Universal Qualification of Near Ultraviolet Circular Dichroism Spectroscopy: Method Performance Parameters and Limits of Detection for Structural Differences.

Analytical methods must be qualified as part of the method development lifecycle for product characterization of biotherapeutics. For higher order structure characterization methods, such as near ultraviolet circular dichroism spectroscopy, qualification is performed to determine the expected variability of the method and to establish criteria for analytical product comparability, reference standard qualification, and analytical similarity evaluations. Typical method qualifications require a single product to be tested across several days with multiple replicates, essential to establish a quantitative limit for future product evaluation studies, which may be burdensome with respect to time, instrumentation, and material requirements. In this note, a methodology is proposed to expedite the qualification process for the near ultraviolet circular dichroism spectroscopy method, decreasing the number of required qualification runs, in many cases, to just one for each product. The significant reduction in the number of assays for qualification is achieved by utilizing historical data that applies universally across products of variable classification, size, and test date. Despite their differences, the products exhibit comparable method performance when compared to a product-specific reference standard, and a universal detection threshold is established for application to future product evaluations that meet pre-determined method suitability criteria following a single verification run.