Standard Operating Procedure for Online Sensor Calibration in Bioreactor Operations for Biosimilars
| Department | Biosimilars |
|---|---|
| SOP No. | SOP/BS/082/2025 |
| Supersedes | SOP/BS/082/2022 |
| 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 the procedure for online calibration of bioreactor sensors including pH, Dissolved Oxygen (DO), and temperature sensors to ensure accuracy and regulatory compliance during biosimilar production.
2. Scope
This SOP applies to all bioreactor systems equipped with online sensors in the upstream processing of biosimilars within GMP manufacturing facilities.
3. Responsibilities
- Bioprocess Technicians: Execute sensor calibration as per schedule and record observations.
- Engineering/Maintenance Team: Assist with hardware troubleshooting and calibration validation.
- QA Officer: Review calibration records and verify GMP compliance.
4. Accountability
The Bioprocessing Manager is accountable for ensuring online sensor calibration is performed, documented, and verified as per standard timelines.
5. Procedure
5.1 Calibration Frequency
- Perform calibration:
- Before each batch run
- After sensor replacement
- After significant deviation in readings
5.2 Preparation
- Ensure bioreactor is idle and sensor ports are accessible.
- Wear PPE and sanitize work area and calibration solutions.
- Ensure calibration buffers are within expiry and at room temperature (20–25°C).
5.3 pH Sensor Calibration
- Rinse pH probe with deionized water.
- Immerse probe in pH 7.00 buffer and allow stabilization.
- Set this as the first calibration point.
- Repeat with pH 4.00 or pH 10.00 buffer for second point.
- Record millivolt (mV) readings and slope in Annexure-1.
5.4 DO Sensor Calibration
- Two-point calibration:
- 0%: Immerse in nitrogen-purged solution
- 100%: Air-saturated water
- Stabilize sensor in each condition before logging readings.
- Ensure DO slope is within 90–110% for validation.
5.5 Temperature Sensor Verification
- Compare displayed temperature with NIST-traceable reference thermometer.
- Allow system to reach equilibrium before logging variance (±0.2°C acceptable).
5.6 Post-Calibration
- Rinse all probes with sterile water and reinstall in reactor.
- Secure sensors and verify values are stable on HMI/SCADA screen.
- Document all calibration entries in Calibration Log (Annexure-1).
6. Abbreviations
- DO: Dissolved Oxygen
- pH: Potential of Hydrogen
- HMI: Human Machine Interface
- SCADA: Supervisory Control and Data Acquisition
7. Documents
- Sensor Calibration Log – Annexure-1
8. References
- USP <1058> – Analytical Instrument Qualification
- WHO TRS 986 – GMP for Biotechnological Products
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Sensor Calibration Log
| Date | Sensor Type | Calibration Points | Slope | Variance | Calibrated By |
|---|---|---|---|---|---|
| 04/05/2025 | pH | 7.00 / 4.00 | 98.6% | — | Rajesh Kumar |
| 04/05/2025 | DO | 0% / 100% | 102.2% | — | Rajesh Kumar |
| 04/05/2025 | Temperature | — | — | +0.1°C | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 04/05/2025 | 2.0 | Added slope validation, temperature verification, updated annexures | GMP Enhancement |