools Qualification Pathway
for Biomarkers
To facilitate the enhancement of the drug development tools
qualification pathway for biomarkers, FDA will conduct the
following activities during PDUFA VII:
a. FDA will continue to retain and enhance the staff
capacity to enhance biomarker qualification review by
increasing base capacity. FDA will also pilot processes to
engage external experts to support review of biomarker
qualification submissions.
b. FDA will continue to publish information on its website
regarding biomarker qualification submissions under section
507 of the FD&C Act, consistent with the requirements in
section 507(c), and to update the website quarterly.
c. Sponsors who do not use this qualification pathway will
have an opportunity to interact with the Agency through
traditional channels.
M. Enhancement and Modernization of the FDA Drug Safety
System
FDA will continue to use user fees to enhance the drug
safety system, including adopting new scientific approaches,
improving the utility of existing tools for the detection,
evaluation, prevention, and mitigation of adverse events,
modernizing REMS assessments, and coordinating regulatory
activity in the pre-market and post-market settings.
Enhancements to the drug safety system will improve public
health by increasing patient protection while continuing to
enable access to needed medical products.
User fees will provide support for 1) modernization and
improvement of REMS assessments and 2) optimization of the
Sentinel Initiative through a) maintenance of Sentinel
Initiative capabilities and continued integration into FDA
drug safety activities and b) enhancement of the analytic
capabilities of the Sentinel Initiative to address questions
of product safety and advance the understanding of how real-
world evidence can be used for studying effectiveness.
1. Modernization and Improvement of REMS Assessments
FDA will use user fee funds to modernize and improve REMS
assessments by incorporating REMS assessment planning into
the design of REMS, clarifying its expectations regarding
methods to evaluate the performance of REMS, increasing the
efficiency of FDA's review of REMS assessment reports, and
establishing FDA performance goals for review of REMS
assessment methods and study protocols.
a. By March 31, 2024, update relevant guidances to
incorporate REMS assessment planning into the design of the
REMS by providing recommendations regarding: 1) linking the
design with the assessments 2) ensuring sufficient and
appropriate data collection, and 3) identifying key metrics
for success (e.g., primary and secondary).
b. By March 31, 2024, FDA will issue new or update existing
policies and procedures for reviewing methodological
approaches and study protocols used to assess a REMS program.
c. Improve the efficiency of FDA's review of REMS
assessment reports.
i. By March 31, 2024, FDA will issue new or update existing
policies and procedures to systematically determine, as part
of the review of REMS assessment reports, if modifications to
the REMS or revisions to the REMS assessment plan are needed,
including the timing of the REMS assessments and to determine
whether the REMS is still necessary to ensure the benefits
outweigh the risks of the drug.
ii. By March 31, 2026, FDA will develop draft guidance
regarding the format and content of a REMS assessment report,
including the type of data that can support elimination of a
REMS. 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
[[Page S5188]]
after the close of the public comment period on the revised
draft guidance.
d. Establish FDA review performance goals and provide
feedback and comments on REMS methodological approaches and
study protocols used to assess a REMS program for products
within 90 days of receipt. FDA proposes the following staged
implementation of review performance goals for review of
methodological approaches and study protocols for REMS
assessments in PDUFA VII:
i. FY 2024, review and notify sponsor with concurrence or
comments within 90 days of receipt for 50% of REMS assessment
methods and protocols
ii. FY 2025, review and notify sponsor with concurrence or
comments within 90 days of receipt for 70% of REMS assessment
methods and protocols
iii. FY 2026 and FY 2027, review and notify sponsor with
concurrence or comments within 90 days of receipt for 90% of
REMS assessment methods and protocols
2. Optimization of the Sentinel Initiative
The user fee funds initially provided in PDUFA VI to expand
the Sentinel program will continue to systematically
implement and integrate Sentinel and BEST (Biologics
Effectiveness and Safety) Systems in FDA drug safety
activities by sustaining the high quality and large quantity
of data available, allowing continued application of advanced
methods for determining when and how those data are utilized,
and ensuring comprehensive training of review staff on the
use of Sentinel and BEST. These capabilities will support the
use of the Sentinel Initiative for regulatory decision making
to address questions of product safety and advance our
understanding of how real-world evidence can be used for
studying effectiveness.
a. Maintenance of the Sentinel Initiative Capabilities and
Continued Integration into FDA Drug Safety Activities
FDA will use user fee funds to maintain the quality and
quantity of data available through the Sentinel Initiative
(Sentinel and BEST), to maintain the processes and tools for
determining when and how those data are utilized, and to
support comprehensive training of review staff on the use of
Sentinel.
i. FDA will maintain the Sentinel's sources of data and
core capabilities for the safety surveillance of drugs and
biologics, including the multisite ARIA system.
ii. FDA will continue its communication with sponsors and
the public regarding general methodologies for Sentinel
queries, including what the Agency has learned regarding the
most appropriate ways to query and use Sentinel data.
iii. By the end of FY 2025, FDA will publish on its website
an update on facilitation of public and sponsor access to
Sentinel's distributed data network to conduct safety
surveillance.
iv. FDA will continue to post study results, study
parameters and analysis code online and maintain a strong
Sentinel web presence to host this information.
v. FDA will continue to maintain a comprehensive FDA
Sentinel training program for all relevant staff (e.g.,
epidemiologists, statisticians, project managers, medical
officers, clinical analysts, and other review team members)
to ensure that staff have a working knowledge of Sentinel,
can identify when Sentinel can inform important regulatory
questions and decisions, and are able to consistently
participate in use of Sentinel to evaluate safety issues.
vi. By the end of FY 2025, FDA will analyze, and report on
the use of Sentinel for regulatory purposes, e.g., in the
contexts of labeling changes, PMRs, or PMCs.
vii. For FY 2023-2027, FDA will report its obligations for
updated PDUFA VI commitments for PDUFA VII Sentinel
Initiative annually in the PDUFA Financial Report. This
reporting will provide detail for spending categories (e.g.,
data infrastructure, analytical capabilities, safety issue
analyses, dissemination of relevant product and safety
information, and Sentinel system development).
b. Enhancement of the Analytic Capabilities of the Sentinel
Initiative to Address Questions of Product Safety and Advance
the Understanding of How Real-World Evidence Can Be Used for
Studying Effectiveness
FDA will use user fee funds to advance the analytic
capabilities of the Sentinel Initiative by i) developing a
consistent approach to post-market requirements and
commitments during NDA and BLA review related to assessing
the outcomes of pregnancies in women exposed to drugs and
biological products and clarifying the optimal use and value
of pregnancy registries and electronic healthcare data for
assessing pregnancy safety and ii) supporting the use of
real-world evidence to address questions of product safety
and advancing our understanding of how real-world evidence
may be used for studying effectiveness.
i. Pregnancy Safety
The goal of pregnancy safety post-market requirements and
commitments studies is to inform labeling on the safety of
use in pregnancy and to detect or evaluate safety signals in
a timely manner.
(1) FDA will develop a framework describing how data from
different types of post-market pregnancy safety studies might
optimally be used, incorporating knowledge of how different
types of postmarket studies have been used by FDA and
industry and identifying gaps in knowledge needed to be
filled by demonstration projects. The framework would
consider factors such as, but not limited to, purpose of
study, types of post-market studies, anticipated exposure in
females of reproductive potential (FRP) and pregnant women,
potential toxicity of the drug and proposed risk mitigation,
benefits of the drug, and magnitude and type of risk to be
detected. The framework would specifically address the use of
pregnancy registries and electronic healthcare data sources
including Sentinel, with a goal of ensuring the most
efficient means of obtaining highest quality safety data
available.
(a) FDA will review published literature and conduct a
review of types of post-market pregnancy data that have been
included in pregnancy labeling.
(b) By September 30, 2023, FDA will hold a public workshop
on post-market safety studies in pregnant women to facilitate
determination of the ideal post-market study design(s),
including industry experience and use of Sentinel Initiative
and other real-world data resources.
(c) By September 30, 2024, FDA will publish a workshop
report describing the proposed framework.
(2) Incorporating feedback from (1), conduct 5
demonstration projects to address gaps in knowledge about
performance characteristics of different study designs. FDA
will initiate the following demonstration projects which may
be modified as needed, before September 30, 2024:
(a) Assess the performance of pregnancy registries versus
electronic healthcare database studies to detect a signal
when the exposure to medication in pregnancy is relatively
common.
(b) Assess the performance of single arm safety studies
versus signal identification methods using electronic
healthcare data to detect a signal when the exposure to
medication in pregnancy is anticipated to be low.
(c) Assess the performance of pregnancy registries versus
electronic healthcare database studies to evaluate a signal
when the exposure to medication in pregnancy is relatively
common.
(d) Assess the performance of major congenital
malformations
(MCM) as a composite outcome in signal detection and
evaluation when there is true risk for some but not all
specific malformations.
(e) Assess the performance of an algorithm using electronic
health record (EHR) and claims-linked healthcare data for a
pregnancy-related outcome, or composite of outcomes (e.g.,
spontaneous abortion, stillbirth, congenital malformations),
after use of vaccines in pregnant women. The parameters of
the pregnancy-outcome algorithm will be developed to have
general usability with therapeutic products.
(3) By September 30, 2027, based on the results of
demonstration projects in (2) update the proposed framework
and develop a guidance or MAPP/SOPP as appropriate to
implement a standardized process for determining necessity
and type of pregnancy postmarketing studies including PMRs.
ii. Use of Real-World Evidence--Negative Controls
FDA is building Sentinel/BEST methodology to improve
understanding of robustness evaluations used to address the
consistency of RWE with respect to study design, analysis, or
variable measurement. FDA will develop new methods to support
causal inference in Sentinel/BEST that could address product
safety questions and advance our understanding of how RWE may
be used for studying effectiveness.
(1) By September 30, 2023, FDA will hold a public workshop
on use of negative controls for assessing the validity of
non-interventional studies of treatment and the proposed
Sentinel Initiative projects.
(2) FDA will initiate two methods development projects by
September 30, 2024 to 1) develop an empirical method to
automate the negative control identification process in
Sentinel and integrate it into the Sentinel System tools; and
2) develop a method to use a double negative control
adjustment to reduce unmeasured confounding in studying
effectiveness of vaccines.
(3) By September 30, 2027, FDA will publish a report on the
results of the development projects.
N. Enhancements Related to Product Quality Reviews,
Chemistry, Manufacturing, and Controls Approaches, and
Advancing the Utilization of Innovative Manufacturing
Technologies
To ensure new and innovative products are developed and
available to patients in a timely manner, FDA and industry
will focus on enhancing communications during drug
development and application review, enhancing support for CMC
development and facilitating the CMC readiness of products
with accelerated clinical development timelines, and
advancing the implementation of innovative manufacturing
technologies.
1. Enhancing Communication Between FDA and Sponsors During
Application Review
To promote an efficient and effective application review
process, FDA will conduct the following activities during
PDUFA VII to enhance communication between the FDA review
teams and sponsors:
a. The four essential components of CMC information
requests (referred to as Four-Part Harmony) are intended to
ensure that the FDA requests information that is appropriate
to address the question or issue, in an efficient manner, and
at the appropriate timepoint within the review cycle or
product lifecycle, as applicable. Use of Four-Part Harmony
includes acknowledging what was
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provided and where (e.g., modules, page numbers, as
applicable), identifying the issue or deficiency, clearly
identifying the information needed to achieve resolution and
make a regulatory decision, and identifying specific
references or other information to support FDA's request.
These four essential components of Four-Part Harmony are:
i. What was provided
ii.What is the issue or deficiency
iii. What is needed
v. Why it is needed
By the end of FY 2023, to promote FDA reviewers' use of
Four-Part Harmony, FDA will update and conduct training on
CDER MAPP 5016.8, ``Communication Guidelines for Quality-
Related Information Request and Deficiencies'' and CBER SOPP
8401.1, ``Issuance of and Review of Responses to Information
Request Communications to Pending Applications'' describing
the guidelines for the content of information requests, based
on the principles of Four-Part Harmony.
b. By the end of FY 2023, FDA will update and conduct
training on CMC assessment processes associated with mid-
cycle and late-cycle review meetings with the goal of
ensuring that mid-cycle and late-cycle meeting expectations
are met, including communicating the status of the NDA and
BLA CMC assessment and any identified issues that would
preclude approval.
c. FDA will contract with an independent third party to
assess current practices of FDA (CDER and CBER) and sponsors
in communicating through product quality information requests
(IRs) during application review, not including supplements.
The assessment will focus on the application of Four-Part
Harmony as described in the MAPPs and SOPPs (e.g., did FDA
state why the information is needed for the review of the
application) as well as seek to identify trends across IRs.
The statement of work for this effort will be published for
public comment prior to beginning the assessment. The third
party will be expected to separately engage both FDA staff
and individual sponsors through contractor-led interviews as
part of the assessment. The contractor-led interviews will be
designed to provide feedback from individual sponsors on the
effectiveness of Four-Part Harmony. Due to the significant
volume of IRs in a given year, the assessment will be based
on a subset of drug and biologic applications, not including
supplements, balanced across CDER and CBER, proportional to
the number of applications received by each Center. The third
party will identify best practices and areas for improvement
in communication between FDA review staff and sponsors
through IRs. FDA will publish the final report of the
assessment on FDA's website no later than June 30, 2025, for
public comment.
2. Enhancing Inspection Communication for Applications, not
Including Supplements
FDA and industry believe enhanced communication between
review teams and industry on certain pre-license inspections
and pre-approval inspections can facilitate an efficient
application review process.
When FDA determines for an application, not including
supplements, that it is necessary to conduct the 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 BLA Pre-license Inspections and NDA Pre-approval
Inspections 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.
3. 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.
By 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.
4. Facilitating Chemistry, Manufacturing, and Controls
Readiness for Products with Accelerated Clinical Development
Development programs for CDER- and CBER-regulated drugs and
biologics intended to diagnose, treat, or prevent a serious
disease or condition where there is an unmet medical need may
have accelerated clinical development timelines. Products
with accelerated clinical development activities often face
challenges in expediting CMC development activities to align
with the accelerated clinical timelines. Overcoming these CMC
challenges often requires additional interaction with FDA
during product development and the use of science-and risk-
based regulatory approaches so that the clinical benefits of
earlier patient access to these products can be realized.
a. MAPP: By December 31, 2022, FDA will issue a new MAPP on
approaches to address CMC challenges for CDER-regulated
products (drugs, biologics) with accelerated clinical
development timelines (e.g., products used to diagnose,
treat, or prevent a serious disease or condition where there
is unmet medical need). To address the CMC challenges, the
MAPP will describe early engagement with sponsors of such
products and the different science-and risk-based approaches,
including those described in the FDA Guidance for Industry:
Expedited Programs for Serious Conditions-Drugs and
Biologics, that may be warranted and utilized in CMC
development based upon the anticipated clinical benefit of
earlier patient access to the product. The MAPP will
incorporate modern pharmaceutical principles as well as
modern regulatory tools, such as those detailed in ICH Q12.
b. Pilot: Starting in FY 2023, FDA (CDER and CBER) will
conduct a CMC Development and Readiness Pilot (CDRP) to
facilitate the expedited CMC development of products under an
IND application, where warranted, based upon the anticipated
clinical benefit of earlier patient access to the products.
The goal of the Pilot will be to facilitate CMC readiness for
CBER- and CDER-regulated products with accelerated clinical
development timelines. Due to the differences in product
complexity between CBER- and CDER-regulated products, Pilot
selection criteria may differ between the Centers. In order
to accelerate CMC development and facilitate CMC readiness,
the Pilot will incorporate, as applicable, contemporary
learnings and the use of science- and risk-based approaches
and submission strategies, such as those described in the FDA
Guidance for Industry: Expedited Programs for Serious
Conditions-Drugs and Biologics.
For sponsors participating in the CMC Development and
Readiness Pilot, FDA will provide specific CMC advice during
product development by providing two additional CMC-focused
Type B meetings and an additional limited number of CMC-
focused discussions based on readiness and defined CMC
milestones. The increased communication between FDA review
staff and applicants is intended to ensure a mutual
understanding of what activities must be completed, and what
information should be provided at the appropriate timepoint
(i.e., at the time of NDA or BLA submission, prior to the end
of the review cycle, or post-approval), to ensure CMC
readiness of the product.
i. By December 31, 2022, FDA will publish a Federal
Register Notice (FRN) announcing the Pilot and outlining the
eligibility criteria and process for submitting a request to
participate in the Pilot. For CDER, the eligibility criteria
will focus on the selection of products with accelerated
clinical development timelines that could expand or enhance
the approaches in the CDER MAPP described above. For CBER,
the eligibility criteria will include considerations for
products with accelerated clinical development timelines
(e.g., vaccines and cell and gene therapies).
The FRN will give more specifics on products to be included
in the Pilot and will consider Industry's interest in CBER-
regulated products such as cell and gene therapies. FDA will
select between 8-10 proposals per fiscal year over a 4-year
period.
ii. To promote innovation and understanding in this area,
lessons learned through the Pilot may be presented by FDA
(e.g., in a public workshop) as case studies, including when
the product studied in the Pilot has not yet been approved by
FDA. To be eligible for the Pilot, the sponsor and FDA will
reach an agreement on the information to be publicly
disclosed. When feasible, FDA will notify a sponsor in
advance when the sponsor's program is the planned focus of a
public discussion. Participation in the pilot program,
including such agreement on information disclosure, will be
voluntary and at the discretion of the sponsor.
iii. Sponsors who do not participate in the Pilot will have
an opportunity to interact with the Agency through existing
channels.
c. Public Workshop: By July 31, 2025, FDA will conduct a
public workshop, potentially through a qualified third party,
focused on CMC aspects of expedited development including
case studies, lessons learned, and stakeholder input
regarding the CMC Development and Readiness Pilot. The
workshop will solicit and include industry and public
feedback.
Topics for the workshop will include, but are not limited
to, the use of science and risk-based approaches and
submission strategies to accelerate CMC development,
including predictive stability modeling, risk-based
approaches to product specification setting,
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and alternate process validation approaches, as well as
experiences related to quality by design and platform
technologies.
d. Strategy Document: Following the close of the public
comment period for the public workshop, and no later than
April 30, 2026, FDA will issue a strategy document outlining
the Agency's plans, including proposed timeframes, to develop
or revise, as appropriate, relevant MAPPs or SOPPs, and other
applicable documents (e.g., guidance and process documents)
to incorporate lessons learned from the Agency's experiences
with the CMC Development and Readiness Pilot and other
submissions for products with accelerated clinical
development timelines, as well as industry and public input,
including feedback from the public workshop.
5. Advancing Utilization and Implementation of Innovative
Manufacturing
By the end of FY 2023, FDA will conduct a public workshop
on the utilization of innovative manufacturing technologies
for CDER-and CBER-regulated products, including barriers to
their adoption and submission strategies. The workshop will
solicit and include industry and public feedback.
Topics for the workshop will include but are not limited
to:
a. Best practices and lessons learned from both the CDER
Emerging Technology Team and CBER Advanced Technology Team
programs from both industry and regulatory perspectives;
b. Case studies from previous innovative technology
submissions presented by sponsors;
c. Barriers (technical, regulatory, etc.) to the adoption
of innovative manufacturing technologies;
d. Regulatory strategies for the adoption of advanced
manufacturing technologies, including, but not limited to,
submission strategies for the implementation of certain
innovative technologies across multiple commercial products
and/or multiple manufacturing sites; and
e. Science- and risk-based approaches for developing and
assessing innovative technologies across platform products
and sites to streamline adoption.
Following the close of the public comment period for the
public workshop, and no later than September 30, 2024, FDA
will issue a draft strategy document for public comment that
outlines the specific actions the agency will take over the
course of PDUFA VII to facilitate the utilization of
innovative manufacturing technologies, including addressing
barriers to their adoption. The actions described in the
draft strategy document will be based on lessons learned from
the Agency's experiences with submissions involving advanced
manufacturing technologies as well as feedback from the
workshop and other public input. The strategy document may
include updating or creating new procedures, MAPPs, SOPPs,
guidances, and scientific/other relevant 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 finalize the strategy
document within 9 months after the close of the public
comment period on the draft strategy document.
O. Enhancing CBER's Capacity to Support Development, Review,
and Approval of Cell and Gene Therapy Products
To ensure that new and innovative cell and gene therapy
products are developed and available to patients in a timely
manner, FDA will build on the success of the Cell and Gene
Therapy Program (CGTP) in CBER to further support and advance
a balanced approach to product development and regulation. To
this end, FDA will substantially strengthen staff capacity
and capability in order to meet the increasing challenges and
demands in this growing field. Increasing staff capacity will
overcome existing resource limitations, allowing staff to
spend additional time on meetings and submission reviews
including those with breakthrough or regenerative medicine
advanced therapy designations, expand stakeholder outreach,
invest in new policy and guidance, and facilitate development
and use of regulatory tools and scientific technologies.
The CGTP will be augmented with additional resources to
sustain and expand the program. Staff will be hired for
direct review activities, indirect activities (e.g., policy,
external outreach, postmarket safety), and supporting
activities in the CGTP, with a focus on hiring staff with
technical, scientific, clinical, or other specialized
expertise necessary to understand and advance cell and gene
therapies. Recruiting and hiring of staff will be actively
pursued as a CBER priority and be facilitated by support
staff whose dedicated focus will be attracting and retaining
talent for the CGTP. CBER recognizes the importance of
integration of new staff into the CGTP and will effectively
facilitate growth in staffing using external consultants when
appropriate. For PDUFA VII, resources will also support
onboarding and integration of new staff, regulatory support
and outreach (e.g., webinars, recorded training) to
facilitate industry and stakeholder education and
interaction.
CBER will continue to maintain a highly trained and
experienced CGTP staff, with an emphasis on remaining current
in regulatory science, and the latest scientific,
manufacturing, and clinical advances. The current staff
training will be reviewed, with input from external
consultants, and modified as needed to accommodate and
facilitate training of new staff and maintain the competency
of existing staff.
CBER will continue to organize and manage the CGTP for
optimal performance, leveraging and implementing best
practices from relevant sources. The current CGTP
organization will be evaluated, with input from external
consultants, to determine the optimal organization to
effectively integrate new staff and facilitate operations and
customer service. As part of CBER's modernization program,
CBER will evaluate, streamline, and harmonize CGTP
procedures, processes, and interactions to facilitate
communications, enhance regulatory consistency and review
standards, reduce regulatory burden, optimize operational
efficiency, and update relevant SOPPS and documents as
needed. Change management will be tailored to ensure success
of organizational changes and business modernization.
The CGTP staff will enhance communications with
stakeholders, on an individual and collective level, by
refining and improving best practices for communication,
through public meetings and workshops, and issuance of
guidance, updating relevant SOPPS, and other mechanisms. CBER
will continue to issue new guidance on current cell and gene
therapy topics and update existing guidance to be current
with evolving science and approaches. Staff will increase
awareness of FDA's regulatory programs through on-demand
training (e.g., recorded webcast), to facilitate navigation
by industry through the phases of product development and
approval. CGTP staff will continue to engage in outreach to
industry, patient groups, and other stakeholders in several
areas soliciting views on specific topics and proposals.
Staff will continue to participate in external
collaborations, including public-private partnerships and
international organizations in a variety of areas, including
development of tools (e.g., standards), technologies, and
approaches that support development of cell and gene
therapies. Interactions will also focus on advancing
manufacturing and testing, including facilitating
implementation of new technologies. With stakeholders, staff
will continue discussing use of existing approaches (e.g.,
surrogate endpoints, real world evidence, complex innovative
designs, natural histories) and explore new approaches for
obtaining efficacy and safety information with specific
consideration and attention to rare and ultra-rare diseases.
To advance the field and support the next generation of
cell and gene therapy products, CBER will conduct the
following activities during PDUFA VII.
1. Patient Focused Drug Development
a. By the end of FY 2023, FDA will convene a public patient
focused drug development meeting with key stakeholders,
including patients and patient advocacy organizations, to
better understand patient perspectives on gene therapy
products, including cell-mediated gene therapy. This meeting
should address, among other things, the patient and
caregiver's level of understanding and expectations regarding
the benefits and risks of these therapies, and their
involvement in clinical study design and execution. Within 6
months of the public meeting, FDA will issue a report
summarizing the views expressed at the meeting including:
i. Analysis of current tools or methods used to capture
patient experience data, and/or patient involvement in
clinical studies, including identification of existing
challenges and gaps;
ii. Whether there is a need for the community to develop
specific tools or methods to capture patient experience data,
and/or patient involvement in clinical studies that are
unique to these products, and if so, suggestions for
community engagement strategies; and
iii. Approaches to leveraging existing tools or methods to
capture patient experience and patient preference data that
are unique to these products;
2. Novel Approaches to Development of Cell and Gene Therapy
a. FDA will continue to work with stakeholders including
public-private partnerships to seek public input on questions
and challenges faced by cell and gene therapy developers,
including the use of novel endpoints and the role of
less defined natural histories, and to facilitate
development and approval for cell and gene therapies,
including but not limited to, individualized therapies,
rare disease and therapies for small patient populations.
b. By the end of FY 2025, FDA will issue a draft guidance
on the evaluation of efficacy in small patient populations
using novel trial designs and statistical methods, and how
these concepts can be applied to more common diseases. 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. In order to promote development of cell and gene therapy
products, FDA will issue a Questions and Answers draft
guidance by the end of FY 2024 based on frequently asked
questions, and commonly faced-issues identified by sponsors
or by public-private partnerships. FDA will work towards the
goal of publishing final guidance within 18 months
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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.
d. By the end of FY 2024, FDA will convene a public meeting
to solicit input on methods and approaches (e.g., use of RWE,
registries) for capturing post-approval safety and efficacy
data for cell and gene therapy products. Within 6 months of
the public meeting, FDA will issue a summary report or a
transcript of the meeting. Input from this meeting will be
used to inform development of a draft guidance on this topic.
FDA will issue a draft guidance on this topic by the end of
FY 2025. 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.
