Bioassays are critical and essential components of ensuring the safety, potency, and efficacy of biologics. Designing an appropriate bioassay can take several weeks, even months to develop and validate. New platform technologies, statistical methods, and regulatory strategies are needed to improve development. The authors in this featured report on a novel high-throughput hepatoxicity screening method, a statistical approach to assessing bioassay variations, and an approach to characterizing bioactivity assays for antibody-drug conjugates.
A Novel 3D Culture System for High-Throughput Hepatoxicity Screening
Timothy P. Spicer, Virneliz Fernandez Vega, Louis Scampavia, Lynsey Willetts, and Michelle Vessels
The authors describe a new three-dimensional hepatocellular model system that can offer analysts significant advantages over traditional two-dimensional monolayer cell culture in terms of maintaining morphological and functional characteristics of tissue. The new 3D model also provides a better representation of in vitro drug toxicity. This high-throughput assay effectively identifies hepatocellular toxic compounds and can provide insight into marketed drugs that may not have initially appeared to be hepatotoxic.
Certain Approaches to Understanding Sources of Bioassay Variability
Some contract manufacturing organizations (CMOs) may not do an adequate level of assessing the key sources of variation in a variability assessment. The author outlines the type of model, variance component analysis, and graphical assessments that help in bioassay development.
Biological Stealth Bombers: Potency, Regulatory, and Bioprocessing Concerns of Antibody–Drug Conjugates
Ulrike Herbrand, Christopher Sucato, and Alvaro Jorge Amor
Antibody-drug conjugates (ADCs) combine the best of protein and small-molecule based therapies, whereby antibodies are covalently joined to toxins via a linker to act as drone-like weapons against tumors. By taking advantage of the binding specificity of the antibody portion of the ADC, the toxic nature of the drug moieties are largely masked, until the ADC reaches the intended target. Because ADCs are such complex structures, they can present challenges for testing laboratories not associated with traditional monoclonal antibodies. The antibody needs to be evaluated for both potential and known mechanisms of action, but the a cytostatic compound tethered to the antibody can alter the behavior of the antibody vehicles within typical assays. The authors review how laboratories evaluate the bioactivity and biophysical characterization aspects of ADC development and discuss the correlation between bioactivity and biophysical data that are required before an ADC moves to clinical testing in humans or to the market.