Method definition requirement document

The outcome of planning should include the generation of a method definition requirement document (MDRD) in which all stake holders agree, prior to method development, on the critical attributes of the method. Considerations such as what impurities/degradation products should be monitored, requisite reporting thresholds, the need for an MS-compatible method, if identical methods for DP and DS are required, etc., should be clearly decided and agreed upon by all stakeholders. 

The Canadian Acceptable Methods document [14] gives more or less a combination of the two definitions described above and considers 3 levels in the testing of the ruggedness of a method, with the third level being performed only rarely. Level one requires verification of the basic insensitivity of the method to minor changes in environmental and operational conditions and should include verification of reproducibility by a second analyst . The first part of this definition resembles the French Guide s definition. The second part is a check on the adequacy of the method description and should be done without input from the original analyst. 

In addition to the somewhat empirical and difficult development of NIR applications, thorough documentation must be produced. NIR methods have to comply with the current good manufacturing practice (cGMP) requirements used in the pharmaceutical industry. Various regulatory aspects have to be carefully considered. For example, NIR applications in classification, identification, or quantification require extensive model development and validation, a study of the risk impact of possible errors, a definition of model variables and measurement parameters, and... 

There are many reasons for the need to validate analytical procedures. Among them are regulatory requirements, good science, and quality control requirements. The Code of Federal Regulations (CFR) 311.165c explicitly states that the accuracy, sensitivity, specificity, and reproducibility of test methods employed by the firm shall be established and documented. Of course, as scientists, we would want to apply good science to demonstrate that the analytical method used had demonstrated accuracy, sensitivity, specificity, and reproducibility. Finally management of the quality control unit would definitely want to ensure that the analytical methods that the department uses to release its products are properly validated for its intended use so the product will be safe for human use. 

Particle size measurement is one of the essential requirements in almost all uses of colloids. However, our discussion in Section 1.5 makes it clear that this is no easy task, especially since even the definition of particle size is difficult in many cases. A number of techniques have been developed for measuring particle size and are well documented in specialized monographs (e.g., Allen 1990). Optical and electron microscopy described in the previous section can be used when ex situ measurements are possible or can be acceptable, but we also touch on a few nonintrusive methods such as static and dynamic light scattering (Chapter 5) and field-flow fractionation (see Vignette II Chapter 2) in other chapters. 

An operational definition is considerably more practical. Operationally determined species are defined by the methods used to separate them from other forms of the same element that may be present. The physical or chemical procedure that isolates the particular set of metal species is used to define the set. Metals extracted from soil with an acetate buffer is an operational definition of a certain class. Lead present in airborne particles of less than 10 pm is another. In water analyses, simply filtering the sample before acidification can speciate the analytes into dissolved and insoluble fractions. These procedures are sometimes referred to as fractionation, which is probably a more properly descriptive term than speciation, as speciation might imply that a particular chemical species or compound is being determined. When such operational speciation is done, careful documentation of the protocol is required, since small changes in procedure can lead to substantial changes in the results. Standardized methods are recommended, as results cannot be compared from one laboratory to another unless a standard protocol is followed [124], Improvements in methodology must be documented and compared with the currently used standard methods to produce useful, readily interpretable information. 

The first step in the evaluation process is to define and document the current system use and user requirement specifications. If the system will be changed in the foreseeable future, any resulting changes in the intended use of the system should be described as well. The definition should include a list of system functions, operational parameters and performance limits. For chromatography software required functions may include instrument control, data acquisition, peak integration through quantitation, file storage and retrieval and print-out of methods and data. If the system also includes spectrophotometric detectors, the functions for spectral evaluation should be specified as well. Table 2 lists items that should be included in the system documentation. 

In the case of method transfer, contracts should include specific milestones defining successful completion of parts as well as the whole project. As a minimum, the contract should contain the number of experiments and documentation requirements for the method transfer results. In addition, early definition of criteria for success and failure of experiments and responsibilities for repeating failed experiments, sets the stage for a smoother process throughout the project. The contract should also state, as part of the deliverables, the level of documentation of method protocols and content of the final report. 

As described in previous sections, the standard method for treating durability in EN 206 and Eurocode 2 is based on the definition of the exposure class and determining for each class, the maximum w/c ratio, the minimum cement content and the minimum thickness of the concrete cover. EN 206 provides recommended (informative, that is non-normative) values for concrete composition in terms of maximum w/c ratio, minimum strength class and minimum cement content, assuming an intended working life of 50 y, the use of Portland cement (CEM I) and maximum aggregate size between 20 and 32 mm. In national documents these values and additional requirements can be further specified as normative values, as has been done for example in NEN 8005 (nl) for The Netherlands [12]. 

Document the requirements definition of the standard software by means of semantic modeling methods, making the business logic more understandable. 

The regulatory guides are documents which describe at least one acceptable way to satisfy the various requirements of the GDC or of other texts. The degree of technical detail is high and goes down to the definition of numerical values of key parameters for the analytical demonstrations. The designer can choose to adopt the method indicated... 

Many of these definitions use the concept of fit for purpose. The importance of this is the implication that there is no absolute worth of a method. If the results are sufficient for the requirements of the client, and the client genuinely receives useful results, the method is fit for purpose. How well a client views a method is tied to its intended use and so the process of method validation must be ultimately guided by the requirements of intended use. This appears to imply that every laboratory will need to embark on extensive experimentation with each new job. Sensibly, it is recognized that a particular method is used in a broadly similar manner across the world, and so if an international agency such as American Society for Testing and Materials or Association of Official Analytical Chemists (AOAC) takes on the job of overseeing a validation, the work of the end laboratory will be to make sure that it carries out the method in such a way as to preserve the prior validation, and documents any aspects specific to that laboratory. 

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