SOPP 8117: Issuing Submission Numbers in Advance of the Receipt of the Electronic Submission

Version #1

Effective Date: September 24, 2007

---

1. Purpose

1. The purpose of this document is to describe the policies and procedures Center for Biologics Evaluation and Research (CBER) staff should follow for issuing submission numbers for electronic Biologics License Applications (eBLA), including Trans-BLAs and electronic Investigational Related Applications, (eIRAs) prior to receipt in Center.

2. Definitions

1. CTD: Common Technical Document refers to a standardized format for submitting information to the FDA. This format can be used in either paper or electronic form.

   eCTD: When the CTD is submitted in electronic form with an xml backbone, it is referred to as an eCTD.

   eBLA: receipt of a BLA using electronic format in any of the following formats: PDF, PDF in Common Technical Document (CTD) format, electronic CTD using xml language for the document (eCTD).

   eIRA: receipt of an IRA in electronic format using any of the following formats: PDF, PDF in Common Technical Document (CTD) format, electronic CTD using xml language for the document (eCTD). [An IRA is a generic way of referring to the applications tracked in the Biologics Investigational and Related Applications Management System (BIRAMS) including: Investigational New Drugs (INDs), Investigational Device Exemptions (IDEs), Master Files, and Emergency Use Authorizations (EUAs).]

   Electronic Submissions Gateway (ESG): the Agency web portal by which electronic submissions are received from applicants/sponsors.

   PDF smart form: These forms [Form FDA 1571 and 356(h)] can be obtained from the FDA forms webpage. These presentations have xml coding in the background that facilitate the recovery of information from the form supplied by the sponsor/applicant.

   The Electronic Document Room (EDR) automated submission load programming extracts information from these forms and utilizes it to load CBER submissions. If the appropriate .pdf smart form is not incorporated in the submission, CBER will not be able to leverage the programmatic automation for loading electronic submissions into CBER's EDR and sending load notifications to the appropriate Office and Center staff.

3. Background

1. It has been CBER standard practice to assign/issue a submission number once the submission was received in CBER's Document Control Center (DCC). With the advent of the eCTD as an Agency standard regulatory submission format, the timing of the generation of a submission tracking number changed. The International Conference on Harmonisation (ICH) provided a formatted xml submission backbone that requires sponsors/applicants to include the submission's tracking number in the xml backbone. If the submission tracking number is absent from the submission's xml backbone, errors will be generated during the submission loading and validation process.

   As a result of the implementation of the eCTD format, CBER is changing our standard practice to allow the issuance of submission numbers in advance of the receipt of the submission in order to allow the sponsor/applicant to place the tracking number within the electronic submission xml backbone, and the Form FDA 356(h) or 1571 .pdf smart form. The submission tracking number is extracted from the .pdf smart form and used to obtain the application data from the database. The database information, in combination with the data from the form, is used in the load notifications automatically generated by CBER's EDR's programming.

   The generation of preassigned tracking numbers will aid in the automated routing of licensing supplements received by CBER from the ESG and through our EDR programming. The supplements submission number should be assigned using the same process as the eBLA.

4. Policy

1. It is CBER policy that we will issue a submission tracking number to a sponsor/applicant no earlier than two weeks in advance of the target receipt date for the electronic submission when requested. There will be no pre-assignment of submission tracking numbers for paper based submissions.

   All electronic submissions received through the Agency's Electronic Submissions Gateway (ESG) must contain a pre-assigned submission number with the exception of amendments. The addition of the tracking number allows CBER's programming, the Gateway Integration Application (GIA), to automatically load the submission within the Center's EDR. An additional benefit to the generation of the submission tracking number prior to arrival in the Center is that EDR programming will be able to automatically notify appropriate staff within the Review Offices via email of the arrival of regulatory documentation.

