Standard Operating Procedure for Monitoring and Logging of Critical Parameters in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/101/2025
Supersedes	SOP/BS/101/2022
Page No.	Page 1 of 12
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define the procedure for real-time monitoring and accurate documentation of critical process parameters during biosimilar bioreactor operations, ensuring data integrity and adherence to GMP requirements.

2. Scope

This SOP applies to all small-scale, pilot, and production bioreactor systems used in upstream processing of biosimilars, covering both single-use and stainless-steel systems.

3. Responsibilities

• Production Operator: Monitor and record critical parameters as per defined frequency in the BMR.
• Shift Supervisor: Review logs and intervene if critical limits are approached.
• QA: Verify records and monitor for any deviations or missed entries.

4. Accountability

The Head of Manufacturing is accountable for ensuring that all critical process parameters are monitored and recorded systematically during biosimilar production.

5. Procedure

5.1 Definition of Critical Parameters

1. Identify and monitor the following as critical parameters:
   • Temperature
   • pH
   • Dissolved Oxygen (DO)
   • Agitation Speed
   • Vessel Pressure
   • Foam Level

5.2 Monitoring Frequency and Systems

1. Real-time data must be collected via SCADA/DCS (e.g., DeltaV, Siemens PCS7).
2. Manual cross-verification must be done every 4 hours for each parameter.
3. Record readings in Annexure-1: Critical Parameter Log Sheet.

5.3 Alarm Handling

1. In case of deviation from target range, alarms will trigger in control panel.
2. Operators must acknowledge alarms and take corrective action per deviation SOP.
3. Document all alarms and actions in Annexure-2.

5.4 Data Integrity and Logging

1. Ensure entries are:
   • Legible
   • Initialed with date/time
   • Free from overwriting or erasure
2. Maintain logs for a minimum of 5 years in the controlled archive room.

5.5 Trend Review and Reporting

1. Generate trend charts weekly and review for any process drift.
2. Report abnormalities or excursions to QA within 24 hours.

6. Abbreviations

• DO: Dissolved Oxygen
• BMR: Batch Manufacturing Record
• QA: Quality Assurance
• SCADA: Supervisory Control and Data Acquisition

7. Documents

1. Critical Parameter Log Sheet – Annexure-1
2. Alarm Acknowledgment & Response Record – Annexure-2

8. References

• ICH Q10 – Pharmaceutical Quality System
• 21 CFR Part 11 – Electronic Records and 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: Critical Parameter Log Sheet

Date	Time	Temp (°C)	pH	DO (%)	Agitation (rpm)	Foam	Initials
04/05/2025	08:00	36.9	7.2	45	150	Low	SR

Annexure-2: Alarm Acknowledgment & Response Record

Date	Time	Parameter	Alarm Type	Action Taken	By Whom
04/05/2025	10:20	DO	Low DO	Increased airflow rate	Rajesh Kumar

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added alarm handling section and electronic logging compliance	Regulatory update