Liquid Borne Particle Count (LBPC) – Principle, Procedure, Calculation, and Acceptance Criteria
Liquid Borne Particle Count (LBPC) is a critical quality control test performed to determine the presence and quantity of particulate contamination in pharmaceutical liquids, especially Water for Injection (WFI), Purified Water, and parenteral preparations. The test ensures that the liquid products or water systems meet the particulate matter limits as per pharmacopeial standards such as USP <788>, EP 2.9.19, and ISO 21501.
This test is mandatory in pharmaceutical manufacturing for ensuring that injectable products and critical process waters are free from visible and sub-visible particles that may pose a risk to patient safety or affect product quality.
1. Introduction
Particulate contamination in liquid pharmaceutical products may originate from the manufacturing process, packaging components, or environmental sources. These particles can include fibers, dust, glass, metal fragments, or microbial residues. The Liquid Borne Particle Count (LBPC) test measures the number and size distribution of particles using light obscuration or light scattering principles.
The test is primarily used for:
- Monitoring Water for Injection (WFI) and Purified Water systems.
- Testing parenteral solutions (large volume and small volume injectables).
- Validating filtration systems and ensuring compliance with GMP and regulatory standards.
2. Principle of Liquid Borne Particle Count
The LBPC test is based on the Light Obscuration Principle. When a suspension of liquid containing particles passes through a sensing zone illuminated by a laser beam, each particle causes a reduction in light intensity (shadow effect). This reduction is detected and converted into an electronic pulse proportional to the particle’s size.
The instrument counts and classifies particles according to their size distribution (e.g., ≥10 µm, ≥25 µm). The results are expressed as the number of particles per milliliter of sample.
Alternative Principle: Some instruments may use light scattering where the deflection of light by particles is measured instead of light blockage.
3. Instrumentation
The test is performed using a Liquid Particle Counter or Light Obscuration Particle Counter (LOPC). Major components include:
- Laser light source
- Flow cell or sensor
- Photo detector
- Sample delivery system (syringe or peristaltic pump)
- Data acquisition and analysis software
Commonly used instruments: Beckman Coulter, PAMAS, HIAC Royco, or Particle Measuring Systems (PMS).
4. Materials and Reagents
- Test sample (Purified Water, WFI, or injectable product)
- Instrument calibration standard (e.g., latex polystyrene spheres of known size)
- Clean glassware and sample containers
- Isopropyl alcohol for cleaning (if applicable)
5. Test Procedure
5.1 System Suitability Test (Calibration Check)
- Run the instrument with particle-free water (blank test) to ensure zero background count.
- Check calibration using latex standard particles (typically 10 µm and 25 µm).
- Ensure particle counts are within ±10% of the reference value.
5.2 Sample Testing Procedure
- Mix the sample gently to ensure uniform particle distribution without introducing air bubbles.
- Filter the sample through a 40 µm sieve (if required) to remove large extraneous particles.
- Rinse the system lines with the sample before measurement.
- Collect and analyze at least 5 mL of sample using the particle counter.
- Record the number of particles ≥10 µm and ≥25 µm per mL.
- Repeat the test for three replicates and calculate the average.
6. Acceptance Criteria (as per USP <788> and EP 2.9.19)
For Small Volume Injections (≤100 mL):
| Particle Size | Limit (per mL) |
|---|---|
| ≥10 µm | Not more than 6000 particles per container |
| ≥25 µm | Not more than 600 particles per container |
For Large Volume Injections (>100 mL):
| Particle Size | Limit (per mL) |
|---|---|
| ≥10 µm | Not more than 25 particles/mL |
| ≥25 µm | Not more than 3 particles/mL |
For Water for Injection (WFI):
- As per internal or pharmacopoeial specifications: typically ≤50 particles/mL ≥10 µm.
- Counts should remain consistently below action and alert limits.
7. Calculations
Average Particle Count (per mL) = (Total particles counted) / (Sample volume in mL)
Results are reported separately for each particle size channel (e.g., ≥10 µm and ≥25 µm).
8. Interpretation and Reporting
- Compare results against acceptance limits.
- If the sample fails, recheck for contamination sources such as sampling bottle, tubing, or environment.
- All test results should be documented with batch number, date, operator name, and instrument ID.
- Maintain electronic or printed data records as per GMP documentation practices.
9. Precautions
- Ensure that the sample is free from bubbles and agitation before testing.
- Use only clean, pre-rinsed sample containers.
- Do not reuse the same syringe or tubing for multiple samples without proper rinsing.
- Handle samples under a clean laminar airflow cabinet to prevent external contamination.
10. Applications of LBPC Testing
- Pharmaceutical water system qualification (Purified Water and WFI).
- Routine monitoring of water loops.
- Quality control of injectable formulations.
- Filtration system validation and troubleshooting.
- Environmental control in aseptic processing areas.
11. Common Causes of High Particle Count
- Contaminated sampling container or tubing.
- Improper flushing of the water system before sampling.
- Air bubbles or microbubbles interfering with light beam detection.
- Particulate shedding from pump or pipeline materials.
- Microbial growth and endotoxin release in stagnant lines.
12. Conclusion
The Liquid Borne Particle Count (LBPC) test is a vital component of pharmaceutical quality assurance, ensuring that the purity of critical liquids meets international regulatory standards. Regular LBPC monitoring helps detect early contamination, prevents product failures, and maintains compliance with USP, EP, and ISO guidelines. Accurate LBPC results directly reflect the control level of the manufacturing environment and water system integrity.
13. References
- USP <788> – Particulate Matter in Injections
- EP 2.9.19 – Particulate Contamination: Sub-visible Particles
- ISO 21501 – Determination of Particle Size Distribution
- FDA Guidance for Industry – Sterile Drug Products Produced by Aseptic Processing
- WHO TRS 986 Annex 2 – GMP for Pharmaceutical Products
💬 About the Author
Siva Sankar is a Pharmaceutical Microbiology Consultant and Auditor with extensive experience in sterility testing, validation, and GMP compliance. He provides consultancy, training, and documentation services for pharmaceutical microbiology and cleanroom practices.
📧 Contact: siva17092@gmail.com
Mobile: 09505626106
