Manual of Standard Operating Procedures and Policies

Regulatory - License Applications

Changes to an Approved Application - Administrative Handling and Review of Annual Reports

 

SOPP 8411.1

Version #3

Date: October 26, 2001
  1. Purpose
    2.

    The purpose of this guidance is to describe the administrative procedures for receipt and handling of Annual Reports submitted to CBER as required in the revised 21 CFR 601.12. This document will also describe the procedures for review of these reports.

  2. Background
    3.

    On July 24, 1997, the final rule, "Changes to an Approved Application" was published in the Federal Register. This revision to 21 CFR 601.12 established three reporting categories for changes to product, manufacturing processes, personnel, facilities, equipment and labeling. One of the reporting categories was the Annual Report, a mechanism not previously used for licensed products.

    Annual Report changes do not require the submission of a supplement. The changes described in this category are designed to tighten control on the production process, or have minimal potential to have an adverse impact on the identity, purity, potency, strength or quality of the product as they may relate to its safety or efficacy. For changes in this category, as with all changes, the applicant is responsible for performing appropriate studies and tests to assure that there has been no adverse effect on the identity, purity, potency, strength or quality of the product as they may relate to its safety or efficacy.

  3. Policy

    4. All Annual Reports for changes to an approved application are submitted to CBER through the Document Control Center (DCC). Annual Reports will be logged in, routed for review, reviewed for adequacy, and then filed in DCC. It is the policy of CBER that an initial review of each Annual Report to determine whether the changes are appropriately reported will be completed within 90 days of the receipt of the Report. If changes are inappropriately reported in the Annual Report, the applicant will be notified immediately. Annual Reports should be completely reviewed within 180 days of receipt, and must be reviewed prior to filing by DCC. Generally it is CBER's policy to allow applicants to address problems found on review of Annual Reports with minimal expense and without unnecessary waste. However, if circumstances warrant, the agency may require the change to be immediately discontinued or compliance action may be taken.

  4. Responsibilities
    5.

    DCC

    • Receive all Annual Reports
    • Log all Annual Reports into the tracking system.
    • Route copies of the Annual Report for review.
    • File Annual Reports into appropriate license application folder after review.

    Applications Division Director

    • Identify a Regulatory Project Manager (RPM) for each approved product (or group of products) that will be receiving annual reports
    • Participates in discussions of and decisions pertaining to inappropriate changes.

    Regulatory Project Manager

    • Coordinates the review of the Annual Report
    • Ensure that the Annual Report is routed for review to other reviewers, Divisions, or Offices as necessary
    • Ensure that reviews are performed and documented
    • Review the Annual Report, as appropriate
    • Serve as the point of contact for all correspondence with the applicant concerning the Annual Report

    Reviewer

    • Perform an initial review of the Annual Report, within 90 days, for appropriate categorization of changes
    • Perform a complete review of the Annual Report, within 180 days, for adequacy of information submitted
    • Participate in discussions of and decisions pertaining to inappropriate changes, as necessary
    • Document reviews in memo format, including recommendations for actions needed (e.g., inspection, letter to applicant)
    • Prepare a Memorandum to the File stating that Annual Report is satisfactory (Appendix 1).

  5. Procedures

    1. Upon receipt of an Annual Report, DCC will log it into the Document Accountability and Tracking System (DATS). The original will be maintained as the archival copy.
      • The duplicate copy will be logged out and routed to the RPM in the appropriate office.
      • If only a single copy of the Annual Report is received, it will be logged out and routed to the appropriate Applications Division, so that they may request copies from the applicant. The single copy will be returned to DCC to be maintained in DCC as the archive copy.

    2. Upon receipt of the Annual Report in the Office with review responsibility, the RPM will:
      • Ensure that the report is logged in as a second level document into RMS-BLA
      • Perform an initial review of the Annual Report for appropriate categorization of changes; and
      • Determine appropriate routing of the Annual Report for review
      • If additional review is required by other reviewers, Divisions or Offices, the RPM will request the routing through DCCREQ.

    3. Each reviewer should ensure that, within 90 days of receipt of the Annual Report, the categorization of changes is appropriate for each portion of the review assigned. If a change is found to be inappropriately reported in the Annual Report:

      • the reviewer, RPM, and other reviewers in collaboration with the Division Director, other staff from that division, staff from other Offices or Divisions involved, and the Office of Compliance and Biologics Quality, as appropriate, should determine the alternatives available to the applicant to address the incorrect filing. The following should be considered in these deliberations:
        • CBER's intent to allow applicants to correct these problems with minimal expense and without unnecessary waste, if this is in the best interest of the public health
        • Circumstances that might require the change to be immediately discontinued
        • Indications that the change may have an adverse impact on the safety, purity, or potency of the product, in which case, the product may be in violation of applicable regulations and compliance action may be necessary.

      • The applicant should be notified by telephone immediately that the inappropriately reported change requires the submission of a supplement
        • The applicant should be advised as to the type of supplement that is required
        • The applicant should be notified of any additional actions to be taken to address the incorrect filing.

      • The applicant will also be notified in writing of the inappropriate category designation and actions necessary to address the incorrect filing as soon as possible after telephone notification (refer to Appendix 2, Boilerplate Letter).
      • A copy of the telecon, and letter to the applicant should be routed to DCC for filing.

    1. The reviewer will perform a review of the changes contained in the Annual Report within 180 days of its receipt by CBER. This review is to assure that the changes have had no adverse effect on the product.
      • Requests for additional information from the applicant should be rare. However, if it is necessary, the RPM may make an information request by telephone. Such requests must be documented in the file.
      • The Office of Compliance and Biologics Quality should be notified by memo or e-mail, of any items that require follow-up on inspection. The memo or e-mail should identify the product, facility, date of the annual report, and issues to be covered on inspection. For products other than blood and blood components notification should be made to the Division of Inspections and Surveillance, Program Inspection Branch. For blood and blood components notification should be made to the Division of Inspections and Surveillance, Program Surveillance Branch. This notification must be documented in the file.
      • If no issues that need to be resolved are identified a memo should be prepared. (Appendix 1, Template memorandum).

    2. The RPM will compile the comments and return the annual report and compiled comments (including telecons, memoranda and letters) to DCC with a completed CBER Document Control File Sheet, Regulatory Materials - BLA Related) attached (Appendix 3). Complete all appropriate sections including first and second level STN.

    3. Once the Annual Report is filed, it may be requested from DCC at any time for reference (e.g., prior to an inspection) using the electronic mail document request header, DCCREQ, supplying the appropriate STN Number information.

  6. Appendices

    7.
  7. Effective Date
    8.

October 26, 2001

  1. History
    2.
Comment / Revision
Approved By
Approval Date
Version Number
Comment
RMCC Rebecca Devine
03/10/1999
#1
Original Document
Jules Meisler Robert Yetter, PhD
10/16/2001
#2
Modifications to address changes in DCC procedures, organizational names and add a review closeout memorandum
Leonard Wilson Robert Yetter, PhD
10/26/2001
#3
Corrections of header in Appendix 1

 

 
Updated: November 1, 2001