The EAHP Board, elected for three-year terms, oversees the association’s activities. Comprising directors responsible for core functions, it meets regularly to implement strategic goals. Supported by EAHP staff, the Board controls finances, coordinates congress organization, and ensures compliance with statutes and codes of conduct.
Physicochemical and biological stability study of mogamulizumab in diluted solution
European Statement
Production and Compounding
Author(s)
Emma Pinet, Lionel Barty, Anne Blandine Bouvrain, Françoise Le Cheviller, Nicolas Vaillant, Nathalie Jourdan, Hélène Sauvageon, Isabelle Madelaine
Why was it done?
In order to make hospital preparations in advance and optimize costs, a physicochemical and biological stability study was conducted in the pharmaceutical control laboratory.
What was done?
Mogamulizumab is a monoclonal antibody used in the treatment of Sezary syndrome and mycosis fungoides. The dilution of the 4 mg/ml vial of Poteligeo® in the infusion bag is stable for 24 hours at room temperature between 0.1 to 3 mg/ml.
How was it done?
Four bags of mogamulizumab were prepared in 0.9% NaCl 250 ml (2 at 0.14 mg/ml, 2 at 0.34 mg/ml). Each dilution is evaluated at 20±5°C and at 5±3°C, protected from light for 28 days. Analyses are performed in triplicate by High Performance Liquid Chromatography (HPLC-UV) associated with Chromeleon™ software. Concentrations are measured by HPLC after Flow Injection Analysis (FIA). Physical stability is studied by searching for IgG aggregates by Steric Exclusion Chromatography (Biozen™SEC3 column, 1.8µm 300*4.6mm). Chemical stability is evaluated by assessing acidic and basic variants proportions of the antibody by Cation Exchange Chromatography (CEC) (Biozen™WCX column, 6µm 250*4.6mm). Biological activity is determined by evaluation of the different glycoforms, by affinity chromatography (FcyRIIIa column, 5µm 75*4.6mm Tosoh®). The microbiological stability is performed by seeding the diluted solution on chocolate agar and brain heart broth.
What has been achieved?
At D28, the quantitative determination of mogamulizumab by FIA showed a deviation of less than 10% compared to theoretical concentrations. No aggregates or antibody fragments were found. The proportion of acidic, basic variants and of the main peak did not deviate by more than 5% compared to D0. For all infusion-bags studied by CEC, the main peak rates were between 79.1% and 85.8%, the acidic variant rates between 6.7% and 9.9% and the basic variant rates between 7.8% and 11.2%. The proportion of each antibody species (low, medium, high affinity) did not deviate by 5% from D0. The low affinity rate is between 48.2% and 52.7%, medium between 39.6% and 44.8% and high between 6.9% and 7.9%. No colonies were found on chocolate agar and heart-brain broth.
What next?
Mogamulizumab is physically, chemically and biologically stable for 28 days in diluted solution between 0.14 mg/L and 0.41 mg/L at 5°C and 20°C.
DEVELOPMENT OF A PATIENT-CONTROLLED ANALGESIC MIXTURE FOR POSTOPERATIVE PAIN CONTROL
European Statement
Production and Compounding
Author(s)
María Molinero, Virginia Puebla, Cristina González, Lidia Ybáñez, Gonzalo Hernando, Natalia Sánchez-Ocaña, Javier Corazón, María de la Torre, Jose Manuel Martínez
Why was it done?
This technique provides autonomy to the patient allowing to adjust the dose based on the intensity of pain. It has been demonstrated that small on-demand doses of analgesia provide a reduction in the final dose, thus reducing side effects. In addition, by minimizing the possible delay in the administration of analgesia, the anxiety associated with pain and exacerbations is reduced.
What was done?
Hospital Pharmacy Service in collaboration with Acute Pain Unit has developed a protocol for an analgesic mixture for intravenous administration in continuous infusion based on tramadol, dexketoprofen and haloperidol. It is a patient-controlled analgesia (PCA) administered by pump for the treatment of acute postoperative pain.
