FDA’s implementation of knowledge-aided assessment and structured application for manufacturing assessment of non-sterile solid oral dosage form drug products

Abstract The Knowledge-Aided Assessment and Structured Application (KASA) is an initiative led by the FDA’s Center for Drug Evaluation and Research (CDER) which is launched within CDER’s Office of Pharmaceutical Quality (OPQ). It is a platform designed to conduct the quality assessment of drug product applications more efficiently, effectively, and consistently, promoting OPQ’s “One Quality Voice”. KASA is part of CDER’s broader efforts to support the digital transformation of application submission, assessment, and lifecycle knowledge management for Chemistry, Manufacturing, and Controls (CMC) data. KASA supports CDER’s Office of Pharmaceutical Manufacturing Assessment (OPMA)’s mission which is to assure that quality pharmaceuticals are consistently manufactured over the product lifecycle. This paper provides insights into the OPMA’s implementation of manufacturing section for non-sterile solid oral dosage form (SODF) drug products, covering both manufacturing process and facility aspects, within the KASA platform for Abbreviated New Drug Applications (ANDAs). We provide details how key features of KASA, such as structured applications and knowledge-aided tools, enable manufacturing assessors to perform assessment using scientific and risk-based approaches, and promote lifecycle knowledge management. Additionally, we highlight the quantitative risk models embedded in the KASA manufacturing section for non-sterile SODF drug products, which generate initial risks related to manufacturing process and facility in terms of drug product quality. The paper also describes the risk control strategies implemented within the KASA framework. As of September 2024, over 1,130 manufacturing assessments of original ANDAs for non-sterile SODF drug products have been completed with at least the first review cycle, using the KASA platform since its launch in February 2021. This demonstrates the success of implementation of KASA in OPMA’s manufacturing assessment in support of OPQ’s regulatory assessments.