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Author(s)

Teimori Kaveh, Lunnan Asbjørn , Komnenic Aleksandar, Gleditsch Espen, Duedahl Hende Camilla

Why was it done?

Oslo Hospital Pharmacy is working to standardize and automate 10% of Oslo University Hospital’s annual consumption of two million parenteral medication doses. They aim to provide 200,000 ready-to-administer doses to OUS, starting with a trial in 2025 and scaling up to 200,000 doses by 2028. This initiative addresses efficiency, reduces nurse workload, and minimizes medication errors, addressing healthcare workforce challenges and ensuring timely and accurate medication delivery at Oslo University Hospital.

What was done?

Drugs were selected for inclusion in implementation of automated preparation of ready-to-use syringes and bags.

How was it done?

Oslo Hospital Pharmacy is dedicated to providing market-competitive ready-to-administer medications through a flexible selection process. This process involved a thorough analysis of parenteral medication usage in five reference care units over eight months. We compared consumption in these units (69 beds) to the entire hospital (2,031 beds) to align with Oslo University Hospital’s needs. Collaborations with international partners in the Netherlands and Denmark confirmed shared priorities, especially in ready-to-administer antibiotics, validating their meticulous selection process. Oslo Hospital Pharmacy’s strategy underscores their commitment to addressing healthcare challenges effectively with global validation.

What has been achieved?

The following 12 medications were selected for the initiative: Piperacillin/tazobactam 4g, Ampicillin 2g, Vancomycin 1g, Vancomycin 0.5g, Cefotaxim 2g, Cloxacillin 2g, Cefazolin 2g, Propofol 10 mg/ml, Fentanyl 50 microg/ml, Ketamin 10 mg/ml, Benzylpenicillin 3g and Benzylpenicillin 1.2g.
Results showed that the reference care units consumed 14 ampoules or vials per bed, while Oslo University Hospital consumed 80, suggesting a representative and potentially even larger demand across the hospital.

What next?

The established drug selection procedure offers an organized method for incorporating new medications. This well-defined medication list facilitates the selection of the most appropriate automation system for implementation. Considering the prevalent staff and medication shortages on a global scale, many institutions are increasingly considering the adoption of automation in their drug preparation departments. We aspire that our method can offer valuable assistance in their pursuit.

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Author(s)

Bojan Žagar, Matej Vehovc, Mateja Tršan, Blaž Vehar

Why was it done?

Cefazolin injection 100 mg/mL is a sterile pharmaceutical formulation comprising cefazolin sodium and water for injections. Traditionally, cefazolin injections were prepared on hospital wards by reconstituting cefazolin sodium powder for injections with water for injections and subsequent dilution before intravenous administration.

What was done?

Establish a semi-automatic aseptic preparation process, ensure the production of final products that meet quality standards, develop analytical methodologies for in-process and final product quality control, ensure the reliability and validity of test results, and conduct a stability study to confirm long-term storage.

How was it done?

Product materials include: Pharmacy Bulk Package of Cefazolin for Injection, USP, water for injections, Luer Lock 20 mL sterile polypropylene syringes, steribags. Product is prepared with aseptic technique within a laminar flow unit situated in a pharmaceutical cleanroom. Bulk package is connected to a dispensing device, followed by reconstitution with water for injections. In-process samples are collected and volume-adjusted based on density. Following the preparation and dispensing, syringes undergo labeling and packaging into steribags. They are then promptly stored at -30°C within 4 hours. Final product samples are obtained and analysed (pH value, cefazolin content, endotoxins, sterility) prior to product release.

What has been achieved?

Preparation of cefazolin sodium injections in a controlled, aseptic environment utilizing pre-prepared bags containing the appropriate cefazolin concentration (100 mg/mL) has successfully addressed critical concerns surrounding the safety, efficacy, and quality of these pharmaceuticals when administered on hospital wards. Challenges related to stability and shelf life are being addressed with the storage approach at -30°C within the pharmacy, followed by a carefully monitored transition to ward storage at 5°C for up to 28 days, and subsequent patient administration at room temperature within 2 days.

What next?

This approach not only streamlines the process but also safeguards the well-being of patients, marking a significant advancement in pharmaceutical preparation within our healthcare setting. We are conducting an ICH-compliant stability study with the objective of establishing a combined shelf life of 90 days at -30°C, followed by 28 days at 5°C, and an additional 2 days at room temperature.

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Author(s)

Clara Estaún-Martínez, Catalina Perelló-Alomar, Ángela Bueno, Naiara Tellería, Olga Delgado-Sánchez

Why was it done?

