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By: Rong Liu

Although srong-liu_photomall molecule drugs (< 900 Dalton) are still widely used for different disease indications, large molecule drugs (biologics) have increased exponentially for the treatment of anemia, growth deficiency, diabetes, hepatitis, transplant rejection, cancers, etc. due to new genetic information and better understanding of subcellular cascades and disease processes. What is the fate of a biologic after it is administered to a living organism? How do we determine the concentration of a biologic from the moment that it is administered up to the point at which it is eliminated from the body?

A technique/method called ligand binding assay (LBA) is commonly used for the quantification of biologics present in complex biological matrices. Conventional plate-based LBAs such as ELISA, even though providing high sensitivity, specificity, and multiplexing capability, can be labor-intensive and prone to human error. Automating plate-based LBAs is one solution, but upfront investment in time, infrastructure, resources, and processes are required. Instead of using plate-based LBAs, microfluidic immunoassay platforms such as the Gyrolab™ xP, which uses compact discs (CDs) instead of the standard 96-well plate, is an alternative. This process offers the advantage of automation, fast turnaround time, and low reagent and sample consumption.

The platform has been around for nearly 10 years and is recognized for its utility in discovery bioanalysis for above mentioned advantages. However, when bioanalytical platforms are introduced to support regulated bioanalysis for drug measurement, questions related to data accuracy, precision, reliability and robustness must be addressed to comply with current industry standards and recommended guidance from health authorities. We evaluated the Gyrolab™ xP for its potential to deliver high-quality data at reduced testing timelines for regulated bioanalysis. Multiple LBA methods were validated to support bioanalysis for GLP toxicokinetic and clinical pharmacokinetic studies and thousands of study samples were analyzed. All studies had high run pass rates with good accuracy and precision, ready for the regulatory filing. The data also demonstrated at least half of the time was saved and only 10% of the reagents were consumed compared with regular plate-based LBA assay.  Additionally specific platform related compliance challenges such as LIMS workflow, carry-over evaluation and risk mitigation during sample analysis, microfluidic sampling errors, and applying a single standard curve across multiple CDs were addressed.

Read more about our case examples in The AAPS Journal article Accelerating Regulated Bioanalysis for Biotherapeutics: Case Examples Using a Microfluidic Ligand Binding Assay Platform. Validation, sample analysis, method transfer, and challenges we encountered are described.

Rong Liu is a research scientist in the Department of Bioanalytical Sciences, Bristol-Myers Squibb Company.