[Congressional Record Volume 143, Number 160 (Thursday, November 13, 1997)]
[Senate]
[Pages S12653-S12656]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]




    PERFORMANCE GOALS FOR THE PRESCRIPTION DRUG USER FEE ACT OF 1997

 Mr. JEFFORDS. Mr. President, on November 9 the Senate adopted 
Conference Report 105-399, that accompanied S. 830, the Food and Drug 
Administration Modernization Act of 1997. This legislation puts into 
place long-needed reforms in FDA's regulatory procedures and also 
reauthorizes the Prescription Drug User Fee Act of 1992 [PDUFA] for an 
additional 5 years.
  The original PDUFA has brought faster reviews of drug applications. 
By all accounts the success is due to the underlying collaboration and 
partnership between FDA and the developers of innovative new medicines 
in using the fees paid by industry to bring the necessary review 
resources to bear on applications for new drugs. The 1992 act did not 
set the performance goals for activities funded by user fees into the 
law. Rather, these performance goals were set forth in a side-letter 
from the administration to the chairs and ranking members of the House 
Commerce and Senate Labor and Human Resources committees. These 
performance goals in the side-letter have stood the test of time--FDA 
has honored and met these goals as if they were in statute. Based on 
that experience, the Congress has agreed to use this approach again in 
establishing the performance goals for drug reviews funded by user fees 
over the next 5 years.
  Today, I am submitting for the Record a letter addressed to me and 
signed by Secretary of Health and Human Services, Donna E. Shalala, 
dated November 12, 1997. This letter specifies the performance goals 
for the use of PDUFA fees for fiscal years 1998 through 2002. These 
goals, which were agreed to at the conclusion of negotiations between 
FDA officials and pharmaceutical and biotechnology industry 
representatives, are those referred to in section 101(4) of the Food 
and Drug Administration Modernization Act of 1997.
  Mr. President, it is my hope that the next 5 years will see 
reductions in the drug development time, as well as further reductions 
in the time taken to actual review an applications.

[[Page S12654]]

  The letter follows:

                                                  The Secretary of


                                    Health and Human Services,

                                Washington, DC, November 12, 1997.
     Hon. James M. Jeffords,
     Committee on Labor and Human Resources,
     U.S. Senate, Washington, DC.
       Dear Mr. Chairman: As you are aware, the Prescription Drug 
     User Fee Act of 1992 (PDUFA) expired at the end of Fiscal 
     Year 1997. Under PDUFA, the additional revenues generated 
     from fees paid by the pharmaceutical and biological 
     prescription drug industries have been used to expedite the 
     prescription drug review and approval process, in accordance 
     with performance goals that were developed by the Food and 
     Drug Administration (FDA) in consultation with the 
     industries. To date, FDA has met or exceeded the review 
     performance goals agreed to in 1992, and is reviewing over 90 
     percent of priority drug applications in 6 months and 
     standard drug applications in 12 months.
       FDA has worked with representatives of the pharmaceutical 
     and biological prescription drug industries, and the staff of 
     your Committee, to develop a reauthorization proposal for 
     PDUFA that would build upon and enhance the success of the 
     original program. Title I, Subtitle A of the Food and Drug 
     Administration Modernization Act of 1997, S. 830, as passed 
     by the House and Senate on November 9, 1997, reflects the fee 
     mechanisms developed in these discussions. The performance 
     goals referenced in Section 101(4) are specified in the 
     enclosure of this letter, entitled ``PDUFA Reauthorization 
     Performance Goals and Procedures.'' I believe they represent 
     a realistic projection of what FDA can accomplish with 
     industry cooperation and the additional resources identified 
     in the bill.
       This letter and the enclosed goals document pertain only to 
     Title I, Subtitle A (Fees Related to Drugs) of S. 830, the 
     Food and Drug Administration Modernization Act of 1997.
       OMB has advised that there is no objection to the 
     presentation of these views from the standpoint of the 
     Administration's program.
       We appreciate the support of you and your staff, the 
     assistance of other Members of the Committee, and that of the 
     Appropriations Committees, in the reauthorization of this 
     vital program.
           Sincerely,
                                                 Donna E. Shalala.
       Enclosure.

