Method validation basic principle

In this paper, we have exposed a solution to improve the resolution in Low Frequency Ultrasonic Tomography. Since the basic principle of ultrasonic reflection tomography prohibits the inspection of objects with strong contrast and large extension, we turn down the frequency of the transducer, in order to increase the penetration length of the wave and the validity of the method. But this is done at the expense of resolution. 

Methods development starts with a relatively high number of techniques to characterize and test samples. The number of protocols is often reduced once the critical parameters and the methods that identify them have been defined. The analyst must evaluate the initial techniques with respect to their purposes. If the goal is to generate research data, the practicality of the method and its limitations are not of primary concern if the goal is to use the technique as part of a test procedure, it has to be evaluated in terms of its potential to meet full validation. Critical procedures (e.g., release testing) that cannot be validated will bring a project to an expensive halt. For these reasons, this chapter provides basic principles as well as limitations of capillary electrophoresis (CE) as applied to the analysis of real biopharmaceutical molecules. 

Accreditation is a formal recognition that a laboratory is competent to carry out specific (types of) calibrations or tests [2]. After the use of validated and standardized methods, the introduction and use of appropriate IQC procedures and the participation in PT schemes, accreditation to ISO/IEC 17025 is the fourth basic principle related to laboratory QA in general [4]. Guidelines on the implementation of ISO/IEC 17025, including the estimation of MU (see also Section 8.2.2), are published in the literature and by official accreditation bodies such as Eurachem, CITAC, EA, Eurolab, and ILAC (see Table 1) [2,60, 80, 81,110]. It is worthwile to mention that accreditation, just like participance in PT schemes, does not necessarily indicate good performance of the laboratory [108]. 

This article deals with legal requirements in the European Union on basic principles of laboratory quality assurance for official notification to the EC Commission and on method validation concerning official laboratories. Widespread discussions and activities on measurement uncertainty are in progress, and the European validation standards for official purposes may serve as a basis for world-wide efforts on quality harmonization of analytical results. Although much time has already been spent, definitions and require-... 

In principle, the quality of an analytical method can be expressed through two groups of basic and secondary characteristics or figures of merit, which must be quantified by the user of the method before using it to deliver results. The determination of these quantified figures is achieved in the method validation process (see section 2.3). ba.sic characteristics. ... 

Clinical Simulation Studies. These protocols allow assessment of each of the characteristics of the proposed indications described in Table 4 [27] and include the basic principles articulated by the Antimicrobial I Panel (Table 2). The design is also based on reviewer experiences gained from the development of topical antibiotic and antimicrobial drug products through the NDA process. Examples of changes or recommendations include the incorporation of a positive control to validate the performance of the study, a test product vehicle arm, and proposed statistical methods of analysis to evaluate the data. Studies must be... 

The data reduction of vapor-pressure osmometry (VPO) follows to some extent the same relations as outlined above. However, from its basic principles, it is not an equilibrium method, since one measures the (very) small difference between the boiling point temperatures of the pure solvent drop and the polymer solution drop in a dynamic regime. This temperature difference is the starting point for determining solvent activities. There is an analogy to the boiling point elevation in thermodynamic equilibrium. Therefore, in the steady state period of the experiment, the following relation can be applied if one assumes that the steady state is sufficiently near the vapor-liquid equilibrium and linear non-equilibrium thermodynamics is valid ... 

The approach is based on the use of at least two reference methods with different chemical principles (possibly including a primary method), operated in the same laboratory by at least two independent analysts. Reference methods refer to methods of which the accuracy has been demonstrated by an appropriate validation. The principle of this approach is that an agreement between two or more independent methods will limit the risk that systematic errors are left undetected. The basic question relates to the real independence of the analysts working in the same laboratory, and it is advisable to involve other laboratories, which brings us to the next case. 

Elucidation of how the general principles underlying the concept of validation should be expressed in practice is an evolving process, as exemplified by the ongoing evolution of validation requirements for bioanalytical assays in the pharmaceutical industry (Shah 1992, 2000 FDA 2001 Viswanathan 2007). The complementary principle of fitness for purpose (Section 9.2) applies not only to the assay method but also to the validation process itself. Procedures that are considered to be fit for purpose in validation of an analytical method to be used in drug development, for example, need not necessarily apply to, e.g., methods used to screen pesticide residues in foodstuffs. As noted in Section 9.2, this point of view appears to be consistent with the definition of validation applied to all measurements (ISO 1994) Validation Confirmation by examination and provision of objective evidence that the particular requirements for a specified intended use are fulfilled. Of course, some basic principles are common to all validation schemes. 

A validation protocol adapted from the experiences during the method development defines the scope of the validation study (goal of the study, regulating guidelines, key method parameters, etc.). To investigate the adequate method performance, these features (e.g., range of analyte concentration), together with a statement of any fitness-for-purpose criteria, have to be specified in the validation protocol. A basic check has to provide that the reasonable assumptions about the principles of the method are not seriously flawed. In this process, sources of error in analysis have to be listed (Table 4) and their effects have to be checked. The validation should, as far as possible, be conducted to provide a realistic survey of the number... 

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