Aseptic Compounding Research Articles

Productivity and aseptic process evaluation during batch production simulation of intravenous medications using a semi-automated compounding device.

Intravenous (IV) medications can be prepared using compounding devices to increase productivity, and reduce risks associated with aseptic compounding. This study evaluated the productivity and quality outcomes of the aseptic process for simulated batches of IV medications used in clinical practice produced using a semi-automated compounding device (Gri-fill; Grifols). Simulated batches from 50 to 600 preparations were completed representing hazardous and non-hazardous drugs, including one-step single component (atropine sulfate, cisplatin) and multistep, multiple component (mitomycin C, piperacillin/tazobactam, trastuzumab, 5-fluorouracil and gemcitabine). Productivity, device autonomy, quality of the aseptic process (media-fill test) and sterility of the preparations were evaluated. A total of 2024 final preparations and 460 intermediate products were compounded during 78 working hours. For low and high complexity level preparations, median (minimum-maximum) production speed was 1.3 (0.6-1.7) and 3.7 (2.6-4.3) min per preparation, respectively. The longest process (36.2 min/bag) was the preparation of a simulated gemcitabine 3 L bulk solution bag, which included reconstitution of vials and filling the bulk bag. All operational errors (0.6%) were resolved autonomously by the user. None of the 883 media fill preparations showed microbiological growth and all 114 analyzed preparations passed the sterility test. Using a semi-automated compounding device, preparation efficiency of IV medications ranged from 14 preparations/h for multicomponent preparations from vials requiring reconstitution, to 100 preparations/h for low complexity preparations using a bulk solution bag. The aseptic processes demonstrated the absence of microbial growth in all tested preparations.

Quality assurance standards and their use in the preparation of parenteral systemic anticancer therapy products in healthcare establishments: a scoping review

ObjectivesThe use of parenteral systemic anticancer therapy (SACT) has led to improved cancer survival. A quality assurance (QA) system of the aseptic compounding process is necessary to ensure safe and...

Modernising aseptic compounding through the use of new technology: a validation and proof of concept study

Abstract Introduction There is an urgent need to reform care pathways to keep patients, wherever possible, outside of hospital and in turn freeing up capacity and addressing the elective backlog crisis. To address such issues and futureproof its services, the NHS is modernising its approach to care. Within the aseptic space, current transformation plans1 require the provision of large-scale quantities of injectable medicines and the leveraging of new aseptic technologies to enable the large scale roll out of services such as outpatient antimicrobial therapy (OPAT). Aim CIVAS@IP5 is Wales' first National Pharmacy Technical Services Unit and has recently invested in state-of-the-art technology, which is transforming its aseptic compounding, making it possible to significantly scale up capacity and facilitate the creation of local OPAT services. The technology in question is the Gri-fill®4 2, a semi-automated system for compounding hazardous and non-hazardous sterile preparations. The aim of this study, which is the first in the UK to use the Gri-fill®4, was to report on the suitability of such technology to facilitate the transformation of compounding services. Methods Due to its nature, this pilot study required no ethical approval as no patients were involved nor any patient data collected. Over the course of a number of weeks, validation measurements were carried out on the Gri-fill®4. This included time and motion assessments of the current manual pathway of compounding compared to the semi-automated pathway using the Gri-fill®4. Results Results revealed that the preparation of an infusion bag using the Gri-fill®4 was achieved within an average of 2.64 minutes. This represents a substantial 80% time saving when compared to the average manual preparation time of approximately 13 minutes. Furthermore, batch preparation of 46 infusions was completed with 50% fewer critical manipulations (92 critical manipulations for the Gri-fill®4 versus 184 critical manipulations for the manual pathway), reducing the potential for error whilst also requiring fewer verifications by staff. Once scaled, this increase in productivity will have significant real-world benefits for local services which are reliant on responsive aseptic compounding provisions. On top of productivity improvements, the introduction of semi-automated compounding has afforded sustainability improvements; with less plastic consumables required for the production of each batch. Discussion/Conclusion It is important to note that our data reports on the impact of only one Gri-fill®4 unit. As such there are obvious scalability benefits to our findings but also limitations in regard to the logistics and practicalities of leveraging large scale semi-automated compounding; both of these issues will be explored. In conclusion, the productivity of aseptic units can be drastically improved through the modernisation of compounding technology. This validation study reports on the extent of this improvement and discusses the implications it will have on the future of OPAT and aseptic services.

Use of Science Lab Simulation During a Two-Week Virtual Biomedical Research Training Summer Camp for Underserved Minority Youth: A COVID-19 Adjustment.

