Key elements of bioanalytical method validation for macromolecules
Journal Title: The AAPS Journal - Year 2007, Vol 9, Issue 2
Abstract
The Third American Association of Pharmaceutical Scientists/US Food and Drug Administration (FDA) Bioanalytical Workshop, which was held May 1 and 2, 2006, in Arlington, VA, addressed bioanalytical assays that are being used for the quantification of therapeutic candidates in support of pharmacokinetic evaluations. One of the main goals of this workshop was to discuss best practices used in bioanalysis regardless of the size of the therapeutic candidates. Since the last bioanalytical workshop, technological advancements in the field and in the statistical understanding of the validation issues have generated a variety of interpretations to clarify and understand the practicality of using the current FDA guidance for assaying macromolecular therapeutics. This article addresses some of the key elements that are essential to the validation of macromolecular therapeutics using ligand binding assays. Because of the nature of ligand binding assays, attempts have been made within the scientific community to use statistical approaches to interpret the acceptance criteria that are aligned with the prestudy validation and in-study validation (sample analysis) processes. We discuss, among other topics, using the total error criterion or confidence interval approaches for acceptance of assays and using anchor calibrators to fit the nonlinear regression models.
Authors and Affiliations
Marian Kelley, Binodh DeSilva
Keywords
Related Articles
- EP ID EP681585
- DOI 10.1208/aapsj0902017
- Views 100
- Downloads 0
Highly Stabilized Curcumin Nanoparticles Tested in an In Vitro Blood–Brain Barrier Model and in Alzheimer’s Disease Tg2576 Mice
The online version of this article (doi:10.1208/s12248-012-9444-4) contains supplementary material, which is available to authorized users.
Effects of Selected OATP and/or ABC Transporter Inhibitors on the Brain and Whole-Body Distribution of Glyburide
Glyburide (glibenclamide, GLB) is a widely prescribed antidiabetic with potential beneficial effects in central nervous system injury and diseases. In vitro studies show that GLB is a substrate of organic anion transport...
Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
The online version of this article (doi:10.1208/s12248-013-9493-3) contains supplementary material, which is available to authorized users.
Validation of a Ligand Binding Assay Using Dried Blood Spot Sampling
Dried blood spots (DBS) technology has been introduced as a microsampling alternative to traditional plasma or serum sampling for pharmacokinetics or toxicokinetics evaluation. The application of DBS has been established...
Assessment of Juvenile Pigs to Serve as Human Pediatric Surrogates for Preclinical Formulation Pharmacokinetic Testing
Pediatric drug development is hampered by biological, clinical, and formulation challenges associated with age-based populations. A primary cause for this lack of development is the inability to accurately predict ontoge...