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ENHANCING SAFETY IN CYTOTOXIC DRUG PREPARATION THROUGH SIMULATION-BASED TRAINING

European Statement

Production and Compounding

Author(s)

Bennani I.,Cherif Chefchaouni A.,Alaoui S., Hajjaj S., El Deeb S., Boufaress S., Hafidi Y., El Merrakchi S., Moukafih B., Bandadi F., El Kartouti A.

Why was it done?

A structured training programme was established to improve cytotoxic drug preparation in our hospital pharmacy. The initiative combined updated Standard Operating Procedures (SOPs), simulation sessions using non-hazardous substitutes, and debriefings focused on error prevention and occupational safety.

What was done?

Cytotoxic preparation carries significant risks: dosage errors compromise patient safety, while inadequate protective measures expose staff to hazardous drugs. Audits in our unit revealed inconsistent practices and insufficient adherence to safety protocols. A reproducible, safe method of training was needed to harmonise techniques and reduce risks.

How was it done?

The initiative was implemented through a structured program combining simulation sessions, observation checklists, and debriefing meetings. Teams were trained using standardized SOPs and dummy materials, allowing safe practice of aseptic techniques. Performance indicators were measured before and after simulation training to assess impact on safety and compliance.

What has been achieved?

More than 60 pharmacists and technicians have completed the programme. Error rates in cytotoxic preparations decreased by about 30%, and environmental monitoring showed a 25% reduction in contamination markers. Surveys confirmed improved confidence (92%) and adherence to protective measures (95%). The training is now part of our hospital’s continuous education system.

What next?

The programme will be extended to all new pharmacy staff and residents. Plans include developing e-learning modules and inter-hospital workshops to spread the model nationally and internationally.

IMPLEMENTATION OF GRAVIMETRIC AND VOLUMETRIC CONTROL AFTER THE PREPARATION OF PAEDIATRIC PARENTERAL NUTRITION

European Statement

Production and Compounding

Author(s)

Esperanza Nieto Mártil
Alicia Abril Cabero
José Antonio Hernández Ramos
Isabel García López
Belén Riva de la Hoz
Esther Algarra Sánchez
Luis Fernández Romero
Marta Echávarri de Miguel
Beatriz Leal Pino
Alejandra Merino Pardo
Maite Pozas del Río

Why was it done?

Paediatric PN requires highly precise and methodical preparation due to its narrow safety margins. For this population very small volumes are handled, thus small deviations in added volumes might have a substantial impact, including clinically significant consequences.
Although gravimetric and volumetric control has shown to provide a rapid and cost-saving tool to detect discrepancies, there are no specific publications evaluating its optimality in the context of paediatric PN. Therefore, its assessment in a paediatric setting is essential to ensure the quality of the compounding process.

What was done?

To analyze the results of gravimetric and volumetric control applied to parenteral nutrition (PN) preparations compounded by the Pharmacy Department in a Paediatric Hospital over a two-month period.

How was it done?

A prospective interventional study was conducted including all PN preparations compounded between June and July 2025 in a tertiary paediatric hospital. In order to perform gravimetric control, actual weight of each PN and deviation from theoretical weight were measured. For volumetric control, prescribed volumes of each component were compared with the actual volumes added by compounders to verify concordance between both records. Additionally, the following variables were collected for every preparation: responsible compounder and the need for re-compounding. Erroneous preparations were defined as exceeding an acceptance limit of ±5% for gravimetric control or proven discrepancies for volumetric control.

What has been achieved?

A total of 135 PN preparations were compounded during the study period. Six preparations (4.44%) produced by three different compounders were classified as erroneous. Of these, five (3.70%) were associated to gravimetric control and one (0.74%) to volumetric control. All the preparations failing gravimetric control were re-compounded and their deviation range was 5.32% to 18.2%, with a median of 6.95%. The remaining erroneous preparation was found to lack 10 mL of a 10% amino acid solution, re-compounding was not required since it was considered clinically irrelevant though.

What next?

The incorporation of gravimetric and volumetric control into routine practice would gather strength as an essential safety measure in the preparation of pediatric PN due to its feasibility and utility, specially for gravimetry. Future lines of research should focus on continuous monitoring of outcomes, including comparisons with other hospitals.

