Pharmacokinetics (PK)/Toxicokinetics (TK)

Research on Gyrolab® platform at nanoliter-scale reduces sample requirements and animal use.

Pharmacokinetic (PK) bioanalysis presents challenges at all stages of development for the safety and efficacy of biologics. Early in development, there is a need to support multiple candidates and multiple programs. Preclinical development is subject to aggressive timelines and large sample numbers in a variety of species with limited volumes for both samples and reagents. In regulated bioanalysis, more robust methods with higher throughput are essential for decisions in advancing project timelines. Application of Gyrolab technology for PK bioanalysis provides versatility and flexibility at all stages in an automated, nanoliter-scale format.

Gyrolab benefits for pharmacokinetic studies:

  • Broader dynamic ranges
    Reduces sample dilutions with minimal matrix interference to avoid analyte/sample bias or error
  • Shorter time to results
    Enables faster decisions for study/assay development support
  • Reduced volumes
    Enables serial sampling to obtain a PK profile from a single mouse
  • Automated
    Increases method robustness and unattended runs to shorten project timelines

Discovery PK

In discovery, a flexible assay design is critical to support multiple species and programs with large numbers of samples, conditions and limited reagents. Generic PK assays allow for a platform approach to quantitate multiple human Abs in animal sera while reducing assay development time and increasing automated throughput capacity for proof of concept and rapid assessment of lead candidate identification and optimization. Automation of the assay workflow also removes cumbersome manual or liquid handling setups. In some instances, multiple assays/conditions are run in parallel or on different segments within the CD consumable to allow comparative data for different formats and leads.

Application of miniaturized immunoassays to discovery pharmacokinetic bioanalysis. 
Roman J, Qiu J, Dornadula G, Hamuro L, Bakhtiar R, Verch T.
J Pharmacol Toxicol Methods. 2011 May-Jun;63(3):227-35. doi: 10.1016/j.vascn.2010.12.002. Epub 2010 Dec 13. 

One mouse, one PK profile

Gyrolab systems' nanoliter volume requirements enable an entire PK from a single mouse which significantly reduces the number of mice used and the biological variability of PK endpoints. Obtaining a PK profile from a single mouse using serial sampling is an animal sparing strategy consistent with the 3R research initiative that has been established at multiple biopharmaceutical companies with the Gyrolab platform. This strategy reduces the number of mice needed by 60-80% which not only improves data quality but impacts cost reductions in maintaining animal colonies, husbandry needs/facilities and removal of biological wastes. The ability to execute a one mouse, one PK profile strategy on Gyrolab platforms is especially useful when test articles are in short supply, rank ordering of PK with more than three test articles and with rare animal disease models.

Application of miniaturized immunoassays to discovery pharmacokinetic bioanalysis.
Joyce AP, Wang M, Lawrence-Henderson R, Filliettaz C, Leung SS, Xu X, O'Hara DM.
Pharm Res. 2014 Jul;31(7):1823-33. doi: 10.1007/s11095-013-1286-y. Epub 2014 Jan 24. Read

Regulated PK bioanalysis

Regulated bioanalysis in support of GLP PK studies and clinical trials require increased method robustness as these assays are continually validated and used for long-term study support. GLP studies have a variety of safety toxicology and DMPK endpoints for a multitude of conditions that are required for at least one rodent specie and another relevant animal specie. Regulated bioanalysis for PK clinical trials are long term studies requiring assay robustness and reliability typically demonstrated by assay and in-study validation such as incurred sample reanalysis. Automation of PK bioanalysis on Gyrolab platforms provide higher throughput, minimal staffing, analysis time and reduces the manual sources of error that improve overall method robustness and facilitates assay transfer to CROs.

Read interview with Shawn Fernando, Morphotek Inc., on high-throughput PK assays in Phase II/III trials >

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study
Ann Rheum Dis 2013;72:1605-1612 doi:10.1136/annrheumdis-2012-203091  Read

    Gyrolab Systems
    Gyrolab technology reduces manual labor, assay development time, time to result and material consumption -and it improves workflow efficiency. 

