Band 4, Heft 1 -

Background The production of hospital-compounded medicines with a longer shelf life raises questions about drug-packaging interactions, especially desorption events involving extractables and leachables (E/L). A meta-synthesis of the literature was performed to describe which mass spectrometer is suitable for identifying and quantifying E/L. Methods A meta-synthesis of studies focused on the identification or quantification of E/L published between January 1997 and December 2017 was performed. Inclusion criteria were E/L studies dealing with pharmaceutical products, in which mass spectrometry (MS) coupled to liquid chromatography (LC) or gas chromatography (GC) was used. The full-text articles had to be available and written in English. Articles about food packaging, environmental contamination, counterfeit compounds, pharmacokinetics, or process-related impurity studies were excluded. Two researchers independently assessed the papers according to a score based on a seven-item questionnaire. Results In total, 32 papers matched our criteria and were included in the meta-synthesis. For qualitative analysis with LC, quadrupole time-of-flight (QTOF; n=4) and ion trap (n=4) mass detectors were used the most; and with GC, single quadrupole (n=8). For quantification studies with LC, QTOF (n=3) and triple quadrupole (n=2) were used the most; and with GC, single quadrupole (n=7). Conclusions For simultaneous qualitative and quantitative analysis of E/L with LC, QTOF or Orbitrap is a suitable detector. For quantitative analysis with LC only, triple quadrupole is suitable. For qualitative and quantitative analysis with GC, single quadrupole can be used.

Two automation methods for aseptic preparation in hospital pharmacy, robot and peristaltic pump, were compared to manual process both for risk analysis using Failure Modes Effects and Criticality Analysis (FMECA) method and for productivity using time analysis grids built for each process. The results obtained with the different workflow organizations showed that the worst-case conditions for productivity was production “on demand” of tailor-made preparations. in that case, the manual process was not significantly different from the robotic process ( p -value=0.72). For the standardized preparations, the semi-automatic process preparing a batch from bulk solution from “to be reconstituted” drugs was significantly superior to the robotic process preparing repetitive series of doses ( p -value<0.01). Productivity of the robot was dramatically increased when the robot performed standardized preparations either from ready to use solutions or mixed cycles due to the robot design. When different processes were FMECA analyzed for risk analysis the robotic process was found as the safer process in comparison to others with a total of Criticality Indexes of 1060, 719, 656 for manual, semi-automatic and robot, respectively. Except for the robotic, semi-automatic and manual processes needed additional IT control systems to limit the risk of failures.

Background The objectives were to perform an observation of the administration of injectable drugs in three ICUs, to identify injectable drugs administered by Y-site infusion or mixed in the same container, to compare with physical compatibility data available in the literature and to test the physical compatibility for missing data. Methods An observational study was realised over two weeks and patients receiving more than one injectable drug in the same line simultaneously were included. Physical compatibilities were assessed in pairs by comparing with three databases. For some missing data, three tests were realised for pairs including an anti-infective drug. Visual and subvisual evaluations were performed after the preparation, 1 and a 4-hour storage. Results A total of 389 combinations between two injectable drugs was observed for Y-site infusions and 31 mixtures in the same container. According to the literature, 21.1 % associations were physically compatible, 1.8 % as physically compatible potentially, 8.0 % as physically incompatible, 6.4 % have divergent data according to the databases and 62.7 % have no data. Two mixtures were documented. 37 pairs were tested and 70.3 % were physically compatible, 8.1 % were physically incompatible after visual evaluation and 21.6 % after subvisual evaluation. Conclusions In the majority of cases, no compatibility data are available in the literature. Laboratory tests give additional information.

Background Automated unit-dose dispensing system (ADS) of oral solid medication is a complex and sensitive production process in the drug distribution system. Hence, an appropriate training of hospital pharmacy technicians (HPT) is essential. A basic training (observational and practical) of 3 weeks is first organized to evaluate the HPT, followed by an interview with both the pharmacist and the HPT chief. The importance of the human factor (daily routine and repetitive tasks) showed by the risks analysis within this process has led us to search new learning methods to keep the team engaged. An e-learning training was selected in order to further complete the HPT initial training but also as a continuous training to the HPTs who are already working in the ADS process. Process and Methods The e-learning tool was developed using the Google ® platform and includes four theoretical training modules (Google ® Slides): Module 1 “General organization”, Module 2 “Automatic preparation machine”, Module 3 “Repackaging” and Module 4 “Non-automated drug dispensing”. Each module ends with a self-assessment (Google ® Forms). Various teaching materials are included: links to institutional procedures, videos, photos, quizzes, simulations … A minimum of 75 % of correct answers is requested to validate each module. The e-learning, once final, was validated with a new HPT and with five HPTs already in place for more than a year. A satisfaction form is available at the end of the training. Results The 6 HPTs obtained an average of 17.75/20 correct answers. The most successful modules were 1 and 4 (average per module: M1 =  18.5/20; M2=16.8/20; M3=17/20; M4=18.7/20). For module 3, two HPTs scored below 75 % and therefore had to pass this module again. The average time to complete this training was 1.5 hours. HPTs are 100 % satisfied with the training and the teaching materials used. Discussion/Conclusions The e-learning tool fit well with the initial training and the continuous training of the HPTs. Its set up is simple. The duration length spent on the training is shortened for both the pharmacist and the learner. This tool is tailored to the learner needs and constraints. It allows the integration of playful and interactive teaching tool which were appreciated. An audit will be conducted to assess the impact of this training tool on the overall ADS process.