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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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SOPP 8406: CBER Processing of PDUFA Payment Information

Version #5
Effective Date:  October 7, 2013

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  1. Purpose
    This Standard Operating Policy and Procedure (SOPP) provides guidance to Center for Biologics Evaluation and Research (CBER) staff on the procedures for verifying application payments in accordance with the Prescription Drug User Fee Act (PDUFA).  In addition, this SOPP identifies other billing activities for which CBER’s Office of the Center Director, Associate Director for Review Management, Business Operations Staff (OD/ADRM/BOS) is responsible.

     

  2. Scope
    This SOPP applies to original Biologics License Applications (BLAs), New Drug Applications (NDAs), and efficacy supplements regulated by CBER which are subject to PDUFA.  These include:
    1. Applications submitted for licensure under Section 351(a) of the Public Health Service Act.  These application types are BLAs and efficacy supplements. (See exceptions below in section V.C.)
    2. Applications submitted under Section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).  These application types are NDAs and NDA supplements containing clinical data.

     

  3. Background
    1. The FD&C Act as amended by PDUFA, authorizes FDA to collect fees from the pharmaceutical industry to augment appropriations spent on FDA’s human drug review process.  FDA spends fee revenues to hire, support, and maintain personnel for the review of human drug applications to ensure safe and effective prescription drugs reach the American public more quickly.
    2. PDUFA authorizes FDA to assess and collect fees for certain drug and biologic license applications and supplements as well as product and establishment fees for approved products.  Because user fee application payments are required to be submitted concurrently with applications, review of an application cannot begin until the fee has been submitted.
    3. In certain circumstances, application fees do not apply, but the applications are still subject to PDUFA requirements.  These PDUFA user fee exclusions apply to the following product-types:
      • A drug that is not distributed commercially and is the subject of an application or supplement submitted by a state or United States government entity
      • An orphan drug with only a rare disease indication
    4. An Electronic PDUFA User Fee Cover Sheet is used to submit information on human drug applications and supplements subject to PDUFA.  A Web link to the cover sheet appears in the Reference Section.
    5. Each fiscal year FDA is required to announce prescription drug user fee rates for the coming fiscal year.  Rates are set for product, establishment, and application fees.  The rates are published in the Federal Register 60 days before the start of the fiscal year.  A Web link to the current user fee rates appears in the Reference Section.

     

  4. Definitions
    1. Application - A submission for licensure of a BLA submitted under Section 351 of the Public Health Service Act or an NDA submitted under Section 505 of the FD&C Act.
    2. Efficacy Supplement - A supplement to an approved application proposing to make one or more related changes from among the following changes to product labeling (21 CFR 314.3):
      1. Add or modify an indication or claim;
      2. Revise the dose or dose regimen;
      3. Provide for a new route of administration;
      4. Make a comparative efficacy claim naming another drug product;
      5. Significantly alter the intended patient population;
      6. Change the marketing status from prescription to over-the-counter use;
      7. Provide for, or provide evidence of effectiveness necessary for, the traditional approval of a product originally approved under subpart H of part 314; or,
      8. Incorporate other information based on at least one adequate and well-controlled clinical study.
    3. PDUFA - A United States law enacted in 1992, which is periodically reviewed and revised, authorizing FDA to collect fees from companies that apply for approval and market certain human drug and biological products. The fees are used to hire review staff and for other related drug and biologic review purposes so that application review timeline goals can be met.
    4. PDUFA Payment and Arrears Report - A daily email report from the Office of Financial Management (OFM) which provides a running list of applicants who have made an application/supplement payment as well as a list of applicants in arrears for non-payment of annual product, establishment and/or application fees invoiced. Note: the PDUFA Payment and Arrears Report is posted for reference in CBER's Outlook Public Folder, PDUFA Arrears List & General Information.
    5. PDUFA Receipts Report - A daily email report from OFM which provides payment information for applications and supplements received on that date.
    6. Supplement - A submission requesting approval of a change to an approved BLA (21 CFR 600.3) or NDA.
    7. Unacceptable for Filing - The application/supplement is not accepted by the FDA for review. Note:  PDUFA requires this action when the applicant has not submitted payment for the application/supplement or is determined to be in arrears for non-payment of annual product, establishment or application fees invoiced.

