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EVALUATION AND DECISION-MAKING RELATED TO QUALITY AND WORKLOAD ASSESSMENT OF PARENTERAL NUTRITION COMPOUNDING

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European Statement

Patient Safety and Quality Assurance

Author(s)

Jorge Esquivel Negrín, Amara Magdalena Pérez, Josephine Peña Hernández, Jenifer González Chávez, Carmen Lidia Díaz Díaz, Silvia González Suárez, Alba Domínguez Hernández, Jaime Muñoz Manrique, Esther González Carrillo, Pilar Díaz Ruiz

Why was it done?

PN is a high-risk preparation that carries a significant risk of iatrogenesis, making it essential for staff responsible for its prescription, validation, and preparation to be well-trained, and for a reliable quality assurance plan to be in place. Monthly quality indicators include errors by pharmacists during transcription to nutrition software, errors by technicians in tray preparation, and nursing errors during PN preparation. Acceptable monthly error thresholds were set at 2 for transcription, 25 for tray preparation, and 6 for sterile PN preparation. Additional activity indicators, such as the number of PN preparations per month, episode duration, and reasons for suspension, were also analyzed.

What was done?

A training program centered on audiovisual resources related to parenteral nutrition (PN) procedures was implemented in a tertiary hospital after a quality assessment within the PN department revealed a decline in certain indicators between 2020 and 2022. A shared folder with video tutorials covering various processes was made available to pharmacy staff, mainly intended for nursing staff and pharmacy technicians, who typically have high turnover rates between departments.

How was it done?

The indicators showed a steady increase in PN preparations, rising from 411±74 per month in 2020 to 475±51 in 2023, with a record of 634 preparations in March 2024. Notably, 18.1% of episodes in 2023 lasted over two weeks, partly due to the underutilization of home PN and a lack of hospital beds despite increased outpatient activity. Errors in tray preparation increased from 2020 to 2022, peaking in 2021. This coincided with high staff turnover and an increased workload. In response, the implementation of video tutorial training for rotating staff was introduced in 2022.

What has been achieved?

This initiative reduced tray preparation errors, which decreased to an average of 12±4.9 between January 2023 and March 2024.

What next?

These measures could be adapted and implemented in other departments within the pharmacy service. Regarding PN, we are now aiming to optimize the workload by promoting home PN, and implementing semi-automated systems such as barcodes and gravimetric control, which are also recommended to improve safety and traceability.

FIVE YEARS OF A BIG CONTRIBUTION FOR THE SMALLEST AMONG US – THE IMPLEMENTATION OF AN INTRAVENOUS-SERVICE ON NEONATAL INTENSIVE CARE UNITS BY THE HOSPITAL PHARMACY

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European Statement

Production and Compounding

Author(s)

Boglárka Lengyel
Nadine Haubenwalllner
Ingrid Sattlecker

Why was it done?

The global shortage of nursing staff increases the risk for medication errors due to higher workload and stress. The intravenous (I.V.)-service, launched in March 2020, alleviates nurses’ workload and minimizes application errors by standardizing concentrations and providing pharmaceutical training. Producing all infusions with producing pumps in the hospital pharmacy’s clean rooms improves microbiological quality and dosing accuracy. Standardized concentrations with defined stability and proper documentation practices ensure consistent quality.

What was done?

We implemented the production of patient-specific I.V.-infusions and total parenteral nutrition (TPN) for neonatal intensive care units (NICU) to meet the specialized needs of neonates and enhance individualized care. Additionally, pharmacy staff assembles patient infusion sets daily, focusing on Y-Site compatibility and catheter types tailored to each patient.

How was it done?

After discussing demand with physicians and nurses, data on NICU medications and dosages were systematically collected. Standard infusion concentrations were harmonized, considering fluid intake and physical-chemical stability. Protocols for automated compounding of continuous infusions and TPN were established, alongside standard operating procedures for additional volumetric preparation. I.V. compatibility of the drugs was researched, and compatibility tables were created.

What has been achieved?