How was it done?
We performed a bibliographic search of stability studies in order to standardize the analgesic mixture, guaranteeing its physical-chemical and microbiological stability.
What has been achieved?
A mixture of 600mg tramadol, 300mg dexketoprofen and 5mg haloperidol was prepared and it was filtered through a 5-micron filter. It was diluted in 100mL of 0.9% sodium chloride, obtaining a mixture of 125mL. It was sealed and bagged in a photoprotective bag. After the bibliographic search on stability data and physical-chemical compatibility of the mixture, a stability of 14 days at 2-8 ºC was established. Once elaborated, quality control was performed by gravimetry. It was dispensed weekly by stock to the post-anesthesia resuscitation unit. The established perfusion rate is 1.3 mL/h or 1.7 mL/h for 48h. With each rescue, 8mg of tramadol and 4mg of dexketoprofen are released per hour or 4mg and 2mg every 30min, respectively. The maximum dose that can be administered is 400mg tramadol, 150mg dexketoprofen and 2mg haloperidol, except if the patient weighs less than 50kg: 8mg/kg tramadol. If renal insufficiency, dose adjustment was mandatory.
What next?
The centralization of the preparation of intravenous admixtures from the pharmacy service allow us to adjust the expiry date based on stability studies reported in the literature, to maintain the asepsis of the mixture as it is prepared in horizontal laminar flow cabinets, to increase the safety and to secure the traceability.
TEMPERATURE AND RELATIVE HUMIDITY CONTROL IN THE PACKAGING ENCLOSURE OF SOLID ORAL DOSAGE FORMS (submitted in 2019)
European Statement
Production and Compounding
Author(s)
María Lourdes Recio Blázquez, José Manuel Martínez Sesmero, Lidia Ybáñez García, Gonzalo Hernando Llorente, María Molinero Muñoz
Why was it done?
The purpose is to control two environmental conditions to guarantee the comfort of the workforce and the quality of the finished product quality. 519,321 SODFs have been repackaged in unit doses last year. The 8% of the SODFs come from multidose containers that have been exposed to environmental temperature and humidity during this process. Employees have been exposed to identical conditions.
What was done?
A temperature (t) and relative humidity (RH) control system has been established in the enclosure where the solid oral dosage forms (SODFs) are packaged in unit doses.
How was it done?
Among the diversity of hygrometric sensors commercialised, a device equipped with a condenser was chosen. The operation is based on modifying the capacity when varying the dielectric constant of the medium, in this case, due to varying the amount of water contained in the air between the plates. – C = ε A / D – C: capacity value. – ε: dielectric constant. – A: area of the condenser plates. – D: distance between the condenser plates. The device also incorporates a temperature sensor. The t (ºC) and RH of each moment are shown, for visual inspection, on the device screen. The data obtained with certain time frequency can be stored on a Secure Digital memory card and be downloaded on a computer that has that program installed (on spreadsheet format) helping to obtain graphics as well.
What has been achieved?
The range of t (ºC) has remained stable between 26 and 24ºC for 6 months, with minimal variations from maximum 28.5ºC to minimum 23.4ºC. The UNE 100713: 2005 is met. RH has been below 45% during 68% of the days worked, which has favored the repackaging of the units affected by humidity but not the worker. The range of RH has varied between 56.3% and 23.6%, not complying with the UNE 100713: 2005 standard.
What next?
Metabolic rate, clothing insulation, air temperature, radiant temperature, air speed and humidity shall be addressed when defining conditions for acceptable thermal comfort. It would be helpful to regulate the commercialisation of multidose pharmaceutical specialties susceptible to deterioration when opening the package.
OPTIMIZATION OF RISK MANAGEMENT OF DRUGS COLD CHAIN IN HOSPITAL BY FAILURE MODES, EFFECTS AND CRITICALITY ANALYSIS “FMECA” METHOD
European Statement
Selection, Procurement and Distribution
Author(s)
Ismail Bennani, Amine Cheikh, Hafid Mefetah, Mustapha Bouatia
Why was it done?