The Maryland Action for Drug Discovery and Pharmaceutical Research (MADDPR) Program provides hands-on lab experience and mentoring to underserved minority high school students. With the inability to conduct an in-person STEM summer camp, the program transitioned to a virtual format in 2020. Thirty-three students and their PLTW teacher participated in live sessions using Blackboard Collaborate Ultra®. One highlight of the sessions was program faculty's use of interactive simulation software such as science labs (Labster®), animal behavior (Sniffy the Virtual Rat®), and aseptic compounding (Virtual Interactive Clean Room®). Graduate student mentors worked with students in small virtual breakout sessions. Post-session survey data show that the majority of students felt comfortable participating in the simulation sessions. Students' responses indicated that they enjoyed the virtual labs and appreciated the effort to implement the game-like lab simulation exercises. Remarkably, student ratings of the virtual sessions compared favorably and, in some cases, exceeded those from the same sessions conducted in-person in 2019. In post-camp surveys, 96% of the participants indicated an interest in pursuing careers in pharmacy/other health professions. Student and teacher comments also indicated that the virtual experience of the camp prepared both students and their teacher for the coming fall semester at school.

Chemical Decontamination of Hazardous Drugs: A Comparison of Solution Performances.

Over the past 40 years, numerous actions have been undertaken to decrease the contamination of hospital facilities by intravenous conventional antineoplastic drugs (ICADs) such as centralizing compounding in pharmacies, using personal protective equipment, specific compounding, or infusion devices. As recently proposed in the <USP800> monograph, an additional specific decontamination step must be envisaged. A recent literature review analysed and discussed the different solutions tested in terms of decontamination efficacy. This article aims to discuss the performance of these solutions in the framework of aseptic compounding. The same dataset used in the previous literature review was reanalysed according to other parameters so as to select decontamination solutions: overall decontamination efficiency (EffQ), tested contaminants, and the risks of use in daily practice. Using an EffQ threshold of 90% resulted in discarding 26 out of the 59 solutions. Solutions were tested differently: 8 on 1 contaminant, 11 on 2 contaminants, and 14 solutions on between 3 and 11 contaminants. Three risks were identified to help make choices in routine practice: the mutagenicity of degradation products, the safety of operators and facilities, and respect for the aseptic environment. From the results, performance is discussed according to specific situations: a one-time incident or the basic chemical contamination due to daily practice. Accordingly, the decontamination solution selected then required a risk analysis and an evaluation before implementing it in the daily practice of a compounding unit.

Potency Analyses Provide Insight Into Student Aseptic Compounding Technique Errors

Objective. To determine whether direct observational scores were predictive of the potency of pharmacy students' compounded sterile preparations (CSPs) and to identify any misunderstandings students had regarding individual aseptic technique steps. Methods. P1 students performed aseptic techniques during three observational encounters separated by two weeks. Students' performances were evaluated using an observation-based rubric and were subject to potency analysis. The encounters were transferring a drug solution from a vial, an ampule, and a reconstituted powder to intravenous (IV) bags. Results. The mean potency of the diphenhydramine (vial) and lidocaine (ampule) met the ±10% goal of expected potency. These results were significantly different from those of the ampicillin (reconstitution) encounter, which was outside the goal. The percentage of students meeting the potency goal was 59.3% for the diphenhydramine, 80.3% for the lidocaine, and 50.4% for the ampicillin encounters. The observation scores were significantly different between all three encounters. There were no correlations between the observational scores and the potency for any encounter regardless of whether or not the student met the goal potency. Although their observation scores were acceptable, up to 50% of students did not meet the potency goal for each of the three encounters. Conclusion. The potency data provided the critical insight that P1 students were not adequately trained to account for pressurization when manipulating vials using aseptic compounding processes. The results suggest that both observation scores and potency analysis should be part of an overall assessment of student ability to compound sterile preparations.

Microbiological performance of a robotic system for aseptic compounding of cytostatic drugs

