Jul-Jørgensen Isabella, Hundahl Christian A, Skibsted Erik, Gernaey Krist V
Diabetes Finished Products, Novo Nordisk A/S, 2880 Bagsværd, Denmark; Department of Chemical and Biochemical Engineering, Technical University of Denmark, 2800 Kgs., Lyngby, Denmark.
Diabetes Finished Products, Novo Nordisk A/S, 2880 Bagsværd, Denmark.
J Pharm Biomed Anal. 2022 Jun 5;215:114763. doi: 10.1016/j.jpba.2022.114763. Epub 2022 Apr 19.
Cleaning verification is a critical process for patient safety in pharmaceutical manufacturing in order to keep cross-contamination below acceptable limits. A common cleaning verification method is the total organic carbon (TOC) swab. Others have studied the variances of different factors on the TOC swab in order to establish the best swab method. This paper attempts to quantify the sampling error of the TOC swab in the actual sampling situation using simulation. The study investigates the variability on the drug product recovery due to different analysts, concentration, steel finish and position, as well as the estimation of the given swab area. The results demonstrate that the sampling error leads to a large variation in TOC results. For areas estimated in the laboratory, it leads to an increase in limit of detection, LOD, with 60%, while for areas estimated in a tank, the LOD cannot be determined due to the large heteroscedasticity. Thus, this paper is also to be considered as an invitation to discuss and further investigate the TOC sampling error in the pharmaceutical industry.
清洁验证是药品生产中确保患者安全的关键过程，目的是将交叉污染控制在可接受限度以下。一种常见的清洁验证方法是总有机碳（TOC）擦拭法。其他人研究了不同因素对TOC擦拭法的影响差异，以确定最佳擦拭方法。本文试图通过模拟来量化实际采样情况下TOC擦拭法的采样误差。该研究调查了不同分析人员、浓度、钢材表面处理和位置对药品回收率的影响，以及给定擦拭面积的估计。结果表明，采样误差导致TOC结果出现较大差异。对于实验室估计的面积，检测限（LOD）增加了60%，而对于罐体中估计的面积，由于存在较大的异方差性，无法确定LOD。因此，本文也可被视为对制药行业中TOC采样误差进行讨论和进一步研究的邀请。
