Author(s)

Sadaoui Talwit, Guicheron Gaëlle, Llari Tahina, Jolicart Maude , Bloch Vanessa, Delage Clément, Gasmi Linda, Belaid Imene

Why was it done?

Compounding sterile injectables carries a contamination risk, and sterility of extemporaneously compounded preparations cannot be verified afterwards. In line with national Good Compounding Practices (BPP 2023), we sought to formalise APS to assess and (when needed) rehabilitate operators’ aseptic technique while strengthening patient safety and quality assurance.

What was done?

We implemented an aseptic process simulation (APS; media fill) as a standardised pathway for initial qualification and requalification of operators involved in sterile injectable compounding. The APS challenges the process in worst-case conditions and provides documented evidence of aseptic competence.

How was it done?

We conducted a literature and practice review, including BPP 2023 guidance and NHS recommendations (“Universal Operator Broth Transfer Validation”), canvassed three French hospital pharmacies for return of experience, and selected commercial kits. We drafted a local SOP and protocol defining a worst-case scenario: simulated failure of the microbiological safety cabinet (work on a clean bench in a controlled area), without an assistant, and under real-life constraints. Each session was supervised by an evaluator; glove prints were taken on Count-Tact plates at the end of the run. All filled units were incubated for 14 days (7 days at 20–25 °C, then 7 days at 30–35 °C) with daily visual checks recorded in an electronic log, and final turbidity reading.

What has been achieved?

Four APS runs have been completed to date (pharmacist, pharmacy intern, and technicians), all compliant with no microbial growth detected. One technician remains to be tested due to scheduling constraints. The process now underpins our documented pathway for operator assessment and provides a basis for microbiological trending.

What next?

APS will be rolled out to all staff with annual requalification, and ad-hoc re-testing whenever there are changes to the process, critical equipment (e.g., MSC/BSC), or the classified cleanroom (e.g., grade change, layout/HVAC modifications), or when practice drift is observed. We will add structured behavioural/technical checklists to each run and track KPIs (pass rate, contamination rate, time-to-certification, observation deviations). Microbiological results (glove prints, environmental plates) will be trended with action thresholds, and APS will be complemented by routine observation-based assessments to ensure safe sterile compounding.

Author(s)

Manon Dumoulin, Pharmacy
Caroline Chirk, Pharmacy
Claire Jouans, Pharmacy,
Sylvain Auvity, Pharmacy
Robert Ratiney, Pharmacy
Lamia Haï, Pharmacy
Scarlett Wise, Pharmacy

Why was it done?

This initiative began in March 2024, when patients started treatment.
The necessity of optimizing reconstitution was apparent quickly, to absorb activity increase.
The goal was to optimize reconstitution steps, in terms of time dedicated (human resources) and syringe quality (volume, bubbles quantity).

What was done?

Reconstitution of this first topic gene therapy (GT) consists of mixing the active substance (AS) with the gel excipient and drawing four syringes per vial, total volume 2ml.
Extractable volume is less than 2.5ml due to gel viscosity, making it complex to extract final syringe.
This topic GT is applied weekly, which makes it a time-consuming activity impacting the pharmacy’s advanced therapy medicinal product department.
As a result, the most efficient ways to manipulate the vials have been identified.

How was it done?

All manipulators trained on factice vials to apprehend gel texture. This dry run phase allowed identification of reconstitution process key steps.
Manipulator pairs were followed for 6 months: data on each step was collected (duration, reconstitution tips).

What has been achieved?

Reconstitution process is cut down to four steps: thawing (a), AS and gel mixing (b), vial resting (c) and syringe drawing (d).
a) Keep the gel vial right side up: avoids gel accumulation on the septum when punctured.
b) Use an air intake device; avoids overpressure in the vial and syringe.
c) Gel vial should rest at least 5 minutes after being mixed with AS. When more than one vial is reconstituted, prioritize mixing step in a series: increases vial resting time.
d) Draw syringes right side up: avoids gel loss on vial sides. When volume is adjusted, inject gel excess in the vial while needle bevel in the air: prevents injecting bubbles in the remaining volume.
Data collection on steps duration showed a learning curve for all manipulator pairs. Reconstitution duration for 3 vials decreased by 10 minutes after 3 reconstitutions. Each pair arrived up to an incompressible duration: 1 hour for 1st vial (bio-cleaning, dressing) and 20 minutes more for each additional vial.