The project successfully implemented individualized compounding of infusions and TPN with established standards in the hospital pharmacy’s clean rooms. Complete traceability and continuous monitoring during production ensure high product quality. The initiative enhanced interprofessional collaboration, strengthening confidence among physicians, nurses, and pharmacists and significantly reduced nurses’ workload for preparing medications, TPN, and assembling patient sets. The service currently supports five wards, producing an average of 98 infusions and TPN daily. The assembly of patient sets is provided for 44 care beds across NICU and Intermediate Care (IMC) wards, averaging 25 sets daily.

What next?

The service aims to maximize automated production by implementing new compounding pump plans, increasing output to supply more wards. Plans also include expanding the service to the Pediatric Intensive Care Unit (PICU), where both intermittent infusions and patient set assembly will be offered in addition to the existing continuous infusion supply.

3D-PRINT OF ORALLY DISINTEGRATING TABLETS – HOW TO GET STARTED

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European Statement

Production and Compounding

Author(s)

K. Koch, The Pharmacy of the capital region of Denmark, Quality, Herlev, Denmark
R. Højmark, The Pharmacy of the capital region of Denmark, non-sterile production, Herlev, Denmark
L.R. Duckert, The Pharmacy of the capital region of Denmark, non-sterile production, Herlev, Denmark
T. Schnor, The Pharmacy of the capital region of Denmark, production, Herlev, Denmark

Why was it done?

There is an interest in implementing more safe, affordable, and sustainable treatment methods for patients for whom a personalized approach is beneficial. These treatments can be expensive and associated with patient safety and compliance issues. For the pediatric population, many medications are not available in appropriate form or dose and therefore is being manipulated before administration. Extemporaneous oral solutions often have a limited shelf life and bad physical properties or undesirable excipients.
Patients with impaired renal function or need for accurate dose adjustments are also expected to benefit from 3D-printed orally disintegrating tablets (OTDs).

What was done?

The initial steps necessary before implementing 3D-printing for manufacturing personalized ODTs has been identified and completed. The clinical advantages and barriers of the personalized treatment has been discussed interdisciplinary and the new dosage form has been risk evaluated in dialogue with the competent authority. As a result, the best suited technology has been identified.

How was it done?

The European marked has been searched for technologies suitable for extemporaneous personalized production in hospital pharmacies. 3D-printed OTDs was identified as most easily implemented both concerning technology, GMP and patient acceptance.
A dialogue about risks and benefits regarding 3D-ptinted ODTs was initiated with the hospital staff. Risks identified concerned the number of drugs available for 3D-printing, the need for stability testing and resistance from authorities. Benefits like flexibility, just-in-time preparation and patient safety was identified.
A meeting was held with the competent authority, to establish the level of validation, documentation and analysis needed on the final product and starting materials.

What has been achieved?

The necessary steps to get started have been identified and completed. Risks and benefits were assessed, and the decision about implementing 3D-printed ODTs was made. An equipment that is reliable and automated has been sourced.
An API for the initial manufacture was selected, combining clinical relevance and adequate physical properties.
Ink/matrix for the 3D-printer was evaluated and found safe for medicines for children. The matrix is manufactured according to GMP.
A regulatory framework has been agreed upon with the competent authority.

What next?

Validation of the equipment and printing of the first ODTs to be used in the clinic.

VIDEO CONTENT: FEEDBACK ON THE IMPLEMENTATION AND THE MANAGEMENT OF AN AUTOMATED CYTOTOXIC PRODUCTION UNIT

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European Statement

Production and Compounding

Author(s)

M. SIEGWART, A. BENDJAMA, D. KAROUBY, T. MARTIN, L. CITTADINI, MG. MARTINS, P. COLIAT

Why was it done?

Two automated preparation robots were implemented at ICANS in a context of increased activity in oncology, the need to maintain quality assurance in the preparation process and to reduce pharmacy technician’s exposure to cytotoxic agents. Preliminary professional training is crucial to understand this new technology, master the equipment and interfaces, and adapt to the new circuit and procedures.

What was done?

This work was the development of an educational virtual tour of an automated production unit, enriched by feedback, accessible to any professional interested in implementing an automated preparation robot.

How was it done?