Automated compounding emerges as an alternative for manual compounding, making possible the centralisation of standardised compounded medications in hospital pharmacy aseptic services at a larger scale. This provides sterile, high-quality, safe, traceable ready to administer products to clinical units. Additionally, it could free up nursing time for patient care instead of performing pharmaceutical work.

What was done?

We evaluated productivity, dose accuracy and environmental monitoring of KIRO Fill®, a robotic compounding system (RCS). We also assessed the microbiological results of the sterility tests performed.

How was it done?

We implemented a RCS equipped with ISO 5 aseptic environment, horizontal airflow with HEPA filters and continuous monitoring of: air flow operation, non-viable particle counts (limits for ISO Class 5 are 0.5μm and larger size: not more than 3.520 particles/m3, and 5μm and larger size: not more than 20 particles/m3) and temperature (not more than 25°C). Two automated units work in parallel handling transfer syringes to withdraw solutions from source containers (SC) and fill final containers (syringes or infusion bags) via Luer Lock connections. This technology allows barcode/data matrix verification of source and final containers used and RFID for in-process tracking. An integrated scale is responsible for gravimetric control of the compounded preparations within an acceptable ± 5% error range. Gri-Fill® filling system was used for the preparation of SC.
Drug verification was assured through drug workflow management system and datamatrix verification in RCS.
We performed sterility test of all batches and physicochemical stability studies were developed when not available in the literature.

What has been achieved?

Between January 2022 and September 2022, we have prepared with RCS 2.813 syringes of norepinephrine (base) 0,2 mg/ml in normal saline for critical care unit syringe pumps and 395 morphine hydrochloride 1mg/ml normal saline 250 ml infusion bags for patient-controlled analgesia (PCA) administered in the surgical area.
The average dose accuracy errors for syringes and infusion bags were 0.23% and –0.09%, respectively. Environmental monitoring results and temperature controls met our standards at all times.
Results from sterility tests demonstrated the absence of microbial growth in all tested preparations

What next?

Overall satisfactory results when compounding sterile preparations using KIRO Fill and the positive feedback received from nurses in clinical units, have led us to incorporate new batches, such as morphine syringes for critical care unit syringe pumps, to the production with the RCS. Stability studies are currently being performed for this purpose.

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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)

Alessandro D’Arpino, Fiorenza Enrico, Caterina Donati, Simone Leoni, Giorgia Longobardo, Marco Bellero, Alessandra Bianco, Giuseppe Zacchi, Anna Zaltieri, Stefano Monica, Nicolò Squartini, Matteo Federici

Why was it done?

In most of Italian healthcare organizations, the large majority of non-cytotoxic IV medications are prepared in clinical environment by nursing staff. This is recognized as a complex and labour-intensive process that entails various risks of potential medication errors (microbial contamination, wrong reconstitution/dosing). Centralizing the preparation from the clinical environment to the pharmacy in order to provide ready-to-administer IV medications represents a strategy to improve safety and prevent medication errors.

What was done?

The community of APOTECA technology users is committed to fostering co-de¬sign of technology based on the hospitals’ needs and sharing best practices for improving hospital pharmacy services. During a meeting taken place in September 2021, a panel of hospital pharmacists belonging to APOTECA community laid the groundwork for centralized preparation of non-cytotoxic intravenous (IV) drugs and establishment of Central Intravenous Additive Service (CIVAS) in Italian hospital pharmacies.

How was it done?

The following methodology was adopted to promote a standard profile of centralization: (1) definition of criteria for the selection of drugs suitable for centralized preparation, (2) identification of IV medication classes for which preparation should be centralized due to intrinsic risks and demand, (3) evaluation of potential benefits, (4) discussion on organizational challenges regarding the establishment of CIVAS, (5) assessment of the role of automated preparation with robotics.

What has been achieved?

Five selection criteria to centralize drugs were mentioned: long-term stability data, frequency of use, cost, complexity of preparation, microbial contamination risk. Continuous infusion of antibiotics, vasoactive drugs, anaesthetics, pain medications, intravitreal injections, and patient-individual doses for paediatric patients were chosen as eligible IV medication classes to implement centralized preparation. Major benefits of centralization were pointed out, i.e. proper aseptic preparation, perspective quality controls, process traceability, reduced drug wastage, and releasing nursing time to care. Logistics, inventory management, limited space, and inadequate quality control units were identified as main challenges to the CIVAS establishment. Participants agreed that robotics plays an important role to minimize repetitive manual activities, optimize working efficiency, and increase pharmacy production capacity, thereby streamlining the introduction of CIVAS.

What next?

A close collaboration between healthcare staff and hospital pharmacy will be essential to evaluate the feasibility of centralized preparation as well as its clinical and cost-effectiveness.

