Biomedical subjects
L R Abramson
Publications and source records attributed to L R Abramson.
Automated particulate inspection systems: strategies and implications.
The 1980 human performance based validation procedure for automated particulate inspection systems described by Knapp and Kushner is extended to cover the major imported systems now in use. The original publications considered only inspection machine strategies in which the controlling probability in the determination of the inspection security attained was that of rejecting the "must reject" group of containers. For application to the widely used Japanese machines, this paper also considers machines in which the controlling probability in the determination of the inspection security attained is that of accepting the "must reject" container group. The difference in inspection strategy is traced to the inherent particle detection capability of each inspection system. The effect of inspection strategy on the true and false reject rate is also discussed.
Automated particulate detection for ampuls with use of the probabilistic particulate detection model.
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Particulate inspection of parenteral products: an assessment.
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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.
A new coincidence model for single particle counters, Part I: Theory and experimental verification.
The prerequisites for estimating the effect of signal coincidence on both particle undercounting and the injection of false counts in the implementation of U.S.P. 788 contaminating particle assays by light extinction particle counters are defined. These include a particle concentration measure that varies with particle size and a new model of the counting process. Both prerequisites have been verified empirically: a single normalized equation describes the coincidence effect in all single particle counters. The single parameter of the normalized equation is the number of effective detector volumes per milliliter. A maximum undercount limit of 5% is proposed based on adequately suspended particles. Using the SVP U.S.P. XXII acceptance limits of 10,000 particles per container or the PMA propose 6,000 particles per container maximum for particles > 10 microns in U.S.P. XXIII, undercount errors are estimated for the smallest container sizes. The large concentration of particles below the controlled 10 microns particle size, that has been documented in injectable solutions, can pose an additional 788 measurement hazard. A Poisson model is used to estimate and control the injection of false particle counts into the mandated measurement through particle coincidence. Acceptable counting accuracy limits with present particle counting systems can be achieved by understanding the capabilities of the particle counter measurement system and using a dilution technique when appropriate. The new model of the counting process and the new particle concentration measures can result in standard, conservative, instrument specifications for use in Pharmacopeial contamination testing and in GLP user evaluation tests. Part I of this paper includes the theory of the coincidence effect on particle counting and the particle size distribution measured. A summary of the experimental verification employed to determine coincidence count loss as a function of particle concentration for single particle counters is reported. Part II of this paper describes a practical protocol for the determination of operating limits to achieve a selected coincidence undercount limit for single particle counters.
Application of the new particle counting model to count accuracy determinations.
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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.