The project was developed in collaboration with the Grand Est regional oncology network (NEON). Scripts were written based on a plan, detailing texts and scenarios to create short videos, each addressing a different theme with a voice-over narration. A professional team from NEON shot the film and edited according to the scripts. Location scouting and filming were completed over 3 days, with voice-over recording and editing done afterward.

What has been achieved?

Six scripts were produced. The first introduces the centre, while 4 others detail the management of an automated unit, including the organization and operation of storage areas, decontamination SAS, personal SAS, and the cleanroom (functional parameters, particulate class, airflow schema, dressing and hygiene rules, microbiological controls, cleaning, and the composition of the “breakage kit”). The robots are covered in a dedicated script that discusses the context of automation, their operation, the software used, possible interfaces, preparation procedures, and cleaning. The final script reviews the entire circuit, linking each area and stage of production: pharmaceutical validation, automated production management, material and vial preparation, manufacturing, and pharmaceutical release.

What next?

The virtual tour presents the circuit and the role of each involved personnel, highlighting precautions and subtleties compared to a non-automated circuit according to the most recent french guidelines. Although the practices shown may not be applicable to all centres due to differences in production area layouts, structures, staffing, and equipment, these videos aim to clarify the functioning of an automated unit while adhering to the guidelines. This online training can promote the standardization of practices, helping professionals from other centres install production automation systems. It encourages innovation and supports pharmacists during this critical transition.

ASSESSMENT OF THE APPLICABILITY OF 3D-PRINTED MEDICINES IN A PAEDIATRIC WARD

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European Statement

Clinical Pharmacy Services

Author(s)

M.S. Nielsen, The Pharmacy of the capital region of Denmark, Clinical Pharmacy Rigshospitalet, Copenhagen, Denmark
S.L. Otnes; The Pharmacy of the capital region of Denmark, Clinical Pharmacy Rigshospitalet, Copenhagen, Denmark
M.H. Clemmensen, The Pharmacy of the capital region of Denmark, Clinical Pharmacy Rigshospitalet, Copenhagen, Denmark
L.R. Duckert, The Pharmacy of the capital region of Denmark, non-sterile production, Herlev, Denmark
T. Schnor, The Pharmacy of the capital region of Denmark, production, Herlev, Denmark

Why was it done?

Paediatric medicine has limited availability of on-label, age-appropriate formulations. Drug-related challenges encompass variability in dosing, use of tube administration, and the necessity for child-friendly approaches, including formulation issues as well as taste and acceptability of medications.

What was done?

A clinical assessment of the applicability of 3D-printed medicines from a paediatric perspective, with the limitations of the chosen technique.
The aim of this project was to identify specific areas where 3D-printed medicines provide viable solutions to the complexities surrounding paediatric drug-related challenges.

How was it done?

To minimize the need for individual medicine manipulation, we identified key challenges by reviewing the manufacturer’s API list and comparing it with nationally available compounded products. This analysis offered historical insight on the shortcomings of commercial products in addressing patient needs. Additionally, consultations were held with nurses and doctors in selected paediatric wards for further input.

What has been achieved?

Three key areas were identified where 3D-printed medicines could benefit paediatric wards:
Dosage: 3D-printed medicines enable patient-specific doses or customizable low doses, assisting dose tapering and minimizing dosing errors. However, for APIs with a wide therapeutic index, the dose should be aligned with commercially available products. Patients or APIs that frequently require dose adjustments are better suited to a mixture formulation.
Logistics: Individual packaging and room temperature storage offer advantages for travel and storage compared to liquid mixtures, which often require cold storage and are produced in larger, less flexible containers. Additionally, existing options like mixtures increases the risk of losing the entire dose supply at once.
Patient related inappropriate drug form: The 3D-printed tablets can be chewed or partially dissolved, facilitating administration for patients with swallowing difficulties. Additionally, it allows for customizable flavors, offering more flexibility than commercial products.
However, the technique does not yet address the need for medication administration via tubes, as it requires heating of the tablets, which can be hazardous when handled by untrained parents. Highlighting that 3D-printing should complement, rather than replace, existing options.

