Fedorowicz Filip M, Zerr Andreas, Mathaes Roman, Eisele Matthias, Maas Swen, Koulov Atanas
Clear Solutions Laboratories AG, Mattenstrasse 22, 4058 Basel, Switzerland; and.
Material Analytischer Service (M.A.S.) GmbH, Carl Mez Str. 73, D-79114 Freiburg im Breisgau, Germany.
PDA J Pharm Sci Technol. 2025 Mar 3;79(1):28-58. doi: 10.5731/pdajpst.2024.012994.
The detectability size threshold of visible particles ("visibility" size) in the context of visual inspection of parenteral drug products has been an elusive target for several decades. The current common sense, also reflected in official guidelines, dictates that particles of different shapes and morphologies have different "visibility" size thresholds, which can range between hundreds and thousands of micrometers. This study demonstrates experimentally for the first time that it is possible to define a single, shape- and morphology-independent detectability size threshold, identical across particles of various types, provided that observation conditions and product attributes are kept constant. We propose that, based on the physiology of human visual perception instead of single-dimension measures of particle size (e.g., diameter or length), such a single size-threshold requires the use of area-based size parameters (such as "equivalent circular diameter", or ECD. The experimental results reported here clearly demonstrate that the "visibility" thresholds for particles of various morphologies converge on a single ECD value. In addition, the data reported here show that product attributes, such as container configuration, fill volume, etc. influence the threshold of visibility. Collectively, the findings reported in this paper provide substantial evidence and scientific rationale, as well as unanticipated prospects for standardization of visual inspection qualification practices, ultimately leading to improvement of pharmaceutical product quality.
几十年来，在对注射用药品进行目视检查时，可见颗粒的可检测尺寸阈值（“可见性”尺寸）一直是一个难以捉摸的目标。当前的常识，也反映在官方指南中，表明不同形状和形态的颗粒具有不同的“可见性”尺寸阈值，其范围可以在数百到数千微米之间。本研究首次通过实验证明，只要观察条件和产品属性保持不变，就有可能定义一个单一的、与形状和形态无关的可检测尺寸阈值，该阈值在各种类型的颗粒中都是相同的。我们建议，基于人类视觉感知的生理学，而不是颗粒尺寸的单维测量（例如直径或长度），这样一个单一的尺寸阈值需要使用基于面积的尺寸参数（如“等效圆直径”，或ECD）。这里报告的实验结果清楚地表明，各种形态颗粒的“可见性”阈值收敛于一个单一的ECD值。此外，这里报告的数据表明，产品属性，如容器配置、灌装体积等，会影响可见性阈值。总体而言，本文报告的研究结果为目视检查合格实践的标准化提供了大量证据和科学依据，以及意想不到的前景，最终有助于提高药品质量。
