Standard Operating Procedure for Real-Time pH Monitoring During Elixir Manufacturing
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/192/2025 |
| Supersedes | SOP/ELX/192/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To define the procedure for continuous and accurate monitoring of pH in real-time during elixir manufacturing using in-line or online pH probes to ensure batch consistency and regulatory compliance.
2. Scope
This SOP is applicable to all elixir manufacturing processes requiring pH monitoring using real-time systems including in-line probes and digital pH monitoring devices integrated into manufacturing vessels and transfer lines.
3. Responsibilities
- Production Operator:
- Operate and clean the real-time pH monitoring device and monitor displayed readings during processing.
- Engineering:
- Ensure proper installation, calibration, and maintenance of pH sensors and transmitters.
- QA Officer:
- Verify that real-time pH logs are reviewed and maintained for every batch.
4. Accountability
The Production Head is accountable for implementation and compliance of this SOP. The QA Head is responsible for periodic review and GMP adherence. Engineering Head is responsible for system reliability and performance.
5. Procedure
5.1 Equipment and Setup
- Ensure installation of a calibrated and validated real-time pH sensor in the manufacturing vessel or transfer line.
- Connect pH sensor to the digital display panel or SCADA system for live data visualization.
- Confirm probe calibration using standard pH 4.0 and 7.0 buffer solutions before batch start.
- Document calibration results in the pH Probe Calibration Logbook.
5.2 Real-Time Monitoring During Manufacturing
- Start pH monitoring once the initial solution is formed and maintain throughout mixing and ingredient addition phases.
- Observe the pH display and ensure it remains within the specified range defined in the BMR.
- Take manual note of pH at critical stages:
- Post active ingredient dissolution
- Post buffer addition
- Post final volume adjustment
- If deviation occurs, notify QA and adjust pH using approved buffers (e.g., citric acid, sodium citrate) under supervision.
5.3 Cleaning and Maintenance of pH Probes
- After each batch, remove and clean the pH sensor using purified water followed by mild detergent solution.
- Do not allow probe to dry — store it in pH 4.0 storage solution when not in use.
- Inspect for any cracks, discoloration, or damage. Replace damaged sensors as per SOP.
5.4 Documentation
- Enter real-time pH data in the Real-Time pH Monitoring Logbook (Annexure-1) or electronic batch record system.
- Include:
- Batch No.
- Date and Time
- pH Value
- Stage of Manufacturing
- Operator Initials
- QA to review and sign off each completed pH log.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- SCADA: Supervisory Control and Data Acquisition
- BMR: Batch Manufacturing Record
7. Documents
- Real-Time pH Monitoring Logbook (Annexure-1)
- pH Probe Calibration Log
- BMR Reference Sheet
8. References
- ICH Q8 – Pharmaceutical Development
- 21 CFR Part 211.110 – In-process Controls
- WHO TRS 986 – GMP Guidelines
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Real-Time pH Monitoring Logbook
| Date | Batch No. | Manufacturing Stage | Observed pH | Operator | QA Review |
|---|---|---|---|---|---|
| 11/04/2025 | ELX-0425-011 | Post Final Adjustment | 6.8 | Rajesh Kumar | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial Release | New SOP | QA Head |
| 11/04/2025 | 2.0 | Included SCADA monitoring and calibration log | Process Optimization | QA Head |