Potency assays are crucial in therapeutic product development, allowing researchers to assess whether a product has the required biological activity to achieve its intended therapeutic effect. According to the ICH Q6B guidelines, potency assays are classified into three main categories: 1) animal-based biological assays (in vivo), 2) cell-based biological assays, and 3) biochemical assays (in vitro). Additionally, the guidelines reference ligand-receptor binding assays as a suitable option for potency evaluation, though they do not classify them as a separate category. Below, we dive into each type of assay and its characteristics. 🧪✨
In Vivo Potency Assays: The Use of Animal Models
Animal-based potency assays allow for observation of a product’s effect within a complete organism, providing insight into its broader therapeutic impact. For example, when evaluating a treatment for Parkinson’s disease, an animal model with characteristics similar to human Parkinson’s could help determine if the treatment reduces symptoms, such as tremors, and even measure relevant biomarkers like alpha-synuclein.
Although these assays are highly informative, they come with limitations: high costs, long timelines, and challenges in validation have restricted their use, particularly in advanced therapy products. Ethical considerations further limit the use of animal models, with these assays used only when strictly necessary and typically only at later stages of development as required by regulatory agencies. ⚖️
In Vitro Assays: Cell-Based and Biochemical Methods
Given the complexity and ethical limitations of in vivo assays, in vitro assays have become the preferred method for assessing advanced therapy products. This category includes both cell-based and biochemical methods, each with unique advantages and limitations.
Cell-Based Assays
Cell-based potency assays analyze how cells respond to treatment by measuring biochemical changes (e.g., ATP production or reactive oxygen species) and physiological effects (e.g., cell proliferation or death). This method allows for the evaluation of multiple product effects within an environment that mimics the disease, and it is relatively flexible, supporting both 2D and 3D cultures and various cell populations.
However, as these assays often use immortalized cell lines, they may not fully replicate an organism’s natural biology. Additionally, since cell systems continuously divide, they may undergo phenotypic and genotypic variations that can affect assay results.
Biochemical Assays
Biochemical assays focus on measuring the activity of specific molecules, typically through receptor-ligand interactions, enzymatic reactions, or immunological tests. These assays are faster and less costly than the other methods, and their target-specific nature gives them high sensitivity. However, because they do not capture the full disease microenvironment, they offer a more limited view of the product’s overall therapeutic effect.
Final Thoughts: The Importance of Choosing the Right Assay
Selecting the appropriate potency assay depends on factors such as the type of therapeutic product and its development stage. While in vivo assays provide comprehensive insights, they are reserved for specific cases due to their limitations. In vitro assays, particularly cell-based ones, present a more ethical and accessible option for evaluating advanced therapy products. Each assay type provides distinct and complementary information, so a combined approach is often the best strategy to ensure the safety and efficacy of new therapeutic products.
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