3. Expedited Programs for the Development of Regenerative
Medicine Therapies:
a. By the end of FY 2025, FDA will update the Guidance for
Industry: Expedited Programs for Regenerative Medicine
Therapies for Serious Conditions. Updates will include, for
example, additional thinking on post-approval requirements,
including the use of real-world evidence to confirm clinical
benefit, for products approved under accelerated approval, as
well as for safety monitoring and long-term follow-up.
Updates will also include additional thinking on approaches
and processes relating to CMC including considerations
regarding CMC readiness to take advantage of the expedited
programs. 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.
4. Leveraging Knowledge
a. FDA will continue to work with organizations, including
public-private partnerships, that foster development and
accessibility of non-proprietary knowledge (e.g., standards),
manufacturing advances, and manufacturing components for use
in cell and gene therapy products. FDA will continue to
participate in international organizations sharing knowledge
and perspective to harmonize cell and gene therapy guidance
as appropriate.
b. By the end of FY 2025, FDA will convene a public meeting
to solicit the perspective of cell and gene therapy
manufacturers on how individual sponsors might leverage
internal prior knowledge and public knowledge, including
Chemistry, Manufacturing, and Controls, non-clinical, and
clinical knowledge, across therapeutic contexts in order to
facilitate product development and application review. Input
from this meeting will be used to inform development of a
draft guidance on this topic that FDA will issue by the end
of FY 2026. 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.
P. Supporting Review of New Allergenic Extract Products
FDA will use fee revenues to support the review of new
allergenic extract products that have been incorporated in
the PDUFA program by PDUFA VII. Allergenic extract products
licensed after October 1, 2022 will generally be included in
user fees. Allergenic extract products licensed before
October 1, 2022, and standardized allergenic extract products
submitted pursuant to a notification to the applicant from
the Secretary regarding the existence of a potency test that
measures the allergenic activity of an allergenic extract
product licensed by the applicant before October 1, 2022 will
remain excluded from PDUFA. All performance goals,
procedures, and commitments in this letter apply to the
allergenic products included in the PDUFA program under PDUFA
VII.
II. CONTINUED ENHANCEMENT OF USER FEE RESOURCE MANAGEMENT
FDA is committed to ensuring the sustainability of PDUFA
program resources and to enhancing the operational agility of
the PDUFA program. FDA will build on the financial
enhancements included in PDUFA VI and continue activities in
PDUFA VII 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 capability. FDA will also continue activities to
promote transparency of the use of financial resources in
support of the PDUFA 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
PDUFA resources in PDUFA VII and help ensure alignment of
user fee resources to staff workload.
1. Resource Capacity Planning Implementation
a. By 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 PDUFA VII. This implementation plan
will address topics relevant to the maturation of resource
capacity planning, including, but not limited to, detailing
FDA's approach to:
i. 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.
ii. 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 by the end of the 2nd quarter of each
subsequent fiscal year.
c. FDA will document in the annual PDUFA Financial Report
how the CPA fee revenues are being utilized.
2. Resource Capacity Planning Assessment
By 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:
a. The ability of the CPA to forecast resource needs for
the PDUFA program, including an assessment of the scope of
the workload drivers in the CPA and their ability to
represent the overall workload of the PDUFA program;
b. Opportunities for the enhancement of time reporting
toward informing resource needs; and
c. The integration and utilization of resource capacity
planning information within resource and operational
decision-making processes of the PDUFA 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
PDUFA 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 PDUFA 5-year financial plan no later
than 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 736(b)(1)(C) of the
FD&C Act is subject to renegotiation under a subsequent
reauthorization of PDUFA. FDA will publish updates to the 5-
year plan no later than 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 human drug
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
736(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 PDUFA.
2. FDA will convene a public meeting no later than the end
of the 3rd quarter of each fiscal year to discuss the PDUFA
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.
3. FDA will include in the annual PDUFA Financial Report an
accounting of appropriated user fee funds included in the
operating reserve at the end of each fiscal year, as well as
the carryover balance of user fee funds that are considered
unappropriated and therefore not included in the operating
reserve.
III. IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF
Enhancements to the human drug review program require that
FDA hire and retain sufficient numbers and types of technical
and scientific experts to efficiently conduct reviews of
human drug applications. During PDUFA VII, FDA will commit to
do the following:
A. Set Clear Goals for Human Drug Review Program Hiring
1. FDA will establish priorities for management of the
metric goals for targeted hires within the human drug review
program staff
[[Page S5192]]
for the years of PDUFA VII. These goals for targeted hires
are summarized in Table 6 below:
TABLE 6
----------------------------------------------------------------------------------------------------------------
FY 2023 FY 2024 FY 2025 FY 2026 FY 2027
----------------------------------------------------------------------------------------------------------------
CBER........................................... 132 48 29 15 4
CDER........................................... 77 31 15 0 0
Other FDA...................................... 1 0 0 0 0
Total FTE...................................... 210 79 44 15 4
----------------------------------------------------------------------------------------------------------------
2. FDA will confirm progress in the hiring of PDUFA VI new
staff. FDA will also report on progress against the hiring
goals for FY 2023-2027 on a quarterly basis posting updates
to the FDA website PDUFA Performance webpage.
B. 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 human drug review program. 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 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 human drug 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 human drug review program, if
warranted.
The assessment will be published on FDA's website no later
than the June 30th, 2025 for public comment. FDA will also
hold a public meeting no later than the September 30th, 2025
to discuss the report, its findings, and the Agency's
specific plans to address the report recommendations.
IV. INFORMATION TECHNOLOGY AND BIOINFORMATICS GOALS
A. Enhancing Transparency and Leveraging Modern Technology
Under PDUFA VII, FDA will:
1. Enhance Transparency
FDA will further enhance transparency of its IT activities
and modernization plans, as well as continue to ensure the
usability and improvement of the electronic submissions
gateway (ESG):
a. Quarterly, FDA and industry will jointly plan and
conduct meetings on challenges, emerging needs, and progress
on initiatives relevant to PDUFA, including continued
sustainability of initiatives after completion in PDUFA VII,
progress or activities on harmonization and convergence,
where appropriate, across Center systems for streamlined
compatibility, interoperability, and extensibility. Agendas
and meeting materials will be shared prior to each meeting.
b. Annually, appropriate FDA and industry IT leadership
(e.g., enterprise IT leadership, Center IT leadership) will
participate in a review of PDUFA IT initiatives and provide
an opportunity for industry input.
c. 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.
d. FDA will maintain a current published FDA Data Standards
Catalog, and quarterly publish an updated data standards
action plan.
2. 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.
a. 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:
i. outlining key areas of focus and approach including
leveraging cloud technologies to support Applicant-FDA
regulatory interaction;
ii. articulating enterprise-wide approaches for both
technology and data governance; and
iii. aligning strategic initiatives in support of PDUFA
review goals, drawing a line of sight between initiatives and
the enterprise strategy (i.e. the agency-wide strategy also
supporting components outside PDUFA).
b. The Strategy will be shared and annually updated to
reflect progress and any needed adjustments. Milestones and
metrics for PDUFA initiatives will be included in the
updates.
3. Promote Convergence
As appropriate, FDA will engage with stakeholders and
international consortia (e.g., ICH, ICMRA) on technology and
innovation initiatives that promote convergence in data
interoperability and interpretability for current and future
FDA initiatives throughout the regulatory lifecycle.
a. FDA will seek to adopt international standards where
feasible and appropriate, giving considerations to
cybersecurity risk, international commitments, legal
constraints, and other relevant factors.
4. Accelerate CBER Modernization
During PDUFA VII, CBER will retire its older IT systems and
capabilities, leverage capabilities in other Centers where
feasible, and utilize new data management tools and
technologies in line with Agency strategic plans and
effective use of resources.
In coordination with CDER and CDRH, CBER will accelerate
its data and IT modernization in order to leverage or develop
state-of the art IT technology to provide cloud-based, agile,
and stable integrated platforms, to streamline and improve
its ability to perform complex reviews, access, utilize and
protect data, and redirect IT spending from maintenance of
older IT systems to improving the reviewer experience.
Modernization efforts will enable new capabilities such as
knowledge management, data and analytic reporting, decision
tools, and, workflow and workload management to be developed
sooner. CBER will share its experience and new capabilities
with other Centers.
b. By the end of Q4 FY 2022, CBER will have established a
multi-year modernization roadmap, including concrete
implementation phases and milestones with defined success and
performance criteria and anticipated costs.
i. Criteria may include, for example, retiring a minimum
25% of CBER legacy systems and capabilities by the end of
PDUFA VII; leveraging existing adverse events reporting
capabilities for CBER adverse event reporting; transitioning
regulatory data and analytics to a new shared environment;
using a new electronic review management tool and knowledge
management system.
ii. These and other modernization efforts will allow for
measurable improved review and internal management of novel
and scientifically complex PDUFA biologics, leading to
enhanced review efficiency, effectiveness and quality.
iii. Modernization outcomes will facilitate external
interactions with developers, manufacturers, and other
stakeholders--resulting in faster information exchange, data
analysis, and dissemination of safety information; and better
consistency of advice and decisions to guide and foster
product development and review.
c. Annually and at key milestones, CBER will share its
roadmap, provide updates on its progress including successes,
issues, performance metrics, accomplishments and any issues
or necessary adjustments to accommodate unexpected events
(e.g., contracting, delays outside of CBER control) or
reasonable deviations from its modernization roadmap. This
information will be shared at regularly scheduled FDA-
industry meetings.
d. In order to ensure successful modernization, CBER
maintains active management and oversight of its IT and Data
projects through a structured system of controls that covers
all phases of projects. CBER will not progress to the next
phase of implementation for an IT modernization project
without successful completion of the previous phase.
e. CBER will scope and plan its IT modernization activities
to conclude by the end of FY 2027 with no expectation of
continued additional direct costs funding to support the
effort beyond PDUFA VII.
5. Monitor and Modernize ESG
FDA will continue to ensure the usability and improvement
of the ESG.
a. 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.
a. 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.
b. Annually, FDA will share progress against the
implementation project plan.
c. 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.
6. Leverage Cloud Technology to Progress Regulatory Digital
Transformation
Cloud and cloud-based technology offer significant
advantages over traditional on-premise data repositories and
analytics. Combined with interoperable information exchange
mechanisms, these advantages open a host of new opportunities
to explore, promote and implement innovation in the drug
development and regulatory review process.
[[Page S5193]]
The outcomes of demonstration projects in PDUFA VII will be
the building blocks, informing and positioning FDA and
regulated industry to take best advantage of third-party
hosted capabilities in conjunction with their own
infrastructure, as well as investigating the potential for
such capabilities to be jointly leveraged by other regulatory
authorities and applicants.
a. FDA will engage with external parties to develop and
test reusable and portable core capabilities that can be
supported both with FDA's environment and in trusted third-
party environments. This engagement will be through
mechanisms such as, but not limited to, cooperative
agreements, contracts, Cooperative Research and Development
Agreements (CRADAs) and public-private partnerships.
b. By the end of Q3 FY 2023, FDA will assess challenges or
barriers in FDA's adoption of cloud-based technologies in
applicant-regulator interactions and within 6 months will
publish the findings of this assessment.
c. In FY 2023, FDA, in consultation with industry, will
prioritize and initiate the first of at least 3 demonstration
projects to explore application of cloud-based technologies
to streamline, improve and enable a variety of applicant-
regulator interactions.
i. In support of the use of DHT-derived data in
applications, FDA will enhance its capability to effectively
receive, aggregate, store, and process large volumes of
static or continuously updated DHT-derived data captured as
part of a clinical trial.
ii. Projects will demonstrate applications of cloud
technology to applicant-regulator interactions and secure
shared environments for specific regulatory activities (e.g.,
support labeling negotiations between FDA and applicants,
develop a standard protocol template to accelerate review and
provide usable archive, improve statistical analysis plan
between FDA and applicants).
iii. Projects will develop increasingly rich and flexible
technical capabilities that can be leveraged for multiple
purposes by regulators and industry, either internally within
a regulator's or industry's environment, or through a trusted
third-party, thus promoting convergence through common
components such as Cloud-hosted Individualized Secure
Collaboration Hubs (ISCH) which provide secure and effective
environments for various cloud-based collaboration
initiatives;
1) An example might be to utilize an ISCH for applicant-
regulator label negotiations; another might be to hold
continuously updated DHT-derived data for analysis.
d. Within 6 months of completion of a demonstration
project, a summary of outcomes and next steps will be
compiled and shared with industry at the regularly scheduled
FDA-industry meetings. A description of the project and
summary of outcomes will be posted on the FDA website.
e. FDA will engage industry to provide feedback and/or
participate in testing in advance of implementing significant
changes that impact industry's interaction with the
enterprise-wide systems.
i. FDA will review progress and plans at quarterly meetings
with industry.
f. Demonstration projects and associated capabilities
development will be completed by the end of FY 2027 with no
expectation of additional funding for those activities beyond
PDUFA VII.
7. Provide Bioinformatics IT Support
CDER and CBER are seeing increasing volume and diversity of
bioinformatics and computational biology information and
data, such as Next Generation Sequencing, in sponsor-
regulator interactions. Bioinformaticists play an essential
and expanding role in new drug and biologic application
reviews, providing in-depth independent analysis of submitted
data to support review decisions in close coordination with
clinical and product experts. To be effective entails
appropriate IT support.
a. FDA will assess its bioinformatics capabilities, and
annually, ensure that IT resources are provided to support
bioinformatics activities, including software licensing,
cloud-based storage and computing capacity, operations
support and maintenance.
b. Outcomes will be shared at regularly scheduled FDA-
industry meetings.
B. Expanding and Enhancing Bioinformatics Support
Bioinformatics and computational biology are increasingly
being used to assess product quality, safety and efficacy and
facilitate the development, characterization and manufacture
of human drugs and biologics. Recognizing the substantial
increase in the volume and diversity of bioinformatics and
computational biology information and data, such as Next
Generation Sequencing, in regulatory submissions, FDA will
develop additional expertise and staff capacity in both CDER
and CBER to efficiently review and provide technical and
timely feedback on information and accompanying data in
submissions and meet performance goals, especially for those
submitted early in development. FDA will hire technical
expertise necessary to assess the approaches and evaluate
data as appropriate, validating the results and/or analytic
process using existing tools or through independent analysis
when necessary. Staff with specialized expertise in specific
product/therapeutic areas will also be developed to
facilitate translation of bioinformatic information to
subject matter review experts. FDA will also assess and
strengthen its computational infrastructure to support and
advance its informatics platforms, allowing FDA to remain
current with the most recent technology in the field. To
facilitate submission and review of bioinformatics and
computational biology information, FDA will continue to
develop data standards and revise guidance or issue draft
guidance on this topic including how to submit, and format
submissions, and technical validation criteria. FDA will work
globally to advance harmonization of these standards and
methodologies.
C. Enhancing use of Digital Health Technologies to Support
Drug Development and Review
A Digital Health Technology (DHT) in the context of this
commitment may be considered as a system that uses computing
platforms, connectivity, software, and sensors for healthcare
and related uses. These technologies may span a wide range of
uses, from applications in general wellness to applications
as a medical device to applications generating data that may
be used in the evaluation of drug or biologic products.
DHTs can allow for remote data acquisition from patients
and clinical trial participants to measure a wide range of
activities, behaviors, and functioning in real life settings
that can inform important clinical endpoints. DHTs may
include wearable, implantable, ingestible, and environmental
sensors or software applications on mobile devices, among
other approaches. The use of DHTs can support and enable the
conduct of decentralized clinical trials (DCTs), the clinical
investigations in which some or all trial-related procedures
and data acquisition take place at locations remote from the
investigator.
While the biomedical field has experienced rapid
development and implementation of DHTs, FDA has limited
experience evaluating novel DHT-based measurements in human
drug development. FDA recognizes the potential for DHTs to
provide scientific and practical advantages in supporting the
assessment of patients by generating information outside of
the traditional clinic visit and needs to build capacity and
expertise to advise the biopharmaceutical industry in their
development and implementation and to evaluate DHT outputs
including the impact of regulatory initiatives (or regulatory
science). To support new drug registration, label expansion,
and safety monitoring, DHT-based data need to be fit for the
intended purpose. Toward these ends, FDA will do the
following:
1. By the end of Q2 FY 2023, FDA will establish a DHT
framework document guide the use of DHT-derived data in
regulatory decision-makings for drugs and biological
products. The framework will guide activities such as to:
a. Define objectives for workshops and demonstration
projects;
b. Develop methodologies for evaluating DHTs proposed as
measuring key (primary or important secondary) endpoints or
other important measures (e.g., for safety monitoring, or
baseline characterization) in clinical trials;
c. Manage submissions with extensive and continuous data,
e.g., in order to develop acceptable approaches to capture
adverse events; and
d. Develop a standardized process for data management and
analysis of large datasets from DHTs.
2. By the end of Q2 FY 2023, FDA will establish a committee
including members from CDER and CBER to support
implementation of the commitments in this section. The
establishment of the committee and its purpose will be made
public on the FDA website. Responsibilities will include, but
not be limited to:
a. Oversee the design and implementation of the DHT
framework;
b. Promote consistency across centers regarding DHT-based
policy, procedure, and analytic tool development;
c. Work with the FDA Digital Health Center of Excellence
(DHCoE) to increase consistency across regulatory programs,
to incorporate relevant learnings from review of digital
tools and devices by CDRH, and to consider cross-center
topics;
d. Gather information about the present state of DHTs,
including specific challenges in their use; and
e. Engage with external stakeholders on DHT-related issues.
3. By the end of Q2 FY 2023, FDA will convene the first of
a series of 5 public meetings or workshops with key
stakeholders including patients, biopharmaceutical companies,
DHT companies, and academia to gather input into issues
related to the use of DHTs in regulatory decision-making. The
meetings and workshops will be designed with objectives such
as to:
a. Understand priorities for development of DHTs to support
clinical trials, including the potential for DHTs to increase
diverse patient populations in clinical trials;
b. Identify approaches to DHT validation;
c. Gain understanding of DHT data processing and analysis
and inform need for novel analytical techniques; and
d. Address the regulatory acceptance of safety monitoring
tools.that utilize artificial intelligence/machine learning-
based algorithms for pharmacovigilance purposes, e.g.,
continuous data streams from DHT.
4. FDA will identify at least 3 issue-focused demonstration
projects to inform methodologies for efficient DHT
evaluation. These projects may include engagement with
researchers from academia, biopharmaceutical industry,
patient groups and other stakeholders, and will:
[[Page S5194]]
a. Cover key issues to inform regulatory policy development
and regulatory advice. E.g.,. the projects may examine such
areas as validation methods, analytic approaches to missing
data, the use of multi-channel inputs to characterize an
endpoint, evaluation of continuous data vs discrete
measurements, use and limitations of use of DHTs in DCTs, and
other related efforts.
5. By the end of Q1 FY 2023, FDA will publish draft,
revised or final guidance on the use of DHTs in traditional
and decentralized clinical trials, addressing the validation
of measurements made by DHTs, the development of novel
endpoints using DHTs, the use of DHTs as new ways to measure
existing endpoints, approaches to using the patients' own
DHTs such as cell phones or smart watches, usability
considerations for patients, detection of safety signals
during continuous data acquisition, and issues related to
security and confidentiality of data.
a. Beginning in FY 2024, FDA will publish additional draft
guidances in identified areas of need informed by stakeholder
engagement.
i. For example, acceptable approaches to capturing and
reporting adverse events in clinical trials using DHTs.
b. 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.
6. By the end of FY 2023, FDA will publish draft, revised
or final guidance on regulatory considerations for
Prescription Drug Use-Related Software that includes
information about software that is disseminated by a drug
applicant for use with a prescription drug or biologic
product that may be described in labeling, including
prescribing information. This guidance will cover software
that is distributed with a drug or integrated as part of a
drug- or biologic-led combination product, as well as
software that is distributed by an applicant independent of
an approved product.
7. FDA will expand its capacity to achieve its stated
objectives in this section and to enhance consistency across
the human drugs and biologics program (and as appropriate
with the medical devices program) with regards to
development, use, and review of DHT's and associated
endpoints. Through a combination of expanded staff and
contract support, FDA will:
a. Build technical expertise within the human drugs and
biologics program to enhance internal knowledge, capabilities
for review of IND-and NDA/BLA submissions including DHT
derived endpoints, policy, standards and guidance
development;
b. Train FDA staff in evaluation of DHTs;
c. Develop statistical methodology for the design,
analysis, and interpretation of DHT-derived clinical trial
endpoints;
d. Build review capacity and expertise to respond to DHT
developers and biopharmaceutical applicants who want to use
DHTs; and
e. Apply a consistent approach to review of DHTs across
CDER, CBER, and CDRH as appropriate.
8. FDA will enhance its IT capabilities to support the
review of DHT-generated data:
a. By end of Q2 FY 2023, FDA will enhance its internal
systems to support review of DHT-related submissions
including capturing key information about clinical trials
utilizing DHTs to support tracking the number and rate of
change of DHT-related submissions.
b. In FY 2023, FDA will establish a secure cloud technology
to enhance its infrastructure and analytics environment that
will enable FDA to effectively receive, aggregate, store, and
process large volumes of data from trials conducted using
DHTs.
c. After establishing the cloud environment, FDA will pilot
a secure cloud-based mechanism to support submission and
review of DHT-generated data sets.
d. FDA will work to enhance, recommend and implement
standards that reduce the handling necessary to make data
analyzable.
V. IMPROVING FDA PERFORMANCE MANAGEMENT
A. Studies Will Include:
1. Assessment of the internal activities related to the
STAR pilot program as described in Section I.D.4.
2. Assessment of the current practices of FDA and sponsors
in communicating through product quality IRs during
application review as described in Section I.N.1.c.
3. Evaluation of the resource capacity planning capability
as described in Section II.A.2.
4. Assessment of the hiring and retention of staff for the
human drug review program in CDER and CBER as described in
Section III.B.
5. Assessment of challenges or barriers in FDA's adoption
of cloud-based technologies as described in Section IV.A.6.b.
VI. PROGRESS REPORTING FOR PDUFA VII AND CONTINUING PDUFA VI
INITIATIVES
A. FDA will include in the annual PDUFA Performance Report
information on the Agency's progress in meeting the specific
commitments identified in this document as prescribed in
statute.
B. FDA will include in the annual PDUFA Financial Report
information identified in Section II in this document and as
prescribed in statute.
APPENDIX. DEFINITIONS AND EXPLANATION OF TERMS
1. ``Human drug applications'' refers to new drug
applications submitted under section 505(b) of the Federal
Food, Drug, and Cosmetic Act and biologics license
applications submitted under section 351(a) of the Public
Health Service Act, as defined in the Prescription Drug User
Fee Act.
2. ``Human drug review program'' refers to the activities
to conduct ``the process for the review of human drug
applications,'' as defined in the Prescription Drug User Fee
Act.
3. The term ``review and act on'' means the issuance of a
complete action letter after the complete review of a filed
complete application. The action letter, if it is not an
approval, will set forth in detail the specific deficiencies
and, where appropriate, the actions necessary to place the
application in condition for approval.
4. A resubmitted original application is a complete
response to an action letter addressing all identified
deficiencies.
5. Class 1 resubmitted applications are applications
resubmitted after a complete response letter (or a not
approvable or approvable letter) that include the following
items only (or combinations of these items):
a. Final printed labeling
b. Draft labeling
c. Safety updates submitted in the same format, including
tabulations, as the original safety submission with new data
and changes highlighted (except when large amounts of new
information including important new adverse experiences not
previously reported with the product are presented in the
resubmission)
d. Stability updates to support provisional or final dating
periods
e. Commitments to perform Phase 4 studies, including
proposals for such studies
f. Assay validation data
g. Final release testing on the last 1-2 lots used to
support approval
h. A minor reanalysis of data previously submitted to the
application
i. Other minor clarifying information (determined by the
Agency as fitting the Class 1 category)
j. Other specific items may be added later as the Agency
gains experience with the scheme and will be communicated via
guidance documents to industry
6. Class 2 resubmissions are resubmissions that include any
other items, including any items that would require
presentation to an advisory committee.
7. The performance goals and procedures also apply to
original applications and supplements for human drugs
initially marketed on an over-the-counter (OTC) basis through
an NDA or switched from prescription to OTC status through an
NDA or supplement.
8. As used in this commitment letter, ``regulatory decision
making'' may include, for example, FDA's process for making a
regulatory decision regarding a drug or biological product
throughout the product lifecycle, such as during drug
development, following FDA's review of a marketing
application, including review of proposed labeling for the
product, or in the post-approval period (e.g., FDA's decision
regarding a supplement to an approved application).
9. ``Serious disease or condition,'' ``available therapy,''
``unmet medical need,'' and ``may demonstrate substantial
improvement on clinically significant endpoint(s)'' have the
meanings given in FDA's Guidance for Industry: Expedited
Programs for Serious Conditions, Drugs and Biologics (May
2014).
MDUFA Performance Goals and Procedures, Fiscal Years 2023 Through 2027
General
The performance goals and procedures agreed to by the
Center for Devices and Radiological Health (CDRH) and the
Center for Biologics Evaluation and Research (CBER) of the
United States Food and Drug Administration (``FDA'' or ``the
Agency'') for the medical device user fee program in the
Medical Device User Fee Amendments of 2022, are summarized
below.
FDA and the industry are committed to protecting and
promoting public health by providing timely access to safe
and effective medical devices. Nothing in this letter
precludes the Agency from protecting the public health by
exercising its authority to provide a reasonable assurance of
the safety and effectiveness of medical devices. Both FDA and
the industry are committed to the spirit and intent of the
goals described in this letter.
I. Shared Outcome Goals
The program and initiatives outlined in this document are
predicated on significant interaction between the Agency and
applicants. FDA and representatives of the industry agree
that the process improvements outlined in this letter, when
implemented by all parties as intended, should reduce the
average Total Time to Decision for premarket approval
applications (PMAs) and premarket notification (510(k))
submissions, provided that the total funding of the device
review program adheres to the assumptions underlying this
agreement. FDA and applicants share the responsibility for
achieving this objective of reducing the average Total Time
to Decision, while maintaining standards for safety and
effectiveness. Success of this program will require the
cooperation and dedicated efforts of FDA and applicants to
reduce their respective portions of the Total Time to
Decision.
