Assessment of the surface contamination of the primary packaging of oral antineoplastic drugs and secondary packaging of chemotherapy preparations at a Swiss hospital.

INTRODUCTION: Due to the high toxicity of antineoplastic drugs, handling their packaging could lead to the chemical contamination of hospital environments and exposure risks to healthcare professionals and patients. This study aimed to assess the contamination of two main surfaces: the outer primary packaging of oral antineoplastic drug formulations (n = 36) available on the Swiss market and the surface of secondary packaging of injectable antineoplastic drug preparations (n = 60) produced by the pharmacy of a Swiss hospital and carriers used for transport (n = 5). METHODS: Samples were collected using a validated wipe sampling method. The simultaneous analysis of 24 antineoplastic drugs: 5-fluorouracil, busulfan, carboplatin, cyclophosphamide, cytarabine, dacarbazine, daunorubicin, docetaxel, doxorubicin, epirubicin, etoposide, gemcitabine, idarubicin, ifosfamide, irinotecan, methotrexate, oxaliplatin, paclitaxel, pemetrexed, raltitrexed, topotecan, treosulfan, vinblastine, vincristine) and 1 antiviral compound (ganciclovir) was performed by UHPLC-MS/MS. RESULTS: A total of 58% and 90% positive results were obtained for the primary packaging of oral chemotherapies and for the secondary packaging of injectable preparations, respectively. The highest quantities found on the primary packaging for oral chemotherapies and on the surface of closed leak-proof bags were 111 ng of methotrexate and 19 ng of gemcitabine, respectively. Gemcitabine (69%) and cyclophosphamide (38%) were the two most common contaminants found on the packaging of injectable preparations and carriers, regardless of the chemotherapy preparations. CONCLUSION: Trace levels (ng) of antineoplastic drugs can be found on most surfaces of all evaluated pharmaceutical products. Thus, suitable personal protective equipment is mandatory for healthcare professional handling antineoplastic drugs.

Development and Evaluation of an e-Learning Module for Low- and Middle-Income Countries on the Safe Handling of Chemotherapy Drugs.

Despite the growing use of chemotherapy drugs in resource-constrained settings, training opportunities on safe handling practices are lacking. This study's objectives were to develop and evaluate an e-learning training module on the safe handling of chemotherapy drugs to strengthen knowledge and practices in low- and middle-income countries (LMICs). The module's curriculum was developed using the Six-Step Approach for Curriculum Development for Medical Education. Asynchronous, self-paced, e-learning lessons within the module were created and uploaded onto a free online platform, Pharm-Ed. The study ran online from January to April 2021. Participant recruitment was done using convenience sampling through various channels (social media, communities of practice). Training module effectiveness was evaluated using knowledge assessments (a pre-test and post-test study design) and participant satisfaction. We developed a comprehensive e-learning module on the safe handling of chemotherapy drugs comprising 11 asynchronous, self-paced, e-learning lessons. Eighty-two participants (68% pharmacists and 17% pharmacy students) from 17 countries completed at least one lesson, with a total of 259 lessons completed. Evaluation of the different lessons showed significant improvements in theoretical knowledge (p < 0.01) in all except one lesson and a high degree of participant satisfaction. As the use of anti-cancer drugs in LMICs will continue to increase, this e-learning module is an effective means to address the lack of training opportunities on the safe handling of chemotherapies for healthcare workers in these countries. The module could be integrated into a multi-modal approach aimed at reducing occupational exposure and increasing patient safety in cancer care centers.

Development and Proof of Concept of an Audit Toolkit for the Safe Handling of Cytotoxic Drugs in Low- and Middle-Income Countries.

PURPOSE: Chemotherapies are considered high-risk drugs for patient and staff safety. Considering the rising burden of cancer and the increasing use of chemotherapy drugs in low- and middle-income countries (LMICs), promoting continuous improvements in the safety and quality of practices in these settings is essential. This paper describes the development and proof of concept of a toolkit to audit chemotherapy handling practices in the health care facilities of LMICs. METHODS: A steering committee defined the audit method and the toolkit content. Several checklists were developed to facilitate the audit and data collection. Items included in checklists were derived from key reference works on safe handling. Different tools were validated using Delphi surveys and expert reviews. Audits of pilot sites were performed to test the toolkit's applicability and relevance. RESULTS: The toolkit contains a 134-item global assessment tool for the different processes at each step of the medication pathway and three step-specific observation checklists to assess different health workers' practices during the prescription, preparation, and administration of chemotherapies. The toolkit also proposes using a surface-wipe sampling method to measure any cytotoxic contamination of the immediate environment. The toolkit was tested in three teaching hospitals in Africa. CONCLUSION: The toolkit developed was successfully implemented in a variety of LMIC settings, providing a comprehensive evaluation of the quality and safety of the chemotherapy drug handling practices in participating health care facilities. This toolkit can help facilities in LMICs to implement a new approach to continuously improving the quality and safety of their practices and ultimately ensure patient and staff safety.