The strict control of medicines cold chain is linked to a triple risk for a hospital: a risk for the patient through the efficiency and safety of the drug, a financial risk, and a regulatory risk.
What was done?
Our study aimed to map the process of management of medicines requiring a strict cold chain control at a referral pediatric hospital and to identify the critical points associated to this process in order to realize a risk analysis using the FMEA method
How was it done?
The method used is FMEA for a priori inductive risk analysis which aims to identify potential system failures. These failures are analyzed to determine their criticality by establishing an index for each failure that will be scored and calculated using the formula: Criticality index = frequency × severity × detectability.
The rating of each criterion is based on predetermined rating tables.
What has been achieved?
Process Mapping: The mapping of the process allowed identify 7 major actors: the supplier, the general store, the logistics platform for product reception, the transportation, the logistics department of hospital, the pharmacy and the patient.
Identification of the critical points: All failures modes that were ranked between 201 and 504 on criticality index are considered as main critical points:
Problem of breakdown of electricity and its management: 504
Respect of the cold chain at the level of the care services until administration: 448
Temperature indicators at the level of care services: 384
Conditions of transportation: 315
Temperature monitoring at pharmacy level: means and management: 245
Logistics agents transport time management: 210
Implementation of improvement actions: Corrective and preventive improvement measures have been defined and implemented, such as: setting up alternatives to power outages, periodic temperature assessments at all critical levels, and integration of remote control and monitoring computer devices.
What next?
The continuous improvement of the medicines’ cold chain remains an important topic for the institutions in view of the overall risks associated with the quality of these medicines, therefore to the medical treatment of the patient.
IMPLEMENTATION OF A SAFETY ALERT SYSTEM IN A HOSPITAL
European Statement
Patient Safety and Quality Assurance
Author(s)
MERCEDES GIMENO-GRACIA, TRANSITO SALVADOR-GOMEZ, ROSA MARECA, JOSE IGNACIO GARCIA-MONTERO, MIGUEL ANGEL SALVO, PILAR ABAD, BEATRIZ ABAD, CESAR VELASCO
Why was it done?
The Spanish Agency of Medicines and Health Products (AEMPS) issues drug and health product-related alerts to the health centres through each region’s Department of Health. The means through which said alerts reach the health professional is not always adequate. The procedures for alert dissemination in our hospital hadn’t been standardized yet: some professionals were alerted more tan once while others weren’t alerted at all. Furthermore, there was no record of these alerts
What was done?
We developed a safety alert management and dissemination system implementation in a hospital setting.
How was it done?
In April 2014, a multidisciplinary workgroup was established (3 members of the Preventive Medicine Service, 2 pharmacists, 2 members of the Supplies Service, 2 computer technicians and 2 members of the hospital’s Management) to analyse management and dissemination of alerts within the hospital at that time. Safety alerts can attain to different elements: drugs, medical devices and public health. Throughout 2015 new circuits and actions were established and in 2016 their implementation was initiated.
What has been achieved?
The workgroup held 7 meetings from April 2014 to June 2016. The project started focusing on drug-related alerts. An algorithm was designed to handle them, in which a pharmacist filtered the alerts (via e-mail) and assessed which had to be spread, and among which professionals. Additionally, the pharmacist managed the alert. The dissemination worked as follows: from the Pharmacy Service to Medical or Nursing Directors, who spread the message to the different units recommended by pharmacist, specifically to their respective Manager, Tutor of Residents and Quality Manager. All alerts were recorded in a database, along with how they were handled.
From January to June of 2016, a total of 235 drug-related alerts were sent from AEMPS. The dissemination was as follows: 44.3% (104) were spread among pharmacists, 36.6% among doctors, 5.5% among nurses and 9.4% to other professionals. The types of drug-alert received were classified as: supply problems (84.7%), use recommendations (7.2%), quality alerts (7.7%) and others (0.5%).
What next?
Next step is implantation of this alert management system with medical devices alerts and public health alerts.