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FDA will be reporting Total Time to Decision performance as
described in Section VII. FDA and industry will participate
in the independent assessment of progress toward this
outcome, as described in Section VI below. As appropriate,
key findings and recommendations from this assessment will be
implemented by FDA.
A. PMA
PMA Shared Outcome Total Time to Decision goal: FDA will
report on an annual basis the average Total Time to Decision
as defined in Section VIII.G for the three most recent closed
receipt cohorts. The following PMA Shared Outcome Total Time
to Decision goals are subject to adjustment per Section III
below:
For Original PMA and Panel Track Supplement submissions
received in Fiscal Years (FY) 2023 through 2024, the average
shared outcome Total Time to Decision goal for FDA and
industry is 290 calendar days.
For Original PMA and Panel Track Supplement submissions
received in FYs 2025 through 2027, the average shared outcome
Total Time to Decision goal for FDA and industry is 285
calendar days.
B. 510(k)
510(k) Shared Outcome Total Time to Decision goal: FDA will
report on an annual basis the average Total Time to Decision
as defined in Section VIII.G for the most recent closed
receipt cohort. The following 510(k) Shared Outcome Total
Time to Decision goals are subject to adjustment per Section
III below:
For 510(k) submissions received in FY 2023, the average
Total Time to Decision goal for FDA and industry is 128
calendar days.
For 510(k) submissions received in FY 2024, the average
Total Time to Decision goal for FDA and industry is 124
calendar days.
For 510(k) submissions received in FY 2025, the average
Total Time to Decision goal for FDA and industry is 112
calendar days.
For 510(k) submissions received in FY 2026, the average
Total Time to Decision goal for FDA and industry is 112
calendar days.
For 510(k) submissions received in FY 2027, the average
Total Time to Decision goal for FDA and industry is 112
calendar days.
II. Review Performance Goals--Fiscal Years 2023 Through 2027 As Applied
to MDUFA Cohorts
The overall objective of the review performance goals
stated herein is to assure more timely access to safe and
effective medical devices.
A. Pre-Submissions
FDA will continue the Pre-Submission program as described
in the guidance on ``Requests for Feedback and Meetings for
Medical Device Submissions: The Q-Submission Program'' with
process improvements and performance goals as noted in this
section.
For all Pre-Submissions in which the applicant requests a
meeting or teleconference, the applicant will provide a
minimum of three proposed meeting dates in the initial
submission.
Within 15 calendar days of receipt of a Pre-Submission, FDA
will communicate with the applicant regarding whether the
application has been accepted and, if applicable, regarding
scheduling of the meeting or teleconference. Acceptance will
be determined based on the definition of Pre-Submission in
Section VIII.E below and an acceptance checklist in published
guidance. This communication consists of a written
communication that a) identifies the reviewer assigned to the
submission, b) acknowledges acceptance/rejection of the
submission, and c) if the submission included a request for a
meeting or teleconference and is accepted, either confirms
one of the applicant's requested meeting dates or provides
two alternative dates prior to day 75 from receipt of
accepted submission. A determination that the request does
not qualify as a Pre-Submission will require the concurrence
of the appropriate management or designee and the reason for
this determination will be provided to the applicant in the
above written communication. FDA intends to reach agreement
with the applicant regarding a meeting date within 30 days
from receipt of accepted submission. For all requests for
meetings or teleconferences that do not have such a meeting
or teleconference scheduled by 30 days from receipt of an
accepted submission, a FDA manager will contact the applicant
to resolve scheduling issues by the 40th day.
Pre-Submission Written Feedback goal: FDA will provide
written feedback that addresses the issues raised in the Pre-
Submission request within 70 calendar days of receipt date or
five calendar days prior to a scheduled meeting, whichever
comes sooner, for:
In FY 2023, 90% of Pre-Submissions in the MDUFA Cohort if
the MDUFA Cohort is fewer than 3585, or 75% of Pre-
Submissions in the MDUFA Cohort if the MDUFA Cohort is 3585
or more, up to 4300 submissions.
In FY 2024, 90% of Pre-Submissions in the MDUFA Cohort if
the MDUFA Cohort is fewer than 4060, or 80% of Pre-
Submissions in the MDUFA Cohort if the MDUFA Cohort is 4060
or more, up to 4300 submissions.
In FY 2025-2027, 90% of Pre-Submissions in the MDUFA Cohort
up to 4300 submissions.
These Pre-Submission Written Feedback goals are subject to
adjustment per Section III below.
The MDUFA Cohort will only include Pre-Submissions (as
defined in Section VIII.E below) for devices that are
accepted for review up to a maximum number of accepted
submissions subject to the goal. Pre-Submissions will be
accepted in accordance with the Pre-Submission acceptance
checklist described in FDA's guidance ``Requests for Feedback
and Meetings for Medical Device Submissions: The Q-
Submission Program.''. In addition, the following types of
requests for feedback available to Breakthrough-designated
products and/or products included in the Safer
Technologies Program (STeP) are considered accepted for
review upon receipt:
Sprint discussions;
Requests for review of a data development plan; and
Requests for review of a clinical protocol agreement.
The MDUFA Cohort will not include Pre-Submissions that are
withdrawn at request of applicant or closed due to lack of
applicant response.
For any Pre-Submissions in the MDUFA Cohort for which FDA
does not meet the Pre-Submission Written Feedback goal, FDA
will communicate with the applicant in a timely manner
regarding a timeline for providing written feedback.
After the Pre-Submission MDUFA Cohort reaches the maximum
number of submissions subject to the goal in a fiscal year,
FDA still intends to provide timely feedback for Pre-
Submissions for Breakthrough-designated products and products
included in the Safer Technologies Program (STeP). After the
Pre-Submission MDUFA Cohort reaches the maximum number of
submissions subject to the goal, FDA intends to provide
feedback for other Pre-Submissions as resources permit, but
not to the detriment of meeting quantitative review timelines
and statutory obligations.
Written feedback provided to the applicant will include:
written responses to the applicant's questions; FDA's
suggestions for additional topics for the meeting or
teleconference, if applicable; or, a combination of both. If
all of the applicant's questions are addressed through
written responses to the applicant's satisfaction, FDA and
the applicant can agree that a meeting or teleconference is
no longer necessary, and the written responses will be
considered the final written feedback to the Pre-Submission.
Applicants will be responsible for developing draft minutes
for a Pre-Submission meeting or teleconference, and providing
the draft minutes to FDA within 15 calendar days of the
meeting. At the beginning and end of each meeting, the
applicant will affirmatively state that they will draft
minutes and provide them to FDA within 15 calendar days. The
minutes will summarize the meeting discussions and include
agreements and any action items. FDA will provide any edits
to the draft minutes to the applicant via email within a
timely manner. These minutes will become final 15 calendar
days after the applicant receives FDA's edits, unless the
applicant indicates that there is a disagreement with how a
significant issue or action item has been documented. In this
case, within a timely manner, the applicant and FDA will
conduct a teleconference to discuss that issue with FDA. At
the conclusion of that teleconference, within 15 days FDA
will finalize the minutes either to reflect the resolution of
the issue or note that this issue remains a point of
disagreement.
FDA intends that feedback the Agency provides in a Pre-
Submission will not change, provided the information
submitted in a future IDE or marketing application is
consistent with that provided in the Pre-Submission and
documented in the Pre-Submission, and that the data in the
future submission, changes in the science, or changes in the
standards of care do not raise any important new issues
materially affecting safety or effectiveness. The minutes
described above will serve as the record of the Agency's Pre-
Submission feedback. Modifications to FDA's feedback will be
limited to situations in which FDA concludes that the
feedback does not adequately address important new issues
materially relevant to a determination of safety and/or
effectiveness or substantial equivalence. Such a
determination will be supported by the appropriate management
concurrence consistent with applicable guidance and SOPs.
By March 31, 2024, the Agency will issue draft guidance to
update the guidance on ``Requests for Feedback and Meetings
for Medical Device Submissions: The Q-Submission Program'' to
include additional information to assist applicants and
review staff in identifying the circumstances in which an
applicant's question is most appropriate for informal
communication instead of a Pre-Submission. FDA will provide
an opportunity for the public to comment on the updated
guidance. No later than 18 months after the close of the
public comment period, the Agency will issue a final
guidance. FDA will implement this guidance once final. FDA
will train staff and managers on the updated guidance.
B. Original PMAs, Product Development Protocols, Panel-Track
Supplements, and Premarket Reports
The performance goals in this section apply to all Original
PMAs, Product Development Protocols (PDPs), Panel-Track
Supplements, and Premarket Reports.
FDA will communicate with the applicant regarding whether
the application has been accepted for filing review within 15
calendar days of receipt of the application. This
communication consists of a written communication that a)
identifies the reviewer assigned to the submission, and b)
acknowledges acceptance/rejection of the submission based
upon the review of the submission
[[Page S5196]]
against objective acceptance criteria outlined in a published
guidance document and consistent with the statute and its
implementing regulations.
If the application is not accepted for filing review, FDA
will notify the applicant of those items necessary for the
application to be considered accepted for filing review.
For those applications that are accepted for filing review,
FDA will communicate the filing status within 45 calendar
days of receipt of the application.
For those applications that are not filed, FDA will
communicate to the applicant the specific reasons for
rejection and the information necessary for filing.
If the application is filed, FDA will communicate with the
applicant through a Substantive Interaction within 90
calendar days of the filing date of the application for 95%
of submissions.
When FDA issues a major deficiency letter, that letter will
be based upon a complete review of the application and will
include all deficiencies. Deficiency letters will include a
statement of the basis for the deficiencies, as provided in
Section V.B below. Deficiency letters will undergo
supervisory review prior to issuance to ensure the
deficiencies cited are relevant to a determination of safety
and effectiveness. Any subsequent deficiencies will be
limited to issues raised by the information provided by the
applicant in its response, unless FDA concludes that the
initial deficiencies identified do not adequately address
important new issues materially relevant to a determination
of safety or effectiveness. Such a determination will be
supported by the appropriate management concurrence
consistent with applicable guidance and SOPs. Issues related
to post-approval studies, if applicable, and revisions to
draft labeling will typically be addressed through
interactive review once major deficiencies have been
adequately addressed.
PMA decision goal: For Original PMAs, PDPs, Panel-Track
Supplements, and Premarket Reports that do not require
Advisory Committee input, FDA will issue a MDUFA decision
within 180 FDA Days for 90% of submissions. This PMA decision
goal is relevant for purposes of Section III below.
For submissions that require Advisory Committee input, FDA
will issue a MDUFA decision within 320 FDA Days for 90% of
submissions. FDA will issue a MDUFA decision within 60 days
of the Advisory Committee recommendation, as resources
permit, but not to the detriment of meeting the quantitative
review timelines and statutory obligations. The Office
Director shall review each request for Advisory Committee
input for appropriateness and need for this input.
If in any one fiscal year, the number of submissions that
require Advisory Committee input is less than 10, then it is
acceptable to combine such submissions with the submissions
for the following year(s) in order to form a cohort of 10 or
more submissions, upon which the combined years' submissions
will be subject to the performance goal. If the number of
submissions that require Advisory Committee input is less
than 10 for FY 2027, it is acceptable to combine such
submissions in the prior year(s) to form a cohort of 10 or
more submissions: in such cases, FDA will be held to the FY
2027 performance goal for the combined years' submissions.
To facilitate an efficient review prior to the Substantive
Interaction, and to incentivize submission of a complete
application, submission of an unsolicited major amendment
prior to the Substantive Interaction extends the FDA Day
review clock by the number of FDA Days that have elapsed.
Submission of an unsolicited major amendment after the
Substantive Interaction extends the FDA Day goal by the
number of FDA Days equal to 75% of the difference between the
filing date and the date of receipt of the amendment.
Requests from FDA that a submission be made will not be
considered unsolicited.
For all PMA submissions that do not reach a MDUFA decision
by 20 days after the applicable FDA Day goal, FDA will
provide written feedback to the applicant to be discussed in
a meeting or teleconference, including all outstanding issues
with the application preventing FDA from reaching a decision.
The information provided will reflect appropriate management
input and approval and will include action items for FDA and/
or the applicant, as appropriate, with an estimated date of
completion for each party to complete their respective tasks.
Issues should be resolved through interactive review. If all
of the outstanding issues are adequately presented through
written correspondence, FDA and the applicant can agree that
a meeting or teleconference is not necessary.
For PMA submissions that receive a MDUFA decision of
Approvable, FDA will issue a decision within 60 days of the
sponsor's response to the Approvable letter, as resources
permit, but not to the detriment of meeting the quantitative
review timelines and statutory obligations.
In addition, information about submissions that miss the
FDA Day goal will be provided as part of FDA's Performance
Reports, as described in Section VII.
C. 180-Day PMA Supplements
FDA will communicate with the applicant through a
Substantive Interaction within 90 calendar days of receipt of
95% of submissions.
FDA will issue a MDUFA decision within 180 FDA Days for 95%
of submissions.
D. Real-Time PMA Supplements
FDA will issue a MDUFA decision within 90 FDA Days for 95%
of submissions.
E. De Novo Requests
De Novo decision goal: FDA will issue a MDUFA decision
within 150 FDA Days for 70% of De Novo requests. This De Novo
decision goal is subject to adjustment per Section III below.
Deficiencies identified will be based upon a complete
review of the submission and will include all deficiencies.
Deficiency letters will include a statement of the basis for
the deficiencies, as provided in Section V.B below.
Deficiency letters will undergo supervisory review prior to
issuance to ensure the deficiencies cited are relevant to a
classification determination. Any subsequent deficiencies
will be limited to issues raised by the information provided
by the applicant in its response, unless FDA concludes that
the initial deficiencies identified do not adequately address
important new issues materially relevant to a classification
determination. Such a determination will be supported by the
appropriate management concurrence consistent with applicable
guidance and SOPs. Issues related to revisions to draft
labeling will typically be addressed through interactive
review once major deficiencies have been adequately
addressed.
At the applicant's request and as resources permit, but not
to the detriment of meeting the quantitative review
timelines, if a final decision has not been rendered within
180 FDA days, FDA will discuss with the applicant all
outstanding issues with the submission preventing FDA from
reaching a decision. This discussion will reflect appropriate
management input and approval and will include action items
for FDA and/or the applicant, as appropriate, with an
estimated date of completion for each party to complete their
respective tasks.
F. 510(k) Submissions
FDA will communicate with the applicant regarding whether
the submission has been accepted for review within 15
calendar days of receipt of the submission. For those
submissions that are not accepted for review, FDA will notify
the applicant of those items necessary for the submission to
be considered accepted.
FDA will provide written communication that a) identifies
the reviewer assigned to the submission, and b) acknowledges
acceptance/rejection of the submission based upon the review
of the submission against objective acceptance criteria
outlined in a published guidance document. This communication
represents a preliminary review of the submission and is not
indicative of deficiencies that may be identified later in
the review cycle.
For 510(k) submissions received under the eSTAR program, a
submission that passes the initial technical screening will
be considered accepted for review as of the date the
submission was received.
FDA will communicate with the applicant through a
Substantive Interaction within 60 calendar days of receipt of
the submission for 95% of submissions.
Deficiencies identified in a Substantive Interaction, such
as a telephone/email hold or Additional Information Letter,
will be based upon a complete review of the submission and
will include all deficiencies. Deficiency letters will
include a statement of the basis for the deficiencies, as
provided in section V.B below. Deficiency letters will
undergo supervisory review prior to issuance to ensure the
deficiencies cited are relevant to a determination of
substantial equivalence. Any subsequent deficiencies will be
limited to issues raised by the information provided by the
applicant in its response, unless FDA concludes that the
initial deficiencies identified do not adequately address
important new issues materially relevant to a determination
of substantial equivalence. Such a determination will be
supported by the appropriate management concurrence
consistent with applicable guidance and SOPs.
510(k) decision goal: FDA will issue a MDUFA decision for
95% of 510(k) submissions within 90 FDA Days. This 510(k)
decision goal is relevant for purposes of Section III below.
For all 510(k) submissions that do not reach a MDUFA
decision within 100 FDA Days, FDA will provide written
feedback to the applicant to be discussed in a meeting or
teleconference, including all outstanding issues with the
application preventing FDA from reaching a decision. The
information provided will reflect appropriate management
input and approval and will include action items for FDA and/
or the applicant, as appropriate, with an estimated date of
completion for each party to complete their respective tasks.
Issues should be resolved through interactive review. If all
of the outstanding issues are adequately presented through
written correspondence, FDA and the applicant can agree that
a meeting or teleconference is not necessary.
In addition, information about submissions that miss the
510(k) decision goal will be provided as part of FDA's
Performance Reports, as described in Section VII.
G. CLIA Waiver by Application
FDA will engage in a Substantive Interaction with the
applicant within 90 days for 90% of the applications.
Pre-Submission review timeframes in Section II.A apply to
Pre-Submissions for CLIA Waiver by Application and Dual
submission 510(k)/CLIA Waiver applications.
Industry will inform FDA that it plans to submit a dual
submission (510(k) and CLIA Waiver application) during the
Pre-Submission process. FDA will issue a decision for 90% of
dual submission applications within 180 FDA days.
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For ``CLIA Waiver by application'' submissions FDA will
issue a MDUFA decision for 90% of the applications that do
not require Advisory Committee input within 150 FDA days.
For ``CLIA Waiver by application'' submissions FDA will
issue a MDUFA decision for 90% of the applications that
require Advisory Committee input within 320 FDA days.
If in any one fiscal year, the number of submissions in any
CLIA Waiver by Application category is less than 10, then it
is acceptable to combine such submissions with the
submissions for the following year(s) in order to form a
cohort of 10 or more submissions, upon which the combined
years' submissions will be subject to the performance goal.
For all CLIA waiver by application submissions and dual
submissions that do not reach a decision by 20 days after the
applicable FDA Day goal, FDA will provide written feedback to
the applicant to be discussed in a meeting or teleconference,
including all outstanding issues with the application
preventing FDA from reaching a decision. The information
provided will reflect appropriate management input and
approval, and will include action items for FDA and/or the
applicant, as appropriate, with an estimated date of
completion for each party to complete their respective tasks.
Issues should be resolved through interactive review. If all
of the outstanding issues are adequately presented through
written correspondence, FDA and the applicant can agree that
a meeting or teleconference is not necessary.
In addition, information about submissions that miss the
FDA Day goal will be provided as part of FDA's Performance
Reports, as described in Section VII.
H. Original Biologics Licensing Applications (BLAs)
FDA will review and act on standard original BLA
submissions within 10 months of receipt for 90% of
submissions.
FDA will review and act on priority original BLA
submissions within 6 months of receipt for 90% of
submissions.
I. BLA Efficacy Supplements
FDA will review and act on standard BLA efficacy supplement
submissions within 10 months of receipt for 90% of
submissions.
FDA will review and act on priority BLA efficacy supplement
submissions within 6 months of receipt for 90% of
submissions.
J. Original BLA and BLA Efficacy Supplement Resubmissions
FDA will review and act on Class 1 original BLA and BLA
efficacy supplement resubmissions within 2 months of receipt
for 90% of submissions.
FDA will review and act on Class 2 original BLA and BLA
efficacy supplement resubmissions within 6 months of receipt
for 90% of submissions.
K. BLA Manufacturing Supplements Requiring Prior Approval
FDA will review and act on BLA manufacturing supplements
requiring prior approval within 4 months of receipt for 90%
of submissions.
III. Opportunity for Performance Improvements
MDUFA V will provide for increases in fee revenue above the
annual total revenue amount to support performance
improvements in FY 2025, FY 2026, and/or FY 2027, as detailed
below. If such fee revenue adjustments are not made, the
performance goals in Section II apply.
For the purpose of fee revenue adjustments, performance of
all goals in this section, except for the Pre-Submission
Written Feedback goal, will be determined based on data
available as of 18 months following the close of the fiscal
year at issue. Thus, for a FY 2023 goal, the performance will
be determined based on data available as of March 31, 2025.
For a FY 2024 goal, the performance will be determined based
on data available as of March 31, 2026. For the Pre-
Submission Written Feedback goal, performance will be
determined based on data available as of 6 months following
the close of the fiscal year at issue. Thus, for example, for
the Pre-Submission Written Feedback goal for FY 2023,
performance will be determined based on data available as of
March 31, 2024.
A. PMA and 510(k): Decision Goals and Shared Outcome Total
Time to Decision Goals
I. FDA's 510(k) decision goal, the FDA/Industry 510(k)
Shared Outcome Total Time to Decision goal, FDA's PMA
decision goal, and the FDA/Industry PMA Shared Outcome Total
Time to Decision goal are met for FY 2023, and fee revenue
above the annual total revenue amount is provided in FY 2026
and FY 2027 to support performance improvements, the 510(k)
Shared Outcome Total Time to Decision goal will be adjusted
to 108 days for FY 2026 and FY 2027 and the PMA Shared
Outcome Total Time to Decision goal will be adjusted to 275
days for FY 2026 and FY 2027.
If FDA's 510(k) decision goal, the FDA/Industry 510(k)
Shared Outcome Total Time to Decision goal, FDA's PMA
decision goal, and the FDA/Industry PMA Shared Outcome Total
Time to Decision goal are met in FY 2024, and fee revenues
above the annual total revenue amount are provided in FY 2027
to support performance improvements, the 510(k) Shared
Outcome Total Time to Decision goal will be adjusted to 108
days and the PMA Shared Outcome Total Time to Decision goal
will be adjusted to 270 days for FY 2027.
B. De Novo Requests
If the De Novo decision goal is met for FY 2023, and fee
revenue above the annual total revenue amount is provided in
FY 2026 and FY 2027 to support performance improvements, the
goal will be adjusted to 80% of De Novo requests receiving a
MDUFA decision within 150 FDA days for FY 2026 and 2027.
If the De Novo decision goal is met for FY 2024, and fee
revenue above the annual total revenue amount is provided in
FY 2027 to support performance improvements, the goal will be
adjusted to 90% of De Novo requests receiving a MDUFA
decision within 150 FDA days in FY 2027.
C. Pre-Submissions
If the Pre-Submission Written Feedback goal is met for FY
2023, and fee revenue above the annual total revenue amount
is provided to support performance improvements, the maximum
number of submissions subject to the goal will escalate to
4700 Pre-Submissions in FYs 2025, 2026 and 2027.
If the Pre-Submission Written Feedback goal is met for FY
2024, and fee revenue above the annual total revenue amount
is provided to support performance improvements, the maximum
number of submissions subject to the goal will escalate to
4800 Pre-Submissions in FY 2026 and FY 2027.
If the Pre-Submission Written Feedback goal is met for FY
2025, and fee revenue above the annual total revenue amount
is provided to support performance improvements, the goal
will not be subject to a maximum number of submissions in FY
2027.
The goal for percent of Pre-Submissions in the MDUFA Cohort
receiving timely feedback, as described in Section II.A, will
remain at 90% for FYs 2025, 2026, and 2027.
IV. Infrastructure
A. Quality Management
The CDRH Quality Management and Organizational Excellence
(QMOE) Program is comprised of a team of certified quality
management staff who report to the Center Director. This QMOE
staff are focused on meeting customers' needs by improving
consistency, efficiency, timeliness, and effectiveness of
operations. The QMOE Program establishes and leads the CDRH
Quality Management System (QMS) activities, facilitates
process improvements, independently audits CDRH processes and
activities, and assesses the effectiveness of actions taken
to prevent potential (risk management) and resolve existing
issues (nonconformity management).
At least once per year, the Agency will discuss with
industry the specific areas it intends to incorporate in its
ongoing audit plan with the QMOE Program. FDA will identify,
with industry input, areas to audit, which will include the
effectiveness of CDRH's nonconformity management process. FDA
will continue to expand the scope of its annual audits as it
implements and builds up its auditing capability, as
resources permit. At a minimum, FDA audits in the following
areas will be completed: Pre-Submissions and Third Party
Review Program.
As part of these ongoing audits, high-performing premarket
review best practices utilized in one Office of Health
Technology (OHT) will be identified and shared accordingly
with other OHTs to improve efficiencies and effectiveness.
At least once per year, FDA will report on the results of
the audits, best practices identified and shared across OHTs,
and the actions taken in response to nonconformities
associated with the nonconformity management process.
B. Financial Transparency and Hiring
1. Financial Transparency
FDA will publish a MDUFA 5-year financial plan no later
than the end of the 2nd quarter of FY 2023. The financial
plan will include the Agency's annual hiring targets. No
later than the end of the 2nd quarter of each subsequent
fiscal year, FDA will publish updates to the 5-year plan as
of the end of the prior fiscal year. The annual updates will
include information concerning:
The number of new MDUFA V hires by Office;
The number of new MDUFA V hires made from outside the
Center, as well as the number of new MDUFA V hires made from
current Center employees (if any);
The number of unfilled new MDUFA V hires;
The changes in the personnel compensation and benefit costs
for the process for the review of medical device applications
that exceed the amounts provided by the personnel
compensation and benefit costs portion of the inflation
adjustment;
An accounting of appropriated user fee funds included in
the operating reserves at the end of each fiscal year, as
well as the carryover balance of user fee funds that are
considered unappropriated or unearned and therefore not
included in the operating reserves; and
An accounting of the amount excluded from the designated
amount within the operating reserves, which is intended to
support the Third Party Review program and the Total Product
Life Cycle Advisory Program Pilot.
2. Carryover Balance
MDUFA V will provide for FDA to decrease registration fees
if the Agency has more than 13 weeks of operating reserves in
the carryover balance. In addition, during MDUFA V FDA will
use funds in the carryover balance to support the Third Party
Review program and the Total Product Life Cycle Advisory
Program Pilot. The amount of carryover balance funds intended
to support these programs will be excluded when
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calculating the amount of operating reserves to determine if
registration fees will be decreased. The current statutory
one-month reserve will also be excluded when calculating the
amount of operating reserves to determine if registration
fees will be decreased. User fee funds in the carryover
balance that are considered unappropriated or unearned are
not included in the operating reserves.
