Fit for intended purpose

One thing that is certain with the developments in chiral selectors and their applications that have been described is that they will continue, whether it be by gradual evolutionary fine-tuning in an already mature area or by some yet unforeseen major advances. What is of more importance is how these developments currently shape up with respect to the applications presented by the chiral analysis of pharmaceuticals. 

Perhaps there is scope for further developments in CSP in order to more frequently achieve high enough enantioselectivity for facile preparative isolation to be carried out. However, most of the current developments in terms of preparative chiral separations seems to be in developing technolgies for SFC and SMB and, to a lesser extent, CSP in which there is not even an ultra-trace leakage of the chiral selector. 

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Validation of analytical methods We all know that validation is to assess fitness for intended purpose. It was therefore logical to combine the separate chapters on Fit for purpose and Validation in the first edition into one chapter. 

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 primary aim of this book is to provide readers interested in solid sample pretreatment with an overview of available techniques for development of this step of the analytical process. The title of the book is intended to reflect that it is mainly concerned with the dissolution or removal of target analytes from solid samples. Once they have selected the technique most closely fitting their intended purpose, readers can obtain a deeper knowledge about the technique of choice in the specialized literature — in fact, providing a thorough description of each of the wide variety of sample pretreatment techniques available at present was obviously outside the scope of a book like this. In fact, only those aspects that can be illustrated with reasonable concision are dealt with specifically in it. For identical reasons, the book does not touch on the subsequent steps of the analytical process. The authors therefore assume that the reader will be acquainted with the general principles of chromatography in its different variants, as well as with those of commonplace molecular optical and electroanalytical techniques, and atomic and mass spectrometries. 

One of the fundamental principles of valid, cost-effective analytical measurement is that methodology should demonstrably fit its intended purpose [1], Technical fitness for purpose is usually interpreted in terms of the required accuracy . To provide reasonable assurance of fitness for purpose, therefore, the analyst needs to demonstrate that the chosen method can be correctly implemented and, before reporting the result, needs to be in a position to evaluate its uncertainty against the confidence required. 

Without fully documented and properly validated methods, analysts, or others who use the data provided by analysts, will not have the confidence to ensure that the results that are generated are fit for the purpose for which they were originally intended. Methods should be fully documented, and should clearly and unambiguously describe the determinand being determined as well as the concentration range of the determinand for which the method is applicable, and the matrix, or matrices, to which the method can be applied. In addition, clear details of the procedures to be followed should be documented in such a manner that the text cannot be open to mis-interpretation and that the analyst can precisely carry out that which needs to be done. Without all this information, the scope of the method cannot be clearly defined and the method will often be misused, for example, in the inappropriate determination of parameters... 

The reason for testing is to gain information, thereby ascertaining the acceptability of the test piece in comparison with a specification. That specification should be drawn up so that if all results pass, the material is fit for the purpose that it is intended to fulfil. All tests must be relevant to the use of the material, and must be understood by all the parties involved. This need has led to a series of standard tests British BSI, ASTM, etc. 

Intermediate accuracy is accomplished by permitting the elution of uranium from the chelation resin cartridges to be slightly concentrated rather than diluted, and analyzed with a Q-ICP-MS and a partially desolvat-ing introduction system, rather than a desolvating system on an MS-ICP-MS. However, such an instrumental setup permits greater access of laboratories with more limited funds to acquire useful uranium isotope ratio results and is fit for the purpose as intended. 

To carry out a rigorous LCA, the boundaries must be fit for the purpose of the intended comparison and, importantly, it must be clearly defined. When carrying out comparisons of alternative materials and systems, elements common to both solutions may be excluded because emissions would be identical for this component of the works. An example of this includes site mobilisation, preparatory clearance works or... 

It is sincerely hoped that the information presented in this document will lead to an even more impressive record for the entire industry however, the American Institute of Chemical Engineers, its consultants, CCPS Subcommittee members, their employers, their employers officers and directors, and Arthur D. Little, Inc., disclaim making or giving any warranties or representations, express or implied, including with respect to fitness, intended purpose, use or merchantability and/or correctness or accuracy of the content of the information presented in this document. As between (1) American Institute of Chemical Engineers, its consultants, CCPS Subcommittee members, their employers, their employers officers and directors, and Arthur D. Little, Inc., and (2) the user of this document, the user accepts any legal liability or responsibility whatsoever for the consequence of its use or misuse. 

