Fit for the purpose

If users are to benefit from the implementation and/or verification of traceability in analytical chemistry the unbroken pathway of references must be kept short. The uncertainty of the references (CRMs) used may significantly widen the uncertainty a user must attach to the result of his measiuement when addressing accuracy and traceability through comparison with a CRM. These comparisons should be only considered in a first or second level step as to keep the uncertainties of the results within limits fit for the purpose. The producers of CRMs must keep their uncertainties sufficiently small to allow introduction of the CRM at different points in the analytical pathway, without limiting the usefiilness of results through unduly expanded uncertainties. 

Selection of a suitable analytical method can be made once the reason for carrying out the analysis is well understood. Analytical methods may be (a) qualitative or (b) quantitative or semi-quantitative. The former usually pose few problems if only an indication is required as to whether a particular analyte is present or not - certainly not how much with a value having a small uncertainty. If a negative result is required (i.e. confirmation of absence from the product), then one has only to worry about the limit of detection of the test used. Many tests to confirm the absence of impurities in pharmaceutical products fall into this category. Equally, rapid tests for positive confirmation are often made on unknown substances. These may subsequently be confirmed by other, quantitative tests. Quantitative methods are used in a variety of situations and a variety of different methods can be employed. What you must always remember is that the method used must be fit for the purpose. 

Before considering how one can ensure that analytical data obtained are correct and fit for the purpose required, it is worth thinking about what could go wrong. Then it will be easier to work out how to avoid making mistakes. 

This validation shall demonstrate the ability of the methods and processes to achieve the planned resnlts. This is verified by inspection or measurements that the process output (e.g. the laboratory results) is reasonable and within expectations. Analytical methods and laboratoiy proeesses shall be validated so that to ensure fitness for the purpose (see ehapter 11). 

In chapter 4.2.1 of ISO/IEC 17025 the necessity for a management system and for documentation of policies, systems, procedures etc. is stated. It is important that the system is appropriate for the laboratories activities (fit for the purpose ). The system and documentation only make sense, if they provide feedback to the persoimel. 

Now we turn from detection to quantification of the analyte. The slide shows the definition of the LoQ from the lUPAC Orange Book . Note the word adequately in the sentence. That means that we have to define what is adequate, what is fit for the purpose. 

Warning and action limits calculated in the above way should not be used without considering the fit for the purpose requirement. The limits may be too narrow or too wide for the analytical purpose. If this is the case the limits should be adjusted to such requirements. 

There is no general answer to these questions except that the quality control measures have to be fit for the purpose of the analyses. 

The laboratory manager has to decide, what he thinks is fit for the purpose ... 

The data-processing equipment used by the provider also has to be fit for the purpose. This includes hardware as well as adequate software, which have to be verified and backed up. 

When we can predict the response of the reacting system to changes in operating conditions (how rates and equilibrium conversion change with temperature and pressure), when we are able to compare yields for alternative designs (adiabatic versus isothermal operations, single versus multiple reactor units, flow versus batch system), and when we can estimate the economics of these various alternatives, then and only then will we feel sure that we can arrive at the design well fitted for the purpose at hand. Unfortunately, real situations are rarely simple. 

This term refers to how resistant the precision and accuracy of an assay is to small variations in the method, e.g. changes of instrumentation, slight variations in extraction procedures, sensitivity to minor impurities in reagents, etc. Robust assays may not be capable of the highest precision or specificity but they are regarded as fit for the purpose for which they are designed. 

The authors have evaluated these approaches at considerable length, partly to judge whether one or the other has a clear advantage. Our main concern, however, has been to arrive at the most efficient and cost-effective means of producing RMs which are fit for the purposes of users. The outcome of this evaluation is that both approaches have specific and different merits and should be used as appropriate. In our view, there are some applications for which one or the other approach is clearly... 

It is now internationally recognized that for any laboratory to produce reliable data, an appropriate scheme of QA must be implemented. As a minimum, this must ensure that the laboratory is using methods that have been validated as fit for the purpose before their application to a specific task. These methods should be fully documented, staff should be trained, the laboratory infrastructure should be appropriate to the measurements to be made, and mechanisms ensuring that the procedure is under statistical control should be present. Implementation of appropriate QC measures ensures that the data produced and reported are of known quality and uncertainty. Last but not least, the laboratory should participate in PT schemes in order to demonstrate its competence.6... 

Data conditioning procedures involve the verification, quality control and data levelling processes that are necessary to make data fit for the purpose for which it is to be used. It is something that has to be planned at the outset of any project generating geochemical data. Whether it is in the sampling phase, for example, determining how sites and... 

Where small-scale bioseparations have been developed, particularly in the biopharmaceutical industry, there has been a tendency to retain laboratory type equipment even if this results in more labour and capital intensive processing. The reason for this is often to avoid the need for extended periods of process development work with new equipment designs, which might delay the launch of a product where competitors are not far behind. Manufacturers are also wary of adopting new bioseparation techniques for processes if there is any risk that regulators such as the U.S. Food and Drug Administration (FDA) will require more evidence that the equipment is fit for the purpose. This conservative tendency is understandable and may influence the choice of bioseparation equipment for pharmaceutical manufacturing in particular. 

For the results of an analysis to be of use to a client, the analytical measurements need to be fit for the purpose for which they were intended. Key measures for determining the appropriateness of the analytical method used by a laboratory include bias, accuracy and precision. 

All laboratories need to demonstrate that their methods are fit for the purpose for which they are intended. The process of obtaining data to demonstrate this fitness for purpose and the resulting documented evidence is called method validation. The purpose of method validation is to determine that one or more of the performance characteristics of the method is satisfactory so that the analytical results obtained will be fit for their intended purpose. 

The OFFC Regulation establishes a hierarchy of methods used for sampling and analysis in applying official controls. First priority is given to methods laid down in Community legislation. If these do not exist, methods according to internationally established rules such as those of CEN or those in national legislation should be applied. In the absence of these methods other methods fit for the purpose or developed in accordance with scientific protocols shall be used. In the area of food contact materials analytical methods are laid... 

Analytical measurements would be made using methods and equipment which had been tested to ensure they were fit for the purpose. These would be officially recognised methods or laboratory methods which were validated by analysis of certified samples or interlaboratory comparisons. 

The introduction of GC-high resolution mass spectrometry has added another dimension to the problem because much lower signal-to-noise spectra can be obtained and many interferences screened out. This beacons a new era where detection limits will fall and the number of confirmed positives could well rise. Also, will new problems arise in deciding if the method has been adequately validated That is, is it demonstrably fit for the purpose for which it was designed ... 

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