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Author(s)

Louise Rasmussen Duckert, Marianne Kjettrup Jensen, Mette Lethan, Trine Schnor

Why was it done?

The hospital pharmacy wishes to support the implementation of OPAT and during the process the need for standardised kits with utensils was identified. The availability of kits with necessary utensils for aseptic handling of parenteral infusion would simplify and standardise the work for hospital and home nurses. Considerations regarding patient safety and sustainability were also in favour of the kits, as choice of utensils could secure compliance to regional guidelines considering use of closed systems and rinse of the line after infusion. Kits containing the exact needed utensils for an administration also reduces the possible waste.

What was done?

The hospital pharmacy has composed standard kits with utensils for outpatient parenteral antibiotic therapy (OPAT).

How was it done?

The kit is composed in collaboration between the pharmacy, hospital nurses and home nurses. The best suited infusion set was chosen – a closed system with two spikes for antibiotic mixing and infusion. Hereby nurses avoid direct contact with antibiotics and avoid antibiotic aerosols in the citizen’s home. The infusion set contains no PVC, phthalates or latex. When fully emptied the infusion set can be discarded as regular waste.
The kit also contains a sterile cover for the workstation, sterile ethanol swabs, gloves, pre-filled saline syringes for rinse of the line after infusion and a written manual. All is packed and labelled by the hospital pharmacy and lot numbers are registered for traceability.

What has been achieved?

The kits have been tested in selected municipalities and the content of the kit has been adjusted. As a result of the feedback a film has been recorded showing the handling of the infusion set. The video is used for training and a QR code on the written manual guides the home nurse to the video if needed. The kit is now used widely in the region and response is positive. With the set-up being identical in all municipalities in the region, handling antibiotics and utensils is simpler for the hospital nurse at discharge.

What next?

As the number of patients in home-based OPAT rises, experiences with the kits will probably result in wishes for adjustments. A new kit with utensils for changing PVK is under development.

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Author(s)

Peder Nygard, Helle-Brit Fiebrich-Westra, Elise Smolders

Why was it done?

The aim of this project was to reduce paclitaxel waste caused by cancellation of administrations. Standardised dose bands make interchangeability of already reconstituted paclitaxel bags easier, as more patients use the same dose. This could potentially save drug- and material waste and costs even as manpower.

What was done?

Paclitaxel fixed dose bands were created for patients treated with a weekly dose of 80 mg/m2.

How was it done?

In consultation with prescribers the dose bands for paclitaxel where created (see table). These dosages were implemented as a dose-rounding rules in the drug preparation software (Hix 6.2, ChipSoft BV). The maximum deviation for dose-rounding rules for paclitaxel in our hospital is 10% of the prescribed dose. Dosage ≤72mg or >200mg were rounded as normal.

Prescribed dose (mg) Dose-band (mg) m2 (dose 80 mg/m2
>72 ≤88 78 1.0
>88 ≤102 96 1.2
>102 ≤116 114 1.4
>116 ≤136 126 1.6
>136 ≤152 144 1.8
>152 ≤168 162 2.0
>168 ≤184 174 2.2
>184 ≤200 192 2.4

What has been achieved?

These rules were implemented in April 2022. Data from 1 May 2022 to 31 August 2022 is compared with the same time period in 2021. In 2022, a total of 729 infusions where prepared compared with 872 infusions in 2021.
In this 4 month time period in 2022 a total of 14 different dosages were prescribed, compared with 24 in the same time period in 2021. Additionally, interchangeability was improved as the top 3 dosages prepared by the pharmacy were: 144 mg (36%), 162 mg (22%), and 126 mg (19%) compared with 144 mg (17%), 138 mg (14%), and 126 mg (10%) in 2021.
Furthermore, in 2021 we discarded 33 prepared dosages of paclitaxel of which three infusions could be reused. Compared to 13 discarded dosages in 2022 of which eight were reused giving a reduction of 25 infusions less waste (83% reduction, savings ~2500 euros).

What next?

