A new coincidence model for single particle counters, Part II: Advances and applications.
Accuracy, acceptance limits and methods for U.S.P. (788) contaminating particle assays published in the XXII Revision are refined in U.S.P. XXIII. In both Revisions, although different numerical values and methods are employed, particle contamination limits remain constants for all S.V.I. container volumes. The effect of this quality standard is high particle concentration acceptance limits in the smallest S.V.I. container sizes. The effect of these high concentrations is to introduce both undercount errors and false counts into U.S.P. (788) SVI contaminating particle assays. There is general agreement that the count of high concentrations of particles by a single particle light extinction counter result in an increase of the average size of the distribution of particles reported and a decrease in their total number. The error mechanism is termed "signal coincidence." Understanding and control of both these problems is unified with the introduction of the count efficiency parameter. Part I of this paper makes available two core concepts with which evaluation and control of coincidence error in single particle counters can be accurately quantified. These two core concepts are the "Particle Triggered Poisson Model," a new more accurate statistical model of the particle counting process and a concentration measure that includes the effect of particle size on the counting capability of a detector. Use of these concepts make it possible to evaluate particle detector count efficiency capability from experimental data of the coincidence effect. This is an application paper. It combines the theory in the Part I paper with the replicability of particle counters into a simple test protocol. The test results can be used to calculate a contour of particle size and count within which both undercount errors and the introduction of false counts into U.S.P. (788) particle assays are controlled. From the data analyzed it can be seen that any single particle size test cannot effectively evaluate detector performance. The use of the theory and methodology described can help realize the intent of the U.S.P. (788) SVI particle contamination assay.
Knapp
J Z
JZ
R & D Associates, Inc., Somerset, New Jersey.
Lieberman
A
A
Abramson
L R
LR
D002138:Calibration; D004340:Drug Contamination / Q000517:prevention & control*; D004345:Drug Industry / Q000295:instrumentation* / Q000592:standards; D005069:Evaluation Studies as Topic; D007263:Infusions, Parenteral / Q000592:standards; D015233:Models, Statistical; D010316:Particle Size; D011237:Predictive Value of Tests; D011786:Quality Control; D015203:Reproducibility of Results; D012996:Solutions / Q000592:standards*
D012996:Solutions