Assessment of drug delivery devices working at microflow rates.

Almost every medical department in hospitals around the world uses infusion devices to administer fluids, nutrition, and medications to patients to treat many different diseases and ailments. There have been several reports on adverse incidents caused by medication errors associated with infusion equipment. Such errors can result from malfunction or improper use, or even inaccuracy of the equipment, and can cause harm to patients' health. Depending on the intended use of the equipment, e.g. if it is used for anaesthesia of adults or for medical treatment of premature infants, the accuracy of the equipment may be more or less important. A well-defined metrological infrastructure can help to ensure that infusion devices function properly and are as accurate as needed for their use. However, establishing a metrological infrastructure requires adequate knowledge of the performance of infusion devices in use. This paper presents the results of various tests conducted with two types of devices.

In-line measurements of the physical and thermodynamic properties of single and multicomponent liquids.

Microfluidic devices are becoming increasingly important in various fields of pharmacy, flow chemistry and healthcare. In the embedded microchannel, the flow rates, the dynamic viscosity of the transported liquids and the fluid dynamic properties play an important role. Various functional auxiliary components of microfluidic devices such as flow restrictors, valves and flow meters need to be characterised with liquids used in several microfluidic applications. However, calibration with water does not always reflect the behaviour of the liquids used in the different applications. Therefore, several National Metrology Institutes (NMI) have developed micro-pipe viscometers for traceable inline measurement of the dynamic viscosity of liquids used in flow applications as part of the EMPIR 18HLT08 MeDDII project. These micro-pipe viscometers allow the calibration of any flow device at different flow rates and the calibration of the dynamic viscosity of the liquid or liquid mixture used under actual flow conditions. The validation of the micro-pipe viscometers has been performed either with traceable reference oils or with different liquids typically administered in hospitals, such as saline and/or glucose solutions or even glycerol-water mixtures for higher dynamic viscosities. Furthermore, measurement results of a commercially available device and a technology demonstrator for the inline measurement of dynamic viscosity and density are presented in this paper.

Calibration methods for flow rates down to 5 nL/min and validation methodology.

Improving the accuracy and enabling traceable measurements of volume, flow, and pressure in existing drug delivery devices and in-line sensors operating at very low flow rates is essential in several fields of activities and specially in medical applications. This can only be achieved through the development of new calibrationmethods and by expanding the existing metrological infrastructure to perform micro-flow and nano-flow measurements. In this paper, we will investigate new traceable techniques for measuring flow rate, from 5 nL/min to 1,500 nL/min and present the results of an inter-comparison between nine laboratories for the calibration of two different flow meters and a syringe pump.

Calibration of insulin pumps based on discrete doses at given cycle times.

One application in the medical treatment at very small flow rates is the usage of an Insulin pump that delivers doses of insulin at constant cycle times for a specific basal rate as quasi-continuous insulin delivery, which is an important cornerstone in diabetes management. The calibration of these basal rates are performed by either gravimetric or optical methods, which have been developed within the European Metrology Program for Innovation and Research (EMPIR) Joint Research Project (JRP) 18HLT08 Metrology for drug delivery II (MeDDII). These measurement techniques are described in this paper, and an improved approach of the analytical procedure given in the standard IEC 60601-2-24:2012 for determining the discrete doses and the corresponding basal rates is discussed in detail. These improvements allow detailed follow up of dose cycle time and delivered doses as a function of time to identify some artefacts of the measurement method or malfunctioning of the insulin pump. Moreover, the calibration results of different basal rates and bolus deliveries for the gravimetric and the optical methods are also presented. Some analysis issues that should be addressed to prevent misinterpreting of the calibration results are discussed. One of the main issues is the average over a period of time which is an integer multiple of the cycle time to determine the basal rate with the analytical methods described in this paper.