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Use of a closed-system drug transfer device in the handling and administration of ganciclovir outside the hospital pharmacy unit

European Statement

Production and Compounding

Author(s)

Lucia Ricchi, Gregorio Medici, Porretta Serapiglia Carla, Marzia Bacchelli, Marianna Rivasi

Why was it done?

Hazardous drugs (HDs) may include antineoplastic or cytotoxic agents, biologic agents, antiviral agents, immunosuppressive agents, and drugs from other classes. Healthcare workers, especially nurses and pharmacy personnel, experience occupational exposure to these HDs.
Preparation and administration of ganciclovir should only be performed by health professionals who have been appropriately educated and trained and deemed competent in its use. Until now the preparation of ganciclovir was performed by the pharmacy’s antiblastic drugs unit. However, during closing times, kits for the self-preparation (antiblastic gloves and gowns, FFP3 masks, eye protections and brief instructions for reconstitution) were provided.
Many strategies have been deployed to reduce the risk of occupational exposure to HDs, including control devices designed to act as closed systems and preventing exposure through liquid or vapor leakage. These devices mechanically prohibit the escape of HDs from the system and can be used for preparing and administering these drugs.

What was done?

Some of the intensive care units of our hospital have been enabled to prepare their own ganciclovir bags by using a closed system drug transfer device (CSTDs).

How was it done?

Each nurse involved was instructed by hospital pharmacists on how to handle CSTDs. In addition to this they were also given a short video and an infographic showing the main operations to be carried out.
Ganciclovir bags are prepared using the Tevadaptor® (Simplivia), in a needleless technique, by combination of the Vial adaptor, the Syringe adaptor, the Spike port adaptor and a connector closed male (Spiros, ICU).

What has been achieved?

Use of CSTDs is a simple and effective way to reduce exposure to HDs, provide better protection, better aseptic technique and better containment of waste than the traditional method, as well as allows the preparation of HDs to be carried out outside the antineoplastic drug unit.

What next?

In the future their use could also be extended to the preparation of monoclonal antibodies and antibiotics considering that there is not enough definitive research on the effects of occupational exposure to these agents. And, to date, there is no known safe maximum level of exposure to these drugs.

Expanding hospital pharmacy services by centralizing the preparation of non-cytotoxic intravenous medications: A preliminary overview of the Italian community of APOTECA users

European Statement

Production and Compounding

Author(s)

Alessandro D’Arpino, Fiorenza Enrico, Caterina Donati, Simone Leoni, Giorgia Longobardo, Marco Bellero, Alessandra Bianco, Giuseppe Zacchi, Anna Zaltieri, Stefano Monica, Nicolò Squartini, Matteo Federici

Why was it done?

In most of Italian healthcare organizations, the large majority of non-cytotoxic IV medications are prepared in clinical environment by nursing staff. This is recognized as a complex and labour-intensive process that entails various risks of potential medication errors (microbial contamination, wrong reconstitution/dosing). Centralizing the preparation from the clinical environment to the pharmacy in order to provide ready-to-administer IV medications represents a strategy to improve safety and prevent medication errors.

What was done?

The community of APOTECA technology users is committed to fostering co-de¬sign of technology based on the hospitals’ needs and sharing best practices for improving hospital pharmacy services. During a meeting taken place in September 2021, a panel of hospital pharmacists belonging to APOTECA community laid the groundwork for centralized preparation of non-cytotoxic intravenous (IV) drugs and establishment of Central Intravenous Additive Service (CIVAS) in Italian hospital pharmacies.

How was it done?

The following methodology was adopted to promote a standard profile of centralization: (1) definition of criteria for the selection of drugs suitable for centralized preparation, (2) identification of IV medication classes for which preparation should be centralized due to intrinsic risks and demand, (3) evaluation of potential benefits, (4) discussion on organizational challenges regarding the establishment of CIVAS, (5) assessment of the role of automated preparation with robotics.

What has been achieved?

Five selection criteria to centralize drugs were mentioned: long-term stability data, frequency of use, cost, complexity of preparation, microbial contamination risk. Continuous infusion of antibiotics, vasoactive drugs, anaesthetics, pain medications, intravitreal injections, and patient-individual doses for paediatric patients were chosen as eligible IV medication classes to implement centralized preparation. Major benefits of centralization were pointed out, i.e. proper aseptic preparation, perspective quality controls, process traceability, reduced drug wastage, and releasing nursing time to care. Logistics, inventory management, limited space, and inadequate quality control units were identified as main challenges to the CIVAS establishment. Participants agreed that robotics plays an important role to minimize repetitive manual activities, optimize working efficiency, and increase pharmacy production capacity, thereby streamlining the introduction of CIVAS.

