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Journal ArticleDOI

Bioanalytical Method Validation

03 Nov 2012-Journal of analytical and bioanalytical techniques (OMICS International)-Vol. 2012, Iss: 07
TL;DR: The validation parameters are described, together with an example of validation methodology applied in the case of ch romatographic methods used in bioanalysis, taking into account to the recent Food and Drug Administration (FDA) documents.
Abstract: A syntetic discussion on bioanalytical methods vali dation is presented from the point of view of regul atory documents, scientific articles and books. The validation parameters are described, together with an example of validation methodology applied in the case of ch romatographic methods used in bioanalysis, taking i n account to the recent Food and Drug Administration (FDA) gu idelines and documents of the International Confere nce on Harmonisation of Technical Requirements for Registr ation of Pharmaceuticals for Human Use (ICH).
Citations
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Journal ArticleDOI
TL;DR: A workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays and defined three tiers of assays distinguished by their performance and extent of analytical characterization.

476 citations

Journal ArticleDOI
TL;DR: Standard operating procedures (SOPs) with step-by-step instructions for a number of different validation parameters is included in the present work together with a validation report template, which allow for a well-ordered presentation of the results.
Abstract: Biochemical markers have a central position in the diagnosis and management of patients in clinical medicine, and also in clinical research and drug development, also for brain disorders, such as Alzheimer's disease. The enzyme-linked immunosorbent assay (ELISA) is frequently used for measurement of low-abundance biomarkers. However, the quality of ELISA methods varies, which may introduce both systematic and random errors. This urges the need for more rigorous control of assay performance, regardless of its use in a research setting, in clinical routine, or drug development. The aim of a method validation is to present objective evidence that a method fulfills the requirements for its intended use. Although much has been published on which parameters to investigate in a method validation, less is available on a detailed level on how to perform the corresponding experiments. To remedy this, standard operating procedures (SOPs) with step-by-step instructions for a number of different validation parameters is included in the present work together with a validation report template, which allow for a well-ordered presentation of the results. Even though the SOPs were developed with the intended use for immunochemical methods and to be used for multicenter evaluations, most of them are generic and can be used for other technologies as well.

336 citations

Journal ArticleDOI
TL;DR: The development of a sensitive and specific LC-MS/MS method for quantifying 3β,5α,6β-triol and 7-KC human plasma after derivatization with N,N-dimethylglycine is described, offering for the first time a noninvasive, rapid, and highly sensitive method for diagnosis of NPC1 disease.

225 citations


Cites background from "Bioanalytical Method Validation"

  • ...The results of the QC samples provided the basis of accepting or rejecting the run (22)....

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Journal ArticleDOI
TL;DR: It is too early to expect that the new technological advances will catalyze the anticipated biomarker revolution any time soon, but the journey of a protein biomarker from the bench to the clinic is long and challenging.
Abstract: BACKGROUND: Protein cancer biomarkers serve multiple clinical purposes, both early and late, during disease progression. The search for new and better biomarkers has become an integral component of contemporary cancer research. However, the number of new biomarkers cleared by the US Food and Drug Administration has declined substantially over the last 10 years, raising concerns regarding the efficiency of the biomarker-development pipeline. CONTENT: We describe different clinical uses of cancer biomarkers and their performance requirements. We also present examples of protein cancer biomarkers currently in clinical use and their limitations. The major barriers that candidate biomarkers need to overcome to reach the clinic are addressed. Finally, the long and arduous journey of a protein cancer biomarker from the bench to the clinic is outlined with an example. SUMMARY: The journey of a protein biomarker from the bench to the clinic is long and challenging. Every step needs to be meticulously planned and executed to succeed. The history of clinically useful biomarkers suggests that at least a decade is required for the transition of a marker from the bench to the bedside. Therefore, it may be too early to expect that the new technological advances will catalyze the anticipated biomarker revolution any time soon.

