title: Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform.
abstract: The Gyrolab™ xP is a microfluidic platform for conducting ligand binding assays (LBAs) and is recognized for its utility in discovery bioanalysis. However, few reports have focused on the technology for regulated bioanalysis. This technology has the advantage of low reagent consumption, low sample volume, and automated ligand binding methods. To improve bioanalysis testing timelines and increase the speed at which biotherapeutics are delivered to patients, we evaluated the technology for its potential to deliver high-quality data at reduced testing timelines for regulated bioanalysis. Six LBA methods were validated to support bioanalysis for GLP toxicokinetic or clinical pharmacokinetic studies. Validation, sample analysis, and method transfer are described. In total, approximately 4000 samples have been tested for regulated bioanalysis to support 6 GLP toxicology studies and approximately 1000 samples to support 2 clinical studies. Gyrolab™ xP had high run pass rates (≥83%) and high incurred sample reanalysis (ISR) pass rates (>94%). The maximum total error observed across all QC levels for a given assay was <30% for all six LBAs. High instrument response precision (CV ≤5%) was observed across compact discs (CDs), and methods were validated to use a single standard curve across multiple CDs within a Gyrolab™ xP run. Reduced bioanalysis timelines were achieved compared to standard manual plate-based methods, and methods were successfully transferred across testing labs, paving the way for this platform for use in late-stage clinical development.
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA. rong.liu@bms.com.
authors: Rong
authors: R
authors: Liu
authors: Immunochemistry, PPD Laboratories, Richmond, Virginia, USA.|Smithers AVANZA Bioanalytical Services LLC, Gaithersburg, Maryland, 20878, USA.
authors: Brian
authors: B
authors: Hoffpauir
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Shannon D
authors: SD
authors: Chilewski
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Janice
authors: J
authors: Gamberdella
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Uma
authors: U
authors: Kavita
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Jia
authors: J
authors: Duo
authors: Global Biometric Sciences, Nonclinical Biostatistics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors: Carol
authors: C
authors: Gleason
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Yan
authors: Y
authors: Zhang
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Renuka
authors: R
authors: Pillutla
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.
authors: Binodh
authors: B
authors: DeSilva
authors: Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA.|Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA.
authors: Lora
authors: L
authors: Hamuro
mesh_terms: D000818:Animals; D001331:Automation; D055808:Drug Discovery / Q000295:instrumentation*; D004867:Equipment Design; D006801:Humans; D007118:Immunoassay / Q000295:instrumentation*; D008024:Ligands; D057230:Limit of Detection; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000097:blood; D011485:Protein Binding; D015203:Reproducibility of Results; D012984:Software
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations
keywords: Gyrolab™ xP; ligand binding assay; regulated bioanalysis; sample analysis; study validation