What next?

A close collaboration between healthcare staff and hospital pharmacy will be essential to evaluate the feasibility of centralized preparation as well as its clinical and cost-effectiveness.

Disposable Closed System for Sterile Drug Preparation and administration

European Statement

Patient Safety and Quality Assurance

Why was it done?

Our proposed system comes from the idea of a large clean room with pressure regimes, and airlock, hoods and other ancillary equipment, Which we made from it a very small clean room that is our box, when there will be no need for us as operators to get into it, or very simply take only those parts that are supposed to be sterile, and only those parts that are the two ends of the infusion bag and the end of the medicine vial

What was done?

“Closed” and airtight system for preparation (reconstitution, measurement, dilution) and injection of IV drugs at the patient’s bedside, in the various clinics and further home treatment, Disposable system, All its parts come in one piece without the need for threading, or assembly and disassembly
Estimated dimensions: 10 cm length, 5 cm width and 3.5 cm depth or similar, its shape can be rectangular or any shape convenient for use operation storage and destruction at the end of the process
Intended for a wide range of types of drugs – such as intravenous antibiotics, cytotoxic drugs, biological drugs, etc.
Designed according to its different variations for different types of vials and different amounts of drugs that come as a dry powder for dissolution, and are also suitable for drugs that come in the dissolved liquid form.
It is also intended for use with glass ampoules and there is a wide range of drugs that still come in glass ampoules
Intended for administration of drugs that do not need to be diluted in an infusion bag given in IV PUSH

How was it done?

We designed the device with 3D software (solid wark). It consists of a number of functional parts,
The sterile closed system comprises an airtight enclosure, which is shaped so as to define an enclosure interior; and an infusion-bag receptacle. An infusion-bag seal is configured, when in a sealing state, to make an airtight seal with respective external surfaces of a medication port and an IV tubing port of a bottom region of the infusion bag, when the medication port and an IV tubing port are inserted into the infusion-bag receptacle.

What has been achieved?

The proposed solution and its advantage
– A single-use system built in one piece, without the need for assemblies, disassembles, etc.
It will be possible to perform the entire process in one place, such as at the patient’s bedside or in the clinic, starting with the powdered drug dissolving process, mixing a measured dose, mixing it in an infusion bag and injecting it into the patient’s vein safely and accurately.
Maintains the perfect process under sterile conditions without fear of contamination of the injected drug
– Preparation in a system that is safe for the immediate environment and safe for the caregiver himself from contamination of drugs such as cytotoxic drugs, antibiotics and more
Savings in building very expensive infrastructure of clean rooms
Saving on very expensive disposables, such as closed system transfered deviced, robes and more
Save valuable work time dedicated team of pharmacists, nurses work time, work time transportation, storage places and more
Minimize the chance of errors in administering medications and confusion between different medications
Working with non-exposed needles reduces the chance of needle prick injury

What next?

Applied research will be carried out by pharmacists and nurses, in order to test the efficacy and safety of the device (by using a basic prototype), these experiments will use different IV administration drugs, we will test the method of dilution from a drug vials and glass ampoules, measure the exact dose and transfer to the infusion bag, and remove through the IV line, the accuracy of the preparation, the sterility of the preparation, the quality in terms of leakage or drip, comfort, safety and more are measured.

New frontiers of hospital pharmacy: management and preparation of human tissues used in the surgery room

European Statement

Clinical Pharmacy Services

Author(s)

Andrea Ossato, Giuseppe Giovagnoni, Michele Giannini, Anna Francesca Spada, Francesca Realdon, Valeria Mezzadrelli, Lorenza Cipriano, Nicola Realdon, Teresa Zuppini, Roberto Tessari

Why was it done?

Since 1st October 2019, the regional tissue bank that supplies hospital, stopped sending ready-made tissue to the implant, preferring the shipment of tissues frozen at -80°C. For this reason, the hospital pharmacy developed a procedure for the management of orthopedic allografts ensuring a clear and safe supply chain reducing the waste raised from the obligation of immediate use of the thawed tissue.

What was done?

Hospital pharmacists, in agreement with the hospital administrators and the orthopedic surgery department, developed a new service characterized by procurement, processing, preservation, storage, thawing and preparation of human tissues and cells for orthopedic allografts, according to European and national legislation.

How was it done?

The management of orthopedic allografts took place as follows: was established a dedicated path for communications with orthopedic surgery and bank tissue; tissue thawing and washing was centralized in the clean-room of the hospital pharmacy and were guarantee adequate training of all personnel involved as well as complete standard operating procedure documentation for all stages of the process and appropriate control measures.

