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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.

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Author(s)

Martin Munz, Ewelina Korczowska, Maria Costa, Christine Petter, Shahla Farokhnia, Katharina Kronister, Sandra Dunkler, Thomas Schweiger, Martina Anditsch, Martina Jeske

Why was it done?

Several studies show that contamination with cytostatics is found on various work surfaces in hospitals [e.g., Chauchat L et al. 2018, Hon CY et al. 2014]. Wipe sampling for surface residue of antineoplastic and other hazardous drugs in healthcare settings is currently the method of choice to determine the workplace’s environmental contamination with these drugs [Connor TH et al. 2016].

What was done?

Hospital pharmacists of four Austrian hospitals (Vienna General Hospital, Innsbruck University Hospital, Landesklinikum Horn-Allentsteig, and Landesklinikum Zwettl) differing in size, logistic requirements and production capacity, equipment (but all using Closed System Devices), and involved staff participated in the MASHA (Research about Environmental Contamination by Cytotoxics And Management of Safe Handling Procedures) project of the European Society of Oncology Pharmacy (ESOP).

How was it done?

In the first part of the project, surface contamination by cytostatics was investigated using wipe samples. Subsequently, training materials were developed and used for uniform training of medical staff involved in administering antineoplastic drugs. After the training, a second set of wipe samples of the same surfaces were taken and analyzed.

What has been achieved?

All four hospitals’ results in the first series of measurements were below the reference value given in the project of 0,1ng/cm², indicating “low” contamination. Only a small amount of samples show values between the limit of quantification (LOQ), dependent on the substance and analytical method, and 0,1ng/cm². The same is for the second series of wipe samples after the training. Considering that standards, recommendations or trainings by pharmacists or occupational health professionals has already been in place before this project, the impact of further training for the medical staff could not be quantified by measuring the residues. However, feedback from trained staff was exclusively positive, and our main objective to demonstrate that occupational exposure with cytostatics is low to non-detectable on our wards was achieved.

What next?

We want to encourage more hospitals to get involved in similar projects, and we hope that more powerful analytics will give us more answers for proper handling.

Author(s)

Marianna Rivasi, Gregorio Medici, Lucia Ricchi

Why was it done?

Because of the need to administer DA-EPOCH over a continuous 96-hour period, patients are traditionally hospitalized. Frequently, these admissions may be delayed because of bed shortages. Previous studies have shown that EPOCH-containing regimens can be safely administered in the outpatient setting, thus decreasing inpatient bed use and overall health care costs. Home-based chemotherapy is normally preferred by patients and helps reduce the risk of hospital-acquired infections; furthermore, other aspects such as functional decline and social isolation are minimized. Beginning in August 2019, we introduced an outpatient EPOCH-based chemotherapy model with portable infusion pumps and have already treated 9 patients.

What was done?

DA-EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) -based chemotherapy is traditionally administered inpatient because of its complex protocol and number of involved medications. These routine admissions are costly, disruptive and isolating to patients. Here we describe our experience transitioning from inpatient to outpatient setting.

How was it done?

We purchased 3 CADD-SOLIS infusion pumps (Smiths Medical) and connected them to the bags containing chemotherapy. One of the main issues we observed in this procedure was the flow disturbances due to the presence of small air bubbles in the pump delivery line so we tried to develop a method aiming to reduce this effect.
We changed the first type of device we used with a new one consisting of an irreversible spike needle-free access to IV bag (BTC, Italia) inserted to the medication port of the bag. Into the spiking port we insert the CADD High-Volume administration set. It is crucial to remove all the air inside the IV bag and make sure there is no extra air injected into the bag when adding medication, finally do not forget to fully prime the tubing.

What has been achieved?

Outpatient EPOCH administration was associated with cost savings of approximately 400.000€ for both chemotherapy costs and hospital day avoidance (45 days). In addition to cost savings, outpatient administration improve patient satisfaction, without any apparent decrement in treatment efficacy.

What next?

Outpatient treatments would lead to changes in how both patients and providers relate to cancer care. Transitioning care out of the hospital and related cost reduction allowed for additional investments in public health.

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Why was it done?

In 2017, the hospital pharmacy has started a project for automated chemotherapy preparation aimed at managing the increasing workload, while ensuring highest level of quality and healthcare workers safety. In Denmark, the authorities expect hospital pharmacy preparation to be GMP compliant. To achieve the best implementation of APOTECAchemo, go-live was preceded by thorough qualification process and followed by robot performance evaluation in a GMP-pharmacy.

What was done?

A robotic system for aseptic preparation of cytotoxic drugs was implemented in the pharmacy-based, Grade C cleanroom compliant with Good Manufacturing Practice (GMP). Specific work organisation allowed the integration of APOTECAchemo into the pharmacy workflow, thereby steadily improving the robot productivity.