         PDUFA Reauthorization Performance Goals and Procedures

       The performance goals and procedures of the FDA Center for 
     Drug Evaluation and Research (CDER) and the Center for 
     Biologics Evaluation and Research (CBER), as agreed to under 
     the reauthorization of the prescription drug user fee program 
     in the ``Food and Drug Administration Modernization Act of 
     1997,'' are summarized as follows:


                 I. five-year review performance goals

                            Fiscal year 1998

       1. Review and act on 90 percent of standard original New 
     Drug Application (NDAs) and Product License Applications 
     (PLAs)/Biologic License Applications (BLAs) filed during 
     fiscal year 1998 within 12 months of receipt.
       2. Review and act on 90 percent of priority original NDA 
     and PLA/BLA submissions filed during fiscal year 1998 within 
     6 months of receipt.
       3. Review and act on 90 percent of standard efficacy 
     supplements filed during fiscal year 1998 within 12 months of 
     receipt.
       4. Review and act on 90 percent of priority efficacy 
     supplements filed during fiscal year 1998 within 6 months of 
     receipt.
       5. Review and act on 90 percent of manufacturing 
     supplements filed during fiscal year 1998 within 6 months of 
     receipt.
       6. Review and act on 90 percent of all resubmitted original 
     applications filed during the fiscal year 1998 within 6 
     months of receipt, and review and act on 30 percent of Class 
     1 resubmitted original applications within 2 months of 
     receipt.

                            Fiscal year 1999

       1. Review and act on 90 percent of standard original NDA 
     and PLA/BLA submissions filed during fiscal year 1999 within 
     12 months of receipt and review and act on 30 percent within 
     10 months of recept.
       2. Review and act on 90 percent of priority original NDA 
     and PLA/BLA submissions filed during fiscal year 1999 within 
     6 months of receipt.
       3. Review and act on 90 percent of standard efficacy 
     supplements filed during fiscal year 1999 within 12 months of 
     receipt and review and act on 30 percent within 10 months of 
     receipt.
       4. Review and act on 90 percent of priority efficacy 
     supplements filed during fiscal year 1999 within 6 months of 
     receipt.
       5. Review and Act on 90 percent of manufacturing 
     supplements filed during fiscal year 1999 within 6 months of 
     receipt and review and act on 30 percent of manufacturing 
     supplements requiring prior approval within 4 months of 
     receipt.
       6. Review and act on 90 percent of Class 1 resubmitted 
     original applications filed during fiscal year 1999 within 4 
     months of receipt and review and act on 50 percent within 2 
     months of receipt.
       7. Review and act on 90 percent of Class 2 resubmitted 
     original applications filed during fiscal year 1999 within 6 
     months of receipt.

                            Fiscal year 2000

       1. Review and Act on 90 percent of standard original NDA 
     and PLA/BLA submissions filed during fiscal year 2000 within 
     12 months of receipt and review and act on 50 percent within 
     10 months of receipt.
       2. Review and Act on 90 percent of priority original NDA 
     and PLA/BLA submissions filed during fiscal year 2000 within 
     6 months of receipt.
       3. Review and act on 90 percent of standard efficacy 
     supplements filed during fiscal year 2000 within 12 months of 
     receipt and review and act on 50 percent within 10 months of 
     receipt.
       4. Review and act on 90 percent of priority efficacy 
     supplements filed during fiscal year 2000 within 6 months of 
     receipt.
       5. Review and Act on 90 percent of manufacturing 
     supplements filed during fiscal year 2000 within 6 months of 
     receipt and review and act on 50 percent of manufacturing 
     supplements requiring prior approval within 4 months of 
     receipt.
       6. Review and act on 90 percent of Class 1 resubmitted 
     original applications filed during fiscal year 2000 within 4 
     months of receipt and review and act on 50 percent within 2 
     months of receipt.
       7. Review and act on 90 percent of Class 2 resubmitted 
     original applications filed during fiscal year 2000 within 6 
     months of receipt.

