The article highlights the key points associated with the use-related risk analyses to be conducted with respect to various healthcare products intended to be marketed and used in the US.
Table of content
The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to the purpose and content of use-related risk analyses for drugs, biological products, and combination products. Once finalized, the document will provide an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by manufacturers and other parties involved in order to ensure compliance.
At the same time, it is important to mention that provisions of the guidance documents issued by the FDA are non-binding in their legal nature, nor are they intended to introduce new rules or impose new obligations. Furthermore, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the respective regulations and has been agreed with the authority in advance.
Introduction
In particular, the document provides detailed guidance for both industry professionals and the FDA staff regarding the purpose and content of Use-Related Risk Analyses (URRA). It emphasizes how URRA, alongside other critical information, plays a significant role in determining the need for human factors (HF) data during product development.
Moreover, it is vitally important in supporting marketing applications for drug-led, biologic-led, and combination products. The guidance applies to a broad spectrum of products, including combination products that involve a device component and are subject to regulatory submissions such as Investigational New Drug Applications (INDs), New Drug Applications (NDAs), or Biologics License Applications (BLAs).
It also extends to stand-alone drug and biological products, including both prescription and non-prescription drugs that fall under these applications. It is important to mention that while the guidance outlines the essential content of a URRA, it does not get into specific methodologies for conducting HF studies or comparative analyses.
Instead, it points sponsors toward additional relevant guidance documents that address various aspects of product design, human factors engineering, and risk management. Furthermore, the FDA encourages early engagement between sponsors and the Agency during the product design and development stages, recommending appropriate formal meetings and communications to ensure compliance and effectiveness in meeting regulatory standards.
Regulatory Background
The foundation of this guidance is rooted in the regulatory requirements established by the Federal Food, Drug, and Cosmetic Act (FD&C Act) and the Public Health Service Act (PHS Act). Under these acts, products submitted for approval must be proven safe, effective, and, in the case of biological products, pure and potent.
Additionally, the FDA evaluates human factors study results, especially when such data are necessary to support the product’s user interface. This evaluation is intended to ensure that the products are safe and effective for their intended use.
As further explained by the FDA, the URRA serves as a critical tool in this process, functioning as a risk analysis method to identify and mitigate use-related hazards associated with product use. It supports the human factors engineering process and is a vital component of an overall risk management strategy.
The authority mentions that the URRA aids in minimizing risks throughout the product’s lifecycle, from development through to post-marketing by identifying potential hazards and implementing risk controls.
Purpose and Content of URRA
The URRA is designed to identify use-related risks and hazards linked to a product’s user interface, which could lead to errors or harm during its use. It is an essential part of the human factors engineering process and should be initiated early in product development.
The URRA must be maintained and updated throughout the product’s lifecycle, especially when changes occur in the product design or when new risks are identified.
A comprehensive URRA includes several critical components:
- Task Analysis: A thorough list of all tasks required for the product’s use, identifying potential errors and harms associated with each task.
- Critical Task Identification: Determining which tasks are critical, meaning errors in these tasks could lead to significant harm.
- Risk Controls: Implementing and documenting risk controls in the user interface design to mitigate potential use errors.
- Evaluation Methods: Outlining methods used or planned to evaluate the effectiveness of these risk controls.
These elements help ensure that the product’s design minimizes the likelihood of user errors and enhances overall safety. Furthermore, the URRA plays a key role in deciding whether a sponsor should submit HF validation study results for FDA review as part of the marketing application.
It also informs the development of HF validation study protocols and helps in assessing the acceptability of residual risks associated with the product.
Application and Compliance
In addition to its role in product design and development, the URRA is crucial for demonstrating compliance with applicable regulatory requirements, particularly those codified in 21 CFR part 4 subpart A, which governs combination products. The URRA can also inform comparative analyses and help sponsors determine the necessity of submitting HF validation study results as part of their marketing applications.
Engagement and Communication with FDA
The guidance also stresses the importance of early and continuous engagement between sponsors and the FDA during the product development process. Such interactions can help ensure that the human factors considerations are adequately addressed and that the URRA and other related analyses are appropriately developed and utilized.
Sponsors are advised to follow relevant guidance documents concerning formal meetings and communications with the FDA. This includes requesting feedback on combination products and engaging in formal meetings with the FDA regarding PDUFA (Prescription Drug User Fee Act) and BsUFA (Biosimilar User Fee Act) products.
Effective communication with the FDA is essential for aligning expectations and ensuring a smooth regulatory process.
Conclusion
In summary, this guidance document provides a comprehensive overview of the purpose and content of Use-Related Risk Analyses for drugs, biological products, and combination products. It highlights the critical role of URRA in identifying and mitigating use-related risks, ensuring product safety, and supporting the regulatory process. While not legally binding, the guidance offers valuable recommendations for sponsors to follow, emphasizing the importance of early engagement with the FDA and adherence to human factors engineering principles throughout the product life cycle.
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