Additional Stability Checks

Problems of leakage were observed in some of the bottles containing the reference materials after the certification campaign had been concluded. 

Consequently, it was decided to test other polypropylene bottles with tighter caps for the storage of the reference materials. This additional study was carried out 24 months after the initial stability study and led to the detection of instability problems of the Se species over a long-term period. A clear decrease in selenite content was observed in the new polypropylene bottles after 8 months storage, which was particularly acute for the low-concentration reference materials (Table 8.5), whereas selenate remained stable over the same period. On the basis of these results, if was found necessary to control the 

The reasons for this instability could be attributed to an adsorption process onto the container surface which was not observed in the 60 L tank, owing to a much smaller surface/volume ratio in other terms, the ratio is 11 times smaller in the storage tanks in comparison to the 100 mL bottles, leading to a better stability of the species. Furthermore, the polyethylene material of the tank seems to be more suitable to achieve stability in comparison to polypropylene. 

On the basis of these additional studies, these reference materials were not found to be suitable as CRMs [144,145]. 

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Consideration of the analyses performed on the 8-channel and both models of the 12-channel Technicon equipment in relation to the earlier discussion means that these latest developments in the field of Auto-Analyzer instrumentation demand standardized sera for calibration purposes. In fact, the successful operation of the SMA-12 instrument is entirely dependent upon the careful analysis and subsequent stability of the standardizing serum, since this is used both for the initial calibration of the various analytical channels and for the subsequent monitoring for drift and application of any correction needed as a result of instrumental drift. Apart from this large demand for standardizing serum (about 70 ml in an 8-hour day), the performance of the SMA-12 should in addition be checked by means of control sera, as for any other method or combination of methods in clinical chemistry. The expense of the standardizing (and to a lesser extent the control) sera used in SMA-12 operation constitutes an important but nevertheless essential fraction of the operating costs of these instruments. 

Furthermore, the samples must be similar in type (matrix) to the unknown samples that are routinely analyzed. A matrix different fiom the real life product, e.g., lyophilization or the presence of additives, stabilizers, preservers, etc., could cause a divergence between results from some analytical methods [48]. The coordinator of the scheme should also demonstrate that the target analyte concentration is traceable to CRMs, if they exist, and a quality check should be performed by a different laboratory [6]. 

Comments There are several suggested controls for this assay, including use of yeast total RNA as a negative control (check for probe species specificity) and a no RNAse control to determine probe stability. In Fig. 6.3A, the positive control marker lane was produced by addition of R-luc-4 sites or F-luc mRNA only to the assay. Also, optimal times for RNAse digestion will vary from probe to probe. In addition, for maximum sensitivity a probe with high specific activity is preferable (yet still in molar excess to the mRNA). 

In addition to the consequences due to deviations in the chemical process or the equipment operation, deviations in storage atmospheres need to be checked (e.g. formation of explosive atmospheres, generation of oxidizing gases such as chlorine or NOx, loss of stabilizers in gases capable of decomposition). 

Once the material has been packaged, it must then be checked for uniformity. Any additional characterization of the material, in the form in which it will be distributed (e.g., grain size, color) should be conducted at this stage. Subsequently, the material is analyzed for the analyte(s) of interest for certification purposes, after which the certificate of analysis can be prepared. It is also imperative that a certified reference material or reference material be continually monitored for stability throughout its... 

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