No less than annually, FDA and industry will work together
to seek alignment on how best to utilize available funds in
the carryover balance to improve the process for the review
of device applications--e.g., performance on submission types
with performance goals and/or quality management programs.
FDA and industry will use, as input for the discussion,
workload information, performance objectives, and ongoing
reported performance.
3. Hiring Goals
Enhancements to the medical device review program require
that FDA recruit, hire and retain sufficient numbers and
types of technical, scientific, and other program experts to
support the process for the review of device applications.
MDUFA V provides significant new resources to FDA to support
these activities.
To help ensure that FDA accomplishes hiring in accordance
with the assumptions underlying the agreement, FDA will
establish annual hiring goals for each year of MDUFA V.
The minimum hiring goals for FY 2023-2025 are:
FY 2023: 144 hires
FY 2024: 42 hires
FY 2025: 24 hires
As described in Section III, the MDUFA V agreement provides
for enhancements to the shared outcome total time to decision
goals and to specified review performance goals, provided
that specified goals were met in prior years. These enhanced
goals will be applicable in FY 2025 (for the Pre-Submission
Written Feedback goal) and FY 2026-2027 (for the Pre-
Submission Written Feedback goal, the PMA Shared Outcome
Total Time to Decision goal, the 510(k) Shared Outcome Total
Time to Decision goal, and the De Novo Decision goal).
FDA and Industry have agreed that, if performance
improvement adjustments are triggered for each year per
Section III, the Agency will increase hiring to support the
enhanced goals.
FY 2025
In FY 2025, if performance improvement adjustments are made
to the Pre-Submission Written Feedback goal per Section III,
FDA will increase the hiring goal by 59 hires to a total of
83 hires. As part of the process for establishing the user
fee rates for FY 2025, FDA will also calculate the hiring
goal for that year and include the goal in the associated
Federal Register fee-setting notice.
FY 2026 and FY 2027
In FY 2026 and FY 2027, the number of hires will depend on
(1) which performance improvement adjustments are triggered
for that year, and (2) whether the hiring goal was increased
the prior year. For FY 2026 and FY 2027, as part of the
process for establishing the user fee rates for that year,
FDA will also calculate the hiring goal for that year and
include the goal in the associated Federal Register fee-
setting notice.
Pre-hires
For purposes of determining whether the hiring goal is met
for FY 2023, FDA will include ``pre-hires'' that are made in
FY 2022 for MDUFA V positions. In addition, for subsequent
fiscal years, if FDA exceeds the hiring goal, the additional
hires made above the goal will be counted towards the
following fiscal year goal.
4. Fee Adjustment Related to Hiring
For FY 2023, if the hiring goal is missed by more than 15%
at the end of the fiscal year (i.e., if fewer than 123 hires
are made in FY 2023, including FY 2022 pre-hires), unused
fees that were projected to support these hires for FY 2023
will be used to decrease registration fees for FY 2025.
For FY 2024 or FY 2025, if the hiring goal is missed by
more than 10% at the end of the fiscal year (i.e., if fewer
than 38 hires are made in FY 2024), unused fees that were
projected to support these positions for the applicable
fiscal year will be used to decrease registration fees for FY
2026 and FY 2027, respectively.
The amount of the hiring adjustment fee decrease will be
the product of the number of hires by which the hiring goal
was missed and one-quarter of the inflation-adjusted cost per
full-time equivalent (FTE).
For the purpose of calculating progress toward meeting
these hiring goals, a hire is defined as someone who has been
confirmed as on board by the date indicated in a full-time
position. Hires may be recruited from outside the FDA, or, in
some cases, a hire can also be a current FDA employee who is
changing positions within the agency.
C. IT Infrastructure for Submission Management
FDA will continue to enhance IT infrastructure to support
the process for the review of device applications.
FDA will maintain and improve on the Customer Collaboration
Portal, including the submission progress tracking system
that provides near real-time submission status. By the end of
MDUFA V, the progress tracking system will include 510(k),
Original PMA and Panel-Track Supplements, De Novo, Pre-
Submissions, and IDEs.
FDA will continue to develop electronic submission
templates that will serve as guided submission preparation
tools for industry to improve submission consistency and
enhance efficiency in the review process. Templates for
Original PMA and Panel-Track Supplements, De Novo, Pre-
Submissions, and IDEs will be completed and made available
for voluntary use by the end of MDUFA V.
D. Training
FDA will continue to evaluate and improve training for new
and existing reviewers under this agreement. FDA training
efforts will also be closely coordinated with the QMOE
Program to provide more targeted and personalized training to
staff.
E. Time Reporting
FDA will continue to perform complete time reporting such
that data from time reporting can be used to conduct workload
analysis and capacity planning.
v. process improvements
A. Interactive Review
The Agency will continue to incorporate an interactive
review process to provide for, and encourage, informal
communication between FDA and applicants to facilitate timely
completion of the review process based on accurate and
complete information. Interactive review entails
responsibilities for both FDA and applicants. As described in
the 2014 guidance document, ``Types of Communication During
the Review of Medical Devices Submissions,'' both FDA and
industry believe that an interactive review process for
premarket medical device submissions should help facilitate
timely completion of the review based on accurate and
complete information. Interactive review is intended to
facilitate the efficient and timely review and evaluation by
FDA of premarket submissions and is expected to support
reductions in total time to decision. The interactive review
process contemplates increased informal interaction between
FDA and applicants, including the exchange of scientific and
regulatory information.
B. Deficiency Letters
By January 1, 2023, the Agency will update the 2017
guidance ``Developing and Responding to Deficiencies in
Accordance with the Least Burdensome Provisions; Guidance for
Industry and FDA Staff'' to clarify what constitutes a
statement of the basis for the deficiency and continue
alignment with the following:
Deficiency letters should include a statement of the basis
for the deficiencies (e.g., a specific reference to
applicable section of a rule, final guidance, recognized
standard unless the entire or most of document is
applicable). In the instance when the deficiency cannot be
traced in the manner above and relates to a scientific or
regulatory issue pertinent to the determination, FDA will
cite the specific scientific issue and the information to
support its position.
Deficiency letters will undergo supervisory review prior to
issuance to ensure the deficiencies cited are relevant to a
marketing authorization decision (e.g., 510(k) clearance, PMA
approval, and de novo classification).
FDA will train staff and managers on the updated guidance
and work to make improvements (including incorporating best
practices), as appropriate, to address findings from audits
and consistent with the guidance.
FDA will provide a statement of the basis for the
deficiency, consistent with the updated guidance, in
deficiency letters as follows: 75% of deficiencies in FY
2023, 80% of deficiencies in FY 2024, 85% of deficiencies in
FY 2025, 90% of deficiencies in FY 2026, and 95% of
deficiencies in FY 2027 for Original PMA, Panel-Track
Supplement, 510(k) and De Novo request submissions.
Performance will be determined by means of annual audit
conducted by QMOE. Sampling procedures will incorporate ISO
2859-1:1999 (``Sampling Procedures for inspection by
attributes--Part 1: Sampling schemes indexed by acceptance
quality limit (AQL) for lot-by-lot inspection''). FDA will
review each fiscal year's audit results with industry no
later than the first quarterly meeting of the following
fiscal year.
C. Enhanced Use of Consensus Standards
The voluntary Accreditation Scheme for Conformity
Assessment (ASCA) Pilot is intended to enhance product
reviewers' and device manufacturers' confidence in medical
device testing when manufacturers rely on testing completed
by ASCA-accredited testing laboratories. This should
generally decrease the need for the FDA to request additional
information regarding testing methodologies when a premarket
submission includes ASCA testing. ASCA also incorporates
existing international conformity assessment standards and
practices where practical.
FDA will use lessons learned from implementation of the
ASCA Pilot Program during MDUFA IV to transition from a pilot
to a sustainable and expanded program. Specifically, the
Agency will:
1. By the end of FY 2023, FDA will complete the pilot. In
Q2 of FY 2024, FDA will provide a report on the performance
of the ASCA Pilot Program (to replace the report specified in
the MDUFA IV Commitment Letter, Commitment IV.D.8.a). In the
report, FDA will provide at least the following information:
a. Adequacy of the standards selected to support confidence
by FDA and industry in the methods used and results reported
by ASCA-accredited testing laboratories;
b. Testing laboratory participation in the training and
ASCA program, and areas where any nonconformities were
observed;
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c. Number of submissions containing the ASCA Summary
Report;
d. Summary Report acceptance rate by FDA reviewers; and
e. Summary of commonly cited deficiencies regarding the
Summary Report.
2. FDA will train staff and supervisors so that specific
deficiencies are relevant to the requirements of the Summary
Report.
3. FDA will continue to provide adequate training to
testing laboratories and reviewers to accurately execute the
ASCA process.
4. FDA will report annually on the progress of the ASCA
program.
5. FDA will work with stakeholders for further input on
programmatic improvements and/or consideration for expansion.
D. Third Party Review
The Agency will continue to support the Third Party Review
program, with the objective of eliminating routine re-review
by FDA of Third Party reviews through continuation of the
following activities:
1. Provide training for Third Parties seeking accreditation
by FDA. This training shall include the opportunity for Third
Parties to have access to redacted review memos and other
information as appropriate.
2. When FDA's expectations for a particular device type
change, FDA will maintain a process to convey this
information to the Third Parties and to industry.
3. Audit and provide tailored re-training to accredited
Third Parties based on the results of audits.
4. Publish performance of individual accredited Third
Parties with at least five completed submissions on FDA's
website (e.g., rate of NSE, average number of holds, average
time to SE).
FDA will consider the factors described in the guidance,
``510(k) Third Party Review Program,'' in determining device
type eligibility for the Third Party Review
program. Consistent with that guidance, some device types
that rely on clinical data to demonstrate substantial
equivalence may be eligible for Third Party Review.
E. Patient Science and Engagement
The Agency will take the following actions to continue
engaging patients and incorporating their perspectives in the
regulatory process. Where appropriate, the Agency will
leverage collaborations and partnerships with patients,
healthcare providers, industry, and others, as well as
collaborations across FDA Centers, to advance these actions.
1. Expand clinical, statistical, and other scientific
expertise and staff capacity to respond to submissions
containing applicant-proposed use of voluntary patient
preference information (PPI), voluntary patient reported
outcomes (PROs), and/or patient generated health data (PGHD).
These staff will provide submission review and early
consultation/advice to industry during study planning.
2. Issue a draft guidance providing best practices on
incorporating into premarket studies clinical outcome
assessments including their use as primary or co-primary
endpoints. A clinical outcome assessment (COA) describes or
reflects how a person feels, functions, or survives and can
be reported by a health care provider or a non-clinical
observer (such as a parent), through performance of an
activity or task, or by the patient.
3. Support the use of innovative technologies to capture
patient input and reduce patient burden to inform clinical
study design and conduct, with a goal of reducing barriers to
patient participation and facilitating recruitment and
retention.
4. By the end of FY 2024, hold a public meeting to explore
ways to use patient-generated health data to help advance
remote clinical trial data collection and support clinical
outcome assessments.
5. FDA will undertake the following activities to improve
the regulatory predictability and impact of patient science:
a. Develop case examples of modified or adapted PRO
instruments to make efficient use of existing validated PRO
instruments which may be improved or adapted to other
subpopulations or other regulatory uses in a more streamlined
and expeditious manner than creating novel PROs.
b. Strengthen efforts to expand staff understanding of
Patient Science and Engagement (PSE) topics, and consistent
evaluation in submissions through training curriculum and
internal infrastructure to improve consistency (e.g., Focal
Point Program).
c. Update FDA's existing guidance, ``Patient Preference
Information--Voluntary Submission, Review in Premarket
Approval Applications, Humanitarian Device Exemption
Applications, and De Novo Requests, and Inclusion in Decision
Summaries and Device Labeling,'' with pragmatic insights and
to address common questions for those interested in the
voluntary use of PPI in regulatory submissions.
d. Explore opportunities to improve patient science tools
for medical devices and advance health equity through
targeted incorporation of diverse patient perspectives and
integration of data from diverse patients.
e. Identify high impact opportunities to incorporate
patient perspectives.
6. Facilitate industry efforts to collaborate with patients
in key areas by generating patient-friendly educational
modules on device trials, real-world data, device development
tools, and regulatory frameworks. FDA will also make these
educational modules publicly available, as appropriate.
7. The existing dispute resolution process should be used
in the event of disagreement between the applicant and the
Agency on the need for PPI, PRO and/or other tools to capture
PGHD.
F. Real World Evidence (RWE)
The Agency will use user fee revenue for the continued
development of Real-World Data (RWD) and RWE methods and
policies to advance regulatory acceptance for premarket
submissions, including expanded indications for use and new
clearance/approval of new devices, and clarify related
reporting requirements.
1. FDA will update the 2017 guidance document Use of Real-
World Evidence to Support Regulatory Decision-Making for
Medical Devices to provide more clarity on:
a. Least burdensome general expectations on what is needed
to demonstrate the ``Fit-for-Purpose of RWD'' for premarket
regulatory purposes, including expanded indications for use
and new clearance/approval of new devices;
b. More information, including generalized examples, on
previously used and accepted methodologies; and
c. Best practices for RWE review.
2. FDA will continue to advance CDRH's RWD/RWE Training
program for FDA review teams including the medical review
staff. Topics will include best practices for RWE review and
when to engage with CDRH RWE subject matter experts.
3. FDA will provide transparent program development updates
and financial accounting of User Fee revenue specifically
intended for the activities in this section.
a. FDA will update stakeholders on the RWE program
activities at two or more open public meetings during the
course of MDUFA V.
b. FDA hiring of internal experts to support the review of
RWD/RWE-related submissions will be tracked.
c. In any portion of the user fee funding is distributed to
the National Evaluation System for health Technology (NEST),
the funding should be used to transparently:
i. Support the development of RWD resources to facilitate
appropriate access for research studies;
ii. Convene experts to develop best practices and, advance
innovative methodology approaches with respect to RWE
development and analysis;
iii. Include, on the organization's governing board, no
fewer than 4 representatives of the trade associations that
participated in the MDUFA V negotiations (AdvaMed, MDMA,
MITA, and ACLA), with each association appointing an
individual to serve. Industry representation on the governing
board, if applicable, will make up at least 25% of the
governing board membership at all times, and shall be
selected by the industry associations. The representative
from each trade association may be part of the staff of the
association or appointed from a member company. If any of the
trade associations elects not to participate on the governing
board or for any additional seats allocated to industry, the
participating trade associations will determine how to fill
any vacant Industry positions.
d. By the end of FY 2023, FDA will publish a document
requesting public comment on how FDA should use any portion
of the user fee funding that may be distributed to any
external organization(s) other than NEST to support premarket
RWE.
e. If any portion of the user fee funding is distributed to
an external organization(s) other than NEST, the funding will
be accounted for in FDA's quarterly MDUFA report.
G. Digital Health
The Agency will continue to build its digital health
expertise and continue working to streamline and align FDA
review processes with software lifecycles for digital health
products. Specifically, the Agency will:
1. Continue to develop software and digital health
technical expertise to provide assistance for premarket
submissions that include software, interoperable devices, or
otherwise incorporate digital health technologies, such as
artificial intelligence or machine learning (AI/ML), Virtual,
Mixed, and Augmented Reality (VR/MR/AR) and wearables.
2. Strengthen efforts to expand staff understanding of
digital health topics and enhance consistent evaluation in
submissions through training and internal infrastructure
(e.g., Focal Point Program).
3. Continue to participate in international harmonization
efforts related to digital health, including work on
developing software and other digital health convergence
efforts.
4. Finalize the draft guidance, ``Content of Premarket
Submissions for Device Software Functions,'' by 18 months
from close of the comment period.
5. Publish draft guidance describing a process to evaluate
a predetermined change control plan for digital health
devices.
6. Engage with stakeholders, including patients, users, and
industry, through roundtables, informal meetings, and
teleconferences to explore regulatory approaches to digital
health technologies.
H. Guidance Document Development
FDA will apply user fee revenues to ensure timely
completion of Draft Guidance documents. The Agency will
strive to finalize, withdraw, reopen the comment period, or
issue a new draft guidance for 80% of draft guidance
documents within 3 years of the close of the comment periods
as resources permit. The Agency will strive to finalize,
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withdraw, reopen the comment period, or issue a new draft
guidance for 100% of draft guidance documents within 5 years
of the close of the comment periods as resources permit. The
Agency will continue to develop guidance documents and
improve the development process as resources permit, but not
to the detriment of meeting quantitative review timelines and
statutory obligations.
I. International Harmonization
FDA is committed to improving the efficiency of the global
regulatory systems for medical devices through international
harmonization and convergence of regulatory requirements. The
Agency will take the following actions to advance such
international harmonization. Specifically, the Agency will:
1. Expand engagement in international harmonization and
convergence efforts through participation with international
regulators and other key stakeholders in forums, working
groups, projects, and committees to promote alignment with
international best practices and internationally developed
policies, including exploring the development of harmonized
premarket review processes.
2. Further support regulatory convergence by creating a
mechanism for FDA to work with regulatory partners with whom
we have appropriate confidentiality commitments to inform and
align international regulatory strategy. This may include,
for example, sharing of scientific, clinical, or other
technical information, or policies and practices, as needed
and consistent with applicable disclosure law and policy.
3. Commencing in FY 2023, assess the extent of CDRH
implementation of International Medical Device Regulators
Forum (IMDRF) technical documents and make this information
publicly available to enhance clarity and transparency.
4. Support the creation of a forum to engage with relevant
stakeholders, including industry representatives and other
regulators, to identify opportunities for regulators to
leverage one another's approach to decision making.
5. Participate in outreach activities to other regulatory
authorities that encourage harmonization and may also
encourage such authorities to rely in whole or in part on FDA
marketing authorizations.
6. By the end of FY 2023, issue for public comment a draft
strategic plan with additional details and timelines
associated with achieving the international harmonization
objectives described above.
7. Commencing with FY 2024, publish an annual assessment of
the international harmonization activities described the
strategic plan above, including the progress assessment
described in subparagraph 3 above.
J. Total Product Life Cycle (TPLC) Advisory Program
FDA will establish a pilot of the Total Product Life Cycle
(TPLC) Advisory Program (TAP Pilot) during the course of
MDUFA V.
1. Vision: The long-term vision for a successful TPLC
Advisory Program (TAP) is to help spur more rapid development
as well as more rapid and widespread patient access to safe,
effective, high-quality medical devices of public health
importance. A mature TAP will also help ensure the sustained
success of the Breakthrough devices program.
2. TAP Pilot Objective: The TAP Pilot is intended to
demonstrate the feasibility and benefits of process
improvements to FDA's early interactions with participants
and FDA's facilitation of interactions between participants
and stakeholders that support the vision for TAP. Through the
TAP Pilot, the FDA will provide the following types of
strategic engagement for innovative devices of public health
importance:
Improving participants' experiences with FDA by providing
for more timely premarket interactions;
Enhancing the experience of all participants throughout the
device development and review process, including FDA staff;
Facilitating improved strategic decision-making during
product development, including earlier identification,
assessment, and mitigation of product development risk;
Facilitating regular, solutions-focused engagement between
FDA review teams, participants, and other stakeholders such
as patients, providers, and payers, beginning early in device
development; and
Collaborating to better align expectations regarding
evidence generation, improve submission quality, and improve
the efficiency of the premarket review process
3. Goals: To achieve the above TAP Pilot objective, FDA
will:
a. Begin and support a TAP Pilot, scoped to include the
following:
In FY 2023, enroll up to 15 products in a ``soft launch''
in one Office of Health Technology (OHT); selection of the
OHT will include consideration of the OHT's historical number
of granted Breakthrough designations, workload, and available
staffing and expertise;
In FY 2024, continue to support products enrolled in the
previous fiscal year and expand to enroll up to 45 additional
products in at least two OHTs (i.e., up to 60 total products
enrolled through FY 2024);
In FY 2025, continue to support products enrolled in
previous fiscal years and expand to enroll up to 65
additional products in at least four OHTs (i.e., up to 125
total products enrolled through FY 2025); and
In FY 2026-FY 2027, continue to support products enrolled
in previous fiscal years and expand to enroll up to 100
additional products each fiscal year within existing OHTs or
expand to additional OHTs, depending on lessons learned from
FY 2023-FY 2025 experience (i.e., up to 225 total products
enrolled through FY 2026 and up to 325 total products
enrolled through FY 2027).
For FY 2024-FY 2027, in addition to the considerations
above, selection of the OHTs will include consideration of
experience from prior years and input from industry and other
stakeholders.
b. Beginning in FY 2024, implement and track the following
quantitative performance metrics:
FDA will engage in a teleconference with the participant on
requested topic(s) pertaining to the TAP device within 14
days of the request for 90% of requests for interaction.
FDA will provide written feedback on requested
biocompatibility and sterility topics(s) pertaining to the
TAP device within 21 days of the request for 90% of such
requests for written feedback.
FDA will provide written feedback on requested topic(s)
pertaining to the TAP device other than biocompatibility and
sterility within 40 days of the request for 90% of requests
for written feedback.
c. Regularly review TAP pilot progress with industry, share
feedback, and assess the impact of the TAP Pilot and
opportunities for improvement.
d. Publish an assessment of the TAP Pilot on the FDA web
site no later than January 30, 2026.
For purposes of the annual performance report and
corrective action report, the goals of the TAP pilot are set
forth in Section V.J.3 above.
4. Enrollment. FDA intends to enroll participants in the
pilot using the following criteria:
a. Participation in the pilot will be voluntary.
b. For FY 2023-FY 2025, products will be those with a
granted Breakthrough designation. For FY 2026-FY 2027,
products will be those with a granted Breakthrough
designation or request for inclusion in the Safer
Technologies Program (STeP).
c. Participants have not submitted a Pre-Submission about
the product after granted Breakthrough designation or request
for inclusion in STeP.
d. Products will be early in their product development
process (e.g., have not yet initiated a pivotal study) at
time of pilot enrollment.
e. Each participant will have a maximum of one product
enrolled in the pilot per fiscal year.
f. Participants will be enrolled on first-come, first-
served basis.
FDA will inform potential participants of the TAP Pilot as
part of the Breakthrough designation process or request for
inclusion in STeP process.
If spaces remain available in a participating OHT or if
resources permit, FDA may consider enrolling devices from
additional OHT(s).
5. TAP Pilot Assessment. For informational purposes, FDA
will conduct an assessment of the TAP Pilot using an
independent third party (or parties) to assess the TAP pilot.
This assessment will include a participant survey and
quantitative and qualitative success metrics, starting in FY
2024, that include but are not limited to:
a. The extent to which FDA is successful at meeting the
quantitative goals described in V.J.3.b. above.
b. Participant satisfaction with the timeliness, frequency,
quality, and efficiency of interactions with and written
feedback from FDA.
c. Participant satisfaction with the timeliness, frequency,
quality, and efficiency of voluntary interactions with non-
FDA stakeholders facilitated by FDA (if utilized).
d. An overall assessment of the outcomes of the Pilot and
opportunities for improvement.
6. Other Measures. For informational purposes, FDA will
begin to track other measures of program success, which will
include:
Time from granting of Breakthrough designation or request
for inclusion in the Safer Technologies Program (STeP) to
receipt of marketing submission;
Time from receipt of marketing submission to marketing
authorization; and
Requests for additional information during submission
review.
VI. Independent Assessments
A. Independent Assessment of MDUFA Workforce Metrics
FDA will retain a qualified, independent contractor with
expertise in assessing public sector workforce data analysis
and reporting to conduct an assessment of current
methodologies and data/metrics available to represent the
MDUFA workforce. This will include assessment of positions
(filled/vacant) and MDUFA process FTEs, including the subset
funded by user fees, for each applicable FDA Center and
Office.
The report will include the contractor's findings from the
assessment and recommendations for improved methodologies to
represent MDUFA FTE resources, including the subset funded by
user fees. The assessment will be published on FDA's website
by March 31, 2025.
B. Independent Assessment of Review Process Management
FDA and the industry will participate in a targeted
assessment of the process for the review of device
applications. The assessment
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will include consultation with both FDA and industry at the
start of the assessment and prior to issuance of the final
report. The assessment shall be conducted under contract to
FDA by a private, independent consulting firm capable of
performing the technical analysis, management assessment, and
program evaluation tasks required to address the assessment
scope described below within the budget provided under this
user fee agreement.
The contractor will:
1. Evaluate FDA's premarket review program to identify
efficiencies that were realized as a result of the process
improvements and investments under MDUFA IV and V;
2. Assess the alignment of resource needs with the training
and expertise of hires;
3. Identify and share best practices across OHTs in OPEQ;
4. Assess the effectiveness of program areas targeted for
improvement under this agreement, including the following:
a. Implementation and impact of changes to the guidance
``Developing and Responding to the Deficiencies in Accordance
with the Least Burdensome Provisions,''
b. Implementation and impact of changes to the guidance
``Requests for Feedback and Meetings for Medical Device
Submissions: The Q-Submission Program,''
c. Third Party Review program (continued reduction of
routine re-review by FDA of Third Party reviews),
d. Digital Health program,
e. Patient Science and Engagement program,
f. Real World Evidence program, and
g. International Harmonization.
5. Assess other key areas identified by FDA and industry as
resources permit.
FDA will award the contract no later than March 31, 2025.
However, the contractor would not begin the audit of Pre-
Submissions before October 1, 2025. The contractor will
publish comprehensive findings and recommendations within 1
year, after reviews with FDA and industry and opportunities
to provide feedback for the contractor's consideration prior
to finalizing the final report. For all recommendations the
contractor will provide an estimate of additional resources
needed or efficiencies gained, as applicable.