How was it done?

A multidisciplinary team defined 228 User Requirements Specification (URS) addressed in the tender and associated to GMP regulations to assess that the technology complied with the intended purpose. APOTECAchemo passed through all qualification stages: design qualification (DQ), factory-acceptance testing (FAT), installation qualification (IQ), site-acceptance testing (SAT), operational qualification (OQ), performance qualification (PQ). The implementation of robot was evaluated in terms of doses prepared, active ingredients processed, and % of the total production compounded. Data were taken from the management software and examined from June 2019 to September 2020.

What has been achieved?

The qualification process was completed in 13 months (from April 2018 to May 2019). APOTECAchemo fulfilled the requirements set in accordance with GMP regulations and went live in May 2019. In the first 15 months of operation, 20,968 doses were prepared with the robot, of which 18,242 infusion bags (87%) and 2,726 elastomeric pumps (13%). The number of active ingredients processed were 21, of which five (5-fluorouracil, calciumfolinate, irinotecan, gemcitabine, carboplatin) covered 58% of the total production. Average production of the robot increased by 39%, from 963 doses/month in 2019 to 1,582 doses/month in 2020. The % of the total production operated by APOTECAchemo rose from 20.9% (2019) to 46.4% (2020).

What next?

APOTECAchemo robot was successfully implemented in a fully GMP-compliant hospital pharmacy, thereby enabling the automation of the preparation process and the reduction of the manual operations. Through the evaluation performed, the hospital pharmacy decided to install a second robotic system to further enhance the automated production.

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Author(s)

Isabelle Sommer, David Palmero, Céline Julie Fischer-Fumeaux, Lydie Beauport, Vincent Adamo, Hervé Schwebel, Pascal Bonnabry, Lucie Bouchoud, Farshid Sadeghipour

Why was it done?

PN can be composed of about 50 different ingredients, whereof the majority are amino acids (AA). Therefore, PN represents a complex and high-risk fabrication. ME are often related to PN and may include prescription, transcription, preparation, and administration errors. As the treatment with PN is indispensable for a good cerebral and neurologic development as well as a postnatal weight gain, ME can result in growth retardation, developmental disturbances, and infections.
This project was performed with the aim to reduce ME having an impact on vulnerable newborns and to improve the security and quality of their nutritional treatment.

What was done?

A standardized pediatric parenteral nutrition (PN) solution for the first days of life of newborn infants has been developed. An industrial partner manufactures the ready-to-use double-chamber bag which is available 24/7 and of high-quality allowing a secured administration as well as a reduction of medication errors (ME).

How was it done?

A working group composed of pharmacists, clinicians, neonatologists, and industrials developed a PN solution for the first days of life of newborn infants conforming to the needs of two different neonatal services. An applied standardized PN and the ESPGHAN guidelines haven been used as references. The feasibility of an industrial production of double-chamber bags has been evaluated and implemented.

What has been achieved?

The developed PN solution has been formulated for a peripheral venous administration with an osmolarity under 900 mOsm/L to allow a wider range of application. The production of double-chamber bags has been chosen to increase the stability and shelf-life. The first compartment contains an AA admixture and the second compartment contains glucose and electrolytes (sodium, calcium, organic phosphate). This solution is initially produced by the service of pharmacy and afterwards by the industrial partner. The standardized PN bag has been implemented successfully on the neonatal ward in March 2019. Since then, almost 1800 standardized bags have been used (appr. 90 bags/month), resulting in a reduction of individual on-ward PN preparations of nearly 80%.

What next?

Further standardized PN for newborn infants need to be developed to allow a safe nutritional treatment. On-ward PN preparations must be prohibited to prevent undetectable preparation errors.

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Author(s)

Bastian Mende, Irene Krämer, Jannik Almasi, Christoph Klaas, Bernhard Rainer Kujau, Swantje Eisend, Herwig Heindl, Jacopo Raffaelli, Jochen Schnurrer

Why was it done?

During a two-day meeting in September 2018, the German community of APOTECAchemo users and technology experts developed Best Practices for the optimal implementation and subsequent application of APOTECAchemo technology in pharmacy based aseptic preparation of ready-to-administer antineoplastic medicinal products.

What was done?

Robotic systems, designed for the aseptic preparation of ready-to-administer parenterals in hospital pharmacies, should facilitate a fully integrated workflow and a process organization interconnecting the automated and manual preparation. Despite some differences between the hospital pharmacies, the definition of standards and Best Practices for the automated compounding of cytotoxic preparations facilitates the implementation of the technology in different hospital pharmacies.

How was it done?