STABILITY STUDY OF CONCENTRATED AMOXICILLIN IN RINGER’S LACTATE SOLUTION: AN ALTERNATIVE TO NACL 0.9% TO REDUCE THE RISK OF CRYSTALLURIA?

European Statement

Production and Compounding

Author(s)

K. Lefèvre (1), Vincent Dubée (2,4), Vincent Lebreton (1,3)
(1) Angers University hospital center, Pharmacy Department, Angers, France
(2) Angers University hospital center, Infectious diseases Department, Angers, France
(3) MINT Inserm 1066, CNRS 6021, University of Angers, France
(4) INCIT-Atomyca, UMR 1302/ERL 6001, University of Angers, France

Why was it done?

Amoxicillin (AMX) is a widely used antibiotic, particularly for severe infections requiring high-dose intravenous administration. The two commonly used solvent are 0.9% NaCl (NaCl) and Ringer’s lactate (RL). NaCl may have been associated with cases of crystalluria following hyperchloremic acidosis, leading to impaired renal function. So RL may be considered as a promising alternative, although stability data are lacking.

What was done?

This study aimed to evaluate and compare the stability of AMX in both solvents at different concentrations for 12h at room temperature.

How was it done?

To evaluate AMX stability, injectable AMX was reconstituted according to the product’s specification and diluted in RL or NaCl. Four concentration levels were prepared (10, 12, 15, 20 mg/mL), stored in a climate-controlled chamber (25±2°C; 65± 5%RH) and analysed at various time intervals (0, 3, 6, 9, 12 hours). The study was conducted with a stability indicating method using reverse-phase high-performance liquid chromatography coupled with diode array UV (250 nm) and mass spectrometry detection. The method validation followed ICH guidelines (Q2R2, Q6A, Q3B). Organoleptic characteristics and pH were also monitored.

What has been achieved?

AMX concentrations remained above 90% of the initial value throughout the 12-hours period, regardless of solvent or concentration. However, the chromatograms reveal additional peaks suggesting the formation of degradation products in both NaCl and RL. These degradation products were quantified (maximum% of main peak surface area) and identified [letter corresponding to European Pharmacopeia identification] as penicilloic acid (4.5) [D], phenylpyrazine (1.3) [F], diketopiperazine (1.8) [C], amoxicillin dimers (6.5) [J] and and adduct species of them (Na+ and K+) (0.5). Despite these findings, there were no notable changes in the appearance or color of the solutions, and pH remained relatively stable, decreasing slightly from 8.8 to 8.6.

What next?

The study concluded that while AMX concentrations stayed relatively stable, some of the identified degradation products exceed limits set by ICH Q3B guidelines and European Pharmacopeia for degradations products in both solvents. Therefore, the results should be interpreted cautiously, pending further toxicological and regulatory assessments. If the degradations products are deemed acceptable, Ringer’s lactate could be a clinically viable alternative to NaCl, especially for high-dose AMX infusions, due to its lower sodium content and buffering effect, which helps reduce the risk of metabolic acidosis.

DEVELOPMENT OF AN INTERNAL GUIDELINE TO IDENTIFY THE ORIGIN OF LACTOSE EXCIPIENTS AND IMPROVE SAFETY IN PATIENTS WITH COW’S MILK PROTEIN ALLERGY

European Statement

Patient Safety and Quality Assurance

Author(s)

M. Echávarri de Miguel, C. Varela Guisasola, A. Sánchez Alonso, A. Abril Cabero, E. Nieto Martil, A. Merino Pardo, E. Algarra Sánchez, B. Riva de la Hoz, B. Márquez Arce, B. Leal Pino, M. Pozas del Río

Why was it done?

Lactose used as a pharmaceutical excipient is generally obtained from skimmed milk and purified to remove milk proteins. Pharmacopoeias specify that lactose must be free from protein contaminants; hence, it has been considered safe for patients with cow’s milk protein allergy (CMPA). However, in severe allergies, medicines containing natural lactose should be avoided due to the potential risk of protein contamination. Although rare, cases of anaphylaxis from contaminant milk proteins have been reported, particularly with dry-powder inhalers, injectables, and vaccines.
This initiative arose after a suspected allergic reaction in a patient with severe CMPA following administration of an injectable containing lactose as an excipient. Given limited evidence and lack of transparency about lactose origin, an internal guideline was developed to enhance patient safety.

