Method validation international guidelines

IUPAC method validation International Union of Pure and Applied Chemistry, Harmonized guidelines for single laboratory validation of method of analysis... 

Eor the validation of analytical methods, an international guideline applies [61] that has been elaborated by EDQM, see Sect. 32.16.2. Eor stability studies on pharmacy preparations, where there may be neither the equipment nor the time available to develop and validate an analytical method, as an alternative approach [62-64] can be used. 

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... 

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. 

The guidelines stress, however, that internal quality control is not foolproof even when properly executed. Obviously it is subject to errors of both kinds , i.e. runs that are in control will occasionally be rejected and runs that are out of control occasionally accepted. Of more importance, IQC cannot usually identify sporadic gross errors or short-term disturbances in the analytical system that affect the results for individual test materials. Moreover, inferences based on IQC results are applicable only to test materials that fall within the scope of the analytical method validation. Despite these limitations, which professional experience and diligence can alleviate to a degree, internal quality control is the principal recourse available for ensuring that only data of appropriate quality are released from a laboratory. When properly executed it is very successful. 

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 ... 

It is important to issue a common understanding on the topics of method validation, traceability, and uncertainty of measurements. Here, the interrelationships between method validation, traceability, and MU of results will be elucidated. Throughout the landscape of guidelines and standards, the most relevant information is selected, compiled, and summarized. Great importance is attached to the different method performance parameters and their definitions, ways of expression, and approaches for practical assessment. We discuss the role of method validation within QA as well as the topics of standardization, internal and external quality control (IQC and EQC, respectively), and accreditation and the links between these different aspects. 

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. 

Present-day analytical laboratories are increasingly under pressure to supply objective evidence of their technical competence, of the reliability of their results and performance, and to seek formal certification or accreditation. This pressure may come from the laboratory s customers (e.g., industry and national bodies) but may also be due to scientific considerations. A QM system in place, validation of methods, uncertainty evaluation, the use of primary standards and CRMs, participation in ILCs, and PT, all serve to assure and demonstrate the quality of measurements. Compared to, say, 30 years ago, the stability of the equipment now available is much improved, and a greater range of RMs for method validation and calibration is accessible. Nevertheless, to achieve mutual (international) acceptance of various bodies of evidence for QA activities, a number of protocols have been developed. The most widely recognized protocols used in chemical measurements and testing are the ISO Guide 9000 2000, ISO/IEC 17025 2005, and OECD Guidelines for GLP, as well as its national and sector equivalents. 

All analytical methods must be validated in accordance with international guidelines [59-61] prior to application. As discussed in the first part of this book, minimum criteria that need to be met to in order to satisfy these guidelines are selectivity, matrix effects, extraction efficiency, process efficiency, processed sample stability, linearity, accuracy, precision, and freeze-thaw stability. 

The assay has been validated and the results of validation demonstrate that the standard curve is linear over the concentration range of 100-2000 ng/mL. The assay is reproducible and accurate, with recovery of the analyte and internal standard in the range of 80-90 %. The analysis requires 0.5 mL of plasma and has a limit of quantification of 70 ng/mL. The stability of plasma samples stored at -20 °C has been demonstrated for up to 12 weeks. Autoinjector stability has been demonstrated for over 13 h and freeze-thaw stability has been demonstrated for 3 freeze-thaw cycles. The procedure has a sample throughput of at least 30 specimens per day. The assay meets the guidelines for bioanalytical methods validation for human studies (Shah et al. 1991). 

In 1996 and 1997 the International Conference on Harmonization (ICH) published guidelines for analytical method validation [8]. These documents present a discussion of the characteristics for consideration during the validation of the analytical procedures included as part of registration applications submitted within the European Union, Japan, and the United States. 

As required by regulatory authorities [1-3, 6] and International Conference on Harmonisation (ICH) guidelines [7], analytical method validation is especially important in establishing the assay methods and procedures of quantitative or semi-quantitative measurement of target substances or compounds. Among the specification items for drug products, assay, content uniformity, and dissolution are typical of those which require almost full analytical validation. The purity test, related... 

AOAC, 1999. Qualitative and Quantitative Microbiology Guidelines for Methods Validation, Journal of AOAC International, 82(2). 

There have been various attempts to place the concept of detection limit on a more firm statistical ground. The International Conference on Harmonization (ICH see Chapter 4) of Technical Requirements for Registration of Pharmaceuticals for Human Use has proposed guidelines for analytical method validation (Ref. 18). The ICH Q2B guideline on validation methodology suggests calculation based on the standard deviation, s, of the response and the slope or sensitivity, S, of the calibration curve at levels approaching the limit. For the limit of detection (LOD),... 

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

There are two sources of information from the CAC that provide guidance on the validation of analytical methods. General guidance on method validation, including single-laboratory method validation, may be found in the CAC Procedural Manual.This is supplemented by Codex Alimentarius Commission guidelines, a number of which have been adopted from harmonized guidelines previously developed by independent international scientific... 

There are several resources [1 - 6] available to aid the analytical scientist in performing method validation once a method has been developed. The International Conference on Harmonisation (ICH) guideline on Validation of Analytical Procedures Text and Methodology was recently updated to combine Q2A and Q2B in one document, Q2(R1) [1]. This guideline provides a defined approach to method validation and offers definitions on the validation elements and recommended data that should be included in the final report. 

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... 

As an analytical approach to residue analysis, immunoassay methods are not well characterized, and no validation protocols have been established. The Association of Official Analytical Chemists, whose primary purpose is validation of analytical methods, established a Task Force on Test Kits and Proprietary Methods (2), which has addressed some of the issues relating to immunoassay methods. The International Union of Pure and Applied Chemistry s Commission on Food Chemistry has established a Working Group on Immunochemical Methods, whose first project is to develop draft guidelines on criteria for evaluation, validation, and quality control for r o-immunoassay methods (10). Similar guidelines for EIAs will also be developed. These documents will assist in development and standardization of requirements for precision for both between-laboratories and within-laboratory andyses, accuracy, and ruggedness, and— for qualitative methods— false positive and false negative rates. 

Harmonization of requirements has successfully been made by the International Conference on Harmonisation (ICH), e.g., in guidelines on stability documentation, method validation, and investigation of impurities. Regarding impurities information is given on how the limits should be set and at what level identification is needed. Similar efforts are seen for dissolution testing and how to correlate in vivo and in vitro data. The question of bioavailability and bioequivalence is an important one and has been dealt with as well. As a consequence of the rapid development in chiral separations we can now see a harmonization of requirements also for chiral drugs. 

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