Last Updated: 1 November 2023
See updates at the end of the post.
This post is an attempt to inform the reader about the FDA’s Knowledge-Aided Assessment and Structured Application (KASA) system. Please note that at the time of last update of this post (1 November 2023), the FDA does not yet appear to have a dedicated web page(s) concerning the latest information on KASA. It is therefore quite difficult to present up to date information. Please use this blog post only as a starting point to seek further, more up to date information on KASA. Links to recent presentations, webinars, articles etc. will be provided whenever possible.
About the FDA’s pharmaceutical quality journey
The FDA’s pharmaceutical quality journey has evolved over the years and includes the following initiatives:
- Process Analytical Technology/Emerging Technology Program(PAT/ETP)
- Quality by Design (QbD)
- Integrated Quality assessment (IQA)
- Concept Of Operations for Facility Evaluation and Inspection for Human Drugs (COnOps)
The most recent of these initiatives is the FDA Quality Oversight New Initiative: Knowledge – aided Assessment and Structured Application (KASA).
What is KASA?
KASA is part of the larger CDER effort to modernise regulatory assessment.
It is an advanced IT system for regulatory review and knowledge management using structured submission data in the Office of Pharmaceutical Quality (OPQ).
Structured data is highly-organised and formatted so that it’s easily searchable in relational databases. Unstructured data has no predefined format or organisation, making it much more difficult to collect, process, and analyse.
The KASA system allows the FDA to intake structured application data and capture critical assessment information in a structured information format.
KASA has three main pillars as depicted below.
Essentially, KASA enables the FDA to leverage its knowledge base and drive knowledge management throughout the lifecyle of a product.
Why was KASA deemed necessary?
KASA was deemed necessary because the FDA recognised the need for change in response to the external and internal challenges listed below:
External challenges
- Increasing volume of new applications
- User fee program expectations
- Commisioner, Congress, pharma industry and public expectations
- Technology advancements
Internal challenges
- Freestyle narrative assessment
- Unstructured text
- Summarisation of application information
- ‘Copy and paste’ data tables
- Cumbersome knowledge sharing and knowledge management
- Subjective assessment based on an assessor’s expertise and knowledge at hand
What are the objectives of KASA ?
Broadly, KASA has the following four objectives:
- Deliver a structured regulatory submission and assessment that radically eliminates text-based narratives and summarisation of information from applications
- Institute rules and algorithms for risk management and decision-making
- Perform intelligent data analysis to establish regulatory standards
- Capture and manage knoweldge during the lifecycle of a drug product
All of the above objectives also apply to biological products.
The approach taken in developing KASA
The Office of Pharmaceutical Quality’s (OPQs) Integrated Quality Assessment for NDAs, ANDAs and BLAs relies on expertise from various disciplines that include the drug product, biopharmaceutics, manufacturing and the drug substance. With all these disciplines in mind, OPQ developed KASA in a systematic and stepwise approach, starting with the drug product and then moving on to the rest of the disciplines in the order stated above.
What is the state of progress of KASA for biologics?
KASA for biologics is beginning a pilot to assess its prototype modules. The biologics KASA module builds on the same approach as others but includes unique elements based on the nature of biotechnology products.
What is the roadmap for KASA launch?
The Roadmap for KASA launch provided below as detailed in SLide No 9 in the presentation entitled The Future of FDA Quality Assessment Knowledge-Aided Assessment & Structured Application – KASA delivered at the DMF Workshop: GDUFA III Enhancements and Structured Submissions
November 30, 2022.
| KASA version | Year | Topic(s) | Target |
|---|---|---|---|
| KASA 3.0 ANDAs solid oral dosage forms (including drug product, manufacturing and biopharmaceutics) | 2021 | KASA 3.0 Release (Feb. 2021): Drug product, Biopharm, and Manufacturing KASA modules for generic solid oral drug products | Completed |
| 2022 | KASA 3.2 Release (Feb. 2022): Updates to the interface and data analytics | Completed | |
| KASA 4.0 Drug Substance (DMF, NDA, ANDA), Application Team Lead (ATL) Executive Summary | 2023 | KASA 4.0 Release: Drug substance (DMF, NDA, ANDA) modules KASA 4.0 Release: Drug substance (DMF, NDA, ANDA) modules | Defined |
| KASA 5.0 and Beyond KASA 4.0 Release: Drug substance (DMF, NDA, ANDA) modules NDAs BLAs Post-approval changes | 2024 – 2027 | ANDA liquids dosage forms INDs for NDA NDA Drug product BLA · INDs for BLA · DS/DP/viral safety · Analytics/Biosimilars · ANDA, NDA, BLA Supplements | Tentative |
What are the benefits of KASA?
