Method validation guidelines for

Method validation guidelines for use in trace analysis have been proposed by various authors, but there is little consistency in the recommended approaches. The general validation guidelines proposed by standards organizations such as ISO (International Organization for Standardization), DIN (Deutsches Institut fUr Normung German Institute for Standardization) and others are often not well defined and consequently... 

Method qualification is based on ICH method validation guidelines. Method type (purity or identity) will dictate the level of qualification testing necessary. Several strategies for method qualification and validation exist and are based on needs, resources available, and the project timeframe. One approach is to perform minimal development and qualification, which may be necessary for projects with shorter timelines, but it may place more burden and risk on future validation activities for robustness testing, and can result in failure. As discussed in Chapter 4, an alternate approach would invest more time and resources into method development, followed by extensive qualification and robusmess testing to determine if further development is... 

US FDA, Guidelines for Submitting Samples and Analytical Data for Method Validation, Center for Drugs and Biologies, Department of Health and Human Services, Rockville, MD, USA (1987). 

Government and international agencies have issued guidelines for appropriate method validation, particularly for methods for regulatory submission. Generally, they include studies on ... 

Layloff T, NasrM, Baldwin R, Caphart M, et al (2000) The FDA regulatory methods validation program for new and abbreviated new drug applications. Pharm Technol 24, pp 30-42 International Conference on Harmonization (ICH) (November 1996) Guideline QIB, Photostability testing of new drug substances and products... 

Validation is the procedure which proves that a method yields the expected results with reliability, adequate precision and accuracy. It is a matter of fact that it is not possible to define generally valid guidelines for method validation. However, in any case, several or all of the following points are included ... 

Bioanalytical method validation guidelines recommend using a minimum of three samples at low, mid, and high concentrations across the calibration curve range for precision testing. Measurements should include the evaluation of precision or repeatability within a single analytical run... 

Schemes for validation of quantitative TLC methods under guidelines for...

A variety of national and international guidelines have been formulated to support method validation. Requirements for the components of a method validation may vary between countries depending on the level of approval that has been obtained. For example, in the United States, Food and Drug Administration (FDA)-approved devices must meet Clinical Laboratory Improvement Amendments (CLlAs) requirements for method validation, if they are deemed of medium or high complexity laboratories operating these tests are subject to inspection and must meet the CLl A quality system standards [12]. However, some POCT devices deemed of low complexity by the FDA may be CLlA-waived such that areas operating only these low complexity tests must simply follow the manufacturer s instructions for those tests to meet CLl A requirements. However, it is not always clear if CLlA-waived devices meet the quahty specification for the analytes being measured. 

It is not imcommon for a method that has been shown to be valid based on traditional guidelines to fail when transferred to a testing lab for routine use. While the traditional method validation guidelines just discussed provide a level of assiuance that an analytical method will perform adequately, they do not directly address the piupose of a quantitative method, that is, that the method provides a "reasonable" estimate of the true value of the sample tested. In addition, traditional validation guidelines recommend evaluation of method robustness by... 

The guideline states that the objective of validation is to demonstrate that an analytical method is fit for its purpose and summarizes the characteristics required of tests for identification, control of impurities and assay procedures (Table 13-2). As such, it applies to chiral drug substances as to any other active ingredients. Requirements for other analytical procedures may be added in due course. 

A pharmacopoeial reference substance is intended for the determination of the main component of a substance or for the active ingredient of a pharmaceutical formulation which is usually present at a high proportion of the total. The reference substance is to be used as a primary standard in a specific method validated as prescribed in the ICH Guideline Validation of Analytical Procedure Methodology" (Technical Guide for the Elaboration of Monographs 1996 ICH Guideline 1997). the reproducibility of which is known. This is taken into account when the limits of acceptance (tolerance) for the substance or product are fixed (Daas and Miller 1997,1998). 

AOAC/FAO/IAEA/IUPAC Expert Consultation, Guidelines for Single Laboratory Validation of Analytical Methods for Trace-level Concentrations of Organic Chemicals, Workshop, 8-11 November 1999, Miskolc, Hungary (1999). Also available on the Word Wide Web http //www.iaea.oi trc/(see pesticides —> method validation). 

Once the determinative or confirmatory method has been developed to take full advantage of the chemical properties of the analyte molecule, a study is necessary to prove that the method is valid. Criteria for method validation are outlined in guidelines from the US FDA, US EPA, and EU. A summary of the differences in regulatory requirements for method validation is provided in Table 3. The parameters addressed by all of the regulatory guidelines include accuracy, precision, sensitivity, specificity, and practicability. 

In most situations analysts can achieve a rapid reasonable separation of compounds using an appropriate standard CE method with generic operating conditions [877]. This eliminates or reduces dramatically the need for method development. Major instrumental error sources in CE are detection, integration and injection. General guidelines for validation of CE methods are available and similar to those of HPLC [878]. Validated CE methods often perform the same as, or better than, the corresponding HPLC methods. 

You may have included some other documents with the SOPs and WIs because they are also held in your area of the laboratory. These could be, for example, guides for carrying out particular activities, such as method validation, and international guidelines on how to achieve reliable results. Some areas of activity may be covered by legislation copies of the relevant documents will be kept locally as it may be referenced in the SOP. Equipment manuals are also kept locally. 

By using the combination of specific method accreditation and generic accreditation it will be possible for laboratories to be accredited for all the analyses of which they are capable and competent to undertake. Method performance validation data demonstrating that the method was fit-for-purpose shall be demonstrated before the test result is released and method performance shall be monitored by on-going quality-control techniques where applicable. It will be necessary for laboratories to be able to demonstrate quality-control procedures to ensure compliance with the EN 45001 Standard,3 an example of which would be compliance with the ISO/AOAC/IUPAC Guidelines on Internal Quality Control in Analytical Chemistry Laboratories.12... 

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