What was done?

An internal hospital guideline was developed and implemented to verify the origin—natural or synthetic—of lactose used as an excipient in medicines. The guideline was created through systematic screening assisted by artificial intelligence, followed by verification with manufacturers.

How was it done?

With ChatGPT support, a Python-based code was created to analyze 3,278 pharmaceutical specialties for the presence of lactose. Manual validation of 360 medicines (95% confidence level, ±5% margin of error) confirmed the method’s reliability. The most dispensed medicines and all intravenous formulations, vaccines, and inhalers were reviewed due to higher risk described in literature. Manufacturers were contacted to determine whether lactose was natural or synthetic. Main challenges included delayed responses and limited data due to confidentiality.

What has been achieved?

Of the 3,278 medicines analyzed, 350 contained lactose or mentioned it in their product information, 1,522 did not, and 1,406 were inactive codes. Lactose origin was investigated for 152 products from 58 manufacturers, with responses in 92 cases (60.5%). Only five (5.4%) contained synthetic lactose. High-risk medicines included one inhaler and eight injectables (two vaccines) with natural lactose. Manual validation showed 100% concordance with automated results.

What next?

Next steps include expanding data to over 350 confirmed medicines, publishing results for open access, and developing an app for healthcare professionals. Integration into prescribing and dispensing systems is planned to generate automatic alerts for patients with severe CMPA.

INFLUENCE OF PACKAGING ON STABILITY: EXAMPLE OF 5% LUGOL’S SOLUTION

European Statement

Production and Compounding

Author(s)

K. Lefèvre (1), M. Ramond (1), A. Bourges (1), E. Gueret (1), S. Vrignaud (1), V. Lebreton (1,2)
(1) Angers University hospital center, Pharmacy Department, Angers, France
(2) MINT Inserm 1066, CNRS 6021, University of Angers, France

Why was it done?

Lugol’s solution 5% (iodine/iodide) is used to saturate the thyroid before MIBG scintigraphy. Due to iodine’s high volatility, the stability of the solution depends heavily on its packaging. Random shelf life quality controls revealed out-of-specification iodine levels, raising concerns about iodine loss linked to poor packaging.

What was done?

This study aimed to evaluate iodine loss over time from 5% Lugol’s solution depending on the type of packaging, before opening, in order to propose improvements ensuring better stability.

How was it done?

Three packaging types were tested: Type I amber glass bottle with dropper and no secondary packaging, the same bottle with a cardboard secondary packaging and the same glass bottle with a white Bakelite screw cap and secondary cardboard packaging.
Iodine content was measured weekly in triplicate for at least three months using an automatic titrator (Mettler Toledo T5) with a redox electrode and 0.1M sodium thiosulfate titrant. Previously method was validated according ICH guidelines (ICH Q2A). Parameters such as accuracy, precision, linearity and LOQ were evaluated. Iodine loss was calculated and modeled over time (mean ± 95% confidence interval) with following equation A=Aoe-kt (k and t expressed in Day (D).

What has been achieved?

After 9 weeks, iodine losses reached 28.5 ± 0.8% (with secondary packaging) and 58.9 ± 0.3% (without), even before opening, for the dropper bottles. The iodine concentration followed a first-order kinetic degradation for all packaging, k = -0.01D-1 for both with dropper and k=0.004 D-1 with bakelite cap. The Lugol’s solution no longer met specifications after just 1 month. In contrast, bottles with Bakelite caps remained stable for up to 6 months, with less than 2% iodine loss.

What next?

Packaging has a critical impact on the stability of 5% Lugol’s solution. To improve preservation, several changes were implemented: bottles are now closed wtih Bakelite caps, and droppers are supplied separately in cardboard secondary packaging. The shelf-life before opening was reduced from 1 year to 6 months and limited to 1 week after opening.

