A new coincidence model for single particle counters, part III: realization of single particle counting accuracy.
U.S.P. objective tests for particle contamination in injectable fluids are based on counts of single particles in a specified test volume. Accuracy standards for these tests must therefore be based on single particle count accuracy. A definitive analysis for this purpose is described whose results can be used during a counting experiment. To improve the accuracy of particle counter data, U.S.P.XXIII has added a particle counter accuracy requirement defined in terms of a maximum particle concentration for 10 microns particles at which there is a 10% ratio of coincident occurrences. The 10% coincident count ratio cannot be directly measured: it must be calculated from experimental results using a model of the counting process. The U.S.P.XXIII count accuracy specification relies on vendor statements without definition of the methodology or model to be employed. The model of particle counting described in the literature is the Geometric Poisson model due to Jaenicke (4) and extended by Lieberman (5). Recent publications (1, 2) have shown that calculations based on this model do not agree with experimental data. This conclusion is supported and extended in this paper. The single particle counting error estimate for U.S.P.XXIII (788) SVI (3), using Jaenicke's Geometric model to evaluate a good commercial laser sourced detector, is 9.32%; the single particle count error estimate for this detector using the experimentally validated Particle-Triggered Poisson model is 19%. The count error for the concentration calculated with the Jaenicke Geometric model for the same detector is 40.5% when calculated with the validated Particle-Triggered Poisson model. The estimated count error increases for particles larger than 10 microns. Light extinction particle counters are well behaved instruments fully capable of the workhorse task of making accurate, routine single particle contamination measurements in injectable products. In principle, any particle counter instrument now in use, operated within calculated particle size and concentration contours, can deliver accurate single particle counting data. Operation within these limits both within and below the U.S.P.XXIII (788) (3) size range will assure single particle count accuracy without the injection of false counts or undercounts. These count limits vary with particle size and are determined by the capability of the counter. No single particle test can characterize the complex particle size and concentration response of a detector. In practice, selection of a counter with sufficient capability to provide the desired accuracy without constant dilution is an important consideration. When particle concentration exceeds the selected count accuracy contour, dilution and a repeat of the assay provide a practical solution.
Knapp
J Z
JZ
R & D Associates, Incorporated, Somerset, New Jersey, USA.
Abramson
L R
LR
D004340:Drug Contamination; D010602:Pharmacopoeias as Topic; D016012:Poisson Distribution; D012680:Sensitivity and Specificity