[Congressional Record (Bound Edition), Volume 163 (2017), Part 9]
[Senate]
[Pages 12508-12541]
[From the U.S. Government Publishing Office, www.gpo.gov]




         FOOD AND DRUG ADMINISTRATION USER FEE REAUTHORIZATION

  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record a copy of the commitment letters from the Secretary of 
Health and Human Services to the chairman of the Committee on Health, 
Education, Labor, and Pensions of the Senate and the chairman of the 
Committee on Energy and Commerce of the House of Representatives 
regarding reauthorization of the Biosimilar User Fee Act, Generic Drug 
User Fee Act, Prescription Drug User Fee Act, and Medical Device User 
Fee Amendments.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

                                            Department of Health &


                                               Human Services,

                                  Washington, DC, January 4, 2017.
     Hon. Lamar Alexander,
     Chairman, Committee on Health, Education, Labor and Pensions, 
         U.S. Senate, Washington, DC.
       Dear Mr. Chairman: The Generic Drug User Fee Amendments of 
     2012 (GDUFA) enacted as title III of the Food and Drug 
     Administration Safety and Innovation Act [Pub. L. 112-144], 
     expires at the end of Fiscal Year 2017. With this letter the 
     Administration is providing our recommendations for the 
     reauthorization of GDUFA for the Fiscal Years 2018-2022 
     (GDUFA II).
       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 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 II will average approximately $493.6 million per year, 
     adjusted annually for inflation.
       Throughout this process, the 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 step-wise improvements 
     allowing FDA the resources to establish a generic drug review 
     program that can keep up with the ever-expanding generic drug 
     industry. The recommendations will bring all Abbreviated New 
     Drug Applications (ANDAs) under a common review goals scheme 
     which calls for faster review cycles of 10 months for 
     standard ANDAs and eight months for priority ANDAs. Priority 
     status will be reserved for drug shortages, first generics, 
     sole source generics and other public health priorities. The 
     negotiated recommendations provide that FDA will communicate 
     deficiencies to industry throughout rather than at the end of 
     a review cycle, increasing the chances for applicants to 
     remedy deficiencies and obtain approval in fewer cycles. This 
     will allow for improved predictability and transparency and 
     enable industry advanced business planning.
       The agreement also establishes a robust Pre-ANDA program 
     for complex products. The program will include meetings with 
     applicants, guidance development and regulatory science 
     enhancements aimed at allowing applicants with complex 
     products to submit more complete applications and FDA to be 
     more prepared for such submissions.
       FDA will also make improvements to the facility assessment 
     program in order to increase predictability, transparency and 
     safety. In addition, FDA has committed to accountability and 
     reporting enhancements. FDA will conduct activities to 
     evaluate the financial administration and resource 
     allocations of the GDUFA II program to help identify areas to 
     enhance operational and fiscal efficiency and transparency. 
     FDA will also expand GDUFA program performance reporting to 
     enable the regulated industry, patients and consumer groups, 
     and other stakeholders to better gauge the generic drug 
     program's performance.
       Lastly, the agreement would revamp the user fee structure. 
     GDUFA II will be funded at a level commensurate with the 
     volume of ANDA submissions--the primary workload driver of 
     the program. This will allow FDA the resources necessary to 
     meet all of its commitments. In order to maintain a 
     predictable fee base and to more closely align fee 
     responsibility with program costs and fee-paying ability, FDA 
     and industry have agreed to shift the burden more toward 
     annual program fees. To address specific small business 
     concerns, FDA and industry have proposed three distinct small 
     business considerations. We anticipate that the proposed 
     GDUFA II will increase public access to affordable, generic 
     drug products.
       The following five enclosures are provided for your 
     consideration: The proposed GDUFA II statutory language; a 
     redline of current law; the GDUFA Reauthorization Performance 
     Goals and Procedures--Fiscal Years 2018 through 2022; the 
     Background for the Proposed Changes for Reauthorization of 
     GDUFA in Fiscal Years 2018 through 2022; 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 in order 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,
                                                   Sylvia Burwell,
     Secretary.
                                  ____

                                            Department of Health &


                                               Human Services,

                                  Washington, DC, January 4, 2017.
     Hon. Patty Murray,
     Ranking Member, Committee on Health, Education, Labor and 
         Pensions, U.S. Senate, Washington, DC.
       Dear Senator Murray: The Generic Drug User Fee Amendments 
     of 2012 (GDUFA) enacted as title III of the Food and Drug 
     Administration Safety and Innovation Act [Pub. L. 112-144], 
     expires at the end of Fiscal Year 2017. With this letter the 
     Administration is providing our recommendations for the 
     reauthorization of GDUFA for the Fiscal Years 2018-2022 
     (GDUFA II).
       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 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 II will average approximately $493.6 million per year, 
     adjusted annually for inflation.
       Throughout this process, the FDA has solicited input and 
     worked with various stakeholders, including representatives 
     from consumer, patient, academic research, and

[[Page 12509]]

     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 step-wise improvements 
     allowing FDA the resources to establish a generic drug review 
     program that can keep up with the ever-expanding generic drug 
     industry. The recommendations will bring all Abbreviated New 
     Drug Applications (ANDAs) under a common review goals scheme 
     which calls for faster review cycles of 10 months for 
     standard ANDAs and eight months for priority ANDAs. Priority 
     status will be reserved for drug shortages, first generics, 
     sole source generics and other public health priorities. The 
     negotiated recommendations provide that FDA will communicate 
     deficiencies to industry throughout rather than at the end of 
     a review cycle, increasing the chances for applicants to 
     remedy deficiencies and obtain approval in fewer cycles. This 
     will allow for improved predictability and transparency and 
     enable industry advanced business planning.
       The agreement also establishes a robust Pre-ANDA program 
     for complex products. The program will include meetings with 
     applicants, guidance development and regulatory science 
     enhancements aimed at allowing applicants with complex 
     products to submit more complete applications and FDA to be 
     more prepared for such submissions.
       FDA will also make improvements to the facility assessment 
     program in order to increase predictability, transparency and 
     safety. In addition, FDA has committed to accountability and 
     reporting enhancements. FDA will conduct activities to 
     evaluate the financial administration and resource 
     allocations of the GDUFA II program to help identify areas to 
     enhance operational and fiscal efficiency and transparency. 
     FDA will also expand GDUFA program performance reporting to 
     enable the regulated industry, patients and consumer groups, 
     and other stakeholders to better gauge the generic drug 
     program's performance.
       Lastly, the agreement would revamp the user fee structure. 
     GDUFA II will be funded at a level commensurate with the 
     volume of ANDA submissions--the primary workload driver of 
     the program. This will allow FDA the resources necessary to 
     meet all of its commitments. In order to maintain a 
     predictable fee base and to more closely align fee 
     responsibility with program costs and fee-paying ability, FDA 
     and industry have agreed to shift the burden more toward 
     annual program fees. To address specific small business 
     concerns, FDA and industry have proposed three distinct small 
     business considerations. We anticipate that the proposed 
     GDUFA II will increase public access to affordable, generic 
     drug products.
       The following five enclosures are provided for your 
     consideration: The proposed GDUFA II statutory language; a 
     redline of current law; the GDUFA Reauthorization Performance 
     Goals and Procedures--Fiscal Years 2018 through 2022; the 
     Background for the Proposed Changes for Reauthorization of 
     GDUFA in Fiscal Years 2018 through 2022; 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 in order 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,
                                                   Sylvia Burwell,
     Secretary.
                                  ____

                                            Department of Health &


                                               Human Services,

                                  Washington, DC, January 4, 2017.
     Hon. Greg Walden,
     Chairman, Committee on Energy and Commerce,
     House of Representatives, Washington, DC.
       Dear Mr. Chairman: The Generic Drug User Fee Amendments of 
     2012 (GDUFA) enacted as title III of the Food and Drug 
     Administration Safety and Innovation Act [Pub. L. 112-144], 
     expires at the end of Fiscal Year 2017. With this letter the 
     Administration is providing our recommendations for the 
     reauthorization of GDUFA for the Fiscal Years 2018-2022 
     (GDUFA II).
       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 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 II will average approximately $493.6 million per year, 
     adjusted annually for inflation.
       Throughout this process, the 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 step-wise improvements 
     allowing FDA the resources to establish a generic drug review 
     program that can keep up with the ever-expanding generic drug 
     industry. The recommendations will bring all Abbreviated New 
     Drug Applications (ANDAs) under a common review goals scheme 
     which calls for faster review cycles of 10 months for 
     standard ANDAs and eight months for priority ANDAs. Priority 
     status will be reserved for drug shortages, first generics, 
     sole source generics and other public health priorities. The 
     negotiated recommendations provide that FDA will communicate 
     deficiencies to industry throughout rather than at the end of 
     a review cycle, increasing the chances for applicants to 
     remedy deficiencies and obtain approval in fewer cycles. This 
     will allow for improved predictability and transparency and 
     enable industry advanced business planning.
       The agreement also establishes a robust Pre-ANDA program 
     for complex products. The program will include meetings with 
     applicants, guidance development and regulatory science 
     enhancements aimed at allowing applicants with complex 
     products to submit more complete applications and FDA to be 
     more prepared for such submissions.
       FDA will also make improvements to the facility assessment 
     program in order to increase predictability, transparency and 
     safety. In addition, FDA has committed to accountability and 
     reporting enhancements. FDA will conduct activities to 
     evaluate the financial administration and resource 
     allocations of the GDUFA II program to help identify areas to 
     enhance operational and fiscal efficiency and transparency. 
     FDA will also expand GDUFA program performance reporting to 
     enable the regulated industry, patients and consumer groups, 
     and other stakeholders to better gauge the generic drug 
     program's performance.
       Lastly, the agreement would revamp the user fee structure. 
     GDUFA II will be funded at a level commensurate with the 
     volume of ANDA submissions--the primary workload driver of 
     the program. This will allow FDA the resources necessary to 
     meet all of its commitments. In order to maintain a 
     predictable fee base and to more closely align fee 
     responsibility with program costs and fee-paying ability, FDA 
     and industry have agreed to shift the burden more toward 
     annual program fees. To address specific small business 
     concerns, FDA and industry have proposed three distinct small 
     business considerations. We anticipate that the proposed 
     GDUFA II will increase public access to affordable, generic 
     drug products.
       The following five enclosures are provided for your 
     consideration: The proposed GDUFA II statutory language; a 
     redline of current law; the GDUFA Reauthorization Performance 
     Goals and Procedures Fiscal Years 2018 through 2022; the 
     Background for the Proposed Changes for Reauthorization of 
     GDUFA in Fiscal Years 2018 through 2022; 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 in order 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,
                                                   Sylvia Burwell,
     Secretary.
                                  ____

                                            Department of Health &


                                               Human Services,

                                  Washington, DC, January 4, 2017.
     Hon. Frank Pallone,
     Ranking Member, Committee on Energy and Commerce, House of 
         Representatives, Washington, DC.
       Dear Representative Pallone: The Generic Drug User Fee 
     Amendments of 2012 (GDUFA) enacted as title III of the Food 
     and Drug Administration Safety and Innovation Act [Pub. L. 
     112-144], expires at the end of Fiscal Year 2017. With this 
     letter the Administration is providing our recommendations 
     for the reauthorization of GDUFA for the Fiscal Years 2018-
     2022 (GDUFA II).
       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 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 II will average approximately $493.6 million per year, 
     adjusted annually for inflation.

[[Page 12510]]

       Throughout this process, the 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 step-wise improvements 
     allowing FDA the resources to establish a generic drug review 
     program that can keep up with the ever-expanding generic drug 
     industry. The recommendations will bring all Abbreviated New 
     Drug Applications (ANDAs) under a common review goals scheme 
     which calls for faster review cycles of 10 months for 
     standard ANDAs and eight months for priority ANDAs. Priority 
     status will be reserved for drug shortages, first generics, 
     sole source generics and other public health priorities. The 
     negotiated recommendations provide that FDA will communicate 
     deficiencies to industry throughout rather than at the end of 
     a review cycle, increasing the chances for applicants to 
     remedy deficiencies and obtain approval in fewer cycles. This 
     will allow for improved predictability and transparency and 
     enable industry advanced business planning.
       The agreement also establishes a robust Pre-ANDA program 
     for complex products. The program will include meetings with 
     applicants, guidance development and regulatory science 
     enhancements aimed at allowing applicants with complex 
     products to submit more complete applications and FDA to be 
     more prepared for such submissions.
       FDA will also make improvements to the facility assessment 
     program in order to increase predictability, transparency and 
     safety. In addition, FDA has committed to accountability and 
     reporting enhancements. FDA will conduct activities to 
     evaluate the financial administration and resource 
     allocations of the GDUFA II program to help identify areas to 
     enhance operational and fiscal efficiency and transparency. 
     FDA will also expand GDUFA program performance reporting to 
     enable the regulated industry, patients and consumer groups, 
     and other stakeholders to better gauge the generic drug 
     program's performance.
       Lastly, the agreement would revamp the user fee structure. 
     GDUFA II will be funded at a level commensurate with the 
     volume of ANDA submissions--the primary workload driver of 
     the program. This will allow FDA the resources necessary to 
     meet all of its commitments. In order to maintain a 
     predictable fee base and to more closely align fee 
     responsibility with program costs and fee-paying ability, FDA 
     and industry have agreed to shift the burden more toward 
     annual program fees. To address specific small business 
     concerns, FDA and industry have proposed three distinct small 
     business considerations. We anticipate that the proposed 
     GDUFA II will increase public access to affordable, generic 
     drug products.
       The following five enclosures are provided for your 
     consideration: The proposed GDUFA II statutory language; a 
     redline of current law; the GDUFA Reauthorization Performance 
     Goals and Procedures--Fiscal Years 2018 through 2022; the 
     Background for the Proposed Changes for Reauthorization of 
     GDUFA in Fiscal Years 2018 through 2022; 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 in order 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,
                                                   Sylvia Burwell,
                                                        Secretary.

  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record a copy of the commitment letter for the Generic Drug User 
Fee Act, GDUFA, reauthorization for fiscal years 2018 to 2022, known as 
GDUFA II.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

GDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROGRAM ENHANCEMENTS FISCAL 
                            YEARS 2018-2022

       I. Submission Review Performance Goals
       A. Original ANDAs and ANDA Amendments
       B. PASs and PAS Amendments
       C. Unsolicited ANDA and PAS Amendments
       D. DMFs
       E. Controlled Correspondence
       F. GDUFA I Bridging
       II. Original ANDA Review Program Enhancements
       A. ANDA Receipt
       B. ANDA Review Transparency and Communications Enhancements
       C. Review Classification Changes During the Review Cycle
       D. ANDA Approval and Tentative Approval
       E. Dispute Resolution
       F. Other ANDA Review Program Aspirations
       III. Pre-ANDA Program and Subsequent Mid-Review-Cycle 
     Meetings for Complex Products
       A. Rationale for Pre-ANDA Program, Guidance on Enhanced 
     Pathway for Complex Products
       B. Controlled Correspondence
       C. Product-Specific Guidance
       D. Product Development Meetings
       E. Pre-Submission Meetings
       F. Inactive Ingredient Database Enhancements
       G. Regulatory Science Enhancements
       H. Safety Determination Letters
       I. Other Pre-ANDA Program Aspirations
       IV. DMF Review Program Enhancements
       A. Communication of DMF Review Comments
       B. Teleconferences to Clarify DMF First Cycle Review 
     Deficiencies
       C. DMF First Adequate Letters
       D. DMF No Further Comment Letters
       E. Guidance on Post-Approval Changes to Type II API DMFs
       V. Facilities
       A. Guidance on Risk-Based Site Selection Model
       B. Outreach to Foreign Regulators on Risk-Based Site 
     Selection Model
       C. Export Support and Education of Other Health Authorities
       D. Communications to Foreign Regulators
       E. Communication Regarding Inspections
       F. GDUFA II Facility Compliance Status Database
       VI. Enhanced Accountability and Reporting
       A. Resource Management Planning and Modernized Time 
     Reporting
       B. Financial Transparency and Efficiency
       C. Performance Reporting
       VII. Definitions

GDUFA Reauthorization Performance Goals and Program Enhancements Fiscal 
                            Years 2018-2022

       This document contains the performance goals and program 
     enhancements for the Generic Drug User Fee Act (GDUFA) 
     reauthorization for Fiscal Years (FYs) 2018-2022, known as 
     GDUFA II. 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's) 
     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 review program that are important 
     for facilitating timely access to quality, affordable generic 
     medicines. FDA is committed to meeting the performance goals 
     specified in this letter and to continuous improvement of its 
     performance.
       Unless otherwise stated, goals apply to cohorts of each 
     fiscal year (FY).

  GDUFA Reauthorization Performance Goals And Procedures Fiscal Years 
                               2018-2022

       The performance goals and procedures of the FDA, as agreed 
     to under the first reauthorization of the generic drug user 
     fee program, are summarized below.


                 I. SUBMISSION REVIEW PERFORMANCE GOALS

     A. Original ANDAs and ANDA Amendments
       1. Review and act on 90 percent of standard original 
     Abbreviated New Drug Applications (ANDAs) within 10 months of 
     the date of ANDA submission.
       2. Review and act on 90 percent of priority original ANDAs 
     within the applicable review goal.
       a. Review and act on priority original ANDAs within 8 
     months of the date of ANDA submission, if the applicant 
     submits a Pre-Submission Facility Correspondence 2 months 
     prior to the date of ANDA submission and the Pre-Submission 
     Facility Correspondence is found to be complete and accurate 
     and remains unChanged.
       b. Review and act on priority original ANDAs within 10 
     months of the date of ANDA submission if the applicant does 
     not submit a Pre-Submission Facility Correspondence 2 months 
     prior to the date of ANDA submission or facility information 
     changes or is found to be incomplete or inaccurate.
       3. Review and act on 90 percent of standard major ANDA 
     amendments within the applicable review goal.
       a. Review and act on standard major ANDA amendments within 
     8 months of the date of amendment submission if preapproval 
     inspection is not required.
       b. Review and act on standard major ANDA amendments within 
     10 months of the date of amendment submission if preapproval 
     inspection is required.
       4. Review and act on 90 percent of priority major ANDA 
     amendment submissions within the applicable review goal.
       a. Review and act on priority major ANDA amendments within 
     6 months of the date of amendment submission if preapproval 
     inspection is not required.
       b. Review and act on priority major ANDA amendments within 
     8 months of amendment submission if (i) preapproval 
     inspection is required and (ii) applicant submits a Pre-
     Submission Facility Correspondence 2 months

[[Page 12511]]

     prior to the date of amendment submission and the Pre-
     Submission Facility Correspondence is found to be complete 
     and accurate and remains unchanged.
       c. Review and act on priority major ANDA amendments within 
     10 months of amendment submission if (i) preapproval 
     inspection is required and (ii) the applicant does not submit 
     a Pre-Submission Facility Correspondence 2 months prior to 
     amendment submission, or facility information Changes or is 
     found to be incomplete or inaccurate.
       5. Review and act on 90 percent of standard and priority 
     minor ANDA 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.
Priority Original ANDAs...................  90% within 8 months of
                                             submission date if
                                             applicant meets
                                             requirements under
                                             I(A)(2)(a).
                                            90% within 10 months of
                                             submission date if
                                             applicant does not meet
                                             requirements as described
                                             under I(A)(2)(b).
------------------------------------------------------------------------


             TABLE FOR SECTION I(A)(3)-(5): ANDA AMENDMENTS
------------------------------------------------------------------------
              Submission Type                           Goal
------------------------------------------------------------------------
Standard Major ANDA 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 ANDA 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
                                             I(A)(4)(b).
                                            90% within 10 months of
                                             submission date if
                                             preapproval inspection
                                             required and applicant does
                                             not meet requirements as
                                             described under I(A)(4)(c).
Standard and Priority Minor ANDA            90% within 3 months of
 Amendments.                                 submission date.
------------------------------------------------------------------------

     B. PASs and PAS Amendments
       1. Review and act on 90 percent of standard Prior Approval 
     Supplements (PASs) within the applicable review goal.
       a. Review and act on standard PASs within 6 months of the 
     date of PAS submission if preapproval inspection is not 
     required.
       b. Review and act on standard PASs within 10 months of the 
     date of PAS submission if preapproval inspection is required.
       2. Review and act on 90 percent of priority PASs within the 
     applicable review goal.
       a. Review and act on priority PASs within 4 months of the 
     date of PAS submission if preapproval inspection is not 
     required.
       b. Review and act on priority PASs within 8 months of the 
     date of PAS submission if (i) preapproval inspection is 
     required and (ii) the applicant submits a Pre-Submission 
     Facility Correspondence 2 months prior to the date of PAS 
     submission and the Pre-Submission Facility Correspondence is 
     found to be complete and accurate and remains unchanged.
       c. Review and act on priority PASs within 10 months of PAS 
     submission if (i) preapproval inspection is required and (ii) 
     the applicant does not submit a Pre-Submission Facility 
     Correspondence 2 months prior to the date of PAS submission, 
     or facility information changes or is found to be incomplete 
     or inaccurate.
       3. Review and act on 90 percent of major amendments to 
     standard PASs within the applicable review goal.
       a. Review and act on major amendments to standard PASs 
     within 6 months of the date of amendment submission if 
     preapproval inspection is not required.
       b. Review and act on major amendments to standard PASs 
     within 10 months of the date of amendment submission if 
     preapproval inspection is required.
       4. Review and act on 90 percent of major amendments to 
     priority PASs within the applicable review goal.
       a. Review and act on major amendments to priority PASs 
     within 4 months of the date of amendment submission if 
     preapproval inspection is not required.
       b. Review and act on major amendments to priority PASs 
     within 8 months of the date of amendment submission if (i) 
     preapproval inspection is required and (ii) the applicant 
     submits a Pre-Submission Facility Correspondence 2 months 
     prior to the date of amendment submission and the Pre-
     Submission Facility Correspondence is found to be complete 
     and accurate and remains unchanged.
       c. Review and act on major amendments to priority PASs 
     within 10 months of amendment submission if (i) preapproval 
     inspection is required and (ii) the applicant does not submit 
     a Pre-Submission Facility Correspondence 2 months prior to 
     the date of amendment submission, or facility information 
     changes or is found to be incomplete or inaccurate.
       5. Review 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
                                             I(B)(2)(b).
                                            90% within 10 months of
                                             submission date if
                                             preapproval inspection
                                             required and applicant does
                                             not meet requirements as
                                             described under 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
                                             I(B)(4)(b).
                                            90% within 10 months of
                                             submission date if
                                             preapproval inspection
                                             required and applicant does
                                             not meet requirements as
                                             described under I(B)(4)(c).
Standard and Priority Minor PAS Amendments  90% within 3 months of
                                             submission date.
------------------------------------------------------------------------

