Integrating Quantitative Methods & Modeling and Analytical Techniques in Reverse Engineering; A Cutting-Edge Strategy in Complex Generic Development

Generic drugs are crucial for healthcare, offering affordable alternatives to brand-name drugs. Complex generics, with intricate ingredients, are gaining increasing importance in managing chronic conditions. However, prior to the regulatory market approval, they must demonstrate similarity in active ingredients, formulations, strength, and administration routes to ensure bioequivalence. The primary constraint lies in demonstrating bioequivalence with the innovator drug using traditional methods includes a lack of advanced technologies, and standardized protocols for analysing complex products. Given the multifaceted nature of these products, a single methodology may not suffice to establish in vitro/in vivo bioequivalence. Recognizing this, the USFDA conducts several workshops aiming advancement of complex generic drug product development. Notably, these efforts highlight the need to use Quantitative Methods and Modeling (QMM) approaches to support generic product development. QMM is a scientific approach used to analyze data and simulate drug development processes, ensuring safe, effective, and similar formulations of generic drugs using mathematical, statistical, and computational tools. QMM facilitates the design of formulations and processes, establishes a framework for in vivo BE studies, and suggests alternative ways to demonstrate BE. Appropriate utilization of the QMM approach can reduce the need for unwanted in vivo studies and bolster in vitro approaches for generic product development. Furthermore, use of orthogonal analytical techniques to characterize and decode innovator drugs can provide valuable insights into product attributes. Integrating this data into QMM enables the assessment of critical material attributes, or critical process parameters, thus demonstrating sameness. The combined application of QMM and analytical techniques not only supports regulatory decisions but also enhances the success rate of complex generic drug products.

Graphical Abstract