Using simulation to improve pharmacy operators' handling of cytotoxic spills.

INTRODUCTION: International Society of Oncology Pharmacy Practitioners guidelines recommend having standard operating procedures (SOPs) and initial and yearly retraining programs on cytotoxic spill handling for pharmacy operators (POs). This study aimed to create a simulation-based training (SBT) program on this subject and evaluate its impact on POs' real-life performance. METHODS: Randomly formed pairs of POs underwent a 2.5-hour training program, including two simulation exercises (a broken cytotoxic vial on the floor and a leaking cytotoxic bag) in a simulated pharmacy production unit. Each participant applied the cytotoxic spill handling SOPs. The PO and trainer-pharmacist did a debriefing after each exercise. Satisfaction was recorded on a 0-to-100% scale. A 20-item questionnaire assessed general knowledge about cytotoxic spill handling before and after the training. One month before and one month after the training, the POs underwent a real-life test when the trainer broke a fake cytotoxic vial in the cytotoxic storage area. Their performance in applying the SOPs was assessed on a 20-point checklist, and the time to handle the spill was recorded. RESULTS: Twelve POs participated. Mean satisfaction score was 98.9%. Mean knowledge score improved from 10.8/20 (SD = 2.0) before training to 14.5/20 (SD = 1.6) after training (p < 0.05). Mean real-life SOP performance improved from 78.6% (SD = 7.4%) to 97.1% (SD = 5.2%) (p < 0.05). Mean time to handle cytotoxic spills decreased from 17.3 minutes (SD = 3.6 minutes) to 11.9 minutes (SD = 1.5 minutes) (p < 0.05). CONCLUSION: POs improved their knowledge and real-life competencies for handling cytotoxic spills. This training will be included in POs' initial and continuing training programs.

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.

Game-based learning as training to use a chemotherapy preparation robot.

INTRODUCTION: In 2015, our university hospital pharmacy acquired the PharmaHelp robot system to automate part of its chemotherapy production. Complex technical use, downtime periods, and insufficient training caused a drop in motivation and disparities in operators' knowledge. We created a short, playful, standardized, gamed-based training program to address this, and evaluated its impact. METHODS: Operators were classified as trainers or trainees according to their knowledge about Information and Communication Technologies. Before, after the training, and at 6 months (6M), their robot knowledge was assessed on a 0-24-scale, motivation and self-efficacy in using it on 0-to-100 scales. Pairwise comparison t-test with Bonferroni adjustment was used (p < 0.05 considered significant). Satisfaction was measured using a six-point Likert scale. Trainer/trainee teams participated in 2-hour training sessions with three games and a debriefing. For "Knowing the manufacturing steps," cards with the steps were placed in the correct order. For "Knowing the criteria for using the robot," teams guessed whether certain compounds could be used with the robot. For "Knowing how to handle production errors," the answer to each error (taken from real-life issues) was selected from four options. RESULTS: Participants (n = 14) were very satisfied about sessions' interactivity and playfulness. Knowledge improved from 57% pretraining to 77% (p < 0.005) to 76.6% (6M) (p < 0.05 compared to pretraining). Motivation and self-efficacy, respectively, improved from 57.6% to 86.6% (p < 0.05) to 70.4% (6M) and from 48.5% to 75.6% (p < 0.05) to 60.2% (6M) (p > 0.1 compared to pretraining) (t-test). CONCLUSIONS: This highly appreciated training program efficiently improved knowledge retention out to six months.

A room of errors simulation to improve pharmacy operators' knowledge of cytotoxic drug production.