     C. Unsolicited ANDA Amendments and PAS Amendments
       1. Review and act on unsolicited ANDA amendments and PAS 
     amendments submitted during the review 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)(3), (4) and (5) and (I)(B)(3), (4) and (5), 
     respectively, for the unsolicited amendment.
       2. Review and act on unsolicited ANDA amendments and PAS 
     amendments submitted between review cycles by the later of 
     the goal date for the subsequent solicited amendment or the 
     goal date assigned in accordance with Sections (I)(A)(3), (4) 
     and (5) and (I)(B)(3), (4) and (5), respectively, for the 
     unsolicited amendment.
     D. DMFs
       1. Complete the initial completeness assessment review for 
     90 percent of Type II Active Pharmaceutical Ingredient (API) 
     Drug Master Files (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. Review and respond to 90 percent of controlled 
     correspondences within the applicable review goal.
       a. Review and respond to Standard controlled correspondence 
     within 60 days of the date of submission.
       b. Review and respond to Complex controlled correspondence 
     within 120 days of the date of submission.
       2. In the case of controlled correspondence that raises an 
     issue that relates to one or more pending citizen petitions, 
     the 60- or 120-day time period starts on the date FDA 
     responds to the petition (if there is only one petition) or 
     last pending petition.
       3. FDA will review and respond to 90% of submitter requests 
     to clarify ambiguities in the controlled correspondence 
     response within 14 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
------------------------------------------------------------------------
Standard Controlled Correspondence........  90% within 60 days of
                                             submission date.
Complex 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 request within 14 days of
 request receipt.
------------------------------------------------------------------------

     F. GDUFA I Bridging
       1. Continue to review and act on ANDAs and ANDA amendments, 
     PASs and PAS amendments and controlled correspondence 
     submitted prior to October 1, 2017 that have been assigned 
     GDUFA I goal dates pursuant to the GDUFA I review metrics 
     applicable to those submissions.
       2. Review and act on 90% of ANDAs and ANDA amendments with 
     Target Action Dates (TADs) by the goal date. The TAD for an 
     ANDA or ANDA amendment becomes its GDUFA II goal date. 
     (Attachment A shows how FDA, until September 30, 2017, 
     assigned TADs to ANDA amendments not subject to GDUFA I 
     review goals.)
       3. Review and act on 90% of ANDAs and ANDA amendments 
     pending FDA as of October 1, 2017 that were not subject to 
     GDUFA I goal dates and either (a) were not previously 
     assigned TADs or (b) were previously assigned TADs that came 
     due prior to October 1, 2017 but remain pending in the same 
     review cycle as of October 1, 2017, by GDUFA II ANDA and ANDA 
     amendment goal dates that FDA will assign on October 1, 2017. 
     No such goal date shall be later than July 31, 2018.
       4. Review and act on amendments received on or after 
     October 1, 2017, to any ANDAs submitted prior to October 1, 
     2017, pursuant to the amendment review goals set forth in 
     (A)(3)-(5) of this section.

[[Page 12512]]




             II. ORIGINAL ANDA REVIEW 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 Code of Federal Regulations (CFR) 
     314.101, and with consideration of final agency guidances 
     that address ANDA receipt determinations, FDA will issue a 
     Manual of Policies and Procedures (MAPP) by October 1, 2017 
     setting forth procedures for filing reviewers on 
     communication of minor technical deficiencies (e.g., document 
     legibility); and on deficiencies potentially resolved with 
     information in the ANDA at original submission, in order to 
     provide applicants with an opportunity for resolution within 
     7 calendar days. If such a deficiency is resolved within 7 
     calendar 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 review
     B. ANDA Review Transparency and Communications Enhancements
       To promote transparency and communication between FDA and 
     ANDA applicants, FDA will apply the review program 
     enhancements below to the review 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 review cycles 
     necessary for approval, increase the overall rate of 
     approval, and facilitate greater access to generic drug 
     products.
       1. FDA will issue the appropriate Information Request(s) 
     (IR(s)) and/or Discipline Review Letter(s) (DRL(s)) from each 
     review discipline as soon as the discipline has completed its 
     review, with the first IR(s) and/or DRL(s) at about the mid-
     point of the review.
       2. Following the IR and/or DRL at about the mid-point of 
     the review, IRs and/or DRLs will, as appropriate, continue 
     from each review discipline on a rolling basis.
       3. Neither IRs nor DRLs stop the review clock or add to a 
     GDUFA goal.
       4. If an applicant is unable to completely respond within 
     the time frame requested by FDA, including any extensions 
     that may be granted by FDA, then FDA will generally issue a 
     Complete Response Letter (CRL).
       5. FDA will continue to issue IRs and/or DRLs late in the 
     review cycle, until it is no longer feasible, within the 
     current review cycle, for applicant to develop and FDA to 
     review a complete response to the IR and/or DRL.
       6. FDA should continue to work through the goal date if in 
     FDA's judgment continued work would likely result in an 
     imminent tentative approval that could prevent forfeiture of 
     180-day exclusivity or in an imminent approval.
       7. FDA will strive to act prior to a goal date when the 
     review is done and there are no outstanding issues.
       8. If in the ordinary course a Regulatory Project Manager 
     (RPM) learns that a major deficiency is likely forthcoming, 
     the RPM will notify the Authorized Representative that a 
     major deficiency is likely forthcoming. If the Authorized 
     Representative raises concerns or seeks additional 
     information regarding the forthcoming major deficiency, the 
     RPM will encourage the Authorized Representative to review 
     the forthcoming deficiency upon receiving it.
       9. If in the ordinary course an RPM learns that FDA is 
     likely to miss the goal date for the submission, the RPM will 
     notify the Authorized Representative of the outstanding 
     discipline(s), the general nature of the delay (when 
     possible), and the estimated timeframe for receiving the 
     response.
       10. The Authorized Representative may periodically request 
     a Review Status Update. In response to the Authorized 
     Representative's request, the RPM will timely provide a 
     Review Status Update.
       11. FDA will include in the CRL its basis for classifying a 
     responding amendment Major.
       12. Applicants may opt for 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 major 
     complete response letters. FDA will also grant appropriate 
     requests for teleconferences requested by applicants upon 
     receiving subsequent major complete response letters or minor 
     complete response letters. FDA will provide a scheduled date 
     for 90 percent of post-CRL teleconferences within 10 days of 
     the request for a teleconference, and conduct 90 percent of 
     such post-CRL teleconferences held on the FDA-proposed date, 
     within 30 days of receipt of the written request.
     C. Review Classification Changes During the Review Cycle
       1. If during a review cycle of an ANDA or PAS, the review 
     classification of the ANDA or PAS changes from Standard to 
     Priority, FDA will notify the applicant within 14 days of the 
     date of the change.
       2. If a previous ANDA or ANDA amendment was subject to 
     priority review, but a subsequent ANDA amendment is subject 
     to standard review, FDA will notify applicant within 14 days 
     of the date of receipt of the solicited amendment.
       3. A request for a change may occur at any time during the 
     review.
       4. Once an ANDA or PAS submission is classified as being 
     subject to priority review, the application will retain such 
     priority review classification status until FDA takes an 
     action on the submission.
       5. FDA will include an explanation of the reasons for any 
     denial of a review status reclassification request.
       6. If an applicant requests a teleconference as part of its 
     request to reclassify a major amendment or standard review 
     status, FDA will schedule and conduct the teleconference and 
     decide 90% 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 applicant accepts 
     the first scheduled teleconference date offered by FDA.
     D. ANDA Approval and Tentative Approval
       If applicants submit and maintain ANDAs consistent with the 
     statutory requirements for approval under 505(j); 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 approve approvable ANDAs in the first review cycle; 
     to approve potential first generics on the earliest lawful 
     ANDA approval date, if known to FDA; and to tentatively 
     approve first to file Paragraph IV ANDAs so as to avoid 
     forfeiture of 180-day exclusivity.
     E. Dispute Resolution
       1. An applicant may pursue a request for reconsideration 
     within the review discipline at the Division level or 
     original signatory authority, as needed.
       2. The Office of Generic Drugs (OGD) 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 the 
     September 2015 Guidance, Formal Dispute Resolution: Appeals 
     Above the Division Level.
       4. FDA will respond to appeals above the Division level 
     within 30 calendar days of the Center for Drug Evaluation and 
     Research's (CDER's) receipt of the written appeal pursuant to 
     the applicable goal.
       a. In FY 2018, the goal is 70 percent.
       b. In FY 2019, the goal is 80 percent.
       c. In FY 2020, 2021, and 2022 the goal is 90 percent.
       5. CDER's Formal Dispute Resolution Project Manager (or 
     designee) will track each formal appeal above the Division 
     level through resolution
     F. Other ANDA Review Program Aspirations
       1. FDA aspires to continually improve the efficiency of the 
     ANDA review program.
       2. The absence of a GDUFA II commitment for a specific 
     program function does not imply that the program function is 
     not important. For example, other program functions include 
     determinations whether listed drugs were voluntarily 
     withdrawn from sale for reasons of safety or effectiveness 
     and ANDA proprietary name reviews.


  III. PRE-ANDA PROGRAM AND SUBSEQUENT MID-REVIEW-CYCLE MEETINGS FOR 
                            COMPLEX PRODUCTS

     A. Rationale for Pre-ANDA Program, Guidance on Enhanced 
         Pathway for Complex Products
       The goal of the pre-ANDA program is to clarify regulatory 
     expectations for prospective applicants early in product 
     development, assist applicants to develop more complete 
     submissions, promote a more efficient and effective ANDA 
     review process, and reduce the number of review cycles 
     required to obtain ANDA approval, particularly for Complex 
     Products.
       1. FDA will issue guidance describing an enhanced pathway 
     for Complex Products, including policies and procedures for 
     Product Development Meetings, pre-submission meetings, and 
     mid-review cycle meetings. An ANDA applicant who was granted 
     a Product Development Meeting has the option of a pre-
     submission meeting with FDA and also the option of a mid-
     review-cycle meeting with FDA, subject to policies and 
     procedures to be set forth in the guidance.
     B. Controlled Correspondence
       1. FDA will review and respond to standard controlled 
     correspondence and to complex controlled correspondence with 
     meaningful responses that can more consistently inform drug 
     development and/or regulatory decision making pursuant to the 
     applicable metric goals.
     C. Product-Specific Guidance
       1. FDA will issue product-specific guidance identifying the 
     methodology for developing drugs and generating evidence 
     needed to support ANDA approval, for 90 percent of new 
     chemical entity New Drug Applications that are approved on or 
     after October 1, 2017, at least 2 years prior to the earliest 
     lawful ANDA filing date.
       2. This goal shall not apply to Complex Products. FDA will 
     strive to issue guidance

[[Page 12513]]

     for a Complex Product as soon as scientific recommendations 
     are available.
       3. FDA will continue to develop and issue product-specific 
     guidance based on requests from industry and public health 
     priorities as set forth in the CDER Prioritization MAPP.
       4. Industry may request that FDA develop product-specific 
     guidance via email to [email protected].
     D. Product Development Meetings
       1. 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 Product for which FDA has not 
     issued product-specific guidance or
       ii. An alternative equivalence evaluation (i.e., change in 
     study type, such as in vitro to clinical) for a Complex 
     Product for which FDA has issued product-specific guidance,
       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 review efficiency.
       2. Dependent on available resources, FDA may grant a 
     prospective applicant a Product Development Meeting 
     concerning Complex Product development issues other than 
     those described in Section III(D)(1)(a) above 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 review efficiency.
       3. FDA will grant or deny 90% of Product Development 
     Meeting requests within the applicable goal.
       a. In FYs 2018 and 2019, the goal is 30 days from receipt 
     of the request.
       b. In FYs 2020, 2021 and 2022, the goal is 14 days from 
     receipt of the request.
       4. FDA will conduct Product Development Meetings granted 
     pursuant to the applicable goal.
       a. In FY 2018, FDA will conduct 60 percent of such meetings 
     within 120 days of granting them.
       b. In FY2019, FDA will conduct 70 percent of such meetings 
     within 120 days of granting them.
       c. In FY2020, FDA will conduct 80 percent of such meetings 
     within 120 days of granting them.
       d. In FYs 2021 and 2022, FDA will conduct 90 percent of 
     such meetings within 120 days of granting them.
       5. 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.
       6. 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 
     calendar days before the meeting), and will provide meeting 
     minutes within 30 calendar days following the meeting.
     E. Pre-Submission Meetings
       1. Prospective applicants may request and FDA will conduct 
     pre-submission meetings, subject to Section III(A)(1). An 
     applicant's decision not to request a pre-submission meeting 
     will not prejudice the receipt or review of an ANDA.
       2. FDA will grant or deny 90% of pre-submission meeting 
     requests within the applicable goal.
       a. In FYs 2018 and 2019, the goal is 30 days.
       b. In FYs 2020, 2021, and 2022, the goal is 14 days.
       3. If an applicant did not have a Product Development 
     Meeting, FDA may grant a pre-submission meeting if in FDA's 
     judgment the pre-submission meeting would improve review 
     efficiency.
       4. FDA will conduct pre-submission meetings granted 
     pursuant to the applicable goal.
       a. In FY 2018, FDA will conduct 60 percent of such meetings 
     within 120 days of granting them.
       b. In FY 2019, FDA will conduct 70 percent of such meetings 
     within 120 days of granting them.
       c. In FY 2020, FDA will conduct 80 percent of such meetings 
     within 120 days of granting them.
       d. In FYs 2021 and 2022, FDA will conduct 90 percent of 
     such meetings within 120 days of granting them.
       5. If appropriate to the purpose of the meeting, FDA will 
     provide preliminary written comments 5 calendar days before 
     each meeting, and meeting minutes within 30 calendar days of 
     the meeting.
     F. Mid-Review-Cycle Meetings for Complex Products
       As set forth in guidance issued pursuant to Section 
     III(A)(1), the Project Manager and other appropriate members 
     of the FDA review team will call the applicant 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-review-cycle meeting. The Project Manager will 
     coordinate the specific date and time of the telephone call 
     with the applicant.
     G. Inactive Ingredient Database Enhancements
       1. By October 1, 2020, FDA will complete enhancements to 
     the Inactive Ingredient Database so users can perform 
     electronic queries to obtain accurate Maximum Daily Intake 
     and Maximum Daily Exposure information for each route of 
     administration for which data is available.
       2. FDA will update the Inactive Ingredient Database on an 
     ongoing basis, and post quarterly notice of updates made. 
     Such notices will include each change made and, for each 
     change, the information replaced.
     H. Regulatory Science Enhancements
       FDA will conduct internal and external research to support 
     fulfilment of submission review and pre-ANDA commitments set 
     forth in Sections I and III, respectively.
       1. Annually, FDA will conduct a public workshop to solicit 
     input from industry and stakeholders for inclusion in an 
     annual list of GDUFA II 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.
       2. If Industry forms a GDUFA II 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.
       3. 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 review and timely 
     approval of ANDAs, and the evaluation of generic drug 
     equivalence.
     I. Safety Determination Letters
       1. FDA will issue 90% of safety determination letters 
     within 60 days of the date of submission of disclosure 
     authorization.
     J. Other Pre-ANDA Program Aspirations
       1. FDA aspires to continually improve the effectiveness of 
     its pre-ANDA activity.
       2. The absence of a GDUFA II commitment for a specific 
     program function does not imply that the program function is 
     not important. For example, notwithstanding the absence of a 
     GDUFA II commitment, FDA aspires to respond to Suitability 
     Petitions in a more timely and predictable manner.


                  IV. DMF REVIEW PROGRAM ENHANCEMENTS

     A. Communication of DMF Review Comments
       1. FDA will ensure that DMF review 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. 
     This commitment applies to comments to the applicant issued 
     in any ANDA CRL and comments issued in the first IR letter by 
     the drug product review discipline.
     B. Teleconferences to Clarify DMF First Cycle Review 
         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 20 business 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, 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
       1. Once a DMF has undergone a full scientific review and 
     has no open issues related to the review of the referencing 
     ANDA, FDA will issue a First Adequate Letter.
     D. DMF No Further Comment Letters
       1. Once a DMF has undergone a complete review and the ANDA 
     referencing the DMF has been approved or tentatively 
     approved, FDA will issue a no further comment letter.
     E. Guidance on Post-Approval Changes to Type II API DMFs.
       1. By October 1, 2018, FDA will issue a guidance regarding 
     post-approval changes to a Type II API DMF and submission 
     mechanisms for ANDA applicants who reference the Type II API 
     DMF.


                             V. FACILITIES

       A. Guidance on Risk-Based Site Selection Model--Issue a 
     guidance explaining the Agency's risk-based site surveillance 
     model for

[[Page 12514]]

     human pharmaceutical manufacturing establishments, including 
     a discussion of the risk factors incorporated in the model 
     and how the model is used to help determine which 
     establishments are scheduled to receive a surveillance 
     inspection each year.
       B. Outreach to Foreign Regulators on Risk-Based Site 
     Selection Model--Undertake outreach activities to better 
     inform other pharmaceutical regulators of FDA's risk-based 
     surveillance model.
       C. Export Support and Education of Other Health 
     Authorities--Support the export of safe and effective 
     pharmaceutical products by the U.S.-based pharmaceutical 
     industry, including but not limited to timely updates to 
     FDA's Facility Compliance Status Database as described below, 
     and educating other health authorities regarding FDA's 
     surveillance inspection program and the meaning of inspection 
     classifications.
       D. 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.
     E. Communication Regarding Inspections
       1. By May 31, 2018, when FDA conducts an application-
     related 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. By October 1, 2018, 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. FDA agrees to 
     ongoing periodic engagement with industry stakeholders to 
     provide updates on agency activities and seek stakeholder 
     feedback.
       F. GDUFA II Facility Compliance Status Database--By January 
     1, 2019, FDA will update its existing, publicly available 
     database that describes the compliance status of GDUFA self-
     ID facilities and sites. Compliance status is based on the 
     most recent inspection or related FDA action for facilities 
     involved in any manufacturing activities subject to Current 
     Good Manufacturing Practices (CGMP) inspection and for sites 
     involved in the conduct or analysis of bioanalytical or 
     clinical bioequivalence/bioavailability studies conducted to 
     support an ANDA. The database will be updated every 30 days 
     and will reflect FDA's final assessment of the facility or 
     site following an FDA inspection and review of the inspected 
     entity's timely response to any documented observations. The 
     public website containing the database will also include an 
     explanation of terms used to describe the compliance status 
     of facilities and sites.


               VI. ENHANCED ACCOUNTABILITY AND REPORTING

       FDA will build internal capacity to enable improved 
     productivity and performance through regular assessment of 
     progress towards GDUFA goals, consistent methodologies for 
     and timely reporting of GDUFA metrics, and transparent and 
     efficient administration; allocation and reporting of user 
     fee resources.
     A. Resource Management Planning and Modernized Time Reporting
       FDA is committed to enhancing management of the GDUFA 
     program in GDUFA II.
       1. FDA will conduct activities to develop a resource 
     management planning function and modernized time reporting 
     approach in GDUFA II. FDA will staff a planning team 
     responsible for these activities and for publishing a GDUFA 
     program resource management planning and modernized time 
     reporting implementation plan no later than fourth quarter FY 
     2018.
       2. FDA will obtain through a contract with an independent 
     third party an evaluation of options and recommendations for 
     a new methodology to accurately assess changes in the 
     resource needs of the human generic drug review program and 
     how to monitor and report on those needs moving forward. The 
     report will be published no later than the end of FY 2020 for 
     public comment. Upon review of the report and comments, FDA 
     will implement robust methodologies for assessing resource 
     needs of the program and tracking resource utilization across 
     the program elements.
     B. Financial Transparency and Efficiency
       FDA is committed to ensuring GDUFA user fee resources are 
     administered, allocated, and reported in an efficient and 
     transparent manner. FDA will conduct activities 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.
       1. FDA will contract with an independent third party to 
     evaluate and report on how the GDUFA program is resourced and 
     how those resources are utilized, and recommend improvements 
     to the process.
       2. FDA will use the results of that evaluation to create an 
     ongoing financial reporting mechanism to enhance the 
     transparency of GDUFA program resource utilization.
       3. FDA will publish a GDUFA 5-year financial plan no later 
     than the 2nd quarter of FY 2018. FDA will publish updates to 
     the 5-year plan no later than the 2nd quarter of each 
     subsequent fiscal year.
       4. FDA will convene a public meeting no later than the 
     third quarter of each fiscal year starting in FY 2019 to 
     discuss the GDUFA 5-year financial plan, along with the 
     Agency's progress in implementing modernized time reporting 
     and resource management planning.
     C. Performance Reporting
       1. FDA will publish the following monthly metrics on its 
     website, using a consistent, publicly disclosed reporting 
     methodology:
       a. Number of ANDAs and ANDA amendments, DMFs, Changes Being 
     Effected (CBEs) and PASs submitted in the reporting month 
     delineated by type of submission,
       b. Number each of ANDAs and PASs FDA refused for receipt in 
     the reporting month,
       c. 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, complete response letters, 
     information requests, and discipline review letters (or other 
     such nomenclature as FDA determines to reflect the concepts 
     of an information request or complete response letter), and
       d. Number of first cycle approvals and tentative approvals 
     in the reporting month.
       2. FDA will publish the following quarterly metrics on its 
     website, using a consistent, publicly disclosed reporting 
     methodology:
       a. Number of ANDAs and PASs withdrawn in each reporting 
     month,
       b. Number of ANDAs awaiting applicant action, and
       c. Number of ANDAs awaiting FDA action.
       d. Mean and median approval and tentative approval times 
     for the quarterly action cohort.
       3. FDA will publish the following metrics annually as part 
     of the GDUFA Performance Report:
       a. Mean and median approval and tentative approval times by 
     FY receipt cohort,
       b. Mean and median ANDA approval times, including separate 
     reporting of mean and median times for first cycle approvals,
       c. Mean and median number of ANDA review cycles to approval 
     and tentative approval by FY receipt cohort,
       d. Number of GDUFA related teleconferences requested, 
     granted, denied and conducted, broken down by type of 
     teleconference,
       e. Number of applications received, refused to receive, and 
     average time to receipt decision,
       f. Number of product development, pre-submission and mid-
     review cycle meetings requested, granted, denied and 
     conducted, by face to face or in writing,
       g. Number of inspections conducted by domestic or foreign 
     establishment location and inspection type (Pre-Approval 
     Inspection (PAI), Good Manufacturing Practices (GMP), 
     Bioequivalence (BE) clinical and BE analytical) and facility 
     type (Finished Dosage Form (FDF), API, etc.),
       h. Median time from beginning of inspection to 483 
     issuance,
       i. Median time from 483 issuance to Warning Letter, Import 
     Alert and Regulatory Meeting for inspections with final 
     classification of Official Action Indicated (OAI) (or 
     equivalent),
       j. Median time from date of Warning Letter, Import Alert 
     and Regulatory Meeting to resolution of the OAI status (or 
     equivalent),
       k. Number of ANDAs accepted for standard review and 
     priority review,
       l. Number of suitability petitions pending a substantive 
     response for more than 270 days from the date of receipt,
       m. Number of 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,
       n. Percentage of ANDA proprietary name requests reviewed 
     within 180 days of receipt,
       o. Number of DMF First Adequate Letters issued, and
       p. Number of email exchanges requested and conducted in 
     lieu of teleconferences to clarify deficiencies in first 
     cycle DMF deficiency letters.