Pharmacists need to be instructed to adapt these rounding rules, which must decrease the variation in dosages and thus waste. Secondly, this project will be monitored the upcoming year and evaluated together with prescribers. The aim is to implement dose bands for paclitaxel dosages 175 mg/m2 and other chemotherapeutic drugs (eg, oxaliplatin, docetaxel, cyclophosphamide).

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Author(s)

Caterina Donati, Giulia Moroni, Matteo Federici , Paolo Silimbani

Why was it done?

To evaluate the performances of automated preparation in the oncology pharmacy by assessing productivity, errors interception, and waste reduction achieved by managing vials overfill.

What was done?

Automated preparation, operated by two robots and one gravimetric-assisted workflow system, was introduced to improve productivity and working efficiency [1,2], while reducing the risk of human errors. Furthermore, to optimize resources utilization and reduce waste, a procedure for managing overfill of drug vials during automated preparations was implemented. Indeed, manufacturers fill injectable drug vials with a volume that slightly exceeds the nominal volume (overfill) to ensure proper withdrawing and patient dosing.

How was it done?

The annual throughput in terms of preparations was calculated for automated and manual preparation. Human errors intercepted during automated preparation were clustered into four groups: loading of wrong component (i.e. final container, solvent, drug product), multiple barcodes reading, failed manual reconstitution, wrong expiration date. Overfill was calculated for 17 high-cost drug vials by volumetric verifications performed by experienced pharmacy technicians. The annual number of vials used and the corresponding waste reduction due to the overfill management was determined. All data were taken from the production management software and examined over a two-year period (2019-2020).

What has been achieved?

In total, 82,216 preparations were compounded over two years, 72% of which with robotic systems and 28% manually prepared, either with gravimetric-assisted workflow (13%) or conventional volumetric technique (15%). Overall, automated preparation covered 85% of the total production. The human errors intercepted during automated preparation amounted to 701 in 2019 and 662 in 2020. Most errors were intercepted by robotic systems and were related to loading of wrong component (83%). Vials overfill ranged from 0.2mL (ramucirumab, eribulin, trastuzumab-emtansine, pembrolizumab, nivolumab) to 2.5mL (ipilimumab). The total waste reduction due to overfill management resulted in 1331 vials saved corresponding to 855,013€.

What next?

The study showed that automated preparation of oncology products represents a well-established practice in terms of productivity, and moreover ensuring interception of potential medication errors and waste reduction thanks to the overfill management

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Why was it done?

Different automated production systems (APS) are now available on the market. It is essential not to make a mistake due to the impact on the organization, investments and architecture. Comparative tables of each equipment are not enough to properly make a good choice.

What was done?

We determined a decision tree to choose the most suitable equipment for the cytotoxic drugs production unit.

How was it done?

Based on our experience of using APS and interviews or visits of other users of the equipment, we have compared the different systems by classifying them according to the items that are the most efficient: productivity, precision, diversity of preparations and drugs, installation constraints, autonomy, maintenance of sterility of preparations, chemical contamination. We also used a French calculator, published by the ARS IDF, to determine the cost of a preparation, taking into account the purchase price, personnel, consumables, maintenance, personnel equipment, and operating costs. Then we defined our present and future needs (dose banding, nominative advance preparation, type and quantity of preparation (infusers, syringes, bags), architectural and air treatment constraints. Then we classified the needs and constraints by importance and then determined for each one which equipment was the best answer.

What has been achieved?

We classified the needs and constraints by importance and for each one we determined which equipment was the best answer. From most important to least we had: headroom, floor load, air handling, dose banding, sterility maintenance, productivity, autonomy and calculated price of the preparation. The results for preparation price showed that the highest price per preparation is not the most expensive equipment but one of the cheapest because of the very expensive captive consumables. Unexpectedly, the most expensive equipment has an average price per preparation because it is very productive, autonomous and has few captive consumables. To validate this tree, we applied it to another cytotoxic production unit.

What next?

Using this decision tree, the choice of equipment will be the most suitably adapted for each hospital.