FDA will incorporate findings and recommendations, as
appropriate, into its management of the process for the
review of device applications. FDA will analyze the
recommendations for improvement opportunities identified in
the assessment and, as appropriate, develop and implement a
corrective action plan, and assure its effectiveness.
vii. performance reports
The Agency will report its progress toward meeting the
goals described in this letter, as follows. If, throughout
the course of MDUFA V, the Agency and Industry agree that a
different format or different metrics would be more useful,
the reporting will be modified accordingly as per the
agreement of both FDA and Industry.
1. Quarterly reporting at the CDRH OHT level/CBER Center
level (in recognition of the significantly smaller number of
submissions reviewed at CBER):
1.1. For 510(k) submissions that do not go through a Third
Party, reporting will include:
i. Average and quintiles of the number of calendar days to
Substantive Interaction
ii. Average, and quintiles of the number of FDA Days,
Industry Days, and Total Days to a MDUFA decision
iii. Average number of review cycles
iv. Rate of submissions not accepted for review
1.2. For PMA submissions, reporting will include:
i. Average and quintiles of the number of calendar days to
Substantive Interaction for Original PMA, Panel-Track PMA
Supplement, and Premarket Report Submissions
ii. Average and quintiles of the of FDA Days, Industry
Days, and Total Days to a MDUFA decision
iii. Rate of applications not accepted for filing review,
and rate of applications not filed
1.3. For De Novo requests, reporting will include:
i. Average, and quintiles of the number of FDA Days,
Industry Days, and Total Days to a MDUFA decision
ii. Average number of review cycles
iii. Rate of submissions not accepted for review
1.4. For Pre-Submissions, reporting will include:
i. Number of Pre-Submissions in the MDUFA cohort
ii. Rate of submissions not accepted for review
iii. Average and quintiles of the number of calendar days
from submission to written feedback
iv. Number of Pre-Submissions that require a meeting
v. Percent of submissions with meetings for which industry
provided minutes within 15 days
1.5. For IDE applications, reporting will include:
i. Number of original IDEs received
ii. Average number of amendments prior to approval or
conditional approval of the IDE
1.6. In FY 2023, for marketing submissions for In Vitro
Diagnostics, FDA will report on the status of submissions
received in FY 2020-2021 that remain under review as a result
of being paused while the Agency focused on COVID-19-related
submissions.
2. CDRH will report quarterly, and CBER will report
annually, the following data at the Center level:
2.1. Rate of NSE decisions for 510(k) submissions
2.2. Rate of withdrawals for 510(k), De Novo, and PMA
submissions
2.3. Rate of Not Approvable decisions for PMA submissions
2.4. Rate of Denial decisions for De Novo requests
2.5. Key product areas or other issues that FDA identifies
as noteworthy because of a potential effect on performance,
including significant rates of Additional Information
requests
2.6. Specific topic or product area as it relates to
performance goals, agreed upon at the previous meeting
2.7. Number of submissions that missed the goals and the
total number of elapsed calendar days broken down into FDA
days and industry days
2.8. Newly released draft and final guidance documents, and
status of other priority guidance documents
2.9. Agency level summary of fee collections
2.10. Independent assessment implementation plan status
2.11. Results of independent assessment and subsequent
periodic audits and progress toward implementation of the
recommendations and any corrective action
2.12. Number of fee waivers or reductions granted by type
of submission
3. The Agency will report quarterly the following data for
the MDUFA program:
3.1. Progress towards meeting annual hiring goals
3.2. Per Section V.F.3.e, if any portion of the user fee
funding intended for real world evidence activities is
distributed to an external organization(s) other than NEST,
information regarding use of the user fee funding
4. In addition, the Agency will provide the following
information on an annual basis:
4.1. Review time devoted to direct review of applications
4.2. The number of Premarket Report Submissions received
4.3. Summary information on training courses available to
CDRH and CBER employees, including new reviewers, regarding
device review and the percentage of applicable staff that
have successfully completed each such course. CDRH will
provide information concerning any revisions to the new
reviewer training program curriculum.
4.4. Performance on the shared outcome goal for average
Total Time to Decision
4.5. For 510(k) submissions, reporting will include:
i. Number of submissions reviewed by a Third Party
ii. Number of Special Submissions
iii. Number of Traditional Submissions
iv. Average and number of days to Accept/Refuse to Accept
v. Number of Abbreviated Submissions
4.6. For 510(k) submissions that go through a Third Party,
reporting will include:
i. Time from FDA receipt of Third Party report to FDA
decision at the 90% percentile
ii. Rate of NSE
iii. Average number of holds
iv. Average time to SE
4.7. For PMA submissions, reporting will include the number
of the following types of PMA submissions received:
i. Original PMAs
ii. Priority PMAs
iii. Premarket Reports
iv. Panel-Track PMA Supplement
v. PMA Modules
vi. 180-Day PMA Supplements
vii. Real-Time PMA Supplements
viii. Number of submissions FDA classifies as unsolicited
major, solicited major, and minor amendments
4.8. For De Novo requests, reporting will include:
i. Number of submissions received
ii. Average and number of days to Accept/Refuse to Accept
4.9. For CLIA waiver applications, reporting will include:
i. Number of CLIA waiver applications received
ii. Average and quintiles of the number of calendar days to
Substantive Interaction
iii. Average and quintiles of the number of FDA Days,
Industry Days, and Total Days to a MDUFA decision and a
discussion of any trends in the data
4.10. Report on the ASCA program
4.11. Data regarding the reviewer to manager ratio
4.12. Report on QMOE program
4.13. Summary of QMOE audits, including annual audit of
Deficiency Letters under Section V.B above
4.14. Summary of primary cost drivers that contribute to
change in personnel compensation and benefits costs (e.g.,
cost of living adjustments and increases in agency benefits
contributions, if applicable)
4.15. The return on investment, which may include process
improvements, improved performance, and other enhancements,
under MDUFA V.
FDA will report annual and quarterly data on performance
within goals for 510(k), De Novo, and PMA MDUFA decisions for
devices identified as LDTs by the submitter compared to all
non-LDT IVD devices. The following elements will be reported:
Number and percentage of LDT 510(k)s and non-LDT IVD
510(k)s completed within 90 FDA days
Number and percentage of LDT De Novo requests and non-LDT
IVD De Novo requests completed within 150 FDA days
[[Page S5202]]
Number and percentage of LDT PMAs and non-LDT IVD PMAs
completed within 180 FDA days
To the extent that laboratories make submissions regarding
LDTs that are covered by the MDUFA V agreement, FDA will
treat such LDT submissions no less favorably than other
submissions to which MDUFA V performance goals apply.
VIII. Definitions and Explanations of Terms
A. Applicant
Applicant means a person who makes any of the following
submissions to FDA:
an application for premarket approval under section 515 of
the Federal Food, Drug, and Cosmetic Act (FD&C Act);
a premarket notification under section 510(k) of the FD&C
Act;
an application for investigational device exemption under
section 520(g) of the FD&C Act;
a Pre-Submission;
a De Novo classification request (De Novo request) under
section 513(f)(2) of the FD&C Act;
a CLIA Waiver by application.
B. eSTAR (electronic Submission Template And Resource)
An electronic submission template built within a structured
dynamic PDF that guides a user through construction of an
eSubmission. eSTAR is the only type of electronic submission
template that is currently available to facilitate the
preparation of 510(k) submissions as eSubmissions. For
simplicity, the electronic submission created with this
electronic submission template is often referred to as an
eSTAR.
C. FDA Days
FDA Days are those calendar days when a submission is
considered to be under review at the Agency for submissions
that have been accepted (510(k) or De Novo request), filed
(PMA) or submitted (CLIA Waiver by application). FDA Days
begin on the date of receipt of the submission or of the
amendment to the submission that enables the submission to be
accepted (510(k) or De Novo request) or filed (PMA).
D. MDUFA Decisions
Original PMAs, Product Development Protocols, Panel-Track
Supplements, and Premarket Report Applications: Decisions are
approval, approvable, approvable pending GMP inspection, not
approvable, withdrawal, and denial.
180-Day PMA Supplements: Decisions for 180-Day PMA
Supplements are approval, approvable, and not approvable.
Real-Time PMA Supplements: Decisions for Real-Time PMA
supplements are approval, approvable, and not approvable.
510(k)s: Decisions for 510(k)s are substantially equivalent
(SE) or not substantially equivalent (NSE).
De Novo Requests: Decisions for De Novo requests are grant,
withdrawal, and decline.
CLIA Waiver by Application Submissions: Decisions for CLIA
Waiver by Application Submissions are approval, withdrawal,
and denial.
Submissions placed on Application Integrity Hold will be
removed from the MDUFA cohort.
E. Pre-Submission
A Pre-Submission includes a formal written request from an
applicant for feedback from FDA that is provided in the form
of a formal written response or, if the manufacturer chooses,
formal written feedback followed by a meeting or
teleconference in which any additional feedback or
clarifications are documented in meeting minutes.
A Pre-Submission provides the opportunity for an applicant
to obtain FDA feedback prior to intended submission of an
investigational device exemption or marketing application.
The request must include specific questions regarding review
issues relevant to a planned investigational device exemption
(IDE), CLIA Waiver by Application, Accessory Classification
Request, or marketing application (e.g., questions regarding
pre-clinical testing protocols or data requirements; design
and performance of clinical studies and acceptance criteria).
A Pre-Submission is appropriate when FDA's feedback on
specific questions is necessary to guide product development
and/or submission preparation.
The following forms of FDA feedback to applicants are not
considered Pre-Submissions.
Interactions requested by either the applicant or FDA
during the review of a marketing application (i.e., following
submission of a marketing application, but prior to reaching
an FDA Decision).
TPLC Advisory Program Pilot interactions.
General information requests initiated through the Division
of Industry and Consumer Assistance (DICE).
General questions regarding FDA policy or procedures.
Meetings or teleconferences that are intended to be
informational only, including, but not limited to, those
intended to educate the review team on new device(s) with
significant differences in technology from currently
available devices, or to update FDA about ongoing or future
product development, without a request for FDA feedback on
specific questions related to a planned submission.
Requests for clarification on technical guidance documents,
especially where contact is recommended by FDA in the
guidance document. However, the following requests will
generally need to be submitted as a Pre-Submission in order
to ensure appropriate input from multiple reviewers and
management: recommendations for device types not specifically
addressed in the guidance document; recommendations for
nonclinical or clinical studies not addressed in the guidance
document; requests regarding use of alternative means to
address recommendations specified in a guidance document.
Phone calls or email messages to reviewers that can be
readily answered based on a reviewer's experience and
knowledge and do not require the involvement of a broader
number of FDA staff beyond the routine involvement of the
reviewer's supervisor and more experienced mentors.
F. Substantive Interaction
Substantive Interaction is an email, letter,
teleconference, video conference, or other form of
communication such as a request for Additional Information or
Major Deficiency letters by FDA notifying the applicant of
substantive deficiencies identified in initial submission
review, or a communication stating that FDA has not
identified any deficiencies in the initial submission review
and any further minor deficiencies will be communicated
through interactive review. An approval or clearance letter
issued prior to the Substantive Interaction goal date will
qualify as a Substantive Interaction.
If substantive issues warranting issuance of an Additional
Information or Major Deficiency letter are not identified,
interactive review should be used to resolve any minor issues
and facilitate an FDA decision. In addition, interactive
review will be used, where, in FDA's estimation, it leads to
a more efficient review process during the initial review
cycle (i.e., prior to a Substantive Interaction) to resolve
minor issues such as revisions to administrative items (e.g.,
510(k) Summary/Statement, Indications for Use statement,
environmental impact assessment, financial disclosure
statements); a more detailed device description; omitted
engineering drawings; revisions to labeling; or clarification
regarding nonclinical or clinical study methods or data.
Minor issues may still be included in an Additional
Information or Major Deficiency letter where related to the
resolution of the substantive issues (e.g., modification of
the proposed Indications for Use may lead to revisions in
labeling and administrative items), or if they were still
unresolved following interactive review attempts. Both
interactive review and Substantive Interactions will occur on
the review clock except upon the issuance of an Additional
Information or Major Deficiency Letter which stops the review
clock.
G. Total Time to Decision
Total Time to Decision is the number of calendar days from
the date of receipt of an accepted (with respect to 510(k)s)
or filed (with respect to Original PMAs and Panel Track
Supplements) submission to a MDUFA decision.
For the purpose of calculating and reporting on 510(k)
shared outcome Total Time to Decision goals in section II,
the average Total Time to Decision for 510(k) submissions is
calculated as the average of Total Times to Decision for
510(k) submissions within a 99% closed cohort, with the
following provisions:
FY 2023, the cohort excludes submissions with any one hold
greater than 180 days and excluding the highest 5% of Total
Time to Decision on the remaining cohort.
FY 2024-2027, the cohort excludes the highest 2% and lowest
2% of values and includes all 510(k)s with a MDUFA decision.
In the number of submissions in any MDUFA V receipt cohort
exceeds the number of submissions in the FY 2021 or FY 2022
receipt cohort (whichever is higher) by 5% or more, a 1%
increase in the trim will be applied to the highest values.
A cohort for a FY is closed when 99% of the MDUFA cohort
has reached a MDUFA decision. For the purpose of determining
whether improved performance and fee revenue adjustments in
Section III are applicable, the 510(k) Shared Outcome Total
Time to Decision goal is calculated in the same manner except
that the calculation is conducted based on data available as
of 18 months following the close of the fiscal year to which
the goal applies, and the cohort does not need to be 99%
closed. See Section III.
For the purpose of calculating and reporting on PMA shared
outcome Total Time to Decision goals in Section II, the
average Total Time to Decision for PMAs is calculated as the
three-year rolling average of the annual Total Times to
Decision for Original PMAs and Panel Track supplements (for
example, for FY 2024, the average PMA Total Time to Decision
would be the average of FY 2022 through FY 2024) within a
closed cohort, excluding the highest 5% and the lowest 5% of
values. A cohort for a FY is closed when 95% of the MDUFA V
cohort has reached a MDUFA decision. For the purpose of
determining whether increased performance and fee revenue
adjustments in Section III are applicable, the PMA shared
outcome Total Time to Decision goal is calculated in the same
manner except that the calculation is conducted based on data
available as of 18 months following the close of the fiscal
year to which the goal applies and the cohort does not need
to be 95% closed.
H. Application Types
Original PMA means an application for an approval of a
device submitted under section 515(c) of the FD&C Act. It
does not include a
[[Page S5203]]
supplement to such an application after it has been approved
or a Premarket Report.
Premarket Report means a report submitted under section
515(c)(2) of the FD&C Act seeking premarket approval for a
class III reprocessed single use device.
Panel-Track Supplement means a supplement to an approved
Original PMA or Premarket Report that requests a significant
change in design or performance of the device, or a new
indication for use of the device, and for which substantial
clinical data are necessary to provide a reasonable assurance
of safety and effectiveness.
180-Day PMA Supplement means a supplement to an approved
Original PMA or Premarket Report that is not a panel-track
supplement and requests a significant change in components,
materials, design, specification, software, color additives,
or labeling.
Real-Time PMA Supplement means a supplement to an approved
Original PMA or Premarket Report that requests a minor change
to the device, such as a minor change to the design of the
device, software, sterilization, or labeling, and for which
the applicant has requested and the agency has granted a
meeting or similar forum to jointly review and determine the
status of the supplement.
De Novo Classification Request (De Novo Request) means a
request made under section 513(f)(2) of the FD&C Act with
respect to the classification of a device.
Premarket Notification (510(k)) Submission means a report
submitted under section 510(k) of the FD&C Act.
I. BLA-related Definitions
Review and act on--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.
Class 1 resubmitted applications applications resubmitted
after a complete response letter that includes the following
items only (or combinations of these items):
(a) Final printed labeling
(b) Draft labeling
(c) Safety updates submitted in the same format, including
tabulations, as the original safety submission with new data
and changes highlighted (except when large amounts of new
information including important new adverse experiences not
previously reported with the product are presented in the
resubmission)
(d) Stability updates to support provisional or final
dating periods
(e) Commitments to perform Phase 4 studies, including
proposals for such studies
(f) Assay validation data
(g) Final release testing on the last 1-2 lots used to
support approval
(h) A minor reanalysis of data previously submitted to the
application (determined by the Agency as fitting the Class 1
category)
(i) Other minor clarifying information (determined by the
Agency as fitting the Class 1 category)
(j) Other specific items may be added later as the Agency
gains experience with the scheme and will be communicated via
guidance documents to industry
Class 2 resubmitted applications resubmissions that include
any other items, including any item that would require
presentation to an advisory committee.
GDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROGRAM ENHANCEMENTS FISCAL
YEARS 2023-2027
I. Submission Assessment Performance Goals
A. Original ANDAs and Amendments
B. PASs and PAS Amendments
C. Unsolicited Amendments and PAS Amendments
D. DMFs
E. Controlled Correspondence
II. Original ANDA Assessment Program Enhancements
A. ANDA Receipt
B. ANDA Assessment Transparency and Communications
Enhancements
C. Assessment Classification Changes During the Assessment
Cycle
D. ANDA Approval and Tentative Approval
E. Dispute Resolution
F. Pre-Submission Facility Correspondence
G. Other ANDA Assessment Program Aspirations
III. Pre-ANDA Program
A. Goal of Pre-ANDA Program
B. Suitability Petitions
C. Product-Specific Guidance
D. Product Development Meetings
E. Pre-Submission Meetings
IV. ANDA Assessment Meeting Program
A. Goal of the ANDA Assessment Meeting Program
B. Mid-Cycle Review Meetings and Enhanced Mid-Cycle Review
Meetings
C. Post-CRL Scientific Meeting
V. Additional Program Enhancements and Aspirations
A. Inactive Ingredient Database Enhancement
B. Regulatory Science Enhancements
C. Other Pre-ANDA and Assessment Meeting Program
Aspirations
VI. DMF Assessment Program Enhancements
A. Communication of DMF Assessment Comments
B. Teleconferences to Clarify DMF First Cycle Assessment
Deficiencies
C. DMF First Adequate Letters
D. DMF No Further Comment Letters
E. DMF Review Prior to ANDA Submission
F. FDA Assessment of Solicited DMF Amendments
G. FDA Communication Related to DMF Amendments and ANDAs
VII. Facilities
A. Foreign Regulators
B. Communication Regarding Inspections
C. GDUFA III Inspection Classification Database
D. Post-Warning Letter Meetings
E. Generic Drug Manufacturing Facility Re-inspection
VIII. Continued Enhancement of User Fee Resource Management
A. Sustainability of GDUFA Program Resources
B. Resource Capacity Planning
C. Resource Capacity Planning Assessment
D. Financial Transparency and Efficiency
E. Improving the Hiring of Review Staff
IX. Guidance and Mapps
X. Performance Reporting
A. Monthly Reporting Metrics
B. Quarterly Reporting Metrics
C. Fiscal Year Performance Report Metrics
D. Fiscal Year Web Posting
XI. Definitions
GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal
Years 2023-2027
This document contains the performance goals and program
enhancements for the Generic Drug User Fee Amendments (GDUFA)
reauthorization for fiscal years (FYs) 2023-2027, known as
GDUFA III. It is commonly referred to as the ``Goals Letter''
or ``Commitment Letter.'' The Goals Letter represents the
product of the Food and Drug Administration's (FDA or the
Agency) discussions with the regulated industry and public
stakeholders, as mandated by Congress. The performance goals
and program enhancements specified in this letter apply to
aspects of the generic drug assessment program and build on
the GDUFA program established and enhanced through previous
authorizations. New enhancements to the program are designed
to maximize the efficiency and utility of each assessment
cycle, with the intent to reduce the number of assessment
cycles for abbreviated new drug applications (ANDAs) and
facilitate timely access to quality, affordable, safe and
effective generic medicines. Certain new enhancements are
specifically designed to foster the development, assessment,
and approval of Complex Generic Products. FDA is committed to
meeting the performance goals specified in this letter and to
continuous improvement of the Agency's performance.
GDUFA Reauthorization Performance Goals and Procedures Fiscal Years
2023-2027
The performance goals and procedures of FDA, as agreed to
under the third authorization of the generic drug user fee
program, are summarized below.
Unless otherwise stated, goals apply to cohorts of each
fiscal year. For the purposes of calculating all time periods
in this Commitment Letter, FDA will calculate the goal date
from the day after a submission, to be consistent with FDA's
other user fee programs.
I. SUBMISSION ASSESSMENT PERFORMANCE GOALS
A. Original ANDAs and Amendments
1. Assess and act on 90 percent of standard original ANDAs
within 10 months of the date of ANDA submission, subject to
any adjustments to the goal dates described in section
I(A)(3).
2. Assess and act on 90 percent of priority original ANDAs
within the applicable assessment goal, subject to any
adjustments to the goal dates described in section I(A)(3).
a. Assess and act on priority original ANDAs within 8
months of the date of ANDA submission if the applicant
submits a Pre-Submission Facility Correspondence (PFC) not
later than 60 days prior to the date of ANDA submission, and
the PFC is found to be complete and accurate, subject to the
limitations set forth in section I(A)(2)(b).
b. Assess and act on priority original ANDAs within 10
months of the date of ANDA submission if:
i. the applicant submits a PFC later than 60 days prior to
the date of ANDA submission, or does not submit a PFC;
ii. information in a PFC is found to be incomplete or
inaccurate;
iii. the information submitted in the ANDA differs
significantly from what was submitted in the PFC; or
iv. FDA, upon assessment of a final bioequivalence study
report submitted in the ANDA, determines that an inspection
of the relevant site or sites is necessary.
3. If, upon initial submission, a standard or priority
original ANDA contains a certification that a site/facility
listed on the Form FDA 356h is not ready for inspection
(i.e., the box ``no'' is checked in response to ``is the site
ready for inspection?'' in section 28), FDA will set a goal
date that is 15 months from the date of submission. FDA will
conduct a filing review of such an ANDA but will not commence
substantive assessment of the application until an amendment
described in subsection I(A)(3)(a) is submitted, or the goal
date is reset pursuant to I(A)(3)(b).
a. During the initial 15-month review period, if the
applicant submits an amendment with a Form FDA 356h that
certifies all facilities are ready for inspection, FDA will
set a new goal date that is 8 months from the
[[Page S5204]]
date of submission for priority amendments (if a PFC was
submitted per I(A)(2)(a)), or 10 months from the date of
submission for other amendments.
b. If the applicant does not submit an amendment described
in I(A)(3)(a) by 30 days before the goal date, FDA will reset
the goal date for an additional 15 months, i.e., 30 months
from the date of original ANDA submission. FDA will assess
and act on 90 percent of such ANDAs within 30 months of the
date of the original submission as applicable.
4. Assess and act on 90 percent of standard Major
Amendments within the applicable assessment goal.
a. Assess and act on standard Major Amendments within 8
months of the date of amendment submission if preapproval
inspection is not required.
b. Assess and act on standard Major Amendments within 10
months of the date of amendment submission if preapproval
inspection is required.
5. Assess and act on 90 percent of priority Major Amendment
submissions within the applicable assessment goal.
a. Assess and act on priority Major Amendments within 6
months of the date of amendment submission if preapproval
inspection is not required.
b. Assess and act on priority Major Amendments within 8
months of amendment submission if a preapproval inspection is
required, the applicant submits a PFC not later than 60 days
prior to the date of amendment submission, and the PFC is
found to be complete and accurate, subject to the limitations
set forth in section I(A)(6).
6. Assess and act on priority Major Amendments within 10
months of amendment submission if a preapproval inspection is
required and if:
a. the applicant submits a PFC later than 60 days prior to
the date of the amendment, or does not submit a PFC;
b. information in a PFC is found to be incomplete or
inaccurate;
c. the information submitted in the amendment differs
significantly from what was submitted in the PFC; or
d. FDA, upon assessment of a final bioequivalence study
report submitted in the amendment, determines that an
inspection of the relevant site or sites is necessary.
7. Assess and act on 90 percent of standard and priority
Minor Amendments within 3 months of the date of amendment
submission.
TABLE FOR SECTION I(A)(1) AND (2): ORIGINAL ANDAs
------------------------------------------------------------------------
Submission Type Goal
------------------------------------------------------------------------
Standard Original ANDAs................... 90% within 10 months of
submission date, subject to
any adjustment to the goal
date described in section
I(A)(3).
Priority Original ANDAs................... 90% within 8 months of
submission date if
applicant meets
requirements under section
I(A)(2)(a), subject to any
adjustment to the goal date
described in section
I(A)(3).
90% within 10 months of
submission date if
applicant meets any
limitations as described
under section I(A)(2)(b),
subject to any adjustment
to the goal date described
in section I(A)(3).
------------------------------------------------------------------------
TABLE FOR SECTION I(A)(4)-(7): AMENDMENTS
------------------------------------------------------------------------
Submission Type Goal
------------------------------------------------------------------------
Standard Major Amendments................. 90% within 8 months of
submission date if
preapproval inspection not
required.
90% within 10 months of
submission date if
preapproval inspection
required.
Priority Major Amendments................. 90% within 6 months of
submission date if
preapproval inspection not
required.
90% within 8 months of
submission date if
preapproval inspection
required and applicant
meets requirements under
section I(A)(5)(b).
90% within 10 months of
submission date if
preapproval inspection
required and applicant
meets any limitations as
described under section
I(A)(6).
Standard and Priority Minor Amendments.... 90% within 3 months of
submission date.
------------------------------------------------------------------------
B. PASs and PAS Amendments
1. Assess and act on 90 percent of standard prior approval
supplements (PASs) within the applicable assessment goal.
a. Assess and act on standard PASs within 6 months of the
date of PAS submission if preapproval inspection is not
required.
b. Assess and act on standard PASs within 10 months of the
date of PAS submission if preapproval inspection is required.