Seller warrants that Product delivered to [insert company name] will (1) conform to the descriptions and specifications as set forth in this Agreement (2) be of good quality and workmanship and free from defects, latent or patent and (3) be merchantable and fit and sufficient for [insert company name] s intended purpose. Payment, inspection, acceptance or use of Product will not affect Seller s obligation under this warranty. 

The requirements are specified in terms of the features and characteristics that will make the product or service fit for its intended purpose. A list of typical features and characteristics is given in Part 1 Chapter 1 for both products and services. 

Users should be the prime participants in the preparation process so that the resultant documents reflect their needs and are fit for the intended purpose - hence the requirement that documents be reviewed as well as approved. You will need to be able to demonstrate that your documents have in fact been reviewed prior to issue. The presence of a signature on the front cover is not sufficient evidence. To demonstrate that documents have been reviewed you will need to show that nominated personnel have been issued with drafts for comment and that they have provided comments which have been considered by the approval authorities. A simple method is to employ a standard comment sheet on which reviewers can indicate their comments or signify that they have no comment. During the review process you may undertake several revisions. You may feel it necessary to retain these in case of dispute later, but there is no compulsion for you to do so, providing you have evidence that the review took place. You also need to show that the current issue has been reviewed so your comment sheet needs to indicate document issue status. 

In this article, an analytical method is defined as series of procedures from receipt of a sample to final determination of the residue. Validation is the process of verifying that a method is fit for purpose. Typically, validation follows completion of the development of a method. Validated analytical data are essential for monitoring of pesticide residues and control of legal residue limits. Analysts must provide information to demonstrate that a method intended for these purposes is capable of providing adequate specificity, accuracy and precision, at relevant analyte concentrations and in all matrices analyzed. 

It is equally important for the manufacturer and regulator to know the level of additives in a polymer material to ensure that the product is fit for its intended purpose. Additive analysis marks sources of supply, provides a (total) process signature and may actually be used as a fingerprint of a polymeric material, in particular as molecular characterisation of the polymer... 

If data are produced which are not fit for their intended purpose, there is both the financial penalty and the possible legal penalty to be considered. For instance, if a manufacturer of pharmaceuticals produces a pharmaceutical tablet containing the incorrect amount of active ingredient, the consequences could be disastrous, causing, in the worst circumstances, loss of life. 

The degree of validation of the methods may be quite different. What validation means is that the method has been subject to a study which shows that, as applied in the user s laboratory, it provides results which are fit for their intended purpose. The method satisfies some pre-defined criteria. When standard or internationally agreed methods are being developed, the validation of the method is more complicated and time-consuming than that of methods developed in-house. Such validation involves a collaborative study using analysts working in a number of laboratories. This has already been mentioned in Chapter 1 and the organization of collaborative studies is discussed in Chapter 7. However, this more elaborate procedure does not necessarily mean that the method is more reliable than in-house methods. 

This section has a twofold purpose. First, it is intended to enable minor changes to be made to the text of the method without the need for a full revision and reprint of the method. Secondly, it is recommended that every method should be reviewed periodically for fitness for purpose and the summary serves as a record that this has been done. The summary typically would be located at the front of the method, just inside the front cover. 

All equipment has limitations, for example, the amount of a substance it can detect or the accuracy with which it can make a measurement. If you attempt to make the equipment perform beyond its capabilities, it does not matter how carefully the equipment is operated, it will not be possible to get meaningful results. In terms of a particular instrument, fitness for purpose is interpreted as having appropriate performance capability to do the work required. This applies to all equipment, large or small. For example, a stirrer needs to perform the intended task satisfactorily while remaining essentially inert. There is a formal process for assessing the suitability of equipment to perform a given task - this is called Equipment Qualification or Equipment Validation. This is dealt with in Section 5.6.3. 

The computerized systems, both hardware and software, that form part of the GLP study should comply with the requirements of the principles of GLP. This relates to the development, validation, operation and maintenance of the system. Validation means that tests have been carried out to demonstrate that the system is fit for its intended purpose. Like any other validation, this will be the use of objective evidence to confirm that the pre-set requirements for the system have been met. There will be a number of different types of computer system, ranging from personal computers and programmable analytical instruments to a laboratory information management system (LIMS). The extent of validation depends on the impact the system has on product quality, safety and record integrity. A risk-based approach can be used to assess the extent of validation required, focusing effort on critical areas. A computerized analytical system in a QC laboratory requires full validation (equipment qualification) with clear boundaries set on its range of operation because this has a high... 

Reference Material A material, sufficiently homogeneous and stable with respect to one or more properties, which has been established to be fit for its intended purpose. 

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