Responsibilities

• Production Chemist: Responsible for executing the mixing operations as per batch instructions and SOP.
• QA Executive: To verify uniformity and record data.
• Engineering Department: Responsible for maintenance and calibration of mixing equipment.

4. Accountability

Head – Manufacturing shall be accountable for compliance with this procedure and ensuring that mixing standards are met at all times.

5. Procedure

5.1 Pre-Mixing Checks

1. Verify that all raw materials have been dispensed and labeled as per SOP.
2. Ensure that the mixing vessel is clean, dry, and labeled with the current batch number.
3. Check that agitators and homogenizers are calibrated and functioning properly.
4. Record initial temperature and pH of the batch before mixing begins.

5.2 Mixing Operations

1. Load the gel base and begin low-speed mixing for 5–10 minutes to pre-condition the base.
2. Gradually add APIs, preservatives, and other excipients while maintaining continuous agitation.
3. Increase mixing speed as required for uniform dispersion of ingredients.
4. If required, use a homogenizer at pre-defined RPM for a specified duration (e.g., 1000 RPM for 15 minutes).

5.3 Monitoring Uniformity

1. Draw in-process samples from different points (top, middle, bottom) of the vessel.
2. Test the samples for pH, viscosity, and assay content where applicable.
3. Continue mixing if variation in readings is more than ±5% from the mean value.
4. Record all readings in the Uniformity Log (Annexure-1).

5.4 Mixing Completion Criteria

• Product is considered uniformly mixed if:
  • pH deviation across samples is ≤ ±0.2 units
  • Viscosity deviation across samples is ≤ ±10%
  • Content uniformity is within 90–110% of label claim across locations

5.5 Post-Mixing Operations

1. Stop the mixer and allow the gel to rest for 5–10 minutes for deaeration.
2. Visually inspect the batch for lumps, streaks, or undissolved particles.
3. Record end time of mixing and proceed to filling or storage based on batch instructions.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• QA: Quality Assurance
• SOP: Standard Operating Procedure

7. Documents

1. Uniform Mixing Log – Annexure-1
2. Mixing Equipment Usage Log – Annexure-2

8. References

• ICH Q8 (R2) – Pharmaceutical Development
• WHO TRS 986 Annex 2 – GMP Guidelines for Pharmaceuticals

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Jr. Production Chemist	QA Executive	Head – Manufacturing
Department	Gel Manufacturing	Quality Assurance	Manufacturing

11. Annexures

Annexure-1: Uniform Mixing Log

Date	Batch No.	Sample Point	pH	Viscosity (cps)	Assay (%)	Remarks	Checked By
		Top
		Middle
		Bottom

Annexure-2: Mixing Equipment Usage Log

Equipment ID	Batch No.	Start Time	End Time	RPM	Operator Initials	Remarks

Revision History

Revision Date	Revision No.	Change Description	Reason	Approved By
06/06/2022	1.0	Initial Release	Procedure Establishment	QA Head
02/06/2025	2.0	Included Uniform Mixing Criteria and Annexures	Process Standardization	QA Head