Standard Operating Procedure for Temperature Mapping of Bioreactor Jackets in Biosimilar Operations

Department	Biosimilars
SOP No.	SOP/BS/094/2025
Supersedes	SOP/BS/094/2022
Page No.	Page 1 of 10
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a validated method for temperature mapping of bioreactor jackets to confirm uniform heat transfer across the vessel surface, ensuring optimal growth conditions for biosimilar production processes and compliance with GMP guidelines.

2. Scope

This SOP is applicable to all stainless steel and single-use bioreactors equipped with thermal control jackets used in biosimilar manufacturing processes.

3. Responsibilities

• Engineering Department: Plan and execute temperature mapping studies and maintain calibration of temperature sensors.
• Production Department: Support installation of probes and monitor mapping activities.
• QA Department: Review and approve temperature mapping protocols and reports.

4. Accountability

The Head of Engineering is accountable for ensuring that all bioreactors undergo temperature mapping at defined intervals and upon significant maintenance or relocation.

5. Procedure

5.1 Preparation for Mapping

1. Prepare a temperature mapping protocol detailing:
   • Equipment ID and specifications
   • Sensor placement locations
   • Duration of study and test conditions
2. Calibrate all temperature sensors (RTDs or thermocouples) within ±0.1°C accuracy.
3. Clean and disinfect bioreactor vessel before study initiation.

5.2 Sensor Placement

1. Affix sensors on external jacket surface and at internal points (if non-invasive validation required).
2. Position sensors at:
   • Top, middle, and bottom quadrants
   • Inlet and outlet ports
   • Near agitator and heating zones

5.3 Execution of Mapping

1. Fill the bioreactor with WFI or equivalent fluid to typical process volume.
2. Set jacket temperature to target value (e.g., 37°C for mammalian cells).
3. Run the system under steady-state for at least 3 hours.
4. Record temperature at 1-minute intervals using data acquisition system.

5.4 Data Analysis and Acceptance Criteria

1. Download data and analyze for:
   • Temperature uniformity (±1.0°C)
   • Sensor deviation range
   • Hot or cold spots
2. If deviation exceeds acceptable range, investigate root cause and correct before batch use.

5.5 Documentation and Report

1. Document all raw data in Annexure-1.
2. Prepare a temperature mapping report with:
   • Sensor placement diagram
   • Data summary and conclusion
   • Recommendations for corrective actions if required

6. Abbreviations

• RTD: Resistance Temperature Detector
• WFI: Water for Injection
• QA: Quality Assurance

7. Documents

1. Temperature Mapping Raw Data Sheet – Annexure-1
2. Temperature Mapping Summary Report – Annexure-2

8. References

• WHO TRS 961 – Equipment Qualification and Validation Guidelines
• ICH Q8 – Pharmaceutical Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Temperature Mapping Raw Data Sheet

Sensor ID	Location	Time	Temperature (°C)	Remarks
S1	Top-Left Jacket	10:00	36.8	Within range
S2	Bottom-Center	10:00	37.0	Within range

Annexure-2: Temperature Mapping Summary Report

Summary of test results, deviations, sensor layout diagram, and recommendation to proceed with production or corrective actions.

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Updated criteria for mapping with sensor validation protocol	Annual GMP update