131 citations

Journal ArticleDOI
TL;DR: Enzalutamide has predictable pharmacokinetics, with low intersubject variability, and similar efficacy was observed in patients across the concentration/exposure range associated with a fixed oral dose of enzalUTamide 160 mg/day.
Abstract: Oral enzalutamide (160 mg once daily) is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This article describes the pharmacokinetics of enzalutamide and its active metabolite N-desmethyl enzalutamide. Results are reported from five clinical studies. In a dose-escalation study (n = 140), enzalutamide half-life was 5.8 days, steady state was achieved by day 28, accumulation was 8.3-fold, exposure was approximately dose proportional from 30–360 mg/day, and intersubject variability was ≤30 %. In a mass balance study (n = 6), enzalutamide was primarily eliminated by hepatic metabolism. Renal excretion was an insignificant elimination pathway for enzalutamide and N-desmethyl enzalutamide. In a food-effect study (n = 60), food did not have a meaningful effect on area under the plasma concentration–time curve (AUC) of enzalutamide or N-desmethyl enzalutamide, and in an hepatic impairment study, AUC of the sum of enzalutamide plus N-desmethyl enzalutamide was similar in men with mild (n = 6) or moderate (n = 8) impairment (Child–Pugh Class A and B) versus men with normal hepatic function (n = 14). In a phase III trial, an exposure-response analysis of steady-state predose (trough) concentrations (C trough) versus overall survival (n = 1103) showed that active treatment C trough quartiles for 160 mg/day were uniformly beneficial relative to placebo, and no threshold of C trough was associated with a statistically significant better response. Enzalutamide has predictable pharmacokinetics, with low intersubject variability. Similar efficacy was observed in patients across the concentration/exposure range associated with a fixed oral dose of enzalutamide 160 mg/day.

103 citations

References
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Journal ArticleDOI
TL;DR: The purpose of this report is to represent the progress in analytical methodologies over the last decade and assessment of the major agreements and issues discussed with regard to small molecules at both the conference and the workshop.
Abstract: This report is a synthesis of (1) the earlier conference on Analytical Methods Validation−Bioavailability, Bioequivalence and Pharmacokinetic Studies (Conference held in Arlington, VA, December 3–5, 1990 and the report published in Pharmaceutical Research, 9: 588-592, 1992) and (2) the workshop on “Bioanalytical Methods Validation—A Revisit with a Decade of Progress,” (Workshop held in Arlington, VA, January 12–14, 2000), sponsored by the American Association of Pharmaceutical Scientists and the U. S. Food and Drug Administration. The bioanalytical method validation workshop of January 12–14, 2000 was directed towards small molecules. A separate workshop was held in March 1–3, 2000 to discuss validation principles for macromolecules. The purpose of this report is to represent the progress in analytical methodologies over the last decade and assessment of the major agreements and issues discussed with regard to small molecules at both the conference and the workshop. The report is also intended to provide guiding principles for validation of bioanalytical methods employed in support of bioavailability, bioequivalence, and pharmacokinetic studies in man and in animals.

1,588 citations

Journal ArticleDOI
TL;DR: A detailed step-by-step guide to analytical method validation, considering the most relevant procedures for checking the quality parameters of analytical methods and the estimation of measurement uncertainty and accuracy profiles is given.
Abstract: The objective of analytical method validation is to ensure that every future measurement in routine analysis will be close enough to the unknown true value for the content of the analyte in the sample. Classical approaches to validation only check performance against reference values, but this does not reflect the needs of consumers. A holistic approach to validation also takes into account the expected proportion of acceptable results lying inside predefined acceptability intervals. In this article, we give a detailed step-by-step guide to analytical method validation, considering the most relevant procedures for checking the quality parameters of analytical methods. Using a holistic approach, we also explain the estimation of measurement uncertainty and accuracy profiles, which we discuss in terms of accreditation requirements and predefined acceptability limits.

