all batch sizes and formulations of sterile injectable products prepared in the solution preparation area at [Insert Company Name].

3. Responsibilities

• Manufacturing Operator: To perform solution preparation and mixing as per instructions and document observations.
• Manufacturing Supervisor: To verify process parameters, supervise activities, and ensure compliance with the Master Formula Record (MFR).
• IPQA Officer: To monitor critical mixing steps, perform in-process checks, and verify homogeneity.
• Engineering Personnel: To ensure mixing equipment is calibrated, qualified, and maintained.

4. Accountability

The Head of Manufacturing is accountable for ensuring adherence to the proper mixing procedure and maintaining GMP compliance throughout the operation.

5. Procedure

5.1 Pre-Mixing Preparation

1. Verify the cleanliness status of the solution preparation vessel and mixing equipment.
2. Ensure equipment has valid calibration and cleaning tags attached.
3. Confirm the batch number, product name, and MFR before initiating the process.
4. Cross-check the weighed raw materials (active and inactive) with the Material Dispensing Log.
5. Check availability of purified water for injection (WFI), utilities, and environmental conditions (temperature, RH).
6. Ensure that all personnel involved are in sterile gowning and trained for aseptic handling.

5.2 Equipment Setup

1. Connect the mechanical stirrer, homogenizer, or magnetic mixer to the preparation vessel as per the MFR.
2. Ensure speed controllers and timers are functional.
3. Start a 10-minute pre-operation test run to confirm operational readiness of mixing system.

5.3 Addition of Ingredients

1. Start with the specified volume of WFI as mentioned in the MFR.
2. Add ingredients in a stepwise and sequential manner:
   • Dissolve excipients first (e.g., buffers, stabilizers)
   • Then add active pharmaceutical ingredients (APIs)
   • Add pH adjusters and preservatives as per instruction
3. Record each addition in the Solution Preparation Log (Annexure-1).
4. Monitor temperature during mixing, especially for heat-sensitive compounds.

5.4 Mixing Parameters

1. Operate the mixer at predefined RPM (e.g., 150–300 RPM) for the time specified in the MFR (e.g., 30–90 minutes).
2. Ensure vortex formation (if required) does not lead to air entrapment.
3. Continue mixing until a clear, particle-free, and homogenous solution is achieved.
4. Record start and stop times for each mixing stage.

5.5 In-Process Verification of Mixing

1. Take 3 samples from:
   • Top layer
   • Middle layer
   • Bottom layer
2. Submit samples to QC for:
   • pH test
   • Assay or content uniformity
   • Visual appearance
3. Results should meet specifications to proceed to the next step.
4. IPQA Officer must sign off the Solution Preparation Log upon approval.

5.6 Post-Mixing Activities

1. Transfer the final bulk solution through a 0.22 μm pre-filtration unit to the holding vessel.
2. Label the bulk with name, batch number, volume, and date using the Bulk Holding Label (Annexure-2).
3. Ensure solution is stored under controlled temperature until further processing (e.g., sterile filtration).

5.7 Deviations and Troubleshooting

1. If incomplete dissolution is observed:
   • Continue mixing under same conditions for additional 15–30 minutes
   • Report to Supervisor and QA if no improvement occurs
2. If foaming occurs:
   • Reduce RPM
   • Use defoamers only if mentioned in the MFR and approved by QA
3. Document any deviation in the Deviation Report (Annexure-3).

6. Abbreviations

• SOP: Standard Operating Procedure
• MFR: Master Formula Record
• WFI: Water for Injection
• IPQA: In-Process Quality Assurance
• RPM: Revolutions per Minute
• QA: Quality Assurance

7. Documents

1. Solution Preparation Log – Annexure-1
2. Bulk Holding Label – Annexure-2
3. Deviation Report – Annexure-3

8. References

• WHO Guidelines on Good Manufacturing Practices
• EU GMP Annex 1
• ICH Q8 – Pharmaceutical Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Solution Preparation Log

Date	Batch No.	Material Added	Time	Operator
24/06/2025	INJ0625-001	Sodium Chloride	10:30 AM	Rajesh Kumar

Annexure-2: Bulk Holding Label

Product Name	Sodium Chloride Injection
Batch No.	INJ0625-001
Volume	120 L
Date of Preparation	24/06/2025
Status	Hold for Sterile Filtration

Annexure-3: Deviation Report

Date	Batch No.	Deviation Observed	Action Taken	Approved By
24/06/2025	INJ0625-001	Incomplete Dissolution	Extended Mixing by 20 Minutes	Sunita Reddy

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/01/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Included troubleshooting and verification process	Annual Review	QA Head