[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

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       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

[[Page S5189]]

     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,

[[Page S5190]]

     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

[[Page S5191]]

     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

[[Page S5198]]

     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

[[Page S5201]]

     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

[[Page S5219]]

     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.

[[Page S5220]]

  

       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.

                          ____________________