Advanced prescription of injectable anticancer drugs: Safety assessment in a European Comprehensive Cancer Centre using the risk matrix approach.

AIMS: The purpose of this work was to assess failures in the advanced prescription of parenteral anticancer agents in an adult day oncology care unit with more than 100 patients per day. METHODS: An a priori descriptive analysis was carried out by using the risk matrix approach. After defining the scope in a multidisciplinary meeting, we determined at each step the failure modes (FMs), their effects (E) and their associated causes (C). A severity score (S) was assigned to all effects and a probability of occurrence (O) to all causes. These S and O indicators, were used to obtain a criticality index (CI) matrix. We assessed the risk control (RC) of each failure in order to define a residual criticality index (rCI) matrix. RESULTS: During risk analysis, 14 FMs were detected, and 61 scenarios were identified considering all possible effects and causes. Nine situations (15%) were highlighted with the maximum CI, 18 (30%) with a medium CI, and 34 (55%) with a negligible CI. Nevertheless, among all these critical situations, only three (5%) had an rCI to process (i.e., missed dose adjustment, multiple prescriptions and abnormal biology data); the others required monitoring only. Clinicians' and pharmacists' knowledge of these critical situations enables them to manage the associated risks. CONCLUSIONS: Advanced prescription of injectable anticancer drugs appears to be a safe practice for patients when combined with risk management. The major risks identified concerned missed dose adjustment, prescription duplication and lack of consideration for abnormal biology data.

Errors in prescribing injectable anticancer drugs: benefits of a pharmaceutical long-term monitoring to improve patient safety in a European comprehensive cancer centre.

OBJECTIVES: We aimed to assess the impact of pharmacist interventions on injectable chemotherapy prescription and the safety of early prescription practice in an adult daily care unit. METHODS: Prescription errors were recorded before and after implementing corrective measures. Errors identified from the pre-intervention period (i) were analysed to identify areas for improvement. During the post-intervention period (ii) we compared the errors in anticipated prescription (AP) with those in real-time prescriptions (RTP). We performed Chi-square statistical tests (α=0.05). RESULTS: Before implementing corrective measures (i), 377 errors were recorded (ie, 3.02% of prescriptions). After the implementation of corrective measures (ii), there was a significant decrease in errors, with 94 errors recorded (ie, 1.20% of prescriptions). The error rate in AP and RTP groups was 1.34% and 1.02%, respectively, without a significant difference between the two groups. CONCLUSIONS: This study highlights the importance of prescription review, as well as collaboration between pharmacists and physicians, in reducing prescription errors, whether these prescriptions were anticipated or not.

How can we optimise the pharmaceutical analysis of radiopharmaceutical pediatric prescriptions?

OBJECTIVES: In France, dispensation is defined by the validation of a prescription associated with a pharmaceutical analysis, preparation of medication and provision of information necessary for proper use. There are very few data available in the literature that describe prescription analysis modality in radiopharmacy. The aim was to secure a place for paediatric prescription analysis in radiopharmacy by designing a flow chart validated by experts. METHODS: Experts from different disciplines and health setups (ie, public, private) were selected to represent the various paediatric patient care processes. A review of the literature on pharmaceutical analysis and paediatric prescription in radiopharmacy was conducted. A Delphi approach comprising two rounds (Google Form survey) was used to validate the flow chart. Answers were graded according to a nine-point Likert scale for agreement. Open-ended questions allowed experts to comment on the propositions. A consensus between experts was reached if more than 70% of the experts agreed on an item and fewer than 30% disagreed. RESULTS: Sixty-five experts were solicited: two oncopaediatricians, three nuclear medicine physicians, 46 radiopharmacists, three residents in radiopharmacy, one hospital pharmacist, five medical physicists, one pharmacy technician, two X-ray technicians and two patients who are pharmacists. The first round survey included a draft of the flow chart: 31 experts answered (48%). All professional disciplines were represented except pharmacy technician. The second round survey was sent with a new flow chart that had been improved by the experts' comments. After 3 weeks, 18 answers were obtained (28%). After the first round, consensus was obtained for each item. Experts gave a total of 97 comments. The second flow chart had three steps: regulatory aspects, patient data, and radiopharmaceutical data, and it was accompanied by descriptive text explaining the field of application. CONCLUSION: The resulting flow chart will secure the pharmaceutical analysis step for this special patient population.

