Sartorius Stedim Biotech, August Spindler Strasse 11, 37079 Goettingen, Germany
Sartorius Stedim Biotech, August Spindler Strasse 11, 37079 Goettingen, Germany.
PDA J Pharm Sci Technol. 2021 Jul-Aug;75(4):332-340. doi: 10.5731/pdajpst.2020.012211. Epub 2021 Feb 19.
Single-use systems find increasing application downstream of final filters in the production of antibody, vaccine, gene, and cell therapy drug products. For such critical applications, particulate matter attached to the interior (product-contacting) surfaces of the single-use system could potentially be released and contaminate the drug product. Risk reduction requires methods that reliably detect particulate matter on the inside of single-use systems. Here we describe the results from the development and validation of a manual visual inspection method for the detection of particulate matter inside transparent single-use systems. Test kits consisted of single-use systems (2 D bags, tubing lines, and bag/tubing assemblies) internally seeded with test particles (black, clear, or fiber) ranging from 100 to 2000 µm in size. A designed experiment determined the optimal light intensity, inspection time, and time between inspector breaks required to maximize the probability of detection (POD) for particles. POD > 70% for black and clear particles started at particle sizes exceeding 400 to 1000 µm depending on the single-use system type and size, but the POD for 2000 µm fibers was marginal to poor. Thus, for single-use systems, the particle size to achieve POD > 70% shifted to significantly larger sizes than the 150-250 µm particle size typically detectable in drug products. Overall, the POD decreased as the bag size or tubing line length increased. An attribute gage repeatability and reproducibility study using three inspectors validated the inspection method for reliable detection of black and clear particles ≥ 1000 µm in size over the entire size range of single-use assemblies and tubing lines examined. Fibers of length 1000 and 2000 µm were not reliably detected. The results highlighted the challenges in reliably detecting particulate matter in a visual inspection of the interior surfaces of single-use systems.
一次性系统在抗体、疫苗、基因和细胞治疗药物产品的最终过滤器下游的应用越来越多。对于这种关键应用，附着在一次性系统内部（与产品接触）表面的颗粒物可能会释放出来并污染药物产品。降低风险需要能够可靠检测一次性系统内部颗粒物的方法。在这里，我们描述了开发和验证手动目视检查方法以检测透明一次性系统内部颗粒物的结果。测试套件由内部接种测试颗粒（黑色、透明或纤维）的一次性系统（2D 袋、管线路和袋/管组件）组成，测试颗粒尺寸范围为 100 至 2000μm。一项设计实验确定了最佳的光照强度、检查时间和检查员之间的休息时间，以最大限度地提高颗粒检测概率（POD）。对于黑色和透明颗粒，POD>70%从大于 400 到 1000μm 的颗粒尺寸开始，具体取决于一次性系统的类型和尺寸，但对于 2000μm 纤维的 POD 则较差。因此，对于一次性系统，达到 POD>70%的颗粒尺寸转移到比药物产品中通常可检测到的 150-250μm 颗粒尺寸大得多的尺寸。总体而言，随着袋子尺寸或管线路长度的增加，POD 会降低。使用三名检查员进行的属性量具重复性和再现性研究验证了该检查方法，可可靠检测整个一次性组件和管线路检查范围内尺寸大于等于 1000μm 的黑色和透明颗粒。长度为 1000 和 2000μm 的纤维则无法可靠检测到。结果突出了在一次性系统内部表面的目视检查中可靠检测颗粒物的挑战。
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