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.

Introduction

Knowledge-Aided Assessment and Structured Application (KASA) is an FDA wide initiative led by the FDA’s Center for Drug Evaluation and Research (CDER), which was launched in OPQ in February 2021 for SODF drug products for ANDAs. KASA platform is a system designed to help FDA assessors to conduct quality assessment for drug applications. KASA improves regulatory assessment by incorporating structured data, lifecycle knowledge management, and advanced data analytical tools.

The need for the KASA platform stems from both external and internal challenges faced by OPQ (Yu et al. 2019). Externally, there is an increasing volume of submissions and higher expectations of review process efficiency under the user fee programs. OPQ reviews approximately 1,000 original applications which include New Drug Applications (NDAs), Abbreviated New Drug Applications (ANDAs), and Biologics License Applications (BLAs) each year (Tran et al. 2024). The growing complexity and volume of applications, along with thousands of Investigational New Drug (IND) applications and post-approval submissions per year, present significant challenges to the review process (Tran et al. 2024). Additionally, the widespread use of unstructured data, such as narrative-based submissions, hampers data analysis and management and limits efficiency and improvements. Without the use of KASA, the quality assessment process is dependent on the reliance on freestyle narratives, unguided risk assessments, unstructured text and application assessment summaries. This reduces efficiency and consistency in assessment and decision-making, while also complicating lifecycle knowledge management (Rosencrance et al. 2019, Raw 2022, Chia 2021, Welch 2021).

The FDA has initiated several internal and external projects to streamline pharmaceutical quality information submissions, reviews, and lifecycle knowledge management (Tran et al. 2024). These initiatives include but are not limited to the ICH M4Q(R2) Common Technical Document for Quality Guideline (ICH 2021a, b), ICH Q12 Lifecycle Management, the Knowledge-aided Assessment and Structured Application (KASA), the Quality Surveillance Dashboard (QSD), and the Pharmaceutical Quality/Chemistry, Manufacturing, and Controls (PQ/CMC) for CMC data element submissions and data exchange standards (FDA 2024a). Notably, KASA has already been successfully implemented and is being routinely used as OPQ’s review platform for non-sterile solid oral dosage form (SODF) ANDAs. This includes assessment from multiple quality disciplines such as drug substance, drug product, manufacturing, and biopharmaceuticals.

The Office of Pharmaceutical Manufacturing Assessment (OPMA), part of CDER’s Office of Pharmaceutical Quality (OPQ), assures that quality pharmaceuticals are consistently manufactured over the product lifecycle. It provides the assessment of the proposed manufacturing process and facilities at commercial scale for CDER regulated products. The first KASA prototype of the manufacturing section was developed in-house in 2019 for non-sterile SODF ANDA’s for OPMA office. Multiple versions and improvements were made for the manufacturing section, and pilot tested throughout 2019–2020. In 2021, the FDA transferred the KASA manufacturing section for non-sterile SODF ANDAs to the cloud where the data are stored on FDA servers within a Federal Information Security Management Act (FISMA) high security environment, ensuring the strictest level of protection. The KASA manufacturing section was officially launched for routine assessment of non-sterile SODF ANDAs in February 2021.

Since the publication of the KASA white paper in 2019 (Yu et al. 2019), which provided the vision of the concept of the KASA platform, there has been limited detailed exploration in the literature regarding its implementation, particularly in the manufacturing section of the KASA platform. This paper presents our perspective on the FDA’s implementation of the KASA manufacturing section for non-sterile SODF ANDAs as well as an up-to-date status of its use in the OPMA’s review workflow. We provide detailed insights into the implementation of KASA manufacturing section in the OPMA office, specifically applied to non-sterile SODF ANDAs. Additionally, we summarize KASA’s features as a platform for conducting structured application assessment for manufacturing. We present the models used for facility and manufacturing initial risk assessments, discuss the practical risk control workflow, and provide case studies.

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Wang, Z., Xiao, J., Obrzut, D. et al. FDA’s implementation of knowledge-aided assessment and structured application for manufacturing assessment of non-sterile solid oral dosage form drug products. AAPS Open 12, 6 (2026). https://doi.org/10.1186/s41120-025-00141-3

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