CLOSED-LOOP DIGITAL TRACEABILITY OF DOSE BANDING BAGS

European Statement

Production and Compounding

Author(s)

Paola Cristina Cappelletto, Linda Cappellazzo

Why was it done?

Ensure complete digital tracking in closed loop of batches and expiry dates of anticancer drugs prepared in dose banding. Software Medical80© must be able to identify quickly the batches of the drug and solvent used to prepare the bag in dose banding and administered later to a specific patient, following a medical prescription.

What was done?

In 2018, the Pharmacy Unit of Bolzano Hospital introduced automated preparation of fixed-dose anticancer drugs (gemcitabine, paclitaxel, rituximab, pembrolizumab) using Apoteca Chemo© [3]. Until now, the batches prepared have been partially tracked by the Bolzano hospital’s internal software (Indaco©). In 2025, new software called Medical80© was purchased. To digitalize the entire process of prescribing cytostatic drugs by the departments, it was developed a complete batch tracking in closed loop within the Medical80© software including also dose banding preparations. The hospital pharmacist collaborated with the software developers to ensure a safe and complete batch tracking system, in accordance with current regulations [1] and pharmacovigilance requirements [2].

How was it done?

The pharmacist responsible for the galenic area coordinated the activity. Initially, she requested the coding of dose banding preparation within a national database to assign a unique code to each preparation. Specific records for the individual bags prepared in dose banding were then coded, both in the warehouse software and in the prescription and medical record software. The codes automatically assigned by the warehouse program were then entered into Medical80©.

What has been achieved?

This process has enabled to fully track batches and check stock levels directly from the prescription and validation software. Once the batches have been set up, labels were printed and affixed to the bags, and the technician loaded the preparations into Medical80©, recording the batch and expiry date of the starting drug. This information was also recorded and tracked through barcode. At the time of prescription, the bag set up in advance was associated and tracked until administration to the patient.

What next?

Complete tracking from preparing dose-banded bags to delivery to the patient, ensured safe dispensing of the cytostatic drugs. The future goal is to digitalize the load of batches prepared in dose banding using an optical scanner in Medica80©.

THYROID BLOCKADE IN NUCLEAR MEDICINE: RETHINKING THE APPROACH WITH COMPOUNDED MEDICATION

European Statement

Production and Compounding

Author(s)

Luísa Ávares
António Daniel Mendes
Diana Monteiro
Sara Brandão Madureira
Rafael Sá e Silva
Lúcia Costa
Patrocínia Rocha

Why was it done?

Nuclear medicine procedures involve the administration of Iodine-123, Iodine-131, and Technetium-99m, which are taken up by thyroid tissue and may compromise image quality. Blocking this uptake is essential to ensure diagnostic and therapeutic accuracy while minimizing unnecessary radiation exposure. In clinical practice, competitive inhibitors of the transmembrane sodium-iodide symporter (NIS) are used to prevent radionuclide binding.
The institution previously used an oral sodium perchlorate solution as a compounded medication (CM). Due to difficulties in sourcing high-quality raw materials, the Radiopharmacy Unit, in collaboration with the Pharmaceutics Unit, explored alternative options.

What was done?

Identified active substances for thyroid blockade and evaluated their availability and suitability for use within the institution.
Developed, prepared, and introduced potassium perchlorate capsules into the therapeutic arsenal.
Validated thyroid blockade using potassium perchlorate capsules through imaging studies.

How was it done?

Literature review to select a suitable pharmacological alternative.
Pharmaceutical development of potassium perchlorate capsules, including powder classification, bulk density determination, flowability assessment, and capsule size selection using an algebraic method.
Imaging analysis of radionuclide angiograms acquired at equilibrium after capsule administration.

What has been achieved?