The benefits of KASA are:
for the FDA
- Modernises regulatory review
- Enhances efficiency, consistency and objectivity of regulatory assessment
- Enables knowledge management of information in DMFs, ANDAs, NDAs and BLAs
- Excels regulatory action and decision making
For the FDA, KASA presents an incredible opportunity for knowledge magagement, consistency in decision making and efficiency.
for the Industry and patients
- Clearer communication of regulatory expectations; enhanced transparency and consistency
- Increased 1st cycle approvals (especially generics)
- More affordable and accessible medicines
Further information
| Date | Title | Notes |
|---|---|---|
| 31 Oct 2023 | Modernizing Quality Assessment of New Drugs (zip file) | The presentation by Hong Cai, Ph.D. Division Director (delivered on Day 1 at the Pharmaceutical Quality Symposium on 31 Oct and 1 Nov 2023: Quality, Supply Chain and advanced manufacturing) describes the KASA initiative for IND and NDA Applications to improve consistency and efficiency of quality assessment. Further information is available in this article from RAPS entitled FDA expands KASA review program to drug substances. |
| Jan 25, 2023 | FDA’s KASA and PQ/CMC Initiatives: Perspectives for Biotechnology Products | Slide deck from WCBP 2023 “Diverse Collaborations for Global Innovation” |
| Nov 30 2022 | Q & A Discussion panel – Slide deck entitled The Future of FDA Quality Assessment Knowledge-Aided Assessment & Structured Application – KASA | Drug Master File (DMF) Workshop: GDUFA III Enhancements and Structured Data Submissions |
| June 6 – 10 2022 | Panel Discussion – Q&A, Slide deck entitled Standardizing Quality Submissions and Assessments: PQ/CMC and KASA | Regulatory Education for Industry (REdI) Annual Conference 2022 |
| 17 Feb 2022 | FDA’s KASA and Related PQ/CMC Initiatives on Improving CMC Data Structuring and Sharing Will Help Support ICH M4Q Revision | Post on the International Pharmaceutical Quality website, ipq.com |
| Jan 27, 2022 | What’s in a KASA? Knowledge-Aided Assessment and Structured Application (KASA) For Biological Products | Slide deck from WCBP 2022 “One World, One Submission” |
| Oct 26 – 27 2021 | Regulatory Education for Industry (REdI): Pharmaceutical Quality Symposium October 26 & 27, 2021 (CDER Small Business and Industry Association (SBIA) | The relevant presentations from the seminar are listed below: i) Knowledge-Aided Assessment and Structured Application (KASA): Part 1 Modernising the FDA’s Regulatory assessment (Joanne Chia) The first presentation on this topic covers KASA’s development and implementation for the quality assessment of new and generic drug applications, including drug substance, drug product, and manufacturing (process/facilities). ii) Knowledge-Aided Assessment and Structured Application (KASA): Part 2 (Joel Welch) The second presentation on this topic covers KASA’s development and implementation for the quality assessment of biologics license applications. Here, you can view the above recorded sessions starting at 24 minutes and you can download the slides for presentations from this page. |
| 5 Nov 2021 | FDA taking incremental approach to launching KASA reviews | Article from RAPS regulatory focus |
| Mar 3 & 4, 2021 | Drug Master File (DMF) and Drug Substance Workshop March 3 & 4, 2021 | The relevant section of the seminar is entitled Modernising Drug Substance Assessment through KASA (CDER SBIA API Workshop (Larisa Wu). You can view the presentation here and download the slides from this page.(See links under Day Two) |
| Dec 2019 | FDA’s new pharmaceutical quality initiative: Knowledge-aided assessment & structured applications | (International Journal of Pharmaceutics Volume 1, December 2019, 100010) |
| 25 June 2019 | Video entitled Knowledge Assessment: What is the FDA knowledge aided assessment and structured applications (KASA}? | This video is a summary for an article published in the International Journal of Pharmaceutics entitled FDA’s new pharmaceutical quality initiative: Knowledge-aided assessment & structured applications |
Updates
| Date | Update(s) |
|---|---|
| 1 Nov 2023 | 1) Table in the section Further Information updated to include the presentation by Hong Cai, Ph.D., Division Director (delivered on Day 1 at the Pharmaceutical Quality Symposium on31 Oct and 1 Nov 2023: Quality, Supply Chain and advanced manufacturing) describes the KASA initiative for IND and NDA Applications to improve consistency and efficiency of quality assessment. 2) Section entitled Roadmap for KASA updated. |
| 14 Sep 2023 | Section entitled Further Information updated into a table to facilitate ease of use and more links added. |