                            VII. DEFINITIONS

       A. Act on an application--means FDA will either issue a 
     complete response letter, 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, in FDA's judgment, merits further 
     clarification.
       C. Appropriate, with respect to a request for a post-CRL 
     teleconference--means a complete and clear request for a 
     teleconference where the applicant's goal is to gain an 
     understanding of specific deficiencies and expectations for 
     resolution.
       D. Authorized Representative--means the authorized point of 
     contact identified in applicant's letter of authorization or 
     Form 356h. An Authorized Representative may designate an 
     alternate to serve in the Authorized Representative's 
     absence.

[[Page 12515]]

       E. Change, with respect to facility information--means a 
     change to information in the Pre-Submission Facilities 
     Correspondence that causes FDA to re-evaluate its facility 
     assessment (i.e., assess the impact of the change on its 
     previous recommendation), such as a change in facility (as 
     described by address, FDA Establishment Identification (FEI) 
     number, or Data Universal Numbering System (DUNS) number), 
     change in operation(s) performed by a facility, addition of a 
     new facility, withdrawal of a facility used to generate data 
     to meet application requirements or intended for commercial 
     production, or a change in inspection readiness (i.e., a 
     facility is no longer ready for inspection).
       F. Complete response letter (CRL)--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 abbreviated application (including pending 
     amendments) or a DMF that must be satisfactorily addressed 
     before the ANDA can be approved. Complete response letters 
     will reflect a complete review 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, 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.
       G. Complete review--refers to a full division-level review 
     from all relevant review disciplines, including inspections, 
     and includes other matters relating to the ANDAs and 
     associated DMFs as well as consults with other agency 
     components.
       H. Complex controlled correspondence--means:
       1. Controlled correspondence involving evaluation of 
     clinical content,
       2. Bioequivalence protocols for Reference Listed Drugs with 
     Risk Evaluation and Mitigation Strategies (REMS) Elements To 
     Assure Safe Use (ETASU), or
       3. Requested evaluations of alternative bioequivalence 
     approaches within the same study type (e.g., pharmacokinetic, 
     in vitro, clinical).
       I. 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 and 
     complex ophthalmological products and otic dosage forms that 
     are formulated as suspensions, emulsions or gels) or complex 
     dosage forms (e.g., transdermals, metered dose inhalers, 
     extended release injectables)
       2. Complex drug-device combination products (e.g., auto 
     injectors, 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.
       J. Days--unless otherwise specified, means calendar days.
       K. Discipline review letter (DRL)--means a letter used to 
     convey preliminary thoughts on possible deficiencies found by 
     a discipline reviewer and/or review team for its portion of 
     the pending application at the conclusion of the discipline 
     review.
       L. Earliest lawful ANDA approval date--the first date on 
     which no patent or exclusivity prevents full approval of an 
     ANDA
       M. First adequate letter--a communication from FDA to DMF 
     holder indicating that the DMF has no open issues related to 
     the review of the referencing ANDA. Issued only at the 
     conclusion of the first DMF review cycle that determines the 
     DMF does not have any open issues.
       N. First generic--any received ANDA (1) that is a first-to-
     file ANDA eligible for 180-day exclusivity or for which there 
     are no blocking patents or exclusivities and (2) for which 
     there is no previously approved ANDA for the drug product.
       O. Information Request (IR)--means a letter that is sent to 
     an applicant during a review to request further information 
     or clarification that is needed or would be helpful to allow 
     completion of the discipline review.
       P. Major amendment--means a major amendment as described in 
     CDER's December 2001 Guidance for Industry: Major, Minor and 
     Telephone Amendments to Abbreviated New Drug Applications.
       Q. Mid-review-cycle meeting--after the last key discipline 
     has issued its IR and/or DRL, for ANDAs that were the subject 
     of prior Product Development Meetings or pre-submission 
     meetings, CDER will schedule a teleconference meeting with 
     the applicant to discuss current concerns with the 
     application and next steps.
       R. Minor amendment--means a minor amendment as described in 
     CDER's December 2001 Guidance for Industry: Major, Minor and 
     Telephone Amendments to Abbreviated New Drug Applications.
       S. Complete and accurate Pre-Submission Facility 
     Correspondence--lists all of the following:
       1. All facilities involved in manufacturing processes and 
     testing for the ANDA and corresponding Type II API DMF as 
     required by 21 CFR 314.50(d)(1)(i) and (iii). For each 
     manufacturing or testing facility, the correspondence 
     includes facility name, operation(s) performed, facility 
     contact name, address, FEI number (if a required registrant 
     or one has been assigned), DUNS number, registration 
     information (for required registrants), a confirmation that 
     the facility is ready for inspection, a description of the 
     manufacturing process, and a certification by the applicant 
     that any Type II DMF has similarly complete and accurate 
     facility information as required by 21 CFR 314.50(d)(1)(i), 
     including complete facility information (i.e., facility name, 
     operation, facility contact name, address, FEI number and 
     DUNS number). Facility information that is included in a 
     corresponding Type II DMF is not required to be duplicated in 
     the Pre-Submission Facility Correspondence for the ANDA.
       2. All sites or organizations involved in bioequivalence 
     and clinical studies used to support the ANDA submission as 
     described in 21 CFR 314.94(a)(7). This information is 
     provided using a standardized electronic format and includes 
     unique identifiers that are current and accurate, including 
     site or organization name, address and website; and study 
     information including a listing of study names, dates of 
     conduct and main investigators.
       T. Pre-submission meeting--means a meeting in which an 
     applicant has an opportunity to discuss and explain the 
     format and content of an ANDA to be submitted. Although the 
     proposed content of the ANDA will be discussed, pre-
     submission meetings will not include substantive review of 
     summary data or full study reports.
       U. Priority--means submissions affirmatively identified as 
     eligible for expedited review pursuant to CDER's Manual of 
     Policy and Procedures (MAPP) 5240.3, Prioritization of the 
     Review of Original ANDAs, Amendments and Supplements, as 
     revised (the CDER Prioritization MAPP).
       V. Product Development Meeting--means a meeting involving a 
     scientific exchange to discuss specific issues (e.g., a 
     proposed study design, alternative approach or additional 
     study expectations) or questions, in which FDA will provide 
     targeted advice regarding an ongoing ANDA development 
     program.
       W. Review Status Update--means a response from the RPM to 
     the Authorized Representative to update the Authorized 
     Representative concerning, at a minimum, the categorical 
     status of relevant review disciplines with respect to the 
     submission at that time. The RPM will advise the Authorized 
     Representative that the update is preliminary only, based on 
     the RPM's interpretation of the submission, and subject to 
     change at any time.
       X. Safety determination letter--a letter from FDA stating 
     that a bioequivalence study protocol contains safety 
     protections comparable to applicable REMS for the Reference 
     Listed Drug.
       Y. Standard--means submissions not affirmatively identified 
     as eligible for expedited review pursuant to the CDER 
     Prioritization MAPP.
       Z. Standard controlled correspondence--means controlled 
     correspondence
       1. as described in CDER's September 2015 Guidance for 
     Industry, Controlled Correspondence Related to Generic Drug 
     Development, or
       2. concerning post-approval submission requirements that 
     are not covered by CDER post-approval changes guidance and 
     are not specific to an ANDA.
       AA. Target Action Date (TAD)--Under GDUFA I, FDA's 
     aspirational deadline for action on a pre-GDUFA I Year 3 
     original ANDA and/or a complete response amendment or 
     equivalent IR to an original ANDA. GDUFA I TADs become GDUFA 
     II goal dates on enactment of GDUFA II.
       BB. Teleconference--means a verbal communication by 
     telephone, and not a written response, unless otherwise 
     agreed to by the applicant.
       CC. 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).

[[Page 12516]]



                GDUFA II COMMITMENT LETTER, ATTACHMENT A
------------------------------------------------------------------------
                                                       Pre-cohort Year 3
            Category               Pre-cohort Year 3   ANDAs (expedited
                                         ANDAs              status)
------------------------------------------------------------------------
Major Amendment (Complete         10 months.........  7 months
 Response Letter).
Minor Amendment (Complete         5 months..........  3 months
 Response Letter).
Easily Correctable Deficiency...  3 months..........
Information Request.............  3 months..........
------------------------------------------------------------------------

  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record a copy of the commitment letter for the Medical Device 
User Fee Amendments of 2017.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

 MDUFA Performance Goals and Procedures, Fiscal Years 2018 Through 2022


                                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 2017, 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 PMA applications and 
     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.
       FDA will be reporting total time performance quarterly as 
     described in Section VI. FDA and industry will participate in 
     the independent assessment of progress toward this outcome, 
     as described in Section V below. As appropriate, key findings 
     and recommendations from this assessment will be implemented 
     by FDA.
     A. PMA
       FDA will report on an annual basis the average Total Time 
     to Decision as defined in Section VII.H for the three most 
     recent closed receipt cohorts.
       For Original PMA and Panel Track Supplement submissions 
     received in Fiscal Years 2016 through 2018, the average Total 
     Time to Decision goal for FDA and industry is 320 calendar 
     days.
       For Original PMA and Panel Track Supplement submissions 
     received in Fiscal Years 2017 through 2019, the average Total 
     Time to Decision goal for FDA and industry is 315 calendar 
     days.
       For Original PMA and Panel Track Supplement submissions 
     received in Fiscal Years 2018 through 2020, the average Total 
     Time to Decision goal for FDA and industry is 310 calendar 
     days.
       For Original PMA and Panel Track Supplement submissions 
     received in Fiscal Years 2019 through 2021, the average Total 
     Time to Decision goal for FDA and industry is 300 calendar 
     days.
       For Original PMA and Panel Track Supplement submissions 
     received in Fiscal Years 2020 through 2022, the average Total 
     Time to Decision goal for FDA and industry is 290 calendar 
     days.
     B. 510(k)
       FDA will report on an annual basis the average Total Time 
     to Decision as defined in Section VII.H for the most recent 
     closed receipt cohort.
       For 510(k) submissions received beginning in Fiscal Year 
     2018, the average Total Time to Decision goal for FDA and 
     industry is 124 calendar days.
       For 510(k) submissions received beginning in Fiscal Year 
     2019, the average Total Time to Decision goal for FDA and 
     industry is 120 calendar days.
       For 510(k) submissions received beginning in Fiscal Year 
     2020, the average Total Time to Decision goal for FDA and 
     industry is 116 calendar days.
       For 510(k) submissions received beginning in Fiscal Year 
     2021, the average Total Time to Decision goal for FDA and 
     industry is 112 calendar days.
       For 510(k) submissions received beginning in Fiscal Year 
     2022, the average Total Time to Decision goal for FDA and 
     industry is 108 calendar days.


II. REVIEW PERFORMANCE GOALS--FISCAL YEARS 2018 THROUGH 2022 AS APPLIED 
                           TO RECEIPT 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 on Medical Device 
     Submissions: The Pre-Submission Program and Meetings with FDA 
     Staff'' 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 VII.F below and an acceptance checklist in published 
     guidance. This communication consists of a fax, email, or 
     other 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 branch chief 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, an FDA manager will contact the 
     applicant to resolve scheduling issues by the 40th day.
       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 at least 1,530 Pre-
     Submissions received in FY 2018, at least 1,645 Pre-
     Submissions received in FY 2019, at least 1,765 Pre-
     Submissions received in FY 2020, at least 1,880 Pre-
     Submissions received in FY 2021, and at least 1,950 Pre-
     Submissions received in FY 2022. FDA will provide such timely 
     written feedback for additional Pre-Submissions as resources 
     permit, but not to the detriment of meeting the quantitative 
     review timelines and statutory obligations. Written feedback 
     will be provided to the applicant by email or fax and 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 provided by 
     email or fax will be considered the final written feedback to 
     the Pre-Submission.
       Meetings and teleconferences related to Pre-Submission will 
     normally be limited to 1 hour unless the applicant justifies 
     in writing the need for additional time. FDA may extend the 
     time for such meetings and/or teleconferences.
       Applicants will be responsible for developing draft minutes 
     for a Pre-Submission meeting or teleconference, and provide 
     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

[[Page 12517]]

     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 and other 
     information in the future submission 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 October 1, 2018, the Agency will update the Guidance on 
     ``Requests for Feedback on Medical Device Submissions: The 
     Pre-Submission Program and Meetings with FDA Staff'' to 
     include: additional information to assist applicants in 
     determining the need for a Pre-Submission, an enhanced Pre-
     Submission acceptance checklist, examples of frequently asked 
     Pre-Submission questions that lend themselves to productive 
     Pre-Submission interactions, and edits to reflect the revised 
     process outlined above. FDA will provide an opportunity for 
     the public to comment on the updated guidance. No later than 
     12 months after the close of the public comment period, the 
     Agency will issue a final guidance. FDA will implement this 
     guidance once final.
     B. Original Premarket Approval (PMA), Panel-Track 
         Supplements, and Premarket Report Applications
       The performance goals in this section apply to all Original 
     Premarket Approval, Panel-Track Supplements, and Premarket 
     Report Applications, including those that are accepted for 
     priority review (previously referred to as expedited).
       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 fax, email, or other 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 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. All deficiency letters will 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. All 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.
       For submissions that do not require Advisory Committee 
     input, FDA will issue a MDUFA decision within 180 FDA Days 
     for 90% of submissions.
       For submissions that require Advisory Committee input, FDA 
     will issue a MDUFA decision within 320 FDA Days from receipt 
     of the accepted submission 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 2022, it is acceptable to combine such 
     submissions in the prior year to form a cohort of 10 or more 
     submissions: in such cases, FDA will be held to the FY2022 
     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 VI.
     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 Submissions
       FDA will issue draft and final guidance that includes a 
     submission checklist to facilitate a more efficient and 
     timely review process.
       Deficiencies identified will be based upon a complete 
     review of the submission and will include all deficiencies. 
     All deficiency letters will 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. All 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.
       FDA will issue a MDUFA decision within 150 FDA days of 
     receipt of the submission for: 50% of de novo requests 
     received in FY 2018; 55% of de novo requests received in FY 
     2019; 60% of de novo requests received in FY 2020; 65% of de 
     novo requests received in FY 2021 and 70% of de novo requests 
     received in FY 2022. At Industry'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

[[Page 12518]]

     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.
       This communication includes a fax, email, or other 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.
       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. All deficiency letters will 
     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. All 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.
       FDA will issue a MDUFA decision for 95% of 510(k) 
     submissions within 90 FDA Days. 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 
     FDA Day goal will be provided as part of FDA's Performance 
     Reports, as described in Section VI.
     G. CLIA Waiver by Application
       FDA will engage in a Substantive Interaction with the 
     applicant within 90 days for 90% of the 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.
       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 VI.
       In addition, FDA will:
       1. Hold CLIA Waiver Vendor Days, with the first to occur 
     before the end of FY2018.
       2. Permit discussion of both 510(k) and CLIA waiver process 
     in Pre-Submissions.
       3. Specifically permit discussion of appropriate reference/
     comparator for both 510(k) and CLIA waiver submissions in 
     Pre-Submissions.
       4. Provide a status report on completion and issuance of 
     revisions to Section V of the Guidance on ``Recommendations 
     for CLIA Waiver Applications'' to include appropriate use of 
     comparable performance between a waived user and moderately 
     complex laboratory user to demonstrate accuracy.
     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. Infrastructure

     A. Quality Management
       The Agency will establish a dedicated Quality Management 
     (QM) Unit that reports directly to the CDRH Director or 
     Deputy Director and establish a quality management framework 
     for the premarket submission process in CDRH. The Framework 
     will include infrastructure, senior management 
     responsibility, resource management, lifecycle management, 
     and quality management system evaluation.
       At least once per year, the Agency will discuss with 
     industry the specific areas it intends to incorporate in its 
     ongoing audit plan. FDA will identify, with industry input, 
     areas to audit, which will include the effectiveness of 
     CDRH's Corrective and Preventive Action (CAPA) process. FDA 
     will expand the scope of its annual audits as it implements 
     and builds up its auditing capability. As part of these 
     ongoing audits, high-performing premarket review processes 
     utilized in one division will be identified and shared 
     accordingly with other divisions to improve efficiencies and 
     effectiveness. At a minimum, FDA audits in the following 
     areas will be completed by the end of FY 2020: Deficiency 
     Letters and Pre-Submissions. Additional audits in the 
     following areas will be completed by the end of FY 2022: 
     Submission Issue Meetings, Interactive Review, Withdrawals 
     and Special 510(k) conversions.
       The effectiveness of the QM framework will be evaluated in 
     Phase 2 of the Independent Assessment (see Section V).
     B. Scientific and Regulatory Review Capacity
       The Agency will apply user fee revenues to reduce the ratio 
     of review staff to front line supervisors in the premarket 
     review program to improve consistency. The Agency will also 
     apply user fee revenues to enhance and supplement scientific 
     review capacity by hiring device application reviewers as 
     well as leveraging external experts needed to assist with the 
     review of device applications.
       To ensure such additional positions are filled by qualified 
     experts, the Agency will apply user fee revenues to 
     recruitment and hiring. The Agency will apply user fee 
     revenues to retain high-performing supervisors in the 
     premarket review program.
       CDRH intends to enter into an Inter-Agency Agreement (IAA) 
     with the Office of Personnel Management (OPM) to provide 
     supplemental recruitment and staffing support throughout 
     MDUFA IV to augment existing FDA Human Resources services.
     C. IT Infrastructure for Submission Management
       FDA will enhance IT infrastructure that will allow FDA to 
     perform quality management audits and review consistency.
       FDA will implement a new information management system that 
     provides an industry dashboard that displays near real-time 
     submission status.

[[Page 12519]]

       FDA will 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. By FY 2020, the Agency will issue a draft 
     guidance document on the use of the electronic submission 
     templates. FDA will provide an opportunity for public comment 
     on the guidance. No later than 12 months after the close of 
     the public comment period, the Agency will issue a final 
     guidance. FDA will implement the guidance once final. In 
     addition, the Agency will update the Guidance ``eCopy Program 
     for Medical Device Submissions'' to reflect the respective 
     changes to the technical standards and specifications.
       FDA will link pre-submissions with subsequent premarket 
     submissions when identified by the applicant.
     D. Training
       FDA will continue to improve training for new and existing 
     reviewers under this agreement. FDA will achieve Kirkpatrick 
     Level 3 for curriculum-based premarket training through 
     assessment of work performance behavior change and evaluate 
     the effectiveness of the impact of curriculum-based premarket 
     training activities on relevant premarket program metrics and 
     goals (Kirkpatrick Level 4) by the end of FY 2020. FDA 
     training efforts will also be closely coordinated with the 
     Quality Management Unit described in item III.A above to 
     provide more targeted and personalized training to staff.
     E. Time Reporting
       FDA will implement complete time reporting by the end of 
     MDUFA IV such that data from time reporting can be used to 
     conduct workload analysis and capacity planning.
     F. Fee Setting, Fee Collections, and Workload
       FDA will seek authority to eliminate the fifth-year offset 
     provision and to maintain and use any and all fee 
     collections, including collections over the statutory total 
     revenue targets.
       If the collections are in excess of the resources needed to 
     meet performance goals given the workload, or in excess of 
     inflation-adjusted statutory revenue targets, FDA and 
     industry will work together to assess how best to utilize 
     those resources to improve performance on submission types 
     with performance goals and/or quality management programs, 
     using, as input for the discussion: workload information, 
     performance objectives and ongoing reported performance.


