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STABILITY OF CEFUROXIME AND PIPERACILLIN/TAZOBACTAM SOLUTIONS STORED IN REFRIGERATOR TEMPERATURES

European Statement

Production and Compounding

Author(s)

Jaakko Mustakallio
Sami Sneck
Miia Turpeinen

Why was it done?

Objectives were improved quality of product, longer shelf life and work-time saving for compounding high-volume antibiotic solutions centralized in hospital pharmacy. Alternative option for antibiotic solution compounding is decentralized model done in hospital wards to be used immediately after reconstitution, quality is difficult to measure and it is time consuming for pharmacists and nurses.

What was done?

Chemical quality and microbiological stability of cefuroxime solutions (100mg/ml, 33mg/ml) and piperacillin/tazobactam solution (80/10mg/ml) was evaluated after stored in refrigerator temperatures (2-8°C) for 28 days.

How was it done?

Antibiotic solutions were prepared using centralized intravenous additive services (CIVAS) located in hospital pharmacy. Used automation for compounding was Newicon IV Icon Twins located at class A/B clean room environment. Concentration of solutions was measured with LC-MS analysis in 5 time points: 0, 7, 14, 21 and 28 days after reconstitution. Sterility analysis was concluded after 28 days, pH analysis was also performed in time points 0, 7, 14, 28 days after reconstitution.

What has been achieved?

After 28 days there was no change in composition, microbiological or chemical quality of products. Minor changes were observed in pH value and color of cefuroxime solutions, which had no further effect for studied stability.

What next?

Hospital pharmacies can provide compounding services for high-volume products using specific automation. Stability of products can be significantly longer than given time in summary of product characteristics recommends.

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.

IMPLEMENTATION OF THE ATP BIOLUMINESCENCE TEST AS A MONITORING TOOL FOR CLEANING PROCEDURES IN A CLINICAL COMPOUNDING UNIT OF A HOSPITAL PHARMACY SERVICE

European Statement

Production and Compounding

Author(s)

A. Sousa; B. Martins; J. Gonçalves
ULSGE, Unidade Local de Saúde Gaia e Espinho, Vila Nova de Gaia, Portugal
ana.luisa.sousa@ulsge.min-saude.pt

Why was it done?

The quality and effectiveness of surface cleaning in the Clinical Compounding Unit (CCU) directly impacts the quality and safety of compounded medications. As a routine task, cleaning is often undervalued, and its effectiveness uncertain. The need for a reliable, real-time monitoring method led to the implementation of ATP testing, ensuring cleaning processes are effective and reproducible. Standard operating procedures, work instructions, and audit tools were developed to support its integration, based on the hospital-wide protocol.
High ATP levels indicate poor cleaning performance and increased microbiological risk, enabling immediate corrective action before any clinical compounding takes place.

What was done?

The “Hospital Cleaning Verification Procedure – ATP Bioluminescence Method”, developed by the Local Unit for Infection Prevention and Control and Antimicrobial Resistance (UL-PPCIRA), was adapted and implemented in the CCU of the Hospital Pharmacy Service.
The test is simple and can be performed by any trained healthcare professional. It involves swabbing a surface, followed by luminometric reading. The light intensity from the enzymatic bioluminescent reaction correlates with the amount of ATP, indicating organic contamination.

How was it done?

Key challenges included the time needed for staff training and initial resistance to procedural changes, with some perceiving the tests as personal performance evaluations. These were addressed through training sessions and awareness efforts focused on promoting a culture of quality and collective responsibility. At the end of the year, the test results will be presented to the team during a training session, as part of the annual training program.

What has been achieved?

Monthly internal testing and bimonthly external audits by UL-PPCIRA are conducted, with approximately 120 tests/year. Non-compliant results lead to immediate cleaning repetition. So far, 17% of tests exceeded acceptable ATP levels. The goal is to reduce this to 10% by year-end. The project has actively engaged a multidisciplinary team of pharmacists, pharmacy technicians, and support staff in improving service quality and patient safety through shared responsibility.

What next?

The aim is to maintain a dynamic, continuously improving process and expand ATP testing to other areas: Cytotoxic Preparation Unit, Repackaging Area, and eventually the entire Pharmacy Service. Future goals include identifying contamination sources to complement ATP testing, further enhancing process control.

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.

BE GREAT! BE GREEN… INTRAVENOUS TO ORAL PREMEDICATION SWITCH!

European Statement

Production and Compounding

Author(s)

Q.ADELLE ; S.KALIMOUTTOU ; E.REMY; R.FAVREAU

Why was it done?

Our Healthcare system generate 8% of national greenhouse gas (GHG) yearly. In order to reduce the environmental impact, our hospital adopted an eco-prescription approach to promote oral premeditation instead of intravenous.

What was done?

On Chimio® software, pharmacist and oncologist resumed every chemotherapy protocol by replacing intravenous (IV) premedication (Methylprednisolone, Dexchlorpheniramine, Ondansetron) by their oral alternatives (Prednisone, Dexchlorpheniramine, Ondansetron).

How was it done?

The study was led on a period of one-month. Thanks to Ecovamed®, the carbon footprint of the intravenous forms was compared to the oral one. The data of the protocols were collected from Chimio®. Nurses and oncologists were questioned on the technical and organizational issues.

What has been achieved?