Author(s)

PATRICIA ORTIZ FERNANDEZ, Alba Maria Martinez Soto, PILAR FERNANDEZ-VILLACAÑAS FERNANDEZ, IGNACIO SALAR VALVERDE

Why was it done?

The objective is to improve patient safety, detecting mistake in real time. Review good work practices and achieve greater effectiveness. Improve the communication of the work team.

What was done?

Improve the quality of the reception, conditioning and storage processes that are carried out in the pharmacy service using tools that in the field of quality have shown great effectiveness. Simplify processes and update work instructions and standardize these. Establish quality indicators.

How was it done?

ing the `Lean healthcare´methodology based on eliminating inefficiencies in work processes and identifying opportunities for improvement which are specific, measurable, achievable, relevant and time bounded. Another of the methodologies used is the `5S´ (five basic elements: selection, systematization, cleaning, normalization and self-discipline) and `PDCA´(plan, do, check, act).
1. Establish a multidisciplinary group.
2. Training on the methodology developed in 5 sessions.
3. Elaboration of a project charter with the objetives, the scope and the planning.
4. Analyze the chosen processes with the following dynamics: a) Team visit to the work area, b) Interview an expert from each process, c) Registration of inefficiencies and process data in a value steam mapping, d) Compilation of possible improvement actions, e) Meeting for consensus and realization of an action plan to prioritize and assign those responsible for carrying out the improvement actions.

What has been achieved?

Number of meetings with the multidisciplinary team: 10
Reception process: improvements implemented(II): 11, pending improvements (PI): 2, indicators evaluated (IE): 4
Conditioning process: II: 4, PI: 0, IE: 2
Storage process: II: 13, PI: 2, IE: 2

What next?

Must be maintained and evaluated over time and anytime there that may be a change. These improvements allowed a better anticipation. The process improvement approach aimed to identify solutions was very fruitful and led to outcome practical. This method could be applied to improve other types of processes in our pharmacy service.

Author(s)

Joan-Candy MABIN , Aïssé DIALLO, Hortense LANNELUC-BEAUJARD, Xavier DEVIOT

Why was it done?

The aim of this work is to find a cheaper alternative, reducing the analysis duration and allowing the pharmacy to be laboratory independent.

What was done?

The opening of the production unit (PU) leads to reorganize the parenteral nutrition mixtures (PNM) dosing. Primarily carried out in the biochemistry laboratory of our hospital, potentiometry and colorimetry analysis were long (more than an hour) and costly. PNM composition accelerates the aging of one of the device components that costs 1400 euros and have to be changed every 3 weeks, raising the total around 24300 euros per year only for this component.

How was it done?

Hospitals producing PNM in the region were identified and approached. They were asked about the type of dosed elements, the analysis method and the equipment used, about the analysis duration and localization (laboratory or pharmacy departments) and their overall cost estimation.

What has been achieved?

Five hospitals with different dosing equipment answered. Four of them analyze cations: calcium, magnesium, sodium and potassium by capillary electrophoresis, potentiometry or spectrometry, three of them analyze glucose by chromatography or colorimetry, and two of them determine osmolarity of the PNM mixtures. Dosages are performed by the pharmacy department in three PU where technician are required. Results are provided in about an hour when the activity depends on the laboratory and around five to ten minutes when it is managed by the pharmacy department. The average cost to purchase the equipment for each hospital was around 50000 euros (without the associated materials and the labour cost).

What next?

To conclude, no hospital interviewed can be a model because of either the high costs or the unadapted equipment size to the scale of the room of our PU. Nevertheless, during discussions, an equipment that might answer our needs was suggested, because no technician is needed for analysis, and it is described simple and easy to use. The manufacturer has been reached out asking for demonstration and information before any purchase. If accepted, the device will be qualified before going into production.

Author(s)

Emma Pinet, Lionel Barty, Anne Blandine Bouvrain, Françoise Le Cheviller, Nicolas Vaillant, Nathalie Jourdan, Hélène Sauvageon, Isabelle Madelaine

Why was it done?

