KASA – What You Need To Know About Knowledge-Aided Assessment and Structured Application

What is KASA and how will it impact on getting a drug assessed by the US FDA?  We look at its ‘3 pillars’ and what it aims to be.  Importantly, we look at how the FDA believes it will change how drugs are assessed in the United States of America.

What Is KASA?

Knowledge-Aided Assessment and Structured Application (KASA) has been described by The International Journal of Pharmaceutics as a system that is designed to:

• capture and manage knowledge during the lifecycle of a drug product
• establish rules and algorithms for risk assessment, control, and communication
• perform computer-aided analyses of applications to compare regulatory standards and quality risks across applications and facilities
• provide a structured assessment that minimizes text-based narratives and summarization of provided information

“When fully developed and implemented, KASA will enrich the effectiveness, efficiency, and consistency of regulatory quality oversight through lifecycle management of products and facilities, and information sharing in a standardized and structured format. Ultimately, KASA will advance FDA’s focus on pharmaceutical quality, the foundation for ensuring the safety and efficacy of drugs”

The Office of Pharmaceutical Quality (OPQ) in the U.S.A. is responsible for the quality assessment of Human drug marketing applications. The OPQ has recognised a need to modernise the current text-based assessment approach and is in the process of developing a new data-based assessment tool named KASA. It is designed to perform computer-aided analysis of applications for a comparison of regulatory standards and quality risks across the repository of approved drug products and facilities.

So, how will the new KASA system work and how will it impact on your company’s ability to get a drug assessed?

It is envisioned that KASA will consist of 3 pillars built from a foundation of historical knowledge on product and manufacturing facility. Pillar 1                  Assessment of risk to quality by establishing rules and algorithms Pillar 2                  Risk mitigation by assessing product design, understanding and quality standards Pillar 3                  Risk mitigation by assessing manufacturing and facility and when needed performing pre-approval inspections Pillar 1 to include a Failure Modes Effects and Critical Analysis (FMECA) approach. The FMECA would be applied to the submitted data by the assessor with the aim to objectively and quantitatively assess and rank risks associated with the failure modes of the drug product design and manufacturing. Pillar 2 would evaluate the inherent risks identified in Pillar 1. The identified risks should be mitigated by the design of the product and the use of patient focused quality standards. It is envisioned that the use of drop-down menus in KASA with structured descriptors would facilitate an objective understanding of the product and its control strategy. The knowledge captured on mitigation of product risk could also be compared across applications and facilities. Pillar 3 would evaluate the design of the manufacturing process and the implementation risks. These factors would also be captured using pre-defined descriptors in drop-down menus to facilitate the objective capture of aspects related to manufacturing and facility understanding and control. It is further envisioned that this would enable objective standards to be used to identify the need for a post-approval inspection. KASA is primarily being developed as an assessment tool with a view to eventually alleviating problems such as data mining that are associated with electronic drug applications. The FDA considers the benefits of KASA to include:

• Improvements to consistency, transparency, communication and objectivity of regulatory actions
• Enabling assessors to automatically retrieve historical data and facility information to better inform regulatory evaluation and decision-making process
• Facilitating assessment of risk to reduce subjectivity and time burden
• Allowing detection of outliers in the control strategy and risk attributes compared to the broader KASA database to improve quality and efficiency

KASA is currently in the internal development phase with no established timeline for roll out available. While the European Medicines Agency is aware of this development, there has not been any harmonisation discussion.

Our Recommendation for KASA

KASA is in its early stages at the moment and, as referenced above, there is no timeline set out for its roll out.  However, we recommend that companies developing products for the American market continue to monitor the KASA development. Prior to implementation, the FDA will issue a draft guidance for industry comment. We will be informing our clients  and we will write about this on our website and newsletter when it is published. Acorn Regulatory is already monitoring the situation on behalf of client companies.  If you want to find out more about the possible implications of KASA or other issues related to developing products for the American market, then please contact us by using the form below. [ninja_form id=1]

Further Reading from Acorn Regulatory

Updated for 2020: Development of the Orphan Drug Sector

Much has been written about orphan drugs in recent times.  These products, developed specifically to treat a rare disease, have become more common in the marketplace.  At the time of writing (May 2020), there are almost 770 orphan drugs commercially available and more than 5600 orphan designated drugs in the biopharmaceutical pipeline. As the sector continues to grow there has been a tendency for facts about orphan drugs to get lost in the midst of issues concerning specific patients’ needs, pricing and availability.  We look at some facts about orphan designation that companies considering entering the sector should be aware of. Read more about orphan drugs here.

Medicinal Product Labelling: What You Need To Know

Medicinal products are no exception and must be accompanied by outer and/or immediate packaging information (labelling) and a package leaflet providing information enabling the safe and effective use of the medicinal product. In fact, medicinal products are legally required to have certain information on the labels and package leaflets as defined in Title V of Directive 2001/83/EC on the ‘Community code relating to medicinal products for human use’ (as amended). Read more about medicinal product labelling here.

Outsourced eCTD Publishing Services: An Overview

More countries are implementing eCTD.  As a result, more companies are being forced to make decisions regarding how they manage their electronic submission and eCTD publishing services. We typically encounter three scenarios:

1. Companies that maintain control of electronic publishing at the corporate and head office level
2. Others that have retained the day-to-day eCTD maintenance and lifecycle at a local level
3. Companies that have outsourced eCTD entirely

In this article, we will look at the benefits and the limitations presented by the three options presented above. Find out more about outsourcing eCTD here.