How are potency assays developed for biological products?

Potency assays measure biological activity of biopharmaceuticals, required for lot release. Development involves: 1) Mechanism understanding - identify relevant biological activity reflecting therapeutic effect. 2) Assay selection - cell-based assays (proliferation, reporter genes, cytotoxicity), binding assays (ELISA, SPR), or enzymatic assays depending on product. Cell-based preferred as they measure functional activity. 3) Reference standard - establish and qualify primary reference; working standards for routine use. 4) Assay format - dose-response curve with parallelism assessment between sample and reference; report relative potency. 5) Validation - accuracy, precision, linearity, range, specificity, robustness according to ICH guidelines. 6) Statistical analysis - parallel line analysis (4-parameter logistic fitting) for relative potency calculation. Challenges include assay variability, relevant cell lines, and correlating in vitro potency with clinical efficacy. Surrogate assays may be used with justified correlation.