SOPP 8406: Managing PDUFA User Fee Payments and Billing Activities

Version #4

Effective Date: Date: October 19, 2009

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1. Purpose

This document describes the procedures used to determine the accuracy of information submitted by an applicant and to verify user fee payments relative to the Prescription Drug User Fee Act (PDUFA) of 1992, as reauthorized by the Food and Drug Administration Amendments Act of 2007.  In addition, this document identifies other user fee activities for which the Office of Management’s Regulatory Information Management Staff (RIMS) is responsible.

2. Definitions

Application

An original Biologics License Application (BLA) or New Drug Application (NDA).

Supplement

Any submission requesting approval of a change to an approved BLA or NDA.

Unacceptable for Filing

The application/supplement is not accepted by the Food and Drug Administration for review. PDUFA requires this action in situations in which an applicant is determined to be in arrears for ANY user fees owed the federal government. (This is a different status from an application that has been refused to file based on deficiencies as described in SOPP 8404: Refusal to File Procedures for Biologics License Applications.)

Arrears Status - There are two types of arrears status:

1. In Arrears for Non-payment of Fees Invoiced: An applicant will be determined to be in arrears for any prescription drug user fee owed the federal government if that applicant has not paid all fees by the payment due date to the satisfaction of the FDA Office of Financial Management (OFM). All fees include annual product fees, establishment fees, and application fees for which they have been invoiced. Failure to submit timely payment of the invoice results in the applicant being listed on the Arrears & Payment Report.
2. In Arrears for a specific submission: An applicant will be determined to be in arrears for a particular submission if OFM has not received confirmation that an application fee has been received by the designated bank within five calendar days of the date the submission is received by FDA. The application will not be accepted for filing until payment is made. However, this does notresult in the applicant being placed on the Arrears & Payment Report or being invoiced. Unrelated applications or supplements from the same applicant may be accepted for filing as long as any required fees for those submissions are paid.

Arrears & Payment Report

A daily report from OFM sent via e-mail to RIMS which shows Center for Biologics Evaluation and Research (CBER) and Center for Drugs Evaluation and Research (CDER) regulated applicants who are in arrears for non-payment of fees, or who have made payment for outstanding fees owed. This report is posted in CBER's Outlook Public Folder, “PDUFA Arrears List & General Information.”

CBER Check Receipt Report

A daily report from OFM sent via e-mail to RIMS which shows payment made by applicants for incoming CBER submissions. This report is forwarded by RIMS to the designated contact in the review office receiving the submission.

 

3. Background
On October 29, 1992, the President signed the original PDUFA.  The law sunsets every five years and must be reauthorized by Congress. The Food and Drug Administration Amendments Act of 2007 (FDAAA) embodies the most recent reauthorization.  PDUFA authorizes FDA to assess and collect fees for certain drug and biologics license applications and supplements as well as product and establishment fees for approved products.  Because user fees are required to be submitted concurrently with applications, review of an application cannot begin until the fee has been submitted.  Form FDA 3397, the PDUFA user fee cover sheet, is designed to provide the minimum necessary information to determine whether a fee is required for review of an application, to determine the amount of the fee required, and to help FDA track payments.

Each fiscal year FDA is required to announce prescription drug user fee rates.  Rates are set for annual product, establishment, and application fees.  The fees are announced in the Federal Register on an annual basis usually in August.   

Human drug applications and supplements subject to fees are:

1. those submitted under section 505(b)(1) of the Food, Drug and Cosmetic Act (FD&C Act);
2. those submitted under 505(b)(2) of the FD&C Act after September 30, 1992 and which request approval of a molecular entity which is an active ingredient or new indication for use not previously approved under 505(b)(1) application; and
3. applications for initial certification or initial approval of an antibiotic drug under section 507; and
4. applications for licensure of a biological product under section 351 of the Public Health Service Act.

FDA Form 3397, User Fee Cover Sheet, is an on-line form completed by applicants via the FDA website.

The form provides a cross-reference of the fee submitted for an application by using a unique number tracking system to assign the user fee payment identification number. The information collected is used to initiate the administrative screening of new drug applications, biologics license applications, and supplemental applications for user fee purposes and to reconcile payments with these submissions.