BackgroundCompounding of cytostatic drugs requires strict aseptic procedures, while exposure to toxic drugs and repetitive manual movements should be minimized. Furthermore, reuse of vials is desirable to lower the costs. To assess if all this might be safely achieved with a robot, this study aimed at qualifying the aseptic preparation process with the robotic system APOTECAchemo. MethodsThe aseptic compounding of patient-individual cytostatic solutions was simulated with media fill simulation tests to qualify the performance according to European GMP Annex 1. The contamination in the environment was measured in critical places using settle plates, contact plates, active air sampling and particle counting. Media-fill simulation tests were prepared in 3 production batches.The second part of the study evaluated the microbiological shelf-life of commercial drug vials after repeated puncturing. On six days, fifty syringes of 15 ml media were prepared from the same 50 vials with the robot. After each preparation, vials were covered with an IVA seal upon unloading from the robot to protect them from microbiological contamination. ResultsNo microbiological contamination was found in any of the 96 media fill preparations, nor in any of the 300 syringes that were prepared with repeated puncturing. The compounding area met class A limits, while class A criteria were not fulfilled by the contact plates and settle plates placed on the right side of the loading area. There, the average colony forming units (cfu) were 3 and 1.17, respectively, meeting class B criteria. ConclusionsRobotical compounding of cytostatic drugs with APOTECAchemo meets the microbiological requirements of the European GMP. In addition, the robot can reuse vials repeatedly and safely, thereby enabling extended usage.

Exploratory analysis for the implementation of antineoplastic logarithmic dose banding.

Background Dose banding (DB) is a strategy to rationalise antineoplastic production at Hospital Pharmacy Aseptic Compounding Units (ACUs) and to reduce patient's waiting time. DB allows for optimizing workflows and workloads, facilitating adoption of new technologies, and increasing safety, quality and efficiency of the compounding process. Objective To evaluate the potential impact of implementation of Logarithmic DB and to identify antineoplastic agents and preparations that fulfil criteria published and establish the number and standard doses that could be compounded in advance at the ACU. Setting University and Polytechnic third level general hospital. Method Retrospective observational study (December 2015-May 2016). Antineoplastic dose production was analysed. Investigational drugs were excluded. Three criteria were applied following bibliography reviewed to select candidates to be compounded at our ACU as standardised using logarithmic DB: (a) Antineoplastic preparations > 250 per year; (b) psychochemical stability in optimal storage conditions at least 14days; (c) maximum five logarithmic standardised doses that include at least 60% of all individualised doses compounded for a given drug. Main outcome measure Number of antineoplastic agents, preparations and logarithmic standard doses candidates to DB. Results 15,436 antineoplastic individualised doses corresponding to 69 antineoplastic agents were analysed. At our institution applying selection criteria, 19 (27%) antineoplastic drugs (3 monoclonal antibodies, 16 cytotoxic) were potential candidates to DB. 6285 (40%) of compounded individualised dose preparations could be prepared in 84 logarithmic standard doses in advance. Conclusion Dose banding implementations could contribute to rationalise antineoplastic production and increase the ACUs compounding capacity.

Development and content validation of an assessment tool for medicine compounding on hospital wards.

Background Medicines should be compounded by using an aseptic technique to assure patient safety. The parenteral administration of microbiologically contaminated doses can result in bacteriaemia, other morbidity and even death. Objective The purpose was to develop and content validate an assessment tool for medicine compounding on hospital wards suitable for self-assessment and external audit to ensure the safety of medicine compounding on wards. Setting Finland as setting. Method The first draft of the tool was based on ISMP "Guidelines for safe preparation of sterile compounds" and a systematic literature search. The tool was validated by using a two-rounded Delphi-method with a panel of 19 experts. Suitability and feasibility of each item was evaluated. Main outcome measure An agreement of ≥70% on each item was required. Results The final tool comprises of 64 items under the following topics: (1) general principles of good compounding practices (23 items), (2) recording and confirming medicine orders on the wards (5 items), (3) storage of medicines on the wards (7), (4) aseptic compounding of intravenous medicines (25 items) and (5) quality assurance (4 items). Most items related to General principles of good compounding practices and Compounding of IV medicines (36 and 38% of the items, respectively). Conclusion It was possible to develop and content validate, by the Delphi method, an assessment tool for safe aseptic compounding on hospital wards. A two-round Delphi process yielded consensus on 64 items for this purpose.

Comparison of Aseptic Compounding Errors Before and After Modified Laboratory and Introductory Pharmacy Practice Experiences

To determine whether aseptic compounding errors were reduced at the end of the third professional year after modifying pharmacy practice laboratories and implementing an institutional introductory pharmacy practice experience (IPPE). An aseptic compounding laboratory, previously occurring during the third-year spring semester, was added to the second-year spring semester. An 80-hour institutional IPPE was also added in the summer between the second and third years. Instructors recorded aseptic compounding errors using a grading checklist for second-year and third-year student assessments. Third-year student aseptic compounding errors were assessed prior to the curricular changes and for 2 subsequent years for students on the Oklahoma City and Tulsa campuses of the University of Oklahoma. Both third-year cohorts committed fewer aseptic technique errors than they did during their second years, and the probability was significantly lower for students on the Oklahoma City campus. The probability of committing major aseptic technique errors was significantly lower for 2 consecutive third-year cohorts after the curricular changes. The addition of second-year aseptic compounding laboratory experiences and third-year institutional IPPE content reduced instructor-assessed errors at the end of the third year.