                        IV. 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 guidance document, ``Interactive Review for Medical 
     Device Submissions: 510(k)s, Original PMAs, PMA Supplements, 
     Original BLAs, and BLA Supplements,'' both FDA and industry 
     believe that an interactive review process for these types of 
     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 October 1, 2017, the Agency will publish a level 2 
     update to the final guidance ``Suggested Format for 
     Developing and Responding to Deficiencies in Accordance with 
     the Least Burdensome Provisions of FDAMA; Final Guidance for 
     Industry and FDA Staff'' to reflect the following:
       All deficiency letters will 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. All 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). Any additional best practices identified by 
     quality audits and/or the Independent Assessment will be 
     incorporated in updates to the guidance, as appropriate.
       FDA will train staff and managers on this process 
     improvement and the updated guidance.
     C. Device Accessories
       FDA and Industry will explore additional mechanisms for a 
     streamlined, resource minimal pathway to reclassify 
     accessories previously classified as class III devices as a 
     part of a PMA review if they meet the requirements of a low 
     or moderate risk device.
     D. Enhanced Use of Consensus Standards
       FDA will establish an Accreditation Scheme for Conformity 
     Assessment (ASCA) Program using FDA-recognized consensus 
     standards. FDA will define the `scheme' and oversee the 
     Conformity Assessment (CA) model and ensure that there is 
     appropriate interaction with parties that serve as 
     Accrediting Bodies (ABs) to accredit test laboratories (TLs). 
     When a device type using the `scheme' is evaluated according 
     to a specific recognized standard by an accredited TL, FDA 
     intends to rely on the results from the accredited TL for the 
     purpose of premarket review (i.e., generally accept a 
     determination that a device conforms with the standard) 
     without the need to address further questions related to 
     standards conformance. Assuming that it meets established 
     criteria as outlined in the ASCA program, a device company's 
     internal TL will be eligible to participate in the ASCA 
     program. FDA will not review reports from accredited TLs 
     except as part of a periodic quality audit or if FDA becomes 
     aware of new information materially relevant to safety and/or 
     effectiveness.
       Specific actions that FDA will undertake include the 
     following:
       1. Conduct a Public Workshop by the end of FY 2018 to 
     discuss objectives for the establishment of ABs and TLs. 
     Discussion would include areas (specific FDA-recognized 
     consensus standards) where the ASCA Program can be piloted to 
     maximize initial impact of existing CA activities and 
     potential new areas.
       2. Hold educational sessions with stakeholders by the end 
     of FY 2018 about the purpose of the ASCA Program
       3. Develop and initiate the pilot of the ASCA program with 
     stakeholder input by the end of FY 2020.
       a. FDA intends to pilot inclusion of recognized standards 
     of public health significance where specific pass/fail 
     criteria are part of the standard
       4. Develop an internal IT system to track CA activities of 
     the ASCA Program
       5. Establish a process for accreditation of ABs and TLs. 
     FDA will issue draft guidance by the end of FY 2019 and issue 
     final guidance within 12 months post initiation of the pilot.
       a. In limited circumstances, the FDA may directly accredit 
     third-party TLs. For example, FDA could directly accredit 
     third party TLs, if FDA has not identified and recognized an 
     AB within 2 years after establishing the tenets of the ASCA 
     program.
       6. Establish a process for reaccreditation and the 
     suspension or withdrawal of accreditation of poor performing 
     ABs and TLs. FDA will issue draft guidance by the end of FY 
     2019 and final guidance within 12 months post initiation of 
     the pilot.
       7. Establish a publicly-accessible website listing TLs 
     accredited by ASCA and the FDA-recognized consensus 
     standard(s) for which they are accredited
       8. FDA, in consultation with stakeholders, will identify 
     appropriate recognized consensus standards for consideration 
     as part of the pilot as the specific focus for ASCA.
       a. By the end of FY 2022: FDA will have piloted, and 
     provided a report on the viability of, an ASCA program which 
     utilizes the schema identified in guidance to include 
     utilization of 5 appropriate cross-cutting/horizontal and/or 
     device-specific areas, at least one of which will be device-
     specific.
       b. Standards included as part of the ASCA Program will need 
     to have well established endpoints/acceptance criteria built 
     into the standard to allow effective tracking of TL 
     competence.
       FDA will provide an annual report on the progress of the 
     ASCA program.
       FDA will work with stakeholders for further input on 
     programmatic improvements and/or consideration for expansion.
     E. Third Party Review
       The Agency will take the following actions to improve the 
     Third Party Review program with a goal of eliminating routine 
     re-review by FDA of Third Party reviews:
       1. Strengthen the process for accreditation of Third 
     Parties.
       a. 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.
       b. When FDA's expectations for a particular device type 
     change, FDA will have in place a process to convey this 
     information to the Third Parties and to industry.
       2. By the end of FY 2018, establish a plan for eliminating 
     routine re-review by FDA of Third Party reviews and implement 
     plan within 12 months.
       3. Implement a program to audit reviews conducted by 
     accredited Third Parties.
       a. Provide tailored re-training to accredited Third Parties 
     based on the results of audits.
       4. By the end of FY 2018, issue draft guidance outlining 
     criteria for reaccreditation of 3rd Parties and the 
     suspension or withdrawal of accreditation of a Third Party. 
     FDA will issue final guidance within 12 months of the 
     conclusion of the public comment period.
       5. Publish performance of individual accredited Third 
     Parties with at least five completed submissions on the web 
     (e.g., rate of NSE, average number of holds, average time to 
     SE).

[[Page 12520]]


       6. Require the independent assessment of the Third Party 
     Review Program to evaluate efficiency including the 
     circumstances when FDA re-reviews were conducted; and to 
     suggest process improvements.
       The Agency will seek greater authority to tailor the 
     program. Specifically, FDA intends to expand the scope of the 
     program to some product codes that require clinical data and 
     to remove product codes from eligibility when appropriate, 
     such as if/when safety signals arise.
       As resources permit, FDA will identify pilot device areas 
     to be the specific focus of an effort where FDA would work 
     with willing industry partners to ensure that information 
     allowing for high quality Third Party reviews could be made 
     available to provide a proof of concept in certain device 
     areas and enable the development of a broader successful 
     program.
     F. Patient Engagement & the Science of Patient Input
       The Agency will take the following actions to advance 
     patient input and involvement in the regulatory process. 
     Where appropriate, the Agency will leverage public private 
     partnerships (PPPs) to advance these actions.
       1. Develop clinical, statistical, and other scientific 
     expertise and staff capacity to respond to submissions 
     containing applicant-proposed use of publicly available and 
     validated, voluntary patient preference information (PPI) or 
     voluntary patient reported outcomes (PROs). These staff will 
     provide submission review and early consultation/advice to 
     industry during study planning.
       2. By the end of FY 2020, hold one or more public meetings 
     to discuss the topics below and publish the findings and next 
     steps.
       a. Discuss approaches for incorporating PPI and PRO as 
     evidence in device submissions, as well as other ways of 
     advancing patient engagement;
       b. Discuss ways to use patient input to inform clinical 
     study design and conduct, with a goal of reducing barriers to 
     patient participation and facilitating recruitment and 
     retention;
       c. Public meetings should include specific examples and 
     case histories for PPIs and PROs to ensure clarity and 
     understanding by workshop attendees; and
       d. Identify priority areas where decisions are preference-
     sensitive and PPI data can inform regulatory decision-making, 
     in order to advance design and conduct of patient preference 
     studies in high impact areas. Publish the priority areas in 
     the Federal Register for public comment following the public 
     meeting.
       3. FDA will undertake several activities to improve the 
     regulatory predictability and impact of PROs, including:
       a. Clarify to device review divisions that use of PROs is 
     voluntary and may be one potential way of demonstrating 
     safety or effectiveness (or elements of either or both, such 
     as in a composite endpoint). Consistent with least burdensome 
     principles, applicants may use alternative approaches.
       b. Modify the guidance to outline a flexible framework for 
     PRO validation evidentiary thresholds. These thresholds may 
     vary depending on the particular regulatory use of the PRO.
       c. Work on developing a model for ``bridging studies'' to 
     make efficient use of existing validated PROs which may be 
     improved, or adapted to other subpopulations or other 
     regulatory uses in a more streamlined and expeditious manner 
     than creating novel PROs.
       4. The existing dispute resolution process should be used 
     in the event of disagreement between the applicant and the 
     Agency on the need for PPI or PRO.
     G. Emerging Diagnostics
       FDA will work with industry to continue the pilot for 
     emerging diagnostics started under MDUFA III.
     H. Real World Evidence (RWE)
       1. The Agency will use user fee revenue to support the 
     National Evaluation System for health Technology (NEST) by 
     providing funding for the NEST Coordinating Center and hiring 
     FDA staff with expertise in the use of RWE. The NEST 
     governing board will include no fewer than 4 representatives 
     of the trade associations that participated in the MDUFA IV 
     negotiations (AdvaMed, MDMA, MITA, and ACLA), with each 
     association appointing an individual to serve. Industry 
     representation on the NEST governing board will make up at 
     least 25% of the governing board membership. 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 NEST governing board or for any additional seats 
     allocated to Industry, the participating trade associations 
     will determine how to fill any vacant Industry positions. The 
     governing board also will include, but not be limited to, 
     representation from patient organizations. By the end of 
     FY2019, NEST will implement pilots for at least two product 
     codes (and related product codes), one of which will cover 
     devices approved through the PMA process and the other of 
     which will cover devices cleared through the 510(k) process. 
     The NEST Coordinating Center will seek ways in which to make 
     NEST financially self-sustaining so as not to rely on MDUFA 
     user fees in the long term unless FDA and Industry determine 
     continued user fee support is warranted and provides a 
     sufficient return on investment.
       2. FDA will contract with an organization to serve as the 
     NEST Coordinating Center to facilitate use of real world 
     evidence to support premarket activities. The contract will 
     specify actions the Coordinating Center will take to advance 
     the use of RWE, including:
       a. Establish a framework to fund pilot projects to 
     determine the usability of RWE for:
       i. Expanded indications for use
       ii. New clearances/approvals
       iii. Improved malfunction reporting
       b. No later than October 1, 2020, the Coordinating Center 
     will hold a public meeting to review and evaluate the 
     progress and outcomes (as of the date of the public meeting) 
     of the pilots described in (H)(1) above.
       c. The pilots will take place over a period of three years, 
     including data analysis and the Coordinating Center will 
     issue a publicly available report of the results.
       d. The pilots will include devices not currently subject to 
     a registry.
       e. At the conclusion of the pilots, an independent third-
     party will conduct an assessment to evaluate the strengths, 
     limitations, and appropriate use of RWE for informing 
     premarket decision-making for multiple device types.
       f. If warranted based on the results of the pilot(s) 
     described in (H)(1) above, FDA will revise its guidance on 
     the use of RWE to reflect what has been learned from the 
     pilots as to how RWE can be used to support:
       i. Expanded indications for use; and
       ii. New clearances/approvals.
       If supported by the pilot(s) described in (H)(1) above, the 
     guidance will include discussion of how devices not currently 
     subject to a registry can benefit from RWE.
       3. The Agency will establish criteria for streamlining MDR 
     requirements.
       a. For most, if not all, device procodes, FDA will permit 
     manufacturers of such devices in those procodes to report 
     malfunctions on a quarterly basis and in a summary MDR 
     format. FDA will publish the list of eligible device procodes 
     within 12 months of receiving a proposed list from Industry. 
     The list will include, among other device procodes, Class II 
     implantable and Class III devices, as appropriate, and will 
     reflect FDA's consideration of Industry's proposed list.
       b. FDA may determine that devices under a new procode in 
     existence for less than 2 years are not eligible for 
     reporting of malfunctions on a quarterly basis and in a 
     summary format.
       c. If a new type of malfunction occurs that the 
     manufacturer has not previously reported to FDA, the 
     manufacturer must submit an individual report. The 
     manufacturer will notify FDA when the issue has been 
     resolved, using current requirements per 21 C.F.R. 803, 806.
       d. FDA will maintain on its website the list of eligible 
     device procodes for which manufacturers are permitted to 
     report malfunctions on a quarterly basis and in a summary MDR 
     format.
       e. FDA will establish a mechanism at the time it publishes 
     the list of eligible devices under 3(a) that permits 
     stakeholders to request device procodes be added to the list.
       f. Nothing in this section precludes the Agency from 
     requiring individual malfunction reports from a specific 
     manufacturer and/or for a specific device if necessary to 
     protect public health. In these situations, FDA will notify 
     the manufacturer they are not eligible for quarterly summary 
     MDR reporting and provide an explanation for that decision 
     and the steps necessary to return to eligibility for 
     quarterly summary MDR reporting.
       4. FDA will not require postmarket surveillance studies 
     (i.e., 522 Studies) for devices for which registries and/or 
     other real world data (RWD) sources exist if FDA has access 
     to the information/data in the RWD source and has determined 
     that the information/data in the RWD source is sufficient to 
     take the place of a postmarket surveillance study.
     I. Digital Health
       The Agency will build expertise and streamline and align 
     FDA review processes with software lifecycles for Software as 
     a Medical Device (SaMD) and software inside of medical 
     devices (SiMD). Specifically, the Agency will:
       1. Establish a central digital health unit within CDRH's 
     Office of the Center Director to ensure proper coordination 
     and consistency across the Agency. The Agency will not 
     reorganize staff such that existing review staff would be 
     reassigned to the central digital health unit, while 
     retaining and not disrupting the existing digital health 
     talent within the reviewing divisions who have established, 
     long-term therapeutic and device expertise. The digital 
     health unit will perform, at a minimum, the following tasks:
       a. Develop software and digital health technical expertise 
     (``Technical Experts'') to provide assistance for premarket 
     submissions that include SaMD, SiMD, interoperable devices, 
     or otherwise incorporate novel digital health technologies.
       b. Utilize Technical Experts as appropriate or when 
     requested by the manufacturer for submissions that include 
     SaMD, SiMD, interoperable devices, or otherwise incorporate 
     novel digital health technologies; and

[[Page 12521]]

       c. Incorporate appropriate metrics for digital health 
     improvements to monitor, track, analyze and report the 
     results of digital health premarket review timelines.
       2. Publish final guidance addressing when to submit a 
     510(k) for a software modification to an existing device 
     within 18 months of the close of the comment period.
       3. Explore opportunities to establish premarket approval/
     clearance pathways tailored to SaMD, SiMD, and novel digital 
     health technologies that take into account real world 
     evidence while incorporating principles established through 
     international harmonization. To accomplish this task, the 
     Agency will:
       a. Engage with stakeholders, including industry, through 
     roundtables, informal meetings, and teleconferences;
       b. Hold a public workshop; and
       c. Revise existing and/or publish new relevant guidance 
     documents, including publishing a draft revised version of 
     the ``Guidance for the Content of Premarket Submissions for 
     Software Contained in Medical Devices'' (issued in 2005) by 
     the end of FY2019, and within 12 months of the close of the 
     comment period, publish the final revised version. The Agency 
     will incorporate applicable concepts from its Guidance for 
     ``Off-The-Shelf Software Used in Medical Devices.''
       4. Participate in international harmonization efforts 
     related to digital health, including work on developing SaMD 
     and other digital health convergence efforts through the 
     International Medical Device Regulators Forum (IMDRF).
     J. 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, 
     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.
     K. Total Product Life Cycle (TPLC)
       The establishment of CDRH's Office of In Vitro Diagnostic 
     Device Evaluation and Safety (now the Office of In Vitro 
     Diagnostics and Radiological Health (OIR)) has led to 
     improved consistency and predictability due to the enhanced 
     integration of premarket, postmarket, and compliance-related 
     activities and staff and improved information sharing among 
     staff. In addition, the successful development and evaluation 
     of medical devices depends on the integration of clinical 
     with scientific and engineering disciplines. CDRH will 
     explore transitioning to a similar TPLC model building in the 
     other device areas based on the lessons learned from its 
     experience with OIR and taking into account the Center's 
     mission, vision, strategic priorities, and development of a 
     patient-centric benefit-risk framework for regulatory and 
     non-regulatory decision making across the TPLC. Because an 
     essential element for the success of the Center's benefit-
     risk decision making framework and approach to device 
     regulation (particularly emerging and innovative 
     technologies) is the incorporation of the clinical context 
     and the impact of a decision on patient health and quality of 
     life, CDRH will take steps to increase and enhance the 
     integration of its clinicians into its TPLC activities, 
     amongst themselves, and with the Center's scientists and 
     engineers. Building on the success of considering and 
     incorporating additional expertise and viewpoints into our 
     decision-making, such as through the use of the Network of 
     Experts and the leveraging of patient perspectives, CDRH will 
     also explore ways in which to better learn from and leverage 
     the expertise of clinicians in other parts of the agency and 
     outside of the agency to inform its decision making, enhance 
     consistency, and assure a more holistic clinical perspective. 
     Clinicians involved in device-related activities will have 
     appropriate training on and make recommendations consistent 
     with applicable device statutory provisions, regulations, 
     guidances, and this Commitment Letter. In addition, CDRH will 
     provide managerial oversight of clinician recommendations and 
     device submission decisions, except for those devices subject 
     to CBER oversight.


         V. Independent Assessment of Review Process Management

       FDA and the industry will participate in a comprehensive 
     assessment of the process for the review of device 
     applications. The assessment will include consultation with 
     both FDA and industry. The assessment shall be conducted in 
     two phases 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.


                                Phase 1

       During the first phase, the contractor will complete an 
     evaluation of FDA's implementation of the corrective action 
     plan developed in response to recommendations from the MDUFA 
     III independent assessment.
       For Phase 1, FDA will award the contract by the end of 
     CY2017. The contractor will evaluate the implementation of 
     MDUFA III recommendations and publish a written assessment 
     within 1 year of contract award.


                                Phase 2

       During the second phase, the contractor will:
       1. Evaluate FDA's premarket review program to identify 
     efficiencies that should be realized as a result of the 
     process improvements and investments under MDUFA III and IV;
       2. Evaluate premarket review program infrastructure and 
     allocation of FTEs;
       3. Assess the alignment of resource needs with the training 
     and expertise of hires;
       4. Identify and share best practices across branches in ODE 
     and OIR;
       5. Assess the effectiveness of programs targeted for 
     improvement under this agreement, including the:
       a. Quality Management program,
       b. Proportion of deficiencies in which FDA references the 
     basis for the deficiency determination,
       c. Pre-Submission program (assess whether (a) CDRH is 
     providing guidance specific to the questions being asked; (b) 
     CDRH is using Pre-Submissions appropriately; and (c) CDRH and 
     Industry are adhering to the procedural aspects as set forth 
     in this agreement),
       d. Third Party Review program (assess efficiency of program 
     and suggest process improvements),
       e. Digital Health program,
       f. Patient Engagement program, and
       g. Real World Evidence program;
       6. Analyze conversions of Special 510(k)s to Traditional 
     510(k)s; and
       7. Assess other key areas identified by FDA and industry as 
     resources permit.
       For Phase 2 of the independent assessment, FDA will award 
     the contract no later than 3/31/2020. However, the contractor 
     would not begin the audit of deficiency letters and Pre-
     Submissions before 10/1/2020. The contractor will publish 
     comprehensive findings and recommendations within 1 year. 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 premarket review 
     program. 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.


                        VI. Performance Reports

       The Agency will report its progress toward meeting the 
     goals described in this letter, as follows. If, throughout 
     the course of MDUFA IV, 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 Division 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 3rd 
     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 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, upon 
     final guidance
       1.4. For Pre-Submissions, reporting will include:
       i. Number of all qualified Pre-Submissions received
       ii. Rate of submissions not accepted for review, upon final 
     guidance
       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:

[[Page 12522]]

       i. Number of original IDEs received
       ii. Average number of amendments prior to approval or 
     conditional approval of the IDE
       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 discretionary fee waivers or reductions 
     granted by type of submission
       3. In addition, the Agency will provide the following 
     information on an annual basis:
       3.1. Qualitative and quantitative update on how funding is 
     being used for the device review process, including the 
     percentage of review time devoted to direct review of 
     applications
       3.2. How funding is being used to enhance scientific review 
     capacity
       3.3. The number of Premarket Report Submissions received
       3.4. 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.
       3.5. Performance on the shared outcome goal for average 
     Total Time to decision
       3.6. 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
       3.7. For 510(k) submissions that go through a 3rd party, 
     reporting will include:
       i. Time from FDA receipt of third party report to FDA 
     decision at the 90% percentile
       ii. Once 3rd party program enhancements have been 
     implemented, resources saved as a result of enhancements to 
     the 3rd party review program.
       3.8. 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
       3.9. For De Novo requests, reporting will include:
       i. Number of submissions received
       ii. Average and number of days to Accept/Refuse to Accept, 
     upon final guidance
       3.10. 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
       3.11. Report on the ASCA program
       3.12. Data regarding the reduction in reviewer to manager 
     ratio.
       3.13. Report on implementation of deficiency performance 
     improvements.
       3.14. Report on quality management program
       3.15. Summary of quality system audits
       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 novos and non-LDT IVD de 
     novos completed within 150 FDA days
       Number and percentage of LDT PMAs and non-LDT IVD PMAs 
     completed within 180 FDA days
       FDA commits to treat LDTs no less favorably than other 
     devices to which MDUFA performance goals apply.
       On an annual basis, FDA and Industry will discuss the 
     return on investment, which may include process improvements, 
     improved performance, and other enhancements, under MDUFA IV.