INTRODUCTION: We used an educational healthcare simulation tool called room of errors (ROE) to raise pharmacy operators' awareness of potential errors in a chemotherapy production process and assessed its impact on their knowledge and satisfaction. METHODS: Twenty-five errors (compiled from internal procedures, literature and our hospital's reported incidents) were categorised as static (n = 7, visible by the participant anytime) and dynamic (n = 18, made by a pseudooperator in front of the participant). Our simulated cytotoxic production unit (CPU) hosted the 1 h-simulation. Two pharmacists (supervisor/pseudo-operator) welcomed the trainee for a 10-min briefing. During the 20-min simulation, participants watched the pseudo-operator's gestures in a simulated chemotherapy production process. Participants called out each error observed (recorded by the supervisor). A 20-min debriefing followed. ROE's impact on knowledge was measured through participants' answers to a before-and after 18-item questionnaire about CPU's procedures and certainty about answers on a scale (0%-100%). Participants evaluated the training using a satisfaction questionnaire (Likert scale, 1-6). RESULTS: The 14 participants detected 70.4% ± 11.4% of errors. Least-detected errors were "using non-disinfected vials" (42.9%) and "touching syringe plunger" (0%). Critical errors (expired leftovers or glucose instead of sodium chloride) were detected at 57.1%. Knowledge improved from 60.3% to 94.1% (p < 0.001) and certainty from 75.3% to 98.8% (p < 0.001). Participants appreciated this non-judgmental, informative, and original training (satisfaction 95.7%). Some pointed out difficulties settling into the game quickly and visualising static and dynamic errors simultaneously. CONCLUSION: This ROE simulation improved operators' knowledge and certainty. Longer-term testing should be done to measure knowledge retention over time.

Managing the COVID-19 health crisis: a survey of Swiss hospital pharmacies.

BACKGROUND: The COVID-19 pandemic strained healthcare systems immensely as of 2020. Switzerland's hospital pharmacies' responses during the first wave were surveyed with a view to improving the quality of pharmaceutical management in future health crises. METHODS: An online survey was sent to the heads of all of Switzerland's hospital pharmacies. The questionnaire was organised into eleven sections of questions covering many topics regarding the management of COVID-19's first wave. Data collection occurred from May to June 2020. RESULTS: Analyses were performed using the 43 questionnaires (66%), with at least one answer per questionnaire, out of 65 distributed. Seventeen of 41 pharmacies responding (41%) had existing standard operating procedures or pandemic plans and 95% of these (39/41) set up crisis management steering committees. Twenty-nine of 43 pharmacies responding (67%) created new activities to respond to the pandemic's specific needs. Twenty-six of 39 pharmacies responding (67%) created new drug lists for: COVID-19-specific treatments (85%; 22/26), sedatives (81%; 21/26), anaesthetics (77%; 20/26) and antibiotics (73%; 19/26). Drug availability in designated COVID-19 wards was managed by increasing existing stocks (54%; 22/41 pharmacies) and creating extra storage space (51%; 21/41). Two drugs generated the greatest concern about shortages: propofol (49%; 19/39 pharmacies) and midazolam (44%; 17/39). Remdesivir stocks ran out in 26% of pharmacies (10/39). Twelve of 43 pharmacies (28%) drafted specific new documents to respond to medical needs regarding drug administration, 12 (28%) did so for drug preparation and 10 (23%) did so for treatment choices. CONCLUSIONS: Switzerland's hospital pharmacies encountered many challenges related to the COVID-19 crisis and had to find solutions quickly, effectively and safely. The survey highlighted the key role that hospital pharmacies played in many aspects of the pandemic by providing logistical and clinical support to medical and nursing care teams. The lessons and experiences outlined could be used to improve the quality of hospital pharmacies' readiness for similar future events.

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.

The safe handling of chemotherapy drugs in low- and middle-income countries: An overview of practices.