Prior to the meeting of the user group a survey with 24 statements for the implementation and use of the APOTECAchemo technology was sent to the German APOTECAchemo users. The 24 Best Practices were assigned to 4 categories: Workflow & Organization, Production, Roles & Responsibilities and Quality & Process Control. The survey participants evaluated the proposed Best Practices in view of the practicability in German hospital pharmacies. During the meeting, results of the survey were consented or adapted and additional best practices were defined.

What has been achieved?

The German user group defined the Best practices for the implementation and use of APOTECAchemo technology. The most relevant result for each of the four categories is:
• Workflow and Organisation: The automated preparation should reduce the daily workload of manual preparation and minimize potential errors.
• Production: Optimum interconnection between technicians and the robot will increase the efficiency.
• Role and responsibilities: Pharmacists are responsible for the design of the automated production workflow, while technicians become the manager of the automated compounding process
• Quality & Process Control: Microbiological controls must be performed during manual and automated production

What next?

The best practices defined by the German APOTECAchemo Community support experienced users and are especially useful for hospital pharmacies newly implementing the technology.

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Author(s)

VIDAL CARLOS

Why was it done?

The publication of NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings established that crushing tablets or making solutions
from them means an unasceptable risk at hospitals.

In adtition to this, USP 800 and Directive 2004/37/EC of the European Parliament on the protection of workers from the risks related to exposure to carcinogens or mutagens at work , impose the use of closed system devices and a plastic pouch to contain any dust or particles generated in these operations.

Conversely, there is no closed system device to crush, disperse and administer safely .

What was done?

We developed a new medical device to protect caregivers from exposure risk derived from crushing and dispersing in water hazardous drugs tablets.

How was it done?

We designed a new medical devide by combining existing issues so as to develop a workable solution that could overcome this safety problem and ensure the compliance with occupational regulations , and ensure a complete dosage.

What has been achieved?

We patented a new medical device that will allow a safe administration reducing exposure risk and environmental pollution at : pharmacy departments ( cross contamination in cabinets ) , nursery units and even at patient´s homes to protect caregivers and relatives.

Its design and simplicity of operation will favor its universalization.

This is an initiative of a hospital pharmacist to solve a daily problem and an example of the our potential in healthcare innovation.

What next?

The commercialization of this medical device will fulfill an unmet need in our daily practice at helathcare facilities and patients homes

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Author(s)

Lucía Rubio , Mónica Montero

Why was it done?

Hospital Pharmacy Services staff may be exposed to hazardous substances, involving a risk to health. For this reason, is important to identify these substances and measures must be taken to ensure maximum safety for the staff at work. We decided to review the topic when we saw in the Technical Document on Prevention Measures for the Preparation and Administration of Dangerous Drugs, published by the National Institute for Safety and Hygiene at Work (INSHT) there are no specific recommendations for protection of raw materials used in magistral formulas; it only refers to dangerous drugs.

What was done?

Identify health problems involved in handling raw materials that we use in the preparation of magistral formulations. Define personal protective equipment and installations necessary for handling.
Improve work safety of area’s staff.

How was it done?

We have to update raw materials discharged in 2018 in the Pharmacy Service.
The safety data sheets were reviewed in the National Institute for Occupational Safety and Health, paying special attention to dangerous identification and exposure controls/individual protection sections. In this database there is not all the information, so we have to use data sheets of our supplier.
We studied Regulation (EU) Nº 1272/2008 on classification, labelling and packaging of substances and mixtures to determined 3 variables: health dangerous, using hazard class like REPR B, MUTA 2 and STORE RE 1; personal protective equipment and installations must be used in handling of our raw materials.

What has been achieved?

We obtained a list of 20 raw materials. 40% of raw materials aren´t considered hazardous.
Of 60% that are classified as hazardous, they were divided into 2 levels: the first, with categories such as serious eye injuries, skin disorders, respiratory tract irritation or toxicity if swallowed; it includes 75% of raw materials. The second level, which includes the rest of products considered hazardous (25%), is associated with 3 categories: REPR B or possible carcinogenicity, that influence the fertility and development of the fetus; MUTA 2 or genetic defects, that are associated with germ cell or mutations; and STORE RE 1 that can cause damage to organs after prolonged or repeated exposure. For 40% of raw materials there are no specific recommendations about using personal protective equipment. With 60% it is recommended to use self-filtering masks for particles, protective gloves and glasses. For 16% of materials, protective clothing against chemicals is required too. In 65% of raw materials, no specific installation is required to handle them. However, for 25% it is recommended to have well-ventilated areas and with 10% a chemical smoke cabin.

What next?

Most of raw materials we use to make magistral formulations are considered hazardous according to Regulation (EU) nª1272/2008. For this reason, we developed a protocol that included individual protection measures and laboratory equipment necessary to handle such raw materials. So it is possible to normalise the preparation of magistral formulations guaranteeing the safety of the area’s staff. We have devised a plan for review and update of the protocol, following current regulations.