2. Assess and act on 90 percent of priority PASs within the
applicable assessment goal.
a. Assess and act on priority PASs within 4 months of the
date of PAS submission if preapproval inspection is not
required.
b. Assess and act on priority PASs within 8 months of the
date of PAS submission if a preapproval inspection is
required, the applicant submits a PFC not later than 60 days
prior to the date of PAS submission, and the PFC is found to
be complete and accurate, subject to the limitations set
forth in section I(B)(2)(c).
c. Assess and act on priority PASs within 10 months of PAS
submission if a preapproval inspection is required and if:
i. the applicant submits a PFC later than 60 days prior to
the date of PAS submission, or does not submit a PFC;
ii. information in a PFC is found to be incomplete or
inaccurate;
iii. the information submitted in the PAS differs
significantly from what was submitted in the PFC; or
iv. FDA, upon assessment of a final bioequivalence study
report submitted in the PAS, determines that an inspection of
the relevant site or sites is necessary.
3. Assess and act on 90 percent of Major Amendments to
standard PASs within the applicable assessment goal.
a. Assess and act on Major Amendments to standard PASs
within 6 months of the date of amendment submission if
preapproval inspection is not required.
b. Assess and act on Major Amendments to standard PASs
within 10 months of the date of amendment submission if
preapproval inspection is required.
4. Assess and act on 90 percent of Major Amendments to
priority PASs within the applicable assessment goal.
a. Assess and act on Major Amendments to priority PASs
within 4 months of the date of amendment submission if
preapproval inspection is not required.
b. Assess and act on priority Major Amendments to priority
PASs within 8 months of amendment submission if a preapproval
inspection is required, if the applicant submits a PFC not
later than 60 days prior to the date of amendment submission,
and the PFC is found to be complete and accurate, subject to
the limitations set forth in section I(B)(4)(c).
c. Assess and act on priority Major Amendments to priority
PASs within 10 months of amendment submission if a
preapproval inspection is required and if:
i. the applicant submits a PFC later than 60 days prior to
the date of the PAS amendment, or does not submit a PFC;
ii. information in a PFC is found to be incomplete or
inaccurate;
iii. the information submitted in the PAS amendment differs
significantly from what was submitted in the PFC; or
iv. FDA, upon assessment of a final bioequivalence study
report submitted in the amendment, determines that an
inspection of the relevant site or sites is necessary.
5. Assess and act on 90 percent of Minor Amendments to
standard and priority PASs within 3 months of the date of
amendment submission.
TABLE FOR SECTION I(B)(1) AND (2): PASs
------------------------------------------------------------------------
Submission Type Goal
------------------------------------------------------------------------
Standard PASs............................. 90% within 6 months of
submission date if
preapproval inspection not
required.
90% within 10 months of
submission date if
preapproval inspection
required.
Priority PASs............................. 90% within 4 months of
submission date if
preapproval inspection not
required.
90% within 8 months of
submission date if
preapproval inspection
required and applicant
meets requirements under
section I(B)(2)(b).
90% within 10 months of
submission date if
preapproval inspection
required and applicant
meets any limitations as
described under section
I(B)(2)(c).
------------------------------------------------------------------------
TABLE FOR SECTION I(B)(3)-(5): PAS AMENDMENTS
------------------------------------------------------------------------
Submission Type Goal
------------------------------------------------------------------------
Standard PAS Major Amendments............. 90% within 6 months of
submission date if
preapproval inspection not
required.
90% within 10 months of
submission date if
preapproval inspection
required.
Priority PAS Amendments................... 90% within 4 months of
submission date if
preapproval inspection not
required.
90% within 8 months of
submission date if
preapproval inspection
required and applicant
meets requirements under
section I(B)(4)(b).
90% within 10 months of
submission date if
preapproval inspection
required and applicant
meets any limitations as
described under section
I(B)(4)(c).
Standard and Priority Minor PAS Amendments 90% within 3 months of
submission date.
------------------------------------------------------------------------
C. Unsolicited Amendments and PAS Amendments
1. Assess and act on Unsolicited Amendments and PAS
amendments submitted during the assessment cycle by the later
of the goal date for the original submission/solicited
amendment or the goal date assigned in accordance with
sections (I)(A)(4), (5), (6) and (7) and (I)(B)(3), (4) and
(5), respectively, for the Unsolicited Amendment.
2. Assess and act on Unsolicited ANDA Amendments and PAS
amendments submitted between assessment cycles by the later
of the goal date for the subsequent solicited amendment or
the goal date assigned in accordance with sections (I)(A)(4),
(5), (6), and (7) and (I)(B)(3), (4), and (5), respectively,
for the Unsolicited Amendment.
D. Drug Master Files (DMFs)
Complete the initial completeness assessment for 90 percent
of Type II active pharmaceutical ingredient (API) DMFs within
60 days of the later of the date of DMF submission or DMF fee
payment.
TABLE FOR SECTION I(D): DMFs
------------------------------------------------------------------------
Submission Type Goal
------------------------------------------------------------------------
Type II API DMF........................... 90% of initial completeness
assessments within 60 days
of the later of the date of
DMF submission or DMF fee
payment.
------------------------------------------------------------------------
E. Controlled Correspondence
1. A Controlled Correspondence may be submitted by or on
behalf of a generic drug manufacturer or related industry
prior to ANDA submission. Under the GDUFA II framework,
correspondence seeking regulatory and/or scientific advice
after issuance of a Complete Response Letter (CRL) or
tentative approval, or after ANDA approval, was considered
general correspondence. Under GDUFA III, these types of
correspondence can be submitted as Controlled Correspondence.
During an ANDA assessment cycle, a Controlled Correspondence
may only be submitted if an applicant seeks further feedback
from FDA after a product-specific guidance (PSG)
Teleconference, as described in section III(C)(5)(c), below,
or to seek a Covered Product Authorization. During an ANDA
assessment cycle, all other correspondence will be general
correspondence.
2. Review and respond to 90 percent of Controlled
Correspondence within the applicable review goal.
[[Page S5205]]
a. Review and respond to Level 1 Controlled Correspondence
within 60 days of the date of submission.
b. Review and respond to Level 2 Controlled Correspondence
within 120 days of the date of submission.
3. FDA will review and respond to 90 percent of submitter
requests to clarify ambiguities in the Controlled
Correspondence response within 21 days of receipt of the
request. The response to the submitter's request will provide
clarification or advice concerning the ambiguity in the
Controlled Correspondence response.
TABLE FOR SECTION I(E): CONTROLLED CORRESPONDENCE
------------------------------------------------------------------------
Submission Type Goal
------------------------------------------------------------------------
Level 1 Controlled Correspondence......... 90% within 60 days of
submission date.
Level 2 Controlled Correspondence......... 90% within 120 days of
submission date.
------------------------------------------------------------------------
FDA will review and respond to 90% of submitter requests to clarify
ambiguities in the Controlled Correspondence response within 21 days
of request receipt.
II. ORIGINAL ANDA ASSESSMENT PROGRAM ENHANCEMENTS
A. ANDA Receipt
1. FDA will strive to determine whether to receive ANDAs
within 60 days of the date of ANDA submission.
2. To enable FDA to rapidly determine whether to receive an
ANDA pursuant to 21 CFR 314.101, and with consideration of
final Agency guidances that address ANDA receipt
determinations, FDA will communicate minor technical
deficiencies (e.g., document legibility) and deficiencies
potentially resolved with information in the ANDA at original
submission within 10 days of original ANDA submission. If a
deficiency is resolved within 10 days, that deficiency will
not be a basis for a refuse-to-receive decision.
3. At the time of receipt, FDA will notify the applicant in
the acceptance letter whether the ANDA or PAS is subject to
priority or standard assessment.
B. ANDA Assessment Transparency and Communications
Enhancements
To promote transparency and communication between FDA and
ANDA applicants, FDA will apply the assessment program
enhancements below to the assessment of all ANDAs. The goal
of these program enhancements is to improve predictability
and transparency, promote the efficiency and effectiveness of
the review process, minimize the number of assessment cycles
necessary for approval, increase the overall rate of
approval, and facilitate greater access to generic drug
products.
1. Information Requests (IRs) and Discipline Review Letters
(DRLs):
a. IRs and DRLs do not stop the assessment clock.
b. In the first assessment cycle, FDA will issue the
appropriate IR(s) and/or DRL(s) from each assessment
discipline by the mid-point of the assessment, with the
exception of the Labeling discipline as described in
subsection II(B)(2) below.
i. In a Mid-Cycle DRL, the assessment discipline will
assign a due date for response and identify major and minor
deficiencies.
ii. If an applicant responds by the response due date, FDA
will assess a response to minor deficiencies within the
originally assigned goal date for the submission, subject to
the exceptions described in II(B)(1)(iii).
iii. Responses to any major deficiencies, or to minor
deficiencies that include data and information that require
comparable FDA assessment resources to those required for
major deficiencies, for example, a consult, will be
considered Major Amendments. FDA will extend the goal date
consistent with the number of months needed to assess a
comparable standard or priority Major Amendment (see section
I(A)(4)-(6)).
c. FDA will issue IRs and DRLs after the midpoint of the
first assessment cycle and at any time in subsequent
assessment cycles, when, in FDA's judgment, there are one or
more minor deficiencies in a discipline that, if resolved
using an IR or DRL, could lead to approval or tentative
approval of an ANDA in the current assessment cycle. FDA will
issue the IR or DRL and provide a due date for the
applicant's response before the goal date.
i. If the applicant responds to the minor deficiencies in
the IR or DRL by the due date, and FDA finds the amendment to
satisfactorily address all of the issues identified in the IR
or DRL, and the response does not contain unsolicited
information, FDA may extend the goal date by 90 days from the
date of the applicant's response.
ii. FDA's decision to extend the goal date will be
communicated in an amendment acknowledgement letter.
iii. FDA will continue to issue IRs and/or DRLs late in the
assessment cycle for original submissions and amendments
until it is no longer feasible within the current assessment
cycle for the applicant to develop and FDA to assess a
response to the IR and/or DRL. For IRs and DRLs issued past
the mid-point of the assessment cycle, the assessment
discipline generally will assign a due date for response and
identify major and minor deficiencies. DRLs issued without a
response due date likely will signify a forthcoming CRL.
d. If the applicant does not provide a complete response to
an IR and/or DRL by the response due date (or any agreed-upon
extension), FDA may include the same deficiencies from the IR
or DRL in a CRL and assess the response during the next
assessment cycle.
e. If a discipline identifies a Significant Major
deficiency, that deficiency will be communicated in a CRL as
soon as is feasible.
2. Specific commitments related to IRs and DRLs for
labeling:
a. In the first assessment cycle, the Labeling Discipline
will:
i. upon receiving an ANDA for assessment, make an initial
determination whether there is a need for a consult to be
issued to another review discipline, including for a consult
regarding an applicant's request to ``carve out'' language in
the proposed labeling protected by patents or exclusivities,
and will initiate such consults;
ii. strive to issue any DRL at approximately months 6-7 of
the assessment for those ANDAs with a 10-month goal date, or
months 5-6 of the assessment for those ANDAs with an 8-month
goal date, with the exception that there may be a delay of
the issuance of any labeling deficiencies that result from
changes to the labeling of the reference listed drug (RLD) or
a new exclusivity or patent listing;
iii. limit the assessment of labeling to one IR/DRL if
other disciplines will not be acceptable during the first
cycle; and
iv. continue to assess labeling to enable an action within
the assessment cycle if other disciplines are acceptable.
b. Labeling IRs and DRLs in all assessment cycles:
FDA will minimize issuing CRLs that contain only labeling
deficiencies by, for example, utilizing later-cycle IRs and
the imminent action process.
3. Imminent Actions:
a. FDA will continue assessment of an ANDA past the goal
date if, in FDA's judgment, it may be possible to approve or
tentatively approve an ANDA within 60 days after the goal
date. Such circumstances may include:
i. When the application meets the requirements for
tentative approval by the goal date, but the legally
permissible ANDA approval date is within 60 days after the
goal date, and FDA may be able to approve the ANDA when it
becomes legally permissible to do so.
ii. When FDA may be able to approve or tentatively approve
an application submitted by a first applicant by the 30-month
forfeiture date described in section 505(j)(5)(D)(i)(IV) of
the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21
U.S.C. 355(j)(5)(D)(i)(IV)).
iii. When, at the sole discretion of FDA, and subject to
resources, one or more small issues remain from one or more
disciplines that in FDA's judgment may be resolved within 60
days after the goal date.
b. If an ANDA is approved or tentatively approved within 60
days after the goal date, the goal date will be considered to
have been met.
4. FDA will strive to act prior to a goal date, or the 60-
day period for an imminent action, when the assessment is
complete and there are no outstanding deficiencies.
5. To facilitate the labeling assessment, an applicant will
clearly state in the cover letter to an ANDA, amendment, PAS,
or PAS Amendment that the submission includes a proposed
labeling carve-out.
6. Communication regarding Deficiencies and Actions:
a. With respect to imminent actions, applicants may inquire
and FDA will promptly respond to an applicant inquiry seeking
information as to whether FDA intends to work through the
goal date in accordance with section II(B)(3). This
communication will be preliminary and subject to change.
b. If a regulatory project manager (RPM) learns that a
major deficiency is likely forthcoming, the RPM will notify
the applicant. The RPM will not be expected to discuss the
nature of the specific forthcoming deficiencies prior to
issuance of the CRL.
c. If an RPM learns that FDA is likely to miss the goal
date for an ANDA, the RPM will notify the applicant of the
delay in taking an action, identify the general reason for
the delay including the outstanding discipline(s), if any,
and the estimated time for FDA's action on the application.
d. The applicant may periodically request a Review Status
Update for each discipline. In response to the applicant's
request, the RPM will timely provide a Review Status Update
for each discipline.
7. FDA will indicate the assessment classification for a
responding amendment in a CRL and include FDA's basis for
classifying a responding amendment as Major.
8. Applicants who receive a CRL have the following options
with respect to engaging with FDA prior to responding to the
CRL:
a. A post-CRL teleconference to seek clarification
concerning deficiencies identified in a CRL. FDA will grant
appropriate requests for teleconferences requested by
applicants upon receiving first-cycle CRLs and upon receiving
subsequent CRLs. An appropriate request is one that clearly
identifies the specific deficiencies to be discussed and the
reason why such deficiencies are not clear. FDA will provide
a scheduled date for 90 percent of post-CRL teleconferences
within 14 days of the request for a teleconference and
conduct 90 percent of such post-CRL teleconferences, if
granted, within 30 days of receipt of the written request;
b. Submission of a Controlled Correspondence as described
in section I(E); or
c. A post-CRL Scientific Meeting to request scientific
advice on possible approaches to address deficiencies
identified in
[[Page S5206]]
a CRL related to establishing equivalence, subject to the
conditions described in section IV(C).
C. Assessment Classification Changes During the Assessment
Cycle
1. If during the assessment of an ANDA, ANDA amendment,
PAS, or PAS amendment, the assessment classification changes
from Standard to Priority, FDA will notify the applicant
within 14 days of the date of the change.
2. An applicant may request a change in the assessment
classification at any time during the assessment.
3. Once an ANDA or PAS submission is classified as being
subject to priority assessment, the application will retain
such priority assessment classification status for the
duration of that assessment cycle.
4. FDA will include an explanation of the reasons for any
denial of an assessment status reclassification request.
5. If an applicant requests a teleconference as part of its
request to reclassify a Major Amendment or standard
assessment status, FDA will schedule and conduct the
teleconference and decide 90 percent of such reclassification
requests within 30 days of the date of FDA's receipt of the
request for a teleconference. This goal only applies when the
applicant accepts the first scheduled teleconference date
offered by FDA. This goal does not apply to a Major Amendment
in response to a CRL that was deemed major only due to a
facility deficiency (``Facility-Based Major CRL Amendment'')
described in section II(C)(7).
6. An amendment in response to a CRL classified by FDA as
Minor that is submitted more than one year after the date FDA
issued the CRL will be reclassified as a Major Amendment,
except for ANDAs for products that are on the drug shortage
list under section 506E of the FD&C Act (21 U.S.C. 356e), or
are the subject of a response to a Public Health Emergency as
declared by the Secretary of the U.S. Department of Health
and Human Services under section 319 of the Public Health
Service Act (PHS Act) (42 U.S.C. 247d), or are anticipated to
be subject to the same criteria as apply to such a
declaration, at the time of submission.
7. Reclassification of Facility-Based Major CRL Amendments
a. Upon submission of a Facility-Based Major CRL Amendment,
an applicant can request that FDA reclassify the Major
Amendment to minor.
b. A request for reclassification must be made at the time
of amendment submission and include supporting information
detailing why the facility deficiency has been resolved and
no additional facility assessment is needed.
c. FDA will grant the request to reclassify the Facility-
Based Major CRL Amendment if FDA determines that none of the
following are necessary to complete the assessment of the
amendment:
i. A facility inspection
ii. Use of alternate tools for facility assessment
iii. Continued assessment of inspection deficiency
responses
d. If FDA denies the request, the Agency will communicate
the substantive basis of the denial to the applicant and the
ANDA amendment will be assigned a 6-, 8- or 10-month goal
date, as applicable, from the original date of the amendment
submission.
e. FDA will make a decision on a request for
reclassification of a Facility-Based Major CRL Amendment
within 30 days from the date of submission for priority
amendments, and within 60 days from the date of submission
for standard amendments. If the Facility-Based Major CRL
Amendment is reclassified as minor, the goal date will be 3
months from the end of the 30- or 60-day decisional period,
as applicable.
f. The goal dates for decisions on requests for
reclassification and amendment assessment for which a request
for reclassification is submitted are as follows:
----------------------------------------------------------------------------------------------------------------
FDA Response Regarding New ANDA Goal Date if
Submission Type Major to Minor Reclassification ANDA Goal Date if
Reclassification Granted Reclassification Denied
----------------------------------------------------------------------------------------------------------------
Standard Major Amendment........... Within 60 days of Within 5 months of Within 8 months of
submission date. submission date. submission date if
preapproval inspection is
not required.
Within 10 months of
submission date if
preapproval inspection is
required.
Priority Major Amendment........... Within 30 days of Within 4 months of Within 6 months of
submission date. submission date. submission date if
preapproval inspection is
not required.
Within 8 months of
submission date if
preapproval inspection
required and applicant
meets the requirements
under section I(A)(5)(b).
Within 10 months of
submission date if
preapproval inspection
required and applicant
meets any limitations as
described under section
I(A)(6).
----------------------------------------------------------------------------------------------------------------
D. ANDA Approval and Tentative Approval
If applicants submit and maintain ANDAs consistent with the
statutory requirements for approval under 505(j) of the FD&C
Act; respond to IRs and DRLs completely and within the time
frames requested by FDA; and timely submit all required
information under 21 CFR parts 314 and 210, including
information concerning notice (21 CFR 314.95), litigation
status (21 CFR 314.107), and commercial marketing (21 CFR
314.107); then FDA will strive to:
1. Approve approvable ANDAs in the first assessment cycle;
2. Approve First Generics on the earliest lawful approval
date, if known to FDA; and
3. Tentatively approve or approve ANDAs for ``First
Applicants'' as described in section 505(j)(5)(B)(iv)(II)(bb)
of the FD&C Act to avoid forfeiture of 180-day exclusivity.
E. Dispute Resolution
1. An applicant may pursue a request for reconsideration
within the assessment discipline at the Division level or
original signatory authority, as needed.
2. The Office of Generic Drugs, Office of Regulatory
Operations Associate Director will track each request for
Division-level reconsideration through resolution.
3. Following resolution of a request for reconsideration,
an applicant may pursue formal dispute resolution above the
Division level, pursuant to procedures set forth in Formal
Dispute Resolution: Sponsor Appeals Above the Division Level
Guidance for Industry and Review Staff (May 2019).
4. FDA will respond to 90 percent of appeals above the
Division level within 30 days of CDER's receipt of the
written appeal.
5. CDER's Formal Dispute Resolution Project Manager (or
designee) will track each formal appeal above the Division
level through resolution.
F. Pre-Submission Facility Correspondence
1. For the purposes of section I.A. and I.B. above, FDA
will consider a PFC to be complete and accurate if the
submission consists of the following:
a. For each manufacturing and testing facility involved in
manufacturing processes and testing for the ANDA and
corresponding Type II API DMF:
i. facility name, operation(s) performed, facility contact
name, address, FDA Establishment Identifier (FEI) number (if
a required registrant or one has been assigned), DUNS number,
registration information (for required registrants), and a
confirmation that the facility is ready for inspection,
ii. information needed to inform FDA's decision regarding
the need for a preapproval inspection, such as a description
of the manufacturing process and controls of critical steps,
identification of any anticipated differences between pilot/
exhibit scale and commercial scale processes, and as
otherwise described in the guidance for industry on ANDAs:
Pre-Submission of Facility Information Related to Prioritized
Generic Drug Applications (Pre-Submission Facility
Correspondence) (November 2017) and any revisions, and
iii. a certification by the applicant that any Type II DMF
has similarly complete and accurate facility information,
including complete facility information (i.e., facility name,
operation, facility contact name, address, FEI number and
DUNS number, and a confirmation that the facility is ready
for inspection).
b. Information needed to inform FDA's decision regarding
the need for a preapproval inspection, such as a description
of the drug substance manufacturing process, that is included
in a corresponding Type II DMF is not required to be
duplicated in the PFC for the ANDA if it is included in a
corresponding Type II DMF.
c. For all sites or organizations involved in all
bioequivalence and clinical studies used to support the ANDA
submission: site names, addresses, and website; the study
numbers; a list and description of all study investigators
consistent with the guidance ICH E3 Structure and Content of
Clinical Study Reports (July 1996) section 16.1.4; the study
conduct dates; and study protocols and any available
amendments.
d. For all sites or organizations involved in analytical
studies used to support the ANDA application submission the
following are required: analytical site name, address, and
website. For those studies that were initiated no later than
60 days prior to the ANDA submission, additional requirements
are:
i. a list of investigator name(s)
ii. study conduct dates; and
iii. if the analytical method validation was completed
before dosing, the analytical method validation study
report(s).
e. This information is provided using a standardized
electronic format and includes unique identifiers that are
current and accurate.
2. Changes to information contained in a PFC when submitted
in an ANDA that are considered a ``significant change''
include changes in the identified facilities for manufacture
of the drug substance or drug product, the proposed
manufacturing operations or operating principles, and the
order of manufacturing unit operations, as described in the
guidance ANDAs: Pre-Submission of
[[Page S5207]]
Facility Information Related to Prioritized Generic Drug
Applications (Pre-Submission Facility Correspondence)
(November 2017) and any revisions.
G. Other ANDA Assessment Program Aspirations
1. FDA aspires to continually improve the efficiency of the
ANDA Assessment program.
2. The absence of a GDUFA III commitment for a specific
program function does not imply that the program function is
not important. For example, other program functions include
determining whether listed drugs were voluntarily withdrawn
from sale for reasons of safety or effectiveness and ANDA
proprietary name evaluations.
iii. pre-anda program
A. Goal of Pre-ANDA Program
1. The goal of the pre-ANDA program is to clarify
regulatory expectations for prospective applicants early in
product development, assist applicants in developing more
complete submissions, promote a more efficient and effective
ANDA assessment process, and reduce the number of assessment
cycles required to obtain ANDA approval.
2. Some elements of these programs are tailored to enhance
the development of Complex Generic Products. Complex Generic
Products can raise unique scientific and regulatory
considerations, and FDA is committed to providing further
transparency and clarity on Complex Generic Product
development and assessment to help increase the availability
of these products.
B. Suitability Petitions
1. In FY 2023, FDA will work diligently to enhance the
Agency's processes for reviewing and responding to petitions
submitted under section 505(j)(2)(C) of the FD&C Act
(commonly referred to as ``suitability petitions''), and to
review and respond to pending suitability petitions.
2. Prior to FY 2024, FDA will take appropriate action to
determine if petitioners who submitted suitability petitions
prior to FY 2023 remain interested in a response.
3. FDA will conduct a completeness assessment for
suitability petitions submitted in FY 2024-2027. The
timeframe for the completeness assessment will be:
a. 21 days after the date of petition submission; or
b. If an IR is issued as part of the completeness
assessment and the petitioner submits a response, FDA will
finish the completeness assessment within 21 days after the
date of receipt of the IR response.
4. Any suitability petition submitted in FY 2024-2027 will
receive a goal date described in section III(B)(7). Any
suitability petitions submitted to FDA prior to FY 2024 will
not receive a goal date. If a petitioner wants to receive a
goal date on a suitability petition submitted prior to FY
2024, the petitioner may withdraw and submit a new
suitability petition in FY 2024-2027.
5. The date of submission for the purposes of determining
the fiscal year of submission will be the date of FDA's
completion of the completeness assessment.
6. FDA will prioritize the review of suitability petitions
for a drug product that:
a. could mitigate or resolve a drug shortage and prevent
future shortages;
b. address a public health emergency declared by the
Secretary of the U.S. Department of Health and Human Services
under section 319 of the PHS Act, or anticipated under the
same criteria as apply to such a declaration;
c. is for a new strength of a parenteral product that could
aid in eliminating pharmaceutical waste or mitigating the
number of vials needed per dose by addressing differences in
patient weight, body size, or age; or
d. is subject to special review programs under the
President's Emergency Plan for AIDS Relief (PEPFAR).
7. Beginning in FY 2024, FDA will review and respond to
suitability petitions that have been assigned a goal date
pursuant to the following goals:
a. In FY 2024, 50 percent of submissions within 6 months
after completeness assessment, up to a maximum of 50
suitability petitions completed;
b. In FY 2025, 70 percent of submissions within 6 months
after completeness assessment, up to a maximum of 70
suitability petitions completed;
c. In FY 2026, 80 percent of submissions within 6 months
after completeness assessment, up to a maximum of 80
suitability petitions completed; and
d. In FY 2027, 90 percent of submissions within 6 months
after completeness assessment, up to a maximum of 90
suitability petitions completed.
8. As a general matter, if FDA misses goal dates on
suitability petitions due to increased submissions, FDA will
prioritize the review of suitability petitions for which a
goal date was missed prior to reviewing newly submitted
suitability petitions for the current fiscal year, except for
those suitability petitions that are prioritized under
section III(B)(6). See Appendix for additional information on
FDA's review of suitability petitions in GDUFA III.
