Knapp J Z, Lieberman A, Abramson L R
R & D Associates, Inc., Somerset, New Jersey.
PDA J Pharm Sci Technol. 1994 Sep-Oct;48(5):255-92.
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.
《美国药典》（788）中关于污染粒子检测的准确度、验收限度和方法在《美国药典》第二十三版中得到了完善。在这两个版本中，尽管采用了不同的数值和方法，但对于所有注射用无菌制剂（S.V.I.）容器体积而言，粒子污染限度保持不变。这一质量标准的影响在于，最小的注射用无菌制剂容器尺寸具有较高的粒子浓度验收限度。这些高浓度的影响是在《美国药典》（788）注射用无菌制剂污染粒子检测中引入了漏计误差和假计数。普遍认为，使用单粒子光散射计数器对高浓度粒子进行计数会导致报告的粒子分布平均尺寸增加，总数减少。这种误差机制被称为“信号重合”。通过引入计数效率参数，对这两个问题的理解和控制得以统一。本文第一部分介绍了两个核心概念，利用它们可以准确量化单粒子计数器中重合误差的评估和控制。这两个核心概念是“粒子触发泊松模型”，这是一种关于粒子计数过程的新的、更准确的统计模型，以及一种浓度测量方法，该方法包括粒子大小对探测器计数能力的影响。使用这些概念可以根据重合效应的实验数据评估粒子探测器的计数效率能力。这是一篇应用论文。它将第一部分论文中的理论与粒子计数器的可重复性结合到一个简单的测试方案中。测试结果可用于计算粒子大小和计数的轮廓，在该轮廓范围内，《美国药典》（788）粒子检测中的漏计误差和假计数引入均得到控制。从分析的数据可以看出，任何单一粒径测试都无法有效评估探测器性能。使用所描述的理论和方法有助于实现《美国药典》（788）注射用无菌制剂粒子污染检测的目的。
