Development of method for mobile aseptic preparation of advanced therapy medical products
European Statement
Production and Compounding
Why was it done?
The pharmacy received a request for reconstitution of an ATMP Luxturna. The pharmacy or hospital did not have a suitable aseptic facility that could perform the reconstitution in a way that allowed the ATMP to be administered to patients before the expiry after reconstitution (max. 4 hours).
What was done?
Development of a single use isolator for advanced therapy medical products (ATMP) or gene therapy drug preparation was undertaken. The single use isolator had to be mobile to enable pharmacy staff to preform reconstitution directly on ward or in OP-theatre. It had to comply with Health and Safety regulations and at the same time make it possible for pharmacy staff to use aseptic technique to be able to reconstitute ATMP.
How was it done?
A review of isolator technology was performed, and a suitable solution identified. The set-up was further developed in a team with representatives from pharmacy, the eye department at Rigshospitalet-Glostrup. A manufacturer of the equipment was selected, and development performed. The set-up for ATMP preparation was presented to The Danish Health and Safety (DHS) department responsible for handling this type of treatment. The approval was granted after a standard 90-day period. Pharmacy staff were trained in working with the set-up and a dry run made in the eye theatre with the full surgical team.
What has been achieved?
10 patients (19 eyes) have been treated, 4 male and 6 female patients with age span 12-39 years. After having performed the procedure twice there was enough routine to treat 2 patients per theatre day hence reducing the cost of preparation and increasing efficiency of the team.
The pharmacy and surgical team have established a great working relationship and now consider the set-up as routine.
In spring 2021 the set-up was approved by (DHS) for reconstitution of Zolgensma. On July 1 a pediatric patient was treated with Zolgensma using the method.
What next?
Plan to develop the method further and make it available for coming preparations of ATMPs and share knowledge of the method with other hospital pharmacy organizations.
INCOMPATIBILITIES OF PARENTERAL DRUGS IN INTENSIVE CARE – ANALYSIS AND OPTIMISATION OF ADMINISTRATION SCHEDULES OF CENTRAL VENOUS CATHETERS AND FREQUENTLY USED DRUG COMBINATIONS
Pdf
European Statement
Patient Safety and Quality Assurance
Author(s)
Martina Jeske, Jasmin Stoll, Vanessa Funder, Sabine Bischinger
Why was it done?
Due to the limited number of ports, it is necessary to administer several drug solutions via the same access. Incompatibility reactions can occur and may lead to a reduction or loss of drug efficacy and severe damage to the patient’s health. The objective was to create standardized administration protocols for central venous catheters and verify parenterally administered drugs’ incompatibility reactions. A further purpose was to build multidisciplinary cooperation to improve the drug administration processes.
What was done?
To optimize the drug therapy at four intensive care units (ICUs) of the University Hospital, the pharmacy department, physicians, and care management, jointly implemented a quality assurance project. In multidisciplinary teams, we had to overcome various challenges in different wards to develop standards regarding administering drugs via multi-lumen catheters. We analyzed all frequently used drugs (n=72) for their compatibility and summarized findings in a crosstable.
How was it done?
The current situation was recorded using a questionnaire and collecting individual cases of protocols for central vein catheters. About 2000 drug-drug-combinations were analyzed using three databases, KiK 5.1, Micromedex, Stabilis 4.0, corresponding specialist information, and manufacturer data. Nevertheless, the compatibility check based on the databases is subject to some restrictions. In several cases, the databases give different or contradictory results, and compatibility data are rarely available for some combinations. The project revealed that although infusion therapy is standardized in intensive care units, there are fewer standards regarding administering drugs via multi-lumen catheters. There are significant differences between theory and practice in terms of handling infusion therapy.
What has been achieved?
Different hazardous practices got identified and eradicated. The incompatibility table allows a quick assessment. The advantages/disadvantages of varying software systems were broadly discussed. KiK 5.1 was implemented in the ICUs, Micromedex in the pharmacy department. The team agreed that existing uncertainties must be decided jointly. Different practices in different wards may pose a threat to patient safety. The results were presented in a clinic-wide interdisciplinary training.
