Traditionally, large volumes of blood are collected for pharmacokinetic and toxicokinetic studies. The volumes are basically dictated by the type of collection devices (vacutainers) available as well as the sample size needed for all associated analysis. These volumes typically range from 0.5 to 2.0 mL in non-clinical species and 2 to 5 mL in clinical studies. The 3Rs initiative (reduce, replace, refine) has focused attention on collecting smaller volumes of blood – of for that matter – collecting only what is needed for bioanalysis and the purpose of the study. Advancements in instrumentation, ethical and practical concerns of sampling from pediatric and diseased populations, and minimizing the number of animals required for non-clinical assessments are in line with the 3Rs initiative and have heralded developments in microsampling. Dried blood spot (DBS) sampling and analysis is the most referenced approach but several other microsampling techniques have now been developed over the past decade and used to support both non-clinical and clinical studies.
The purpose of this event is to provide an update on what’s new with microsampling (novel techniques/devices), and how microsampling is being used to support the quantitation of drugs, metabolites and biomarkers in preclinical and clinical development. To conclude the seminar will present a “case-study” on an implementation of DBS on a late-stage clinical program to support population pharmacokinetic modeling and associated regulatory interactions. Staged implementation of in vitro and bioanalytical feasibility, demonstrating a quantitative relationship between the blood and plasma concentrations using population PK (bridging dataset) led to regulatory (FDA and EMA) concurrence with this approach.
Learning Objectives:
- Understand what is microsampling and how/when can it be used.
- Review currently implemented and novel techniques and devices.
- Explore how to implement clinical studies using microsampling (DBS) and planning and executing in late-stage clinical studies.
Contributor 1: Neil is the Founder and Director of Spooner Bioanalytical Solutions, a consultancy based in Hertford, UK. In this role, Neil helps companies to integrate microsampling of biological fluids into pre-clinical, clinical and bioanalytical workflows. He also works with innovator companies to help them develop novel microsampling and microanalytical technologies and introduce them to the market. Neil is also a Senior Visiting Research Fellow at the School of Life and Medical Sciences, University of Hertfordshire (Hertfordshire, UK), the Senior Editor of Bioanalysis Journal and the Deputy-Chair and Secretary of the Reid Bioanalytical Forum. He has published extensively, with over 60 peer reviewed manuscripts and more than 40 podium presentations at International Conferences and Symposia.
Neil has extensive experience in the quantitative bioanalysis of drugs, metabolites and biomarkers in the pharmaceutical industry and contract research organisations in the UK and USA. In over 20 years of industrial practice at GlaxoSmithKline, he has led groups operating in the discovery and regulated arenas of clinical and pre-clinical quantitative bioanalysis and metabolite identification. Neil has extensive experience of successfully leading inter departmental and cross functional initiatives, including implementation of new technologies and workflows (such as microsampling), outsourcing quantitative bioanalysis, development and implementation of automation approaches and design of new scientific facilities.
Contributor 2: Prajakti Kothare (Ph.D.) is Executive Director, Quantitative Pharmacology and Pharmacometrics within Pharmacokinetics, Pharmacodynamics and Drug Metabolism at Merck. As part of this role she provides strategic, personnel and portfolio oversight for translational and quantitative aspects of Infectious Diseases, Cardiometabolic and Opthalmics programs from discovery through life-cycle management. Prajakti is an experienced pharmaceutical research leader with a proven track record of portfolio and regulatory impact across multiple therapeutic areas and across modalities.
Since joining Merck in 2011, Prajakti has assumed leadership positions of increasing responsibility. Prajakti has played a critical leadership role in building quantitative translational sciences at Merck. Prajakti has been instrumental in driving efforts aimed at modernizing clinical trials such as the application of dried blood spots, digital health and home-sampling in clinical trials resulting in faster, efficient decisions. From 2001-2011, while at Eli Lilly and Company (Global Pharmacokinetics and Pharmacodynamics), she was significantly involved in the development and registration of multiple drugs. Prajakti received a Bachelor’s degree in Pharmaceutical Sciences from the University of Bombay, India and a Ph.D. in Pharmaceutics (with a specialization in PKPD) from the University of Minnesota.