A new coincidence model for single particle counters, Part II: Advances and applications

Area of Science:

• Pharmaceutical Science
• Analytical Chemistry
• Quality Control

Background:

• Current United States Pharmacopeia (USP) <788> standards for particle contamination in small volume injectable (SVI) containers have limitations.
• High particle concentrations in small SVI containers lead to undercount and false count errors due to signal coincidence in light extinction counters.
• Existing methods struggle to accurately assess detector performance across various particle sizes and concentrations.

Purpose of the Study:

• To refine accuracy and control errors in USP <788> particle contamination assays for SVI containers.
• To introduce and validate a count efficiency parameter for single particle light extinction counters.
• To develop a test protocol for evaluating and controlling coincidence errors in particle counting.

Main Methods:

• Development of the 'Particle Triggered Poisson Model' for a more accurate statistical model of particle counting.
• Introduction of a concentration measure accounting for particle size effects on detector capability.
• Creation of a simple test protocol combining theoretical concepts with counter replicability to evaluate detector performance.

Main Results:

• The proposed methods enable accurate quantification and control of coincidence errors in particle counting.
• Experimental data can be used to calculate detector count efficiency.
• A contour of particle size and count is defined to control undercount and false counts in USP <788> assays.

Conclusions:

• The developed methodology and test protocol effectively address signal coincidence errors in USP <788> SVI particle assays.
• A single particle size test is insufficient for evaluating detector performance; a comprehensive approach is necessary.
• The findings support the intended accuracy and reliability of USP <788> SVI particle contamination testing.