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COMPUTER DEVELOPMENT OF THE MAGISTRAL FORMULATION MODULE FOR UNIFICATION OF THE PRODUCTION AREA

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European Statement

Production and Compounding

Author(s)

A. Henares-López, V. Collados-Arroyo, C. Mayo-López, R. Fernández-Caballero, L. Carrasco-Piernavieja

Why was it done?

A new magistral formulation and mixes management program was developed in the Farmatools® software to optimize the procedures and records of this area.

What was done?

The correct management of compounded formulation is important for the labor of a pharmacy service, ensuring safe preparation and adequate traceability. In our pharmacy service we only had a simple formula registration program that only allowed formulas to be added to the stock but the rest of the work (protocols, batches, preparation staff, validation) was recorded on paper.

How was it done?

Taking advantage of the implementation of the Farmatools® software in our pharmacy service that already had a simple compounding module, it was necessary to carry out a development to add improvements such as registration of raw materials, quarantine states, expiration notices, creation of manufacturing protocols for each preparation, formula programming calendars, improvement of the traceability system (new batch records and other necessary data in the case of biological material), quality controls such as mass uniformity control for capsules, validation section of the formula prepared for the pharmacist, registration of manufacturing staff, improvement of data present on the manufacturing label.
This work was possible thanks to the help of the farmatools® IT staff with whom we held regular meetings.

What has been achieved?

A correct stock of the amount of real raw materials existing in the pharmacy was achieved, complete computerization of the registry of preparations of magistral formulation, including batches, expiration dates, quarantines and necessary quality control records, creation of an electronic recipe book, approval or rejection of elaborate formulas and eliminating any paper records.

What next?

There are still new developments to be implemented, such as the creation of a calendar of scheduled work and a list that allows viewing the preparations pending validation by the pharmacist. Finally, it would be necessary to implement tablets that contain work protocols to avoid the use of paper.
With this program it has been possible to unify the work of the production area in a single program, which results in an improvement in traceability and fluidity in the work.

IMPLEMENTATION OF AN ADVANCE PREPARATION OF MEDICINES MODEL IN A CYTOTOXIC PREPARATION UNIT

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European Statement

Production and Compounding

Author(s)

Grangeia R, Pereirinha P, Rodrigues R, Salvador R, Marques M, Queirós M, Moreia A, Cunha E, Lebre AC.

Why was it done?

The increase in cancer incidence, combined with new and more innovative oncology treatments, leads to the necessity to increase the compounding capacity of oncology medicines. This consequently has a negative impact on the workload of oncology pharmacists. About 80% of these medicines are to be administered during the morning or early afternoon, affecting the response time due to the large workload and lack of production capacity in short periods.
The ready-to-use model allows to:
1. Reduce the morning workload and distribute tasks equitably throughout the day, since fixed doses are prepared in the afternoon or at the weekend;
2. Medication is readily available for administration;
3. Reduce medication-related errors.

What was done?

A ready-to-use model was implemented for those medicines whose dose is fixed, as part of a strategy to optimize the unit’s human resources.

How was it done?

This model is based on three foundations:
• Standard aseptic handling plus the use of closed system transfer devices (CSTD);
• Microbiological control upon batch release;
• Robust bibliography that supports the physical-chemical stability used as a reference for expiration dates.

It was implemented in two phases:
1- Preparation of a test batch of fixed-doses, with elaboration of the specific protocols, compounding procedures and labels;
2- Full implementation of the model, with implementation of a digital circuit.

The first medicines included were: daratumumab, nivolumab, pembrolizumab and pertuzumab.

What has been achieved?

The ready-to-use model was evaluated at three levels:
1. Financial impact: positive balance. Medicine vials are saved since compounding is done at the same time. The ratio between the investment required to acquire CSTD and the saved is 1:4,5;
2. Preparation time: Similar to normal compounding;
3. Annual effectiveness rate – 54%: This is the percentage of fixed doses that were prepared in advance.