 

4. Policy

Each application and supplement should be accompanied by a Form FDA 3397, User Fee Cover Sheet. Information submitted must be verified to determine that the correct fee has been submitted.

The User Fee Cover Sheet need not be included with applications for the following non-PDUFA products, nor for any manufacturing supplements that do not require clinical data for approval.

• • Human blood and blood components for transfusion;
  • Blood grouping reagents, and blood bags;
  • Certain drugs derived from bovine blood;
  • Cord blood and peripheral blood stem cells separated from whole blood by physical or mechanical means for IV administration (per Office of Chief Counsel, 2005);
  • In vitrodiagnostic devices;
  • Crude Allergenic Extracts
  • Responsibilities

1. Person or Area	Responsibility
   OFM Office of Financial Management	sends daily CBER Check Receipt Report to RIMS annually establishes PDUFA user fee rates and publishes them in the Federal Register receives PDUFA payments sends daily notification to RIMS of Arrears and Payment Report
   RIMS Regulatory Information Management Staff in CBER's Office of Management	posts current user fee rates in CBER public folder enters user fee payment information in RMS-BLA reviews CBER payment check receipt reports received from OFM and verifies proper payment for submissions forwards notification of CBER payment checks received to review office RIS\RHIS staff - official payment date for resetting action due dates is on the report distributes Arrears and Payment Report to review office RIS\RHIS staff and posts report in CBER public folder reviews faxed copy of User Fee Cover Sheet from RPM notifies applicant of payment discrepancies and follows through to resolution; coordinates with RPM as appropriate promptly notifies review office RIS\RHIS staff and RPM of payment by applicant when firm in Arrears submits payment monitors the status of all applications and supplements that have been designated as Unacceptable for Filing serves as the primary point of contact for questions or challenges regarding user fee assessments   Other User Fee Activities for which RIMS alone is responsible (procedures are not included in this SOPP) Annual user fee billing of firms for biologic products Responds to waiver and refund requests for biologic products Maintains the List of User Fee Billable Biologics on the FDA Internet Maintains the List of Discontinued CBER Biologics Responds to inquiries from the review offices and the public on user fee issues   Produces a number of reports on user fee receipts and performance
   Designated review office contacts (usually RIS\RHIS)	reviews Arrears and Payment Report and distributes according to office policy forwards notification of CBER payment checks received to appropriate RPM ensures correct user fee flags have been selected in RMS-BLA as part of quality control (Submission Information screen)
   RPM Regulatory Project Manager(s) in the review office (or office designee)	checks User Fee Cover Sheet for accuracy and completeness; if not accurate or complete RPM will contact applicant to resolve ensures User Fee Cover Sheet is faxed to RIMS (original applications and efficacy supplements only) ensures payment is received from applicant for submission checks Arrears & Payment report in CBER's "Outlook Public Folder" before Acknowledgement letter is prepared ensures user fee flags have been selected in RMS-BLA (Submission Information screen) notifies applicant when application is unacceptable for filing notifies review committee when application is unacceptable for filing that review is halted ensures communication for Unacceptable for Filing letter is entered in RMS-BLA when appropriate reactivates review when notified by RIMS that the applicant is up-to-date on payments ensures close date for Unacceptable for Filing milestone is entered in RMS-BLA using the "official payment date" provided by RIMS or as indicated on the CBER payment check report

