Standard Operating Procedure for Data Integrity in Cell Line Development Operations

Department	Biosimilars
SOP No.	SOP/BS/056/2025
Supersedes	SOP/BS/056/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define a systematic approach for preserving data integrity in all Cell Line Development (CLD) operations associated with biosimilar research and manufacturing by following ALCOA+ principles and current GMP requirements.

2. Scope

This SOP covers all electronic and paper-based data generated during clone selection, gene transfection, expression screening, MCB/WCB creation, and analytical assessments performed within the CLD department.

3. Responsibilities

• CLD Staff: Responsible for recording, reviewing, and safeguarding data in accordance with ALCOA+ standards.
• Data Custodian: Ensures secure storage, controlled access, and periodic backup of digital records.
• QA: Audits data integrity compliance, investigates breaches, and implements corrective actions.

4. Accountability

The Head of Biosimilars is accountable for ensuring the integrity of all data used for decision-making, regulatory filing, and product development.

5. Procedure

5.1 ALCOA+ Principles Implementation

1. Ensure that all data adheres to:
   • Attributable: Identify who performed the activity and when.
   • Legible: Data must be readable and permanent.
   • Contemporaneous: Entries made at the time of activity.
   • Original: Source data must be preserved.
   • Accurate: Free from errors or manipulation.
   • Complete, Consistent, Enduring, Available (CCE+A): Data must be uninterrupted, long-term, and retrievable on demand.

5.2 Documentation Controls

1. All entries in lab notebooks must be:
   • Dated and signed by the performer and reviewer
   • Recorded using indelible ink
   • Free from blank spaces; strike-through for corrections with justification
2. Electronic data must include metadata, audit trails, and timestamp logs.

5.3 Electronic System Compliance

1. All instruments generating electronic data (e.g., qPCR, ELISA readers) must be:
   • Validated for 21 CFR Part 11 compliance
   • Integrated with secure, access-controlled storage systems
2. User ID and password must be unique to each individual. No shared logins permitted.

5.4 Data Review and Archival

1. Data must be reviewed by a second person within 5 working days of generation.
2. Archival of paper data should follow SOP/QA/009/2025; soft copies must be backed up weekly and stored in QA-controlled servers.

5.5 Deviation and Breach Management

1. Any suspected or confirmed data integrity issue must be reported immediately to QA.
2. QA to conduct a Root Cause Analysis and initiate CAPA using the Breach Investigation Form (Annexure-1).
3. Trend analysis for breaches to be conducted quarterly.

6. Abbreviations

• CLD: Cell Line Development
• ALCOA+: Attributable, Legible, Contemporaneous, Original, Accurate, Complete, Consistent, Enduring, Available
• CAPA: Corrective and Preventive Action
• QA: Quality Assurance

7. Documents

1. Breach Investigation Form (Annexure-1)
2. Weekly Data Backup Log (Annexure-2)
3. Electronic System Access Control Log (Annexure-3)

8. References

• MHRA GxP Data Integrity Guidance
• WHO TRS 996 – Annex 5: Data Integrity in GMP
• 21 CFR Part 11 – Electronic Records; Electronic Signatures

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Breach Investigation Form

Date	Observed By	Description of Breach	Root Cause	CAPA Assigned
02/05/2025	Ajay Verma	Backdated entry in clone logbook	Lack of review	Training and re-audit

Annexure-2: Weekly Data Backup Log

Date	Performed By	Location	Remarks
03/05/2025	Sunita Reddy	QA Secure Server	Successful

Annexure-3: Electronic System Access Control Log

User ID	Name	System	Access Level	Date Added
CLD101	Vinay Pawar	qPCR Analysis	Editor	01/05/2025

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Expanded scope to electronic system validation and audit trails	Regulatory Update