               VII. 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 (FDCA);
       a premarket notification under section 510(k) of the FDCA;
       an application for investigational device exemption under 
     section 520(g) of the FDCA;
       a Pre-Submission;
       a de novo request (evaluation of automatic class III 
     designation) under section 513(f)(2) of the FDCA;
       a CLIA Waiver by application.
     B. Electronic Copy (e-Copy)
       An electronic copy is an exact duplicate of a submission, 
     created and submitted on a CD, DVD, or in another electronic 
     media format that FDA has agreed to accept, accompanied by a 
     copy of the signed cover letter and the complete original 
     paper submission. An electronic copy is not considered to be 
     an electronic submission.
     C. Electronic submission template
       An electronic submission template, or eSubmission template, 
     is a guided submission preparation tool for industry. Similar 
     to an online form, the eSubmission template walks industry 
     through the relevant contents and components for the 
     respective premarket submission type and device in order to 
     facilitate submission preparation and enhance consistency, 
     quality, and efficiency in the premarket review process.
     D. 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 classification 
     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 filed (PMA).
     E. MDUFA Decisions
       Original PMAs: Decisions for Original PMAs are Approval, 
     Approvable, Approvable Pending GMP Inspection, Not 
     Approvable, withdrawal, and Denial.
       180-Day PMA Supplements: Decisions for 180-Day PMA 
     Supplements include Approval, Approvable, and Not Approvable.
       Real-Time PMA Supplements: Decisions for Real-Time PMA 
     supplements include 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 Program Hold 
     will be removed from the MDUFA cohort.
     F. Pre-Submission
       A Pre-Submission includes a formal written request from an 
     applicant for feedback from FDA which is provided in the form 
     of a formal written response or, if the manufacturer chooses, 
     a meeting or teleconference in which the feedback is 
     documented in meeting minutes. A Pre-Submission meeting is a 
     meeting or teleconference in which FDA provides its 
     substantive feedback on the Pre-Submission.
       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 IDE 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 application 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).
       General information requests initiated through the Division 
     of Industry and Consumer Education (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

[[Page 12523]]

     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 to use an 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.
     G. Substantive Interaction
       Substantive Interaction is an email, letter, 
     teleconference, video conference, fax, 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.
     H. Total Time to Decision
       Total Time to Decision is the number of calendar days from 
     the date of receipt of an accepted or filed submission to a 
     MDUFA decision.
       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 closed cohort, excluding the 
     highest 2% and the lowest 2% of values. A cohort is closed 
     when 99% of the accepted submissions have reached a decision.
       The average Total Time to Decision for PMA applications is 
     calculated as the three-year rolling average of the annual 
     Total Times to Decision for applications (for example, for 
     FY2018, the average Total Time to Decision for PMA 
     applications would be the average of FY2016 through FY2018) 
     within a closed cohort, excluding the highest 5% and the 
     lowest 5% of values. A cohort is closed when 95% of the 
     applications have reached a decision.
     I. Accreditation Scheme for Conformity Assessment
       Conformity Assessment is the demonstration that specified 
     requirements relating to a product, process, system, person 
     or body are fulfilled.
       Accreditation is the formal recognition by an independent 
     body, generally known as an accreditation body, that an 
     organization is competent to carry out specific conformity 
     assessment activities. Accreditation is not obligatory but it 
     adds another level of confidence, as `accredited' means the 
     organization has been independently checked to make sure it 
     operates according to international standards.
       A conformity assessment scheme is a system for assessing 
     the conformity of specified objects (e.g., medical devices or 
     management processes) to one or more consensus standards. The 
     system specifies the applicable standards as well as the 
     rules, procedures, and management requirements for carrying 
     out the conformity assessment to meet a regulatory need. 
     Informally, such a scheme may be referred to as an 
     accreditation scheme.
       Testing laboratory is an organization that possesses the 
     necessary technical competence and capabilities to conduct 
     testing to making a determination that one or more 
     characteristics of an object are in conformance with a set of 
     predefined requirements.
     J. 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.
  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record a copy of the commitment letter for the Prescription Drug 
User Fee Act, PDUFA, reauthorization for fiscal years 2018 to 2022, 
known as PDUFA VI.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

  PDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROCEDURES FISCAL YEARS 
                           2018 THROUGH 2022

       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. First Cycle Review Management
       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
       I. Enhancing Regulatory Science And Expediting Drug 
     Development
       J. Enhancing Regulatory Decision Tools To Support Drug 
     Development And Review
       K. Enhancement And Modernization Of The FDA Drug Safety 
     System
       II. Enhancing Management of User Fee Resources
       A. Resource Capacity Planning And Modernized Time Reporting
       B. Financial Transparency And Efficiency
       III. Improving FDA Hiring and Retention of Review Staff
       A. Completion Of Modernization Of The Hiring System 
     Infrastructure And Augmentation Of System Capacity
       B. Augmentation Of Hiring Staff Capacity And Capability
       C. Complete Establishment Of A Dedicated Function To Ensure 
     Needed Scientific Staffing For Medical Product Review
       D. Set Clear Goals For Drug Review Program Hiring
       E. Comprehensive And Continuous Assessment Of Hiring And 
     Retention
       IV. Information Technology Goals
       A. Objective
       B. Improve The Predictability And Consistency Of PDUFA 
     Electronic Submission Processes
       C. Enhance Transparency And Accountability Of FDA 
     Electronic Submission And Data Standards Activities
       V. Improving FDA Performance Management
       VI. Progress Reporting for PDUFA VI and Continuing PDUFA V 
     Initiatives
       VII. Definitions and Explanation of Terms

  PDUFA REAUTHORIZATION PERFORMANCE GOALS AND PROCEDURES FISCAL YEARS 
                           2018 THROUGH 2022

       This document contains the performance goals and procedures 
     for the Prescription Drug User Fee Act (PDUFA) 
     reauthorization for fiscal years (FYs) 2018-2022, known as 
     PDUFA VI. 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

[[Page 12524]]

     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 VI. 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 
     supplement 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 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.--ORIGINAL AND RESUBMITTED APPLICATIONS AND SUPPLEMENTS
------------------------------------------------------------------------
        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, 2017, through September 30, 2022. 
     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 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

[[Page 12525]]

     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.
       Expedited Reviews. In certain cases, an application 
     reviewed in the Program will be for a product that the FDA 
     review team identifies as meeting an important public health 
     need. If the FDA review team determines that a first-cycle 
     approval is likely for such an application, the 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. Expedited reviews are typically characterized by 
     frequent contact between the applicant and the FDA review 
     team throughout the review process. Any parameters of the 
     Program that are intended to facilitate expedited reviews are 
     noted throughout Section I.B.
       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 
     standard approach to the review of priority NME NDAs and 
     original BLAs (as described in this section), and will inform 
     the applicant accordingly.
       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.
       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 Section 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.
       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 
     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 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 regarding risk management, 
     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.
       b. 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:

[[Page 12526]]

       i. 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.
       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 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 and brief 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 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. First Cycle Review Management
       FDA and industry share a commitment to ensuring an 
     efficient and effective first cycle review process for all 
     applications subject to the PDUFA program. This commitment 
     was first articulated in the GRMP guidance finalized in 2005. 
     FDA will update this guidance in PDUFA VI to include review 
     activities (e.g., the NME Program, REMS) that have been added 
     to the human drug review program since the guidance was 
     finalized, principles regarding notification to applicants 
     regarding issues identified during FDA's initial review of 
     the application, principles regarding FDA's notification to 
     applicants regarding planned review timelines, and the 
     importance of internal review timelines that govern aspects 
     of the human drug review program that are not part of PDUFA 
     performance goals. FDA will publish a revised draft guidance 
     for public comment no later than the end of FY 2018.
     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 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. 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).
       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 NDA/BLA proprietary name submissions filed 
     within 90 days of receipt. Notify sponsor 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 (IND phase after end-of-phase 2) 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 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.
     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 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

[[Page 12527]]

     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.
     H. Meeting Management Goals
       Formal PDUFA meetings between sponsors and FDA consist of 
     Type A, B, B(EOP), and C meetings. 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 other type of meeting.
       1. 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
------------------------------------------------------------------------

       i. For any type of meeting, the sponsor may request a 
     written response to its questions rather than a face-to-face 
     meeting, videoconference or teleconference. FDA will review 
     the request and make a determination on whether a written 
     response is appropriate or whether a face-to-face meeting, 
     videoconference, or teleconference 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 and Type C 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.
       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.
       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. 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 Written
             Meeting Type                         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
------------------------------------------------------------------------

       b. Performance goal: 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.
       3. 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.

                                 TABLE 5
------------------------------------------------------------------------
             Meeting Type                 Receipt of Background 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*
------------------------------------------------------------------------
*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.

       4. 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) and C meetings.
       b. Performance goal: 90% of preliminary responses to 
     questions for Type B(EOP) meetings are issued by FDA no later 
     than five calendar days before the meeting date.
       5. 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) 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.
       6. Meeting Minutes
       a. Procedure: The Agency will prepare minutes that 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 required if the Agency 
     transmits a written response for any meeting type.
       b. Performance goal: 90% of minutes are issued within 30 
     calendar days of the date of the meeting.
       7. 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 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.
       8. Guidance
       FDA will publish revised draft guidance on formal meetings 
     between FDA and sponsors no later than September 30, 2018.
     I. Enhancing Regulatory Science and Expediting Drug 
         Development
       To ensure that new and innovative products are developed 
     and available to patients

[[Page 12528]]

     in a timely manner, FDA will build on the success of the 
     FDA's regulatory science program that included advancing the 
     science of meta-analysis methodologies, advancing 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, establishing 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.
       To continue to enhance timely interactive communication 
     with sponsors during drug development in PDUFA VI, FDA will 
     do the following:
       a. Independent Assessment. FDA will contract with an 
     independent third party to assess current practices of FDA 
     and sponsors in communicating during drug development. 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. Due to the significant volume of FDA-
     sponsor interactions in a given year, the assessment will be 
     based on a random subset of drug development programs 
     identified by IND number. The third party will identify best 
     practices and areas for improvement in communication by FDA 
     review staff and sponsors. FDA will publish the final report 
     of the assessment on FDA's website no later than the end of 
     FY 2020.
       b. Public Workshop. FDA will convene a public workshop by 
     the end of March 2021 to discuss the findings of the 
     independent assessment, including anonymized, aggregated 
     feedback from sponsors and FDA review teams resulting from 
     the contractor interviews.
       c. Guidance. FDA will consider the third party's 
     recommendations for best practices in communication and 
     update the current draft or final guidance on ``Best 
     Practices for Communication Between IND Sponsors and FDA 
     During Drug Development'' if appropriate. If FDA determines 
     that the guidance should be updated, based on the 
     recommendations of the third party and the feedback received 
     from the public workshop, FDA will update the guidance no 
     later than one year following the public workshop.
       2. Ensuring Sustained Success of Breakthrough Therapy 
     Program
       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. Additional resources will 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.H 
     of this document will apply.
       4. Advancing Development of Drugs for Rare Diseases
       FDA will build on the success of the Rare Disease Program 
     (RDP) 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 Disease Program staff in CDER will 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 RDP 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 RDP staff as 
     members of the core review team to help ensure consistency of 
     scientific and regulatory approaches across applications and 
     review teams.
       RDP staff will continue to engage in outreach to industry, 
     patient groups, and other stakeholders to provide training on 
     FDA's RDP. 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 RDP 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 RDP staff 
     participated as core team members, and metrics related to

[[Page 12529]]

     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.
       5. Advancing Development of Drug-Device and Biologic-Device 
     Combination Products Regulated by CBER and CDER
       a. FDA will develop staff capacity and capability across 
     the medical product centers and the Office of Combination 
     Products (OCP) to more efficiently, effectively, and 
     consistently review and respond to submissions that include 
     combination products. These staff will advance the 
     development of combination products by providing combination 
     product expertise as part of the core review team as 
     applicable, and through promoting best practices for review 
     of combination products. The additional capacity will include 
     staff who will focus on review of cGMP, engineering aspects, 
     human factors and bridging study protocols and study reports, 
     and labeling, to include instructions-for-use materials.
       b. FDA will streamline the process for combination product 
     review and improve the Agency's ability to assess workload 
     and allocate resources to the review of combination products.
       i. By no later than December 31, 2017, FDA will complete a 
     lean process mapping for combination product review in order 
     to inform changes to review work flow to improve the inter-
     center consultation process.
       ii. By no later than December 31, 2017, FDA will begin 
     tracking workload and timelines for cross-center 
     consultations to enable appropriate allocation of resources 
     and regularly assess the progress of combination product 
     review throughout PDUFA VI.
       iii. By no later than September 30, 2018, for each 
     component within FDA that is consulted to participate in 
     review of combination products, FDA will outline in 
     appropriate internal documents the Agency's process for 
     resolving internally any scientific or regulatory issues that 
     arise, as well as a commitment for the medical product 
     centers and OCP to coordinate and complete reviews and 
     related activities when consulted in timelines set forth by 
     PDUFA and other published documents (e.g., the GRMP guidance 
     and GRMP MAPP).
       c. FDA will establish Manuals of Policies and Procedures 
     (MAPPs) and Standard Operating Policy and Procedures (SOPPs) 
     to promote efficient, effective, and consistent combination 
     product development and review. The documents will describe 
     processes and procedures for conducting review of combination 
     products, including the expectations for consultation of 
     internal experts outside the reviewing Center. FDA will 
     describe the responsibilities of staff in each Center and 
     Office, expectations for core review team members and for 
     other consultant staff in activities and meetings related to 
     the combination product development program and application 
     review. FDA will define the key terms to be used by staff in 
     review of combination products to foster clear communication 
     within FDA and to regulated industry. The topic areas and 
     expected completion dates of these documents are specified 
     below:
       i. Human Factors Assessments (March 31, 2019)
       ii. Quality assessment of combination products, including 
     coordination of facility inspections (September 30, 2019)
       iii. Patient-oriented labeling, including instructions-for-
     use materials for those drug-device and biologic-device 
     combination products regulated by CBER and CDER (September 
     30, 2019)
       d. By no later than December 31, 2018, FDA will make 
     available on FDA's website key points of contact in OCP and 
     the medical product centers for combination product review. 
     FDA agrees to maintain and update this information 
     periodically.
       e. FDA will establish submission procedures for Human 
     Factors protocols no later than September 30, 2018. Beginning 
     in FY 2019, FDA will establish timelines to review and 
     provide comment on the protocols for Human Factors studies of 
     combination drug-device and biologic-device products within 
     60 days.
       i. Procedure for review of human factors protocols for 
     combination products: Upon specific request by a sponsor 
     (including specific questions that the sponsor desires to be 
     answered) consistent with the steps below, the Agency will 
     evaluate human factors protocols and issues to assess whether 
     the design is adequate to meet scientific and regulatory 
     requirements identified by the sponsor.
       (1) The sponsor should submit a limited number of specific 
     questions about the human factors protocol design and 
     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).
       (2) 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.
       (3) Performance goals for FDA will be phased in, starting 
     in FY 2019 as follows:
       a. By FY 2019, review 50% of human factors protocol 
     submissions within 60 days and provide sponsor with written 
     comments.
       b. By FY 2020, review 70% of human factors protocol 
     submissions within 60 days and provide sponsor with written 
     comments.
       c. By FY 2021, review 90% of human factors protocol 
     submissions within 60 days and provide sponsor with written 
     comments.
       f. By no later than December 31, 2018, FDA will begin staff 
     training related to development, review, and approval of 
     drug-device and biologic-device combination products reviewed 
     in CDER and CBER. The training will be provided to all CDER, 
     CBER, Center for Devices and Radiological Health (CDRH), and 
     Office of Combination Products (OCP) staff, and will be part 
     of the reviewer training core curriculum. The key purposes of 
     this training include familiarizing review staff with the 
     regulatory requirements and challenges associated with 
     combination product applications and strategies to address 
     these challenges; promoting best practices for review and 
     regulation of combination products regulated by CDER and 
     CBER, and helping ensure coordination and consistent 
     approaches within the Centers in the review and regulation of 
     combination product applications. The training will also 
     emphasize the role of various experts in the Centers as 
     members of the review team and OCP's roles and 
     responsibilities in order to help ensure consistency of 
     scientific and regulatory approaches across applications and 
     review teams.
       g. FDA will contract with an independent third party to 
     assess current practices for combination drug product review. 
     This study will focus on areas where the needs for inter-
     center coordination and consistent approaches are greatest, 
     including such areas as the Request-for-Designation, cGMPs/
     facilities topics, human factors and bridging studies, and 
     labeling. The contractor will be expected to engage both FDA 
     staff and individual sponsors as part of the assessment. The 
     assessment will be based on a randomly selected subset of 
     combination products in various phases of development. The 
     assessment will identify best practices and areas for 
     improvement by FDA review staff and sponsors in the 
     submission and review of combination products for 
     consideration by both FDA and sponsors. FDA will publish the 
     final report of the assessment on FDA's website no later than 
     the end of FY 2020. FDA will consider the assessment findings 
     regarding best practices on the part of FDA review staff and 
     sponsors in any updates to relevant documents such as MAPPs, 
     SOPPs, and submission procedures for human factors protocols, 
     and in the review and submission of Combination Product 
     applications.
       h. By the end of FY 2019, FDA will publish draft guidance 
     or update previously published guidance issued by the medical 
     product centers and OCP for review staff and industry 
     describing considerations related to drug-device and 
     biologic-device combination product on the topics noted 
     below. The draft guidance(s) will be finalized by the end of 
     FY 2022.
       i. Bridging studies, including the bridging of data from 
     combination products that employ different device components 
     for the same drug or biologic and the same device component 
     across different drugs and biologics.
       ii. Patient-oriented labeling (e.g., instructions-for-use).
       6. Enhancing Use of Real World Evidence for Use in 
     Regulatory Decision-Making
       As we participate in the current data revolution, it is 
     important that FDA consider the possibilities of using so-
     called ``real world'' data as an important tool in evaluating 
     not only the safety of medications but also their 
     effectiveness. To accomplish this will require an 
     understanding of what questions to ask, including how such 
     data can be generated and used appropriately in product 
     evaluation, what the challenges are to appropriate generation 
     and use of these data, and how to address such challenges. 
     Towards this end, FDA will do the following:
       a. By no later than the end of FY 2018, FDA will complete 
     one or more public workshop(s) with key stakeholders, 
     including patients, biopharmaceutical companies, and 
     academia, to gather input into issues related to Real World 
     Evidence (RWE) use in regulatory decision-making. The 
     workshop(s) should address, among other things, the following 
     topics:
       Benefits to patients, regulators, and biopharmaceutical 
     companies of RWE in regulatory decision making;
       RWE availability, quality, and access challenges, and 
     approaches to mitigate these;
       Methodological approaches for the collection, analysis, and 
     communication of RWE; and
       Appropriate contexts of use of RWE in regulatory decision-
     making regarding effectiveness.

[[Page 12530]]