     

  5. Policy
    1. Each application and efficacy supplement should include a completed PDUFA User Fee Cover Sheet, unless specifically exempted below. The cover sheet is completed by the applicant on FDA’s User Fee Web site.
    2. The PDUFA User Fee Cover Sheet should be included with applications or supplements which meet one of the following user fee exclusions under the FD&C Act.  The exclusion is entered by the applicant when completing the PDUFA User Fee Cover Sheet:
      • A large volume parenteral drug product approved under Section 505 of the FD&C Act before September 1, 1992
      • The application qualifies for the orphan exception under Section 736(a)(1)(F) of the FD&C Act
      • The application is submitted by a State or Federal government entity for a drug that is not distributed commercially
      • The applicant has been granted a small business waiver
    3. Manufacturing supplements and labeling supplements do not include user fee defined clinical data and therefore do not require a PDUFA User Fee Cover Sheet.
    4. The PDUFA User Fee Cover Sheet need not be included with applications or supplements for the following non-PDUFA products:
      • Whole blood or blood components for transfusion
      • Blood bags
      • Bovine blood products for topical application licensed before September 1, 1992
      • Cord blood and peripheral blood stem cells separated from whole blood by physical or mechanical means for transfusion
      • Crude allergenic extracts
      • An in vitro diagnostic biologic product (these BLAs are for biologics that are also medical devices and are subject to MDUFA rather than PDUFA). Refer to SOPP 8704: Managing MDUFA User Fee Payments and Billing Activities.
      • Biological products for further manufacturing use only
    5. Not all supplements containing clinical data are subject to user fees.  The Guidance for Industry: Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User Fees provides the definition of clinical data for user fee purposes.  In addition, the Regulatory Management System-Biologics License Application (RMS-BLA) Data Dictionary provides descriptions of each supplement type which may also help determine the appropriate classification.
    6. When there is a question as to how a submission should be classified contact  OD/ADRM/BOS by emailing ‘CBER PDUFA Staff’ for guidance.
    7. When an applicant fails to submit timely payment of an invoice issued by FDA, the applicant is listed on OFM’s PDUFA Payment and Arrears Report. All applications and supplements including manufacturing and labeling supplements received by an applicant on arrears for non-payment of fees invoiced are deemed Unacceptable for Filing.
    8. When an applicant fails to submit payment for a BLA, NDA or efficacy supplement that is subject to a user fee, the application or supplement is Unacceptable for Filing.  There is a five (calendar) day grace period within which the payment must be received before the application/supplement is deemed Unacceptable for Filing.  Note: failure to submit payment for a specific application or supplement does not result in the applicant being placed on OFM’s PDUFA Payment and Arrears Report.  Other applications and supplements from the applicant may be accepted for filing as long as any required fees for those submissions are received.

     

  6. Responsibilities
    1. FDA/Office of the Commissioner (OC)
      1. Annually establishes PDUFA user fee rates and publishes them in the Federal Register.
    2. FDA/ Office of Financial Management (OFM)
      1. Receives notice of PDUFA payments from the U.S. Bank.
      2. Sends daily PDUFA Payment and Arrears Report to CBER PDUFA Staff.
      3. Sends daily PDUFA Receipts Report to CBER PDUFA Staff.
    3. Office of the Center Director, Associate Director for Review Management, Business Operations Staff (OD/ADRM/BOS)
      1. Monitors the CBER PDUFA Staff email account.
      2. Provides guidance to review offices on whether or not a submission is subject to user fees.
      3. Reviews the PDUFA Receipts Report and notifies the Regulatory Project Manager (RPM) of payment receipts for incoming applications/supplements via the CBER PDUFA Staff email account.
      4. Reviews the PDUFA User Fee Cover Sheet for accuracy and completeness; if missing, inaccurate or incomplete, contacts the applicant to resolve the issue.
      5. Verifies that any exclusion checked on the PDUFA User Fee Cover Sheet is accurate. Enters user fee payment data in RMS-BLA based on reconciliation of the subject PDUFA User Fee Cover Sheetwith the PDUFA Receipts Report.
      6. Contacts the applicant if there are any payment discrepancies, e.g., applicant did not pay current fiscal year rate.  Coordinates with OFM until resolved.
      7. Monitors the daily PDUFA Payment and Arrears Report for CBER applicants and notifies review offices of firms in arrears when applicable.
      8. Monitors status of all applications/supplements that have been designated as Unacceptable for Filing. Notifies the RPM when payment is received.
      9. Restarts the review clock in RMS-BLA when payment is received for an application/supplement that is deemed Unacceptable for Filing.
      10. Posts current user fee rates and list of firms in arrears in CBER’s Outlook public folder: PDUFA Arrears List & General Information.
      11. Identifies biologic products and establishments subject to annual user fees and provides product and applicant information to the Center for Drug Evaluation and Research (CDER) for invoicing.
      12. Responds to biologic product refund and waiver requests for application, product and establishment fees.
      13. Maintains the PDUFA list of User Fee Billable Biologic Products and Potencies on FDA’s Internet Web site.
      14. Maintains the PDUFA list of Discontinued Biologics on FDA’s Internet Web site.
    4. Regulatory Project Manager (RPM)
      1. Receives the submission and determines type of application/supplement for classification in RMS-BLA and whether it is subject a user fee.
      2. Emails the PDUFA User Fee Cover Sheet or Electronic Document Room (EDR) link to the cover sheet to CBER PDUFA Staff email account.
      3. Verifies user fee payment receipt for the application/supplement with OD/ADRM/BOS via the CBER PDUFA Staff email account.
      4. Notifies the applicant when a user fee has not been received for the application/supplement and that the review is on hold pending receipt of payment.
      5. Verifies that any exclusion checked on the PDUFA User Fee Cover Sheet is accurate.
      6. Alerts the review committee when the application/supplement is Unacceptable for Filing that review may not begin.
      7. Issues an Acknowledgment/Unacceptable for Filing letter to the applicant.
      8. Ensures the Acknowledgement/Unacceptable for Filing letter is entered into RMS-BLA. (Entry of this communication stops the review clock.)
      9. Notifies review committee to resume review when payment for the application/supplement is received.