What next?

The model proved to be effective in improving human resources management. With the effectiveness rate obtained, 4% of the total medicines that are administered are previously prepared. This value could reach 8% when the model is fully implemented.
It can be replicated in a dose-banding system12. Selecting, for example, rituximab, 5-FU and azacitidine, 25% of the daily preparations depends only on the time profitability of the cytotoxic preparation unit.

ANALYTICAL CONTROL OF INJECTABLE PREPARATIONS: TAKE THE TIME TO ANALYZE YOUR ACTIVITY

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European Statement

Production and Compounding

Author(s)

Guillaume BOUGUEON1,2 ; Mélissa WANG1 ; Jean-Marc Bernadou1, Maîté Sangnier 1, Aude BERRONEAU1
1 Pharmaceutical Technology Department, Bordeaux University Hospital, Avenue de Magellan, 33604 Pessac, France
2 ARNA Laboratoire ChemBioPharm U1212 INSERM – UMR 5320 CNRS, Université de Bordeaux, France

Why was it done?

We work within a university hospital, in an injectable drug production unit. We produce around 55,000 preparations a year, and ten years ago decided to implement analytical control (identification and dosing) (i.e. HPLC then followed by UV-Raman spectrophotometry (QCRX®)) as a post-process control method. To date, around one hundred assays are carried out daily (representing 50% of preparations produced), and some thirty different active substances are analyzed.
For the past 4 years, a monthly meeting has been devoted to monitoring the compliance of analytical assays for our preparations.

What was done?

We felt it was essential to take a step back from our control activity, to enable us to monitor and analyze assay compliance in detail, to distinguish between preparation errors and errors linked to control equipment, and to detect upstream any deviations in assay methods or material damage.

How was it done?

Monthly one-hour meetings have been set up. These multidisciplinary meetings are attended by 6 people, including senior and student pharmacists, pharmacy technician and a laboratory technician.
During these meetings, the following are presented: the number of assays and their nature (1st assay or 2nd assay following a 2nd sample); the number of non-compliant assays (outside the limit of +/- 15% of the target concentration), the overall compliance rate; an analysis of rejected and destroyed preparations, with an investigation into the causes of non-compliance.
Corrective action may then be taken: early maintenance of equipment, quarantine of analytical methods and research into the causes of drift, implementation of new dosing methods. Feedback is then given to the whole team.

What has been achieved?

These monthly meetings have enabled us to anticipate analytical drifts and reinforce our team’s compliance to this type of control. They also enable us to limit the downtime of dosing methods and the need for double visual checks, a potential source of errors.

What next?

The aim is to eventually increase the proportion of analytical control to over 50% of preparations produced. This will involve the introduction of new dosing methods for preparations usually controlled by double visual inspection, and the acquisition of additional equipment

RELOCATING A UNIVERSITY HOSPITAL’S INJECTABLE CHEMOTHERAPY PREPARATION PROCESS TO A MOBILE UNIT: A CHALLENGE MET!

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European Statement

Production and Compounding

Author(s)

K.LEROUET; M. DELAMOTTE; F.VITET. S.CRAUSTE-MANCIET; A.LEBRETON; F.LAGARCE

Why was it done?

Our Chemotherapy Reconstitution Unit (CRU) needed to replace its two double workstation isolators and high efficiency particulate air filters, taking the unit out of service for six weeks. With 40,000 injectable chemotherapy treatments performed each year, outsourcing was not an option. We had to find a solution to temporarily relocate the activity to a new area within our facility.

What was done?

Our aim was to ensure continuity of the manufacturing process for injectable anticancer drugs in accordance with Good Preparation Practices in a temporary CRU.

How was it done?

Eighteen months ahead of schedule, we set up multidisciplinary working groups consisting of pharmacists, pharmacy technicians, biomedical and technical service staff and health care managers.
Inspired by the few french hospitals that had already carried out this project, we studied the process and the choice of space and equipment required. We also drew up procedures and a backlog schedule.

