A Comprehensive Review of the FDA Draft Guidance on Use-Related Risk Analysis (URRA)
Introduction
The FDA's recent draft guidance on Use-Related Risk Analysis (URRA) for drugs, biologics, and combination products formalizes practices that have been common in the pharmaceutical industry for decades. Its primary focus is to codify established methodologies to ensure drug delivery devices and related combination products are safe, effective, and user-friendly. However, a key shift introduced by this guidance is the potential requirement for URRA in drug products with complicated regimens, a notable addition to the existing focus on devices or combination products. This presents an opportunity for pharmaceutical companies to extend their human factors evaluations to drug products where such analyses were less common before.
This article reviews the key aspects of the guidance, explores its implications, and provides practical insights from my own experience in the field. We will also touch on the guidance’s recommendation to submit URRA documentation to potentially streamline regulatory submissions, emphasizing how this can be a strategic advantage for manufacturers. For additional background on URRA development and its applications, check the full FDA guidance here.
Key Takeaways from the Guidance
The draft guidance underscores the importance of integrating human factors and usability engineering early in the development lifecycle. Here are the primary components of URRA development:
Identify User Tasks: A detailed task analysis is foundational, breaking down every interaction a user has with the product (see "Creating a Task Analysis for a Drug Delivery Device" for a detailed approach to task analysis).
Identify Potential Use Errors and Harms: Consider all foreseeable use errors and their potential clinical impacts.
Categorize Tasks as Critical or Non-Critical: Focus resources on critical tasks where errors could compromise safety or treatment efficacy. Remember that the definition of critical task according to Center for Drug Evaluation and Research (CDER) is user tasks that if performed incorrectly or not performed at all, would or could cause harm to the patient or user, where harm is defined to include compromised medical care.
Identify and Evaluate Risk Controls: Prioritize eliminating risks through design before relying on labeling or training. This is normal practice recommended by ISO14971.
Iterative Updates: The URRA should evolve throughout the product’s lifecycle, adapting to new risks or design changes.
While much of this aligns with established best practices in drug delivery medical devices and combination products, the guidance introduces a key change regarding drug products. Specifically, if a drug product has a complicated dosing regimen, the FDA may now require a URRA. Moreover, if the URRA identifies critical tasks warranting further assessment, a human factors evaluation must be conducted to validate the device’s usability and safety. For additional context, see "Effective Summative Evaluations in the Pharmaceutical Industry". Additionally, see the article "FDA Issues Draft Guidance On Use-Related Risk Analysis".
Strategic Implications for Manufacturers
One of the guidance's most notable elements is the provision to submit URRA documentation as part of a marketing application. This can potentially justify not submitting human factors validation study results if the URRA demonstrates adequate risk mitigation. For example, during the development of an emergency-use auto-injector, we combined a threshold analysis with the comparative risk assessment to align with regulatory expectations, leveraging all the previous knowledge and fastening the approval process.
The ability to demonstrate rigorous use-related risk mitigation without duplicating effort in validation studies could be a game-changer for efficiency. To understand how to engage with the FDA and discuss these approaches, consider reviewing the FDA guidance "Requests for Feedback and Meetings for Medical Device Submissions".
The Role of Task Analysis in URRA
A robust task analysis underpins a successful URRA. Breaking down tasks into perception, cognition, and action elements ensures that every step is scrutinized for potential errors. For example, during the development of a drug delivery pen, our task analysis revealed a high risk of errors during cap removal due to the potential dexterity issues presented in one of the user groups. By redesigning the cap with visual and tactile cues, we mitigated this risk, demonstrating the power of informed design interventions. For detailed methodologies, see "Case Study: Creating a Task Analysis for an Auto Injector."
Conclusion: Embracing the URRA Framework
The FDA’s draft guidance on URRA formalizes what has been standard practice in the pharmaceutical industry for years. It primarily puts into writing what human factors professionals have long recognized as essential for drug delivery devices and combination products. However, the notable change lies in extending these principles to drug products, especially those with complicated dosing regimens, where a URRA and potentially a human factors evaluation may now be required.
From my perspective, this guidance represents a compelling opportunity to refine our approach to human factors. It provides a structured framework to proactively address use-related risks while optimizing the design and development process. By submitting well-crafted URRA documentation, companies can streamline their regulatory pathways and enhance their competitive position in the market.
For more information about this new URRA guidance I recommend to check the RAPS article "FDA Releases Draft Guidance On Use-Related Risk Analysis For Combo Products".
I encourage stakeholders to embrace the principles outlined in the guidance and share their feedback with the FDA. The collaborative refinement of these guidelines will pave the way for a future where drug delivery devices are safer, more effective, and truly user-centered.
