Assessment of Applications of Design of Experiments in Pharmaceutical Development for Oral Solid Dosage Forms

Abstract

The concept of quality by design (QbD) was introduced to the pharmaceutical industry about a decade ago. Design of experiments (DoE) is an excellent and important tool for a QbD approach. This project’s aim is to obtain an overview of how DoE is being applied to assist pharmaceutical development in New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) submissions for oral solid dosage forms including immediate release (IR) tablet, extended release (ER) tablet, IR capsule, and ER capsule. A total of 131 NDA submissions and 606 randomly selected ANDA submissions with submission dates between 2012 and 2016 were chosen based on the Biopharmaceutics Classification System (BCS) of drug substances. The ratios of applying DoE studies in NDA and ANDA submissions were calculated and compared based on the BCS classes of the active pharmaceutical ingredients (APIs). For the Reference Listed Drug (RLD)-based cluster ANDA submissions, the percentage of applying DoE studies in BCS II ANDA submissions is statistically higher than those of the ANDA submissions in the other three BCS classes. Some common issues of the DoE studies were found in the selected submissions. DoE has been used as an important tool for QbD approach in NDA submissions but has not yet become a routine common practice to assist the implementation of QbD approach during the pharmaceutical development for NDA and ANDA submissions for oral solid dosage forms. By conducting DoE studies, researchers can gather critical information (i.e., CMAs, CQAs, CPPs, potential interactions) during the pharmaceutical development which can help to improve the quality of applications.