To improve the accuracy and efficiency of patient treatment, methods need to be developed for the reliable and accurate delivery of drugs to patients. In order to do this, the metrological infrastructure for pharmaceutical drug delivery needs improvement; it requires validated primary standards for flow rates from 100 ml/min down to 10 nl/min, the characterisation of flow meters and flow generators and the validation of infusion pumps. The existing primary standard goes down to 16 ul/min, however below 100 ml/min there has never been a formal validation of primary standards by means of a (key) comparison.
The extremely low flow rates are not easy to measure. Different parameters affect the infusion pump flow rate and hence the drug delivery, for example the drug type (e.g. viscosity), (hydrostatic) pressure, temperature and pump usage pattern. Flow rate (and concentration) accuracy deteriorates further if multi-pump infusion is involved. An additional issue with drug delivery is that typically the drug delivery characteristics are not known and understood, for example the time it takes to reach a stable flow rate. This can also result in unexpected flow rates.
This joint research project requires a close cooperation with experts and practitioners from the relevant medical areas and will lead to:
- traceable calibration services for drug delivery systems for flow rates down to 1 nl/min transfer standards for onsite calibration
- assessment of the drug delivery devices
- a best practice guide for drug delivery
There are various examples where adverse incidents, morbidity and/or mortality, can be traced back to poor drug delivery. Consequently, the health community using (multi-pump) infusion technology is in need of new calibration services and improved knowledge and understating of the equipment they are using. Infusion technology suppliers need traceability and lower calibration uncertainties in order to improve their products. Finally, hospital technicians in charge of the maintenance of the infusion pumps need a better understanding of the impact of the physical parameters and need better equipment for their cross checks.
The ultimate goal of this joint research project is to make drug delivery more reliable and robust, especially for multi-pump infusion and applications involving very low flow rates (lower than 25 ul/min). This goal is aimed for by realising the required metrological infrastructure and an assessment of existing drug delivery devices.
- The infrastructure will consist of traceable calibration services for drug delivery systems for flow rates down to 10-100 nl/min, which is several orders of magnitude lower than the lowest calibration service available in Europe today.
- Transfer standards will be developed so that drug delivery equipment can also be calibrated on site. This is important in case the required equipment cannot be readily transported or the equipment is in constant use. Additionally, the shear wealth of instruments typically used in a hospital makes it more efficient to perform the calibration on site.
- The assessment of the drug delivery devices will focus on their performance (e.g. accuracy and reproducibility), dependency on operating conditions (e.g. density, viscosity) and clinical characteristics (e.g. start-up time to steady state, flow rate stability). Classic drug delivery devices will be considered, as well as multi-pump infusion, drug delivery with mobile devices and the influence of drug delivery accessories (such as needles, splitters, valves, tubing, etc.).
Furthermore, the project will deliver a best practice guide for drug delivery and will improve calibration services for drug delivery devices. The best practice guide will be based on the assessment carried out for drug delivery devices. It will focus on the safe and sound usage of various types of drug delivery devices.
In order to achieve the goals, the following work packages have been determined:
- Development and improvement of measurement services for liquid flow rates (ambient pressure and temperature) for flow rates from 100 ml/min down to 1 nl/min. This will lead to the development of the world’s first traceability chain for liquid flow rates from 150 μl/ min to 1 nl/min with a target uncertainty of 0.5 %.
- A thorough assessment of (commercial) flow meters. The assessment includes the performance (e.g. accuracy and reproducibility) and the dependency on operating conditions (e.g. viscosity and temperature). One of the focal points will be the effect of pulsation on meter performance. This will help in developing a robust micro-flow meter.
- A thorough assessment of drug delivery devices. The assessment includes the performance (e.g. accuracy and reproducibility), dependency on operating conditions (e.g. viscosity and density) and clinically relevant characteristics (e.g. start-up time and flow rate stability). This will lead to characterisation of various types of drug delivery devices.
- The development/ feeding into existing best practice guide(s) for a safe and sound usage of infusion technology.
The project runs until the end of 2015.