FDA taking incremental approach to launching KASA reviews

Regulatory NewsRegulatory News | 05 November 2021 |  By 

The US Food and Drug Administration (FDA) is taking a “step-wise” approach to implementing its Knowledge-Aided Assessment and Structured Application (KASA) drug review program. The review program has already launched for abbreviated new drug applications (ANDAs) for solid oral dosage forms and will eventually be rolled out for new drug applications (NDAs) and ANDA liquid dosage forms in FY 2023. KASA will be phased in for investigational new drug applications (INDs) and post-approval changes in FY 2024, with work on biologics license applications (BLAs) modules continuing in FY 2025.
Officials described their implementation plans at a 26 October Pharmaceutical Quality Symposium sponsored by the Small Business and Industry Assistance (SBIA) program at FDA’s Center for Drug Evaluation and Research (CDER). They also touted this review model as informing a more objective and efficient approach for reviewing applications.
Joanne Chia, director of the Division of New Drug Products III in CDER’s Office of New Drug Products in CDER’s Office of Pharmaceutical Quality (OPQ), explained that “the KASA system allows FDA to intake structured application data and capture critical assessment information in a structured format.” The information technology system that forms the architecture for KASA facilitates organized structured submission data in a way that facilitates the agency’s regulatory review process.
Joel Welch, the associate director for science and biosimilar strategy at OPQ’s Office of Biotechnology Products, characterized the existing review system as “poorly designed for knowledge management.” Current reviews involve the submission of “freestyle narrative assessments with unstructured text, copy and paste data tables, cumbersome knowledge-sharing and knowledge management and a subjective assessment based on the assessor’s expertise and knowledge at hand,” said Welch. Reviewers also often have to sort through these applications to extract pertinent information.
Welch said that “a series of external and internal challenges drove the need for KASA,” including “the crushing number of new applications” along with user fee expectations to review applications in a timely manner, and the need for “agile assessment decisions.”
FDA announced the new KASA system in 2019 as part of a larger CDER effort to modernize regulatory assessments. (RELATED: FDA Explains Plans for New Pharmaceutical Quality Assessment System, Regulatory Focus 16 September 2019; FDA’s OPQ reports on drug quality efforts in 2020, Regulatory Focus 11 February 2021)
These changes were first pushed by former FDA Commissioner Scott Gottlieb in 2018. (RELATED: End of the eCTD? FDA Pushes for New KASA System to Improve Assessments, Regulatory Focus, 20 September 2018)
Biologics development shows OPQ’s step-wise approach
Chia noted that KASA facilitates an integrated approach to quality assessment across different elements of drug submissions, including assessment of  drug product, biopharmaceutics, manufacturing and the drug substance. The initiative supports OPQ’s “One Quality Voice” approach that seeks to create “a uniform drug quality program across all sites of manufacture -- domestic or foreign -- and across all human drug product areas including new drugs and biologics, generics, biosimilars, and also over-the-counter drugs and compounded drug products,” according to OPQ’s home page.
Biological products differ from drug products in many ways, said Welch. Still, the four key objectives of KASA still apply to biologics, despite the differences in process, molecular function and context, and the nature of data submitted.
Welch used the development of a KASA biologics module as an illustration of OPQ’s stepwise approach to KASA implementation. The office is currently developing a risk-based assessment prototype module for the manufacturing portion of a BLA for a monoclonal antibody (mAb). These products, said Welch, constitute “the majority of BLA submissions.” KASA modules do not yet address mAb microbiology or facility issues.
The basic algorithm module consists of five parts: an initial risk assessment based on the information submitted in the structured format, the characterization of the MAb, validation parameters, whether process parameter critical ranges are supported, and a final risk ranking and recommendation.
Welch said the module “will allow the assessor to make a good risk-based decision where the data submitted by the applicant drives up or down the risk ranking” and whether to approve the application.
Eventually, KASA will be rolled out to other types of BLA products, and will address other aspects of biologics production.
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