Standard Operating Procedure for pH Adjustment Using Buffers in Elixir Manufacturing

Department	Elixir Department
SOP No.	SOP/ELX/060/2025
Supersedes	SOP/ELX/060/2022
Page No.	Page 1 of 8
Issue Date	11/04/2025
Effective Date	15/04/2025
Review Date	11/04/2026

1. Purpose

To outline the procedure for adjusting and maintaining the pH of elixir formulations using appropriate buffer solutions to ensure product stability and efficacy.

2. Scope

This SOP applies to all elixir batches in the Elixir Department where pH adjustment is required during or after mixing, prior to filtration or filling.

3. Responsibilities

• Manufacturing Operator:
  • Prepare and add buffer solutions as per batch instructions.
  • Perform in-process pH measurement and record values.
• Production Supervisor:
  • Verify pH range compliance and authorize pH correction steps.
• QA Officer:
  • Cross-verify final pH values and ensure SOP compliance.

4. Accountability

The Production Head is accountable for ensuring pH is maintained within specified limits for each batch and all adjustments are documented and verified.

5. Procedure

5.1 Pre-Check for pH

1. Stop mixing and allow batch to stabilize for 5–10 minutes before sampling.
2. Using a calibrated pH meter, take samples from the top, middle, and bottom of the tank.
3. Record pH values and compare them with batch specifications (as per BMR).

5.2 Buffer Preparation

1. Prepare buffer solutions using pharmaceutical-grade materials (e.g., citric acid, sodium citrate, sodium acetate, acetic acid).
2. Dissolve measured quantity of buffer in purified water using clean glassware.
3. Label each prepared buffer with:
   • Name of buffer
   • Concentration
   • Prepared on and used by dates

5.3 pH Adjustment

1. If pH is lower than specified, add alkaline buffer (e.g., sodium citrate).
2. If pH is higher than specified, add acidic buffer (e.g., citric acid).
3. Add buffer solution slowly under continuous stirring at moderate speed (50–80 RPM).
4. After each addition, stir for 10 minutes and recheck the pH.
5. Continue the process until the pH falls within acceptable range.

5.4 Post-Adjustment Checks

1. Perform final pH check from three points (top, middle, bottom).
2. Document pH values in the pH Adjustment Log (Annexure-1).
3. Get verification from Supervisor and QA before proceeding to the next manufacturing step.

5.5 Meter Calibration

1. Ensure the pH meter is calibrated with standard buffer solutions (pH 4.0, 7.0, and 10.0) before use.
2. Enter calibration details in the pH Meter Calibration Log (Annexure-2).

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• QA: Quality Assurance
• pH: Potential of Hydrogen

7. Documents

1. pH Adjustment Log (Annexure-1)
2. pH Meter Calibration Log (Annexure-2)
3. Buffer Preparation Record (Annexure-3)

8. References

• USP General Chapter <781> pH
• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria
• 21 CFR 211.160 – Laboratory Controls

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: pH Adjustment Log

Date	Batch No.	Initial pH	Buffer Used	Final pH	Adjusted By	Verified By
11/04/2025	ELX-1006	4.2	Sodium Citrate	4.8	Rajesh Kumar	Sunita Reddy

Annexure-2: pH Meter Calibration Log

Date	Instrument ID	Buffer Used	Calibrated By	Verified By
11/04/2025	PHM-03	pH 4.0, 7.0	Ajay Mehta	Manju Sharma

Annexure-3: Buffer Preparation Record

Date	Buffer Type	Concentration	Prepared By	Used By
11/04/2025	Citric Acid Buffer	0.1 M	Rajesh Kumar	12/04/2025

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
01/01/2024	1.0	Initial SOP Release	New SOP	QA Head
11/04/2025	2.0	Added Calibration and Multi-point Sampling	Process Optimization	QA Head