Application of an Environmental Monitoring to Assess the Practices and Control the Risk of Occupational Exposure to Cyclophosphamide in Two Sites of a French Comprehensive Cancer Center.

OBJECTIVES: The risk of chronic exposure to antineoplastic agents in hospitals, mainly by skin contact with contaminated surfaces, is well established. The aim of this study was to assess indirectly the risk of occupational exposure to antineoplastics drugs at two hospitals by using an environmental monitoring, and to suggest ways of improving the exposure to healthcare workers. METHODS: An observational study of care practices on both sites was carried out. A wipe sampling campaign was then designed to study environmental contamination throughout the chemotherapy process: receipt, storage, compounding, transport, administration, and elimination areas. Samples were analyzed by a validated LC-MS/MS method allowing trace quantification of cyclophosphamide. A guidance 'safe value' of 0.10 ng/cm2 was considered. RESULTS: A total of 293 samples were analyzed, of which 58% were found to be positive. In the compounding units, the drug vials were contaminated before [range = (non-quantifiable [NQ]-0.71) ng/cm2] and after cleaning procedure [(NQ-0.62) ng/cm2], particularly when the flip-off lid was removed during cleaning. The contamination found on manual preparations was operator-dependent: [non-detectable (ND)-3.51] ng/cm2 on infusion bag surfaces; (780.61-24 698.98) ng/cm2 on medication ports. In the case of automated preparations, the average contamination was higher on infusion bag surfaces [(2.43-36.86) ng/cm2] and lower on medication ports [(0.43-7.65) ng/cm2] than manual preparations. Contamination of the analytical control area was also highlighted. In the daily care unit, the contamination was located near the infusion area (armchairs, infusion stands, floor, and patient toilets), and varied somewhat between the two sites, especially on the floor with (0.46-27.32) compared to (ND-0.18) ng/cm2. We did not detect contamination on the transport boxes, on the door handles or in the disposal areas. CONCLUSIONS: The variability of contamination observed between the two sites can be explained in part by the difference in routine practices, especially training of the staff, and cleaning procedures. Findings were communicated to healthcare workers, and news interventions were implemented based on wipe sampling results. This study demonstrated a method for routine environmental monitoring and worker education as a strategy to reduce occupational exposure.

Ultra-fast liquid chromatography method coupled with ultraviolet detection to quantify dimethylsulfoxide, dimethylformamide and dimethylacetamide in short half-lives radiopharmaceuticals.

Radiolabelling with short half-lives radionuclides (e.g., fluorine-18 and carbon-11) must be as efficient and as fast as possible. Nucleophilic radiofluorinations and radiomethylations are conducted in polar aprotic solvents, such as dimethylsulfoxyde (DMSO), N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA), at high temperature. Those solvents are classified as toxic according to the ICH guidelines and must be evaluated in drug such as radiopharmaceuticals. Headspace gas chromatography is the standard method for the quantification of residual solvents but is not optimized for a rapid quantification of low vapor pressure solvents such as DMSO, DMF and DMA in radiopharmaceuticals. Direct injection gas chromatography is an interesting option without incubation step but the analysis run-time remains beyond 10 min long. In consequence, we developed a very simple ultra-high performance liquid chromatography method coupled with UV detection. Following the EMA requirements, we successfully validated a 3-min run-time analysis for quantification of three solvents in short half-lives radiopharmaceuticals. We currently use this method for the quality control of radiopharmaceuticals produced in our PET center.

Validation of an ergonomic method to withdraw [99mTc] radiopharmaceuticals.

The main objective of the present work was to ensure quality of radiopharmaceuticals syringes withdrawn with a "Spinal needle/obturator In-Stopper" system. Methods: Visual examinations and physicochemical tests are performed at T0 and T+4h for [99mTc]albumin nanocolloid and T+7h for [99mTc]eluate, [99mTc] HydroxyMethylene DiPhosphonate and [99mTc]Human Serum Albumin. Microbiological validation was performed according to European pharmacopoeia. Fingertip radiation exposure was evaluated to confirm the safety of the system. Results: Results show stable visual and physicochemical properties. The integrity of the connector was not affected after 30 punctures (no cores). No microbiological contamination was found on tested syringes. Conclusion: The system could be used 30 times. The stability of syringes drawing with this method is guaranteed up to 4 hours for [99mTc]albumin nanocolloid and 7 hours for [99mTc]eluate, [99mTc]HydroxyMethylene DisPhosphonate and [99mTc]Human serum albumin.