Gravimetric-based technology-assisted workflow system for injectable anticancer drugs compounding: Design and qualification of an original weighing scale anchored inside an isolator.

Abstract

Technology-assisted manufacturing such as computer-assisted gravimetric control (CAGC) is a well-established method for injectable anticancer drugs (AD) compounding. The aim of this study was to validate an innovative weighing scale (WS) anchored inside an isolator for in-process gravimetric control (GC) of injectable AD compounding in a French Comprehensive Cancer Centre. The weighing scale studied Cyto-TopControl^® was designed by hospital pharmacists and the manufacturer LDI. Operational and performance qualification were carried out using weights ranging from 1 to 2000 g to assess fidelity, accuracy, linearity, eccentricity, precision and inter-test precision. The performance of the Cyto-TopControl^® were compared to the standard WS model Cytocontrol^® (LDI) by using a Bland-Altman plot. Infusion bags of four drugs (paclitaxel, docetaxel, epirubicin and trastuzumab) were then compounded by using CAGC associated with this new WS. For each preparation, an analytical control (AC) was carried out to validate the GC as a reference method. A total of 1530 weighings were performed. The maximum tolerated deviation and the accuracy deviations were not exceeded for each of the weights studied (<0.1 g for weights up to 100 g; <0.2 g for weight up to 2000 g). The standard deviations remained less than 5x 0.02 g and the linearity coefficients were above 0.9999. Eccentric weights coefficients of variation were less than 0.05%. The measurements obtained between Cyto-TopControl^® and CytoControl^® were consistent. Sixty bags were manufactured with the accuracy of 0.19% for GC and 5.07% for AC. This work confirms the reliability of this innovative WS for the in-process GC of injectable AD compounding.