What has been achieved?

Evaluation of the process showed that it was favourable in terms of practicality, safety, traceability and cost saving. Especially, the centralization of tissue preparation within clean‐rooms with aseptic technique, allows microbiologically safer setups reducing clinical risk. A further guarantee of safety is given by the sterility process’s validation through Media Fill test. This organisation allowed us to reduce the waste through a more effectively management of the tissues shelf life and any missed surgery with a cost saving and an ethical behaviour.

What next?

Optimise patient outcomes through working collaboratively within multidisciplinary teams and using the limited health systems resources responsibly, are two main goals expressed by the last European Statements of Hospital Pharmacy (ESHP). This study demonstrated how the centralization of tissues management in the hospital pharmacy make the process more efficient and safer and thus comply with the ESHP’s goals; leading to a clinical advantage for patients and better economic impact for the hospital.

Compounding an extemporaneous sterile antibiotic solution for treating an infected wound

European Statement

Production and Compounding

Why was it done?

To solve a problem with a foot wound of a young man not responding on the standard secondary surgical healing intention wound treatments, that appeared at the General surgery department of our hospital.The wound was infected with 2 bacteria, S. aureus and Enterococcus species.The patient was quite long time treated with i.v. antibiotics without result.The wound infections are one of the biggest common nosocomial problems that demand special professional team engagement.

What was done?

Compounded an extemporaneous sterile vancomycine and gentamycine solution for secondary healing intention wound treatment.

How was it done?

A responsible pharmacist being alone on an afternoon duty, initiated a topical application of sterile antibiotic solution according to wound’s antibiogram.The surgeon demonstrate suspicion due to lack of that kind of experience/practice.So 100 ml solution was prepared under sterile conditions of the Department for infusion solutions production in our hospital, containing 50 mg/ml vancomycine and 1.2 mg/ml gentamycin in a 0.9% sodium chloride sterile and nonpyrogenic solution for i.v. administration.According to the SmPCs of the antibiotics manufacturers we determined 7 days expire after production, kept on room temperature.

What has been achieved?

A departmental surgeon has accepted the initiative and treated the wound twice daily at the surgery department.On the second day of applying, the wound edges held closely together and the wound has started epithelialisation.There were not any allergic reactions, significant tingling, itching and pain on the skin around the wound.On the third afternoon of introducing the solution use, the patient was discharged home and reassigned for an ambulatory treatment i.e. daily hospital, for once daily wound washing with the sterile solution.We prepared the second dose of the solution on the 7th treatment day and the wound was healed on the 13th day.

What next?

To incorporate this GPI into daily surgical standard procedures for bacterially infected wounds for a best patient issues.

SARS-CoV-2 specimen collection kits: maintaining supply through in-house production

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European Statement

Production and Compounding

Author(s)

Nikolaus Lindner, Doris Haider

Why was it done?

In Austria, Covid-19 infection rates began to increase in March. At Clinic Favoriten, over 700 patients were treated during the first wave. This resulted in an increasing demand of specimen collection sets. Even though various wholesalers and contractors were contacted, the orders could not be served in a quantitative or timely manner. These circumstances forced the pharmacy to look for alternative solutions.

What was done?

During the first wave of SARS-CoV-2 infections the hospital pharmacy of Clinic Favoriten, Vienna’s specialised Covid-19 center, assembled specimen collection sets manually to meet rising demands, compensate for shortages and secure vital diagnostics supply.

How was it done?

In collaboration with the laboratory department and other clinics of the Vienna health care group appropriate materials with CE-certification were sought to assemble a set that is easy to handle concerning production, distribution and application.
Sterile plastic tubes were filled aseptically with physiologic saline and labelled. Tubes and sterile swabs were then packed in a plastic bag that was sealed with a label providing general instructions for use. Manufacturing protocols as well as batch documentation ensured quality assurance and traceability.
Major obstacles included availability and suitability of the needed materials. Manufacturers of tubes and swabs had to be changed over time, which required close communication with medical wards and the laboratory department.

What has been achieved?

Over a period of seven weeks 2.033 specimen collection sets were assembled. In detail, a total of 20.330 swabs were packed and 10.165 tubes were filled. Through this measure a continuous supply of specimen collection sets, essential for further Covid-19 testing, was secured.
Moreover, the importance of a pharmacy in-house production with the aim of maintaining supply security was acknowledged throughout the entire hospital.

What next?

