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INTRODUCTION: Intravenous vedolizumab is a widely used monoclonal antibody for outpatients with inflammatory bowel disease. Drug preparation is performed on the day of administration, but is time consuming, causing unnecessary in-hospital patient delay and inefficient logistics for preparation and distribution. Storage of vedolizumab ready-to-administer infusions and distribution via pneumatic air tubes could streamline logistics in the outpatient setting. The aim of this study was to test the shelf life and stability of ready-to-administer intravenous infusion bags containing vedolizumab. METHODS: For assessing in-use shelf life, the reconstituted product (300 mg fixed dose) was diluted to a concentration of 1.2 mg/mL in 0.9% NaCl under aseptic conditions, and stored in polyolefin infusion bags at 2-8°C prior to analysis. On replicate samples, we measured concentration, physical and chemical stability using sodium dodecyl sulphate polyacrylamide gel electrophoresis, size exclusion chromatography, and multi-angle laser light scattering, as well as biological activity using a biolayer interferometry assay to study target engagement, and endotoxin content to assess microbiological stability. Stability of ready-to-use vedolizumab was assessed also after transportation via pneumatic tube system. Samples were taken at different time points over an observation period of 30 days on four replicate samples. RESULTS: For all parameters assessed, the ready-to-use solution of vedolizumab remained stable over a period of at least 30 days. There were no signs of protein aggregation, chemical instability, or loss of binding of the antibody to the α4ß7 integrin target. There was no increase in endotoxin concentration over time. No significant difference was seen in antibody structural stability and protein aggregation between samples before and after transportation via pneumatic tube system. CONCLUSION: When prepared under aseptic conditions, dissolved ready-to-administer vedolizumab infusion bags can be stored long term at 2-8°C and transported via pneumatic air tube, without observable loss of antibody stability or binding activity.
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INTRODUCTION: Drug shortages have become an issue of growing interest for pharmacists. Both number and type of shortages have increased over the past decade and it is challenging to provide drug continuity. Aim To describe management and impact of drug shortages for the hospital pharmacy. To gain insight into the causes of shortages. METHODS: The management process for drug shortages was analysed for the hospital pharmacies of the Ghent University Hospital (GUH) and the Acute Care Hospital Sint-Lucas Ghent. Insights in possible causes were obtained by semi-structured interview with the Federation for Belgian Pharmacists (Association Pharmaceutique beIge (APB)), the Belgian association of the pharmaceutical industry (pharma.bel and the Federal Agency for Medicines and Health Products (FAMHPI. A database of 1329 drug shortages (Jan 2001-Feb 2014 of the GUH was used to define drug classes affected by shortages (mean shortage days per year, standard deviation (SDI), type of shortage [urgent/ important] %, total number (n)), formulation (parenteral:oral and duration of the shortages (median, interquartile range (IQR)). The total cost impact for the GUH pharmacy was estimated by calculating average, minimum and maximum time investment by the pharmacy team (Delphi-techniquel and by calculating the cost difference between original and alternative drug acquisition costs. Impact is presented as base case scenario (minimum as best and maximum as worst case scenario). RESULTS: The different management phases for the pharmacist are problem identification, preparation of solution and implementation. Communication and extensive administration are essential components. Causes are production related, next to distribution inequivalences, quota and European market flows. Shortages with anti-infectious, cardiovascular and hormonal system drugs have the highest and constant proportion of drug shortage days, with recently appearance of other important drug classes such as anticancer therapy [2011 and further). The average number of drug shortage days in 2011-2013 is 8020 (SD 2142 compared to period 2001-2010 with on average 4633 days (SD 1731]. Fifty-four percent of the shortages is important for the direct hospital care and 22.9% needs urgent action. The proportion parenteral versus oral in the database is 3.3:1. Median duration of a shortage is 29 [IQR 11-65]1 days. The average excess cost of an equipotent dose of the alternative drug was 4.9 (SD 31.3) Euro. Total cost impact (gross salary and drug acquisition cost] for GUH pharmacy in 2013 is 117 281.4 Euro (best case: 88 345.06 and worst case: 151,208.2 Euro. CONCLUSION: The importance of the shortages and the diversification of the drug classes involved have an impact on the hospital pharmacy management. For the GUH this represents an important workload and an increased drug acquisition cost. Causes of shortages are production related but also distributional inequivalences and quota play an important role.
