For a generic drug, the objective is to develop a formulation/process that would result in the product performance equivalent to that of the reference (innovative) product throughout the product life-cycle.
At the development stage, physiologically based pharmacokinetic (PBPK) modeling and simulation is a useful tool to characterize the reference product and define parameters for the performance that becomes target for the product development. GastroPlus modeling is mainly based on physicochemical/PK properties of the API and on in vitro release and PK parameters of the reference drug product. By conducting a series of GastroPlus simulations, critical material attributes (CMA), such as particle size distribution, or critical process parameters (CPPs), can be defined to ensure adequate in vivo performance. In this webinar, the applicability of GastroPlus modeling and simulations at the early development stage is illustrated using BCS 4 and BCS 2 drugs as examples, formulated as immediate-release solid oral dosage forms.
At later stages, upon completion of clinical bioequivalence studies, GastroPlus modeling and simulation can serve multiple roles, as will be illustrated using examples of BCS 1 and BCS 3 drugs, formulated as extended-release, matrix based formulations. GastroPlus modeling and simulation is utilized to: (a) identify biorelevant dissolution test conditions and establish clinically meaningful acceptance criteria; (b) justify bio-study waiver for the additional strengths, (c) assess impact of post-approval changes in the composition/manufacturing process with respect to the drug product performance, and (d) define boundaries for critical material attributes of a rate–controlling excipient.
Jasmina Novakovic, Ph.D.