Standard Operating Procedure for Biosensor Integration and Verification in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/140/2025
Supersedes	SOP/BS/140/2022
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 standardized process for integrating biosensors into upstream bioreactors and conducting routine verification and calibration to ensure accurate, real-time process monitoring in biosimilar manufacturing operations.

2. Scope

This SOP applies to the installation, configuration, calibration, and verification of online biosensors including pH, dissolved oxygen (DO), glucose, lactate, and biomass sensors used in pilot and production-scale bioreactors.

3. Responsibilities

• Engineering: Install and integrate biosensors into SCADA systems and perform initial configuration.
• Production: Conduct in-process sensor calibration and document readings during fermentation.
• QA: Review sensor performance data and approve sensor validation reports.

4. Accountability

The Head of Upstream Operations is accountable for ensuring biosensor integration is compliant with validation and performance qualification standards as per regulatory and GMP guidelines.

5. Procedure

5.1 Sensor Selection and Compatibility Check

1. Verify that biosensors selected are compatible with process fluids, temperature ranges, and SCADA integration.
2. Refer to Annexure-1: Biosensor Specification Checklist before installation.

5.2 Installation and Integration

1. Ensure sensors are installed in sterile conditions using validated ports or weld-in housings.
2. Connect sensors to the bioreactor control system and confirm signal reception in SCADA or PLC panel.
3. Label sensor with ID number, calibration date, and status tag.

5.3 Sensor Calibration and Verification

1. Calibrate pH, DO, and conductivity sensors using certified calibration standards:
   • pH: Buffer pH 4.01, 7.00, and 10.00
   • DO: Zero point (nitrogen purging) and 100% air-saturated water
2. Document calibration in Annexure-2: Sensor Calibration Log.
3. Perform online verification using process correlation methods (e.g., offline samples).

5.4 Sensor Performance Monitoring

1. During batch run, monitor biosensor trends through SCADA.
2. Investigate anomalies such as signal drift, noise, or flatlining immediately.
3. QA must be notified of sensor failures and replacement initiated.

5.5 Reusability and Maintenance

1. For reusable sensors:
   • Clean with WFI post-batch
   • Store in designated storage solution
   • Inspect for membrane integrity or signal decay before reuse

6. Abbreviations

• SCADA: Supervisory Control and Data Acquisition
• PLC: Programmable Logic Controller
• DO: Dissolved Oxygen
• QA: Quality Assurance

7. Documents

1. Biosensor Specification Checklist – Annexure-1
2. Sensor Calibration Log – Annexure-2
3. Sensor Performance Verification Report – Annexure-3

8. References

• ICH Q8 – Pharmaceutical Development
• FDA Guidance on Process Analytical Technology (PAT)
• EU GMP Annex 11 – Computerized Systems

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Biosensor Specification Checklist

Sensor Type	Make/Model	Range	Material Compatibility	Approved (Y/N)
DO Sensor	Hamilton VisiFerm	0–200%	316L SS, PTFE	Yes

Annexure-2: Sensor Calibration Log

Date	Sensor ID	Parameter	Calibration Standard	Performed By
03/05/2025	DO-001	DO	Air/N₂	Ajay Verma

Annexure-3: Sensor Performance Verification Report

Sensor ID	Batch No.	Online Value	Offline Value	Deviation	Status
PH-004	BS-UP-093	7.15	7.12	+0.03	Pass

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added sensor reuse and storage conditions	GMP Enhancement