Standard Operating Procedure for Monitoring of Reaction Parameters in API Manufacturing

Department	API Manufacturing
SOP No.	SOP/API/022/2025
Supersedes	SOP/API/022/2022
Page No.	Page 1 of 11
Issue Date	13/04/2025
Effective Date	15/04/2025
Review Date	13/04/2026

1. Purpose

To establish a procedure for consistent and controlled monitoring of critical reaction parameters during API manufacturing to ensure process safety, quality, and reproducibility.

2. Scope

This SOP applies to all chemical reactions conducted in reactor systems within the API manufacturing facility, including pilot and production scale operations.

3. Responsibilities

• Production Operators: Monitor and record reaction parameters as per BMR.
• Process Engineer: Ensure instruments are calibrated and parameter ranges are validated.
• QA Personnel: Review batch records for compliance with defined ranges and investigate any excursions.

4. Accountability

The Production Manager and QA Manager are accountable for ensuring the defined process parameters are maintained, documented, and investigated in case of deviations.

5. Procedure

5.1 Pre-Reaction Verification

1. Confirm calibration status of temperature sensors, pressure gauges, pH meters, and timers.
2. Review the BMR for specified setpoints and permissible tolerance limits for:
   • Temperature
   • Reaction time
   • Pressure (if applicable)
   • Agitation speed
   • pH range (for aqueous/acid-base reactions)
3. Ensure LOTO (Lockout Tagout) is not applied and reactor is safe to operate.

5.2 Parameter Monitoring During Reaction

1. Temperature:
   • Monitor using digital display or DCS interface.
   • Record every 15 minutes during heating or cooling phase.
2. Pressure (if applicable):
   • Check gauge pressure continuously in case of closed systems.
   • Log every 30 minutes during pressurized reactions.
3. pH:
   • Use calibrated pH meter and sample every 30 minutes or as specified in BMR.
   • Record in the “Reaction Monitoring Log” (Annexure-1).
4. Agitation:
   • Set RPM as per BMR and observe for uniform mixing.
   • Note any noise or unusual vibration and inform engineering immediately.
5. Time:
   • Note reaction start and end time with operator initials.
   • Ensure minimum and maximum dwell times are followed.

5.3 Handling Excursions

1. If any parameter exceeds the acceptable range:
   • Pause the process if it poses safety risk.
   • Document the deviation in the “Reaction Deviation Form” (Annexure-2).
   • Inform the shift supervisor and QA immediately.
2. Investigate root cause and implement corrective action before resuming process.

5.4 Documentation and Record-Keeping

1. Record all observations in the BMR and “Reaction Monitoring Log.”
2. Attach printed trends from automated systems (if available) for archival.
3. Retain records as per documentation SOP and regulatory retention requirements.

6. Abbreviations

• SOP: Standard Operating Procedure
• QA: Quality Assurance
• BMR: Batch Manufacturing Record
• DCS: Distributed Control System
• LOTO: Lockout-Tagout

7. Documents

1. Reaction Monitoring Log (Annexure-1)
2. Reaction Deviation Form (Annexure-2)
3. Calibration Certificates (Annexure-3)

8. References

• ICH Q7 – GMP Guidelines for Active Pharmaceutical Ingredients
• 21 CFR Part 211.100 – Written procedures and deviations
• ISPE Baseline Guide – Volume 6: Biopharmaceutical Manufacturing Facilities

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Reaction Monitoring Log

Time	Temp (°C)	pH	RPM	Pressure (bar)	Observed By
09:00	65.0	6.8	120	1.2

Annexure-2: Reaction Deviation Form

Date	Batch No.	Parameter	Deviation	Corrective Action	Approved By
13/04/2025	API-202504	Temp	Exceeded 70°C	Reduced heating rate

Annexure-3: Calibration Certificates

Instrument	ID	Calibrated On	Due Date	Status
pH Meter	PH-002	01/04/2025	01/10/2025	Calibrated

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2022	1.0	Initial Issue	New SOP	QA Head
13/04/2025	2.0	Added DCS and LOTO Requirements	Process Enhancement	QA Head