6. Procedures

Routine Processing

1. Each application and supplement should be accompanied by FDA Form 3397, User Fee Cover Sheet (see exceptions under the Policy section of this SOPP). The User Fee Cover Sheet will be forwarded by the Document Control Center (DCC) with the application to the appropriate review division. The original User Fee Cover Sheet will be retained with the original copy of the application in DCC.
2. The RPM will review the User Fee Cover Sheet and verify that any exclusion checked on the cover sheet is accurate (e.g., orphan drug designation exemption, small business waiver, etc.). A complete list of exclusions can be found on the User Fee Cover Sheet.
3. The RPM will fax a copy of the User Fee Cover Sheet to RIMS (all original applications and efficacy supplements, only) at 301-827-2875.
4. An STN (Submission Tracking Number) will be assigned to the application following division standard operating procedures.
5. At the time of STN assignment, as part of the initial administrative regulatory review, the RPM will compare the User Fee Cover Sheet with the submission to determine if the application is subject to user fees. The RPM will also check the current Arrears and Payment Report to ensure the applicant is not in arrears.
   1. If the submission is NOT subject to fees and the applicant is not in arrears, there are no further steps to follow.
   2. Whether or not the submission is subject to fees, if the applicant is in arrears the submission will be deemed Unacceptable for Filing. The RPM will contact the applicant to advise of the unacceptable status, prepare an Unacceptable for Filing acknowledgment letter and notify RIMS.
6. Finally, for submissions subject to user fees, the RPM will confirm as necessary with RIMS that payment has been received for the submission. If the payment was received and there is a discrepancy in the amount received, RIMS will notify the applicant of the correct amount to be submitted or refunded.

Note: Review of the submission should continue while payment discrepancies are resolved.

Submissions Received Without a User Fee Cover Sheet or With an Incomplete Sheet

If an application or supplement is received without an accompanying User Fee Cover Sheet, the RPM will contact the applicant by telephone and request immediate submission of a completed form.

If an incomplete or inaccurate form is submitted with an application, the RPM will contact the firm by telephone to obtain the necessary information or relay the inaccuracy.

An application or supplement should not proceed to a filing action until the information is obtained.

Failure to Submit Payment

1. If no payment is received within 5 calendar days of the CBER receipt date of the submission, the RPM (or office designee) will:
   1. notify the review committee to halt the review
   2. notify the applicant by telephone that the application is unacceptable for filing
   3. prepare a notification letter using the CBER Unacceptable for Filing letter template
   4. enter a communication in RMS-BLA for the Unacceptable for Filing letter. This entry changes the status of the submission to Unacceptable for Filing and removes the due/hold dates of any pending milestones.

Note: The Act stipulates that the failure to pay an application fee causes that application to be Unacceptable for Filing. This is a different status from an application that has been Refused to File based on deficiencies in content of the submission.

2. The application may be sent to DCC for storage until the review is reactivated. (This is the exception to the rule. Please contact DCC if this is necessary.)
3. Any applications from the in-arrears applicant that were pending prior to the applicant going into arrears will continue to be reviewed.
4. Any applications submitted by the applicant while the applicant is in arrears will be deemed Unacceptable for Filing.
5. When RIMS notifies the review office that fees owed have been paid, the review process will be reactivated. The RPM will:
   1. notify the committee that the review process may proceed
   2. if the application was stored in DCC, instruct DCC to forward the submission to the committee
   3. prepare a notification letter using CBER Notification of Receipt of Fees Owed letter template
   4. reset the user fee action due dates; enter close date for the Unacceptable for Filing milestone in RMS-BLA. The RPM should use the payment receipt date indicated on the CBER Check Receipt Report. RMS-BLA automatically calculates the new action due dates based on the close date (payment receipt date).

 

8. References

The current prescription drug user fee rates

Prescription Drug User Fee Act (PDUFA) of 1992

Food and Drug Administration Amendments Act of 2007 (FDAAA)

 

9. Effective Date

October 19, 2009

 

10. History

9. Written By	Approved By	Approval Date	Version Number	Comment
   CBER Application Policy Task Force	M. Beatrice	3/23/1994	1	Reissued as SOPP 8406 in August 1997. No change to Guide content
   Roger Eastep Gilliam Conley Chris Nemoff Darcel Bigelow Carla Vincent	Robert Yetter, PhD	4/11/2001	2	This revision further clarifies the responsibilities and procedures. It supercedes version 1 of this SOPP issued August 27, 1997 [originally issued as #OD-R-6-94 on March 23, 1994]
   Roger Eastep	Robert Yetter, PhD	8/10/2001	3	Removal of plasma volume expanders from the non-User Fee list in Section 5
   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.