European nebulizer standard

A draft European Nebulizer Standard (30) has been submitted for formal approval to CEN (Comite Europeen de Normalisation European Committee for Standardization). CEN is responsible for European standardization in all fields except Electrotechnical (CENELEC) and Telecommunications (ETSl). Publication of the European Nebulizer Standard is expected during 2001. Included within the European standard are detailed descriptions of two test methods for (1) assessing nebulizer aerosol output inhaled using breath simulation similar to that described previously and (2) assessing nebulized aerosol droplet size using low-flow cascade impaction. Because this standard is expected to be adopted throughout Europe (and possibly more widely), a summary of its contents may be useful to readers. 

Currently, there are no U.S. Pharmacopeia or European Pharmacopoeia standard tests for characterizing the output of respiratory solutions or suspensions generated by air-jet or ultrasonic nebulizers. 

Draft European Nebuliser Standard. prEN13544 13544-1. Respiratory Therapy Equipment Part 1 Nebulizing Systems (available through all national European Standards bodies, e.g., in UK available through BSI ref BS 99/5662734DC). 

The reservoir incorporated within the Circulaire nebulizer system may help increase the inhaled proportion of aerosol from a given fill volume compared to the same driving nebulizer without incorporation of the valved reservoir bag system. Like the Halolite, this implies reconsideration of prescribed doses and volume fills of drug solution to avoid overdosing. The extent to which the droplet size from conventional nebulizers is affected by adaptations in Halolite and Circulaire nebulizer system is not clear. Meaning in vitro measurements (e.g., European standard) characterizing droplet size from either system is not available. 

The first attempt by any nation to establish a standard method for assessing nebulizer performance was made in the U.K. in 1994. Though now outdated and technically limited (29), this published standard set a precedent and a foundation for further research and development of test methods. Much has happened to progress the understanding of nebulizer performance in recent years which has, in part, led to the development of the widely resourced European standard in assessing nebulizer performance. 

B. European Standard on In Vitro Assessment of Nebulizer Performance... 

Since the 1970s laser sizers have offered convenient and rapid estimation of the optical size distributions of nebulized aerosol size distributions. However, just as weight loss as a measure of aerosol output is confounded by evaporation, droplet size distributions are now clearly understood also to be affected by evaporation once the aerosol cloud is mixed with drier ambient air. The methodology adopted within the European standard was inevitably a compromise but may arguably present the most representative clinical compromise. 

Figure 14 In vitro assessment of droplet size measurement in the European Standard. Simulated patient inhalation at 15 L/min draws air over (or through) the nebulizer where entrained ambient air mixes with nebulized aerosol. A sample of the air at 2 L/min is drawn into a Marple Series 290 cascade impactor, which sizes aerosol droplets in relation to aerodynamic diameter. Impacted aerosol solute (e.g., NaF or drug) can be subsequently desorbed and quantified from each impaction stage.

During development of the European standard, an interlaboratory trial was organized involving six laboratories within Europe to follow a defined protocol to assess aerosol output and size from two fundamentally different nebulizer systems. Results demonstrated that the methods were repeatable within +/- 10% of mean return for both aerosol output and aerosol size (unpublished data). Results of preliminary research investigating the correlation between in vivo response and in vitro estimate of aerosol output and size show a promising correlation (33), though further work is needed in this area. 

A decision to establish an ERS Task Force to draft clinical nebulizer guidelines was made by the ERS executive in early 1998. Technical (34) and clinical workshops (35) have since helped formulate draft guidelines, which will be submitted to the ERS Executive in 2000. An important aspect of the ERS nebulizer guidelines is that they will recommend performance data obtained from European standard methodology to help guide clinicians in chosing a suitable nebulizer system. 

The European Standard presents a set of in vitro methods that are expected to reflect in vivo deposition and have been shown to provide repeatable and consistent results. It is clear that some nebulizer designs cannot easily be adapted into this or any other standard and that some flexibility is required in interpreting and applying such to these systems. In particular, obtaining a realistic profile of aerosol size distribution from the small aerosol boluses mixed with entrained ambient air from the Halolite, Circulaire, and AERx is particularly problanatic. However, such technical difficulties can be overcome and realistic measures of... 

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