The initiative has demonstrated that pharmacists play a vital role in handling product shortages and maintaining supply security. In the future, the pharmacy will reinforce to monitor trends even more and will thus be able to balance changing demands and non-availabilities. Like this, the existence of an in-house pharmacy department securing appropriate supply will gain more and more significance. In times of increasing shortages, the initiative serves as a model for other healthcare systems confronted with similar difficulties.

The introduction of an emergency intravenous antibiotic reconstitution service during the COVID-19 pandemic.

European Statement

Patient Safety and Quality Assurance

Author(s)

Joanne Rhodes, Chris Bidad

Why was it done?

There was concern that there was a risk of reconstitution errors, missed doses or variation in dosing intervals which could impact on treatment efficacy and patient safety due to:
• a sudden increase in demand for IV antibiotics,
• depleted numbers of front-line nursing staff, and
• nurses being deployed to unfamiliar clinical environments and encumbered by PPE.
The emergency IV antibiotic reconstitution service was designed to mitigate these risks.

What was done?

In the absence of aseptic dispensing facilities an emergency intravenous (IV) antibiotic reconstitution service was set up in a laminar flow operating theatre. Nurses who could not work in a patient-facing role during the pandemic prepared ready-to-use infusions under the direct supervision of a pharmacist.

How was it done?

It was determined that a manufacturer’s licence was not required under part one, section three of the Human Medicines Regulations 2012 providing strict criteria were adhered to. Stability data was collated for the most frequently used IV antibiotics. Even where stability data supported a longer period, a maximum expiry of 24 hours after preparation was assigned. Processes were designed to adhere as closely as possible to the GMP principles described within The Rules and Guidance for Pharmaceutical Manufacturers and Distributors 2017. Specially tailored IV reconstitution training was delivered to the nurses.

What has been achieved?

Over a period of 4 weeks at the peak of the pandemic 1000 doses of IV antibiotics were prepared and supplied, enabling ward-based nurses to focus directly on patients. There were no reports of any incidents of delayed or missed doses, or administration errors relating to IV antibiotics supplied to the wards involved during this period. The time saved on the wards was equivalent to having 3 additional nurses on the wards each day.

What next?

With a reduction in the number of COVID-19 positive patients now presenting to the hospital the service has been paused but placed on standby so that it can be resumed in the event of a second wave. Work is underway to determine if there would be value in the team preparing a wider range of products, particularly those which may be of particular use in critical care areas such as sedatives and inotropes.

IMPROVING ANTIBIOTIC STEWARDSHIP AT A HOME HOSPITAL UNIT BY IMPLEMENTING THE PRODUCTION OF ELASTOMERIC PUMPS CONTAINING BENZYLPENICILLIN (submitted in 2019)

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European Statement

Production and Compounding

Author(s)

Maria Rautamo, Niina Laihanen , Laura Lehtola

Why was it done?

Erysipelas was the most commonly treated infectious disease at the home hospital unit in 2015. Previously the standard treatment was broad-spectrum antibiotic cefuroxime three times daily. The infectious disease specialist wanted to improve the antibiotic stewardship by shifting from cefuroxime to a continuous infusion of narrow spectrum benzylpenicillin. The aim of the initiative was also to improve patient care and reduce the number of treatment visits and thus overall treatment costs.

What was done?

The production unit at the hospital pharmacy began preparing elastomeric pumps containing benzylpenicillin for Helsinki city home hospital unit for the treatment of outpatients suffering from erysipelas. A pilot study was conducted in November 2018 before further implementation of the elastomeric pumps.

How was it done?

A benzylpenicillin 10 million IU infusion solution was prepared and transferred to elastomeric pumps (Folfusor LV10, Baxter) in the production unit at the hospital pharmacy. The production method was developed by pharmacists at the hospital pharmacy in cooperation with Baxter and the formulation as well as stability information was received from Baxter. The pilot study was planned and executed in cooperation with Helsinki city home hospital unit. The batch size of prepared elastomeric pumps was 7 pumps a week and the overall pilot period consisted of 5 weeks. A total of 8 patients were treated during this period. The opinions of nurses and patients about the use of elastomeric pumps were investigated through a questionnaire. The impact on treatment costs were also evaluated.

What has been achieved?

Elastomeric pumps containing benzylpenicillin have been implemented as a standard treatment for erysipelas at the home hospital unit. Cost savings from the pilot period of 5 weeks were 125 nurse visits corresponding to approximately 100 hours of work as well as 200 km of driving for nurses to patients’ homes. The patients were very pleased with the elastomeric pumps and the fact that the pump had to be changed only once daily.

What next?