What next?

A prioritized and condensed list of APIs will be conducted based on the identified key areas and assessed by pharmacists, doctors, and nurses.
Appropriate wards will be selected for the pilot implementation of 3D-printed medicines.

COST SAVINGS ASSOCIATED WITH EMICIZUMAB REPACKAGING IN PEDIATRIC PATIENTS WITH HEMOPHILIA A

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European Statement

Production and Compounding

Author(s)

Saldaña Soria Raquel, Florit Sánchez María, Yunquera Romero Lucía, Fernández Martín Jesús, Gallego Fernández Carmen, Tortajada Goitia Begoña

Why was it done?

The aim of this protocol is to evaluate and quantify the cost saving of the optimisation of the use of emicizumab vials through repackaging into syringe under aseptic conditions.

What was done?

Emicizumab is indicated for routine prophylaxis of bleeding episodes in patients with hemophilia A. This drug has a significant economic impact, so it has been decided to initiate a protocol for the use of emicizumab in which it has been established to group patients and dispense pre-filled syringes of repackaged emicizumab for each patient, dividing the vials according to the patient’s dose in the syringes as a savings strategy.

How was it done?

Two male patients, aged 4 and 5 years, with hemophilia A, have been treated with emicizumab in our hospital from February 2022 to September 2024. A protocol was implemented consisting of dispensing repackaged pre-filled syringes of emicizumab (expiry date 7 days according to the Good Practice Guide for the preparation of medicines) to each patient, grouping the patients receiving treatment with emicizumab on the same day for dispensing and dividing the vial into syringes to adjust it to the recommended dose according to the Technical Data Sheet in a laminar flow cabinet.

What has been achieved?

This treatment would have cost 337.125,95€ from February 2022 to September 2024. However, since patients (grouped on the same day of the week) were dispensed repackaged emicizumab pre-filled syringes and emicizumab repackaging was performed under aseptic conditions, the total cost has been 168.562,98€. Therefore the cost savings would be 168.562,98€ (63.211,12 €/year).
In conclusion, this new way of working can allow us to save 63.211,12€ (43 vials of 30 mg) every year. For this reason, the repackaging could represent a significant economic saving in patients with hemophilia A, while contributing to maintaining the sustainability of the national health system.

What next?

We hope to include all patients from our hospital in the emicizumab optimization protocol to continue contributing to the sustainability of the national health system.

STOCK PRODUCTION OF INTRAVITREAL SYRINGES OF BEVACIZUMAB RANIBIZUMAB AND AFLIBERCEPT

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European Statement

Production and Compounding

Author(s)

MC. SÁNCHEZ ARGAIZ, A. TRUJILLANO RUIZ (presenting author) , M. GALLEGO GALISTEO, A. VILLA RUBIO, E. CAMPOS DÁVILA

Why was it done?

Weekly consultations are held for the administration of intravitreal injections, serving around 50 patients per week. To optimize preparation and ensure efficient use of vials, we implemented a system to repackage pre-filled syringes, taking advantage of the drugs’ physico-chemical stability for up to 28 days. This centralized process, handled by the hospital pharmacy, follows Good Manufacturing Practices (GMP) for sterile medicines, ensuring quality and efficiency.

What was done?

We established a production process to repackage intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs, specifically bevacizumab, ranibizumab, and aflibercept, for use in ophthalmic treatments such as age-related macular degeneration (AMD), retinal vein occlusion (RVO), and diabetic macular edema (DME).

How was it done?

The preparation process for intravitreal injections was reviewed to improve batch traceability. A literature review was conducted on the physicochemical and microbiological stability of bevacizumab, ranibizumab, and aflibercept. Based on the GMP risk matrix, intravitreal injections were classified as high-risk. Batch preparation protocols were developed for these three drugs, and microbiological control measures were put in place to ensure aseptic handling and product quality. All processes were validated according to regulatory standards, including environmental, instrumental, and maintenance controls.

What has been achieved?