INTRODUCTION: The rising burden of cancer in low- and middle-income countries (LMICs) has led to substantial efforts to improve access to chemotherapy. The present study's objectives were to obtain an overview of the safe handling practices implemented in LMICs' healthcare facilities when dealing with chemotherapy drugs and to prioritize opportunities for improving them. METHODS: We conducted an online survey, from June 2018 to April 2019, among LMIC healthcare facilities dealing with chemotherapy drugs. Facilities were asked to self-assess their chemotherapy handling processes using Cyto-SAT, a self-assessment tool incorporating 134 items organized into 10 domains (management, personnel, logistics, prescription, preparation, administration, incident management, waste management, cleaning, and patient counselling). Data were recorded on an online platform (www.datapharma.ch/cyto-SAT). RESULTS: The survey enrolled 53 healthcare facilities (15 from low-income, 26 from lower-middle-income, and 12 from upper-middle-income countries). The median level of implementation of safe practices was 63% (Q1:39%-Q3:77%). Facilities in low-income countries (LICs) reported lower median levels of safe practices than middle-income countries (MICs) [LICs: 32% (Q1:24%-Q3:62%), Lower-MICs: 63% (Q1:49%-Q3:70%), Upper-MICs: 85% (Q1:77%-Q3:93%)]. The biggest differences between country categories were observed in the domains related to personnel, preparation processes, and incident management. CONCLUSION: This overview of practices highlighted a large variability and major gaps in the safe handling of chemotherapy drugs in LMICs. Improvement strategies are needed to increase patient and staff safety and limit environmental contamination, especially in LICs. Safe handling programs should be part of continuing efforts to improve access to quality cancer drugs and should be integrated into national cancer control programs.

Full-scale simulations to improve disaster preparedness in hospital pharmacies.

PURPOSE: Assess whether full-scale simulation exercises improved hospital pharmacies' disaster preparedness. METHODS: Swiss hospital pharmacies performed successive full-scale simulation exercises at least four months apart. An interprofessional team created two scenarios, each representing credible regional-scale disasters involving approximately fifty casualties (a major road accident and a terrorist attack). Four exercise assessors used appraisal forms to evaluate participants' actions and responses during the simulation (rating them using five-point Likert scales). RESULTS: Four hospital pharmacies performed two full-scale simulation exercises each. Differences between exercises one and two were observed. On average, the four hospitals accomplished 69% ± 6% of the actions expected of them during exercise one. The mean rate of expected actions accomplished increased to 84% ± 7% (p < 0.005) during exercise two. Moreover, the average quality of actions improved from 3.0/5 to 3.6/5 (p = 0.01), and the time required to gather a crisis management team drastically decreased between simulations (from 23 to 5 min). The main challenges were communication (reformulation) and crisis management. Simulation exercise number one resulted in three hospital pharmacies creating disaster action plans and the fourth improving its already existing plan. CONCLUSION: This study highlighted the value of carrying out full-scale disaster simulations for hospital pharmacies as they improved overall institutional preparedness and increased staff awareness. The number of expected actions accomplished increased significantly. In the future, large-scale studies and concept dissemination are warranted.

Development and assessment of PharmaCheck: an electronic screening tool for the prevention of twenty major adverse drug events.