    Gyrolab Kits, CDs and Rexxip Buffers
    Gyrolab Kits, CDs and Rexxip Buffers - Designed for best results 

    Gyrolab Generic PK-TK Kits
    Gyrolab Generic PK/TK Kits quantifies human IgG1, IgG2, or IgG4 titer over a broad range in a number of matrices. 
    [Product information sheet]

    Quantitation of Antibody-Drug Conjugates
    Using Gyrolab systems, a generic IgG assay and an assay to measure payloads of ADCs can quickly be developed in parallel. 
    [Application Note]

    Maximizing productivity in biopharmaceutical research and clinical development
    Three case studies are presented: "Obtaining an entire PK profile form a single mouse", "Earlier and more sensitive detection of drug-induced kidney toxicity in preclinical studies" and "Ramping up Phase II/III PK studies to meet critical deadlines". 
    [Application Note]

    Miniaturizing immunoassays for improved performance (AR 207)
    Application Report data courtesy of Lund University and Cambridge Antibody Technology. 
    [Application Report]

    Insulin quantification: save sample and increase efficiency (AR 204)
    Application Report data courtesy of Karolinska Institute and Novo Nordisk. 
    [Application Report]

    Capillary microsampling of liquid matrices. Better Science – Fewer Animals
    New opportunities for collection and handling of extremely small volumes of biofluids – From early screen to late clinic. Ove Jonsson Global DMPK, AstraZeneca R&D, Södertälje, Sweden. 

    Quantitative Ligand Binding Assay for Determination of Antibody Drug Conjugate Using Gyrolab Immunoassay Platform
    Aidong Wu, Tracey Clark, Chad Ray, Frank Barletta, Erick Kindt, Scott Fountain, Pfizer Global R&D, USA 

    One mouse one PK The magic of capillary microsampling and the Gyrolab assay platform
    Sufyan Maqbool, Jo Goodman, David Fairman, Dominic Corkill, BSU & Bioanalytical Sciences, Clinical Pharmacology & DMPK (CPD) Ove Jonsson, Michael Spreadborough, Christopher Smith. MedImmune 

    Development and validation on a pharmacokinetic assay on Gyrolab platform for use in Phase II/III clinical studies
    M. Dula, S. Fernando et. al. Morphotek Bioanalytical Dev. 

    A Simplified Process to Develop “Fit-for-Purpose” PK/PD Assays in Support of Early Drug Discovery Programs
    Rong Liu, Renuka Pillutla, Binodh Desilva, Yan Zhang. BAS-Biologics, Bristol Myers Squibb, Princeton, NJ 

    A Generic Pharmacokinetic (PK)/ Toxicokinetic (TK) Assay Kit for Analysis of Biotherapeutic Antibodies in Sera from Several Species for Early-stage Development using Gyrolab™ Platforms
    Ready to use Gyrolab Generic PK/TK kits streamlines evaluation of drug candidates for multiple programs using only nanoliter volumes and eliminates the time and resources needed for assay development and reagent screening.  

    Gyrolab Generic PK Assay: Determination of Human IgG in Preclinical Matrices
    Recorded Webinar: Daniel Forsström, Scientist at Gyros Protein Technologies, presents data using a high performance generic PK assay kit optimized for use with Gyrolab automated nanoliter-scale immunoassay systems.  

    Combine DOE and Gyrolab system to quickly develop robust immunoassays
    Two assay development teams at Pfizer have combined the systematic approach of DOE and the Gyrolab platform to streamline the development of robust immunoassays.  
    [Case Study]

    Validation and implementation of a pharmacokinetic assay on the Gyrolab™ platform for use in GLP toxicology study
    Case study based on a poster by P. Verdier, A Choquart, N. Macé, and M-H Pascual, Biomarkers and Clinical Bioanalyses, Translational Medicine and Early Development, Sanofi, Paris, France. The poster was presented at the European Gyrolab Seminar in Paris, June 2017. 
    [Case Study]

    The challenging road to success: from ELISA to Gyrolab™ via MSD
    Envigo were asked by a client to develop and validate a PK/TK assay for a monoclonal antibody used to treat cancer at levels as low as 10 ng/ml in cyno samples. The company first transferred the assay from ELISA to the MSD platform before finally transferring it to Gyrolab™ system, where the development and validation work was completed. Sarah Geen described the challenges encountered throughout this process and the strategies used to overcome them at the European Gyrolab Seminar in Amsterdam in June 2016.  
    [Case Study]

    One Mouse, One PK…the Magic of Capillary Microsampling and Gyrolab
    Sufyan Maqbool is an Associate Scientist in Clinical Pharmacology and DMPK at MedImmune, in Cambridge, UK. His recent work has focused on developing capillary microsampling (CMS) methodologies for PK assays. On June 2, 2014 he presented his work at the Gyrolab User Seminar in Copenhagen, Denmark.  
    [Case Study]

    Shawn Fernando PK assays: Gyrolab helps to meet tight deadlines
    Recorded Seminar: Shawn Fernando,  Senior Researcher, Bioanalytical Development, Morphotek, Exton, PA, USA, presents ‘Development and Validation of a Pharmacokinetic Assay on the Gyrolab Platform for Use in Phase II/III Clinical Trials'. 