                            Fiscal year 2001

       1. Review and act on 90 percent of standard original NDA 
     and PLA/BLA submissions filed during fiscal year 2001 within 
     12 months and review and act on 70 percent within 10 months 
     of receipt.
       2. Review and act on 90 percent of priority original NDA 
     and PLA/BLA submissions filed during fiscal year 2001 within 
     6 months of receipt.
       3. Review and act on 90 percent of standard efficacy 
     supplements filed during fiscal year 2001 within 12 months 
     and review and act on 70 percent within 10 months of receipt.
       4. Review and act on 90 percent of priority efficacy 
     supplements filed during fiscal year 2001 within 6 months of 
     receipt.
       5. Review and act on 90 percent of manufacturing 
     supplements filed during fiscal year 2001 within 6 months of 
     receipt and review and act on 70 percent of manufacturing 
     supplements requiring prior approval within 4 months of 
     receipt.
       6. Review and act on 90 percent of Class 1 resubmitted 
     original applications filed during fiscal year 2001 within 4 
     months of receipt and review and act on 70 percent within 2 
     months of receipt.
       7. Review and act on 90 percent of Class 2 resubmitted 
     original applications within 6 months of receipt.

                            Fiscal year 2002

       1. Review and act on 90 percent of standard original NDA 
     and PLA/BLA submissions filed during fiscal year 2002 within 
     10 months of receipt.
       2. Review and act on 90 percent of priority original NDA 
     and PLA/BLA submissions filed during fiscal year 2002 within 
     6 months of receipt.
       3. Review and act on 90 percent of standard efficacy 
     supplements filed during fiscal year 2002 within 10 months of 
     receipt.
       4. Review and act on 90 percent of priority efficacy 
     supplements filed during fiscal year 2002 within 6 months of 
     receipt.
       5. Review and act on 90 percent of manufacturing 
     supplements filed during fiscal year 2002 within 6 months of 
     receipt and review and act on 90 percent of manufacturing 
     supplements requiring prior approval within 4 months of 
     receipt.
       6. Review and act on 90 percent of Class 1 resubmitted 
     original applications field during fiscal year 2002 within 2 
     months of receipt.
       7. Review and act on 90 percent of Class 2 resubmitted 
     original applications within 6 months of receipt.
       These review goals are summarized in the following tables:

            ORIGINAL NDAs/BLAs/PLAs AND EFFICACY SUPPLEMENTS
------------------------------------------------------------------------
  Submission cohort           Standard                  Priority
------------------------------------------------------------------------
Fiscal year:
  1998..............  90 pct. in 12 mos.......  90 pct. in 6 mos.
  1999..............  30 pct. in 10 mos.......  90 pct. in 6 mos.
                      90 pct. in 12 mos.......  ........................
  2000..............  50 pct. in 10 mos.......  90 pct. in 6 mos.
                      90 pct. in 12 mos.......  ........................
  2001..............  70 pct. in 10 mos.......  90 pct. in 6 mos.
                      90 pct. in 12 mos.......  ........................
  2002..............  90 pct. in 10 mos.......  90 pct. in 6 mos.
------------------------------------------------------------------------


                        MANUFACTURING SUPPLEMENTS
------------------------------------------------------------------------
                               Manufacturing supplements that--
                     ---------------------------------------------------
  Submission cohort     Do not require prior        Do require prior
                             approval\1\                approval
------------------------------------------------------------------------
Fiscal year:
  1998..............  90 pct. in 6 mos........  90 pct. in 6 mos.
  1999..............  90 pct. in 6 mos........  30 pct. in 4 mos.
                                                90 pct. in 6 mos.
  2000..............  90 pct. in 6 mos........  50 pct. in 4 mos.
                                                90 pct. in 6 mos.
  2001..............  90 pct. in 6 mos........  70 pct. in 4 mos.
                                                90 pct. in 6 mos.
------------------------------------------------------------------------
\1\ Changes being effected or 30-day supplements.