What has been achieved?

Twenty-three work sessions of 1 hour were organised. We chose a chemo-truck (ModuGuard®), with three workstations inside two positive pressure isolators. We acquired new equipment to adapt to the spaces created specifically for this project (transport crates, walky-talkies, operating room gowns). We planned the qualification of the mobile grade D controlled area and isolators. The production flow was rethought, with extended production hours and more human resources. Our production was divided into 4 zones with different tasks: tray preparation and pharmaceutical validation, chemotherapy preparation, pharmaceutical release and preparation dispatch. Good communication between the different areas was essential to the success of our project. In comparison to the reference process, no additional non-conformity where noticed. We communicated with the care units many months ahead to anticipate logistic issues.

What next?

The overall feedback from the teams was good, thanks to the cohesiveness that was created, although staff were tired. No adverse events were reported, although occasional delays in preparation were noted. Anticipation of needs and day-to-day adaptability were essential to the success of this project. A budget of €80,000 was required to complete our project. This organisation allowed us to maintain a level of production equivalent to our CRU. This publication is intended to help inform healthcare organisations undertaking similar projects.

DEVELOPMENT AND IMPLEMENTATION OF A POST-AUDIT IMPROVEMENT PLAN IN A PARENTERAL NUTRITION PRODUCTION UNIT

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European Statement

Production and Compounding

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.

DEVELOPMENT OF PHARMACY CRRT SOLUTIONS SERVICE AT KING CHULALONGKORN MEMORIAL HOSPITAL, THE THAI RED CROSS SOCIETY

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European Statement

Production and Compounding

Author(s)

Phontep Wongkrasoe; Wongsathorn Padungsupalai

Why was it done?

Premixed customize CRRT solutions were compounded by sterile pharmacy.

What was done?

According to the medication management policy, CRRT solution was defined as
High Alert Drugs that require the independent double check throughout the
medication use system. Conventional methods (prepared by nurses) take many
risks and may affect the quality of ICU-patients care by spending more time
for preparing.

How was it done?

Nephrologists, nurses, and pharmacists made a consensus for standard
customized CRRT solution formulas and clarified the ordering (for physician),
dispensing (for pharmacist) and preparing (for nurse to add potassium)
instructions. The procedure for compounding CRRT solutions by sterile
pharmacy was established to optimize traceability aspects as a quality
assurance. With the large batch size compounding, we mockup the preliminary
batch to identify the risk and assure the consistency of compounding process.
Quality control was planned to measure electrolyte content and test sterility
at D0, D7 and D14 at room temperature and refrigerated storage. After the
preliminary batch test was accepted, we started a pilot service in one ward
and reached the maximum service capacity at only one patient per day. The
pharmacists redesigned the compounding process, and the repeater pump was
introduced to increase capacity. Because the product was changed in total
volume from one liter to 1.2 liter, we conducted the preliminary batch test
again. Teams revised the ordering, dispensing, and preparing instructions and
expanded the service to 7 ICU wards.

What has been achieved?

We formulated 2 CRRT solutions in the name of “Chulasol-22 1.2 liter” and
“Chulasol-35 1.2 liter” with BUD 14 days at room temperature storage. The
results were (1) we can provide the CRRT solution for maximum 5 patients per
day compared to only one patient per day in the initial period, (2) the cost
of pharmacy compounded solution was much lower than conventional method or
comparable commercial solution and (3) most nurses (91%) were satisfied in
product quality and had more time for patient care.

What next?

The success of this model was a multidisciplinary engagement that resulted in
improvement of patient care. We use this model in other services such as pain
preparations and eye preparations.

Intrahospital circuit of autologous eye drops

European Statement

Patient Safety and Quality Assurance

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.

Analysis of quality indicators in the compounding area through a mobile application

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European Statement

Patient Safety and Quality Assurance

Why was it done?

