correct particle size distribution is achieved during the manufacturing process and that the analysis is performed as required.

Regulatory Affairs Team: Ensures that the particle size analysis process complies with all relevant regulatory guidelines for aerosol products, including those related to drug delivery if applicable.

4. Accountability

The R&D Manager is accountable for ensuring that this SOP is followed during the particle size analysis process. The overall compliance with this SOP is under the supervision of the Quality Assurance (QA) Manager.

5. Procedure

5.1. Selection of Particle Size Measurement Method

1. Select an appropriate particle size measurement method based on the product requirements. Common methods include:
   • Laser Diffraction: Used for measuring a wide range of particle sizes.
   • Dynamic Light Scattering (DLS): Used for submicron particle size analysis.
   • Cascade Impaction: Used for assessing the aerodynamic properties and deposition behavior of aerosol particles.
2. Ensure that the selected method is validated for the specific aerosol formulation and that the equipment is properly calibrated.

5.2. Sample Preparation

1. Prepare the sample for particle size analysis according to the type of formulation (e.g., liquid suspension, powder). For liquid formulations, ensure proper homogenization to avoid sedimentation or clumping of particles.
2. For aerosol formulations, spray the product into a collection chamber or onto a substrate if using cascade impaction. For other methods, ensure that the sample is adequately dispersed and homogenized before testing.
3. Ensure that the correct volume of sample is used for the analysis, based on the method and equipment specifications.

5.3. Particle Size Analysis

1. Perform particle size analysis according to the selected method and equipment instructions. For laser diffraction and DLS, ensure that the laser beam passes through the sample correctly and that the system is properly calibrated for accuracy.
2. For cascade impaction, collect aerosol particles on the various stages of the impactor and measure the mass or number of particles collected on each stage. This provides insight into the size distribution and the deposition pattern of the aerosol particles.
3. Record the particle size distribution results, including parameters such as:
   • Mean particle size
   • Particle size range (e.g., 10th, 50th, 90th percentile)
   • Span (the width of the particle size distribution)
4. Ensure that all results meet the required specifications for the aerosol product (e.g., particle size range, distribution, and performance characteristics).

5.4. Data Analysis and Interpretation

1. Analyze the results of the particle size analysis to ensure that the product meets the desired specifications. The particle size distribution should be uniform and consistent with the desired spray characteristics, including proper atomization and delivery.
2. If the particle size does not meet the specifications, investigate the cause (e.g., formulation issue, equipment malfunction, improper sample preparation) and implement corrective actions.
3. Interpret the results in relation to the product’s intended use. For example, for an inhalable aerosol product, the particle size should be optimized for deep lung deposition, usually requiring a mass median aerodynamic diameter (MMAD) of 1-5 microns.

5.5. Documentation and Reporting

1. Document the results of the particle size analysis in the Particle Size Analysis Report (Annexure-1). This report should include:
   • Method used for particle size analysis
   • Test conditions (e.g., temperature, humidity, equipment calibration)
   • Particle size distribution results (mean, range, and span)
   • Observations and interpretations of the data
   • Any deviations or corrective actions taken
2. Ensure that the report is reviewed and approved by the QC team, R&D team, and regulatory affairs team as required.

5.6. Corrective and Preventive Actions (CAPA)

1. If particle size analysis reveals deviations from the required specifications, initiate corrective actions to resolve the issue. These actions could include adjustments to the formulation, the manufacturing process, or the particle size analysis method.
2. Preventive actions should include revising procedures, improving equipment calibration, or enhancing training for personnel involved in particle size analysis.
3. Document all corrective and preventive actions in the CAPA Log (Annexure-2) 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. Particle Size Analysis Report (Annexure-1)
2. CAPA Log (Annexure-2)

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
• International Pharmacopoeia (Ph. Int.) – Aerosol Delivery

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Particle Size Analysis Report

Formulation Name	Test Method	Mean Particle Size	Size Range	Span
Example Aerosol	Laser Diffraction	3.2 μm	2.0-4.5 μm	1.5

Annexure-2: CAPA Log

Issue	Root Cause	Corrective Action	Preventive Action	Follow-up Date
Particle size inconsistency	Improper sample dispersion	Revised dispersion method	Improved training on dispersion	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 particle size analysis process	To comply with updated GMP regulations	Anjali Sharma	Page 1	[Ref Point]	Updated procedures