5. Responsibilities and Procedures

1. Electronic Biologics License Applications (eBLA) and electronic Biologics License Supplements (eBLS)

   1. When an applicant intends to submit an eBLA or eBLS, the applicant may request a Submission Tracking Number (STN) from the Regulatory Project Manager (RPM) in the appropriate Application Division, the Regulatory Management Staff in the Office of Cellular, Tissue, and Gene Therapies (OCTGT) or the Division of Manufacturing and Product Quality (DMPQ) in the Office of Compliance and Biologics Quality (OCBQ).
   2. A request for a number can be made by an applicant, no more than two weeks in advance of the expected submission.
   3. The RPM should instruct the applicant that if the applicant's plans change and there will not be a submission in the timeframe indicated, the RPM should be notified in order to void the submission tracking number.
   4. The RPM should instruct the applicant that if the submission is not received within two weeks of the target submission date, CBER will void the pre-assignment submission tracking number.
   5. The RPM enters the appropriate information in the Regulatory Management System- Biologics License Application (RMS-BLA), including the RPM assigned, in order to obtain the STN. 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.
   6. The RPM will notify the applicant of the submission tracking number, usually within two business days of the request.
   7. The RPM should remind the applicant to place the BLA or BLS STN on the cover page of the submission and on the Form FDA 356(h) (.pdf smart form) as well as in the xml backbone for a submission in the eCTD format.
   8. For electronic submissions received through CBER's DCC:
      1. DCC assigns a Document Accountability and Tracking System (DATS) log number and
      2. The RPM links the DATS Log number to the STN using the Submissions Screen in RMS-BLA.
      3. The receipt date will automatically be changed in RMS-BLA.
      4. DCC staff will send a load notification to the appropriate Center staff including the Office Electronic Submissions Coordinators (ESC), EDR Office of Information Technology (OIT) staff, DCC EDR team and RPM.
   9. For submissions received through the Gateway,
      1. The submission automatically receives a DATS number,
      2. Is uploaded to CBER's EDR and
      3. The receipt date in RMS-BLA is updated.
      4. A load notification is automatically sent to the staff listed in RMS-BLA for the application as well as the Office ESCs and the EDR OIT staff.

   Electronic Investigational Related Applications (eIRA) (IND, IDE, MF, EUA)

   1. When a sponsor intends to submit an electronic original IRA, the sponsor may request a submission number from the RPM in the appropriate Applications Division, the Regulatory Management Staff in OCTGT or DMPQ/OCBQ. IRA amendments do not need a pre-assigned number.
   2. A request for a number can be made by a sponsor no more than two weeks in advance of the expected filing.
   3. The RPM should instruct the sponsor that if the sponsor's plans change and there will not be a filing, the RPM should be notified in order to void the number.
   4. The RPM should instruct the sponsor that if the submission is not received within two weeks of the target submission date, CBER will void the pre-assignment submission number.
   5. The RPM enters the appropriate information in the Pre-Assignment screen of the BIRAMS in order to obtain the IRA number. The Pre-Assignment screen generates an IRA with an IRA status of “Pre-Assignment.” All date fields should reflect the date the IRA number was assigned.
   6. The RPM will notify the sponsor of the submission number, usually within two business days of the request.
   7. The RPM should remind the sponsor to place the IRA number on the cover page of the submission and on the Form FDA 1571, (.pdf smart form) as well as in the xml backbone for a submission in the eCTD format.
   8. For electronic submissions received through CBER's DCC:
      • the FDA Receipt Date and the CBER Receipt date will be updated in the BIRAMS and
      • the status will be changed to the appropriate value based on the application type.
      • DCC staff will send a load notification to the appropriate Center staff including the RPM, Office ESCs, EDR OIT staff and the DCC EDR team.
   9. For submissions received through the Gateway,
      1. It will be uploaded to CBER's EDR
      2. The receipt date in BIRAMS will be automatically updated.
      3. A load notification is automatically sent to the staff listed in BIRAMS for the application as well as the Office ESCs, and the EDR OIT staff.

6. References

A.  Web links to the references below can be found in the list following the History Section

• Guidance for Industry: Providing Regulatory Submissions in Electronic Format--Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications - 4/19/2006
• Guidance for Industry: Providing Regulatory Submissions in Electronic Format - Content of Labeling - 4/20/2005
• FEDERAL REGISTER Requirements for Submission of Labeling for Human Prescription Drugs and Biologics in Electronic Format; Final Rule - 12/11/2003
• Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format - General Considerations - 10/22/2003
• Guidance for Industry: Part 11, Electronic Records; Electronic Signatures - Scope and Application - 9/3/2003
• Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format--Annual Reports for New Drug Applications and Abbreviated New Drug Applications - 8/27/2003
• Guidance for Industry: Providing Regulatory Submissions to CBER in Electronic Format - Investigational New Drug Applications (INDs) - 3/26/2002
• Draft Guidance for Industry: Providing Regulatory Submissions in Electronic Format -- Prescription Drug Advertising and Promotional Labeling - 1/31/2001
• REVISED Guidance for Industry: Providing Regulatory Submissions to the Center for Biologics Evaluation and Research (CBER) in Electronic Format - Biologics Marketing Applications [Biologics License Application (BLA), Product License Application (PLA) / Establishment License Application (ELA) and New Drug Application (NDA)] - 11/12/1999, REVISED 11/22/1999

7. Effective Date

1. September 24, 2007

8. History

1. Written/Revised	Approved	Approval Date	Version Number	Comment
   BPWG/RMCC	R. Yetter	September 18, 2007	1	First issuance of this SOPP