New FDA Guidance on Risk Analyses for Drugs, Biologics and Combination Products

Last year, the FDA issued a draft guidance on the risk assessment of medicinal products, biologics and combination products.
The guideline has a total of 13 pages, divided into five chapters, a glossary and a sample table. It is therefore relatively straightforward.

What is it about?

The content of the guidelines describes user-related risk analyses (URRA) and how they can be integrated into human factor studies (HFS). The guideline does not include methods for the design, execution or analysis of human factor studies in comparative studies.

In addition, explicit reference is made to five other guidelines:

• Guidance for Industry and FDA staff Applying Human Factors and Usability Engineering to Medical Devices (February 2016) 
• Guidance for Industry Safety Considerations for Product Design to Minimize Medication Errors (April 2016)
• Guidance for industry Safety Considerations for Container Labels and Carton Labeling Design to Minimize Medication Errors (May 2022) 
• Guidance for Industry and FDA staff Application of Human Factors Engineering Principles for Combination Products: Questions and Answers (September 2023) 
• Draft guidance for industry and FDA staff Contents of a Complete Submission for Threshold Analyses and Human Factors Submissions to Drug and Biologic Applications (October 2018)

The draft guidance also describes an offer by the FDA to discuss the human factor studies in meetings with the FDA.

The URRA is an element in the evaluation of human factor studies and supports the entire HFS process as part of an overall risk analysis process.

The FDA is relatively clear about the required scope of an URRA:

• A summarized list of all tasks related to the use of the product
• The potential user error and harms associated with the tasks
• The determination of whether a task is a critical task
• Risk controls incorporated into the user interfaces to mitigate risks
• Assessments of methods used to evaluate the effectiveness of risk controls

The URRA is described as a key document to create a human factor validation plan. The URRA may also be used to demonstrate compliance with 21 CFR 4 ("Regulation of Combination Products").

Initial conclusion: The URRA is a key element in the development of a human factor validation while taking residual risks into account.
Chapter III provides highly detailed information on the development of a URRA in seven steps. The steps are

• Identify User Tasks
• Identify Potential Use Errors
• Identify the Potential Harms
• Categorize Tasks
• Identify Risk Controls
• Identify Evaluation Methods
• Update the URRA

Chapter IV describes the submission of an URRA using two examples. One shows why no HF validation plan needs to be developed, the other why it does.

Chapter V then presents four practical examples of how a URRA can be used to determine HFS results and for marketing authorization of

• a pre-filled syringe used by experienced personnel
• an autoinjector for emergencies, used by laypersons
• an autoinjector for laypersons, in which URRA is used in conjunction with comparative analyses
• a drug with a complicated dosage regimen

The draft document ends with a half-page glossary and a one-page URRA sample table.

Overall conclusion: At 13 pages, the draft is relatively concise, but nevertheless provides interesting information on the preparation of URRAs, including a URRA sample table.

The draft is available on FDA´s website.