What next?

Training videos are being created to highlight key steps for reconstitution campaigns.
Process and time standardization, allows fluid organization of a complex activity and improves production efficiency.

Author(s)

Susana Redondo-Capafons, Laura Soriano, Carmen Roger, Oriol Arroyo, Raquel Mayoral, Ana Morales, Andrés Reyner, Marta Rueda, Rosario Bueno, Mónica Gómez-Valent, Andrés Joaquim Reyner

Why was it done?

In aseptic cleanroom environments, correct donning and doffing of personal protective equipment (PPE) and adherence to hand hygiene protocols are essential to prevent contamination and ensure both patient and operator safety. Despite existing standard operating procedures (SOPs), interindividual variability in compliance often remains undetected, increasing the risk of deviation from aseptic standards. Our pharmacy department identified the need for a practical tool to systematically monitor and improve these critical procedures. With the aim of continuous improvement in clinical practice and service quality, and in the context of incorporating new staff into the cytotoxic preparation area, this initiative was developed.

What was done?

Two structured checklists were designed and implemented to evaluate compliance with SOPs:
1. Donning and doffing of PPE – assessing sequence, technique, and timing.
2. Hand hygiene – assessing product use, duration, and areas of the hands washed.

How was it done?

The checklists were based on international guidelines (WHO, GMP) and local SOPs. Trained observers performed random assessments of pharmacy technicians during routine cleanroom entry and exit. Each step was scored for compliance, and procedure times were recorded.

What has been achieved?

The use of checklists enabled objective, individualized assessment of compliance. The mean compliance score for donning and doffing PPE was 9.4 ± 0.8, while for hand hygiene it was 8.9 ± 1.2. The 100% of pharmacy technicians acquired the minimum score established in the procedure (7/10). The main issues identified were related to the location where PPE was removed (17%), the duration of hand washing (25%), and the volume of alcohol-based hand rub used (42%). These findings guided targeted retraining sessions and continuous quality improvement actions. This approach increased awareness among staff and promoted more consistent aseptic practices in daily operations.

What next?

The checklists have been integrated into routine training and quality monitoring. They are easy to replicate in other hospital pharmacies with cleanroom facilities, requiring minimal resources. The initiative provides a model to strengthen aseptic procedures, reduce contamination risks, and enhance overall compliance with safety standards.

Pdf

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.

Pdf

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.

Pdf

Author(s)

F. Gaume, A. Ifrah, S. Vrignaud

Why was it done?

In 2023, an evaluation of professional practices (EPP) targeting the risk of microbiological contamination was carried out in our parenteral nutrition production unit. This EPP took the form of an internal observational practice audit and revealed several non-conformities (compliance with disinfectant exposure time, identification of right times for change gloves and performance of surface sampling) requiring the implementation of a structured and collaborative improvement plan.

What was done?

From January to October 2024, an improvement plan in 3 phases has been performed.

How was it done?

Phase 1 – Audit results: Presentation to unit technicians by pharmacists, followed by a discussion session.
Phase 2 – Development of improvement actions: Brainstorming sessions with the team to generate ideas for corrective actions / Evaluation of proposals collected according to 6 criteria (speed, relevance, feasibility, motivation, safety and cost) using an impact matrix / Creation of a structured action plan based on the selected proposals.
Phase 3 – Implementation of actions: Creation of working groups / Monitoring of the improvement process / Development of a plan to assess the effectiveness of actions.

What has been achieved?

Phase 1 – Audit results presentation: 2 sessions were held in January 2024 with the 13 technicians of the unit. The discussions allowed us to discuss the non-conformities observed during the audit and ensured understanding of the challenges identified.
Phase 2 – Development of improvement actions: 2 sessions were held in March 2024 /10 improvement actions were listed and evaluated. 4 actions were considered as priority, 4 as recommended and 2 as non-priority / Setting up of a Gantt chart to give an overview of the actions to be carried out, their estimated duration and deadlines.
Phase 3 – Implementation of actions: implementation of the 4 priority actions and the 4 recommended actions / Creation of a quality document concerning glove changes and modification of 8 quality documents / Consideration of ways of evaluating actions: quick audit, questionnaire, etc.