Production and delivery of elastomeric pumps containing benzylpenicillin has expanded to other home hospital units. The implementation of elastomeric pumps containing other active ingredients is under investigation.

IMPLEMENTATION OF INTRAVITREAL TISSUE PLASMINOGEN ACTIVATOR INJECTION INTO PRACTICE (submitted in 2019)

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European Statement

Production and Compounding

Author(s)

Liisa Eesmaa, Katrin Sõnajalg, Ülle Helena Meren

Why was it done?

Intravitreal tissue plasminogen activator (tPA) injection is a guideline recommendation for patients with medium, large or thick submacular haemorrhage mainly due to exudative age-related macular degeneration (AMD). This treatment hasn´t been available: off-label use, rare demand, high price (generic unavailable, the cost uncovered by health insurance).

What was done?

Ophthalmologists contacted the pharmacy to work out a plan for emergent cases of patients with large submacular haemorrhage in the better seeing eye. The pharmacists worked out the logistically simplest, economical affordable solution to prepare the injection in a cleanroom setting.

How was it done?

The pharmacy came up with two models: 1. Compound intravitreal injection (50 μg/dose) from Actilyse 50mg vial (€375) containing substance for intravenous infusion. The rest of the vial would possibly be used in the neurology department during the next 24 hours. The costs would be shared based on microgram use. 2. Use unregistered Actilyse cathflo 2mg vial. Application for permission and delivery would take up to 6 weeks and drug shortages would be usual. The price for 50 μg would be €65. For the first two patients the first model was used. It was logistically complicated for the neurology department as they needed to change their everyday practice. The second model has now been introduced into practice and used for another two cases. It is accepted by the doctors and pharmacists.

What has been achieved?

Four patients have received new treatment with intravitreal tPA in addition to the common practice of pneumatic displacement of the haemorrhage with intravitreal anti-VEGF (vascular endothelial growth factor) injections or intravitreal anti-VEGF monotherapy. The treatment was well tolerated by the patients with some benefit to visual function. The pharmacy is ready to prepare tPA injections during working days. The price of the injection is acceptable.

What next?

The University hospital became interested to start the same treatment. The second model was presented to their hospital pharmacy. Our ophthalmology department is now equipped to inject tPA into the subretinal space during vitrectomy to increase the efficacy of the procedure and improve patients’ visual outcome.

MICROBIOLOGICAL CLEANLINESS IN A CHEMOTHERAPY ROBOT DEPENDING ON DIFFERENT INTERVALS OF INTENSIVE CLEANING IN THE WORKING AREA (submitted in 2019)

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European Statement

Production and Compounding

Author(s)

Jannik Almasi, Irene Krämer

Why was it done?

Aim of the study was to evaluate if the microbiological cleanliness of the working area of APOTECAchemo® is affected by extending the interval of intensive cleaning from biweekly to monthly cleaning intervals.

What was done?

Automated preparation of ready-to-administer chemotherapy products with the APOTECAchemo® robot is well established in a number of pharmacy departments. One of the few disadvantages is the time-consuming, intensive cleaning and disinfection of the working area (clean room class A) by wiping with cleaning and disinfection solutions.

How was it done?

Every two weeks (period 1: 07-12/2018) or every four weeks (period 2: 01-06/2019) all surfaces in the working area of APOTECAchemo® were wiped with ethanolic NaOH solution in order to inactivate or remove cytotoxic spillages. In a second work step all surfaces are disinfected by wiping with spore-free alcohol. The procedure lasts about one hour. The working area is at the end of each working session irradiated with UV light for 4 hours. Microbiological monitoring of the working area is done weekly in operation by passive air sampling (2 settle plates at predefined locations S1, S2) and surface sampling (3 contact plates at predefined locations O1, O2, O3) and colony-forming units (CFU) are counted after incubation. Results of the microbiological samples (CFU ± standard deviation) were compared for period 1 and 2. On average, 0 CFU (n=52) were detected (period 1) and 0.04±0.2 CFU (n=44) (period 2) on settle plates. During period 1 on average 0.04±0.19 CFU were found at O1, 0 CFU on O2, and 0.81 CFU±4.23 at O3 (n=27 each). During period 2, 0 CFU were detected at O1, O2 and 0.04±0.2 CFU at O3 (n=25 each). The extended interval for the intensive cleaning process did not affect the microbiological cleanliness. The CFU limits set for clean room class A were met.

What has been achieved?

Maintaining the daily cleaning procedure, the interval of intensive cleaning can be extended to one month without increasing the microbiological contamination risk and saving two hours of cleaning.

What next?

Monthly intensive cleaning will be attended by trending the microbiological results.

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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.