New missions of a hospital pharmaceutical technology unit during the COVID-19 pandemic.

The pharmaceutical technology unit of the Geneva University Hospitals played a significant role in the fight against COVID-19 through four different missions: (1) providing enough hydroalcoholic solution at the peak of the pandemic; (2) facing supply chain management issues; (3) adapting the workload to the crisis and, above all, (4) managing the human resources necessary to handle these activities.

Learning good manufacturing practices in an escape room: Validation of a new pedagogical tool.

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.

Work overload is related to increased risk of error during chemotherapy preparation.

PURPOSE: Chemotherapy preparation units face peaks in activity leading to high workloads and increased stress. The present study evaluated the impact of work overloads on the safety and accuracy of manual preparations. METHOD: Simulating overwork, operators were asked to produce increasing numbers of syringes (8, 16, and 24), with markers (phenylephrine or lidocaine), within 1 h, in an isolator, under aseptic conditions. Results were analyzed using qualitative and quantitative criteria. Concentration deviations of < 5%, 5%-10%, 10%-30%, and >30% from the expected concentration were considered as accurate, weakly accurate, inaccurate, and wrong concentrations, respectively. RESULTS: Twenty-one pharmacy technicians and pharmacists carried out 63 preparation sessions (n = 1007 syringes). A statistically significant decrease in the manufacturing time for one syringe was observed when workload increased (p < 0.0001). Thirty-nine preparation errors were recorded: 30 wrong concentrations (deviation > 30%), 6 mislabeling, 2 wrong diluents, and 1 wrong drug. There was no statistically significant difference in the mean concentration accuracy of final preparations across the three workloads. The overall error rate increased with the number of preparations made in 1 h: 1.8% for 8 preparations, 2.7% for 16 preparations, and 5.4% for 24 preparations (p < 0.05). CONCLUSION: Although pharmacy technicians and pharmacists were able to increase production speeds with no effect on mean concentration accuracy under stressful conditions, there were greater probability errors being made. These results should encourage actions to spread workloads out over the day to avoid peaks in activity.

Determination of 16 antineoplastic drugs by capillary electrophoresis with UV detection: Applications in quality control.

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.

Reliability of chemotherapy preparation processes: Evaluating independent double-checking and computer-assisted gravimetric control.

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.

[A medical-pharmaceutical partnership model as a contributor to the success in conditioning regimen for allogenic hematopoietic stem cell transplantation in adults: a cross-reflection on our organizations]. / Modèle de coopération médico-pharmaceutique comme contributeur au succès du conditionnement de la greffe allogénique de cellules souches hématopoïétiques chez l'adulte : un regard croisé sur nos organisations.

Allogeneic hematopoietic stem-cell transplant (allo-SCT) remains the only cure for many hematological malignancies and some benign and congenital diseases. Busulfan, proposed in its injectable form, has quickly become a mainstay of pharmacological and myeloablative (or non-myeloablative) conditioning. This is following the outbreak in 2010 of a multicenter international clinical phase II trial, we tested the robustness and reliability of our organization in a complex model of organization and multifactorial partnership. In this type "BuCy2" protocol based on a classical treatment duration of 4 consecutive days, the administration of IV busulfan is given in one single daily infusion instead of the conventional 16 infusions, while keeping the same total dose. Under these conditions, the treatment is totally secured using a therapeutic drug monitoring of busulfan, applied in real-time. The process is technically complex and requires the very close cooperation of the teams involved. A strength, weakness, opportunity and threat (SWOT) analysis has been constructed; it fully supports continuous quality improvement to the triple benefit of the nursing chain, the patients and their environment. Several critical points were identified and corrected. The experiment strongly contributes to the safety and security of the medication circuit at the hospital and, improves the performance of allo-SCT. It also contributes to the protection of all actors in the health field and their working environment via a well-functioning quality management system.