Author(s)

Lidia Ybañez, Virginia Puebla , Cristina Gonzalez, María Molinero, Estefanía Rosón, Gonzalo Hernando, Natalia Sanchez-Ocaña, María De la Torre, Javier Corazón, Jose Manuel Martinez-Sesmero

Why was it done?

In 2020, Compounding laboratory’s activity increased as a result of COVID-19 pandemic. In order to achieve new needs and requirements, we decided to introduce a mixing and emulsifying robot. Improvement in productivity would also allow us to elaborate formulas that were previously outsourced (such as selective digestive decontamination (SDD) solution and oropharyngeal paste), thus saving money. The effectiveness of this measures was evaluated from April 2020 to April 2021.

What was done?

An emulsifying-mixing device for non-sterile oral and topical formulation was introduced at the pharmacy’s compounding laboratory. A reorganization of laboratory workflows was implemented to ensure an optimal use of the device.

How was it done?

We performed a needs assesments plan to determine what needs to be accomplished to reach our project goals (Good Manufacturing Practices (GMP) compliant. Formulas suitable to be compounded in the robot were selected. A reorganization of the daily practice was performed to achieve an optimal workflow.

What has been achieved?

Seven product formulations and 3 excipient formulations were suitable for being produced by robot (SDD solution and oropharyngeal paste being two of them, (11536 single dose packages of SDD solution and 5977 of oropharyngeal paste have been prepared throughout the year ).
37202€ have been saved by producing the SDD solution and paste instead of outsourcing its production. The investment required to purchase and operate the robot was approximately 2600 euros.

What next?

Compounding automation improves efficiency and productivity (as we have been able to produce formulas that were previously outsourced), saving costs. Robot has been successfully incorporated into daily practice in a Hospital Pharmacy compounding laboratory. Its implementation has allowed the optimization of available resources (especially during the pandemic) and significant financial savings for the Hospital.
By implementing this device, other hospitals will be able to improve their production processes for non-sterile medicines in compliance with GMP.

Author(s)

CARMEN MARÍA VALENCIA SOTO , ADELA GARCÍA-AVELLO FERNÁNDEZ-CUETO, SARA BARBADILLO VILLANUEVA, MARÍA OCHAGAVÍA SUFRATEGUI, MARÍA VICTORIA VILLACAÑAS PALOMARES, VIRGINIA MARTÍNEZ CALLEJO , MARÍA MARTÍN LÓPEZ, MARÍA RIOJA CARRERA, PAULA DEL RIO ORTEGA, MARTA VALERO DOMÍNGUEZ

Why was it done?

This project aimed to optimize security in the production workflow through automation of anti-cancer drugs compounding.
The use of recognition systems and gravimetric control guarantee traceability and accuracy in the compounding process, therefore improving patient safety.
Robotic systems avoid exposure to cytotoxic drugs, promoting healthcare operator safety. Moreover, once loaded, it runs automatically, liberating the operator for more complex preparations.

What was done?

In 2021, our hospital pharmacy implemented APOTECA platform, including management software (APOTECAmanager), two guided preparation systems for semiautomatic compounding (APOTECAps) and a robotic system for aseptic preparation of antineoplastic drugs (APOTECAchemo).

How was it done?

We configured each drug in the management software: dimensions, density, stability and expiration data, solvent, bags and transfer set information, QR code, etc.
A 3-phases process was scheduled:
– Integration between APOTECA and the hospital’s Electronic Prescribing Software (EPS). Carried out between November and December 2020.
– Training period: 8 weeks between May and July 2021, including pharmacists and technicians with progressively incorporation to real compounding.
– Real production analysis: 8 weeks between July-September 2021 (38 days, excluding weekends and bank holidays). Previously trained staff gradually trained the rest of the personnel.

What has been achieved?

During the 8 weeks considered, 4629 doses were elaborated, excluding clinical trials preparations.
APOTECA production supposed 85% (3944) of our daily compounding: 62,8% (2475) with the 2 semiautomatic systems and 37,2% (1469) with the robot. 99% of the doses prepared in APOTECAchemo were infusion bags and 1% syringes. In APOTECAps, 85% were infusion bags and 15% syringes.
Average dosage error for all preparations was 0,95% (±1,13) for APOTECAchemo and 1,57% (±1,31) for APOTECAps.
Up to data collection, 67 substances that fulfilled the criteria had been processed in APOTECA system and 41 of these in APOTECAchemo.
The top five ingredients compounded in APOTECA were: paclitaxel, carboplatin, pembrolizumab, etoposide and fuorouracil.

What next?

The implementation of this technology has improved patient and operator safety, as well as our daily workflow.
To ensure an optimal use we need to increase robot production by optimizing its operating hours and promoting more preparations in advance.