       b. By no later than the end of FY 2019, FDA will initiate 
     (or fund by contract), appropriate activities (e.g., pilot 
     studies or methodology development projects) aimed at 
     addressing key outstanding concerns and considerations in the 
     use of RWE for regulatory decision making.
       c. By no later than the end of FY 2021, considering 
     available input, such as from activities noted above, FDA 
     will publish draft guidance on how RWE can contribute to the 
     assessment of safety and effectiveness in regulatory 
     submissions, for example in the approval of new supplemental 
     indications and for the fulfillment of postmarketing 
     commitments and requirements. 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.
     J. Enhancing Regulatory Decision Tools to Support Drug 
         Development and Review
       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 VI:
       a. FDA will strengthen the staff capacity to facilitate 
     development and use of patient-focused methods to inform drug 
     development and regulatory decisions. This staff, composed 
     primarily of clinical, statistical, psychometric, and health 
     outcomes research expertise, will be integrated into review 
     teams as core members of the team during drug development and 
     application review where the sponsor intends to use patient 
     input or clinical outcome assessment (COAs) such as patient-
     reported outcomes (PROs) as part of the development program. 
     A core responsibility of the staff will be to engage patient 
     stakeholders and provide timely development-phase 
     consultations to sponsors developing new tools to collect 
     patient and caregiver input. This additional capacity is 
     expected to advance the science of COA development and 
     analysis, and the staff will also support the public 
     qualification activities for COAs.
       b. FDA will develop a series of guidance documents to focus 
     on approaches and methods to bridge from initial patient-
     focused drug development meetings, like those piloted under 
     PDUFA V, to fit-for-purpose tools to collect meaningful 
     patient and caregiver input for ultimate use in regulatory 
     decision making. Prior to the issuance of each guidance, as 
     part of the development, FDA will conduct a public workshop 
     to gather input from the wider community of patients, patient 
     advocates, academic researchers, expert practitioners, 
     industry, and other stakeholders.
       i. By the end of FY 2018, FDA will publish a draft guidance 
     describing approaches to collecting comprehensive and 
     representative patient and caregiver input on burden of 
     disease and current therapy. The guidance will address topics 
     including: standardized nomenclature and terminologies, 
     methods to collect meaningful patient input throughout the 
     drug development process, and methodological considerations 
     for data collection, reporting, management, and analysis.
       ii. By the end of FY 2019, FDA will publish a draft 
     guidance describing processes and methodological approaches 
     to development of holistic sets of impacts that are most 
     important to patients. The guidance will address topics 
     including: methods for sponsors, patient organizations, 
     academic researchers, and expert practitioners to develop and 
     identify what are most important to patients in terms of 
     burden of disease, burden of treatment, and other critical 
     aspects. The guidance will address how patient input can 
     inform drug development and review processes, and, as 
     appropriate, regulatory decision making.
       iii. By the end of FY 2020, FDA will publish a draft 
     guidance describing approaches to identifying and developing 
     measures for an identified set of impacts (e.g., burden of 
     disease and treatment), which may facilitate collection of 
     meaningful patient input in clinical trials. The guidance 
     will address methods to measure impacts in a meaningful way, 
     and identify an appropriate set of measure(s) that matter 
     most to patients.
       iv. By the end of FY 2021, FDA will publish a draft 
     guidance on clinical outcome assessments, which, when final, 
     will, as appropriate, revise or supplement the 2009 Guidance 
     to Industry on Patient-Reported Outcome Measures. The draft 
     guidance will also address technologies that may be used for 
     the collection, capture, storage, and analysis of patient 
     perspective information. The guidance will also address 
     methods to better incorporate clinical outcome assessments 
     into endpoints that are considered significantly robust for 
     regulatory decision-making.
       v. For each of the above, 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 on the draft 
     guidance.
       c. FDA will create and maintain a repository of publicly 
     available tools on FDA's website as a resource for 
     stakeholders. The repository will also include FDA's clinical 
     outcome assessment compendium, patient-focused drug 
     development meeting resources, and ongoing efforts on 
     patient-focused drug development.
       d. As appropriate, FDA will revise existing MAPPs and SOPPs 
     to include suggested approaches for incorporating an 
     increased patient focus in other on-going or planned FDA 
     public meetings (e.g., FDA scientific workshops). In 
     addition, as appropriate, FDA will develop and implement 
     staff training related to processes, tools, and methodologies 
     described in this section.
       e. By the end of FY 2019, FDA will conduct a public 
     workshop, through a qualified third party, with the primary 
     purpose of gathering ideas and experiences of the patient and 
     caregiver community and their recommendations on approaches 
     and best practices that would enhance patient engagement in 
     clinical trials. The meeting may also gather input from 
     sponsors, academic researchers, and expert practitioners. The 
     meeting will result in a published report on proceedings and 
     recommendations from discussions at the meeting.
       2. Enhancing Benefit-Risk Assessment in Regulatory 
     Decision-Making
       FDA will further the agency's implementation of structured 
     benefit-risk assessment, including the incorporation of the 
     patient's voice in drug development and decision-making, in 
     the human drug review program through the following 
     commitments to be accomplished during PDUFA VI:
       a. By March 31, 2018, FDA will publish an update to the 
     implementation plan titled ``Structured Approach to Benefit-
     Risk Assessment in Drug Regulatory Decision-Making.'' The 
     update will include a report on the progress made during 
     PDUFA V and a plan for continued implementation during FYs 
     2018-2022.
       b. By the end of FY 2019, FDA will convene and/or 
     participate in, at least one meeting, conducted through a 
     qualified third party, to gather industry, patient, 
     researcher, and other stakeholder input on key topics. This 
     would include applying the benefit-risk framework throughout 
     the human drug lifecycle, including best approaches to 
     communicating FDA's benefit-risk assessment.
       c. By the end of FY 2020, FDA will publish a draft guidance 
     on benefit-risk assessments for new drugs and biologics. This 
     guidance will:
       i. Articulate FDA's decision-making context and framework 
     for benefit-risk assessment, illustrating the application of 
     the benefit-risk framework throughout the human drug 
     lifecycle, using a case study approach, if appropriate.
       ii. Discuss appropriate interactions between a sponsor and 
     FDA during drug development to understand the therapeutic 
     context (i.e., the severity of disease that represents the 
     targeted indication and the extent of unmet medical need in 
     the target population) regarding regulatory decisions for the 
     product at the various stages of drug development and 
     evaluation.
       iii. Discuss appropriate approaches to communicate to the 
     public FDA's thinking on a product's benefit-risk assessment, 
     such as through product-specific discussions using the 
     benefit-risk framework at AC meetings.
       d. Beginning in FY 2021, FDA will conduct an evaluation of 
     the implementation of the benefit-risk framework in the human 
     drug review program. This evaluation will assess how 
     reviewers across the organization apply the benefit-risk 
     framework and identify best practices in use of the benefit-
     risk framework. The evaluation of the benefit-risk framework 
     implementation conducted in PDUFA V will serve as a baseline 
     for this PDUFA VI assessment.
       e. As appropriate, FDA will revise relevant MAPPs and SOPPs 
     to include new approaches that incorporate FDA's benefit-risk 
     framework into the human drug review program.
       3. Advancing Model-Informed Drug Development
       To facilitate the development and application of exposure-
     based, biological, and statistical models derived from 
     preclinical and clinical data sources, herein referred to as 
     ``model-informed drug development'' (MIDD) approaches, FDA 
     will conduct the following activities during PDUFA VI:
       a. FDA will develop its regulatory science and review 
     expertise and capacity in MIDD approaches. This staff will 
     support the highly-specialized evaluation of model-based 
     strategies and development efforts.
       b. FDA will convene a series of workshops to identify best 
     practices for MIDD. Topics will include: (1) physiologically-
     based pharmacokinetic modeling; (2) design analysis and 
     inferences from dose-exposure-response studies; (3) disease 
     progression model development, including natural history and 
     trial simulation; and (4) immunogenicity and correlates of 
     protection for evaluating biological products, including 
     vaccines and blood products. Each workshop will focus on 
     current and emerging scientific approaches, including 
     methodological limitations. FDA will produce a written 
     summary of the topics discussed in each workshop.
       c. Starting in FY 2018, FDA will conduct a pilot program 
     for MIDD approaches. For sponsors participating in the pilot 
     program, FDA will grant a pair of meetings specifically 
     designed for this pilot program, consisting of an initial and 
     a follow-up meeting

[[Page 12531]]

     on the same drug development issues, to occur within a span 
     of approximately 120 days. These meetings will be led by the 
     clinical pharmacology or biostatistical review components 
     within CDER or CBER.
       i. FDA will publish a Federal Register Notice announcing 
     the pilot program and outlining the eligibility criteria and 
     process for submitting to FDA requests to participate in the 
     pilot program.
       ii. FDA will select 2-4 proposals (e.g., 1-2 per Center) 
     quarterly each year. FDA will convene an internal review 
     group to review proposals on a quarterly basis and provide 
     recommendations on prioritization and selection of proposals 
     and share knowledge and experience. Program selection will 
     take into account development programs where clinical data 
     are limited such that integration across non-traditional 
     sources may be needed, and for which MIDD can assess 
     uncertainties about issues such as dosing, duration, and 
     patient selection in a way that can inform regulatory 
     decision-making.
       iii. Sponsors who do not participate in the pilot will have 
     an opportunity to interact with the Agency through 
     traditional channels.
       d. By end of FY 2019, FDA will publish draft guidance, or 
     revise relevant existing guidance, on model-informed drug 
     development.
       e. By end of FY 2021, FDA will develop or revise, as 
     appropriate, relevant MAPPs or SOPPs, and/or review templates 
     and training, to incorporate guidelines for the evaluation of 
     MIDD approaches.
       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 VI:
       a. FDA will develop the 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.
       b. Starting in FY 2018, FDA will conduct a pilot program 
     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. For INDs in the pilot program, FDA will 
     grant a pair of meetings specifically designed for this pilot 
     program, consisting of an initial and follow-up meeting on 
     the same design, to occur within a span of approximately 120 
     days. These meetings will be led by the biostatistical review 
     components within CDER or CBER. 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 will provide better 
     clarity on the acceptance of different types of trial designs 
     that should facilitate their use in future development 
     programs.
       i. FDA will publish a Federal Register Notice announcing 
     the pilot program, clarifying pilot program eligibility, and 
     describing the proposal submission and selection process.
       ii. FDA will select up to 2 proposals (e.g., 1 per Center) 
     quarterly each year. FDA will convene an internal review 
     group to review proposals on a quarterly basis and provide 
     recommendations on prioritization and selection of proposals 
     and share knowledge and experience. 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 pilot program may be presented by FDA 
     (e.g., in a guidance or public workshop) 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. Participation in 
     the pilot program, including such agreement on information 
     disclosure, will be voluntary and at the discretion of the 
     sponsor.
       iv. FDA may periodically review the progress of the pilot 
     program and determine whether it is appropriate to adjust any 
     aspects of the program.
       v. Sponsors who do not participate in the pilot will have 
     an opportunity to interact with the Agency through 
     traditional channels. The pilot program will not affect FDA's 
     existing procedures for providing advice on trial designs.
       c. By end of 2nd Quarter FY 2018, FDA will convene a public 
     workshop to discuss various 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, and the 
     acceptability of those designs in regulatory decision-making.
       d. By end of FY 2018, FDA will publish draft guidance on 
     complex adaptive (including Bayesian adaptive) trial designs.
       e. By end of FY 2020, FDA will develop or revise, as 
     appropriate, relevant MAPPs, SOPPs and/or review templates 
     and training to incorporate guidelines on evaluating complex 
     clinical trial designs that rely on computer simulations to 
     determine operating characteristics.
       5. Enhancing Capacity to Support Analysis Data Standards 
     for Product Development and Review
       To support the enhancement of analysis data standards for 
     product development and review in the human drug review 
     program, FDA will conduct the following activities during 
     PDUFA VI:
       a. FDA will develop the staff capacity to efficiently 
     review and provide feedback to sponsors on the readiness of 
     submitted analysis data sets and programs for statistical 
     review. This staff will support pre- and post-submission 
     discussion of standardized datasets and programs, and 
     maintain the knowledge of and engage in collaborations about 
     standards models used in the design, analysis and review of 
     clinical and non-clinical studies. Examples of these 
     standards models could include the Standard for Exchange of 
     Nonclinical Data (SEND), Clinical Data Acquisition Standards 
     Harmonization (CDASH), Study Data Tabulation Model (SDTM), 
     and Analysis Data Model (ADaM).
       b. In parallel, FDA will improve staff capacity to assist 
     with FDA development and updating of therapeutic area user 
     guides (TAUGs) to include the appropriate content for the 
     analysis data standards used in submission and review.
       c. By end of FY 2019, FDA will convene a public workshop to 
     advance the development and application of analysis data 
     standards.
       d. FDA will collaborate with external stakeholders and 
     participate in public workshops held by third parties such as 
     standards development organizations, on development of data 
     standards, processes, documentation and continuous 
     improvement of clinical trials and regulatory science.
       e. By end of FY 2020, FDA will develop or revise, as 
     appropriate, relevant guidance, MAPPs, SOPPs and training 
     associated with submission and utilization of standardized 
     analysis datasets and programs used in review, and on the 
     processes, procedures, and responsibilities related to the 
     receipt, handling, and documentation of submitted analysis 
     data and programs.
       6. 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 VI:
       a. FDA will develop 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. By the end of FY 2018, FDA will convene a public meeting 
     to discuss 1) taxonomy for biomarkers used in drug 
     development, and 2) a framework with appropriate standards 
     and scientific approaches to support biomarkers under the 
     taxonomy, including scientific criteria to determine 
     acceptance of a biomarker qualification submission and 
     essential elements of a formal biomarker qualification plan.
       c. By the end of FY 2018, FDA will publish draft guidance 
     on proposed taxonomy of biomarker usage and related contexts 
     of use.
       d. By the end of FY 2020, FDA will publish draft guidance 
     on general evidentiary standards for biomarker qualification 
     to be supplemented with focused guidance on specific 
     biomarker uses and contexts.
       e. FDA will develop or revise, as appropriate and 
     necessary, relevant MAPPs and SOPPs on the biomarker 
     qualification process.
       f. FDA will list biomarker qualification submissions that 
     are in the qualification process on a public website, to be 
     updated quarterly. Inclusion of a submission on this list 
     will be based on the consent of the submitter for FDA to 
     publish information about the submission, including stage and 
     current status of qualification and the proposed use of the 
     biomarker. Following qualification of a biomarker FDA will 
     post reviews and summary documents that outline the 
     qualification program and data supporting a qualification 
     decision.
       g. Sponsors who do not use this qualification pathway will 
     have an opportunity to interact with the Agency through 
     traditional channels.
     K. Enhancement and Modernization of the FDA Drug Safety 
         System
       FDA will continue to use user fees to enhance and modernize 
     the current U.S. drug safety system, including adoption of 
     new scientific approaches, improving the utility of existing 
     tools for the detection, evaluation, prevention, and 
     mitigation of adverse events, standardization and integration 
     of REMS into the healthcare system, enhancing communication 
     and coordination between postmarketing and pre-market review 
     staff, and improving tracking, communication and oversight of 
     postmarketing safety issues. 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 A) advancing 
     postmarketing drug safety evaluation through expansion of the 
     Sentinel System and integration into FDA

[[Page 12532]]

     pharmacovigilance activities, and B) timely and effective 
     evaluation and communication of postmarketing safety findings 
     related to human drugs.
       1. Advancing Postmarketing Drug Safety Evaluation Through 
     Expansion of the Sentinel System and Integration into FDA 
     Pharmacovigilance Activities
       FDA will use user fee funds to conduct a series of 
     activities to systematically implement and integrate Sentinel 
     in FDA pharmacovigilance practices. These activities will 
     involve augmenting the quality and quantity of data available 
     through the Sentinel System, improving methods for 
     determining when and how that data is utilized, and 
     comprehensive training of review staff on the use of 
     Sentinel.
       a. FDA will work toward expanding the Sentinel System's 
     sources of data and enhancing the system's core capabilities.
       b. FDA will enhance 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. This can be 
     done through enhancement of existing mechanisms and/or 
     greater frequency of such mechanisms.
       c. FDA will evaluate additional ways to facilitate public 
     and sponsor access to Sentinel's distributed data network to 
     conduct safety surveillance.
       d. By the end of FY 2019, FDA will hold or support a public 
     meeting engaging stakeholders to discuss current and emerging 
     Sentinel projects and seek stakeholder feedback and input 
     regarding gaps in the current system to facilitate the 
     further development of Sentinel and its system of Active Risk 
     Identification and Analysis (ARIA).
       e. By the end of FY 2020, FDA will establish policies and 
     procedures (MAPPs and SOPPs) to facilitate informing sponsors 
     about the planned use of Sentinel to evaluate a safety signal 
     involving their respective products. These MAPPs and SOPPs 
     will address what types of evaluations and what information 
     about the evaluations will be shared with sponsors, and the 
     timing of such communications.
       f. By the end of FY 2020, FDA will facilitate integration 
     of Sentinel into the human drug review program in a 
     systematic, efficient, and consistent way through staff 
     development and by updating existing SOPPs and MAPPs, as 
     needed.
       g. By the end of FY 2020, FDA will develop a comprehensive 
     training program for review staff (e.g., epidemiologists, 
     statisticians, medical officers, clinical analysts, project 
     managers, 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 are 
     able to consistently participate in use of Sentinel to 
     evaluate safety issues.
       h. By the end of FY 2022, FDA will analyze, and report on 
     the impact of the Sentinel expansion and integration on FDA's 
     use of Sentinel for regulatory purposes, e.g., in the 
     contexts of labeling changes, PMRs, or PMCs.
       2. Timely and Effective Evaluation and Communication of 
     Postmarketing Safety Findings Related to Human Drugs
       FDA will use user fee funds to continue to support the 
     review, oversight, tracking, and communication of 
     postmarketing drug safety issues.
       a. FDA will make improvements to its current processes that 
     capture and track information, including enhancements to its 
     information technology systems, as needed, in order to 
     support the management and oversight of postmarketing drug 
     safety issues.
       b. By the end of FY 2019, FDA will update existing policies 
     and procedures (MAPPs and SOPPs) concerning tracking 
     postmarketing safety signals to include consistent and timely 
     notification to a sponsor (1) when a serious safety signal 
     involving a product is identified and (2) to the extent 
     practicable, not less than 72 hours before public posting of 
     a safety notice under section 921 of the Food and Drug 
     Administration Amendments Act of 2007.
       c. By the end of FY 2022, FDA will conduct, or fund by 
     contract, an assessment of how its data systems and 
     processes, as described in MAPPs and SOPPs, support review, 
     oversight, and communication of postmarketing drug safety 
     issues.


             II. ENHANCING MANAGEMENT OF USER FEE RESOURCES

       FDA will modernize the user fee structure to improve the 
     predictability of FDA funding and sponsor invoices, improve 
     efficiency by simplifying the administration of user fees, 
     and enhance flexibility of financial mechanisms to improve 
     management of PDUFA program funding. FDA is committed to 
     enhancing management of PDUFA resources and ensuring PDUFA 
     user fee resources are administered, allocated, and reported 
     in an efficient and transparent manner. FDA will conduct a 
     series of resource capacity planning and financial 
     transparency activities to enhance management of PDUFA 
     resources in PDUFA VI.
     A. Resource Capacity Planning and Modernized Time Reporting
       FDA is committed to enhancing management of PDUFA resources 
     in PDUFA VI. FDA will conduct activities to develop a 
     resource capacity planning function and modernized time 
     reporting approach in PDUFA VI.
       1. FDA will publish a PDUFA program resource capacity 
     planning and modernized time reporting implementation plan no 
     later than the 2nd quarter of FY 2018. FDA will continue to 
     utilize information and recommendations from a third party 
     assessment of resource capacity planning, financial 
     analytics, and modernized time reporting for PDUFA as part of 
     the implementation plan.
       2. FDA will staff a resource capacity planning team that 
     will implement and manage a capacity planning system across 
     the PDUFA program in PDUFA VI.
       3. FDA will obtain through a contract with an independent 
     accounting or consulting firm an evaluation of options and 
     recommendations for a new methodology to accurately assess 
     changes in the resource and capacity needs of the human drug 
     review program. The report will be published no later than 
     end of FY 2020 for public comment. Upon review of the report 
     and comments, FDA will implement robust methodologies for 
     assessing resource needs of the program. This will include 
     the adoption of a new resource capacity adjustment 
     methodology, in place of the current PDUFA workload adjuster, 
     that accounts for sustained increases in PDUFA workload.
       4. FDA recognizes that revenue generated by the workload 
     adjuster and the resource capacity adjustment will be 
     allocated to and used by organizational review components 
     engaged in direct review work to enhance resources and expand 
     staff capacity and capability. FDA will document in the 
     annual financial report how the workload adjuster and 
     resource capacity adjustment fee revenues are being utilized.
     B. Financial Transparency and Efficiency
       FDA is committed to ensuring PDUFA user fee resources are 
     administered, allocated, and reported in an efficient and 
     transparent manner. FDA will conduct activities to evaluate 
     the financial administration of the PDUFA program to help 
     identify areas to enhance efficiency. FDA will also conduct 
     activities to enhance transparency of PDUFA program 
     resources.
       1. FDA will contract with an independent third party to 
     conduct an evaluation of PDUFA program resource management 
     during FY 2018 to ensure that PDUFA user fee resources are 
     administered, allocated, and reported in an efficient and 
     transparent manner in PDUFA VI. The study will include, but 
     is not limited, to the following areas:
       a. Evaluate all components of the PDUFA program resource 
     planning, request, and allocation process from when FDA 
     receives the user fee funds through when funds are spent. The 
     contractor will recommend options to improve the process and 
     data needed to enhance resource management decisions.
       b. Assess how FDA administers PDUFA user fees 
     organizationally, including, but not limited to, billing, 
     user fee collection, and execution. The contractor will 
     recommend options to enhance the efficiency of user fee 
     administration.
       c. Evaluate FDA's existing PDUFA program financial and 
     administrative oversight and governance functions. Assess 
     alternative governance models including roles and 
     responsibilities, organizational location, and personnel 
     skill sets required. The contractor will recommend options on 
     the most effective governance model to support the human drug 
     review program.
       d. Assess FDA's technical capabilities to conduct effective 
     financial management and planning in the context of generally 
     accepted government resource management and planning 
     practices. The contractor will recommend options for the 
     technical capabilities needed by financial personnel involved 
     in PDUFA resource management to enhance financial management 
     and planning.
       e. Evaluate how FDA estimates fee paying units for annual 
     fee setting. The contractor will recommend options to enhance 
     the accuracy of FDA's PDUFA user fee estimation methods.
       2. FDA will publish a PDUFA 5-year financial plan no later 
     than the 2nd quarter of FY 2018. FDA will publish updates to 
     the 5-year plan no later than the 2nd 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 2019 to 
     discuss the PDUFA 5-year financial plan, along with the 
     Agency's progress in implementing modernized time reporting, 
     resource capacity planning, and the modernized user fee 
     structure.


        III. IMPROVING FDA HIRING AND RETENTION OF REVIEW STAFF

       To speed and improve development of safe and effective new 
     therapies for patients, 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. In order to 
     strengthen this core function and increase the public health 
     impact of new therapies, the FDA will commit to do the 
     following:
     A. Completion of Modernization of the Hiring System 
         Infrastructure and Augmentation of System Capacity:
       1. Complete implementation of FTE-based position management 
     system capability.

