device can be used as intended by the end user, which aligns with the overarching goals of human factors engineering.

Similarly, in the UK, the MHRA remains aligned with EU regulations following Brexit and emphasizes usability testing as an integral component of product design. Regulatory bodies across these regions stress the importance of systematic assessment of user interactions to mitigate errors that could affect safety and efficacy.

Documentation Requirements

The documentation required for HFE in combination products typically consists of a human factors file (HFF) or human factors engineering report. This report should comprehensively detail the HFE activities undertaken, the findings from usability testing, the lessons learned, and the corrective actions or design changes made as a result.

• Conduct a thorough literature review on existing human factors engineering guidelines.
• Outline your user profile: consider existing users, potential users, and their environments.
• Document the risk assessment results related to human factors, including potential use errors.
• Include a description of the HFE process, including your methods for formative and summative assessments.
• Present findings from user studies, including quantitative and qualitative data.
• Provide justifications for any major design decisions related to HFE.

Review/Approval Flow

FDA Submission Process

For combination products submitted to the FDA, the review process will differ based on the primary mode of action (PMOA) of the product. The modes of action determine the regulatory pathway—whether as a device or a drug—which impacts user evaluation requirements. This may include:

1. Pre-submission meetings—interact with FDA staff to confirm the HFE strategy.
2. Compile the human factors file as part of the submission dossier.
3. Respond to FDA inquiries during the review period regarding human factors engineering findings.

EU and UK Submission Process

For the EU and UK, manufacturers must ensure compliance with MDR/IVDR and provide the necessary human factors documentation as part of the Technical Documentation during Notified Body (NB) review. The submission process includes:

1. Conducting usability tests following ISO 62366 guidelines.
2. Integrating HFE studies into the clinical evaluation plan if applicable.
3. Ensuring that the human factors report is part of the Technical Document to satisfy regulatory requirements.

Common Deficiencies

When preparing human factors engineering documents for regulatory submission, several common deficiencies can be identified that may lead to delays in approval or additional queries from the regulatory agencies. These include:

• Inadequate Justifications: Lacking clear rationale for design choices related to usability increases the risk of user error.
• Poorly Defined User Profiles: Failing to describe the intended users and use environments inhibits effective risk analysis.
• Insufficient Test Data: Incomplete or non-representative data from usability studies may not fully capture the user experience.
• Unaddressed Risk Factors: An inadequate response to identified risks during testing can raise significant concerns with regulators.
• Documentation Gaps: Missing or poorly formatted documentation undermines the overall presentation of the human factors file.

Decision Points in Regulatory Affairs

Variation vs. New Application

A critical decision in regulatory affairs is determining whether a change in a combination product should be classified as a new application or a variation. The key factors in this decision include:

• If the change alters the PMOA significantly, then a new application may be required.
• Submit a variation for less significant adjustments that do not fundamentally alter the product’s safety or efficacy profile.
• Document the rationale for your choice to facilitate understanding and approval from the regulatory agency.

Justifying Bridging Data

Bridging data may be necessary when there is a reliance on previous products to justify a new or modified device. The decision-making process requires:

• Assessing prior data for relevance to ensure consistency in user experience and outcomes.
• Providing explicit comparison and validation of any changes made in device design or functionality.
• Documenting any assumptions made during the bridging process to clarify the basis for regulatory acceptance.

Conclusion

In conclusion, human factors engineering plays a pivotal role in the development of combination products, directly influencing regulatory success. By understanding and adhering to the relevant guidelines and regulatory expectations, regulatory professionals can navigate the complexities of HFE documentation, submission processes, and common pitfalls. A well-prepared human factors plan and report not only meets regulatory agency requirements but also fundamentally enhances product safety and usability for end users.