By standardizing batch protocols for bevacizumab, ranibizumab, and aflibercept, we have significantly reduced the weekly workload and optimized the use of anti-VEGF vials. We strictly follow national guidelines for validating aseptic techniques in intravitreal preparation and have thoroughly trained our technical staff.

What next?

This practice is recommended for broader implementation in hospital settings, as it provides significant cost savings while maintaining high-quality and safe treatments for patients. Looking forward, we aim to expand this approach to include emerging therapies such as faricimab, ensuring that our repackaging protocols can adapt to new treatments as they become available, maintaining both efficiency and patient safety in line with evolving clinical practices.

IMPLEMENTATION OF CPFARMA® SOFTWARE TO OPTIMIZE THE MANAGEMENT OF MAGISTRAL FORMULATION IN A TERTIARY UNIVERSITY HOSPITAL

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European Statement

Production and Compounding

Author(s)

Castejón Grao, I; García Zafra, V; RodrÍguez Morote, M; Jiménez Pulido, IP; Andujar Mateos, A; Murcia López, AC.

Why was it done?

The pharmacist is responsible for magistral formulations in hospitals. Paper-based methods can lead to errors so the software was integrated between 07/2022-06/2023 aiming to reduce human errors,optimize preparation times,standardize procedures,improve stock management, formula traceability and enable statistical analysis capabilities of the area.

What was done?

CPFarma® software was implemented to control the programming, preparation, validation, and dispensing of magistral formulas. It facilitated proper management of the processes involved in galenic preparations at a tertiary-level university hospital.

How was it done?

The implementation of CPFarma® software involved the following stages:
1. Creation of user accounts and permissions.
2. Introduction of active pharmaceutical ingredients and raw materials, including batch and expiry details.
3. Inclusion of packaging materials,tools and required clothing for each preparation.
4. Transfer of Standard Operating Procedures(SOPs) in three phases:
4.1. Integration of the original SOP for each formula.
4.2. Revision and validation of SOPs and associated calculations.
4.3. Determination of active and passive SOPs.
5. Association of patient information sheets.
6. Drafting of a programme use protocol.
7. Training personnel on software use.
8. Validation in daily practice situations.

What has been achieved?

Until August 31, 2024, 249 SOPs (averaging 85 monthly) have been incorporated into the database, 74,7%(186) active and 25,3%(63) passive status, standardizing procedures. The system also includes 67 primary packaging materials and 275 components (185 active ingredients,16 base formulations and 74 excipients), improving stock control.
A total of 1279 magistral formulas have been prepared and validated by a pharmacist:54%(693) for usual stock,40%(510) for specific patients and 6%(76) with no record available. Each formula includes a preparation guide that includes detailed records to ensure traceability, such as patient information,prescriber details and preparation order number. There is also a computerized recipe book with histories filterable for statistical analysis.
No human errors have been detected in the preparation since the program’s implementation, and the patient information sheet helps prevent medication errors.

What next?

Efforts are being made to improve the system by adding features like a barcode reader for batch entry and registering personnel that dispense and collect medication. CPFarma® has optimized magistral formulation management, so Pharmacy Services without specialized software could benefit to improve their practices through its implementation.

COMPOUNDING OF A VISCOUS ORAL, PRESERVATIVE- AND FLAVOUR-FREE GEL FOR TREATING PAIN IN AN INFANT WITH EPIDERMOLYSIS BULLOSA

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European Statement

Production and Compounding

Author(s)

G. Penocchio, F. Bertola, F. Bozza, F. Caravaggio, M. Ferrighi, M.P. Ghilardi, A. Pozzi, G. Trainini, C. Galloni, T.E. Testa.

Why was it done?

Epidermolysis bullosa (EB) comprises a group of rare disorders with multisystem effects. In the postnatal period, a 37-week -old infant presented with dysepithelialized lesions on the body, as well as involvement of the oral cavity, characterized by discoloration of the hard palate and gums. The multidisciplinary team diagnosed EB and deemed it necessary to apply lidocaine gel because the infant was unable to feed due to pain from the sores. Initially, several commercially available products were used, but their irritating excipients led to poor tolerance. Consequently, it was necessary to prepare an extemporaneous formulation devoid of preservatives and flavorings.

