Q1 and Q2 selection, Q3, IVRT, IVPT, pharmacokinetic and pharmacodynamic evaluation of topical generic product.

Abstract

Objective: To establish a detailed step-by-step example for the topical development of generic products.

Significance: Topical semisolids are complex products requiring extensive research for bioequivalence by establishing Q1/Q2/Q3.

Methods: The detailed process establishes Q1/Q2 selection and Q3 evaluation of the innovator and proposed formulation. The proposed generic product along with the innovator formulation has been evaluated for physicochemical properties. Once the Q3 structure is matched with innovator formulation, the invitro release and in-vitro permeation study have been conducted to move forward for the bioequivalence study. Pharmacokinetic and pharmacodynamic studies were employed for bioequivalence with an innovator in humans.

Results: Selection of Q1 and Q2 establish the formulation composition through literature search and reverse engineering. The test and reference products are pharmaceutically equivalent through Q3 characterization, IVRT, and IVPT. In the PK study, test and reference samples were compared for Cmax, T_max, and t_1/2 and found bioequivalent. The PD study was performed in pilot and pivotal study to establish dose duration response relationship and bioequivalence respectively without adverse events. A crucial study has exhibited that reference and test formulations are bioequivalent with a 90% confidence interval and results in 84.67%-101.09%.

Conclusion: The Cutivate^® cream 0.05%, and proposed generic product Fluticasone Propionate cream 0.05% formulations are bioequivalent and have a favorable safety profile.