What next?
The awareness towards the need for cooperation and hospital pharmacists’ competence concerning incompatibility reactions strongly increased, leading to more standardization in the infusion therapy and avoiding incompatible drug combinations. The aim is to initiate a continuous improvement process.
RESOURCES OPTIMISATION OF LOPINAVIR/RITONAVIR IN THE SANITARY EMERGENCY DUE TO SARS-CoV-2 IN A THIRD-LEVEL HOSPITAL IN THE ULTRA-PERIPHERY
Pdf
European Statement
Selection, Procurement and Distribution
Author(s)
Lierni Goitia Barrenetxea, Natalia Toledo Noda, Moisés Pérez León, Victoria Morales León
Why was it done?
Lopinavir/ritonavir is a HIV-1 and HIV-2 proteases inhibitor indicated for HIV. It was used in patients with a positive SARS-CoV-2 test after being recommended by the Chinese health authorities. The hospital protocol guideline was: 400/100mg every 12 hours orally. It was presented in both tablets and oral solution, which was reserved for patients intubated in the ICU and those who were not able to take tablets.
What was done?
Optimizing the use of lopinavir/ritonavir solution during the state of sanitary emergency.
How was it done?
Descriptive study of resources optimization for lopinavir/ritonavir and actions carried out to ensure the availability of the antiviral in intubated SARS-CoV-2 positive patients. Preparation and stability data were obtained from official sources (Spanish Agency for Medicines and Health Products) and from the Spanish Society of Hospital Pharmacy.
What has been achieved?
The Pharmacy Service designed a protocol to repackage lopinavir/ritonavir 80/20mg/mL solution in syringes containing the exact amount for a single dose (400/100mg in 5ml), for single use. The solution is formulated on an alcoholic basis and there is an interaction with the polyurethane nasogastric tube because the polyurethane absorbs alcohol causing the catheter to swell and deteriorate, which is why, other services were notified to use polyvinyl chloride catheters or silicone. Likewise, the syringes used to repackage the solution were exclusive for oral administration used in pediatrics, with the aim of reducing medication administration errors, since it is not possible to connect parenteral injection needles with them. These measures were intended to make the dispensing system as efficient as possible, as once the drug entered a unit with patients with a positive test, it was contaminated, therefore it could not be reused. Additionally, the fact that the hospital is located on an island made it even more difficult to acquire the medicine, given the supply problems nationwide, the great restriction of air and maritime traffic and loan limitations from other hospitals.
What next?
The measures adopted managed to ensure the availability of lopinavir/ritonavir solution in all admitted patients, optimizing the scarce availability of a solution medication whose presentation is formulated in multidose containers. By adding the use of syringes for exclusive oral use, administration errors were prevented.
DRUG-DELIVERY-SYSTEMS FOR OPAT SELF-ADMINISTRATION: A GRAPHIC GUIDE
Pdf
European Statement
Clinical Pharmacy Services
Author(s)
Tania Truelshoej
Why was it done?
Department of infectious diseases at Aarhus Universitetshospital, Denmark, has succesfully implemented OPAT as a standard modality for certain patients requiring long-term intravenous antibiotic therapy e.g. patients with cystic fibrosis. This also include a guideline to OPAT self-administration at home.
To implement the OPAT guidelines throughout the hospital there was a need for an overview of available ready-to-use antibiotics for OPAT. The graphic guide is a help for the physicians in choosing the right drug-delivery-system suitable for OPAT self-administration.
What was done?
A graphic guide showing the ready-to-use antibiotics for outpatient parenteral antimicrobial therapy (OPAT) with special emphasis on drug-delivery-systems suitable for self-administration was developed.
How was it done?
Most information about the available ready-to-use antibiotics were obtained at the hospital pharmacy. In addition, the requirements for the different drug-delivery-system were obtained by interviewing nurses from different wards
What has been achieved?
Available ready-to-use antibiotics was listed in a graphic form with the following information: type of antibiotics, drug-delivery-system, available doses recommendations to time of administration and storage time and temperature. The drug-delivery-system were all illustrated with a photo.
