Standard Operating Procedure for Sequence-Level QC Sign-Off Prior to Filing
| Department | Regulatory Affairs |
| SOP No. | RA/2026/701 |
| Supersedes | NA |
| Page No. | 1 of X |
| Issue Date | 13/04/2026 |
| Effective Date | 13/04/2026 |
| Review Date | 13/04/2028 |
Purpose
This Standard Operating Procedure (SOP) establishes the mandatory steps and controls for the quality control (QC) sign-off of sequence-level documents prior to their official filing in regulatory submissions. The purpose of this SOP is to ensure accuracy, compliance, and completeness of the submission sequences, minimizing risks of filing errors, regulatory delays, and non-conformance with applicable guidelines.
Scope
This SOP applies to all regulatory affairs personnel involved in the preparation, review, and quality control of electronic Common Technical Document (eCTD) submission sequences across all product types and dosage forms. It covers sequence compilation, document verification, QC sign-off, and electronic filing readiness. Activities excluded include the content authoring process and post-filing submission activities.
Responsibilities
The following roles are responsible under this SOP:
- Regulatory Affairs Associate: Prepares and compiles submission sequences for QC review.
- Quality Control Reviewer: Performs detailed sequence-level quality checks, cross-verifies documents, and identifies discrepancies.
- Regulatory Affairs Manager: Reviews and approves the QC findings and provides final sign-off prior to filing.
- Document Control Coordinator: Ensures proper documentation, version control, and storage of QC records.
Accountability
The Regulatory Affairs Head holds overall accountability for implementing this SOP, ensuring compliance with quality standards, reviewing the procedure effectiveness periodically, addressing escalations related to QC failures, and facilitating corrective actions as required.
Procedure
1. Preparation: Regulatory Affairs Associate collates the complete submission package for the intended sequence, including appendices, cover letters, and regulatory forms. Verify that all documents are the approved final versions signed off by the respective departments.
2. Prerequisites: Confirm availability of the latest approved templates, checklists, and access permissions to the eCTD management system. Ensure all personnel involved are trained on QC requirements and tools.
3. Initial Verification: Perform a preliminary check to confirm sequence numbering, correct hyperlinking of documents, and completeness of the submission dossier.
4. Detailed Quality Control: The QC Reviewer conducts a line-by-line review of the sequence content against source documentation for accuracy, consistency, and compliance with regulatory guidelines. Verify document metadata such as version numbers, dates, and author signatures. Check for formatting errors, missing pages, or incorrect annexures.
5. In-Process Controls: If discrepancies or deviations are found, document them in the QC non-conformance log. Notify the Regulatory Affairs Associate for correction and resubmission. Re-run quality checks as necessary.
6. Acceptance Criteria: The QC Reviewer signs off only when all sequence components meet defined quality standards without any unresolved issues. Any critical deviations must be escalated to the Regulatory Affairs Manager.
7. Final Approval & Sign-Off: The Regulatory Affairs Manager reviews the QC findings, ensures compliance, and provides the final sign-off authorization for filing. Document the approval date, signatory details, and version of the sequence.
8. Electronic Filing Preparation: Following QC sign-off, prepare the sequence for electronic submission by uploading to the designated submission gateway. Confirm system acknowledgments and archiving of submission confirmation receipts.
9. Documentation & Record Retention: All QC checklists, non-conformance records, sign-off forms, and related correspondence must be filed in the quality management system and retained as per archival policy.
10. Closure: Close the QC activity only when all documentation is complete and the filing has been successfully completed. Conduct a post-filing review meeting if necessary to identify improvement areas.
This procedure ensures rigorous quality oversight at the sequence level, maintaining regulatory compliance and submission integrity.
Abbreviations
eCTD: Electronic Common Technical Document
QC: Quality Control
SOP: Standard Operating Procedure
RA: Regulatory Affairs
QMS: Quality Management System
Documents
- Sequence-Level QC Checklist (Annexure-1)
- QC Non-Conformance Report Form (Annexure-2)
- Sequence QC Sign-Off Form (Annexure-3)
References
– ICH M4 Guideline on eCTD
– FDA Guidance for Industry: eCTD Specifications
– Internal Regulatory Quality Management System Procedures
– Good Documentation Practices (GDP) Guidelines
– Company Document Control Policy
Version
1.0
Approval
| Prepared By | |
| Checked By | |
| Approved By |
Annexures
Annexure-1: Sequence-Level QC Checklist
Purpose: To verify completeness, accuracy, compliance, and formatting of eCTD sequence documents prior to filing.
| Check Item | Pass/Fail | Remarks |
|---|---|---|
| Sequence Number Correct | Pass | – |
| All Documents Present | Pass | – |
| Versioning Accurate | Pass | – |
| Document Metadata Verified | Pass | – |
| Hyperlinks Functional | Pass | – |
| Formatting As per Guidelines | Pass | – |
| No Missing Pages | Pass | – |
| Cross-References Correct | Pass | – |
Reviewer: QC Reviewer Initials ________ Date: 13/04/2026
Annexure-2: QC Non-Conformance Report Form
Purpose: To document any discrepancies, deviations, or non-conformances identified during sequence-level QC review.
| Non-Conformance ID | NC-RA-20260413-01 |
| Date Identified | 13/04/2026 |
| Sequence Number | 005 |
| Description of Issue | Incorrect version number found on Module 2 document. |
| Impact Assessment | May cause submission rejection if not corrected. |
| Corrective Action | Update document version and re-upload corrected file. |
| Action Completion Date | 15/04/2026 |
| Reviewed By | |
| Closed By |
Annexure-3: Sequence QC Sign-Off Form
Purpose: To formally document the final approval of sequence-level QC review prior to regulatory filing.
| Sequence Number | 005 |
| Date of QC Completion | 13/04/2026 |
| QC Reviewer | |
| Review Comments | All documents verified and compliant. No pending issues. |
| Regulatory Affairs Manager Approval | |
| Date of Approval | 13/04/2026 |
| Remarks | Sequence approved for filing. |
Revision History
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
| 13/04/2026 | 1.0 | Initial issue | New SOP creation |