are calibrated and functioning.

4. Accountability

The Head – Manufacturing is accountable for adherence to this SOP and implementation of thermosensitive gel-specific controls during production.

5. Procedure

5.1 Pre-Manufacturing Preparation

1. Receive approved BMR and formulation from R&D/TT department.
2. Perform line clearance as per SOP/QA/003/2025 and document in Annexure-1.
3. Ensure all equipment (mixing vessels, temperature baths, chillers) are calibrated and clean.
4. Verify the HVAC system is operational and temperature settings are within defined range (20°C–25°C ambient).

5.2 Weighing and Dispensing

1. Weigh raw materials in a temperature-controlled dispensing area using calibrated balances.
2. Dispense thermo-sensitive polymers (e.g., Poloxamer 407, Pluronic F127) at cool ambient temperature (typically 4–8°C).
3. Label all containers as per SOP/GM/017/2025 and store under cold conditions until used.

5.3 Preparation of Thermosensitive Gel

1. Charge required quantity of purified water into the mixing vessel.
2. Cool the water to 4°C using jacketed tank or glycol chiller before adding polymer.
3. Gradually add thermosensitive polymer while continuously stirring at low speed to prevent agglomeration.
4. Once completely dissolved, maintain at low temperature to prevent gelation.
5. Add APIs and excipients (preservatives, pH adjusters) sequentially, maintaining cold conditions.
6. Filter the batch through a 0.45 µm or as required filter.

5.4 pH Adjustment and Final Mixing

1. Measure pH of gel and adjust to formulation range using chilled acid/base solution.
2. Perform final mixing at low shear to ensure homogeneity.

5.5 Filling and Packing

1. Use cold-room or temperature-controlled areas for filling to avoid premature gelation.
2. Fill into pre-sterilized tubes/jars using positive displacement pumps suitable for viscous materials.
3. Seal, label, and over-pack as per product specifications.

5.6 In-process and Finished Product Checks

1. Check for viscosity, gelation temperature, homogeneity, and pH as per IP/BP/USP standards.
2. Collect retain samples and send for stability studies (Annexure-2).
3. Complete batch documentation including cleaning log, calibration status, and yield reconciliation.

6. Abbreviations

• API: Active Pharmaceutical Ingredient
• BMR: Batch Manufacturing Record
• GMP: Good Manufacturing Practice
• HVAC: Heating, Ventilation, and Air Conditioning
• TT: Technology Transfer

7. Documents

1. Batch Manufacturing Record – Annexure-1
2. Stability Sample Register – Annexure-2
3. Equipment Cleaning Log – Annexure-3
4. pH Adjustment Record – Annexure-4
5. Thermal Profile Monitoring Sheet – Annexure-5

8. References

• ICH Q8: Pharmaceutical Development
• Schedule M: GMP Guidelines for Pharmaceuticals (India)
• USP General Chapter <1059> – Thermosensitive Dosage Forms

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 (BMR)

To be completed during each stage of thermosensitive gel production. Includes batch number, yield, ingredient weights, and deviations.

Annexure-2: Stability Sample Register

Batch No.	Storage Condition	Sampling Date	Tested By	Remarks
	25°C/60% RH

Annexure-3: Equipment Cleaning Log

Equipment ID	Cleaning Date	Cleaned By	Verified By (QA)

Annexure-4: pH Adjustment Record

Record initial and final pH, quantity of acid/base added, solution temperature, and signature.

Annexure-5: Thermal Profile Monitoring Sheet

Monitor and record batch temperature during mixing and filling stages. Include start time, end time, and observations.

Revision History

Revision Date	Revision No.	Description of Change	Reason	Approved By
28/04/2022	1.0	Initial release	New product line	QA Head
09/06/2025	2.0	Added new annexures and pH adjustment SOP linkage	Process standardization	QA Head