The graphic guide is now part of the implemented guideline for OPAT at the hospital and is also available as a printed poster to place e.g. in the medicine room.
The guide is a help for the physicians in choosing the right drug-delivery-system suitable for OPAT self-administration and helps to raise overall awareness of the possibility of OPAT as self-administration at the hospital.
What next?
Implementation of the OPAT guideline and the included graphic guide has increased awareness of the need for the hospital pharmacy to deliver ready-to-use antibiotics that can match the needs for safe and efficient treatment at home. This is an important strategic focus for the hospital pharmacy in the coming years.
A multi-disciplinary teams’ collaborative approach to transition benralizumab dependent severe eosinophilic asthmatic patients to self-administration in response to the COVID-19 pandemic
Pdf
European Statement
Clinical Pharmacy Services
Author(s)
Grainne D’Ancona, Niall Stewart-Kelcher, Schaya Bains, Andrew Hearn, Joanne Kavangh, Cris Roxas, Linda Green, Linda Thomson, Marianna Fernandes, Brian Kent, Alexandra NanzerKelly, David Jackson, Jaideep Dhariwal
Why was it done?
The COVID-19 pandemic necessitated the rapid transition of benralizumab dependent SEA patients onto home administration to facilitate on-going therapy in a cohort of patients who were “shielding” under UK government guidance.
What was done?
246 severe eosinophilic asthmatic (SEA) patients treated with benralizumab; a biologic agent targeting the human interleukin-5 receptor (IL-5Rα), at a specialist NHS asthma clinic, were transferred to self-administration at home in response to the COVID-19 pandemic. Alongside this, patients continued to need to be newly initiated on benralizumab therapy in spite of the pandemic and innovative pathways were created to ensure rapid initiation of therapy and home administration.
How was it done?
A varied multi-disciplinary team including pharmacists, pharmacy technicians, specialist nurses, doctors, physios and phycologist conducted a variety of in-person and virtual (telephone and video) consultations to consent and train patients on self-administration in their own homes in a rapid transfer to home administration.
What has been achieved?
We have investigated this patient cohort for any unwarranted effects by comparing the last Asthma Control Questionnaire-6 (ACQ6) measured in clinic with that collected by telephone consultation 8-12 weeks after transition to home administration. 246 benralizumab patients were included in the analysis, of whom 49 (20%) were new. There was no significant difference in pre-biologic ACQ6, pre-homecare (baseline) ACQ6 or post-homecare ACQ6 between the new and established patient groups. Both cohorts exhibited a similar magnitude of improvement in their ACQ6 following the transition to home administration (-0.73 in the established group vs -0.73 in the new group, both P<0.0001). We have demonstrated that early transition to home administration in patients treated with benralizumab is not associated with worse clinical outcomes as assessed by ACQ6.
What next?
Evaluation of patient experience on the switch to self-administration is currently being carried out via patient surveys with this data due to be completed in early 2021. Further research is required to understand the potential influence of lockdown and/or telephone vs face-to-face ACQ reporting.
A multi-disciplinary teams’ collaborative approach to transition mepolizumab dependent severe eosinophilic asthmatic patients to self-administration in response to the COVID-19 pandemic
Pdf
European Statement
Clinical Pharmacy Services
Author(s)
Grainne D’Ancona, Niall Stewart-Kelcher, Schaya Bains, Andrew Hearn, Joanne Kavanagh, Cris Roxas, Linda Green, Louise Thomason, Marianna Fernandes, Brian Kent, Alexandra NanzerKelly, David Jackson, Jaideep Dhariwal
Why was it done?
The COVID-19 pandemic necessitated the rapid transition of the remaining 41 mepolizumab dependent SEA patients onto home administration to facilitate on-going therapy in a cohort of patients who were “shielding” under UK government guidance.
What was done?
87 severe eosinophilic asthmatic (SEA) patients treated with mepolizumab; a biologic agent targeting interleukin-5 (IL-5), at a specialist NHS asthma clinic, were transferred to self-administration at home compared to usual practice of administration in a hospital setting. 40 patient were transferred in late 2019 as a planned ‘pilot’ transition and 47 patients were transferred unplanned due to the COVID-19 pandemic. We investigated whether there was a change in asthma control following the transition to home administration and whether a differential response to treatment exists following transition to homecare before and after the onset of the COVID-19 pandemic.