What was done?

This intervention presents the development of an extemporaneous preparation of lidocaine hydrochloride 0.5% w/w viscous oral topical gel, free of preservatives and flavors. The gel was distributed to the neonatal intensive care unit staff in pre-filled syringes and applied to the oropharyngeal mucosa of a neonate diagnosed with EB.

How was it done?

The components of the preparation included lidocaine hydrochloride, carboxymethylcellulose sodium (CMC), and sterile water. CMC was chosen for its hydrophilic properties and excellent gelling capabilities. The gel was prepared using a high-shear magnetic stirrer, with increasing concentrations of CMC (0.75%, 2.25%, 3%, and 4%). After discussions with the multidisciplinary team, the pharmacist recommended using the 4% gel, as its density allowed it to adhere well to the oropharyngeal mucosa. This adherence is crucial for preventing absorption and minimizing potential cardiac side effects of lidocaine.

What has been achieved?

The gel was successfully prepared with 0.5% lidocaine and 4% CMC, and packaged in pre-filled syringes with the daily dosage. Due to the absence of preservatives and stability data, the shelf life was established at 15 days when stored at 2-8°C. The viscous oral gel was administered three times a day, 20 minutes before feeding, to exert its anesthetic effect and facilitate breastfeeding.

What next?

The hospital pharmacist’s extensive expertise was instrumental in determining the optimal concentration of CMC and customizing the formulation to meet the patient’s unique requirements. This pivotal contribution led to a highly personalized therapy, ultimately resulting in the successful discontinuation of artificial nutrition in this critically ill patient.”

CIRCUIT FOR THE PREPARATION, CONTROL, AND DISPENSATION OF AUTOLOGOUS SERUM EYE DROPS IN A PHARMACY SERVICE

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European Statement

Production and Compounding

Author(s)

Eva Gómez-Costa; María Begoña Feal-Cortizas; María Mateos-Salvador; Sandra Rotea-Salvo; Andrea Luaces-Rodríguez; Laura Caeiro-Martínez; Clara Fernández-Diz; Andrés Torres-Pérez; Luis Margusino-Framiñán; María Isabel Martín-Herranz

Why was it done?

Implement a circuit for the preparation, microbiological control, analytical control of patients, and dispensation of autologous serum eye drops in the Pharmacy Service (PS) of a tertiary-level hospital.

What was done?

Autologous serum eye drops are classified as a special medication that must be prepared in authorized centers with an up-to-date patient registry. This initiative aims to ensure the safe use of autologous serum eye drops, guaranteeing quality and safety in their preparation and administration.

How was it done?

The circuit was established in the PS in 2015. After prescription by the Ophthalmology Service, pharmaceutical validation confirms that the treatment is optimal and complies with regulatory requirements. Blood samples are collected from patients under controlled conditions, and the serum is prepared in a vertical laminar flow hood. Once prepared, the eye drops are stored frozen in the PS until dispensation to the patient. The pharmacist reviews the microbiological control of each batch and the patient’s serological results. When collecting the eye drops, the pharmacist records batch traceability and provides the patient with necessary information on storage and administration.

What has been achieved?

Between January and August 2024, 294 patients were treated, with 477 blood extractions performed and a 11,925 eye drops prepared. Autologous serum concentration: 20%(76.9%), 30%(11.5%), 50%(11.2%), and 100%(0.4%). Microbiological control of the eye drops: 98.1% negative and 1.9% false positives, confirmed by a second negative control. Infectious diseases were detected in the serology of 3 patients: hepatitis C(1), hepatitis B(1) and syphilis(1). These data reflect a high success rate in the preparation and quality control, as well as the effectiveness of the implemented circuit. Additionally, the system has allowed for the early detection of viral infections, reinforcing treatment safety.

What next?

The implementation of this circuit has proven effective in ensuring the safety and efficacy of autologous serum eye drops, providing rigorous control over treatments and the quality of dispensed products. Future steps will involve pharmacists requesting serological tests and developing protocols for managing patients with identified infections. Furthermore, patient surveys will evaluate treatment effectiveness and overall patient experience.

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