The measurement of potency (strength) is a regulatory requirement for all pharmaceuticals. For chemical drugs, the potency is determined by measuring the amount of the specific active pharmaceutical ingredient (API) that is present. However, for biopharmaceuticals, the potency is not simply the amount of specific API present but the functional (biological) activity in the amount present. While the amount of biopharmaceuticals can be tracked through the manufacturing process, functional activity is much more difficult. Knowing how the manufacturing process—whether for protein-based biopharmaceuticals (recombinant proteins and monoclonal antibodies) or for gene-based biopharmaceuticals (viral vectors, non-viral vectors, genetically modified patient cells)—could impact this functional activity is a significant part of the potency assurance strategy. Required testing for functional activity—whether by bioassay, surrogate assay, or assay matrix—for batch-to-batch release, stability confirmation, assurance of comparability after a manufacturing process change, is the other important part of the potency assurance strategy. Application of the minimum CMC regulatory compliance continuum risk-based approach for biopharmaceutical potency requirements will be examined.