ISO 21501-3:2019

Overview - ISO 21501-3:2019 (LELPC)

ISO 21501-3:2019 specifies calibration and verification methods for the light extinction liquid-borne particle counter (LELPC) used to determine particle size distribution and particle number concentration in liquids. The standard covers single-particle light extinction measurements for particles typically in the 1 µm to 100 µm range. It is intended to ensure reliable, traceable measurements for applications such as pharmaceutical product cleanliness and general liquid contamination monitoring.

Key topics and technical requirements

The standard defines measurement principles, instrument configuration and mandatory performance checks. Key technical topics include:

• Measurement principle: single-particle light extinction - particle passage attenuates an incident light beam; pulse height relates to optical particle size.
• Size setting error: maximum permissible error (MPE) for size settings; size setting must be verified before shipment and during periodic calibration.
• Counting efficiency: required to be within specified limits (100 ± 20 %) when tested per the standard.
• Size resolution: defined performance limit (≤ 10 %) and test procedures.
• Maximum particle number concentration: manufacturer must specify maximum measurable concentration; coincidence loss at that maximum shall be ≤ 10 %.
• Sampling performance: requirements for sampling flow rate error, sampling time error (±1 % MPE), and sampling volume error (±5 % MPE) where applicable.
• Calibration interval: recommended at least annually (one year or shorter).
• Reporting requirements: test/calibration reports must include date, calibration particles used (e.g., CRMs such as PSL suspensions), and results for parameters including size setting error, counting efficiency, size resolution, maximum concentration, sampling errors and calibration interval.

Terminology and traceability: the standard references Certified Reference Materials (CRM) for size and concentration characterization and includes guidance on uncertainty evaluation.

Applications and who uses ISO 21501-3

ISO 21501-3 is applied in settings that require rigorous liquid-borne particle monitoring and traceable calibration:

• Pharmaceutical manufacturers and QC labs - testing injections, infusions, water for injections for particulate contamination.
• Instrument manufacturers - LELPC design validation, size calibration, and factory verification before shipment.
• Metrology and calibration laboratories - routine instrument calibration, reporting and uncertainty estimation.
• Process and R&D labs - characterizing particle size distributions in process fluids, quality control and method validation.

Using ISO 21501-3 helps ensure comparability of particle counts and sizes across instruments and sites, supporting compliance, product safety and quality control.

Related standards

• Other parts of the ISO 21501 series (particle sizing by single particle light interaction methods) for complementary instrument types and methods.
• General ISO/IEC directives and guidance on traceability and uncertainty relevant to calibration and metrology.