FDA expands KASA review program to drug substances

The US Food and Drug Administration (FDA) is now piloting its Knowledge-aided Assessment and Structured Application (KASA) drug review program for drug substances as part of its effort to improve quality reviews of drug applications and speed products to market.

The review program has already been implemented in abbreviated new drug applications (ANDAs) for solid oral dosage forms.
 

FDA’s Hong Cai, division director for the Office of New Drug Products in the Center for Drug Evaluation and Research (CDER), discussed some of the agency’s review challenges and how KASA will be used to help overcome some of these obstacles during the Pharmaceutical Quality Symposium sponsored by the Small Business and Industry Assistance (SBIA) program at CDER, held on 31 October.

In March 2023, FDA completed its KASA review template for drug substances for new and generic drugs, Cai said. FDA is currently testing prototypes for KASA for Phase 1 for commercial investigational new drugs (INDs). In 2024, FDA plans to develop KASA for new drug application (NDA) biopharmaceutical classifications and for the review of manufacturing information.

Plans are also in the works to reconcile existing templates for reviewing new drugs with KASA, Cai said.

The KASA program was first announced in 2019 as part of FDA’s work to improve and modernize the quality assessment of drug applications, and the agency has since said it would take a step-wise approach to implementing KASA in drug reviews (RELATED: FDA Explains Plans for New Quality Assessment System, Regulatory Focus 16 September 2019; FDA taking incremental approach to launching KASA reviews, Regulatory Focus 5 November 2021).

For INDs, Cai described how KASA can be used to expedite assessments. These applications involve large amounts of data that are dispersed throughout multiple parts of the IND. Additionally, data is often located in PDFs and stored on local servers that are not easily searchable. These documents also contain unstructured text, which creates further review challenges.

FDA’s growing workload is another problem for reviewers. The number of INDs is trending upward, from 11,223 in CY 2018 to 14,268 in CY 2022. “This is a tremendous quality review task for the agency,” Cai said.

Under the KASA review program for drug substances, FDA will be able to use a machine-readable structured data field, enabling reviewers to quickly identify information, such as high-risk impurities, and to apply consistent standards in assessing applications.

For example, the structured data fields for chemical structures will now include tables of information that can be easily searched. This template makes it easier to review applications and to share information with other reviewers. Reviewers will no longer have to search through various PDF files to locate pertinent information, Cai said.

CDER SBIA meeting