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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 Pharmacopoeia identification] as penicilloic acid (4.5) [D], phenylpyrazine (1.3) [F], diketopiperazine (1.8) [C], amoxicillin dimers (6.5) [J] and adduct species of them (Na+ and K+) (0.5). Despite these findings, there were no notable changes in the appearance or colour 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.

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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, 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 to ICH guidelines (ICH Q2A). Parameters such as accuracy, precision, linearity and LOQ were evaluated. Iodine loss was calculated and modelled 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 with 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.

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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.

Author(s)

Emma Pinet, Lionel Barty, Anne Blandine Bouvrain, Françoise Le Cheviller, Nicolas Vaillant, Nathalie Jourdan, Hélène Sauvageon, Isabelle Madelaine

Why was it done?

In order to make hospital preparations in advance and optimize costs, a physicochemical and biological stability study was conducted in the pharmaceutical control laboratory.

What was done?

Mogamulizumab is a monoclonal antibody used in the treatment of Sezary syndrome and mycosis fungoides. The dilution of the 4 mg/ml vial of Poteligeo® in the infusion bag is stable for 24 hours at room temperature between 0.1 to 3 mg/ml.

How was it done?

Four bags of mogamulizumab were prepared in 0.9% NaCl 250 ml (2 at 0.14 mg/ml, 2 at 0.34 mg/ml). Each dilution is evaluated at 20±5°C and at 5±3°C, protected from light for 28 days. Analyses are performed in triplicate by High Performance Liquid Chromatography (HPLC-UV) associated with Chromeleon™ software. Concentrations are measured by HPLC after Flow Injection Analysis (FIA). Physical stability is studied by searching for IgG aggregates by Steric Exclusion Chromatography (Biozen™SEC3 column, 1.8µm 300*4.6mm). Chemical stability is evaluated by assessing acidic and basic variants proportions of the antibody by Cation Exchange Chromatography (CEC) (Biozen™WCX column, 6µm 250*4.6mm). Biological activity is determined by evaluation of the different glycoforms, by affinity chromatography (FcyRIIIa column, 5µm 75*4.6mm Tosoh®). The microbiological stability is performed by seeding the diluted solution on chocolate agar and brain heart broth.

What has been achieved?

At D28, the quantitative determination of mogamulizumab by FIA showed a deviation of less than 10% compared to theoretical concentrations. No aggregates or antibody fragments were found. The proportion of acidic, basic variants and of the main peak did not deviate by more than 5% compared to D0. For all infusion-bags studied by CEC, the main peak rates were between 79.1% and 85.8%, the acidic variant rates between 6.7% and 9.9% and the basic variant rates between 7.8% and 11.2%. The proportion of each antibody species (low, medium, high affinity) did not deviate by 5% from D0. The low affinity rate is between 48.2% and 52.7%, medium between 39.6% and 44.8% and high between 6.9% and 7.9%. No colonies were found on chocolate agar and heart-brain broth.

What next?

Mogamulizumab is physically, chemically and biologically stable for 28 days in diluted solution between 0.14 mg/L and 0.41 mg/L at 5°C and 20°C.

Author(s)

María Molinero, Virginia Puebla, Cristina González, Lidia Ybáñez, Gonzalo Hernando, Natalia Sánchez-Ocaña, Javier Corazón, María de la Torre, Jose Manuel Martínez

Why was it done?

This technique provides autonomy to the patient allowing to adjust the dose based on the intensity of pain. It has been demonstrated that small on-demand doses of analgesia provide a reduction in the final dose, thus reducing side effects. In addition, by minimizing the possible delay in the administration of analgesia, the anxiety associated with pain and exacerbations is reduced.

What was done?

Hospital Pharmacy Service in collaboration with Acute Pain Unit has developed a protocol for an analgesic mixture for intravenous administration in continuous infusion based on tramadol, dexketoprofen and haloperidol. It is a patient-controlled analgesia (PCA) administered by pump for the treatment of acute postoperative pain.

How was it done?

We performed a bibliographic search of stability studies in order to standardize the analgesic mixture, guaranteeing its physical-chemical and microbiological stability.

What has been achieved?

A mixture of 600mg tramadol, 300mg dexketoprofen and 5mg haloperidol was prepared and it was filtered through a 5-micron filter. It was diluted in 100mL of 0.9% sodium chloride, obtaining a mixture of 125mL. It was sealed and bagged in a photoprotective bag. After the bibliographic search on stability data and physical-chemical compatibility of the mixture, a stability of 14 days at 2-8 ºC was established. Once elaborated, quality control was performed by gravimetry. It was dispensed weekly by stock to the post-anesthesia resuscitation unit. The established perfusion rate is 1.3 mL/h or 1.7 mL/h for 48h. With each rescue, 8mg of tramadol and 4mg of dexketoprofen are released per hour or 4mg and 2mg every 30min, respectively. The maximum dose that can be administered is 400mg tramadol, 150mg dexketoprofen and 2mg haloperidol, except if the patient weighs less than 50kg: 8mg/kg tramadol. If renal insufficiency, dose adjustment was mandatory.

What next?

The centralization of the preparation of intravenous admixtures from the pharmacy service allow us to adjust the expiry date based on stability studies reported in the literature, to maintain the asepsis of the mixture as it is prepared in horizontal laminar flow cabinets, to increase the safety and to secure the traceability.

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Author(s)

María Lourdes Recio Blázquez, José Manuel Martínez Sesmero, Lidia Ybáñez García, Gonzalo Hernando Llorente, María Molinero Muñoz

Why was it done?

