Evaluation of a Biologic Formulation Using Customized Design of Experiment and Novel Multidimensional Robustness Diagrams.

Formulation development includes selection of appropriate excipients to stabilize the active pharmaceutical ingredient throughout its recommended shelf life, against potential excursions in its life cycle and sometimes to aid in the delivery of therapeutics into the patient. Identity and quantity of every ingredient in a therapeutic formulation are critical to achieve their intended purpose. Deviations from a target composition can result in manufacturing, safety, and efficacy challenges. It is mandatory to establish robustness of a formulation for the expected changes in its composition arising from the qualified "process variability" of the impacting process steps during manufacture. The approach for carrying out a robustness study evolved through improved understanding of a therapeutic stability and exploration of new tools, including the quality by design elements strongly recommended by regulatory agencies. An approach is presented here to study formulation robustness in multidimensional space using a customized experimental design and novel multidimensional diagrams, which present a unique way of identifying robustness limits. The concept is universally applicable to any multivariate analysis and such diagrams would be useful to comprehend the outcome on all variables at a glance. Interpretation of these diagrams is discussed, some of which are applicable in general to any statistical design of experiment.