Evaluating the Effects of Flexible Learning about Aseptic Compounding on First-year Students in a Pharmacy Skills Laboratory

To evaluate how flexible learning via online video review affects the ability and confidence of first-year (P1) pharmacy students to accurately compound aseptic preparations. Customary instructions and assignments for aseptic compounding were provided to students, who were given unlimited access to 5 short review videos in addition to customary instruction. Student self-confidence was assessed online, and faculty members evaluated students' aseptic technique at the conclusion of the semester. No significant difference on final assessment scores was observed between those who viewed videos and those who did not. Student self-confidence scores increased significantly from baseline, but were not significantly higher for those who viewed videos than for those who did not. First-year students performed well on final aseptic compounding assessments, and those who viewed videos had a slight advantage. Student self-confidence improved over the semester regardless of whether or not students accessed review videos.

A 2-year retrospective review of vial sharing options for the compounding of cytotoxics

ObjectivesVial sharing practices introduce risk to aseptic compounding. This review aims to quantify the financial gain that can be achieved from taking on this additional risk.MethodBy looking at all drug...

TCH-013 Disinfectant Efficacy of Ultraviolet Light Irradiation in an Automated Systems For the Aseptic Compounding.

Background Ultraviolet (UV) light irradiation is used in a variety of applications, such as food, air and water purification. The mechanism of UV disinfection differs considerably from chemical disinfectants: UV...

The effect of prior experience with aseptic techniques on learning outcomes in a sterile compounding laboratory course

The goal of this study was to investigate the effect of prior experience in aseptic techniques on learning outcomes in the sterile compounding laboratory course among second-year professional pharmacy students. Data were collected via self-reports using pre and post course questionnaires on proficiency in 21 practical skills in aseptic compounding. In the precourse questionnaire, students were asked about prior experience with compounding of sterile preparations. A 20-question test on knowledge related to practical skills was given with the questionnaire. Student responses collected pre and post course were analyzed. Comparisons were made between two groups: students without prior experience and students with prior experience in aseptic techniques, referred to as Novices and Experienced, respectively. Differences in skills and knowledge between Novices and Experienced students identified before the course were significant and persisted after the course. Improvement in practical skills was significantly higher in Novices than Experienced students. Students with prior experience performed better on the test and in practical skills that required engagement of higher levels of the thinking process. The findings from this study address a poorly investigated but nevertheless important aspect of pharmacy education: the impact of prior experience on pharmacy students' performance in required curricular courses. Implications from this study relate to student-centered instruction and addressing the differences in knowledge and skills among students.

Potential for airborne contamination in turbulent- and unidirectional-airflow compounding aseptic isolators

The ability of turbulent- and unidirectional-airflow compounding aseptic isolators (CAIs) to control airborne contamination during aseptic compounding of compounded sterile preparations (CSPs) was studied. A three-phase challenge of the comparative airborne-contamination management capabilities of five CAIs was conducted using augmented, industry-standard visual tracer and discrete particle counting methods. In phase 1, a visual smoke tracer was used to conduct a standardized, comparative challenge. In phase 2, CAI operational contamination-control capabilities were measured in accordance with the International Organization for Standardization (ISO) class 5 air cleanliness conditions using a standardized CSP process qualification procedure. Alcohol drying times were also compared. In phase 3, the gross contamination clearance interval required to achieve the ISO class 5 condition after a gross contamination event was measured for each CAI. All four unidirectional-airflow CAIs met ISO class 5 cleanliness requirements throughout all testing phases and areas of the work zone and demonstrated alcohol drying times of 16 seconds or less. The turbulent-airflow CAI tested failed to achieve the ISO class 5 operating condition at any time during the testing and required alcohol drying times of six minutes. The unidirectional-airflow CAIs tested met the laminar-airflow workstation-equivalency requirements of chapter 797 of the United States Pharmacopeia, pharmaceutical aseptic processing standards, the industry-standard definition of a closed isolator, and the rigorous demands of pharmacy and nursing sterile compounding. The performance of four unidirectional-flow CAIs supports their use in pharmacy and nursing CSP operations, whereas the performance of one turbulent-flow CAI does not.

Basics of Aseptic Compounding Technique Video Training Program

Basics of Aseptic Compounding Technique Video Training Program