     

  7. Procedures
    1. Routine Processing of Submission Cover Sheets
      1. Compares the PDUFA User Fee Cover Sheet with the submission to determine if the application or supplement is subject to user fees. [RPM]
        1. If there is a question about whether the application or supplement is subject to a user fee, contacts review office management and/or OD/ADRM/BOS via the CBER PDUFA Staff email account for guidance.
        2. If the application/supplement is subject to user fees, verifies payment receipt with OD/ADRM/BOS via the CBER PDUFA Staff email account.  If payment was received and there is a discrepancy in the payment amount, OD/ADRM/BOS resolves it.  Note: Payment discrepancies do not affect the review clock.
      2. Verifies that any application fee exclusion checked on the PDUFA User Fee Cover Sheet is accurate (e.g., orphan drug designation, small business waiver, etc.). See list of exclusions under section V.B. above.[RPM and OD/ADRM/BOS]
      3. Emails a copy of the PDUFA User Fee Cover Sheet or EDR link to CBER PDUFA Staff. [RPM]
    2. Processing submissions Received Without a PDUFA User Fee Cover Sheet or With an Incomplete Cover Sheet
      1. Contacts the applicant and requests immediate submission of a completed form if an application or efficacy supplement is received without a PDUFA User Fee Cover Sheet.  Once the PDUFA Cover Sheet is received follows the procedures under Section A above. [RPM]
      2. Contacts the applicant to obtain the necessary information or relay the inaccuracy, if an incomplete or inaccurate form is submitted with an application.  An application/supplement should not proceed to a filing action until the information is obtained. [OD/ADRM/BOS]
    3. Processing submissions received without Payment
      1. If payment is not received within five calendar days of the CBER receipt date of the application/supplement:
        1. Notifies the review committee to halt the review. [RPM]
        2. Notifies the applicant that the application/supplement is Unacceptable for Filing (by phone and/or email). [RPM]
        3. Prepares a notification letter using the CBER Acknowledgement/ Unacceptable for Filing letter template for issuance. [RPM]
        4. Enters the Acknowledgement/Unacceptable for Filing letter in RMS-BLA which stops the review clock.  This letter entry also changes the status of the submission in RMS-BLA to Unacceptable for Filing. [RPM]
      2. Once payment has been received the review process is reactivated.
      3. Notifies the RPM when fees owed have been paid. [OD/ADRM/BOS]
      4. Notifies the review committee that the review process may proceed. [RPM]
      5. Enters the payment date in RMS-BLA based on the payment date indicated in the PDUFA Receipts Report and resets the STN status to pending. [OD/ADRM/BOS]

        Note: RMS-BLA automatically calculates the new action due dates based on the payment receipt date.

     

  8. Appendix – N/A

     

  9. References
    1. The Reference below is located on CBER’s Intranet Web Page (unless otherwise noted)
      1. RMS-BLA Data Dictionary (accessed via RMS-BLA)
    2. Web links to the References below can be found in the list following the History Table
      1. PDUFA User Fee Cover Sheet
      2. PDUFA User Fee Rates
      3. Guidance for Industry Submitting Separate Marketing Applications and Clinical Data for Purposes of Assessing User Fees

     

  10. History
Written/Updated By Approved By Approval Date Version Number Comment
Carla Vincent Robert Yetter, PhD 10/7/2013 5 Updated to new standard SOPP format and to reflect minor changes in process since last revision.
Carla Vincent Robert Yetter, PhD 10/5/2009 4 Updated to reflect changes to the process due to the on-line user fee cover sheet and FDAAA and to include other user fee activities for which RIMS is responsible.  Comments from BPWG and RMCC incorporated.
Roger Eastep Robert Yetter, PhD 8/10/2001 3 Removal of plasma volume expanders from the non-User Fee list in Section 5.
Gilliam Conley
Darcel Bigelow
Roger Eastep
Chris Nemoff
Carla Vincent
Robert Yetter, PhD 4/11/2001 2 This revision further clarifies the responsibilities and procedures. It supersedes version 1 of this SOPP.
CBER Application Policy Task Force M. Beatrice 3/23/1994 1 Reissued as SOPP 8406 in August 1997. No change to Guide content.
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References

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