Reliable measurements of quality attributes of medical products are required for quality control and verification of safety and efficacy. To reduce (i) the risk of measurement bias and (ii) the uncertainty in decision-making during product development, a combination of orthogonal and complementary analytical techniques are generally recommended. However, despite frequent reference to “orthogonal” and “complementary” measurements in guideances and the literature, neither term is clearly defined. How does one determine if two analytical methods are orthogonal or complementary to one another? Definitions are needed to design a robust characterization strategy for a medical product. Definitions for "orthogonal" and "complementary" are proposed that are compatible with existing metrological terminology and are applicable to complex measurement problems. Orthogonal methods target the quantitative evaluation of the true value of a product attribute to address unknown bias or interference. Complementary measurements include a broader scope of methods that reinforce each other to support a common decision.
Simon CG, Borgos SE, Calzolai L, Nelson BC, Parot J, Petersen EJ, Roesslein M, Xu X, Caputo F (2023) Orthogonal and complementary measurements of properties of drug products containing nanomaterials. Journal of Controlled Release 354, 120-127. https://doi.org/10.1016/j.jconrel.2022.12.049