How was it done?
A varied multi-disciplinary team including pharmacists, pharmacy technicians, specialist nurses, doctors, physios and phycologist conducted a variety of in-person and virtual (telephone and video) consultations to consent and train patients on self-administration in their own homes in a rapid transfer to home administration
What has been achieved?
Patients receiving mepolizumab at home were stratified according to those who had a planned transition prior to 1st Feb 2020 versus those who had an unplanned transition after this date necessitated by the COVID-19 pandemic. The last Asthma Control Questionnaire-6 (ACQ6) measured in clinic (“baseline”) was compared with that collected by telephone consultation 6-8 weeks after transition. Immediately prior to transition to homecare (baseline), the planned group had a lower mean ACQ6 than those in the unplanned group (1.19 vs 1.90, P=0.004). The ACQ6 on home administration decreased significantly in both groups (-0.47 in the planned group vs -0.56 in the unplanned group, both P<0.001). The ACQ6 for the planned cohort during homecare was significantly lower than that for the unplanned group (0.72 vs 1.34, P=0.012).
What next?
Evaluation of patient experience on the switch to home administration is currently being carried out via patient surveys with this to be completed in early 2021. Further research is required to understand the potential influence of lockdown and/or telephone vs face-to-face ACQ reporting.
NEW TECHNOLOGIES TO IMPROVE SAFETY IN PREPARATION AND ADMINISTRATION OF INTRAVENOUS ANTINEOPLASTIC DRUGS
Pdf
European Statement
Patient Safety and Quality Assurance
Author(s)
Carlos Aparicio Carreño, Arantxa Gándara Ande, Beatriz Fernández González, Andrea Forneas Sangil, Belén Rodríguez de Castro, Rubén Pampín Sánchez, Cristina Martínez-Múgica Barbosa, Paloma NIeves Terroba Alonso
Why was it done?
To improve safety during preparation and administration of IAD.
What was done?
A new computerized system was established to improve quality control and traceability in preparation and administration of intravenous antineoplastic drug (IAD).
How was it done?
The software currently in use was updated, checking densities of IAD, weights of diluents and consumables. Protocols in pharmacology were adapted and maximum permissible error rates during elaboration were established. The Aseptics Pharmacy Department was equipped with a barcode label printer (BLP), a barcode scanner (BS), a precision scale and an All In One computer for the biological safety cabinet (BSC). The Haematology and Oncology Day Treatment Unit (DTU) was equipped with a BLP (for hospital bracelets) and portable computers with BS.
Regarding elaboration, a qualitative control was performed in the BSC by scanning data matrix or barcodes, recording batches and expiration dates, both of the diluent and antineoplastic agents. A quantitative gravimetric test was also performed using weight measurement of the diluent and devices before and after adding the drug. When the mixture was correctly prepared a label was printed with an identifying barcode.
Administration of the right bag to the right patient was also ensured by scanning barcodes in DTU: A hospital bracelet with a barcode was printed to identify each patient at their arrival to DTU. Prior to administration, double scan confirmation was made, checking patient´s bracelet and treatment (label), by using BS, ensuring that each patient received the drug, at the right dose, on time and by the correct route of administration.
What has been achieved?
All intravenous cancer therapies have been administered with double scan confirmation in DTU since the new system was established (November 2019).
This new way of processing IAD has been completely installed, but not all the antineoplastic treatments have been prepared with quality control.
The whole process has also left a complete computer record of the staff, task performed, time, duration and potential incidents.
What next?
We will gradually implement quality control while processing all intravenous antineoplastic treatments.
DEVELOPMENT OF A STANDARDISED PAEDIATRIC PARENTERAL NUTRITION FOR THE FIRST DAYS OF LIFE OF A TERM OR PRETERM NEWBORN
Pdf
European Statement
Production and Compounding
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.
HAZARDOUS DRUG ENTERAL DEVICE
Pdf
European Statement
Production and Compounding
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
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.