The purpose is to control two environmental conditions to guarantee the comfort of the workforce and the quality of the finished product quality. 519,321 SODFs have been repackaged in unit doses last year. The 8% of the SODFs come from multidose containers that have been exposed to environmental temperature and humidity during this process. Employees have been exposed to identical conditions.

What was done?

A temperature (t) and relative humidity (RH) control system has been established in the enclosure where the solid oral dosage forms (SODFs) are packaged in unit doses.

How was it done?

Among the diversity of hygrometric sensors commercialised, a device equipped with a condenser was chosen. The operation is based on modifying the capacity when varying the dielectric constant of the medium, in this case, due to varying the amount of water contained in the air between the plates. – C = ε A / D – C: capacity value. – ε: dielectric constant. – A: area of the condenser plates. – D: distance between the condenser plates. The device also incorporates a temperature sensor. The t (ºC) and RH of each moment are shown, for visual inspection, on the device screen. The data obtained with certain time frequency can be stored on a Secure Digital memory card and be downloaded on a computer that has that program installed (on spreadsheet format) helping to obtain graphics as well.

What has been achieved?

The range of t (ºC) has remained stable between 26 and 24ºC for 6 months, with minimal variations from maximum 28.5ºC to minimum 23.4ºC. The UNE 100713: 2005 is met. RH has been below 45% during 68% of the days worked, which has favored the repackaging of the units affected by humidity but not the worker. The range of RH has varied between 56.3% and 23.6%, not complying with the UNE 100713: 2005 standard.

What next?

Metabolic rate, clothing insulation, air temperature, radiant temperature, air speed and humidity shall be addressed when defining conditions for acceptable thermal comfort. It would be helpful to regulate the commercialisation of multidose pharmaceutical specialties susceptible to deterioration when opening the package.

Author(s)

Ismail Bennani, Amine Cheikh, Hafid Mefetah, Mustapha Bouatia

Why was it done?

The strict control of medicines cold chain is linked to a triple risk for a hospital: a risk for the patient through the efficiency and safety of the drug, a financial risk, and a regulatory risk.

What was done?

Our study aimed to map the process of management of medicines requiring a strict cold chain control at a referral pediatric hospital and to identify the critical points associated to this process in order to realize a risk analysis using the FMEA method

How was it done?

The method used is FMEA for a priori inductive risk analysis which aims to identify potential system failures. These failures are analyzed to determine their criticality by establishing an index for each failure that will be scored and calculated using the formula: Criticality index = frequency × severity × detectability.
The rating of each criterion is based on predetermined rating tables.

What has been achieved?

Process Mapping: The mapping of the process allowed identify 7 major actors: the supplier, the general store, the logistics platform for product reception, the transportation, the logistics department of hospital, the pharmacy and the patient.
Identification of the critical points: All failures modes that were ranked between 201 and 504 on criticality index are considered as main critical points:

Problem of breakdown of electricity and its management: 504
Respect of the cold chain at the level of the care services until administration: 448
Temperature indicators at the level of care services: 384
Conditions of transportation: 315
Temperature monitoring at pharmacy level: means and management: 245
Logistics agents transport time management: 210

Implementation of improvement actions: Corrective and preventive improvement measures have been defined and implemented, such as: setting up alternatives to power outages, periodic temperature assessments at all critical levels, and integration of remote control and monitoring computer devices.

What next?

The continuous improvement of the medicines’ cold chain remains an important topic for the institutions in view of the overall risks associated with the quality of these medicines, therefore to the medical treatment of the patient.

Author(s)

MERCEDES GIMENO-GRACIA, TRANSITO SALVADOR-GOMEZ, ROSA MARECA, JOSE IGNACIO GARCIA-MONTERO, MIGUEL ANGEL SALVO, PILAR ABAD, BEATRIZ ABAD, CESAR VELASCO

Why was it done?

The Spanish Agency of Medicines and Health Products (AEMPS) issues drug and health product-related alerts to the health centres through each region’s Department of Health. The means through which said alerts reach the health professional is not always adequate. The procedures for alert dissemination in our hospital hadn’t been standardized yet: some professionals were alerted more tan once while others weren’t alerted at all. Furthermore, there was no record of these alerts

What was done?

We developed a safety alert management and dissemination system implementation in a hospital setting.

How was it done?

In April 2014, a multidisciplinary workgroup was established (3 members of the Preventive Medicine Service, 2 pharmacists, 2 members of the Supplies Service, 2 computer technicians and 2 members of the hospital’s Management) to analyse management and dissemination of alerts within the hospital at that time. Safety alerts can attain to different elements: drugs, medical devices and public health. Throughout 2015 new circuits and actions were established and in 2016 their implementation was initiated.

What has been achieved?

The workgroup held 7 meetings from April 2014 to June 2016. The project started focusing on drug-related alerts. An algorithm was designed to handle them, in which a pharmacist filtered the alerts (via e-mail) and assessed which had to be spread, and among which professionals. Additionally, the pharmacist managed the alert. The dissemination worked as follows: from the Pharmacy Service to Medical or Nursing Directors, who spread the message to the different units recommended by pharmacist, specifically to their respective Manager, Tutor of Residents and Quality Manager. All alerts were recorded in a database, along with how they were handled.
From January to June of 2016, a total of 235 drug-related alerts were sent from AEMPS. The dissemination was as follows: 44.3% (104) were spread among pharmacists, 36.6% among doctors, 5.5% among nurses and 9.4% to other professionals. The types of drug-alert received were classified as: supply problems (84.7%), use recommendations (7.2%), quality alerts (7.7%) and others (0.5%).

What next?

Next step is implantation of this alert management system with medical devices alerts and public health alerts.