Manual of Standard Operating Procedures and Policies

1. Purpose

The purpose of this document is to describe the policies and procedures for Center for Biologics Evaluation and Research (CBER) staff to follow when initiating and tracking second level Submission Tracking Numbers (STNs) for Biologics License Applications (BLAs) for CBER correspondence not in response to an applicant submission.

2. Definitions

CBER staff should refer to the Regulatory Management System- Biologics License Application (RMS-BLA) Data Dictionary for an explanation of terms used in this SOPP.

3. Background

When CBER regulatory tracking databases were developed, the assumption was that an STN would only be generated based on an incoming submission from an applicant. Because of the changes in statutes and business procedures, the need has arisen for documenting and tracking outgoing CBER correspondence not directly related to a submission with a pending STN. Generally, we will be expecting that CBER initiated correspondence will be in response to an applicant submission. However, there will be occasions as outlined below when CBER will need to contact an applicant for an issue not specifically related to a pending submission. In these cases, this SOPP will be followed. For all correspondence related to an applicant submission, CBER staff will follow the appropriate SOPPs, for example, SOPP 8405: Complete Review and Issuance of Action Letters.

4. Policy

The following CBER initiated document types will be entered in RMS-BLA as a pre-assigned STN:

• Post Marketing Requirements/Commitment (PMR/PMC) or REMS assessment requests for overdue information.
• Safety Labeling change request based on new safety information.
• Request for Risk Evaluation and Mitigation Strategies (REMS) based on new safety information.
• Request for Post Marketing Requirement (PMR) follow up for clinical study/trial based on new safety information.

The following CBER initiated document types will be entered in RMS-BLA as a stand alone second level STN:

• Filing foreign post approval inspection reports (DCC Procedure Guide #14)

If an Office needs to send another letter type to an applicant, the Office may contact the Associate Director for Review Management to see if the letter type would qualify as a one time exception.

5. Responsibilities and Procedures

The procedures for review and processing of safety labeling change requests based on new safety information, requests for REMS, and requests for PMR follow up for clinical study/trial based on new safety information can be found on CBER's Intranet Review web page (see Reference 1).

The RPM in the product office will:

• Pre-assign a second level STN in the RMS-BLA regulatory database for the expected applicant response, and reference that pre-assigned STN in the initial outgoing document from CBER, i.e., don't assign a second level STN to the CBER document.
  • The STN is generated using the Enter New Submission screen with an STN Status = Pre-assigned.
  • All date fields should reflect the date the STN was assigned.
  • For a Post-marketing requirement or commitment, the information should be entered in the PMC screen.
• Notify the applicant of the STN in the outgoing letter and request the STN be used in their response.
• The RPM should remind the applicant to place the BLS STN on the cover page of the submission and on the Form FDA 356(h). All applicant responses will be processed according to current procedures.
• Use the appropriate letter template posted on CBER's Intranet Letter Templates web page.
• Enter the CBER document as a communication to the pre-assigned STN.
• Review the outstanding pre-application submission numbers report to determine which pre-assigned second level STNs have not received applicant submissions.
• Initiate follow up with the applicant as appropriate, depending on the CBER initiated corr type.
6. References

Interim Procedure: Title IX, Section 901: New FDAAA Required Post-Marketing Safety Labeling Changes, Risk Evaluation and Mitigation Strategies (REMS) and Post-market Studies/Clinical Trials (PMR)

DCC Procedure Guide #14: Procedure for Filing Foreign Post Approval Inspection Reports for Marketing Applications

7. Effective Date

September 23, 2008

8. History

Written/Revised	Approved	Approval Date	Version Number	Comment
Dixon	R. A. Yetter, PhD	September 12, 2008	1	First issuance of this SOPP