To identify improvement opportunities in the Pharmacy Compounding Area through the analysis of indicators obtained from a traceability App.

What was done?

In 2022, a mobile application (App) was designed and implemented to facilitate the traceability of preparations compounded in the Pharmacy (parenteral nutrition, chemotherapy and other individualized sterile preparations). In addition, the analysis of data registered in the App has provided valuable information about the compounding unit performance.

How was it done?

Monthly reports from May to December 2022 were analysed, focusing only on chemotherapy preparations. The indicators selected were: the average number of monthly preparations, weekly workload distribution, daytime distribution of compounded preparations, preparations returned to the Pharmacy, percentage of treatments prepared on the same day of administration, and percentage of preparations compounded after the scheduled administration time.

What has been achieved?

An average of 139 chemotherapy preparations per day was recorded. The daily distribution highlights that Thursdays and Fridays are the busiest days with the 45% of the total weekly preparations. Furthermore, the morning shift carries out most of the compounding work, with 79% of the preparations being compounded before 3 PM. This information might be useful to the management team to better distribute tasks and resources. Data analysis indicates that 62% of the preparations are compounded in advance, while the remaining 38% are prepared on the same day of administration, which is also valuable information to organize the compounding workflow. On average, 59 preparations were returned per month. Finally, we found that 8.1% of the chemotherapy drugs were prepared with a median delay of 47 minutes from the expected time of administration. All these items are currently being monitored as quality indicators in order to find the way to minimize them.

What next?

The analysis of data recorded in the App provides us valuable management indicators for organizing work in the preparation area.
Tracking these indicators serves as a quality tool for the area and helps us identify opportunities for improvement.

The pharmaceutical approach to the processing of donor human milk in a human milk bank

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European Statement

Production and Compounding

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.

Development of a compact, disposable filter to reduce the discharge of pharmaceutical waste into the sewer

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European Statement

Production and Compounding

Author(s)

Annemarie Aart van der – Beek van der, Mattijs Maris, Erwin Koetse, Alex Hol, Meilof Feiken

Why was it done?

Hospital Pharmacies and especially the laboratories produce wastewater containing medicine residue. When this wastewater is discharged into sewage it contributes to the load of pharmaceutical residue and ultimately to pollution of surface-, ground and drinking water. To reduce this load, waste can be collected and transported to a processing facility for incineration and deactivation or alternatively treated locally. Our goal was to develop a practically applicable method that could effectively reduce the pharmaceutical sewage load locally, at the source.

What was done?

We developed a practical, compact, disposable filtration system that can be used on-site to reduce the amount of pharmaceutical residue in wastewater of our pharmaceutical laboratory. We tested and optimized the composition of the filter to effectively collect organic substances from locally produced wastewater (influent). We monitored filter performance and durability by analysis of filtrates (effluent).

How was it done?

Laboratory wastewater was collected during one month to yield 10 L influent. Portions of influent were filtered through 9 different types of filter packing and the effluents collected for analysis.
The influent reference and effluent samples were analysed using an iontrap LC/MS screening method using diazepam-D5 as an internal standard. The signal abundance 12 most relevant substances was chosen to evaluate the level of reduction by filtration. Based on these analyses, the optimal filter packing was determined.

What has been achieved?

In the effluent of the best performing filter packing, the abundance of 9 substances was reduced by 91,5-99,9%. The abundance for the other 3 substances was below detection limit.
Substances removed more >99%: atorvastatine, carbamazepine, clarithromycine, diclofenac, granisetron, midazolam, naproxen, propranolol and rocuronium. Substances removed between 91-99%: cefazolin, ephedrine and ropivacaine.

What next?

The optimal filter composition will be tested in practice in a test setup. In addition, cost effectiveness and sustainability compared to alternative waste collection methods will be evaluated.

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BOOST is where visionaries, innovators, and healthcare leaders come together to tackle one of the biggest challenges in hospital pharmacy—medicine shortages.