In order to make hospital preparations in advance and optimize costs, a physicochemical and biological stability study was conducted in the pharmaceutical control laboratory.

What was done?

Mogamulizumab is a monoclonal antibody used in the treatment of Sezary syndrome and mycosis fungoides. The dilution of the 4 mg/ml vial of Poteligeo® in the infusion bag is stable for 24 hours at room temperature between 0.1 to 3 mg/ml.

How was it done?

Four bags of mogamulizumab were prepared in 0.9% NaCl 250 ml (2 at 0.14 mg/ml, 2 at 0.34 mg/ml). Each dilution is evaluated at 20±5°C and at 5±3°C, protected from light for 28 days. Analyses are performed in triplicate by High Performance Liquid Chromatography (HPLC-UV) associated with Chromeleon™ software. Concentrations are measured by HPLC after Flow Injection Analysis (FIA). Physical stability is studied by searching for IgG aggregates by Steric Exclusion Chromatography (Biozen™SEC3 column, 1.8µm 300*4.6mm). Chemical stability is evaluated by assessing acidic and basic variants proportions of the antibody by Cation Exchange Chromatography (CEC) (Biozen™WCX column, 6µm 250*4.6mm). Biological activity is determined by evaluation of the different glycoforms, by affinity chromatography (FcyRIIIa column, 5µm 75*4.6mm Tosoh®). The microbiological stability is performed by seeding the diluted solution on chocolate agar and brain heart broth.

What has been achieved?

At D28, the quantitative determination of mogamulizumab by FIA showed a deviation of less than 10% compared to theoretical concentrations. No aggregates or antibody fragments were found. The proportion of acidic, basic variants and of the main peak did not deviate by more than 5% compared to D0. For all infusion-bags studied by CEC, the main peak rates were between 79.1% and 85.8%, the acidic variant rates between 6.7% and 9.9% and the basic variant rates between 7.8% and 11.2%. The proportion of each antibody species (low, medium, high affinity) did not deviate by 5% from D0. The low affinity rate is between 48.2% and 52.7%, medium between 39.6% and 44.8% and high between 6.9% and 7.9%. No colonies were found on chocolate agar and heart-brain broth.

What next?

Mogamulizumab is physically, chemically and biologically stable for 28 days in diluted solution between 0.14 mg/L and 0.41 mg/L at 5°C and 20°C.

Author(s)

Marta García-Queiruga, Begoña Feal-Cortizas, José María Gutiérrez-Urbón, Andrea Luaces-Rodríguez, Alejandro Martínez-Pradeda, Sandra Rotea-Salvo, Carla Fernandez-Oliveira, Víctor Giménez-Arufe, Luis Margusino-Framiñán, Isabel Martín-Herranz

Why was it done?

Daptomycin is an intravenous antibiotic usually prepared in Hospital Pharmacy services. Normally it is dosed based on body weight, which requires each intravenous mixture to be prepared in an individual manner for each patient. This might lead to an increased assistance workload in elaboration areas, a higher number of errors in the preparation and high costs due to waste materials generated during preparation.

What was done?

The aim of this study is to describe the preparation of intravenous daptomycin by dose banding, a system in which daptomycin doses are rounded up or down in order to standardize and protocolize the preparation of intravenous mixtures as much as possible.

How was it done?

In order to improve this situation, dose banding strategy was implemented in February 2019: the obtained final dose was rounded in such a way that only mixtures of 500, 700 and 850 mg were prepared (in agreement with Hospital Pharmacy and Infectious and Microbiology medical teams) , following this scheme:
PRESCRIBED DOSE PREPARED DOSE
< 400 mg Prescribed dose (individualized) 400–599 mg 500 mg ≥600–799 mg 700 mg ≥800 mg 850 mg

What has been achieved?

