Cell-based assays are critical for every stage of drug seember discovery and development. Cell-based assays are a crucial component of assay development services provided from drug discovery and preclinical studies to clinical trials and post-marketing assessments. Cell-based assay development measures analytes present in complex biological samples based on a set of reagents that can produce a detectable and quantifiable signal.Â
Compared to biochemical and non-cell-based assays, cell-based assays are more biologically relevant in assessing and predicting complex therapeutic responses in biological study matrices. Moreover, cell-based assays can quickly enhance and accelerate drug development timelines and help drug therapeutics reach the market audience more quickly and efficiently. Hence, the current article discusses advanced strategies for cell-based in vitro assay development and cell-based assay qualification and validation.Â
Advanced strategies for cell-based assay development and validation
From in vitro evaluations and cell proliferation assays to neutralizing antibody assays in clinical trials, cell-based assays have numerous applications, including:
• Drug efficacy
• Safety data
• Selection of lead candidate
• Toxicity evaluations
• Off-target effects
• Information about the drug mechanism of action
Besides, cell-based assays can stratify patients according to response to therapy and help monitor immunogenicity and pharmacodynamic assessments. They are also vital for evaluating target saturation or engagement, monitoring resistance mechanisms, and determining safety markers.Â
Furthermore, cell-based assays have multiple biochemical and functional applications, such as assessing cell viability, cytotoxicity, signal transduction, gene activity, vector binding, complement-dependent cytotoxicity, proliferation, enzyme activity, and receptor occupancy. Moreover, cell-based assay signal readout can either be fluorescence, calorimetric, luminescence, or absorbance, depending on the assay variables and available equipment.
However, as the complexities in therapeutics mature, researchers will need more sophisticated bioanalytical tools and strategies in cell-based assay development. Today, therapeutics have evolved from monoclonal antibodies to cell and gene therapy and antibody-drug conjugates. These modern therapeutics have complex mechanisms of action and involve interaction at several levels. Hence, they will require robust analytical assay development initiatives.
Selecting appropriate cell-based assays
Cell-based assays are complex and depend on numerous factors. Researchers must evaluate individual factors while considering a cell-based assay for biotherapeutic drug development. The primary step is to have a clear understanding of the intended application of a cell-based assay and how the data shall support drug development programs. These considerations are crucial to yield high-quality assay results. Besides, as the drug therapeutic progresses from early drug discovery to later stages of clinical trials, the cell-based assays used will evolve depending on the complexity of information needed at each step of drug development.
Considerations for cell-based assay
A cell-based assay should reflect the mechanism of drug action to ensure its biological relevance. This assurance requires identifying an appropriate cell line, either immortalized or primary, that will reflect some aspects of the therapeutic mechanism of action.
Cell-based assay endpoints can either be early or later assay endpoints. Each has its advantages and limitations. For instance, early cell-based assay endpoints generating a measurable signal are advantages over later assay endpoints such as toxicity and cell proliferation, which may require several days to develop and deliver robust results.
Hence, researchers must thoroughly consider the time needed for developing and delivering cell-based assays during drug discovery and development studies.