BACKGROUND: Adverse drug events (ADEs) can be prevented by deploying clinical decision support systems (CDSS) that directly assist physicians, via computerized order entry systems, and clinical pharmacists performing medication reviews as part of medical rounds. However, physicians using CDSS are known to be exposed to the alert-fatigue phenomenon. Our study aimed to assess the performance of PharmaCheck-a CDSS to help clinical pharmacists detect high-risk situations with the potential to lead to ADEs-and its impact on clinical pharmacists' activities. METHODS: Twenty clinical rules, divided into four risk classes, were set for the daily screening of high-risk situations in the electronic health records of patients admitted to our General Internal Medicine Department. Alerts to clinical pharmacists encouraged them to telephone prescribers and suggest any necessary treatment adjustments. PharmaCheck's performance was assessed using the intervention's positive predictive value (PPV), which characterizes the proportion of interventions for each alert triggered. PharmaCheck's impact was assessed by considering clinical pharmacists as a filter for ruling out futile alerts and by comparing the final clinical PPV with a pharmacist (the proportion of interventions that led to a change in the medical regimen) to the final clinical PPV without a pharmacist. RESULTS: Over 132 days, 447 alerts were triggered for 383 patients, leading to 90 interventions (overall intervention PPV = 20.1%). By risk class, intervention PPVs made up 26.9% (n = 65/242) of abnormal laboratory value alerts, 3.1% (4/127) of alerts for contraindicated medications or medications to be used with caution, 28.2% (20/71) of drug-drug interaction alerts, and 14.3% (1/7) of inadequate mode of administration alerts. Clinical PPVs reached 71.0% (64/90) when pharmacists filtered alerts and 14% (64/242) if they were not doing it. CONCLUSION: PharmaCheck enabled clinical pharmacists to improve their traditional processes and broaden their coverage by focusing on 20 high-risk situations. Alert management by pharmacists seemed to be a more effective way of preventing risky situations and alert-fatigue than a model addressing alerts to physicians exclusively. Some fine-tuning could enhance PharmaCheck's performance by considering the information quality of triggers, the variability of clinical settings, and the fact that some prescription processes are already highly secured.

Determination of antiretroviral drugs for buyers' club in Switzerland using capillary electrophoresis methods.

Human immunodeficiency virus-acquired immunodeficiency syndrome continues to be a major global public health issue, having claimed almost 33 million lives to date. Due to the high cost of antiretroviral treatment, access to these drugs remains difficult for vulnerable populations, such as migrants and people living in prisons, who often do not have health insurance. These factors lead to poorer health outcomes and higher transmission rates. The personal importation scheme for unapproved generics from foreign countries is one option to access affordable human immunodeficiency virus treatment. However, the risk of importing falsified medicine remains high, and the quality control of unapproved drugs is lacking. In this context, three CE methods for the analysis of nine antiviral drugs found in commercial pharmaceutical formulations were evaluated. The selected compounds were emtricitabine, tenofovir disoproxil, tenofovir alafenamide, rilpivirine, efavirenz, raltegravir, dolutegravir, abacavir, and lamivudine. The developed methods were successfully applied to determine the active pharmaceutical ingredients of commercial formulations and unapproved generics. The quality control of unapproved generics by CE is an attractive approach due to its good standard of quality, low cost, ecofriendliness, and ease of implementation.

Cyto-SAT: A self-assessment tool for the safe handling of cytotoxic drugs adapted for use in low- and middle-income countries.

INTRODUCTION: The handling of cytotoxic medicines is a high-risk process for human and environmental health. Considering the rising burden of cancer in low- and middle-income countries (LMICs), we aimed to develop, validate, and pilot test a self-assessment tool to support the implementation of safe handling practices and promote continuous quality improvement for cytotoxic drug management in LMICs. METHODS: First, the self-assessment tool Cyto-SAT was developed and validated. Key sources on the safe handling of cytotoxic medicines were reviewed to derive items addressing safety and quality aspects at every stage of the process. A two-round online Delphi survey was conducted to validate and prioritize the items. The validation rules in the first and second rounds were defined as ≥65% and ≥75% agreement, respectively. Then, intended users in healthcare facilities in LMICs evaluated the Cyto-SAT tool in a pilot test. They were asked to fill out an online evaluation questionnaire. RESULTS: Twenty-seven experts from 13 high-income countries and LMICs participated in the Delphi survey. Final expert consensus was achieved for 134/137 (97.8%) items. Consensus on priority was achieved for 52 of 134 (38.8%) items. The final Cyto-SAT tool comprises 134 items in 10 domains and 28 subdomains covering the whole cytotoxic drug handling process (https://pharmed.datapharma.ch/cyto-sat_en/). Staff from 34 institutions in 28 LMICs completed the Cyto-SAT evaluation. Almost all of them reported total agreement or agreement with its usefulness (96%), applicability (94%), usability (98%), and acceptability (97%). CONCLUSION: Cyto-SAT is the first self-assessment tool designed to assist professionals in LMICs in the safe handling of cytotoxic drugs. The pilot test revealed that Cyto-SAT is a useful and highly appreciated tool that supports practice improvement in LMICs. Cyto-SAT will be used in an international survey to obtain a global overview of handling practices in various LMIC settings.