C. Product-Specific Guidance
1. FDA will continue to issue PSG identifying the
methodology for generating evidence needed to support ANDA
approval.
2. FDA will issue PSGs consistent with the following goals:
a. For Complex Products approved in new drug applications
(NDAs) on or after October 1, 2022, a PSG will be issued for
50 percent of such NDA products within 2 years after the date
of approval, and for 75 percent of such NDA products within 3
years after the date of approval.
b. FDA will continue to develop PSGs for Complex Products
approved prior to October 1, 2022, for which no PSG has been
published.
c. For non-complex drug products approved in NDAs on or
after October 1, 2022, that contain a new chemical entity
(NCE) (as described in section 505(j)(5)(F)(ii) of the FD&C
Act), a PSG will be issued within 2 years after the date of
approval for 90 percent of such products.
3. Information on PSG Development:
a. FDA will provide on its website information related to
upcoming new and revised PSGs to support the development and
approval of safe and effective generic drug products,
including the projected date of PSG publication, which may be
subject to change. When FDA becomes aware that it will not
meet the issuance date listed on the website, FDA will update
the website to provide a new projected issuance date in the
next scheduled update.
b. FDA routinely will update the information on this
website approximately every 4 months.
c. PSGs will be developed (or revised) and issued in
accordance with FDA's Good Guidance Practices and will be
reviewed by senior management and other designated subject
matter experts prior to publication and after consideration
of any public comments submitted to the relevant docket of a
published draft or final PSG.
4. Prioritization of PSG Development:
a. FDA will make available on its website information on
how the Agency prioritizes the development of PSGs.
b. Industry may request via the portal for Controlled
Correspondence that FDA develop a PSG. FDA will consider this
request in prioritizing PSG development but will not consider
this to be a Controlled Correspondence.
c. FDA will seek public input on prioritization of PSGs
annually during the public meeting on research prioritization
described in section V(B)(2).
d. For Complex Products, FDA generally will prioritize the
development of PSGs for Complex Products that contain a NCE
(as described in section 505(j)(5)(F)(ii) of the FD&C Act)
over Complex Products that do not contain an NCE.
5. When a new or revised PSG is published and an applicant
or prospective applicant has already commenced an in vivo
bioequivalence study (i.e., the study protocol has been
signed by the study sponsor and/or the contract research
organization) the applicant or prospective applicant may
request a PSG Teleconference to obtain Agency feedback on the
potential impact of the new or revised PSG on its development
program.
a. To be eligible for a PSG Teleconference, the applicant
or prospective applicant must submit with the meeting request
the signature page of the relevant in vivo study protocol
signed by the study sponsor and/or the contract research
organization.
b. FDA will hold a PSG Teleconference within 30 days after
the receipt of the meeting request. The PSG Teleconference
will be scheduled for 60 minutes.
c. If the applicant seeks further feedback from FDA after a
PSG Teleconference, the applicant may utilize the Controlled
Correspondence process or request an additional meeting. The
purpose of this meeting is to provide a forum in which
industry can discuss the scientific rationale for an approach
other than the approach recommended in the PSG to ensure that
the approach complies with the relevant statutes and
regulations.
i. If the applicant has not submitted an ANDA, the
prospective applicant can submit a request for a Pre-
Submission PSG Meeting. FDA will grant or deny the meeting
within 14 days after receipt of the request and if granted,
will schedule the meeting within 120 days after receipt of
the request.
ii. If the applicant has submitted an ANDA, the applicant
can submit a request for a Post-Submission PSG Meeting. FDA
will grant or deny the meeting within 14 days after receipt
of the request, and if granted, will schedule the meeting
within 90 days after receipt of the request.
iii. FDA may deny a Pre- or Post-Submission PSG Meeting if
the request is incomplete, or the inquiry would be more
appropriately resolved through a Controlled Correspondence.
FDA may grant a Pre- or Post-Submission Meeting request after
such a Controlled Correspondence if the Agency determines
that any issue(s) remain unresolved or would be more
appropriately resolved in a meeting.
iv. Applicants and prospective applicants are eligible to
request a Pre-Submission PSG Meeting or Post-Submission PSG
Meeting regardless of whether they have had a Product
Development Meeting or a post-CRL Scientific Meeting.
6. When FDA intends to issue a new or revised PSG and there
are ANDAs under review that may be impacted by changes to the
new or revised PSG, FDA will ensure that at least division-
level program leadership is aware of the potential impact on
the pending ANDAs for drug products with related new or
revised PSGs.
D. Product Development Meetings
1. A prospective applicant can request a pre-ANDA
submission Product Development Meeting. The purpose of the
meeting is to provide a forum for a scientific exchange on
specific issues (e.g., a proposed study design,
[[Page S5208]]
alternative approach, additional study expectations, or
questions) in which FDA will provide targeted advice
regarding an ongoing ANDA development program.
2. FDA will grant a prospective applicant a Product
Development Meeting if, in FDA's judgment:
a. The requested Product Development Meeting concerns:
i. Development of a Complex Generic Product for which FDA
has not issued a PSG; or
ii. An alternative equivalence evaluation, i.e., change in
study type, such as in vitro to clinical, for a Complex
Generic Product for which FDA has issued a PSG;
b. The prospective applicant submits a complete meeting
package, including a data package and specific proposals;
c. A Controlled Correspondence response would not
adequately address the prospective applicant's questions; and
d. A Product Development Meeting would significantly
improve ANDA assessment efficiency.
3. Dependent on available resources, FDA may grant a
prospective applicant a Product Development Meeting
concerning development issues other than those described in
Section III(D)(2) if, in FDA's judgment:
a. The prospective applicant submits a complete meeting
package, including a data package and specific proposals;
b. A Controlled Correspondence response would not
adequately address the prospective applicant's questions; and
c. A Product Development Meeting would significantly
improve ANDA assessment efficiency.
4. FDA will grant or deny 90 percent of Product Development
Meeting requests within 14 days after receipt of the meeting
request.
5. FDA will conduct 90 percent of Product Development
Meetings within 120 days after the meeting is granted.
6. FDA can meet the Product Development Meeting goal by
either conducting a meeting or providing a meaningful written
response that will inform drug development and/or regulatory
decision-making to the prospective applicant, within the
applicable goal date.
7. Unless FDA is providing a written response to satisfy
the Product Development Meeting goal, FDA will provide
preliminary written comments before each Product Development
Meeting (and aspire to provide the written comments 5 days
before the meeting) and will provide meeting minutes within
30 days following the meeting.
E. Pre-Submission Meetings
1. Prospective applicants may request a Pre-Submission
Meeting. The purpose of a Pre-Submission Meeting is to
provide an applicant the opportunity to present unique or
novel data or information that will be included in the ANDA
submission such as formulation, key studies, justifications,
and/or methods used in product development, as well as the
interrelationship of the data and information in the ANDA.
FDA will grant a Pre-Submission Meeting, if the applicant was
granted a Product Development Meeting for the same Complex
Generic Product or FDA believes in its sole discretion that
the Pre-Submission Meeting would improve assessment
efficiency.
2. For Pre-Submission Meetings, FDA will:
a. Identify the ANDA assessment team members who will
attend the meeting;
b. I entify additional content for the meeting in the
letter granting the meeting request, including information on
what topics should be addressed in the meeting in addition to
those identified in the meeting request by the applicant; and
c. Identify at the meeting, items or information for
clarification before the applicant's submission of the ANDA.
3. FDA will not provide a substantive assessment of summary
data or full study reports at the meeting.
4. An applicant's decision not to request a Pre-Submission
Meeting will not prejudice the receipt or assessment of an
ANDA.
5. FDA will grant or deny 90 percent of Pre-Submission
Meeting requests within 30 days.
6. If. granted, FDA will conduct 90 percent of Pre-
Submission Meetings within 60 days of the meeting request.
7. FDA will provide preliminary written comments 5 days
before each meeting, and meeting minutes within 30 days after
the meeting.
IV. ANDA Assessment Meeting Program
A. Goal of the ANDA Assessment Meeting Program
1. The goal of the ANDA Assessment Meeting Program is to
provide or continue to provide targeted, robust advice to
ANDA applicants as they work to meet the standards for ANDA
approval.
2. Some elements of this program are tailored to enhance
the development of Complex Generic Products.
B. Mid-Cycle Review Meetings and Enhanced Mid-Cycle Review
Meetings
1. If an applicant for a Complex Generic Product was
granted a Product Development Meeting for the same product,
they may, within 7 days of receiving the last mid-Cycle DRL,
submits a request for a Mid-Cycle Review Meeting or an
Enhanced Mid-Cycle Meeting. The request should describe the
specific deficiency(ies) to be discussed.
2. Mid-Cycle Review Meetings:
a. The purpose of a Mid-Cycle Review Meeting is for the
applicant to ask for the rationale for any deficiency
identified in the mid-cycle DRL(s), and/or to ask questions
related to FDA's assessment of the data or information in
the ANDA. An applicant may not present any new data or
information at this meeting.
b. The Mid-Cycle Review Meeting will take place within 30
days after the date the sponsor submits a meeting request.
3. Enhanced Mid-Cycle Review Meetings:
a. The purpose of this meeting is for the applicant to ask
questions related to a proposed scientific path to address
possible deficiencies identified in the mid-cycle DRL(s). An
applicant may ask questions about potential new data or
information to address any possible deficiencies identified
in the mid-cycle DRL(s). FDA will discuss the data and
information but will not provide substantive assessment of
data or information provided by the applicant at the meeting.
b. If an Enhanced Mid-Cycle Review Meeting is requested,
the meeting will take place within 90 days after issuance of
the last mid-cycle DRL.
c. FDA will extend the ANDA goal date by 60 days if an
applicant requests an Enhanced Mid-Cycle Review Meeting. FDA
also will extend the response due date for the relevant
DRL(s) by recalculating the response due date starting from
the date of the meeting, e.g., if the response was due 30
days after the DRL was issued, it will now be due 30 days
after the Enhanced Mid-Cycle Review Meeting.
d. An applicant may submit an Unsolicited Amendment after
an Enhanced Mid-Cycle Review Meeting, which could result in
an additional goal date extension consistent with section
I(C).
C. Post-CRL Scientific Meetings
1. An applicant can request a Post-CRL Scientific Meeting.
The purpose of this meeting is to provide an applicant
scientific advice on possible approaches to address
deficiencies identified in a CRL related to establishing
equivalence.
a. An applicant's meeting request must discuss:
iii. a new equivalence study needed to address the
deficiencies in the design identified in the CRL,
iv. an approach that is different from that submitted in
the ANDA, e.g., a change in study type from in vivo to in
vitro,
v. a new comparative use human factors study, or
vi. a new approach to demonstrating sameness of a complex
active ingredient; and
b. FDA will grant the meeting if it is for a Complex
Generic Product or in FDA's judgment the request raises
issues that are best addressed via this meeting process and
cannot be adequately addressed through Controlled
Correspondence.
c. An applicant may have a post-CRL teleconference
described in section II(B)(8)(a) prior to requesting this
meeting.
2. FDA will grant or deny the Post-CRL Scientific Meeting
request within 14 days after receipt of the request.
3. FDA will hold the Post-CRL Scientific Meeting within 90
days after the date the meeting is granted.
4. Applicants are eligible to request a Post-CRL Scientific
Meeting even if they have not had a Product Development
Meeting.
V. ADDITIONAL PROGRAM ENHANCEMENTS AND ASPIRATIONS
A. Inactive Ingredient Database Enhancement
FDA will update the Inactive Ingredient Database on an
ongoing basis, and post quarterly notices of updates made.
Such notices will include for each change made during the
previous quarter, the new information, and the information
that was replaced.
B. Regulatory Science Enhancements
1. FDA will conduct internal and external research to
support fulfilment of submission assessment and pre-ANDA
commitments set forth in Sections I and III, respectively.
2. Annually, FDA will conduct a public workshop to solicit
input from industry and stakeholders for inclusion in an
annual list of GDUFA III regulatory science initiatives.
Interested parties may propose regulatory science initiatives
via email to [email protected]. After considering
Industry and stakeholder input, FDA will post the list on
FDA's website.
3. If Industry forms a GDUFA III regulatory science working
group, then upon request of the working group to the Director
of the Office of Research and Standards in the Office of
Generic Drugs, FDA will meet with the working group twice
yearly to discuss current and emerging challenges and
concerns. FDA will post minutes of these meetings on its
website.
4. Annually, FDA will report on its website the extent to
which GDUFA regulatory science-funded projects support the
development of generic drug products, the generation of
evidence needed to support efficient assessment and timely
approval of ANDAs, and the establishment of new approaches to
evaluate generic drug equivalence.
C. Other Pre-ANDA and Assessment Meeting Program Aspirations
FDA aspires to continually improve the effectiveness of its
Pre-ANDA and ANDA Assessment Meeting activities.
VI. DMF ASSESSMENT PROGRAM ENHANCEMENTS
A. Communication of DMF Assessment Comments
1. FDA will ensure that DMF assessment comments submitted
to the DMF holder are issued at least in parallel with the
issuance of review comments relating to the DMF for the ANDA.
2. This commitment applies to comments to the applicant
issued in any ANDA CRL
[[Page S5209]]
and comments issued in the first IR letter by the drug
product assessment discipline.
B. Teleconferences to Clarify DMF First Cycle Assessment
Deficiencies
1. FDA will grant and conduct teleconferences when
requested to clarify deficiencies in first cycle DMF
deficiency letters.
2. DMF holders must request such teleconferences in writing
within 30 days of issuance of the first cycle DMF deficiency
letter, identifying specific issues to be addressed. FDA may
initially provide a written response to the request for
clarification, but if the DMF holder indicates that a
teleconference is still desired, FDA will schedule the
teleconference.
3. FDA will strive to grant such teleconferences within 30
days of receipt of the initial teleconference request, giving
priority to DMFs based on the priority of the referencing
ANDA.
4. In lieu of a teleconference, the DMF holder may submit a
request for an email exchange between FDA and the DMF holder.
The request must identify specific issues to be addressed.
After FDA responds to the request, the DMF holder may
submit, and FDA will respond to, one follow-up email to
obtain additional clarification.
C. DMF First Adequate Letters
Once a DMF has undergone a full scientific assessment and
has no open issues related to the assessment of the
referencing ANDA, FDA will issue a First Adequate Letter.
D. DMF No Further Comment Letters
Once a DMF has undergone a full scientific assessment and
the ANDA referencing the DMF has been approved or tentatively
approved, FDA will issue a ``no further comment'' letter.
E. DMF Review Prior to ANDA Submission
1. A holder of a DMF may submit a request for assessment of
the DMF six months prior to the planned submission date for:
1) an original ANDA, 2) an ANDA amendment containing a
response to a CRL, or 3) an amendment seeking approval of an
ANDA that previously received a tentative approval. In each
case, the submission must include reference to a DMF for
which FDA has not conducted a substantive assessment, and one
of the following criteria must be met:
a. All patents and exclusivities will expire within 12
months of the planned submission date;
b. The submission is for a drug product for which there are
not more than three approved drug products listed in FDA's
Approved Drug Products With Therapeutic Equivalence
Evaluations (the ``Orange Book''), for which there are no
blocking patents or exclusivities listed for the RLD, and the
ANDA applicant is not seeking approval for less than all of
the conditions of use on the RLD labeling, e.g., a ``carve-
out.'' In other words, there are fewer than four approved
therapeutically equivalent drug products, including the RLD,
listed in the Orange Book, no blocking patents or unexpired
exclusivities for the RLD in the Orange Book, and the
applicant is not seeking to ``carve out'' any conditions of
use;
c. The submission is for a drug product that could help
mitigate or resolve a drug shortage and prevent future
shortages, including submissions related to products that are
listed on FDA's Drug Shortage List at the time of the
submission;
d. The submission is for a drug product that either could
help address a public health emergency declared by the
Secretary of the U.S. Department of Health and Human Services
under section 319 of the PHS Act, or anticipated under the
same criteria as apply to such a declaration; or
e. The submission is for a drug product for which (1) there
is only one approved drug product listed in the Prescription
Drug Product List (i.e., the ``Active Section'') of the
Orange Book and that product is approved under an ANDA (i.e.,
the RLD is in the ``Discontinued Section'' and there is not
more than one ANDA in the ``Active Section''); (2) the
approved ANDA for the drug product listed in the ``Active
Section'' was not approved pursuant to a suitability petition
under section 505(j)(2)(C) of the FD&C Act; (3) there are no
blocking patents or exclusivities for the RLD; and (4) the
submission does not qualify for prioritization under any
other factor listed in MAPP 5240.3 Rev. 5: Prioritization of
the Review of Original ANDAs, Amendments, and Supplements.
2. A holder of a DMF may submit a request for assessment of
the DMF six months prior to the planned submission date for a
PAS to add a new API source, provided that:
a. The PAS is for a drug product that could help mitigate
or resolve a drug shortage and prevent future shortages,
including submissions related to products that are listed on
FDA's Drug Shortage List at the time of the submission; or
b. The PAS is for a drug product that either could help
address a public health emergency declared by the Secretary
of the U.S. Department of Health and Human Services under
section 319 of the PHS Act, or anticipated under the same
criteria as apply to such a declaration.
3. To be eligible for this review, a DMF holder must submit
with its request for review:
a. at least one Letter of Authorization with one pre-
assigned ANDA number;
b. a reference to the corresponding RLD listed in the
Orange Book; and
c. documentation that the DMF holder has paid a GDUFA DMF
fee as described in section 744B(a)(2)(A) of the FD&C Act (21
U.S.C. 379j-41(a)(2)(A)) for the current fiscal year.
F. FDA Assessment of Solicited DMF Amendments
1. FDA will assess solicited DMF amendments related to
original ANDAs and PASs upon receipt even if the original
ANDA or PAS in which the DMF is referenced is not currently
under assessment.
2. Such assessments will be conducted based on the
assessment status of the DMF and other disciplines in the
related ANDAs, with priority being given to those amendments
related to ANDAs for which acceptability of the DMF
assessment may result in an approval.
G. FDA Communication Related to DMF Amendments and ANDAs
FDA will communicate publicly to industry that prior to
submitting a DMF amendment, the DMF holder should coordinate
with the ANDA applicant that references the DMF to avoid
delaying approval or tentative approval of the ANDA.
VII. FACILITIES
A. Foreign Regulators
1. Export Support and Education of Other Health
Authorities: FDA will support the export of safe and
effective pharmaceutical products by the U.S.-based
pharmaceutical industry, including but not limited to
providing timely updates to FDA's Inspection Classification
Database as described below, and educating other health
authorities regarding FDA's surveillance inspection program
and the meaning of inspection classifications.
2. Communications to Foreign Regulators: Upon receipt of a
written or email request by an establishment physically
located in the U.S. that has been included as part of a
marketing application submitted to a foreign regulator, issue
within 30 days of the date of receipt of the request a
written communication to that foreign regulator conveying the
current compliance status for the establishment.
B. Communication Regarding Inspections
1. When FDA conducts a preapproval inspection of a facility
or site named in the ANDA, PAS, or associated Type II DMF and
identifies outstanding issues that could prevent approval of
an ANDA or PAS, the applicant will be notified that issues
exist through an IR, DRL or CRL pursuant to Section II(B)
above.
2. FDA agrees to communicate to the facility owner final
inspection classifications that do not negatively impact
approvability of any pending application within 90 days of
the end of the inspection.
3. FDA agrees to ongoing periodic engagement with industry
stakeholders to provide updates on Agency activities and seek
stakeholder feedback.
C. GDUFA III Inspection Classification Database
The Inspection Classification Database will be updated
every 30 days and will reflect FDA's final assessment of the
facility or site following an FDA inspection and assessment
of the inspected entity's timely response to any documented
observations. FDA will update the existing publicly available
Inspection Classification Database webpage and will develop
communication materials to provide further information to
industry and foreign regulators on how FDA determines which
facilities to select for a drug surveillance inspection,
including how FDA uses its risk-based site selection model to
determine the frequency of surveillance inspections.
D. Post-Warning Letter Meetings
1. An eligible facility described in section VII(D)(3) may
request a meeting with FDA regarding the facility's
remediation for deviations identified in a warning letter
(Post-Warning Letter Meeting).
a. This meeting generally will take place 6 months or later
after the facility submits an initial response to an FDA
warning letter.
b. A facility may request that the meeting take place prior
to 6 months after an initial response to a warning letter has
been submitted. However, it is at FDA's discretion to grant
an earlier meeting if the Agency determines it would be
beneficial to both parties.
2. The purpose of the Post-Warning Letter Meeting is to
obtain preliminary feedback from FDA on the adequacy and
completeness of the facility's corrective action plans.
3. To be eligible for the Post-Warning Letter Meeting:
a. The facility Current Good Manufacturing Practice (CGMP)
compliance status is ``Official Action Indicated'' as a
result of an FDA inspection;
b. The facility has paid a GDUFA facility fee as described
in section 744B(a)(4) of the FD&C Act for the current fiscal
year, or is named in a pending ANDA application; and
c. The regulatory action (e.g., warning letter) is limited
only to violations or deviations from Section 501 of the FD&C
Act (21 U.S.C. 351) related to human drug manufacturing,
including manufacturing of a drug-device combination product.
4. The meeting request will be granted only if the facility
has submitted to FDA a thorough and complete corrective
action and preventive action (CAPA) plan that addresses all
items cited in the warning letter, and reasonable progress
has been made toward remediation.
5. Any supplemental information submitted by a facility on
remediation progress to be discussed at the meeting must be
submitted at least 60 days prior to the meeting.
[[Page S5210]]
6. FDA may deny a request for a Post-Warning Letter Meeting
if FDA determines that a facility is ineligible for a meeting
or does not appear to be ready for a meeting as evidenced by
an incomplete CAPA plan, and/or insufficient progress being
made to remediate the facility issues. If FDA denies the
meeting:
a. In general, FDA intends to respond briefly with comments
regarding why the meeting package is not sufficiently
developed or complete (e.g., where the facility has not
presented a proposed CAPA plan for all items in the warning
letter or where the firm does not appear to have made
reasonable efforts to implement its proposed CAPA plan).
b. A facility may resubmit a new meeting request no sooner
than 3 months after the first meeting request is denied by
FDA.
7. Only two Post-Warning Letter Meeting requests per
warning letter may be made under this section.
8. FDA may defer a Post-Warning Letter Meeting if FDA has
made a decision that a reinspection is the most appropriate
next step (i.e., defer in favor of re-inspection). In this
case, FDA will notify the facility of the decision to re-
inspect rather than grant a meeting.
9. FDA may schedule meetings by video conference,
teleconference, or face-to-face, at FDA's discretion.
10. The following goals apply to FDA's decision to grant,
deny, or defer in favor of reinspection a Post-Warning Letter
Meeting:
a. In FY 2024, 50 percent of eligible requests within 30
days of request.
b. In FY 2025, 70 percent of eligible requests within 30
days of request.
c. In FY 2026 and FY 2027, 80 percent of eligible requests
within 30 days of request.
11. The commitment to hold a Post-Warning Letter Meeting:
a. Does not preclude FDA from taking any regulatory actions
necessary, including a follow-up inspection at any time
(including prior to the Post-Warning Letter Meeting); and
b. As with other regulatory meetings, FDA advice is not
binding on the Agency.
12. Guidance related to Post-Warning Letter Meeting process
set forth in this section VII(D):
a. FDA will issue guidance regarding the Post-Warning
Letter Meeting process, including recommendations on items
facilities should submit as part of a meeting request.
b. If more than 50 percent of first-time meeting requests
are denied because FDA makes an assessment that the facility
is not ready, FDA agrees to take appropriate action to
provide additional information on meeting requests, which
could include updating the guidance described in
VII(D)(12)(a) to provide further information on how
facilities can avoid issues that have commonly led to meeting
requests being denied.
E. Generic Drug Manufacturing Facility Re-inspection
1. An eligible facility as described in section VII(E)(2)
may request a re-inspection.
2. To be eligible for the facility re-inspection process
reflected in this section:
a. The facility CGMP compliance status is ``Official Action
Indicated'' as a result of an FDA inspection;
b. The facility has paid a GDUFA facility fee as described
in section 744B(a)(4) of the FD&C Act for the current fiscal
year, or is named in a pending ANDA application; and
c. The regulatory action (e.g., warning letter) is limited
only to violations or deviations from Section 501 of the FD&C
Act related to human drug manufacturing, including
manufacturing of a drug-device combination product.
3. FDA will review the request and if FDA determines that
the requesting facility has appropriately completed CAPAs
that sufficiently address all of the deficiencies in a
warning letter, with the exception of ongoing monitoring, and
FDA agrees that the facility appears ready for inspection,
FDA will generate an inspectional assignment.
4. FDA agrees to notify the facility of the Agency's
decision to re-inspect within 30 days of receipt of the
request for re-inspection.
5. If FDA declines the request to reinspect:
a. FDA agrees to notify the facility of its decision and
provide a brief high-level explanation, for example, that the
firm has not made sufficient progress to complete certain
CAPAs identified as necessary to resolve a violation cited in
the warning letter.
b. The facility may submit a second request for a re-
inspection no earlier than 3 months after receiving FDA's
initial decision.
c. If the second request is denied, facility will be
considered to no longer meet the eligibility criteria in
section VII(E)(2).
6. The processes and timelines set forth in this section
apply only to the first reinspection after a warning letter.
If the warning letter is not resolved after reinspection, the
facility will be considered to no longer meet the eligibility
criteria in section VII(E)(2).
7. If a re-inspection request is granted, FDA agrees to
notify the facility and issue an inspectional assignment in
conjunction with the notification. The applicable goals for
domestic facilities are:
a. In FY 2024, for 60 percent of the requests for
reinspection that are granted, FDA will re-inspect the
facility within 4 months of the letter to the facility
indicating FDA's intent to reinspect.
b. In FY 2025, for 70 percent of the requests for
reinspection that are granted, FDA will re-inspect the
facility within 4 months of the letter to the facility
indicating FDA's intent to reinspect.
c. In FY 2026 and FY 2027, for 80 percent of the requests
for reinspection that are granted, FDA will re-inspect the
facility within 4 months of the letter to the facility
indicating FDA's intent to reinspect.