[[Page 12533]]

       a. FDA will complete development of Position Management 
     baseline accounting of all current positions and FTE counts 
     engaged in the human drug review program for each applicable 
     Center and Office including filled and vacant positions, a 
     governance structure for on-going position management that 
     will be accountable to FDA senior management, and Position 
     Management policy and guidance ratified by FDA senior 
     management, outlining processes for adding new positions, 
     deleting positions, and changing established positions.
       b. FDA will complete implementation of the new Position-
     Based Management System.
       2. Complete implementation of an online position 
     classification system.
       a. FDA will finalize the establishment of an online 
     Position Description (PD) library. The library will include 
     all current well-classified PDs and current standardized PDs. 
     Once operational, any new PDs classified using the on-line 
     classification tools, and any newly created standardized PDs, 
     will be stored and accessible within FDA's PD library and 
     available for FDA-wide use as appropriate.
       3. Complete implementation of corporate recruiting.
       a. For key scientific and technical disciplines commonly 
     needed across offices engaged in the human drug review 
     program, FDA will complete the transition from the use of 
     individual vacancy announcements for individual offices to 
     expanded use of a common vacancy announcement and certificate 
     of eligible job applicants that can be used by multiple 
     offices. As a part of this effort, FDA will complete the 
     transition from use of individual announcements that are 
     posted for a limited period to common vacancy announcements 
     with open continuous posting to maximize the opportunity for 
     qualified applicants to apply for these positions.
     B. Augmentation of Hiring Staff Capacity and Capability
       In recognition of the chronic and continuing difficulties 
     of recruiting and retaining sufficient numbers of qualified 
     Human Resources (HR) staff, FDA will engage a qualified 
     contractor to provide continuous support throughout PDUFA VI 
     to augment the existing FDA HR staff capacity and 
     capabilities. The utilization of a qualified contractor will 
     assist FDA in successfully accomplishing PDUFA goals for 
     recruitment and retention of human drug review program staff.
     C. Complete Establishment of a Dedicated Function to Ensure 
         Needed Scientific Staffing for Human Drug Review Program
       1. Rapid advances in the science and technology of human 
     drug development and manufacturing require FDA's human drug 
     review program staff to keep pace with science and learn 
     innovative methods and techniques for review of new 
     therapies. FDA will complete the establishment of a new 
     dedicated unit within the Office of Medical Products and 
     Tobacco charged with the continuous recruiting, staffing, and 
     retention of scientific, technical and professional staff for 
     the process for the review of human drug applications.
       a. The unit will continuously develop and implement 
     scientific staff hiring strategies and plans, working closely 
     with the center review offices and the FDA HR office, to meet 
     discipline-specific hiring commitments and other targeted 
     staffing needs. It will function as a scientific-focused 
     recruiter conducting ongoing proactive outreach to source 
     qualified candidates, and conducting competitive recruiting 
     to fill vacancies that require top scientific, technical and 
     professional talent.
       b. The unit will conduct analyses, no less than annually, 
     of compensation and other factors affecting retention of key 
     staff in targeted disciplines, providing leadership and 
     support for agency compensation oversight boards that 
     currently exist or may be established as needed to ensure 
     retention of key scientific, technical and professional 
     staff.
     D. 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 for the years of PDUFA VI. These goals for 
     targeted hires are summarized in Table 6 below:

                                                     TABLE 6
----------------------------------------------------------------------------------------------------------------
                                                   FY 2018      FY 2019      FY 2020      FY 2021      FY 2022
----------------------------------------------------------------------------------------------------------------
CDER...........................................           43           57           45           17            9
CBER...........................................           16            8            7            1            0
Other FDA......................................           12            9            6            0            0
                                                ----------------------------------------------------------------
    Total FTE..................................           71           74           58           18            9
----------------------------------------------------------------------------------------------------------------

       2. FDA will confirm progress in the hiring of PDUFA V FTEs. 
     FDA will report on progress against the hiring goals for FY 
     2018-2022 on a quarterly basis posting updates to the FDA 
     website PDUFA Performance webpage.
     E. Comprehensive and Continuous Assessment of Hiring and 
         Retention
       FDA hiring and retention of staff for the human drug review 
     program will be evaluated by a qualified, independent 
     contractor with expertise in assessing HR operations and 
     transformation. This will include continuous assessments 
     throughout the course of implementation of the performance 
     initiatives identified in sections III.A-D, and metrics 
     including, but not limited to, those related to recruiting 
     and retention in the human drug review program including, but 
     not limited to, specifically targeted scientific disciplines 
     and levels of experience. The contractor will conduct a 
     comprehensive review of current hiring processes and hiring 
     staff capacity and capabilities that contribute to 
     achievement of successes, potential problems, or delays in 
     human drug review program staff hiring. This includes the 
     entire hiring function and related capabilities. FDA and 
     regulated industry leadership will periodically and regularly 
     assess the progress of hiring and retention throughout PDUFA 
     VI.
       1. Initial Assessment: The assessment will include an 
     initial baseline assessment to be conducted and completed no 
     later than December 31, 2017. The initial baseline study will 
     include an evaluation of the current state and provide 
     recommended options to address any identified gaps or areas 
     identified as priorities for improvement, and a study report 
     to be published no later than December 31, 2017. FDA will 
     hold a public meeting no later than December 31, 2017, to 
     present and discuss report findings, and present its specific 
     plans, including agency senior management oversight, and 
     timeline for implementing recommended enhancements to be 
     fully operational by no later than December 31, 2018.
       2. Interim Assessment: An interim assessment will be 
     published by March 31, 2020, for public comment. By June 30, 
     2020, FDA will hold a public meeting during which the public 
     may present their views. FDA will discuss the findings of the 
     interim assessment, including progress relative to program 
     milestones and metrics, and other aggregated feedback from 
     internal customers and participants in HR services that may 
     be included in the continuous assessment. FDA will also 
     address any issues identified to date including actions 
     proposed to improve the likelihood of success of the program.
       3. Final Assessment: A final assessment will be published 
     by December 31, 2021, for public comment. FDA will hold a 
     public meeting by no later than March 30, 2022, during which 
     the public may present their views. FDA will discuss the 
     findings of the final assessment, including progress relative 
     to program milestones and metrics, and other aggregated 
     feedback from internal customers and participants in HR 
     services that may be included in the continuous assessment. 
     FDA will also address any issues identified and plans for 
     addressing these issues.


                    IV. INFORMATION TECHNOLOGY GOALS

     A. Objective
       FDA is committed to achieve the long-term goal of improving 
     the predictability and consistency of the electronic 
     submission process (Section IV.B), and enhancing transparency 
     and accountability of FDA information technology related 
     activities (Section IV.C). FDA is pursuing these objectives 
     through IT investments that support the PDUFA program.
     B. Improve the Predictability and Consistency of PDUFA 
         Electronic Submission Processes
       1. Electronic Submission Documentation:
       By December 31, 2017, FDA will publish and maintain up-to-
     date documentation for the following:
       a. The electronic submission process, including key 
     electronic submission milestones and associated sponsor 
     notifications. The description should cover the complete 
     process undergone by a submission from the completion of its 
     upload to the Electronic System Gateway (ESG) through the 
     time the submission is made available to the review team.
       b. The rejection process for electronic submissions.
       c. The electronic submission validation criteria.
       d. Software names and versions for Electronic Common 
     Technical Document (eCTD) validation and data validation 
     tools.
       2. Electronic Submission and System Status:
       By September 30, 2018, FDA will:
       a. Publish targets for and measure ESG availability overall 
     (including scheduled

[[Page 12534]]

     downtime) and during business hours (8am to 8pm Eastern 
     Time). ESG availability is defined for the purposes of this 
     commitment letter as the ability for an external user to 
     complete a submission from each entry point to its delivery 
     to the appropriate FDA Center.
       b. Post current ESG operational status on its public 
     website.
       c. Publish submission instructions to use in the event of 
     an ESG service disruption.
       3. By December 31, 2017, FDA will publish target time 
     frames for the 1) expected submission upload duration(s) and 
     2) timeframe between key milestones and notifications as 
     defined in 1(a).
       4. By September 30, 2018, FDA will implement the ability to 
     communicate electronic submission milestone notifications, 
     including final submission upload status (e.g., successfully 
     processed or rejected), to sender/designated contact.
       5. FDA will provide expert technical support for electronic 
     submissions to FDA review staff for submission navigation and 
     troubleshooting.
       6. For those systems that sponsors interact with directly, 
     FDA will invite industry to provide feedback and/or 
     participate in user acceptance testing in advance of 
     implementing significant changes that impact industry's 
     interaction with the system.
       7. By December 31, 2017, FDA will document and implement a 
     process to provide ample advance notification of systems and 
     process changes commensurate with the complexity of the 
     change and the impact to sponsors for ESG scheduled 
     unavailability and user interface changes.
     C. Enhance Transparency and Accountability of FDA Electronic 
         Submission and Data Standards Activities
       1. FDA staff and industry will jointly plan and hold 
     quarterly meetings and will share performance updates prior 
     to each meeting. The meeting will address current challenges 
     and emerging needs.
       2. Beginning no later than September 30, 2018, FDA will 
     hold annual public meetings to seek stakeholder input related 
     to electronic submission system past performance, future 
     targets, emerging industry needs and technology initiatives 
     to inform the FDA IT Strategic Plan and published targets.
       3. By December 31, 2017, FDA will post, at least annually, 
     historic and current metrics on ESG performance in relation 
     to published targets, characterizations and volume of 
     submissions, and standards adoption and conformance.
       4. By December 31, 2017, FDA will incorporate strategic 
     initiatives in support of PDUFA goals into the FDA IT 
     Strategic Plan. Milestones and metrics for PDUFA initiatives 
     will be included in the plan. The plan will be updated and 
     discussed annually during a meeting described in Section 
     IV.C.1.
       5. FDA will:
       a. Collaborate with Standards Development Organizations and 
     stakeholders to ensure long-term sustainability of supported 
     data standards.
       b. Publish a data standards action plan updated at least 
     quarterly.
       c. Publish and maintain a current FDA Data Standards 
     Catalog.


                V. IMPROVING FDA PERFORMANCE MANAGEMENT

     A. The Studies Conducted Under This Initiative are Intended 
         to Foster
       1. Development of programs to improve access to internal 
     and external expertise
       2. Reviewer development programs, particularly as they 
     relate to the human drug review program
       3. Advancing science and use of information management 
     tools
       4. Improving both inter- and intra-Center consistency, 
     efficiency, and effectiveness
       5. Improved reporting of management objectives
       6. Increased accountability for use of user fee revenues
       7. Focused investments on improvements in the process for 
     the review of human drug applications
       8. Improved communication between the FDA and industry
     B. Studies Will Include
       1. Assessment of current practices of FDA and sponsors in 
     communicating during drug development as described in Section 
     I.I.1.
       2. Assessment of the current practices for combination drug 
     product review as described in Section I.I.5.
       3. Evaluation of how reviewers across the organization 
     apply the benefit-risk framework and identify best practices 
     in use of the benefit-risk framework as described in Section 
     I.J.2.
       4. Analysis of the impact of the Sentinel expansion and use 
     for regulatory purposes as described in Section I.K.1.
       5. Assessment of how FDA data systems and processes, as 
     described in MAPPs and SOPPs, support review, oversight, and 
     communication of postmarketing drug safety issues, as 
     described in Section I.K.2.
       6. Evaluation of options and recommendations for a new 
     methodology to accurately assess changes in the resource and 
     capacity needs of the human drug review program as described 
     in Section II.A.3.
       7. Evaluation of PDUFA program resource management to 
     ensure that PDUFA user fee resources are administered, 
     allocated, and reported in an efficient and transparent 
     manner in PDUFA VI as described in Section II.B.1.
       8. Comprehensive and continuous assessment of hiring and 
     retention as described in Section III.E.


 VI. PROGRESS REPORTING FOR PDUFA VI AND CONTINUING PDUFA V INITIATIVES

       A. FDA will include in the annual PDUFA Performance Report 
     information on the Agency's progress in meeting the specific 
     commitments identified in Sections I.I-K of this document.
       B. FDA will include in the annual PDUFA Financial Report 
     information on the Agency's progress in the hiring of new 
     staff used to support the new initiatives as identified in 
     Section III.


               VII. 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).

  Mr. ALEXANDER. Mr. President, I ask unanimous consent to have printed 
in the Record a copy of the commitment letter for the Biosimilar User 
Fee Act, BsUFA, reauthorization for fiscal years 2018 to 2022, known as 
BsUFA II.
  There being no objection, the material was ordered to be printed in 
the Record, as follows:

  Biosimilar Biological Product Reauthorization Performance Goals and 
               Procedures Fiscal Years 2018 Through 2022

       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. First Cycle Review Management for Supplements with 
     Clinical Data
       D. Guidance
       E. Review of Proprietary Names to Reduce Medication Errors
       F. Major Dispute Resolution
       G. Clinical Holds
       H. Special Protocol Question Assessment and Agreement
       I. Meeting Management Goals
       II. Advancing Development of Biosimilar Biological Products 
     Through Further Clarification of the 351(k) Regulatory 
     Pathway
       III. Enhancing Capacity for Biosimilar Regulations and 
     Guidance Development, Reviewer Training, and Timely 
     Communication

[[Page 12535]]

       IV. Enhancing Management of User Fee Resources
       A. Resource Capacity Planning and Modernized Time Reporting
       B. Financial Transparency and Efficiency
       C. Management of Carryover Balance
       V. Improving FDA Hiring and Retention of Review Staff
       A. Completion of Modernization of the Hiring System 
     Infrastructure and Augmentation of System Capacity
       B. Augmentation of Hiring Staff Capacity and Capability
       C. Complete Establishment of a Dedicated Function to Ensure 
     Needed Scientific Staffing for Human Drug Review Including 
     for Review of Biosimilar Biological Products
       D. Set Clear Goals for Biosimilar Biological Product Review 
     Program Hiring
       E. Comprehensive and Continuous Assessment of Hiring and 
     Retention
       VI. Definitions and Explanation of Terms

   Biosimilar Biological Product Authorization Performance Goals and 
             Procedures for Fiscal Years 2018 Through 2022

       This document contains the performance goals and procedures 
     for the Biosimilar User Fee Act (BsUFA) reauthorization for 
     fiscal years (FYs) 2018-2022, known as BsUFA II. 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 II, 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. In addition, FDA is 
     committed to the principles articulated in the Good Review 
     Management Principles and Practices (GRMP) guidance, which 
     FDA intends to update and apply to the review of biosimilar 
     and interchangeable products.
       FDA and the regulated industry will periodically and 
     regularly assess the progress of the biosimilar biological 
     product review program throughout BsUFA II. 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. Biosimilar Biological Product Application Submissions 
     and Resubmissions
       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. Supplements with Clinical Data
       a. Review and act on 90 percent of original supplements 
     with clinical data within 10 months of receipt.
       b. Review and act on 90 percent of resubmitted supplements 
     with clinical data within 6 months of receipt.
       3. Original Manufacturing Supplements
       a. In FY 2018, review and act on 70 percent of 
     manufacturing supplements requiring prior approval within 4 
     months of receipt.
       b. In FY 2019, review and act on 75 percent of 
     manufacturing supplements requiring prior approval within 4 
     months of receipt.
       c. In FY 2020, review and act on 80 percent of 
     manufacturing supplements requiring prior approval within 4 
     months of receipt.
       d. In FY 2021, review and act on 85 percent of 
     manufacturing supplements requiring prior approval within 4 
     months of receipt.
       e. In FY 2022, review and act on 90 percent of 
     manufacturing supplements requiring prior approval within 4 
     months of receipt.
       f. 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 SUPPLEMENTS
------------------------------------------------------------------------
 
------------------------------------------------------------------------
Original Biosimilar Biological Product      90% in 10 months of the 60
 Application Submissions.                    day filing date.
Resubmitted Original Biosimilar Biological  90% in 6 months of the
 Product Applications.                       receipt date.
Original Supplements with Clinical Data...  90% in 10 months of the
                                             receipt date.
Resubmitted Supplements with Clinical Data  90% in 6 months of the
                                             receipt date.
------------------------------------------------------------------------


                   TABLE 2.--MANUFACTURING SUPPLEMENTS
------------------------------------------------------------------------
                                    Prior approval         All other
------------------------------------------------------------------------
Manufacturing Supplements.......   FY 2018:   90% in 6 months of
                                   70% in 4 months     the receipt date.
                                   of the receipt
                                   date.
                                   FY 2019:
                                   75% in 4 months
                                   of the receipt
                                   date
                                   FY 2020:
                                   80% in 4 months
                                   of the receipt
                                   date
                                   FY 2021:
                                   85% in 4 months
                                   of the receipt
                                   date
                                   FY 2022:
                                   90% in 4 months
                                   of the receipt
                                   date
------------------------------------------------------------------------

       5. Review Performance Goal Extensions
       a. Major Amendments
       i. A major amendment to an original application, supplement 
     with clinical data, or resubmission of any of these 
     applications, submitted at any time during the review cycle, 
     may extend the goal date by three months.
       ii. A major amendment may include, for example, a major new 
     clinical study report; major re-analysis of previously 
     submitted study(ies); submission of a risk evaluation and 
     mitigation strategy (REMS) with elements to assure safe use 
     (ETASU) not included in the original application; or 
     significant amendment to a previously submitted REMS with 
     ETASU. Generally, changes to REMS that do not include ETASU 
     and minor changes to REMS with ETASU will not be considered 
     major amendments.
       iii. A major amendment to a manufacturing supplement 
     submitted at any time during the review cycle may extend the 
     goal date by two months.
       iv. Only one extension can be given per review cycle.
       v. Consistent with the underlying principles articulated in 
     the 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, 2017, 
     through September 30, 2022. 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 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

[[Page 12536]]

     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 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:

[[Page 12537]]

       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.
       8. Assessment of the Program: The Program described in this 
     Section I.B shall be evaluated to determine its impact on the 
     efficiency and effectiveness of the first review cycle for 
     biosimilar biological products. The assessment shall be 
     conducted by an independent contractor with expertise in 
     assessing the quality and efficiency of biopharmaceutical 
     development and regulatory review programs. The statement of 
     work for this effort will be published for public comment 
     prior to beginning the assessment. The assessments will occur 
     continuously throughout the course of the Program.
       Aspects and other measures of the Program that will be 
     assessed by the independent contractor include, but are not 
     limited to the following:
        adherence by the applicant and FDA to the current GRMP 
     guidance or the GRMP guidance as updated in accordance with 
     Section I.D, as applicable
        completeness and quality of the submitted application
        number of unsolicited amendments submitted by the 
     applicant
        timing and adequacy of Day 74 letters
        conduct of the mid-cycle communication
        any DR letters issued
        late-cycle meeting background package
        conduct of the late-cycle meeting
        time to approval
        percentage of applications that are approved during the 
     first review cycle
        percentage of application reviews that are extended due to 
     a major amendment
        number of review cycles for applications that are 
     ultimately approved
        time to resubmission for applications that receive a 
     complete response in the first review cycle
       This assessment will also include a de-identified analysis 
     of the issues typically discussed during the mid-cycle 
     communication and the late-cycle meeting and the ability of 
     the additional FDA-applicant communications to (a) achieve 
     resolution of these issues during the remainder of the review 
     clock, or (b) allow the applicant to better prepare for a 
     resubmission of the application. Following an FDA regulatory 
     action, the independent contractor will conduct separate 
     interviews of the applicant and the FDA review team to 
     understand each party's perspectives on the review of the 
     application, including whether issues were or should have 
     been identified at the BPD meetings to facilitate application 
     review.
       An interim and final assessment of the Program will be 
     published for public comment, with each report followed by a 
     public meeting during which public stakeholders may present 
     their views on the success of the Program to date, including 
     the ability of the Program to help ensure that patients have 
     timely access to safe, effective, and high quality biosimilar 
     biological products. During each public meeting, FDA and the 
     independent contractor will discuss the findings of the 
     interim assessment, including anonymized aggregated feedback 
     from sponsors and FDA review teams resulting from independent 
     contractor interviews. FDA will discuss any issues identified 
     to date including any proposed plans to improve the 
     likelihood of the Program's success.
       a. Interim Assessment: An interim assessment of the Program 
     will be published by December 31, 2020, and FDA will hold a 
     public meeting by March 31, 2021.
       b. Final Assessment: A final assessment of the Program will 
     be published by June 30, 2022, and FDA will hold a public 
     meeting by September 30, 2022.
     C. First Cycle Review Management for Supplements with 
         Clinical Data
       1. Notification of Issues Identified during the Filing 
     Review
       a. Performance Goal: For supplements with clinical data, 
     FDA will report substantive review issues identified during 
     the initial filing review to the applicant by letter.
       b. The timeline for such communication will be within 74 
     calendar days from the date of FDA receipt of the supplement.
       c. If no substantive review issues were identified during 
     the filing review, FDA will so notify the applicant.
       d. 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.
       e. FDA will notify the applicant of substantive review 
     issues prior to or on the goal date for 90% of applications.
       2. Notification of Planned Review Timelines
       a. Performance Goal: For supplements with clinical data, 
     FDA will inform the applicant of the planned timeline for 
     review of the application. The information conveyed will 
     include a target date for communication of feedback from the 
     review division to the applicant regarding proposed labeling, 
     postmarketing requirements, and postmarketing commitments the 
     Agency will be requesting.
       b. The planned review timeline will be included with the 
     notification of issues identified during the filing review, 
     within 74 calendar days from the date of FDA receipt of the 
     original supplement.
       c. The planned review timelines will be consistent with the 
     GRMP guidance.
       d. The planned review timeline will be based on the 
     supplement as submitted.
       e. FDA will inform the applicant of the planned review 
     timeline for 90% of all supplements with clinical data.
       f. In the event FDA determines that significant 
     deficiencies in the supplement preclude discussion of 
     labeling, postmarketing requirements, or postmarketing 
     commitments by the target date identified in the planned 
     review timeline (e.g., significant safety concern(s), need 
     for a new study(ies) or extensive re-analyses of existing 
     data before approval), FDA will communicate this 
     determination to the applicant in accordance with GRMPs and 
     no later than the target date. In such cases the planned 
     review timeline will be considered to have been met. 
     Communication of FDA's determination may occur by letter, 
     teleconference, facsimile, secure e-mail, or other expedient 
     means.
       g. To help expedite the development of biosimilar 
     biological products, communication of the deficiencies 
     identified in the supplement may occur through issuance of a 
     DR letter(s) in advance of the planned target date for 
     initiation of discussions regarding labeling, postmarketing 
     requirements, and postmarketing commitments the Agency may 
     request.
       f. If the applicant submits a major amendment(s) (refer to 
     Section I.A.5.a for additional information on major 
     amendments) and the review division chooses to review such 
     amendment(s) during that review cycle, the planned review 
     timeline initially communicated (under Section I.C.2.a and b) 
     will generally no longer be applicable. 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 
     supplement deficiencies and leads toward a first cycle 
     approval when possible.
     D. Guidance
       FDA and industry share a commitment to ensuring an 
     efficient and effective first cycle

[[Page 12538]]

     review process for all applications subject to the BsUFA 
     program. This commitment is consistent with the principles 
     articulated in the GRMP guidance, which FDA applies to the 
     review of biosimilar and interchangeable products. FDA will 
     update the GRMP guidance during BsUFA II to ensure that it 
     encompasses all review activities for biosimilar and 
     interchangeable products, including principles regarding 
     notification to applicants regarding issues identified during 
     FDA's initial review of the application, principles regarding 
     FDA's notification to applicants regarding planned review 
     timelines, and the importance of internal review timelines 
     that govern aspects of biosimilar and interchangeable product 
     review that are not part of BsUFA performance goals. FDA will 
     publish a revised draft guidance for public comment no later 
     than the end of FY 2018. 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.
     E. Review of Proprietary Names to Reduce Medication Errors
       To enhance patient safety, FDA is committed to various 
     measures to reduce medication errors related to look-alike 
     and sound-alike proprietary names and such factors as unclear 
     label abbreviations, acronyms, dose designations, and error 
     prone label and packaging design. The following performance 
     goals apply to FDA's review of biosimilar biological product 
     proprietary names during the biosimilar biological product 
     development (BPD) phase and during FDA's review of a 
     marketing application:
       1. Proprietary Name Review Performance Goals During The BPD 
     Phase
       a. Review 90% of proprietary name submissions filed within 
     180 days of receipt. Notify sponsor of tentative acceptance 
     or non-acceptance.
       b. If the proprietary name is found to be unacceptable, the 
     sponsor can request reconsideration by submitting a written 
     rebuttal with supporting data or request a meeting within 60 
     days to discuss the initial decision (meeting package 
     required).
       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/non-acceptance.
       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.
     F. Major Dispute Resolution
       1. Procedure: For procedural or scientific matters 
     involving the review of biosimilar biological product 
     applications and supplements (as defined in BsUFA) that 
     cannot be resolved at the signatory authority level 
     (including a request for reconsideration by the signatory 
     authority after reviewing any materials that are planned to 
     be forwarded with an appeal to the next level), the response 
     to appeals of decisions will occur within 30 calendar days of 
     the Center's receipt of the written appeal.
       2. Performance goal: 90% of such responses are provided 
     within 30 calendar days of the Center's receipt of the 
     written appeal.
       3. Conditions:
       a. Sponsors should first try to resolve the procedural or 
     scientific issue at the signatory authority level. If it 
     cannot be resolved at that level, it should be appealed to 
     the next higher organizational level (with a copy to the 
     signatory authority) and then, if necessary, to the next 
     higher organizational level.
       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.
     G. 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.
     H. 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 2 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.
     I. 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.
        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 2 Meeting is a meeting to discuss a specific 
     issue (e.g., proposed study design or endpoints) or questions 
     where FDA

[[Page 12539]]

     will provide targeted advice regarding an ongoing biosimilar 
     biological product development program. Such term 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. Such term 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 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 and background package. Table 1 below 
     indicates the timeframes for FDA's response to a meeting 
     request.

