Standard Operating Procedure for Particle Size Distribution Monitoring in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/068/2025 |
| Supersedes | SOP/API/068/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for monitoring particle size distribution (PSD) in API manufacturing using validated analytical techniques, ensuring batch-to-batch consistency, regulatory compliance, and product performance.
2. Scope
This SOP applies to all APIs and intermediates requiring PSD testing during in-process control or final release. It includes both dry sieving and laser diffraction methods used in the QC laboratory.
3. Responsibilities
- QC Analyst: Perform PSD testing and document results accurately.
- QC Supervisor: Review test reports and ensure compliance with method validation.
- QA Department: Ensure documentation adherence and regulatory compliance.
4. Accountability
The QC Head is accountable for accurate execution and review of PSD testing. QA is responsible for SOP and data integrity compliance.
5. Procedure
5.1 Method Selection
- Select appropriate method:
- Dry Sieving: for coarse APIs or intermediates with size >75 microns
- Laser Diffraction: for micronized or sub-75 µm materials
- Verify method validation status before performing analysis.
5.2 Sieving Method
- Use a validated mechanical sieve shaker with certified sieves (e.g., 850 µm to 75 µm).
- Weigh a known quantity of sample (e.g., 25 g) and distribute over stacked sieves.
- Run shaker for specified time (e.g., 10 minutes at 30 rpm).
- Weigh residue on each sieve and record weights.
- Calculate cumulative retained and particle size distribution profile.
5.3 Laser Diffraction Method
- Turn on laser diffraction analyzer and complete calibration check.
- Prepare sample by dispersing in suitable medium (e.g., IPA or air dispersion unit).
- Ensure obscuration is within acceptable range (e.g., 10–20%).
- Run analysis in triplicate and calculate average D10, D50, D90 values.
- Compare values to product specifications.
5.4 Documentation and Reporting
- Document raw data in “PSD Analysis Log” (Annexure-1).
- Attach graphical printouts or summary reports to the Batch Manufacturing Record (BMR).
- If results are out of specification, initiate deviation and inform QA immediately.
5.5 Cleaning and Calibration
- Clean sieves, funnels, and sample holders with appropriate solvents or air jet after use.
- Maintain daily instrument log and calibration certificate for laser diffraction analyzers.
6. Abbreviations
- SOP: Standard Operating Procedure
- PSD: Particle Size Distribution
- QC: Quality Control
- QA: Quality Assurance
- D10/D50/D90: Percentiles of the cumulative volume distribution
- BMR: Batch Manufacturing Record
7. Documents
- PSD Analysis Log (Annexure-1)
- Instrument Calibration Record
- Test Method SOP
8. References
- USP <786> Particle Size Distribution Estimation
- ICH Q6A – Specifications
- Internal Method Validation Protocols
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: PSD Analysis Log
| Date | Batch No. | Method | D10 (µm) | D50 (µm) | D90 (µm) | Analyst |
|---|---|---|---|---|---|---|
| 13/04/2025 | API-PSD-20250413 | Laser Diffraction | 2.3 | 5.1 | 9.7 |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | Method Implementation | QA Head |
| 13/04/2025 | 2.0 | Integrated Laser Diffraction and Sieving Methodology | GMP Enhancement | QA Head |