Three alternatives were identified: sodium perchlorate, potassium iodide, and potassium perchlorate; none are commercially available in Portugal. Importing sodium perchlorate solution was costly and impractical. Potassium iodide (5% Lugol’s solution) has a short shelf-life and requires administration up to 48 hours before the procedure.
The 200 mg potassium perchlorate capsules offer several advantages: adjustable dosing (400–600 mg), administration up to one hour before the procedure, greater stability, and suitability for patients allergic to iodine. Cervical and thoracic imaging confirmed effective thyroid blockade without compromising image interpretation, demonstrating reproducibility and reduced thyroid radiation exposure.
Potassium perchlorate capsules, prepared as a CM, were effective, suitable, and enriched the institution’s therapeutic options, representing a viable alternative to sodium perchlorate. Clinical validation confirmed no negative impact on image quality.

What next?

Future steps include monitoring long-term clinical outcomes and exploring broader implementation of potassium perchlorate capsules in routine nuclear medicine practice.

INHALATION GENE THERAPY: PROTECTIVE EQUIPMENT IMPLEMENTED

European Statement

Production and Compounding

Author(s)

Scarlett Wise, Pharmacy
Sandrine Gotty, Infectious risk prevention
Sylvain Auvity, Pharmacy
Robert Ratiney, Pharmacy
Caroline Chirk, Pharmacy
Aude Boyer, Clinical investigation center

Why was it done?

Inhalation GTMP’s nature are various, such as mRNA vectorized in lipid nanoparticles and virus GMO therapies. Hospital staff needs reassurance and protective equipment (PE) facing the management of these new ATMPs.

What was done?

Before administrating a new advanced therapy medicinal product (ATMP), including gene therapy medicinal product (GTMP), precaution measures must be implemented for the safety of health care personal at every step of the pharmaceutical process. Administration of GTMP by inhalation generates volatile active substance particles in the air during and after inhalation.
As a result, protection measures were established to secure hospital personal during administration and all through patient hospitalisation.

How was it done?

The dedicated ATMP pharmacist and healthcare manager, identified each key parameter: GTMP nature, persistence on surfaces and types of contamination: airborne, droplet or contact.
The exposition phases in patient’s room were cut down to 3 periods:
1) Administration and instant post administration
2) Hospitalisation post administration
3) Patient discharge
For each period, precautionary measures for entering and exciting patients’ room were discussed:
a. PE
b. Safety distance between personal and patient
c. Bio-cleaning
d. Waste management
Isolation signs for each ATMP were created, approved by the hygiene department and displayed at the entrance of every patient’s room. These signs summarized the good behaviour for every period and detailed the necessary PE.

What has been achieved?

Two isolation signs were created: mRNA and virus-vectorized GTMP.
For 1st period:
Entering: FFP2 mask (airborne), gown, covering glasses, mobcap, gloves and 1.5m distance during administration were identified for both GTMPs. Virus-vectorized GTMP required additional doubled gloves, overshoes and disposable pants.
Room exit: all objects needed decontamination when brought out of patient’s room (contact) for virus-vectorized GTMP.
For 2nd period:
Entering: surgical mask, gown and gloves were identified for both GTMPs. Virus-vectorized GTMP required a surgical mask for the patient (droplets).
For 3rd phase: floor and wall bio-cleaning were necessary and furniture for virus-vectorized GTMP. PE was thrown away in usual waste for mRNA. For virus-vectorized GTMP, PE follows biohazard waste and laundry is identified.
Room exit in all periods required hand washing with hydroalcoholic solution.

What next?

Isolation signs will be created to accompany each new ATMP handling and administration.

OPTIMIZATION OF PEGASYS® DOSING THROUGH SYRINGES IN THE HOSPITAL PHARMACY: ENSURING SUPPLY DURING A GLOBAL SHORTAGE

European Statement

Selection, Procurement and Distribution

Author(s)

Torres-Pérez, Andrés
Iglesias-Valín, Ana Rut
Mateos-Salvador, María
Fernandez-Gabriel, Elena
Feal-Cortizas, María Begoña
Fernandez-Diz, Clara
Gómez-Costa, Eva
Caeiro-Martinez, Laura
Margusino-Framiñán, Luis

Why was it done?

An individualized dosing procedure for Pegasys® (peginterferon alfa-2a) was implemented, using syringes adjusted to the prescribed dose. The primary aim was to guarantee continuous and safe patient treatment during the global shortage, while also optimizing the use of 90 µg vials.

What was done?

