ISO 21748:2010 gives guidance for evaluation of measurement uncertainties using data obtained from studies conducted in accordance with ISO 5725-2:1994; comparison of collaborative study results with measurement uncertainty (MU) obtained using formal principles of uncertainty propagation. (ISO 5725-3:1994 provides additional models for studies of intermediate precision. However, while the same general approach may be applied to the use of such extended models, uncertainty evaluation using these models is not incorporated in ISO 21748:2010.)
ISO 21748:2010 is applicable in all measurement and test fields where an uncertainty associated with a result has to be determined. It does not describe the application of repeatability data in the absence of reproducibility data.
ISO 21748:2010 assumes that recognized, non-negligible systematic effects are corrected, either by applying a numerical correction as part of the method of measurement, or by investigation and removal of the cause of the effect.
The recommendations in ISO 21748:2010 are primarily for guidance. It is recognized that while the recommendations presented do form a valid approach to the evaluation of uncertainty for many purposes, it is also possible to adopt other suitable approaches. In general, references to measurement results, methods and processes in ISO 21748:2010 are normally understood to apply also to testing results, methods and processes.
The measurement uncertainty was calculated according to UNI CEI ENV 13,005:2000 (Ente Italiano di Normazione 2000) and ISO 21748:2010 (International Organization for Standardization 2010). The following sources of uncertainty were evaluated and included in the final calculation: net counting, sample weight, Sr chemical yield, counting efficiency, Y-90 decay time, and repeatability.
The sensitivity of this procedure was higher than those of various previously established approaches for the determination of Sr-90 in solid matrices (Heilgeist 2000; Kabai et al. 2011; Shuzhong et al. 2015; Temba et al. 2011) and comparable to several others (Gerstmann and Tschöpp 2006; Lopes et al. 2010; Suomela et al. 1993).
All sources of uncertainty with substantial contributions to overall uncertainty were evaluated, as proposed by the UNI CEI ENV 13,005:2000 standard and in accordance with the ISO 21748:2010 standard, which accounts for repeatability. The relative contributions of sources uncertainties were as follows: net counts (2.80%), sample mass (0.01%), strontium yield (11.2%), counting efficiency (3.7%), ingrowth of Y-90 (3.0%), and repeatability (3.9%). Thus, the overall measurement uncertainty was 13.1%.
The main advantage of this method over other methods used for foodstuffs analysis (Lopes et al. 2010; Iammarino et al. 2016a) is the ability to obtain fast and accurate results without waiting for Y-90 ingrowth. Thus, the method enables the final quantification of Sr-90 in 48 h (excluding the ashing step), while the Y-90 analysis requires more than 15 days to reach secular equilibrium. As a consequence, the times and cost are significantly reduced. Comprehensive validation, with analyses of all radiochemical parameters, was performed in this study. Lopes et al. (2010) reported some relevant parameters, such as the CV% and recovery percentage. However, only three repetitions were performed for each level, using very high concentration activities, not common in the routine control of food and feed. Compared to the validation parameters reported by Iammarino et al. (2016a), the CV% is similar, the mean recovery is higher, and the measurement uncertainty is slightly lower for the newly proposed method. For samples of equal weights, the LOD and LOQ values are lower. Accordingly, the present method is more sensitive due to the higher counting efficiency and chemical recovery, even compared with the method published by Pan et al. (2017). Using this method, it is important to control the precise measurement of the time between Sr-90 elution and instrumental counting. In fact, in this method, the determination of the contribution of Y-90 is crucial for the precise quantification of the Sr-90 activity concentration.
11.- NB/ISO 21748:2011 : Guía para el uso de estimados de repetibilidad, reproducibilidad y veracidad en la estimación de la incertidumbre de la medición (Correspondiente a la norma ISO 21748:2010) Brinda orientación sobre la evaluación de las incertidumbres de la medición usando datos obtenidos de estudios realizados de acuerdo con la norma NB/ISO 5725-2
15.- NB/ISO/TS 21748:2011 : Guía para el uso de estimados de repetibilidad, reproducibilidad y veracidad en la estimación de la incertidumbre de la medición (Correspondiente a la norma ISO/TS 21748:2010) -
In 2010, the European Federation of Pharmaceutical Industries and Associations (EFPIA) Subteam on Analytical Methods introduced the concept of applying QbD principles to analytical methods (5) where they described two main objectives: improved method performance and increased regulatory flexibility. As yet, no pharmaceutical regulatory standards (analaogous to ICH Q8-Q11) exist that describe how to apply QbD principles to analytical procedures. This article, therefore, focuses on how QbD tools may be used to obtain improved chromatographic method performance in such a way that is aligned with holistic drug product and substance control strategies (regulatory flexibility will not be addressed here). 1e1e36bf2d