                 RESUBMISSION OF ORIGINAL NDAs/BLAs/PLAs
------------------------------------------------------------------------
  Submission cohort            Class 1                   Class 2
------------------------------------------------------------------------
Fiscal years:
  1998..............  90 pct. in 6 mos........  90 pct. in 6 mos.
                      30 pct. in 2 mos........  ........................
  1999..............  90 pct. in 4 mos........  90 pct. in 6 mos.
                      50 pct. in 2 mos........  ........................
  2000..............  90 pct. in 4 mos........  90 pct. in 6 mos.
                      70 pct. in 2 mos........  ........................
  2001..............  90 pct. in 2 mos........  90 pct. in 6 mos.

[[Page S12655]]

 
  2002..............  90 pct. in 2 mos........  90 pct. in 6 mos.
------------------------------------------------------------------------

            II. NEW MOLECULAR ENTITY (NME) PERFORMANCE GOALS

       The performance goals for standard and priority original 
     NMEs in each submission cohort will be the same as for all of 
     he original NDAs (including NMEs) in each submission cohort 
     but shall be reported separately.
       For biological products, for purposes of this performance 
     goal, all original BLAs/PLAs will be considered to be NMEs.


                     iii. meeting management goals

                    A. Responses to Meeting Requests

       1. Procedure: Within 14 calendar days of the Agency's 
     receipt of a request from industry for a formal meeting 
     (i.e., a scheduled face-to-face, teleconference, or video 
     conference) CBER and CDER should notify the requester in 
     writing (letter or fax) of the date, time, and place for the 
     meeting, as well as expected Center participants.
       2. Performance Goal: FDA will provide this notification 
     within 14 days for 70% of requests (based on request receipt 
     cohort year) starting in FY 1999; 80% in FY 2000; and 90% in 
     subsequent fiscal years.

                         B. Scheduling meetings

       1. Procedure: The meeting date should reflect the next 
     available date on 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. If the requested date for 
     any of these types of meetings is greater than 30, 60, or 75 
     calendar days (as appropriate) from the date the request is 
     received by the Agency, the meeting date should be within 14 
     calendar days of the date requested.
       Type A Meetings should occur within 30 calendar days of the 
     Agency receipt of the meeting request.
       Type B Meetings should occur within 60 calendar days of the 
     Agency receipt of the meeting request.
       Type C Meetings should occur within 75 calendar days of the 
     Agency receipt of the meeting request.
       2. Performance goal: 70% of meetings are held within the 
     time frame (based on cohort year of request) starting in FY 
     1999; 80% in FY 2000; and 90% in subsequent fiscal years.

                           C. Meeting minutes

       1. 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.
       2. Performance goal: 70% of minutes are issued within 30 
     calendar days of date of meeting (based on cohort year of 
     meeting) starting in FY 1999; 89% in FY 2000; and 90% in 
     subsequent fiscal years.

                             D. Conditions

       For a meeting to qualify for these performance goals:
       1. A written request (letter or fax) should be submitted to 
     the review division; and
       2. The letter should provide: a. A brief statement of the 
     purpose of the meeting; b. a listing of the specific 
     objectives/outcomes the requester expects from the meeting; 
     c. a proposed agenda, including estimated times needed for 
     each agenda item; d. a listing of planned external attendees; 
     e. a listing of requested participants/disciplines 
     representative(s) from the Center; f. the approximate time 
     that supporting documentation (i.e., the ``backgrounder'') 
     for the meeting will be sent to the Center (i.e., ``x'' weeks 
     prior to the meeting, but should be received by the Center at 
     least 2 weeks in advance of the scheduled meeting for Type A 
     or C meetings and at least 1 month in advance of the 
     scheduled meeting for Type B meetings); and
       3. 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'' meeting will be honored 
     except in the most unusual circumstances.


                           iv. clinical holds

                              A. 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.

                          B. Performance goal

       75% of such responses are provided within 30 calendar days 
     of the Agency's receipt of the sponsor's response starting in 
     FY 98 (cohort of date of receipt) and 90% in subsequent 
     fiscal years.


                      v. major dispute resolution

                              A. 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 divisional level 
     (including a request for reconsideration by the Division 
     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.

                          B. Performance goal

       70% of such answers are provided within 30 calendar days of 
     the Center's receipt of the written appeal starting in FY 
     1999; 80% in FY 2000; and 90% in subsequent fiscal years.

