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)
Pdf
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)
Pdf
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)
Pdf
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.
REPACKAGING OF INTRAVITREAL BEVACIZUMAB (submitted in 2019)
Pdf
European Statement
Production and Compounding
Author(s)
MARGHERITA GALASSI, CHIARA DELLA COSTANZA, CLAUDIA TIRONE, ELENA ALIPRANDI, ERNESTO RUFFINO, SARA BERTOLI, ELEONORA FERRARI, ELISABETTA MARTINELLI, VITO LADISA
Why was it done?
Intravitreal bevacizumab is refunded by National Health System for AMD and diabetic macular oedema but the splitting process must be carried out only by authorised pharmacies. Recently the established regional refund price was lowered to €55/dose that covers the costs of intravitreal bevacizumab but not the other authorised drugs ranibizumab and aflibercept. Our Centralized Pharmacy operated the repackaging of intravitreal bevacizumab for internal patients but we implemented a new process and a new procedure in order to provide doses to hospitals not equipped in performing sterile preparations.
What was done?
We implemented a production process to repackage a drug to be used in treatments not covered by marketing authorisation. Bevacizumab was split into fractional doses for off-label intravitreal injections; the doses obtained were given to our hospitalised patients as therapy for uveal melanoma and provided to hospitals in our region as therapy for patients with age-related macular degeneration (AMD) and diabetic macular oedema.
How was it done?
The procedure for preparing intravitreal injections was reviewed to optimise traceability aspects of processing batches, individual doses of finished products and particularly to choose the most suitable packaging for transport to hospitals that will administer the drug. Further quality control to regional law was established on processes and finished product: environmental, instrumental, maintenance controls. All processes were validated in accordance with applicable regulations. Agreements related to prescription, purchase, conservation and transport of bevacizumab doses were signed with the hospitals that administer the drug.
What has been achieved?
The price refunded for a single intravitreal dose of an anti-VEGF (vascular endothelial growth factor) drug from August 1 2019 is €55, previously the price for each single dose of ranibizumab was €600. Considering that AMD therapy requires a monthly injection for about a year we can assume a standard average cost saving of €6540/patient.
What next?
AMD is the leading cause of blindness among populations over 50 years old. To provide treatments to all those affected by degenerative eye diseases in the next years, we must operate cost savings policies safeguarding patient security. The practice described is worthy of implementation in hospital realities.