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Author(s)

MARIA MUROS ORTEGA, INMACULADA SANCHEZ MARTINEZ, ARANTXA ANDUJAR MATEOS, ISABEL ALARCON FUENTES, FRANSCISCO VALIENTE BORREGO, ANGELA SANCHEZ , ASUNCION SARABIA, ANTONIA RODRIGUEZ, NURIA LUCAS VILLA

Why was it done?

Condylomata acuminata or genital warts are produced by human papillomavirus (HPV). They are considered one of the most common sexually transmitted diseases that must be treated on an individual basis. Imiquimod increases the local immune response mediated by interferon and other cytokines; it is marketed as a 5% cream for topical administration 3 times a week, for a maximum of 16 weeks.

What was done?

The aim of the study is to describe the formulation and results obtained after treatment with imiquimod suppositories manufactured by the Pharmacy Hospital Service.

How was it done?

Suppositories of imiquimod 6.25mg were prepared from Aldara® 5% cream sachets; stearic mass was used as excipient to convey the active principle adding about 2.2g/suppository and molds of 2g for its preparation. The bain-marie was used for fusion and mixing the components. A sterile gauze was included to facilitate extraction if there was anal irritation. The established shelf life was 6 months between 2−8ºC. Suppositories were dispensed individually wrapped in aluminium foil and protected from light added a diptych of information to the patient.

What has been achieved?

The case of a 33-year-old male, VHP 6 positive, with anal condylomatosis and high-grade epithelial dysplasia, most of which had been resected and burned previously without satisfactory results. Imiquimod was added as an adjuvant treatment in suppositories for administration three days a week at night. Twelve suppositories were dispensed each month, and the duration of treatment was 2 months. During treatment the patient reported good tolerance, no itching, no pain in the area of administration. One month after finishing the treatment, no new macroscopic lesions were observed, nor recurrence of previous ones in anoscopic examination.

What next?

The contribution of the Pharmacy Service through the development of imiquimod suppositories has facilitated the achievement of early health results in a complex treatment pathology, allowing rectal administration through suppositories made from a specialty marketed in envelopes for topical use and reducing the duration of treatment to 8 weeks, with very good tolerance on the part of the patient.
References:
1. Bastida C et al. Formulation of imiquimod suppositories for the treatment of intra-anal neoplasms by human papillomavirus. 57th SEFH Congress.
2. PNT elaboration of the Reina Sofía General University Hospital.
3. Lacey C et al. 2012 European guideline for the management of anogenital warts. J Eur Acad Dermatol Venereol 2013 Mar;27(3):e263-70.
4. AEPCC-Guide: Condylomata acuminata. AEPCC Publications, November 2015.

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Author(s)

Jane Francomb, Dirk Leutner

Why was it done?

Formularies for extemporaneous formulations of paediatric medicines of appropriate quality are currently available in some regions or countries, but no pan-European equivalent exists. Some formulations in use are not appropriate due to a lack of knowledge of best practices. The idea behind the new formulary is to collect, review and then select the most appropriate formulations currently used in Europe which meet today’s requirements.

What was done?

The European Paediatric Formulary was launched at the end of 2019. It is a freely available online publication for pharmacists and clinicians that is intended to provide guidance on the use and preparation of standardised paediatric medicines of an appropriate quality when a suitable licensed medicinal product is not available. The first two monographs and two explanatory texts of the European Paediatric Formulary have now been published by the European Directorate for the Quality of Medicines & HealthCare (EDQM).

How was it done?

Criteria for selection and evaluation of formulations were developed by 2015. Since then the current work is carried out by the European Paediatric Formulary Working Party under the supervision of the European Pharmacopoeia Commission and the European Committee on Pharmaceuticals and Pharmaceutical Care (CD-P-PH). The EDQM provides the scientific secretariat. Monographs for development were prioritised based on patient need. Many formulations currently described in national formularies and other well-established formulations have been gathered from stakeholders throughout Europe. The information available for the most appropriate formulation was transferred into a common format with full quantitative composition details, extemporaneous preparation instructions, validated test methods for quality control and storage conditions.

What has been achieved?

Monographs for hydrochlorothiazide 0.5mg/mL oral solution and sotalol hydrochloride 20mg/mL oral solution were published at the end of 2019. These were accompanied by an introduction and general principles which describe the purpose and content of the European Paediatric Formulary.

What next?

Monographs for Azathioprine oral suspension, Chloral hydrate oral solution, Furosemide oral solution, Isoniazid oral solution, Omeprazole oral suspension and Ranitidine oral solution and a monograph on an oral vehicle are currently under development. Further prioritised items will subsequently be added. Draft monographs for public consultation and final texts will be made available on https://paedform.edqm.eu.