Howard Hill

Bio: Howard Hill is an academic researcher from Huntingdon Life Sciences. The author has contributed to research in topics: Bioanalysis & Productivity. The author has an hindex of 9, co-authored 37 publications receiving 2407 citations.

Bioanalytical method validation--a revisit with a decade of progress.

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.

Recommendations for the Bioanalytical Method Validation of Ligand-binding Assays to Support Pharmacokinetic Assessments of Macromolecules

Abstract: Purpose.With this publication a subcommittee of the AAPS Ligand Binding Assay Bioanalytical Focus Group (LBABFG) makes recommendations for the development, validation, and implementation of ligand binding assays (LBAs) that are intended to support pharmacokinetic and toxicokinetic assessments of macromolecules.

Bioanalytical method validation for macromolecules in support of pharmacokinetic studies.

Abstract: The development and validation of ligand binding assays used in the support of pharmacokinetic studies has been the focus of various workshops and publications in recent years, all in an effort to establish a guidance document for standardization of these bioanalytical methods. This summary report of the workshop from 2003 focuses on the issues discussed in presentations and notes points of discussion and areas of consensus among the participants.

Validation issues arising from the new FDA guidance for industry on bioanalytical method validation

Abstract: In late May 2001 the FDA issued their final Guidance for Industry on Bioanalytical Methods Validation. Different types and levels of validation, dependent on the status or changes to the validated method, are now defined and characterised. Additional experiments with the emphasis on the newer hyphenated analytical techniques and changes to quality control and calibration acceptance criteria are now required. A number of inconsistencies, in terms of the minimum number of calibration points required to define a calibration curve, exist in the current document. It is therefore important to understand the underlying philosophy of this guidance and what are the most appropriate ways of implementing this philosophy.

AMS method validation for quantitation in pharmacokinetic studies with concomitant extravascular and intravenous administration

Abstract: A technique has emerged in the past few years that has enabled a drug’s intravenous pharmacokinetics to be readily obtained in humans without having to conduct extensive toxicology studies by this route of administration or expend protracted effort in formulation. The technique involves the intravenous administration of a low dose of 14C-labelled drug (termed a tracer dose) concomitantly with a non-labelled extravascular dose given at therapeutically levels. Plasma samples collected over time are analysed to determine the total parent drug concentration by LC–MS (which essentially measures that arising from the oral dose) and by LC followed by accelerator mass spectrometry (AMS) to determine the 14C-drug concentration (i.e., that arising from the intravenous dose). There are currently no published accounts of how the principles of bioanalytical validation might be applied to intravenous studies using AMS as an analytical technique. The authors describe the primary elements of AMS when used with LC seperat...

Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays

Abstract: The Third AAPS/FDA Bioanalytical Workshop, entitled “Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays” was held on May 1–3, 2006 in Arlington, VA. The format of this workshop consisted of presentations on bioanalytical topics, followed by discussion sessions where these topics could be debated, with the goal of reaching consensus, or identifying subjects where addition input or clarification was required. The discussion also addressed bioanalytical validation requirements of regulatory agencies, with the purpose of clarifying expectations for regulatory submissions. The proceedings from each day were reviewed and summarized in the evening sessions among the speakers and moderators of the day. The consensus summary was presented back to the workshop on the last day and was further debated. This communication represents the distillate of the workshop proceedings and provides the summary of consensus reached and also contains the validation topics where no consensus was reached.

Fit-for-purpose method development and validation for successful biomarker measurement.

Abstract: Despite major advances in modern drug discovery and development, the number of new drug approvals has not kept pace with the increased cost of their development. Increasingly, innovative uses of biomarkers are employed in an attempt to speed new drugs to market. Still, widespread adoption of biomarkers is impeded by limited experience interpreting biomarker data and an unclear regulatory climate. Key differences preclude the direct application of existing validation paradigms for drug analysis to biomarker research. Following the AAPS 2003 Biomarker Workshop (J. W. Lee, R. S. Weiner, J. M. Sailstad, et al. Method validation and measurement of biomarkers in nonclinical and clinical samples in drug development. A conference report. Pharm Res22:499–511, 2005), these and other critical issues were addressed. A practical, iterative, “fit-for-purpose” approach to biomarker method development and validation is proposed, keeping in mind the intended use of the data and the attendant regulatory requirements associated with that use. Sample analysis within this context of fit-for-purpose method development and validation are well suited for successful biomarker implementation, allowing increased use of biomarkers in drug development.