Head – Manufacturing is accountable for ensuring strict compliance to this SOP.

5. Procedure

5.1 Material Preparation and Verification

1. Collect and verify raw materials as per the BMR and approved bill of materials.
2. Ensure all thermosensitive agents (e.g., poloxamers, methylcellulose) are handled at controlled temperatures.
3. Confirm the presence of specific thermal transition temperatures and material compatibility.

5.2 Equipment Preparation

1. Use jacketed mixing vessels with integrated temperature sensors and chillers.
2. Calibrate temperature probes and ensure uniform cooling/heating across the vessel.
3. Perform cleaning and line clearance as per the equipment logbook and cleaning SOPs.

5.3 Gel Preparation Process

1. Charge purified water into the vessel at the pre-determined temperature (usually 4–10°C).
2. Add excipients and stir gently using slow agitation to prevent air entrapment.
3. Gradually add thermosensitive agents (e.g., Poloxamer 407) under continuous stirring until fully hydrated.
4. Allow swelling for the defined duration (often overnight at refrigerated conditions).

5.4 Drug Incorporation and Homogenization

1. Warm the mixture to the predefined transition temperature (typically 20–30°C) to achieve sol-to-gel transformation behavior.
2. Disperse or dissolve the active pharmaceutical ingredient (API) under continuous stirring until uniform.
3. Use a homogenizer to achieve a consistent gel texture without disrupting the temperature-sensitive properties.

5.5 pH Adjustment and Final Processing

1. Measure the pH and adjust if necessary using pre-approved acid or base (e.g., citric acid, sodium hydroxide).
2. Pass the gel through a filtration system if required (based on product specification).
3. Conduct viscosity and temperature shift behavior tests before approving the batch for filling.

5.6 Filling and Packaging

1. Transfer the gel under a nitrogen blanket (if applicable) to avoid oxidation.
2. Fill into containers using thermostatically controlled nozzles to prevent premature gelling.
3. Seal and label as per batch packaging record (BPR) and transfer for final QC testing.

5.7 Documentation and Cleaning

1. Record all manufacturing parameters in the batch manufacturing record.
2. Clean all equipment as per the validated cleaning procedure for thermosensitive products.
3. Submit samples to Quality Control for release testing.

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• BPR: Batch Packaging Record
• API: Active Pharmaceutical Ingredient

7. Documents

1. Batch Manufacturing Record – Annexure-1
2. Temperature Monitoring Log – Annexure-2
3. Transition Temperature Verification Sheet – Annexure-3
4. Equipment Calibration Certificate – Annexure-4
5. Homogenization Verification Log – Annexure-5

8. References

• ICH Q8: Pharmaceutical Development
• WHO GMP Guidelines – Annex 2: Manufacturing of Semi-Solid Dosage Forms
• USP General Chapter <795> – Pharmaceutical Compounding

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: Batch Manufacturing Record

Date	Batch No.	Shift	Operator	Remarks

Annexure-2: Temperature Monitoring Log

Stage	Time	Temp (°C)	Checked By	Remarks

Annexure-3: Transition Temperature Verification Sheet

Sample	Observed Temp (°C)	Expected Temp (°C)	Result	Remarks

Annexure-4: Equipment Calibration Certificate

Equipment ID	Date of Calibration	Due Date	Calibrated By	Status

Annexure-5: Homogenization Verification Log

Batch No.	RPM	Time (min)	Performed By	Remarks

Revision History

Revision Date	Revision No.	Change Description	Reason	Approved By
03/03/2022	1.0	Initial issue	New SOP	QA Head
10/06/2025	2.0	Added temperature transition testing and documentation updates	Process enhancement	QA Head