8. The applicable goals for international facilities are:
a. In FY 2024, for 60 percent of the requests for
reinspection that are granted, FDA will re-inspect the
facility within 8 months of the letter to the facility
indicating FDA's intent to re-inspect.
b. In FY 2025, for 70 percent of requests for reinspection
that are granted, FDA will re-inspect the facility within 8
months of the letter to the facility indicating FDA's intent
to re-inspect.
c. In FY 2026 and FY 2027, for 80 percent of requests for
reinspection that are granted, FDA will re-inspect the
facility within 8 months of the letter to the facility
indicating FDA's intent to re-inspect.
VIII. CONTINUED ENHANCEMENT OF USER FEE RESOURCE MANAGEMENT
A. Sustainability of GDUFA Program Resources
1. FDA is committed to ensuring the sustainability of the
GDUFA program resources and to enhancing the operational
agility of the GDUFA program.
2. FDA will build on the financial enhancements included in
GDUFA II and continue activities in GDUFA 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 capability.
3. FDA also will continue activities to promote
transparency of the use of financial resources in support of
the GDUFA program.
B. Resource Capacity Planning
1. FDA will continue activities to mature the Agency's
resource capacity planning function, including utilization of
modernized time reporting to support enhanced management of
GDUFA resources in GDUFA III and implementation of the
Capacity Planning Adjustment (CPA).
2. Resource Capacity Planning Implementation
a. By the end of the second quarter of FY 2023, FDA will
publish an implementation plan that will describe how
resource capacity planning and time reporting will continue
to be utilized during GDUFA 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:
i. The continued maturation of the Agency's resource
capacity planning capability;
ii. The continual improvement of time reporting and its
utilization in the CPA;
iii. The integration of resource capacity planning analyses
in the Agency's resource and operational decision-making
processes; and
iv. The implementation of the CPA, with a first year of
adjustment for FY 2024 user fees.
b. FDA will provide annual updates on the FDA website on
the Agency's progress relative to activities detailed in this
implementation plan by the end of the second quarter of each
subsequent fiscal year.
c. FDA will document in the annual GDUFA Financial Report
how any CPA fee revenues are being utilized.
d. Resources obtained from the CPA shall be used,
consistent with user fee appropriations, to support CDER or
ORA staff engaged in GDUFA program work, or other non-CDER
staff who are directly supporting GDUFA review work.
e. The CPA shall be limited to workload driven by:
i. ANDA Originals and Resubmissions/Amendments
ii. ANDA Supplements (PAS and ``Changes Being Effected''
(CBE) supplements) and Amendments
iii. Controlled Correspondence as defined in Section XI(I)-
(J)
iv. Pre-ANDA Meetings, which include Pre-Submission,
Product Development, and Pre-Submission PSG Meetings
v. Surveillance inspections
vi. Post-marketing safety activities
vii. Suitability Petitions
C. Resource Capacity Planning Assessment
1. By 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:
a. The ability of the CPA to forecast resource needs for
the GDUFA program, including an assessment of the scope of
the workload drivers in the CPA and their ability to
represent the overall workload of the GDUFA program;
b. Opportunities for the enhancement of time reporting
toward informing resource needs; and
c. The integration and utilization of resource capacity
planning information within resource and operational
decision-making processes of the GDUFA program.
2. 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
GDUFA 5-year financial plan public meeting. The findings and
recommendations of the evaluation may inform the CPA
methodology for future reauthorizations.
D. Financial Transparency and Efficiency
1. FDA is committed to ensuring GDUFA user fee resources
are administered, allocated, and reported in an efficient and
transparent manner. FDA will conduct activities
[[Page S5211]]
to evaluate the financial administration of the GDUFA program
to help identify areas to enhance operational and fiscal
efficiency. FDA will also conduct activities to enhance
transparency of how GDUFA program resources are used.
2. FDA will publish a GDUFA 5-year financial plan no later
than the second quarter of FY 2023. FDA will publish updates
to the 5-year plan no later than the second quarter of each
subsequent fiscal year.
3. FDA will convene a public meeting no later than the
third quarter of each fiscal year starting in FY 2024 to
discuss the GDUFA 5-year financial plan, along with the
Agency's progress in implementing modernized time reporting
and resource management planning.
E. Improving the Hiring of Review Staff
1. Enhancements to the generic drug review program require
that FDA hire the necessary technical and scientific experts
to efficiently conduct assessments of generic drug
applications and supporting activities.
2. During GDUFA III, FDA will:
a. Hire 128 staff for the generic drug review program in FY
2023; and
b. Confirm progress in the hiring of GDUFA III staff in the
GDUFA 5-year financial plan.
IX. GUIDANCE AND MAPPS
A. FDA will draft or modify relevant Manuals of Policies
and Procedures (MAPPs) to reflect the commitments and goals
in this Commitment Letter, including, but not limited to, the
following:
1. To direct project managers, assessors, and other
assessment program staff to actively work towards an action
for an ANDA with a missed or extended goal date.
2. To revise MAPP 5200.12 Communicating Abbreviated New
Drug Application Review Status Updates with Industry, to
include communications related to imminent actions on or
before April 30, 2023.
B. FDA will issue a Federal Register Notice on or before
April 30, 2023, to solicit public comment on the content of
Appendix A in the guidance for industry on ANDA Submissions--
Amendments to Abbreviated New Drug Applications Under GDUFA
(July 2018) and will use evaluations and/or training to
assure consistency in ANDA amendment classification.
C. FDA will issue a MAPP on the process for
Reclassification of Facility-Based Major CRL Amendments set
forth in section II(C)(7) on or before June 30, 2024.
D. FDA will issue a MAPP on the prioritization of FDA
assessment of solicited DMF amendments described in section
VI(F)(2) on or before June 30, 2024.
E. FDA will issue guidance clarifying the regulatory status
of active pharmaceutical ingredient-excipient mixtures for
GDUFA purposes.
X. PERFORMANCE REPORTING
A. Monthly Reporting Metrics: FDA will publish the
following monthly metrics on its website, using a consistent,
publicly disclosed reporting methodology:
Number of ANDAs and amendments, CBE supplements, and PASs
submitted in the reporting month delineated by type of
submission:
2. Number of ANDAs and PASs FDA refused for receipt in the
reporting month:
3. Number of actions taken in the reporting month
delineated by the type of action. For purposes of the
metrics, actions shall include final approvals, tentative
approvals, CRLs, IRs, and DRLs (or other such nomenclature as
FDA determines to reflect the concepts of an information
request or CRL):
4. Number of finalized DMF Completeness Assessments in the
reporting month;
5. Number of DMF fees paid in the reporting month; and
6. Number of first-cycle approvals and tentative approvals
in the reporting month.
B. Quarterly Reporting Metrics: FDA will publish the
following quarterly metrics on its website, using a
consistent, publicly disclosed reporting methodology:
1. Number of ANDAs and PASs withdrawn in each reporting
month;
2. Number of ANDAs awaiting applicant action;
3. Number of ANDAs awaiting FDA action;
4. Mean and median approval and tentative approval times
for the quarterly action cohort,
5. Number of original ANDAs for Complex Generic Products
submitted;
6. Number of requests for reclassification of a Facility-
Based Major CRL Amendment received, and number of requests
granted and denied; and
7. Number of Level 1 and Level 2 Controlled Correspondence
submitted.
C. Fiscal Year Performance Report Metrics: FDA will publish
the following metrics annually as part of the GDUFA
Performance Report:
1. Mean and median approval and tentative approval times
for ANDAs by FY receipt cohort;
2. Mean and median ANDA approval times, including separate
reporting of mean and median times for first-cycle approvals
FY receipt cohort;
3. Mean and median number of ANDA assessment cycles to
approval and tentative approval by FY receipt cohort;
4. Number of applications received and refused to receive,
and average time to receipt decision;
5. Number of GDUFA-related meetings and teleconferences
requested, granted, denied, and conducted, broken down by
type of meeting or teleconference, and in addition for Post-
Warning Letter Meetings, the number deferred in favor of re-
inspection;
6. Number of inspections conducted by domestic or foreign
establishment location and inspection type (preapproval
inspection, surveillance, bioequivalence clinical and
bioequivalence analytical) and facility type (finished dosage
form, API);
7. Median time from beginning of inspection to Form FDA 483
issuance;
8. Median time from Form FDA 483 issuance to Warning
Letter, Import Alert and Regulatory Meeting for inspections
with final classification of ``Official Action Indicated''
(or equivalent),
9. Median time from date of Warning Letter, Import Alert or
Regulatory Meeting to resolution of the ``Official Action
Indicated'' status (or equivalent);
10. Number of ANDAs accepted for standard assessment and
priority assessment;
11. Percentage of suitability petitions completed within 6
months after FDA completes the completeness assessment, the
total number submitted, and total number completed;
12. Number of citizen petitions to determine whether a
listed drug has been voluntarily withdrawn from sale for
reasons of safety or effectiveness pending a substantive
response for more than 270 days from the date of receipt;
13. Percentage of ANDA proprietary name requests evaluated
within 180 days of receipt;
14. Number of DMF First Adequate Letters issued;
15. Number of teleconferences granted, and number of email
exchanges requested and conducted in lieu of teleconferences
to clarify deficiencies in first cycle DMF deficiency
letters;
16. Percent of PSGs for non-Complex Product NCE NDAs within
two years of NDA approval;
17. Percent of PSGs for Complex Product NDAs, including
NCEs, published within two and three years of NDA approval;
18. Percentage of facility re-inspections carried out
within 4 or 8 months after the letter to the facility
indicating FDA's intent to reinspect for domestic or foreign
facilities, respectively;
19. For the total number of original ANDAs, amendments,
PASs, PAS amendments, and meeting requests submitted in a
fiscal year, FDA will publish the number of actions completed
(as of the annual publication date), and the percent
completed by the goal date. FDA also will publish this data
annually on its website, further enumerated by goal-date
subcategory, and will include metrics regarding timeframes
for acting on meeting requests;
a. For example, in the GDUFA Performance Report, the
priority PAS submission goal will be reported as the number
of actions and the percent completed combined for the 4-, 8-
and 10-month goals
b. For the Annual Web Posting, the priority PAS submission
goals will be reported as the number of actions and the
percent completed individually for the 4-, 8- and 10-month
goals; and
20. Percent Controlled Correspondence Level 1 and Level 2
responded to within the applicable goal date (i.e., 60 and
120 days, respectively);
21. Number of missed goal dates for original ANDAs by more
than 6, 9, and 12 months.
D. Fiscal Year Web Posting
In addition to the data that will be reported annually on
the web described in section XI(C)(19), FDA will also post
the following data annually on its website:
1. The number of requests for review of a DMF prior to ANDA
or PAS submission, as describe in sections VI(E)(1) and
VI(E)(2), the number granted, and the number completed;
2. Number of priority and non-priority ``off-cycle''
solicited DMF amendments reviewed as described in section
VI(F); and
3. Number of original approvals taken that are Imminent
Actions.
XI. DEFINITIONS
A. Act on--with respect to an application, means FDA will
either issue a CRL, an approval, a tentative approval, or a
refuse-to-receive action.
B. Ambiguity in the Controlled Correspondence response--
means the Controlled Correspondence response or a critical
portion of it merits further clarification.
C. Review Status Update--means a response from the RPM to
the applicant to update the applicant concerning, at a
minimum, the categorical status of relevant assessment
disciplines with respect to the submission at that time. The
RPM will advise the applicant that the update is preliminary
only, based on the RPM's interpretation of the submission,
and subject to change at any time.
D. Capacity Planning Adjustment--Methodology that annually
adjusts inflation-adjusted target revenue to account for
additional resource needs due to sustained increases in
workload for the GDUFA program.
E. Complete Response Letter--refers to a written
communication to an applicant or DMF holder from FDA usually
describing all of the deficiencies that the Agency has
identified in an ANDA (including pending amendments) or a DMF
that must be satisfactorily addressed before the ANDA can be
approved. Complete response letters will reflect a Complete
Assessment, which includes an application-related facilities
assessment and will require a complete response from industry
to restart the clock. Refer to 21 CFR 314.110 for additional
details. When a citizen petition may impact the approvability
of the ANDA,
[[Page S5212]]
FDA will strive to address, where possible, valid issues
raised in a relevant citizen petition in the complete
response letter. If a citizen petition raises an issue that
would delay only part of a complete response, a response that
addresses all other issues will be considered a complete
response.
F. Complete Assessment--refers to a full division-level
assessment from all relevant assessment disciplines,
including inspections, and includes other matters relating to
the ANDAs and associated DMFs as well as consults with other
Agency components.
G. Complex Product--generally includes:
1. Products with complex active ingredients (e.g.,
peptides, polymeric compounds, complex mixtures of APIs,
naturally sourced ingredients); complex formulations (e.g.,
liposomes, colloids); complex routes of delivery (e.g.,
locally acting drugs such as dermatological products, complex
ophthalmological products, and otic dosage forms that are
formulated as suspensions, emulsions or gels) or complex
dosage forms (e.g., transdermal systems, metered dose
inhalers, extended release injectables)
2. Complex drug-device combination products (e.g., pre-
filled auto-injector products, metered dose inhalers); and
3. Other products where complexity or uncertainty
concerning the approval pathway or possible alternative
approach would benefit from early scientific engagement.
H. Complex Generic Product--refers to a generic version of
a Complex Product.
I. Controlled Correspondence--Level 1--means correspondence
submitted to the Agency, by or on behalf of a generic drug
manufacturer or related industry:
1. Requesting information on a specific element of generic
drug product development:
a. Prior to ANDA submission;
b. After a PSG Teleconference if a prospective applicant or
applicant seeks further feedback from FDA;
c. After issuance of a CRL or tentative approval;
d. After ANDA approval; or
2. Concerning post-approval submission requirements that
are not covered by CDER post-approval changes guidance and
are not specific to an ANDA.
J. Controlled Correspondence--Level 2--means correspondence
that meets the definition of Level 1 correspondence, and:
1. Involves evaluation of clinical content;
2. Requests a Covered Product Authorization and review of
bioequivalence protocols for development and testing that
involves human clinical trials for an ANDA where the RLD is
subject to a Risk Evaluation and Mitigation Strategy (REMS)
with Elements to Assure Safe Use (ETASU);
3. Requests a Covered Product Authorization to obtain
sufficient quantities of an individual covered product
subject to a REMS with ETASU when development and testing
does not involve clinical trials;
4. Requests evaluations of alternative bioequivalence
approaches (e.g., pharmacokinetic, in vitro, clinical); or
5. Requires input from another office or center, e.g.,
questions regarding device constituent parts of a combination
product.
K. Covered Product Authorization--a letter from FDA
authorizing an eligible product developer to obtain
sufficient quantities of an individual covered product
subject to a REMS with ETASU for product development and
testing purposes, as described in section 610 of Division N
of the Further Consolidated Appropriations Act, 2020 (21
U.S.C. 355-2), commonly referred to as the ``CREATES Act.''
L. Days--unless otherwise specified, means calendar days.
M. Discipline Review Letter--means a letter used to convey
preliminary thoughts on possible deficiencies found by a
discipline assessor and/or assessment team for its portion of
the pending application at the conclusion of the discipline
assessment.
N. Earliest lawful ANDA approval date--the first date on
which no patent or exclusivity prevents approval of an ANDA.
O. First Adequate Letter--a communication from FDA to DMF
holder indicating that the DMF has no open issues related to
the assessment of the referencing ANDA. This communication is
issued only at the conclusion of the first DMF assessment
cycle that determines the DMF does not have any open issues.
P. First Generic--any received ANDA: (1) for a First
Applicant as described in section 505(j)(5)(B)(iv)(II)(bb) of
the FD&C Act or for which there are no blocking patents or
exclusivities; and (2) for which there is no previously
approved ANDA for the drug product.
Q. Information Request--means a communication that is sent
to an applicant during an assessment to request further
information or clarification that is needed or would be
helpful to allow completion of the discipline assessment.
R. Major Amendment--means a Major Amendment as described in
the guidance for industry on ANDA Submissions Amendments to
Abbreviated New Drug Applications Under GDUFA (July 2018),
and any subsequent revision.
S. Mid-point of assessment cycle The mid-point of an
assessment cycle is half the length of an assessment period
plus or minus 30 days.
T. Minor Amendment--means a minor amendment as described in
the guidance for industry on ANDA Submissions Amendments to
Abbreviated New Drug Applications Under GDUFA (July 2018),
and any subsequent revision.
U. Priority--means submissions affirmatively identified as
eligible for expedited assessment pursuant to MAPP 5240.3,
Prioritization of the Review of Original ANDAs, Amendments
and Supplements, as revised (the CDER Prioritization MAPP).
V. Significant Major deficiency--means a major deficiency,
the resolution of which is required before the continued
assessment by multiple disciplines, e.g., a reformulation, or
a major deficiency that impacts the test drug product used in
a bioequivalence study.
W. Small Issue--for the purposes of Imminent Actions in
section II(B)(3), means a deficiency that can be assessed by
FDA within 60 days because it can be addressed by: 1)a
clarification of scientific information regarding data
already submitted, 2) the limited submission of additional
data, or 3) the submission of administrative information
(e.g., completion of a form or a change in an address).
X. Standard--means submissions not affirmatively identified
as eligible for expedited assessment pursuant to the CDER
Prioritization MAPP.
Y. Teleconference--means a verbal communication by
telephone, and not a written response, unless otherwise
agreed to by the applicant.
Z. Unsolicited Amendment--an amendment with information not
requested by FDA except for those unsolicited amendments
considered routine or administrative in nature that do not
require scientific review (e.g., requests for final ANDA
approval, patent amendments, and general correspondence).
Appendix: Prioritization of Suitability Petitions
Prior to GDUFA III, FDA received approximately 20-30
suitability petitions per year and had approximately 170
suitability petitions currently pending as of July 2021.
Pursuant to this Commitment Letter, in GDUFA III FDA has
agreed to set goal dates for review and response to
suitability petitions. To receive a goal date, pending
petitions submitted prior to FY 2024 must be withdrawn and
resubmitted.
If FDA does not respond to all petitions submitted in a
given fiscal year, FDA has committed to prioritizing
suitability petitions that are carried over to the following
fiscal year over new petitions received in that fiscal year
(subject to the prioritization outlined in section
III(B)(6)). The following hypothetical example describes how
FDA will prioritize suitability petitions if FDA is unable to
respond to all suitability petitions in a given fiscal year.
This example assumes a significantly higher number of
incoming petitions and a high number of carryover petitions
to illustrate how petitions that are carried over will be
prioritized.
Example
For FY 2024, FDA's goal is to respond to 50 percent of all
suitability petitions received within six months of the
completeness assessment, up to a maximum of 50 suitability
petitions. In FY 2024, FDA receives and performs the
completeness assessment for 100 suitability petitions. To
meet the goal, FDA must respond to 50 of those petitions
within six months after the completeness assessment. At the
end of FY 2024, FDA has responded to 50 petitions within 6
months, and 10 in greater than six months. FDA therefore met
the FY 2024 goal of 50 percent within six months (i.e., 50
petitions), and the additional 40 petitions still pending
roll into FY 2025.
For FY 2025, FDA's goal is to respond to 70 percent of all
suitability petitions received within six months of the
completeness assessment, up to a maximum of 70 suitability
petitions. In FY 2025, FDA receives 40 suitability petitions.
To meet the FY 2025 goal, FDA must respond to 28 of those
petitions within six months of the completeness assessment.
FDA will prioritize any suitability petitions received in FY
2025 prioritized as outlined in section III(B)(6) and the 40
pending petitions from FY 2024 over any other suitability
petitions received in FY25, in that order. By the end of FY
2025, FDA has responded to all 40 petitions from the FY 2024
cohort and 28 of the 40 from FY 2025 within 6 months of the
completeness assessment. Twelve petitions from the FY 2025
cohort remain pending. FDA has met the FY 2025 goal, and the
remaining 12 petitions still pending will be carried over
into FY 2026 and prioritized.
Biosimilar Biological Product Reauthorization Performance Goals and
Procedures Fiscal Years 2023 Through 2027
I. ENSURING THE EFFECTIVENESS OF THE BIOSIMILAR BIOLOGICAL
PRODUCT REVIEW PROGRAM
A. Review Performance Goals
B. Program for Enhanced Review Transparency and
Communication for Original 351(k) BLAs
C. Guidance
D. Review of Proprietary Names to Reduce Medication Errors
E. Major Dispute Resolution
F. Clinical Holds
G. Special Protocol Question Assessment and Agreement
H. Meeting Management Goals
II. ENHANCING BIOSIMILAR AND INTERCHANGEABLE BIOLOGICAL
PRODUCT DEVELOPMENT AND REGULATORY SCIENCE
A. Promoting Best Practices in Communication between FDA
and Sponsors During Application Review
B. Inspections and Alternate Tools to Evaluate Facilities
[[Page S5213]]
C. Advancing Development of Biosimilar Biological-Device
Combination Products Regulated by CDER and CBER
D. Advancing Development of Interchangeable Biosimilar
Biological Products
E. Regulatory Science to Enhance the Development of
Biosimilar and Interchangeable Biological Products
III. CONTINUED ENHANCEMENT OF USER FEE RESOURCE MANAGEMENT
A. Resource Capacity Planning
B. Financial Transparency
C. Management of Carryover Balance
IV. IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF
A. Set Clear Goals for Biosimilar Biological Product Review
Program Hiring
B. Comprehensive and Continuous Assessment of Hiring and
Retention
V. INFORMATION TECHNOLOGY GOALS
A. Develop Data and Technology Modernization Strategy
B. Monitor and Modernize Electronic Submission Gateway
(ESG)
VI. DEFINITIONS AND EXPLANATION OF TERMS
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.
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:
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
TABLE 1--ORIGINAL AND RESUBMITTED APPLICATIONS AND CATEGORY A-F
SUPPLEMENTS
------------------------------------------------------------------------
------------------------------------------------------------------------
Original Biosimilar Biological Product 90% in 10 months of the 60 day
Application Submissions. filing date
Resubmitted Original Biosimilar 90% in 6 months of the receipt
Biological Product Applications. date
FY 2023: 70% in 3
months of the receipt date
FY 2024: 80% in 3
months of the receipt date
Category A Supplements.................
FY 2025: 90% in 3
months of the receipt date
(original and resubmitted).......
FY 2026: 90% in 3
months of the receipt date
FY 2027: 90% in 3
months of the receipt date
FY 2023: 70% in 4
months of the receipt date
FY 2024: 80% in 4
months of the receipt date
Category B and C Supplements...........
FY 2025: 90% in 4
months of the receipt date
(original and resubmitted).........
FY 2026: 90% in 4
months of the receipt date
FY 2027: 90% in 4
months of the receipt date
FY 2023: 70% in 6
months of the receipt date
FY 2024: 80% in 6
months of the receipt date
Category D Supplements.................
FY 2025: 90% in 6
months of the receipt date
(original and resubmitted).........
FY 2026: 90% in 6
months of the receipt date
FY 2027: 90% in 6
months of the receipt date
Original Category E and F Supplements.. 90% in 10 months of the receipt
date
Resubmitted Category E and F 90% in 6 months of the receipt
Supplements. date
------------------------------------------------------------------------
[[Page S5214]]
TABLE 2--MANUFACTURING SUPPLEMENTS
------------------------------------------------------------------------
Prior approval All other
------------------------------------------------------------------------
Manufacturing Supplements....... 90% in 4 months of 90% in 6 months of
the receipt date. 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
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. 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 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.
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 (pre-351(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.
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
[[Page S5215]]
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 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.
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;
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. In the proprietary name is found to be unacceptable, the
sponsor can request reconsideration by submitting a written
rebuttal with supporting data or request a meeting within 60
days to discuss the initial decision (meeting package
required).
c. If the proprietary name is found to be unacceptable, the
above review performance goals also would apply to the
written request for reconsideration with supporting data or
the submission of a new proprietary name.
d. A complete submission is required to begin the review
clock.
2. Proprietary Name Review Performance Goals During
Application Review
a. Review 90% of 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
[[Page S5216]]
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.
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 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 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:
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.
Imunogenicity 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.
[[Page S5217]]
TABLE 1
------------------------------------------------------------------------
Response Time
Meeting Type (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 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 face-to-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.
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 Scheduling or
Meeting Type 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
-------------------------------------------
-------------------------------------------
------------------------------------------------------------------------
b. Performance goal:
TABLE 3
------------------------------------------------------------------------
Meeting Type Goal
------------------------------------------------------------------------
BPD Type 2a............................... 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
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 90% of meetings are held or
2b. 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.
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;
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 canceled. 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 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
[[Page S5218]]
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.
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 BIOLOGICAL-DEVICE
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 safe and effective use of a biosimilar biologic-
device combination product. FDA will establish the following
procedures for review of URRAs for combination products:
a. 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.
b. 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.
c. 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
non-agreement 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
non-agreement 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
non-agreement 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
non-agreement with comments for 90% of filed submissions,
within 60 days of receipt of submission.
d. 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.
e. 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:
a. 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).
b. 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:
c. 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.
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
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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.
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 science-based 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. 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 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 decision-making 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 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:
i. 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.
ii. 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:
a. 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;
b. Opportunities for the enhancement of time reporting
toward informing resource needs; and
c. 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.
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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.
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
----------------------------------------------------------------------------------------------------------------
FY 2023 FY 2024 FY 2025 FY 2026 FY 2027
----------------------------------------------------------------------------------------------------------------
CDER.......................................................... 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.
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:
a. outlining key areas of focus and approach including
leveraging cloud technologies to support Applicant-FDA
regulatory interaction;
b. articulating enterprise-wide approaches for both
technology and data governance; and
c. 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.
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.
____________________