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Author(s)

Schoening Tilman, May Cornelia , Hoppe-Tichy Torsten

Why was it done?

Results of the wipe tests should be used to adapt the existing cleaning protocols in a way that residual contamination with cytotoxic drugs on parts of the robot, gloves and infusions bags are either reduced or avoided.

What was done?

At Heidelberg University Hospital the semi-automated device “Smartcompounder Chemo” (Smartcompounders, Enschede, NL) has been operated since 2019. We conducted three sets of wipe tests at three consecutive dates to identify contamination on parts of the robot, bags and gloves for selected drugs happening during the preparation process depending upon changes in cleaning protocols.

How was it done?

Wipe tests had been provided by Institute for Energy- and Environment Technics (IUTA, Duisburg, Germany) and analysed according to the published standards. Before and after a preparation run of gemcitabine as well as paclitaxel there had been performed two wipe tests sets of potentially exposed surfaces: Gloves after loading and unloading of the device, robot head, syringe holder, vial adapters, bag adapters, infusion bags and vials. After evaluation of the results of the first wipe test set, we adapted cleaning agent and techniques and a second set was performed.

What has been achieved?

Both wipe test sets did not show any positive results for paclitaxel. For gemcitabine residual contamination was shown on gloves after loading and unloading, syringe holder and robot head before and after preparation run, vial adapter before and after preparation and bag adapter after preparation run. The second wipe test set after adaptation of cleaning procedures showed considerably smaller numbers of positive tests and smaller amounts of gemcitabine contamination as well.

What next?

Results demonstrate that contamination patterns associated with automated preparation of cytotoxic drugs are related to the design of the device and effective cleaning procedures of the robot parts and the vials can result in lower contamination values of surfaces. Therefor it is vital to analyze the effectiveness of cleaning protocols when working with these devices and to adapt them if necessary. We were also able to demonstrate, that the final container was not relevantly affected by residual contamination during automated preparation process of Smartcompounder Chemo meaning a positive impact on staff safety.

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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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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

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)

Mathilde Roche, Annabelle Angapin, Vincent Blazy, Alexandre Hyvert, Loretta Moriconi, Matteo Federici, Bintou Diawara, Cindy Monnel, Lison Ferreol, Assia Mitha, Hail Aboudagga, Romain Desmaris

Why was it done?

Initially, robot’s operations required prescription re-transcription and chemotherapy relabelling by technicians, leading to manual data entry risks. Robots are known for high-standardised procedures, great repeatability and limited human intervention: adding bidirectional interface enabled improvement of patient safety. Moreover, it shows significant benefits during the compounding process, streamlining pharmacy workflows and ensuring full and paperless traceability.

What was done?

In 2018, our chemotherapy production unit implemented an automated anticancer drugs compounding platform, embedding two APOTECAchemo robots. This aims to meet the increasing patient-specific chemotherapy demands (78,000 preparations/year). In order to minimise human risk and optimise work efficiency, implementation of a bidirectional interface between the robots and the hospital’s Electronic Prescribing Software (EPS) was considered as mandatory, to allow exchange and clinical information retrieval.

How was it done?

In 2020, pharmacists and the IT team defined the interface specifications. Bidirectional information flow was implemented using Health Level Seven (HL7) standards. Interface between EPS and APOTECAmanager was developed and a comparative robot performance analysis was undertaken by evaluating processed drug products, compounded preparation numbers and actual average usage time per day. The staff (i.e. two technicians) remained identical. Data were retrieved from robot’s embedded statistical tool over three months, before (March-May 2020) and after interface implementation (July-September 2020).

What has been achieved?

During these six months, 13,746 preparations were compounded, with 95% infusion bags and 5% elastomeric pumps. Most of these preparations were produced in advance (administration on day+2 or day+3). After interface implementation, the average production raised by 40.5% (from 1,905 to 2,676/month). Interface implementation increased also the average robot operating hours from 3.6 hours/day/robot to 5.8 hours/day/robot (+61.1%). In total, 19 different molecules were compounded, including conventional anticancer drugs and monoclonal antibodies with the number of reconstituted drug vials increasing by 38.1% (from 625 to 863).

What next?

Interface between robots and the EPS was successfully implemented, thereby enabling improved safety and efficiency. Today, syringes and paediatric preparations are still made manually. They require visual and analytical controls to verify their conformity. Mid 2021, a third robot customized for syringes and paediatric preparations will be installed in the compounding unit, to secure these preparations in a more efficient way.

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Why was it done?

In 2017, the hospital pharmacy has started a project for automated chemotherapy preparation aimed at managing the increasing workload, while ensuring highest level of quality and healthcare workers safety. In Denmark, the authorities expect hospital pharmacy preparation to be GMP compliant. To achieve the best implementation of APOTECAchemo, go-live was preceded by thorough qualification process and followed by robot performance evaluation in a GMP-pharmacy.

What was done?

A robotic system for aseptic preparation of cytotoxic drugs was implemented in the pharmacy-based, Grade C cleanroom compliant with Good Manufacturing Practice (GMP). Specific work organisation allowed the integration of APOTECAchemo into the pharmacy workflow, thereby steadily improving the robot productivity.

How was it done?

A multidisciplinary team defined 228 User Requirements Specification (URS) addressed in the tender and associated to GMP regulations to assess that the technology complied with the intended purpose. APOTECAchemo passed through all qualification stages: design qualification (DQ), factory-acceptance testing (FAT), installation qualification (IQ), site-acceptance testing (SAT), operational qualification (OQ), performance qualification (PQ). The implementation of robot was evaluated in terms of doses prepared, active ingredients processed, and % of the total production compounded. Data were taken from the management software and examined from June 2019 to September 2020.

What has been achieved?

The qualification process was completed in 13 months (from April 2018 to May 2019). APOTECAchemo fulfilled the requirements set in accordance with GMP regulations and went live in May 2019. In the first 15 months of operation, 20,968 doses were prepared with the robot, of which 18,242 infusion bags (87%) and 2,726 elastomeric pumps (13%). The number of active ingredients processed were 21, of which five (5-fluorouracil, calciumfolinate, irinotecan, gemcitabine, carboplatin) covered 58% of the total production. Average production of the robot increased by 39%, from 963 doses/month in 2019 to 1,582 doses/month in 2020. The % of the total production operated by APOTECAchemo rose from 20.9% (2019) to 46.4% (2020).

What next?

APOTECAchemo robot was successfully implemented in a fully GMP-compliant hospital pharmacy, thereby enabling the automation of the preparation process and the reduction of the manual operations. Through the evaluation performed, the hospital pharmacy decided to install a second robotic system to further enhance the automated production.