In 2024, a worldwide supply disruption of Pegasys® occurred, creating a risk of treatment interruption for hematology patients. Since many prescriptions were below 90 µg, direct vial use caused significant drug waste and aggravated the shortage. A fractionation system was developed, combining coordinated workflow and a risk-based stability assignment, to ensure continuity of care for all patients with the additional benefit of reducing economic impact. The project started on 21 October 2024 and remains ongoing.

How was it done?

A structured workflow between hematology and the hospital pharmacy was established. After each medical visit, the hematologist contacted the pharmacist responsible for the hematology outpatient clinic, who reviewed the prescription and informed the compounding pharmacists of the preparation schedule and updated doses. Syringes were filled under aseptic conditions, stored at 2–8°C protected from light, and delivered to the hematology pharmacy clinic the day before dispensing.
The 30-day stability was assigned according to the hospital’s risk assessment matrix, supported by published stability data from similar products. The process was internally validated in line with hospital compounding standards.

What has been achieved?

To date, the strategy has allowed treatment of 18 patients, with 332 syringes obtained from 90 µg vials, the majority of which corresponded to 45 µg or lower doses. This approach achieved a 51% reduction in the number of vials used, representing savings of €20,791.
Most importantly, no patient experienced treatment delays or interruptions, ensuring therapeutic continuity and safe handling during the global shortage. No stability issues or administration-related problems were reported.

What next?

The protocol will be maintained in our hospital and could be adapted by other centers facing similar shortages. This experience highlights the key role of hospital pharmacists not only in cost management, but above all in the guarantee of safe and continuous access to essential medicines.

STRUCTURED INNOVATION GOVERNANCE: AN INTERPROFESSIONAL COMMITTEE IN HOSPITAL PHARMACY

European Statement

Introductory Statements and Governance

Author(s)

Vanusa Barbosa Pinto, Cleuber Esteves Chaves, Andréa Cássia Pereira Sforsin, , Priscila Faria França, Mayara Araújo Dias, Erik Magnus Lindh, Caroline Sandoli de Almeida Souza, Maria Cleusa Martins, Maristela Barros De Sousa, Rafael Alves de Souza,

Why was it done?

We implemented a structured, interprofessional Innovation Committee within the hospital pharmacy to systematically manage the entire innovation pipeline. The team, comprising pharmacists, nutritionists, physicians, and Information Technology (IT) specialists, established a formal process to guide high-potential projects from initial ideation to final submission for competitive funding. This governance model was successfully applied in 2025 at the pharmacy of a public teaching hospital.

What was done?

Innovation often lacks strategic coordination in hospital pharmacy, limiting the translation of valuable ideas into robust projects. Our objective was to overcome this unstructured environment by creating a governance framework. The committee began its work by specifically focusing on identifying deep clinical “pain points,” such as fragmentation in antimicrobial management, difficulty in customizing medication dosages, and low adherence to training programs for Generation Z staff.

How was it done?

Projects were prioritized based on a methodology that weighed clinical impact, economic feasibility, and technical executability. The team utilized agile management tools, including the value-versus-effort matrix and the problem-solution canvas, complemented by sprint rituals to ensure progress and alignment. The committee successfully generated and developed three large, scalable proposals, validating the model’s capacity to identify and mature high-impact ideas. These proposals were submitted to a competitive institutional innovation grant (In.Cube-InovaHC).

What has been achieved?

The structured process resulted in a robust innovation pipeline with three high-potential proposals: PrintPharma (3D-printed personalized medications), FarmáciaLab (a gamified platform for team training), and Sentinela-ATB (an antimicrobial stewardship hub). The PrintPharma project, which aimed to develop an in-hospital 3D printing solution for personalized medicines, was ranked 8th among 134 highly competitive proposals in a major institutional innovation grant (In.Cube-InovaHC). This ranking validated the quality and maturity of the committee’s output.

What next?

This structured, pharmacy-managed innovation pipeline is a feasible and high-impact strategy that significantly strengthens the institution’s capacity to drive change. It should be considered a best practice example because the governance model and its agile tools are fully replicable and adaptable by any other hospital pharmacy, establishing the pharmacist as a protagonist in healthcare innovation.