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Author(s)

FRANCESCA VAGNONI, ANDREA MARINOZZI, SABRINA GUGLIELMI, CHIARA CAPONE, FRANCESCA MURA, ADRIANA POMPILIO, SIMONE LEONI

Why was it done?

The management of CT requires thorough documentary evidence and well-organized reporting system in compliance with the Good Clinical Practice. Since 2009, the entire onco-haematology workflow is fully-controlled by information technology devices and robotic systems to prevent medication errors and guarantee data integrity. The implementation of APOTECAtrial was aimed to extend the same level of control to CTs.

What was done?

In 2018, a clinical trial (CT) managing system (APOTECAtrial) was integrated into the existing fully-automated workflow of the chemotherapy production unit. APOTECAtrial was developed to enable real-time visualization of CT-related data and trace the processing of investigational (IMP) and non-investigational (NIMP) medical products, such as delivery, assignment, preparation, return, and disposal.

How was it done?

A team of hospital pharmacists, physicians, clinical data managers, and IT specialists analysed the CT workflow and defined the system specifications. Data related to IMP/NIMPs (both for parenteral and oral administration), patients enrolled, and investigator/sponsor affiliations were entered into APOTECAtrial and sorted by CT. The onco-haematology unit’s electronic prescribing system was bidirectionally interfaced with APOTECAtrial. Aseptic preparation of patient-specific injectable therapies was implemented in the supporting device for manual preparation that checks dosage accuracy and identity by photographic and barcode recognition.

What has been achieved?

Since 2018, the overall number of CTs managed was 95. In total, 81 IMPs/NIMPs and 135 patients were entered into the system, while 2740 injectable therapies were prepared, 690 oral medications and 60 pre-filled syringes delivered. The following major objectives were achieved: automated inventory accounting and stock management, reduced manual time-consuming activities (i.e. documentation, transcription), standardized reports in digital not-editable format, and full traceability. In addition, audit trail tool tracks all user edits and changes performed at any stages of the CT management by electronically recording user’s name, date, and time. APOTECAtrial was evaluated by clinical research associates (CRA), clinical research organizations (CRO) and CT sponsors and approved for use in the daily clinical practice.

What next?

The project represents a good example of multidisciplinary collaboration focused on improving the quality of the processes in healthcare settings. The implementation of information technology and automation ensures improved data integrity, safety, and working efficiency, which are key determinants for managing CTs in hospital pharmacies.

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Author(s)

Jemos Costantino, Martina Milani, Mariantonietta Piccoli, Mara Provenzi, Paola Paochi, Ilaria Clerici, Cinzia Lucia Ursini, Claudio Colosio, Fabrizio Mastrilli, Emanuela Omodeo Salè

Why was it done?

In outpatient setting, WT between medical visits and administration is strongly conditioned by time needed for preparation. We needed to reduce our WT caused by the use of an automated system by ensuring the same standards of quality control checks and traceability, not achievable with manual preparation.

What was done?

We introduced an assisted system for chemotherapy preparation, with a gravimetric and barcode verification. We started to switch part of preparations previously prepared by an automated system to this assisted system. We performed an analysis to measure the impact of a different strategy in preparing chemotherapy on patients WT.

How was it done?

Time needed for preparation was monitored in the first trimester of 2016, where drugs were prepared using an automated system or manually, and compared to the first trimester in 2017, when we introduced the assisted system.
In the first period we used a “WT optimization” criteria in selecting the preparing technology, while in the second period we decide to use a “risk based” criteria.
Risk based criteria consists of selecting the automated system for cytotoxics, assisted system for antibodies and low risk drugs and manual procedure when no other options are available.
In order to evaluate bias introduced by the risk based selection of different drugs, we performed a contest comparing preparation times of a defined sequence of representative preparations typologies. Three technicians are involved in order to reduce human factor impact.

What has been achieved?

Average WT (AWT) in the first period was 1h36m and median WT (MWT) was 1h22m (sample = 2365 preparations in 3 months). AWT in the second period (sample = 3437 preparations in 3 months) was 1h17m (-19,79%) and MWT 1h1m (-25,61%). The percentage of therapies dispensed after 2 hours waiting decreased by 55,69%. WT was stratified by preparation technology (assisted system: AWT =50m; MWT=44m – automated system: AWT=1h26m; MWT=1h07m).
The contest results were (average of three series) : manual preparation 15m19s; assisted 26m42s; automated 1h14m3s.

What next?

Assisted systems are able to guarantee quality standards for patients similar to automated ones, but with an important reduction in WT when compared with an automated one and an improvement in traceability compared to the manual procedure.