    Annette Wu shows how Gyrolab xP workstation speeds up ADC assay development and throughput
    Recorded Seminar: Annette Wu in the PDM group at Pfizer, La Jolla, CA, USA, presents ‘Case study: Antibody-drug conjugates TK study on Gyros' immunoassay platform'. 

    Rapid Reagent Screening and Characterization using Automated Nanoliter-scale Immunoassays
    Recorded Webinar: Gyrolab is a reliable immunoassay platform that streamlines reagent selection and characterization during method development for biotherapeutics. Presenters: Frank Zambito, Research Scientist I, Bioanalytical Sciences, Bristol-Myers Squibb and Shawn Fernando, Senior Principal Researcher, Morphotek, Inc. 

    Using Automated Nanoliter-Scale Immunoassays for Improved Performance and Efficiency
    Recorded Webinar: Christophe Henry, Ph.D., Laboratory Head / Translational Medicine, Sanofi, presents case studies featuring reagent screening and method development for a variety of different biotherapeutics – traditional and non-conventional constructs. 

    Automating Pharmacokinetic Bioanalysis at Nanoliter-Scale: Strategies for Development, Validation and Transfer
    Recorded Webinar: “Detection of human IgG matrices: A universal approach”, Sufyan Maqbool, Associate Scientist I, Clinical Pharmacology and DMPK, MedImmune Cambridge UK and “Transfer and validation of a Gyrolab PK assay to a CRO”, Emilie Escoffier, MSc Biochemistry & Biotechnology, Research Assistant, Exploratory Science and,Translational Medicine, NovImmune SA, Geneva, Switzerland. 

    Automated Pharmacokinetic Bioanalysis at Nanoliter-Scale: From Early Stage Development to Validation and Transfer for Clinical Studies
    Recorded webinar focusing on the implementation of the Gyrolab workstation for automated PK bioanalysis in support of early stage development, regulated bioanalysis and clinical trials. Presenters: Vimal Patel, Senior Associate Scientist, Amgen, Thousand Oaks, CA, USA, Jo Goodman, Senior R&D Manager, MedImmune, Cambridge, UK, and Shawn Fernando, Senior Researcher, Bioanalytical Development, Morphotek, Exton, PA, USA. 

    Challenges of supporting multiple programs for PK Bioanalysis: a CRO perspective
    Recorded Webinar: Contract Research Organisations (such as Envigo) are required to transfer, develop, validate and carry out sample analysis on a wide range of drug products from clients. Discussed are various aspects that must be considered when choosing a suitable assay platform for pharmacokinetic (PK) studies. Presenter: Deborah McManus Senior Technical Specialist in the Department of Biomarkers, Bioanalysis and Clinical, Envigo UK. 

    Overcoming Disease Specific Matrix Effects in a Clinical Pharmacokinetic Assay
    Recorded Webinar. Presenter Kathi J. Williams, Senior Scientific Researcher Assay Development and Technology, Genentech, Inc 

    Biopharmaceutical drug development:from CMC to clinical PK
    Please view the recorded webinar. Presenter: Rikke Hald, M.Sc., Ph.D., Senior Scientist, Bioassays, Symphogen A/S 

    Panel discussion: considerations and challenges of ligand binding assays
    Please view the recorded panel discussion.  

    A Gyrolab Assay for the Quantitation of Free Complement Protein C5a in Human Plasma96
    Please visit the recorded webinar. Presenter Mark Dysinger, M.S., Development Scientist III, Alexion Pharmaceuticals 

    Generic PK methods for the quantification of mAbs using Gyrolab® and LC–MS/MS
    Johannes Stanta, PhD Senior Scientific Manager Covance Laboratories (NJ, USA)