A total of 271 protocols were resumed. 219 patients were treated by a protocol of immuno-chemotherapy: 83 didn’t need premedication, 7 could not swallow (esophagogastric cancer) and 129 had an oral premedication. 13 of these ones forgot to take it at home, which led to an oral administration at the hospital.
Among the 129 protocols, the carbon footprint rates of patients premedicated orally with Prednisone, Ondansetron, and Dexchlorpheniramine were 45184 +/- 290 gCO2eq, 12908 +/- 116 gCO2eq, and 2688 +/- 900 gCO2eq, respectively. The calculated carbon footprint rate, if premedicated IV, for Methylprednisolone, Ondansetron, and Dexchlorpheniramine IV would be 81181 +/- 334 gCO2eq, 49696 +/- 370 gCO2eq, and 17806 +/- 297 gCO2eq, respectively. The total carbon footprint of oral premedication is 60780 +/- 134 gCO2eq versus 148683 +/- 332 gCO2eq for IV.

What next?

The switch of IV premedication to oral ones reduced the total carbon footprint by 59 %: 148683 ± 332 gCO₂ vs 60780 ± 134 gCO₂eq respectively.
Main limits concerned patients unable to swallow, needing an on-site IV administration with all the infectious risks. And patients who forgot, required an on-site oral administration which could extend the stay because of pharmacokinetics differences and led to changes on the organization. We have to evaluate the economic impact and develop strategies to ensure that patients take their treatment at home.

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.

WHEN PHARMACEUTICAL TECHNOLOGY NEVER SLEEPS: ORGANIZATIONAL MODELS FOR CONTINUITY OF CARE IN FRANCE

European Statement

Production and Compounding

Author(s)

M. Cosson1, A. Quintard1, A. Jalabert1, G. Baroux1
(1) : Service Pharmacotechnie et Essais Cliniques, Pôle Pharmacie, CHU Montpellier

Why was it done?

Continuity of pharmaceutical care—particularly in pharmaceutical technology activities—is a key factor in patient safety. In the absence of specific regulatory guidelines for out-of-hours coverage, this study aims to explore the organizational strategies implemented in hospital pharmacies across France.

What was done?

This work aimed to provide a national overview of how continuity of pharmaceutical technology activities is organized.

How was it done?

A national descriptive survey was conducted online between May and June 2025, targeting healthcare institutions with pharmaceutical technology units, including general hospitals (CH), university hospitals (CHU), and cancer centers (CLCC). The questionnaire focused on the organization of continuity in pharmaceutical technology: existence of on-call services, institutional validation, and types of activities covered.

What has been achieved?

A total of 32 institutions responded: 2 CH, 22 CHU, and 8 CLCC. Among them, 17 (53%) reported having an established continuity plan for pharmaceutical technology activities. In 16 of these (94%), the on-call system was formally approved by hospital management. The main activities covered included chemotherapy reconstitution (15 sites, 88%), sterile preparations excluding chemotherapy (7 sites, 41%), non-sterile preparations (4 sites, 24%), and clinical trials excluding chemotherapy and Advanced Therapy Medicinal Products (ATMPs) (1 site, 6%). No institution reported performing ATMP-related activities outside regular working hours

What next?

This survey highlights the heterogeneity of organizational models for ensuring continuity in pharmaceutical technology across French healthcare institutions. While over half of respondents have implemented an on-call system, it is predominantly focused on chemotherapy reconstitution. Other areas—such as sterile and non-sterile preparations or clinical trials—are covered less consistently. These findings underscore the need to harmonize practices across institution types to ensure equitable pharmaceutical care continuity nationwide.

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 THE COMPOUNDING AND DISPENSING WORKFLOW FOR VANCOMYCIN-HEPARIN CATHETER LOCK SOLUTIONS: FROM STABILITY DATA TO PRACTICAL IMPLEMENTATION

European Statement

Production and Compounding

Author(s)

D. Samitier; G. Domínguez; JM Montes; P. Ruíz; FJ. García; B. Torroba; C. Jiménez; M. Díaz; M. Guembe; A. Herranz; M. Sanjurjo

Why was it done?

A new standard operating procedure (SOP) was implemented, introducing frozen storage (-20 ºC) to enable large-batch preparation of vancomycin–heparin catheter lock solutions.

What was done?

Vancomycin–heparin lock solution is the most frequently prepared antimicrobial catheter lock in our institution. However, short expiration date limited its efficiency: batches of 16 syringes were prepared and stored under refrigeration (2-8 ºC), with a three-day expiry period, resulting in a high proportion of discarded units.
An in-house physicochemical stability study was carried out. It demonstrated that vancomycin–heparin lock solutions remain stable for up to 12 weeks when frozen and 7 days after thawing, a new preparation and storage protocol was established to optimize workflow, ensure availability and improve sustainability.

How was it done?

The new workflow was implemented in March 2025. Lock solutions (vancomycin 2 mg/mL + heparin 100 IU/mL) were prepared aseptically in 100-syringe batches, stored frozen for up to 3 months, and thawed in sets of 10 for daily use, assigning a 7-day expiry under refrigeration. Implementation required recalculating batch volumes, reorganising storage capacity and performing sterility testing.

What has been achieved?

A six-month comparison period (July–December 2024 vs. April–September 2025) showed that the number of locks prepared decreased from 1024 (64 batches) to 700 (7 batches), while administered locks syringes increased from 605 to 659. Discarded units were reduced from 419 (40.9 %) to 61 (8.7 %). Preparation time per batch increased from 22 minutes (16 locks) to 42 minutes (100 locks), but the overall production time decreased by 79.1 %, waste was reduced by 78.6 %, and the proportion of successfully used locks increased by 35 percentage points. The initiative show to reduce workload, improve product availability, and decrease environmental impact of pharmaceutical waste.

What next?

The frozen-storage strategy has been incorporated in routine practice and is being extended to other antimicrobial lock formulations. This initiative demonstrates how evidence-based stability data can be translated into practical and sustainable improvements in hospital pharmacy operations. The model is transferable to other healthcare settings, particularly those facing limited resources or high discard rates of these preparations.