598 citations

Journal ArticleDOI
TL;DR: The report presents the assessment of the major agreements and issues discussed at the conference on analytical methods validation and provides guiding principles for validation of analytical methods used in bioavailability, bioequivalence, and pharmacokinetics studies in humans and animals.
Abstract: 0 This is a summary report of the conference on "Analytical Methods Validation: Bioavailability, Bioequivalence and Pharmacokinetic Studies." The conference was held from December 3 to 5,1990, in the Washington, D.C., area and was sponsored by the American Association of Pharmaceutical Scientists, the US. Food and Drug Administration, Federation International Pharmaceutique, Health Protection Branch (Canada), and the Association of Official Analytical Chemists. The report presents our assessment of the major agreements and issues discussed at the conference. The report is also intended to provide guiding principles for validation of analytical methods used in bioavailability, bioequivalence, and pharmacokinetics studies in humans and animals. The objectives of the conference were as follows: (1) to reach a consensus on what should be required in analytical methods validation and the procedures to establish validation; (2) to determine processes of application of the validation procedures in bioavailability, bioequivalence, and pharmacokinetics studies; and (3) to develop a report on analytical methods validation that may be referred to in developing future formal guidelines. Acceptable standards for documenting and validating analytical methods with regard to processes, parameters, or data treatments are discussed because of their importance in assessing pharmacokinetic, bioavailability, and bioequivalence studies. Other topics that were considered essential in the conduct of pharmacokinetic studies or in establishing bioequivalency criteria, including measurement of drug metabolites and stereoselective determinations, are also discussed. ___ -. ~. ~ _ _ Analytical methods that are used for the quantitative determination of drugs and their metabolites in biological samples play a significant role in evaluation and interpretation of bioavailability, bioequivalence, and pharmacokinetic data. It is essential to use well-characterized and fully validated analytical methods to yield reliable results that can be satisfactorily interpreted. Analytical methods and techniques are constantly being changed and improved; in many instances, these methods are at the cutting edge of the technology. It is also important to emphasize that each analytical technique has its own characteristics, which will vary from drug to drug. Moreover, the appropriateness of the technique may be influenced by the ultimate objective of the study. Specific validation criteria are needed for methods intended for analysis of each analyte (drug and/or metabolite). Although validation of each method will be independent of those of other methods, there may be situations in which comparison of the methods will be necessary (e.g., when more than one method has been used in a long-term study). When sample analysis is conducted at more than one site, it is necessary to validate the analytical methodb) at each site and provide appropriate validation information for different sites to establish interlaboratory reliability. Unless a method is used on a regular basis, providing confidence in its continued validity, it is essential to document that the method is still valid before analysis of samples in the study. Adequate validation for methods not used on a regular basis often consists of running a standard curve with new quality-control samples to show that the responses, relationship, and general characteristics of the method are similar to previous valida-

582 citations

Journal ArticleDOI
TL;DR: Current thinking on validation requirements as described in the current FDA Guidance and subsequent 2006 Bioanalytical Methods Validation Workshop white paper are presented.
Abstract: Method validation is a process that demonstrates that a method will successfully meet or exceed the minimum standards recommended in the Food and Drug Administration (FDA) guidance for accuracy, precision, selectivity, sensitivity, reproducibility, and stability. This article discusses the validation of bioanalytical methods for small molecules with emphasis on chromatographic techniques. We present current thinking on validation requirements as described in the current FDA Guidance and subsequent 2006 Bioanalytical Methods Validation Workshop white paper.

339 citations

Journal ArticleDOI
TL;DR: How to evaluate the calibration line, devise experiments to estimate precision and bias and how to determine the stability of the analyte between the time of the sample collection and the analysis of the processed sample is explained.

291 citations


"Bioanalytical Method Validation" refers background in this paper

  • ...• Hartmann et al. (1998) review on validation of bioanalytical chromatographic methods - theoretical and practical issues were discussed in detail10....

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