testing for performance, stability, and packaging compatibility.

Regulatory Affairs Team: Ensures that pilot-scale batches meet regulatory requirements and that all necessary documentation is completed for submission to regulatory authorities.

4. Accountability

The R&D Manager is accountable for ensuring that this SOP is followed during the pilot-scale batch design process. The overall compliance with this SOP is under the supervision of the Quality Assurance (QA) Manager.

5. Procedure

5.1. Review of Laboratory-Scale Formulation

1. Before scaling up, ensure that the laboratory-scale formulation has been thoroughly tested and optimized. The formulation should meet the required stability, performance, and regulatory criteria.
2. Review all formulation components, including active ingredients, excipients, propellants, and packaging materials, to ensure they are suitable for scaling up.
3. Ensure that the formulation’s performance and characteristics (e.g., spray pattern, droplet size, aerosol delivery) have been adequately evaluated and documented in the laboratory-scale testing phase.

5.2. Determination of Pilot-Scale Equipment

1. Select appropriate equipment for the pilot-scale batch. The equipment should closely mimic the commercial manufacturing process, including scale-up factors such as batch size, mixing time, and pressure.
2. Ensure that the selected equipment (e.g., homogenizer, mixer, aerosol filling machine) is capable of accurately producing the aerosol formulation while maintaining the desired product characteristics.
3. Verify that all equipment is calibrated and properly maintained according to the equipment calibration schedule.

5.3. Pilot-Scale Batch Formulation

1. Scale up the formulation from the laboratory batch to the pilot-scale batch. Adjust ingredient quantities based on the desired batch size, ensuring that all components are included in the proper proportions.
2. Mix the components under controlled conditions, ensuring that temperature, pressure, and mixing speed are optimized for the scale-up process.
3. Ensure that the propellant and active ingredients are mixed and incorporated thoroughly to maintain uniformity in the formulation.

5.4. Pilot-Scale Batch Processing

1. Monitor the pilot-scale manufacturing process closely, including mixing, homogenization, and filling of aerosol containers, to ensure that it closely matches the laboratory process.
2. Conduct in-process testing to ensure that the formulation meets the required specifications for viscosity, pH, appearance, and consistency.
3. Ensure that the packaging materials (e.g., aerosol cans, valves, actuators) are compatible with the formulation and that no leakage or damage occurs during filling.
4. Fill the aerosol containers with the pilot-scale formulation under controlled conditions. Record the batch number, manufacturing date, and other relevant details in the batch record.

5.5. Quality Control Testing of Pilot-Scale Batches

1. Perform QC testing on the pilot-scale batch to evaluate product characteristics and ensure that the product meets the desired quality attributes. This includes testing for:
   • Spray pattern and droplet size distribution
   • Active ingredient concentration
   • Viscosity and stability
   • Packaging integrity (e.g., leak tests, valve functionality)
2. Document all test results and observations in the Pilot-Scale Batch Testing Log (Annexure-1).
3. If the pilot-scale batch fails to meet any of the required specifications, initiate corrective actions (e.g., formulation adjustments, equipment modifications) and retest the batch.

5.6. Stability Testing of Pilot-Scale Batches

1. Subject the pilot-scale batch to stability testing under accelerated conditions (e.g., 40°C ± 2°C and 75% RH ± 5%) to simulate real-world storage conditions.
2. Monitor the formulation for signs of degradation, phase separation, or other stability issues during the testing period. Record the stability data in the Stability Testing Log (Annexure-2).
3. If any stability issues are detected, perform root cause analysis and make necessary adjustments to the formulation or process.

5.7. Documentation and Reporting

1. Document all aspects of the pilot-scale batch process, including formulation development, equipment used, batch records, in-process testing, and stability testing, in the Pilot-Scale Batch Report (Annexure-3).
2. The report should include the following details:
   • Formulation details (active ingredients, excipients, propellants)
   • Batch number, production dates, and batch sizes
   • Testing results, including in-process testing and QC testing
   • Stability testing results and any adjustments made to the formulation or process
3. Submit the report for review and approval by the QC team and regulatory affairs team.

5.8. Corrective and Preventive Actions (CAPA)

1. If issues arise during the pilot-scale batch process (e.g., formulation instability, poor spray pattern), initiate corrective actions to address the issue. This may involve adjusting the formulation, changing the process parameters, or improving equipment performance.
2. Implement preventive actions to avoid recurrence of similar issues, such as revising formulation procedures, enhancing equipment calibration, or improving training for operators.
3. Document all corrective and preventive actions in the CAPA Log (Annexure-4) and track the effectiveness of the actions taken.

6. Abbreviations

• GMP: Good Manufacturing Practice
• QC: Quality Control
• CAPA: Corrective and Preventive Actions
• R&D: Research and Development

7. Documents

1. Pilot-Scale Batch Testing Log (Annexure-1)
2. Stability Testing Log (Annexure-2)
3. Pilot-Scale Batch Report (Annexure-3)
4. CAPA Log (Annexure-4)

8. References

This SOP is based on the following regulatory guidelines and industry standards:

• Good Manufacturing Practice (GMP) Guidelines
• FDA Code of Federal Regulations (CFR) Title 21, Part 211
• ISO 9001:2015 – Quality Management Systems

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Pilot-Scale Batch Testing Log

Test Parameter	Test Date	Test Result	Observations	Tested By
Spray Pattern	06/02/2025	Pass	No clogging	Rajesh Patel

Annexure-2: Stability Testing Log

Test Parameter	Test Date	Test Result	Remarks	Tested By
Viscosity	06/02/2025	Pass	No change	Ravi Kumar

Annexure-3: Pilot-Scale Batch Report

Batch No.	Formulation	Test Results	Final Recommendations	Approval Date
12345	Example Aerosol	Pass	Proceed to full-scale production	06/02/2025

Annexure-4: CAPA Log

Issue	Root Cause	Corrective Action	Preventive Action	Follow-up Date
Phase separation	Improper mixing	Reformulated with better mixing method	Enhanced mixing procedure	06/03/2025

12. Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By	Page No.	Ref. Point No.	Details of Revision
01/01/2024	V 1.0	Initial Release	First Issue	Anjali Sharma	Page 1	[Ref Point]	First Release
01/01/2025	V 2.0	Updated batch scaling process	To comply with updated GMP regulations	Anjali Sharma	Page 1	[Ref Point]	Updated procedures