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Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform

  • Protocols in Pharmaceutical Sciences
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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.

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Author notes

  1. Brian Hoffpauir

    Present address: Smithers AVANZA Bioanalytical Services LLC, Gaithersburg, Maryland, 20878, USA

  2. Lora Hamuro

    Present address: Clinical Pharmacology and Pharmacometrics, Bristol-Myers Squibb, Princeton, New Jersey, USA

Authors and Affiliations

  1. Immunochemistry and Biomarkers, Analytical and Bioanalytical Operations, Bristol-Myers Squibb, Route 206 and Province Line Road, Princeton, New Jersey, 08543, USA

    Rong Liu, Shannon D Chilewski, Janice Gamberdella, Uma Kavita, Jia Duo, Yan Zhang, Renuka Pillutla, Binodh DeSilva & Lora Hamuro

  2. Immunochemistry, PPD Laboratories, Richmond, Virginia, USA

    Brian Hoffpauir

  3. Global Biometric Sciences, Nonclinical Biostatistics, Bristol-Myers Squibb, Princeton, New Jersey, USA

    Carol Gleason

Authors
  1. Rong Liu
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  2. Brian Hoffpauir
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  3. Shannon D Chilewski
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  4. Janice Gamberdella
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  5. Uma Kavita
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  6. Jia Duo
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  7. Carol Gleason
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  8. Yan Zhang
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  9. Renuka Pillutla
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  10. Binodh DeSilva
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  11. Lora Hamuro
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Corresponding author

Correspondence to Rong Liu.

Electronic Supplementary Material

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Supplemental Figure 1

The method Total Error (%) for all LBAs validated on the Gyrolab™ xP workstation. Six QC for each LBA are plotted that includes LLOQ, LQC, MQC, HQC, ULOQ and DilQC. % Total Error = |%Dev| + Total %CV. (DOCX 125 kb)

Supplemental Table S1

(DOCX 13 kb)

Supplemental Table S2

(DOCX 13 kb)

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Liu, R., Hoffpauir, B., Chilewski, S.D. et al. Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform. AAPS J 19, 82–91 (2017). https://doi.org/10.1208/s12248-016-0006-z

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  • DOI: https://doi.org/10.1208/s12248-016-0006-z

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