What next?

As a follow-up to this work, a questionnaire will be prepared for the technicians to assess the overall approach. A quick audit focusing on glove changes will be introduced soon to assess the impact of the improvement plan.

Why was it done?

The number of patients treated with autologous eye drops has increased significantly in recent years, which has led to the need to create an intra-hospital circuit to ensure the traceability of samples throughout the extraction, processing and dispensing process.

What was done?

Create a circuit to ensure traceability of the patient’s plasma at all times, thus avoiding any confusion.

How was it done?

In order to avoid the transport of samples by patients and consequently the loss of samples or possible errors, the following circuit was developed:
– The extraction and centrifugation of the patient’s blood is agreed with the Biochemistry Service, the orderly is in charge of taking it to the pharmacotechnics laboratory, in the Pharmacy Service, where the time of delivery will be noted.
– If the plasma arrives before 12:00 noon, the patient will be called late in the morning for dispensing. If the delivery is later, it will be scheduled for the following day.
– The eye drops are then prepared.
– Finally, they are dispensed directly from the laboratory by the pharmacists or by the technicians trained for this purpose, always under the supervision of the pharmacist responsible for the area. Traceability is maintained throughout the entire process.
To make everything possible, several training meetings had to be held with Bioquimica.

What has been achieved?

Since the implementation of this circuit at the beginning of 2023, 166 batches of autologous eye drops have been produced for 72 patients, with only one error recorded, where a plasma that was not correctly identified was delivered and discarded.
In addition, the waiting time for dispensing the preparation was reduced by 33%, from 30 minutes to less than 10 minutes, thus achieving greater patient satisfaction.

What next?

The application of this circuit prevents samples from being transported by the patient, avoiding any type of accident, as well as ensuring the correct traceability of the samples. On the other hand, patient waiting times are reduced by dispensing samples directly from the laboratory area, thus avoiding waiting times for consultations.

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Author(s)

Susana Fraga, Cláudia Cunha, Susana Pissarra , Carla Sampaio, Diana Silva, Pedro Soares, Teresa Soares, Renata Barbosa

Why was it done?

Human milk banks (HMBs) must use rigorous quality assurance practices to protect infants and milk processing, and post-pasteurization procedures are important in maintaining high-quality breast milk and safeguarding its quality.
The compounding pharmacist has all the knowledge and experience needed to implement processing circuits based on good handling practices and sterile technique, combined with quality assurance procedures to ensure their safety.

What was done?

Pharmacy implementation of the Donor Human Milk (DHM) processing circuit (by pasteurization) and conditions.

How was it done?

Bibliographical research and critical analysis of the functioning of HMB worldwide, with multidisciplinary meetings to define the best and most secure quality practices.
Equipment choice, in accordance with recommendations and assessment of their technical requirements.
Adaptation of the informatic medical integrated system to the DHM prescription, processing, quality control and dispensing circuit.
Design of the DHM circuit based on good practices for the safe use of products of human origin and on a robust quality assurance plan.

What has been achieved?

A DHM circuit was put into practice, with pharmacist intervention in DHM processing, quality control, and batch release.
Procedures for aseptic handling, quality control with check points and risk analysis, packaging, and labelling of DHM were outlined.
Work instructions were also established for handling equipment (pasteuriser, bottle sealer, laminar flow chamber) as well as procedures for cleaning facilities and material/equipment, with training sessions for the professionals involved.
The multidisciplinary circuit was adapted to the organisational management of the Neonatal Intensive Care Unit (NICU), HMB, and Pharmaceutical Services, certified on 18 April 2023 according to ISO 9001:2015 recommendations.
Guidelines for the correct use of equipment in accordance with its recommendations and technical requirements were established.

What next?

Opening more HMB worldwide is an inevitability. Prevailing know how at the level of hospital pharmacies represent several advantages to these projects, based on experience and expertise in manipulating biological products and maintaining a controlled circuit based on safety and quality standards.

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Author(s)

Bojan Žagar, Matej Vehovc, Mateja Tršan, Blaž Vehar

Why was it done?