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.

Efficiency of degradation or desorption methods in antineoplastic drug decontamination: A critical review.

Although considerable efforts have been made over the last 40 years, occupational exposure to antineoplastic drugs is still a daily concern, since eradicating such contamination from workplaces seems unattainable. Considerable data are currently available on the risks associated with their use at work. Hospital facilities are often cleaned with marketed antimicrobials whose chemical decontamination efficacy certainly differs but remains unknown. To keep compounding facilities sterile, alcohol-based solutions are frequently used but with very limited efficiency. It would be particularly useful if a decontamination method could be added to the means already available so that all conventional antineoplastic drug contamination could be removed. Several degradation methods or desorption methods have previously been experimented, with varying success. They have never been compared or discussed in terms either of efficiency or usability. This review aims to analyse and discuss the results of each degradation or decontamination procedure and to compare them. This should facilitate selection of the method to be implemented in daily practice.

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.

A comparison of new drugs approved by the FDA, the EMA, and Swissmedic: an assessment of the international harmonization of drugs.

INTRODUCTION: This study compared the characteristics of new human drugs approved by the Food and Drug Administration (FDA), the European Medicine Agency (EMA), and Swissmedic (SMC) in the period 2007 to 2016. METHODS: The list of new drugs and therapeutic biologics approved by the FDA, the EMA, and SMC in the period 2007 to 2016 was collected from websites of those agencies. The study included regulatory information, approval date, and indication for each drug. Descriptive statistical t tests and x2-tests were performed for the analysis. RESULTS: From 2007 to 2016, 134 new drugs were approved by all three regulatory agencies. Overall, 66.4% of the drugs were first approved by the FDA, 30.6% by the EMA, and 3.0% by SMC. The difference in approval dates between SMC and the EMA, SMC and the FDA, and the FDA and the EMA were statistically significant. The indications approved by the FDA, the EMA, and SMC for the same drugs were similar in content for 23.1% drugs and different in 76.9% of the drugs. Significant differences in indications existed between the FDA and SMC and the FDA and the EMA, but not between the EMA and SMC. CONCLUSION: There were differences in the characteristics of new drugs approved by the EMA, the FDA, and SMC in the period 2007-2016. Overall, two thirds of the new drugs were first approved by the FDA. Differences in indications were found in three out of four new drugs approved by the three regulatory agencies. Despite international drug regulation harmonization efforts, significant differences in the characteristics of new drugs approved by different agencies persist.

Antineoplastic drugs and their analysis: a state of the art review.

The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

Long-term stability of ganciclovir in polypropylene containers at room temperature.

Purpose Ganciclovir is increasingly provided by hospital pharmacy production unit in a ready-to-use form, in order to improve the safety of healthcare workers and the efficiency of the organisation. The objective of this study was to develop a stability-indicating method to assay ganciclovir and determine the stability of ganciclovir in syringes (5 mg/mL) and infusion bags (0.25 and 5 mg/mL) at two different temperatures. Method Ganciclovir solutions (0.25 mg/mL and 5 mg/mL) in 0.9% sodium chloride were prepared in 50 mL polypropylene syringes or 100 mL polypropylene infusion bags and stored at 2-8℃ and 23-27℃. The chemical stability was measured using a stability-indicating Ultra High Performance Liquid Chromatography coupled to mass spectrometry method. Physical stability was assessed by visual inspection. Results No significant loss of ganciclovir under any of the tested conditions was observed in this study. All solutions remained clear through the study period. Conclusion All tested formulations remained stable for at least 185 days independently of container type, temperature or concentration studied.

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.