                                 TABLE 1
------------------------------------------------------------------------
                                                         Response time
                     Meeting type                       (calendar days)
------------------------------------------------------------------------
Biosimilar Initial Advisory..........................                 21
BPD Type 1...........................................                 14
BPD Type 2-4.........................................                 21
------------------------------------------------------------------------

       For Biosimilar Initial Advisory and BPD Type 2 meetings, 
     the sponsor may request a written response to its questions, 
     rather than a face-to-face meeting, videoconference or 
     teleconference. If a written response is deemed appropriate, 
     FDA will notify the requester of the date it intends to send 
     the written response. This date will be consistent with the 
     timeframes specified in Table 2 below for the specific 
     meeting type.
       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. 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 2 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 written
              Meeting type                        response time
------------------------------------------------------------------------
Biosimilar Initial Advisory............  75 calendar days from receipt
                                          of meeting request and
                                          background package.
BPD 2..................................  90 calendar days from receipt
                                          of meeting request and
                                          background package.
Meeting Scheduling Time                  ...............................
BPD 1..................................  30 calendar days from receipt
                                          of meeting request and
                                          background package.
BPD 3..................................  120 calendar days from receipt
                                          of meeting request and
                                          background package.
BPD 4..................................  60 calendar days from receipt
                                          of meeting request and
                                          background package.
------------------------------------------------------------------------

       b. Performance goal:

                                 TABLE 3
------------------------------------------------------------------------
              Meeting type                             Goal
------------------------------------------------------------------------
BPD Type 2.............................  FY 2018-2019: 80% of meetings
                                          are held or written responses
                                          are sent within the timeframe.
                                         FY 2020-2022: 90% of meetings
                                          are held or written responses
                                          are sent within the timeframe.
Biosimilar Initial Advisory............  90% of meetings are held or
                                          written responses are sent
                                          within the timeframe.
BPD Type 1, 3, and 4...................  90% of meetings are held within
                                          the timeframe for each meeting
                                          type.
------------------------------------------------------------------------

       3. Preliminary Responses
       a. Procedure: The Agency will send preliminary responses to 
     the sponsor's questions contained in the background package 
     no later than five calendar days before the face-to-face, 
     videoconference or teleconference meeting date for BPD Type 2 
     and Type 3 meetings.
       b. Performance goal:

                                 TABLE 4
------------------------------------------------------------------------
              Meeting type
------------------------------------------------------------------------
BPD Type 2.............................   FY 2018: 70% of
                                          preliminary responses to
                                          questions are issued by FDA no
                                          later than five calendar days
                                          before the meeting date.
                                          FY 2019, 75% of
                                          preliminary responses to
                                          questions are issued by FDA no
                                          later than five calendar days
                                          before the meeting date.
                                          FY 2020, 80% of
                                          preliminary responses to
                                          questions are issued by FDA no
                                          later than five calendar days
                                          before the meeting date.
                                          FY 2021, 85% of
                                          preliminary responses to
                                          questions are issued by FDA no
                                          later than five calendar days
                                          before the meeting date.
                                          FY 2022, 90% of
                                          preliminary responses to
                                          questions are issued by FDA no
                                          later than five calendar days
                                          before the meeting date.
BPD Type 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 
     and BPD Type 2 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.
       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 2 
     meetings only);
       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 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 2, 3, and 4 Meetings will be 
     honored except in the most unusual circumstances.
       The Center may determine that a different type of meeting 
     (i.e., Biosimilar Initial Advisory, or BPD Type 1-4) is more 
     appropriate and it may grant a meeting of a different type 
     than requested, which may require the payment of a biosimilar 
     biological product development fee as described in section 
     744H of the Federal Food, Drug, and Cosmetic Act before the 
     meeting will be provided. If a biosimilar biological product 
     development fee is required under section 744H, and the 
     sponsor does not pay the fee within the time frame required 
     under section 744H, the meeting will be cancelled. If the 
     sponsor pays the biosimilar biological product development 
     fee after the meeting has been cancelled due to non-payment, 
     the time frame described in section I.I.1.a will be 
     calculated from the date on which FDA received the payment, 
     not the date on which the sponsor originally submitted the 
     meeting request.
       Sponsors are encouraged to consult available FDA guidance 
     to obtain further information on recommended meeting 
     procedures.
       6. Guidance
       a. FDA will publish revised draft guidance on Formal 
     Meetings Between the FDA and Biosimilar Biological Product 
     Sponsors or Applicants no later than September 30, 2018.
       b. FDA will update the current draft or final guidance on 
     Best Practices for Communication Between IND Sponsors and FDA 
     During Drug Development, as appropriate, to apply to 
     communications between IND sponsors and FDA during biosimilar 
     biological product development. FDA will publish a revised 
     draft or final guidance by December 31, 2018.


  II. advancing development of biosimilar biological products through 
         further clarification of the 351(k) regulatory pathway

       A. On or before December 31, 2017, FDA will publish draft 
     guidance describing considerations in demonstrating 
     interchangeability with a reference product. FDA will work 
     toward the goal of publishing a revised draft or final 
     guidance within 24 months after the close of the public 
     comment period.
       B. On or before December 31, 2017, FDA will publish draft 
     guidance describing statistical considerations for the 
     analysis of analytic similarity data intended to support a 
     demonstration of ``highly similar'' for biosimilar biological 
     products. FDA will work toward

[[Page 12540]]

     the goal of publishing a revised draft or final guidance 
     within 18 months after the close of the public comment 
     period.
       C. On or before March 31, 2019, FDA will publish draft 
     guidance describing processes and further considerations 
     related to post-approval manufacturing changes for biosimilar 
     biological products. 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. FDA will work towards the goal of publishing revised 
     draft guidance or final guidance documents on or before May 
     31, 2019 for draft guidances published between January 1, 
     2014 and September 30, 2017, other than those described in 
     (II.A-C). These draft guidances will include:
       1. Clinical Pharmacology Data to Support a Demonstration of 
     Biosimilarity to a Reference Product (draft guidance 
     published in May 2014)
       2. Nonproprietary Naming of Biological Products (draft 
     guidance published in August 2015)
       3. Labeling for Biosimilar Biological Products (draft 
     guidance published in March 2016)


    III. enhancing capacity for biosimilar regulations and guidance 
        development, reviewer training, and timely communication

       A. FDA will strengthen the staff capacity to develop new 
     regulations and guidance to clarify scientific criteria for 
     biosimilar development and approval to provide certainty to 
     industry and other stakeholders related to key regulatory 
     issues including the scope of eligible biosimilar biological 
     products.
       B. FDA will strengthen staff capacity to develop or revise 
     MaPPs, SOPPs, and review templates to facilitate rapid update 
     and application of new policies and guidance by review staff, 
     and to develop and deliver timely comprehensive training to 
     all CDER and CBER review staff and special government 
     employees involved in the review of 351(k) BLAs.
       C. FDA will strengthen staff capacity to deliver timely 
     information to the public to improve public understanding of 
     biosimilarity and interchangeability.
       D. FDA will strengthen staff capacity to deliver 
     information concerning the date of first licensure and the 
     reference product exclusivity expiry date, to be included in 
     the Purple Book.
       FDA will update the Purple Book to include the following 
     information: the BLA number, product name, proprietary name, 
     date of licensure, interchangeable or biosimilar 
     determination, and whether the BLA has been withdrawn. FDA 
     will update this information in the Purple Book within 30 
     days after approval or withdrawal. In addition, within 30 
     days after FDA determines the date of first licensure, the 
     date of first licensure and the reference product exclusivity 
     expiry date will be included in the Purple Book.


             IV. enhancing management of user fee resources

       FDA will establish an independent user fee structure and 
     fee amounts to ensure stable and predictable user fee 
     funding, improve the predictability of FDA funding and 
     sponsor invoices, improve efficiency by simplifying the 
     administration of user fees, and enhance flexibility of 
     financial mechanisms to improve management of BsUFA program 
     funding. FDA is committed to enhancing management of BsUFA 
     resources and ensuring BsUFA user fee resources are 
     administered, allocated, and reported in an efficient and 
     transparent manner. FDA will conduct a series of resource 
     capacity planning and financial transparency activities to 
     enhance management of BsUFA resources in BsUFA II.
     A. Resource Capacity Planning and Modernized Time Reporting
       FDA is committed to enhancing management of BsUFA resources 
     in BsUFA II. FDA will conduct activities to develop a 
     resource capacity planning function and modernized time 
     reporting approach in BsUFA II.
       1. FDA will publish a resource capacity planning and 
     modernized time reporting implementation plan that includes 
     BsUFA no later than the 2nd quarter of FY 2018. FDA will 
     continue to utilize information and recommendations from a 
     third party assessment of resource capacity planning, 
     financial analytics, and modernized time reporting for BsUFA 
     as part of the implementation plan.
       2. FDA will staff a resource capacity planning team that 
     will implement and manage a capacity planning system across 
     the BsUFA program in BsUFA II.
       3. FDA will obtain through a contract with an independent 
     accounting or consulting firm an evaluation of options and 
     recommendations for a new methodology to accurately assess 
     changes in the resource and capacity needs of the biosimilar 
     biological product review program. The BsUFA evaluation will 
     be conducted under the same contract and by the same 
     independent accounting or consulting firm that will evaluate 
     options and recommendations for a new methodology to 
     accurately assess changes in the resource and capacity needs 
     of the human drug review program in PDUFA VI. The report will 
     be published no later than end of FY 2020 for public comment. 
     Upon review of the report and comments, FDA will implement 
     robust methodologies for assessing resource needs of the 
     program. This will include the adoption of a new resource 
     capacity adjustment methodology that accounts for sustained 
     increases in BsUFA workload.
       4. FDA recognizes that revenue generated by the capacity 
     adjustment will be allocated to and used by organizational 
     review components engaged in direct review work to enhance 
     resources and expand staff capacity and capability. FDA will 
     document in the annual financial report how the capacity 
     adjustment fee revenues are being utilized.
     B. Financial Transparency and Efficiency
       FDA is committed to ensuring BsUFA user fee resources are 
     administered, allocated, and reported in an efficient and 
     transparent manner. FDA will conduct activities to evaluate 
     the financial administration of the BsUFA program to help 
     identify areas to enhance efficiency. FDA will also conduct 
     activities to enhance transparency of BsUFA program 
     resources.
       1. FDA will contract with an independent third party to 
     conduct an evaluation of BsUFA program resource management 
     during FY 2018 to ensure that BsUFA user fee resources are 
     administered, allocated, and reported in an efficient and 
     transparent manner in BsUFA II. The BsUFA evaluation will be 
     conducted under the same contract and by the same independent 
     third party that will conduct an evaluation of the PDUFA 
     program resource management. The study will include, but is 
     not limited to, the following areas:
       a. Evaluate all components of the BsUFA program resource 
     planning, request, and allocation process from when FDA 
     receives the user fee funds through when funds are spent. The 
     contractor will recommend options to improve the process and 
     data needed to enhance resource management decisions.
       b. Assess how FDA administers BsUFA user fees 
     organizationally, including, but not limited to, billing, 
     user fee collection, and execution. The contractor will 
     recommend options to enhance the efficiency of user fee 
     administration.
       c. Evaluate FDA's existing BsUFA program financial and 
     administrative oversight and governance functions. Assess 
     alternative governance models including roles and 
     responsibilities, organizational location, and personnel 
     skill sets required. The contractor will recommend options on 
     the most effective governance model to support the biosimilar 
     biological product review program.
       d. Assess FDA's technical capabilities to conduct effective 
     financial management and planning in the context of generally 
     accepted government resource management and planning 
     practices. The contractor will recommend options for the 
     technical capabilities needed by financial personnel involved 
     in BsUFA resource management to enhance financial management 
     and planning.
       2. FDA will publish a BsUFA five-year financial plan no 
     later than the 2nd quarter of FY 2018. FDA will publish 
     updates to the five-year plan no later than the 2nd 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 2019 to 
     discuss the BsUFA five-year financial plan, report on the 
     contribution of the BsUFA spending trigger to the BsUFA 
     program, along with the Agency's progress in implementing 
     modernized time reporting, resource capacity planning, and 
     the modernized user fee structure.
     C. Management of Carryover Balance
       FDA is committed to reducing the carryover balance to no 
     greater than 21 weeks of the FY 2022 target revenue by the 
     end of FY 2022. However, if FDA is unable to reduce the 
     carryover balance to no greater than 21 weeks during the 
     final year (e.g., over collections in FY 2022 that increase 
     the carryover balance beyond 21 weeks), FDA will (1) outline 
     its plan to reduce the carryover balance to no greater than 
     21 weeks in the FY 2022 BsUFA financial report and (2) update 
     the BsUFA five-year financial plan.


         V. improving fda hiring and retention of review staff

       To speed and improve development of safe and effective 
     biosimilar biological products for patients, enhancements to 
     the biosimilar biological 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. In order to strengthen this core function and 
     increase public access to biosimilar biological products, the 
     FDA will commit to do the following:
     A. Completion of Modernization of the Hiring System 
         Infrastructure and Augmentation of System Capacity
       1. Complete implementation of FTE-based position management 
     system capability.
       a. FDA will complete development of position management 
     baseline accounting of all current positions and FTE counts 
     engaged in the biosimilar biological product review program 
     for each applicable Center and Office including filled and 
     vacant positions, a governance structure for on-going 
     position management that will be accountable to FDA senior 
     management, and position management policy and guidelines 
     ratified by FDA senior management, outlining processes for 
     adding new positions, deleting positions, and changing 
     established positions.

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       b. FDA will complete implementation of the new position-
     based management system.
       2. Complete implementation of an online position 
     classification system
       a. FDA will finalize the establishment of an online 
     Position Description (PD) library. The library will include 
     all current well-classified PDs and current standardized PDs. 
     Once operational, any new PDs classified using the on-line 
     classification tools, and any newly created standardized PDs, 
     will be stored and accessible within FDA's PD library and 
     available for FDA-wide use as appropriate.
       3. Complete implementation of corporate recruiting
       a. For key scientific and technical disciplines commonly 
     needed across offices engaged in the biosimilar biological 
     product review program, FDA will complete the transition from 
     the use of individual vacancy announcements for individual 
     offices to expanded use of a common vacancy announcement and 
     certificate of eligible job applicants that can be used by 
     multiple offices. As a part of this effort, FDA will complete 
     the transition from use of individual announcements that are 
     posted for a limited period to common vacancy announcements 
     with open continuous posting to maximize the opportunity for 
     qualified applicants to apply for these positions.
     B. Augmentation of Hiring Staff Capacity and Capability
       In recognition of the chronic and continuing difficulties 
     of recruiting and retaining sufficient numbers of qualified 
     Human Resources (HR) staff, FDA will engage a qualified 
     contractor to provide continuous support throughout BsUFA II 
     to augment the existing FDA HR staff capacity and 
     capabilities. The utilization of a qualified contractor will 
     assist FDA in successfully accomplishing BsUFA II goals for 
     recruitment and retention of biosimilar biological product 
     review program staff.
     C. Complete Establishment of a Dedicated Function to Ensure 
         Needed Scientific Staffing for Human Drug Review 
         Including for Review of Biosimilar Biological Products
       1. Rapid advances in the science and technology of 
     biosimilar biological product development and manufacturing 
     require FDA's biosimilar biological product review program 
     staff to keep pace with science and learn innovative methods 
     and techniques for review of new therapies. FDA will complete 
     the establishment of a new dedicated unit within the Office 
     of Medical Products and Tobacco charged with the continuous 
     recruiting, staffing, and retention of scientific, technical, 
     and professional staff for the PDUFA and BsUFA review 
     programs.
       a. The unit will continuously develop and implement 
     scientific staff hiring strategies and plans, working closely 
     with the center review offices and the FDA HR office, to meet 
     discipline-specific hiring commitments and other targeted 
     staffing needs. It will function as a scientific-focused 
     recruiter conducting ongoing proactive outreach to source 
     qualified candidates, and conducting competitive recruiting 
     to fill vacancies that require top scientific, technical, and 
     professional talent.
       b. The unit will conduct analyses, no less than annually, 
     of compensation and other factors affecting retention of key 
     staff in targeted disciplines and provide leadership and 
     support for agency compensation oversight boards that 
     currently exist or may be established as needed to ensure 
     retention of key scientific, technical, and professional 
     staff.
     D. Set Clear Goals for Biosimilar Biological Product Review 
         Program Hiring
       1. FDA will establish priorities for management of the 
     metric goals for targeted hires within the biosimilar 
     biological product review program staff for BsUFA II. In 
     particular, FDA will target hiring 15 FTE in FY 2018, to 
     enhance capacity for biosimilar guidance development, 
     reviewer training, and timely communication.
       2. FDA will confirm progress in the hiring of BsUFA I FTEs. 
     FDA will report on progress against the hiring goal for BsUFA 
     II on a quarterly basis posting updates to the FDA website 
     BsUFA Performance webpage.
     E. Comprehensive and Continuous Assessment of Hiring and 
         Retention
       FDA hiring and retention of staff for the biosimilar 
     biological product review program will be evaluated by a 
     qualified, independent contractor with expertise in assessing 
     HR operations and transformation. The BsUFA II 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 VI. It will include continuous 
     assessments throughout the course of implementation of the 
     performance initiatives identified in Sections V.A-D, and 
     metrics including, but not limited to, those related to 
     recruiting and retention in the PDUFA and BsUFA review 
     programs including, but not limited to, specifically targeted 
     scientific disciplines and levels of experience. The 
     contractor will conduct a comprehensive review of current 
     hiring processes and hiring staff capacity and capabilities 
     that contribute to achievement of successes, potential 
     problems, or delays in PDUFA or BsUFA review program staff 
     hiring. This includes the entire hiring function and related 
     capabilities. FDA and regulated industry leadership will 
     periodically and regularly assess the progress of hiring and 
     retention throughout BsUFA II.
       1. Initial Assessment: The assessment will include an 
     initial baseline assessment to be conducted and completed no 
     later than December 31, 2017. The initial baseline study will 
     include an evaluation of the current state and provide 
     recommended options to address any identified gaps or areas 
     identified as priorities for improvement, and a study report 
     to be published no later than December 31, 2017. FDA will 
     hold a public meeting no later than December 31, 2017, to 
     present and discuss report findings, and present its specific 
     plans, including agency senior management oversight, and 
     timeline for implementing recommended enhancements to be 
     fully operational by no later than December 31, 2018.
       2. Interim Assessment: An interim assessment will be 
     published by March 31, 2020, for public comment. By June 30, 
     2020, FDA will hold a public meeting during which the public 
     may present their views. FDA will discuss the findings of the 
     interim assessment, including progress relative to program 
     milestones and metrics, and other aggregated feedback from 
     internal customers and participants in HR services that may 
     be included in the continuous assessment. FDA will also 
     address any issues identified to date including actions 
     proposed to improve the likelihood of success of the program.
       3. Final Assessment: A final assessment will be published 
     by December 31, 2021, for public comment. FDA will hold a 
     public meeting by no later than March 30, 2022, during which 
     the public may present their views. FDA will discuss the 
     findings of the final assessment, including progress relative 
     to program milestones and metrics, and other aggregated 
     feedback from internal customers and participants in HR 
     services that may be included in the continuous assessment. 
     FDA will also address any issues identified and plans for 
     addressing these issues.


                V. DEFINITIONS AND EXPLANATION OF TERMS

       A. The term ``review and act on'' means the issuance of a 
     complete action letter after the complete review of a filed 
     complete application. The action letter, if it is not an 
     approval, will set forth in detail the specific deficiencies 
     and, where appropriate, the actions necessary to place the 
     application in condition for approval.
       B. A resubmitted original application is a complete 
     response to an action letter addressing all identified 
     deficiencies.

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