Cefazolin injection 100 mg/mL is a sterile pharmaceutical formulation comprising cefazolin sodium and water for injections. Traditionally, cefazolin injections were prepared on hospital wards by reconstituting cefazolin sodium powder for injections with water for injections and subsequent dilution before intravenous administration.

What was done?

Establish a semi-automatic aseptic preparation process, ensure the production of final products that meet quality standards, develop analytical methodologies for in-process and final product quality control, ensure the reliability and validity of test results, and conduct a stability study to confirm long-term storage.

How was it done?

Product materials include: Pharmacy Bulk Package of Cefazolin for Injection, USP, water for injections, Luer Lock 20 mL sterile polypropylene syringes, steribags. Product is prepared with aseptic technique within a laminar flow unit situated in a pharmaceutical cleanroom. Bulk package is connected to a dispensing device, followed by reconstitution with water for injections. In-process samples are collected and volume-adjusted based on density. Following the preparation and dispensing, syringes undergo labeling and packaging into steribags. They are then promptly stored at -30°C within 4 hours. Final product samples are obtained and analysed (pH value, cefazolin content, endotoxins, sterility) prior to product release.

What has been achieved?

Preparation of cefazolin sodium injections in a controlled, aseptic environment utilizing pre-prepared bags containing the appropriate cefazolin concentration (100 mg/mL) has successfully addressed critical concerns surrounding the safety, efficacy, and quality of these pharmaceuticals when administered on hospital wards. Challenges related to stability and shelf life are being addressed with the storage approach at -30°C within the pharmacy, followed by a carefully monitored transition to ward storage at 5°C for up to 28 days, and subsequent patient administration at room temperature within 2 days.

What next?

This approach not only streamlines the process but also safeguards the well-being of patients, marking a significant advancement in pharmaceutical preparation within our healthcare setting. We are conducting an ICH-compliant stability study with the objective of establishing a combined shelf life of 90 days at -30°C, followed by 28 days at 5°C, and an additional 2 days at room temperature.

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Author(s)

Lucija Tominović Gjivić, Gabrijela Kos, Anita Šimić

Why was it done?

In order to ensure correct use of voretigene neparvovec and minimise the risks associated with its administration, the product can be distributed only through treatment centres where qualified staff (vitreoretinal surgeons and pharmacists) have participated in the mandatory risk management plan (RMP) education program required by EMA.
Since voretigene neparvovec has to be transported and stored frozen at ≤-65 ºC, has short shelf life after dilution (4 hours), contains genetically modified organisms and must be handled according to local biosafety guidelines, there was a need for establishing standard operating procedures (SOPs) for each step of the treatment process.

What was done?

The University Eye Clinic, University Hospital Sveti Duh in Zagreb, Croatia, was designated as the world’s 6th gene therapy centre in 2020.
Hospital pharmacists, as part of a multidisciplinary team, play an important role in preparation and administration of the gene therapy product voretigene neparvovec which is indicated for the treatment of patients with vision loss due to inherited retinal dystrophy caused by biallelic RPE65 (retinal pigment epithelium-specific 65 kilodalton protein) mutations.

How was it done?

The multidisciplinary team consists of a paediatric ophthalmologist, an inherited retinal disease specialist, retinal surgeons, pharmacists and nurses.
SOPs were created for: ordering process, storage of the product, coordination between members of the multidisciplinary team, preparation of the product, administration and disposal of waste.
Preparation of voretigene neparvovec is performed under aseptic conditions in a Class II vertical laminar flow biological safety cabinet (BSC) according to Pharmacy Manual which was ensured by the manufacturer.

What has been achieved?

Since 2020. there had been 47 dose applications of voretigene neparvovec (26 patients, Croatian and nonCroatian citizens).
The prevalence of inherited retinal dystrophy associated with biallelic RPE65 mutation is 1:200 000 and it is expected that there are 19 individuals (population of 3,8, million) with biallelic RPE65 mutation in Croatia, and 13 of them were detected since 2020.
There were no registered side effects which could be associated with errors during the preparation or administration of voretigene neparvovec.

What next?

With the increasing number of gene and cell-based therapies, the need for continuous education of hospital pharmacists and exchange their experiences is greater than ever.