Human factors studies for injectable combination products: from planning to reporting.

Interest in human factors usability testing has seen a sharp increase from manufacturers bringing new injectable pharmaceutical combination products to market and from regulators reviewing and approving submissions. This paper highlights the special regulatory considerations in the planning, execution, and reporting of human factor usability studies for injectable combination products. The paper describes recent human factors examples that capture and convey important sponsor learning for drug/device combination products. Special emphasis is placed on the recent focus across U.S. Food and Drug Administration centers, offices, and divisions in issuing new draft guidance outlining expectations in the execution and reporting of usability testing. Insight is provided into how the new guidance has been put into practice in the development and review of injectable combination products, and some of the unwritten recommendations/expectations that have been gleaned from these regulatory interactions are identified. The paper also describes future areas of opportunity for regulatory guidance based on reflections from over two dozen recent combination product human factor studies covering from early design development and testing through to the reporting of human factors results in the final submission. LAY ABSTRACT: Human factors is the study of the interaction of people and technology to ensure the safety and effectiveness of that interaction and to improve human/device compatibility, including the user interface, instructions, and training programs to avoid use error. The enhanced focus on human factors usability assessments for injectable combination products is an acknowledgement by regulators and industry that the device mechanics are typically quite reliable and that device risk hazards are likely due to device usability. Use errors can occur when the device is not being used as intended or the design features are less than optimal. Human factors testing, analysis, and validation helps to identify and eliminate use errors by informing appropriate mitigation strategies to ensure the device design provides the optimum use of injectable drug/device combination products.

Recommendations regarding technical standards for follow-on biologics: comparability, similarity, interchangeability.

BACKGROUND: Policy makers around the world are currently considering the creation of a regulatory pathway for follow-on biologics (FOB), which will have to account for the substantial technical challenges associated with FOB development. These challenges will likely involve more complexity than comparability assessments of process changes made by the same manufacturer. The history of industry-regulator comparability discussions helps explain why the same degree of testing and flexibility now applied to change-control within a manufacturer's own process, at this time, cannot be extrapolated to the observed and possibly unknown differences between two manufacturing processes that are independently developed by different (non-collaborating) parties. OBJECTIVES: This commentary provides recommendations on the technical aspects that should be considered in the creation of an approval pathway for FOB products. CONCLUSIONS: In the authors' view, analytical methodology in its current state cannot alone provide full assurance that the FOB is sufficiently similar to the innovator product. Moreover, the FOB manufacturer will not have access to the extensive knowledge accumulated by the innovator manufacturer from early development through marketing. Thus, extensive clinical evaluation will likely be necessary to provide assurance that the FOB is safe and efficacious. If such testing demonstrates the FOB is safe and efficacious per existing regulatory standards, the product should receive marketing approval as a 'similar' product. Since 'similarity' is a fundamentally different determination than establishing interchangeability between the two products, an interchangeability determination must be based on additional testing and market experience to ensure patient safety. Post-marketing surveillance of the FOB should be conducted to ensure that the approved molecule has similar clinical safety and efficacy as the innovator product, prior to any consideration of interchangeability.