Background and objectives Centralized chemotherapy preparation units have established systematic strategies to avoid errors. Our work aimed to evaluate the accuracy of manual preparations associated with different control methods. Method A simulation study in an operational setting used phenylephrine and lidocaine as markers. Each operator prepared syringes that were controlled using a different method during each of three sessions (no control, visual double-checking, and gravimetric control). Eight reconstitutions and dilutions were prepared in each session, with variable doses and volumes, using different concentrations of stock solutions. Results were analyzed according to qualitative (choice of stock solution) and quantitative criteria (accurate, <5% deviation from the target concentration; weakly accurate, 5%-10%; inaccurate, 10%-30%; wrong, >30% deviation). Results Eleven operators carried out 19 sessions. No final preparation (n = 438) contained a wrong drug. The protocol involving no control failed to detect 1 of 3 dose errors made and double-checking failed to detect 3 of 7 dose errors. The gravimetric control method detected all 5 out of 5 dose errors. The accuracy of the doses measured was equivalent across the control methods ( p = 0.63 Kruskal-Wallis). The final preparations ranged from 58% to 60% accurate, 25% to 27% weakly accurate, 14% to 17% inaccurate and 0.9% wrong. A high variability was observed between operators. Discussion Gravimetric control was the only method able to detect all dose errors, but it did not improve dose accuracy. A dose accuracy with <5% deviation cannot always be guaranteed using manual production. Automation should be considered in the future.

Introduction Chemotherapies are handled using Good Manufacturing Practices, which ensure asepsis and high-quality production. Continuous education is compulsory and usually includes theoretical and practical exercises. Objectives This work aimed to validate an innovative method of teaching good manufacturing practices based on an escape room mixing simulation and gaming. Method Pairs of learners were locked in a simulated clean room (Esclean Room) and had 1 hour to produce a chemotherapy and escape by finding solutions to 23 “Good Manufacturing Practices mysteries” linked to combination locks. To measure the experiment’s impact on teaching, questionnaires including the 23 mysteries (in different orders) were filled in before, just after and one month after escape from the Esclean Room. Pharmacy staff’ degrees of certainty were noted for each question. A satisfaction survey was completed. Results Seventy-two learners (29% senior pharmacists, 14% junior pharmacists, and 57% pharmacy technicians) escaped the Esclean Room and 56 answered every questionnaire. The educational intervention resulted in increases in correct answers and certainty. Correct answers rose from 57% in the first questionnaire to 80% in the third ( p < 0.001). Certainty scores rose from 50% before the experiment to 70% one month afterwards ( p < 0.001). Despite 68% of learners having never taken part in an escape room game before, 79% liked this educational method. Conclusion This study built and tested a pedagogical escape room involving a high risk, professional, pharmacy process. The use of this pharmacy technology simulation had a positive impact on pharmacy staff theoretical knowledge.

Purpose To evaluate the chemical contamination of surfaces by cytotoxic agents during preparation of injectable chemotherapies in hospital pharmacies. Methods 526 wipe samples collected in 24 Swiss hospital pharmacies were analysed using a validated liquid chromatography–mass spectrometry/mass spectrometry method able to quantify 10 cytotoxic agents: cytarabine, gemcitabine, cyclophosphamide, ifosfamide, methotrexate, etoposide phosphate, irinotecan, doxorubicin, epirubicin and vincristine. Information on chemotherapies produced, equipment and production processes used were collected from all the hospital pharmacies on a voluntary basis in order to investigate their association with contamination rates. Results In two pharmacies, no trace of the 10 cytotoxic agents was detected. Chemical contamination was found in the other 22 hospital pharmacies, with combined total contamination of the 10 cytotoxic agents ranging from 8 ng to more than 41 000 ng per sample. Most contaminated samples came from inside biosafety cabinets, but some came from other clean room areas and logistics rooms. Statistically significant associations were observed between contamination rates and sampling locations, the number of chemotherapies prepared per year and types of cleaning solutions used. Conclusions This study demonstrated that most of the hospital pharmacies tested had some contamination of surfaces by different cytotoxic agents. Even if highest levels of contamination were mainly detected inside biosafety cabinets, technicians were also exposed to cytotoxic agents detected in logistical and storage areas. Protective measures should therefore be maintained or even reinforced in these areas in order to limit technicians’ risks of exposure when handling cytotoxic products

Abstract Background Use of automated systems for the production of chemotherapy will increase in answer to hospitals’ needs to rationalise production. The aim of the study was to evaluate the performance of a PharmaHelp® automated system for compounding chemotherapy. Methods Viable and non viable particles in air and liquid were measured by particle counter. Surface chemical contamination was simulated with a quinine solution. Microbiological contamination and aseptic processes were studied using media-fill tests. Dose accuracy was evaluated using a gravimetric method, in simulation studies and with real products in daily practice. Productivity was calculated by batch of ten IV-bags. Results No particles or microbiological contamination were detected. Filling was accurate for all the volumes of non-viscous solution studied (97–103 %). Minimum volumes which could be prepared accurately were 2 mL and 5 mL for the non-viscous and viscous solutions, respectively. For 2–5 mL volumes, the robot was less accurate than average, and 0–2 % of bags were rejected (deviation>10 %). Average fill deviations were from 0–3 % for 2–5 mL volumes and<1 % for volumes above 5 mL. Average production time for ten bags was 61±11 min. Conclusions The automated system was able to produce chemotherapy effectively, delivering appropriate quality with productivity comparable to manual preparations. These results confirmed that such automated systems have the potential to guarantee optimal safety for patients and technicians.

Two capillary electrophoresis (CE) methods were developed for the analysis of 16 antineoplastic drugs contained in injectable pharmaceutical formulations. A capillary zone electrophoresis (CZE) method coupled to UV was developed with a background electrolyte (BGE) made of a 100 mM phosphate buffer at pH 2.5 containing 50% v/v of acetonitrile and dynamic coating of capillaries with Ceofix®. This method allowed the analysis of doxorubicin, epirubicin, idarubicin, daunorubicin, irinotecan, topotecan, vincristine, vindesine, vinblastine, and vinorelbine in less than 8 min. A micellar electrokinetic chromatography (MEKC) method coupled to UV was also developed for the determination of methotrexate, pemetrexed, etoposide, etoposide phosphate, fludarabine phosphate, and 5-fluorouracil. A run time of 16 min was obtained with a BGE made of 50 mM borate buffer at pH 9.2 with 80 mM of sodium dodecyl sulfate (SDS) and 20% v/v of acetonitrile. For both methods, the applied voltage was 30 kV and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in fused silica capillaries with an internal diameter of 50 μm and a total length of 64.5 cm. Both methods were validated and trueness values between 99.4 and 101.3% were obtained with repeatability and intermediate precision values of 0.5-1.8% for all drugs. These methods were found appropriate for controlling injectable pharmaceutical formulations containing antineoplastic drugs and successfully applied in quality control.