Validation characteristics

For criteria development we used systematical application of an insignificancy principle (IP). Uncertainty is insignificant in comparison with on the level of 95% if their pooled uncertainty is at most 5% exceeds A. It results in an inequality A < 0.32-A that is the main instiximent in development of acceptability criteria of validation characteristics. 

Validation is critical for any assays to be used in pharmaceutical development. Validating an NMR assay is fairly straightforward. Some validation characteristics for an NMR assay are briefly discussed in this section. 

Validation is the process of collecting documented evidence that the method performs according to the intended purpose. " The validation characteristics and the acceptance criteria to be applied in validation of HPLC methods for MAA/NDA filings and marketed products should comply with the international guidelines on method validation. Table 11 details validation activities to be conducted for type 1, type 2, and type 3 methods ... 

For each test it is advised to analyze the samples with replicates (e.g., n=6). The acceptance criteria are based on the method purpose and on the validation characteristics. A recommended approach would be to propose acceptance limits based on the results of the Gage R R study. If this study is not performed the Horwitz equation can be used to relate method repeatability with method reproducibility. Typically the difference in average assay values for DS methods should be within 2.0% and the precision should be less than 1.0% RSD in each laboratory. For DP, these limits are 3.0% and 2.0% for average assay difference and for the precision in each lab, respectively. The impurities are usually considered at a 0.5% level and the typically allowed difference between labs... 

Following method optimization a number of important method validation characteristics are checked in a brief pre-validation study. If the method would still show significant deficiencies, method optimization may need to be repeated. Suggested parameters to be checked may include... 

This chapter deals with the validation of capillary electrophoresis (CE) methods. It describes the various validation characteristics, namely accuracy, precision, specificity, detection limit, quantitation limit, linearity, and range in accordance with the official guidelines. Practical aspects related to the calculation of these parameters and factors affecting them in CE analysis have also been described. Validation requirements have been described according to the goal of the method. The chapter contains numerous tables and diagrams to illustrate these ideas. It also covers other related aspects such as instrument qualification, revalidation, and method transfer. 

Validation is the process of proving that a method is acceptable for its intended purpose. It is important to note that it is the method not the results that is validated. The most important aspect of any analytical method is the quality of the data it ultimately produces. The development and validation of a new analytical method may therefore be an iterative process. Results of validation studies may indicate that a change in the procedure is necessary, which may then require revalidation. Before a method is routinely used, it must be validated. There are a number of criteria for validating an analytical method, as different performance characteristics will require different validation criteria. Therefore, it is necessary to understand what the general definitions and schemes mean in the case of the validation of CE methods (Table 1). Validation in CE has been reviewed in references 1 and 2. The validation of calibrations for analytical separation techniques in general has been outlined in reference 3. The approach to the validation of CE method is similar to that employed for HPLC methods. Individual differences will be discussed under each validation characteristic. 

This chapter sheds light on the different validation requirements and methods to investigate them. Evaluation of the typical validation characteristics, namely accuracy, precision, specificity, DL, QL, linearity, and range in CE, has been discussed in details. Validation in CE is similar to validation in other separation techniques such as HPEC, but in CE, the capillary surface properties and namely the EOF have to be especially addressed. Eurther, the instrument performance has to be carefully considered during validation and method transfer. Here, the condition of the lamp and the thermostating system is of particular importance. 

ANALYTICAL METHOD VALIDATION CHARACTERISTICS Method development... 

Typical analytical performance characteristics that should be considered in the validation of the types of procedures described in this chapter are listed below. Each validation characteristic is defined to ensure consistency in usage of terminology and interpretation ... 

Association of Official Analytical Chemists (AOAC) International (2000), Method validation programs (OMA/PVM Department), including Appendix D Guidelines for collaborative study procedures to validate characteristics of a method of analysis, available http //www.aoac.org/vmeth/devmethno.htm. 

Different approaches may be used to validate the potency method. However, it is important to understand that the objective of validation is to demonstrate that a procedure is suitable for its intended purpose. With this in mind, the scientist will need to determine the extent of validation required. It is advisable to design experimental work such that the appropriate validation characteristics be considered simultaneously to obtain overall knowledge of the capabilities of the analytical procedure. 

The most important consideration for strategies of method validation is to design experimental work so that the appropriate validation characteristics are studied simultaneously, thereby minimizing the number of experiments that need to be done. It is therefore important to write some form of protocol to aid the planning process. Executing the experimental work without prior planning will be a disaster for the validation. 

ICH Validation Characteristic Data Reported Summary Validation Results... 

The validation requirements are discussed as they apply to both the sample preparation and sample analysis aspects of a dissolution method. The focus of the discussion in this chapter is on the validation considerations that are unique to a dissolution method. Validation is the assessment of the performance of a defined test method. The result of any successful validation exercise is a comprehensive set of data that will support the suitability of the test method for its intended use. To this end, execution of a validation exercise without a clearly defined plan can lead to many difficulties, including an incomplete or flawed set of validation data. Planning for the validation exercise must include the following determination of what performance characteristics to assess (i.e., strategy), how to assess each characteristic (i.e., experimental), and what minimum standard of performance is expected (i.e., criteria). The preparation of a validation protocol is highly recommended to clearly define the experiments and associated criteria. Validation of a test method must include experiments to assess both the sample preparation (i.e., sample dissolution) and the sample analysis. ICH Q2A [1] provides guidance for the validation characteristics of the dissolution test and is summarized in Table 4.1. 

In this chapter, validation studies for developing the quantitative and JP limit test methods for heavy metals described in Specifications and Testing Methods of the drug substance section are described. Procedures to evaluate validation characteristics concerning the validation items of each test method are described. Table 7.1 summarizes the validation characteristics required by JP for testing of impurities. 

The quantitation of heavy metals in a drug substance is a method to determine the quantity of lead by determining the intensity of coloring with sodium sulfide based on the absorbance at 400 nm by spectrophotometry. It is a prerequisite to set up the limit test according to the JP requirements. With regard to validation characteristics of the quantitation method, specificity is not required because of... 

The preparation and execution should follow a validation protocol, in which the scope of the method and its validation criteria should first be defined (46). The scope of the analytical method should be clearly understood since this will govern the validation characteristics that need to be evaluated. For example, if the method is to be used for qualitative trace residue analysis, there is no need to examine and validate its linearity over the full dynamic range of the equipment. The scope of the method should also include the different types of equipment and the locations where the method will be run. In this way, experiments can be limited to what is really necessary. For example, if the method is intended for use in one specific laboratory, there is no need to include other laboratories and different equipment in the validation experiments. 

Table 3 ICH Analytical Methods and Validation Characteristics Type of analytical procedure...

Guidelines for Collaborative Study Procedure to Validate Characteristics of a Method of Analysis, J. Assoc. Anal. Chem., 72 694 (1989). 

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