conformance to compendial limits and product quality standards.

2. Scope

This SOP applies to the Analytical Method Development and Quality Control departments for routine and validation testing of visible and sub-visible particulate matter in large-volume and small-volume parenterals using automatic particle counters.

3. Responsibilities

• Analytical Scientist: Conducts testing using calibrated light obscuration equipment and records results.
• QC Analyst: Prepares test samples, ensures cleanliness of glassware and test environment.
• QA Executive: Verifies results, ensures method alignment with pharmacopeial standards (USP, Ph. Eur.).

4. Accountability

The Head of Analytical Method Development is accountable for ensuring validated methodology, equipment calibration, and compliance with regulatory guidelines on particulate matter control.

5. Procedure

5.1 Equipment and Materials

1. Automatic Particle Counter (e.g., HIAC or equivalent)
2. Calibrated standards and blank solution (WFI)
3. Cleaned sample containers and syringes
4. Laminar airflow workstation

5.2 Equipment Calibration

1. Calibrate the instrument using polystyrene latex beads traceable to NIST standards.
2. Verify detection sensitivity at ≥10 µm and ≥25 µm size ranges.
3. Perform system suitability with blank WFI: Should show <10 particles/mL ≥10 µm and <2 particles/mL ≥25 µm.

5.3 Sample Preparation

1. Visually inspect vials for visible particles prior to testing.
2. Gently invert to homogenize without generating bubbles.
3. Withdraw sample aseptically into syringe and transfer to clean test chamber of particle counter.

5.4 Test Conditions and Measurement

1. Ensure background particle level in environment is minimal.
2. Flush instrument with blank before sample testing.
3. Run sample in duplicate; each run must test not less than 5 mL (SVP) or 10 mL (LVP).
4. Count particles at ≥10 µm and ≥25 µm thresholds.

5.5 Acceptance Criteria (USP <788>)

• Small-Volume Injections (≤100 mL):
  • ≥10 µm: NMT 6000 particles per container
  • ≥25 µm: NMT 600 particles per container
• Large-Volume Injections (>100 mL):
  • ≥10 µm: NMT 25 particles/mL
  • ≥25 µm: NMT 3 particles/mL

5.6 Method Validation Parameters

1. Specificity: Blank samples must be free from interference.
2. Precision: RSD ≤10% for replicate readings.
3. Linearity: Confirm across standard concentrations using PSL beads.
4. Robustness: Evaluate instrument performance at varied flow rates and temperatures.

6. Abbreviations

• USP: United States Pharmacopeia
• WFI: Water for Injection
• PSL: Polystyrene Latex
• RSD: Relative Standard Deviation
• QA: Quality Assurance

7. Documents

1. Particulate Matter Test Log – Annexure-1
2. Calibration Report – Annexure-2
3. Validation Summary Report – Annexure-3

8. References

• USP <788>: Particulate Matter in Injections
• Ph. Eur. 2.9.19: Particulate Contamination
• ICH Q6A: Specifications Guidelines

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Sandeep Bhaskar	Kavita Jain	Sunita Reddy
Designation	Senior Analyst	QA Reviewer	Head – AMD
Department	Analytical Method Development	QA	Analytical Method Development

11. Annexures

Annexure-1: Particulate Matter Test Log

Sample ID	Volume (mL)	≥10 µm (Count)	≥25 µm (Count)	Status
INJ-268-01	10	230	12	Pass

Annexure-2: Calibration Report

Date	Standard Size (µm)	Observed Count	Acceptance Range	Status
20/05/2025	10.0	1480	1400–1600	Pass
20/05/2025	25.0	245	230–270	Pass

Annexure-3: Validation Summary Report

The light obscuration method was validated for multiple injection types. Results met USP acceptance limits for particulate counts. Precision (RSD = 5.4%), specificity, and robustness across sample types confirmed. The method is approved for routine release and stability testing.

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
21/05/2025	2.0	Aligned with Ph. Eur. 2.9.19 and added new annexures	Annual Review	Sunita Reddy
15/04/2022	1.0	Initial Release	New SOP	QA Head