                             C. Conditions

       1. Sponsors should first try to resolve the procedural or 
     scientific issue at the Division level. If it cannot be 
     resolved at that level, it should be appealed to the Office 
     Director level (with a copy to the Division Director) and 
     then, if necessary, to the Deputy Center Director or Center 
     Director (with a copy to the Office Director).
       2. 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 
     deny or grant the appeal.
       3. If the decision is to deny the appeal, the response 
     should include reasons for the denial and any actions the 
     sponsor might take in order to persuade the Agency to reverse 
     its decision.
       4. 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).
       5. 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.
       6. 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 in order to persuade the 
     Agency to reverse its decision.
       7. N.B. If the Agency decides to present the issue to any 
     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 in order to allow 
     conformance with advisory committee administrative 
     procedures.


         VI. SPECIAL PROTOCOL QUESTION ASSESSMENT AND AGREEMENT

                              A. 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.
       1. 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).
       2. 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, data analyses are adequate to 
     achieve the goals of the sponsor, the reasons for the 
     disagreement will be explained in the response.
       3. 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.)
       4. 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 trails that will form the primary basis of an 
     efficacy claim no matter what phase of drug development in 
     which they happen to be conducted.
       5. If a protocol is reviewed under the process outline 
     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.

                          B. Performance goal

       60% of special protocols assessments and agreement requests 
     completed and returned to sponsor within time frames (based 
     on cohort year of request) starting in FY 1999; 70% in FY 
     2000; 80% in FY 2001; and 90% in FY 2002.


              vii. electronic applications and submissions

       The Agency shall develop and update its information 
     management infrastructure to allow, by fiscal year 2002, the 
     paperless receipt and processing of INDs and human drug 
     applications, as defined in PDUFA, and related submissions.

[[Page S12656]]

                      viii. additional procedures

                  A. Simplification of action letters

       To simplify regulatory procedures, the CBER and CDER intend 
     to amend their regulations and processes to provide for the 
     issuance of either an ``approval'' (AP) or a ``complete 
     response'' (CR) action letter at the completion of a review 
     cycle for a marketing application.

   B. Timing of sponsor notification of deficiencies in applications

       To help expedite the development of drug and biologic 
     products, CBER and CDER intend to submit deficiencies to 
     sponsors in form of an ``information request'' (IR) letter 
     when each discipline has finished its initial review of its 
     section of the pending application.


                ix. definitions and explanation of terms

       A. The term ``review and act on'' is understood to mean 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 major amendment to an original application submitted 
     within three months of the goal date extends the goal date by 
     three months.
       C. A resubmitted original application is a complete 
     response to an action letter addressing all identified 
     deficiencies.
       D. 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):
       1. Final printed labeling;
       2. Draft labeling;
       3. 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);
       4. Stability updates to support provisional or final dating 
     periods;
       5. Commitments to perform Phase 4 studies, including 
     proposals for such studies;
       6. Assay validation data;
       7. Final release testing on the last 1-2 lots to support 
     approval;
       8. A minor reanalysis of data previously submitted to the 
     application (determined by the agency as fitting the Class 1 
     category);
       9. Other minor clarifying information (determined by the 
     Agency as fitting the Class 1 category); and
       10. Other specific items may be added later as the Agency 
     gains experience with the scheme and will be communicated via 
     guidance documents to industry.
       E. Class 2 resubmissions are resubmissions that include any 
     other items, including any item that would require 
     presentation to an advisory committee.
       F. A Type A Meeting is a meeting which is necessary for an 
     otherwise stalled drug development program to proceed (a 
     ``critical path'' meeting).
       G. A Type B Meeting is a (1) pre-IND, (2) end of Phase 1 
     (for Subpart E or Subpart H or similar products) or end of 
     Phase 2/pre-Phase 3, or (3) a pre-NDA/PLA/BLA meeting. Each 
     requestor should usually only request 1 each of these Type B 
     meetings for each potential application (NDA/PLA/BLA) (or 
     combination of closely related products, i.e., same active 
     ingredient but different dosage forms being developed 
     concurrently).
       H. A Type C Meeting is any other type of meeting.
       I. 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.

                          ____________________