Previous year before starting dose banding strategy (2018), 5493 individualized doses of daptomycin were prepared for 437 patients in our Pharmacy service. Between June 2020 and June 2021, 2680, 2555 and 997 units of daptomycin 500, 700 and 850 mg, respectively, were prepared for 360 patients. Batches of standardized doses were prepared in advance and kept refrigerated (stability of 10 days in 100 ml of physiological saline) until dispensation. In addition, during the same period, 15 patients (4 from pediatrics) received 209 individualized doses (3.2% of the total doses) due to their low body weight.

What next?

This strategy might decrease the number of errors in preparation and reduce processing times, which is essential since early appropriate antibiotic treatment in severe infection has been associated with better outcomes. Dose banding model could be extrapolated to other drugs with good physical, medical and microbiological stability in dilution, which are frequently prescribed and when few dose bands can cover most of the prescriptions.

Author(s)

Lucia Ricchi, Gregorio Medici, Porretta Serapiglia Carla, Marzia Bacchelli, Marianna Rivasi

Why was it done?

Hazardous drugs (HDs) may include antineoplastic or cytotoxic agents, biologic agents, antiviral agents, immunosuppressive agents, and drugs from other classes. Healthcare workers, especially nurses and pharmacy personnel, experience occupational exposure to these HDs.
Preparation and administration of ganciclovir should only be performed by health professionals who have been appropriately educated and trained and deemed competent in its use. Until now the preparation of ganciclovir was performed by the pharmacy’s antiblastic drugs unit. However, during closing times, kits for the self-preparation (antiblastic gloves and gowns, FFP3 masks, eye protections and brief instructions for reconstitution) were provided.
Many strategies have been deployed to reduce the risk of occupational exposure to HDs, including control devices designed to act as closed systems and preventing exposure through liquid or vapor leakage. These devices mechanically prohibit the escape of HDs from the system and can be used for preparing and administering these drugs.

What was done?

Some of the intensive care units of our hospital have been enabled to prepare their own ganciclovir bags by using a closed system drug transfer device (CSTDs).

How was it done?

Each nurse involved was instructed by hospital pharmacists on how to handle CSTDs. In addition to this they were also given a short video and an infographic showing the main operations to be carried out.
Ganciclovir bags are prepared using the Tevadaptor® (Simplivia), in a needleless technique, by combination of the Vial adaptor, the Syringe adaptor, the Spike port adaptor and a connector closed male (Spiros, ICU).

What has been achieved?

Use of CSTDs is a simple and effective way to reduce exposure to HDs, provide better protection, better aseptic technique and better containment of waste than the traditional method, as well as allows the preparation of HDs to be carried out outside the antineoplastic drug unit.

What next?

In the future their use could also be extended to the preparation of monoclonal antibodies and antibiotics considering that there is not enough definitive research on the effects of occupational exposure to these agents. And, to date, there is no known safe maximum level of exposure to these drugs.

Author(s)

Quentin Misandeau, Romain Bosc, Muriel Paul, Valérie Archer, Lionel Tortolano

Why was it done?

The plastic surgery department bought two 3D printers in order to design and create custom-made medical devices. The main objective was to decrease the delay between mandibular cancer diagnosis and the surgery. The delays of production in the medical device manufacturers may exceed 2 weeks. Those delays are considered as a lost of chance for the patients.

What was done?

We helped our surgeons to secured the production procedure and reduce the risks for patients. We create a management quality system for supply, production, sterilization and using of our homemade personalized 3D printed guides.

How was it done?

First, we created a task force of pharmacist and surgeons.
The main work was a risk analysis with the FMECA method for all the steps in the procedure (software, tools, actors and materials).

What has been achieved?

Some correctives actions were taken. The riskier points were the plastic materials toxicity risk, the sterilization procedure that has been validated and the production traceability. A biocompatibility evaluation was performed. A clinical evaluation has been initiated in the same period.

What next?

Since the new medical device regulatory (2017 /745 CE) was published in 2017, the article five, that regulate the 3D printing in hospital, changes the possibilities. In fact, as personalized 3D printed guides are available on the EU market, homemade personalized 3D printed guides for mandibular reconstruction could be not authorized anymore. The only way would be for the hospital to obtain the regulatory statut of manufacturer and comply with the essential requirements.