How do you know when you have the correct higher structure of your product? How do you know when you have a structural variant present? How do you know if the structure has changed significantly, meaning that there would be a clinical difference? And consequently, how do you know that change is important? And to what extent can we answer these questions using the various physicochemical tests that we have available?
One of the important tools in determining the correct structure for a protein is the potency assay. The determination of biological potency plays a key role in the development, registration, and control of biological and biotechnology-derived products. Advances in science and regulatory requirements have affected both the way these assays are carried out experimentally and how they are analyzed statistically.
Potency assays are used for characterization of a biological or biotechnology product, stability testing, and lot release. Potency assays help provide assurance of the quality and consistency of the product.
The focus is on relative potency - because of the inherent variability in test systems (from animals, cells, instruments, and reagents, and day-to-day and between-lab variation), an absolute measure of potency may not be possible. This has led to the adoption of the relative potency methodology. Assuming that the Standard and Test materials contain samples with biologically similar (if not identical) activity, the Test sample can be expected to behave like a concentration or dilution of the Standard, and parallelism should be present. Relative potency is determined by comparison of Test to Standard assay response, which means that the assay does not need to achieve a specific observable response. The potency of the Standard is usually assigned a value of 1 (or 100%). For samples that are biologically similar, the horizontal displacement between the curves is interpreted as log relative potency.