From Decisions to Evidence: A Context-of-Use Framework for Immune Safety Assessment Workshop

Workshop Background and Rationale: Over the past decade, new approach methodologies (NAMs)—including in vitro systems, computational tools, and human-relevant platforms—have rapidly expanded in immune safety assessment. Concurrently, global regulatory momentum to reduce animal use has intensified, increasing the need to understand how non-animal evidence can support decision-making across drug development and regulatory evaluation.

Despite this progress, the central challenge is not the availability of new methods, but how to translate diverse data streams into decision-relevant insight. Immune safety assessment is inherently decision-centric rather than method-centric: confidence is rarely derived from a single assay, but instead from the integration of multiple lines of evidence to evaluate risks such as cytokine release syndrome, immune-mediated toxicities (e.g., hypersensitivity, autoimmunity), and immunosuppression.

However, current discussions around NAMs often remain tool-focused, rather than addressing how evidence is integrated to inform decisions. This has contributed to persistent uncertainty regarding how NAM-derived data should be interpreted and applied. Evidence expectations remain inconsistent across regions and modalities, and some immune safety liabilities—particularly for biologics and emerging therapies—still lack mature non-animal approaches. As a result, confidence in NAM-based evidence frequently exists in a “gray zone,” shaped more by experience than by clearly defined frameworks.

To address these challenges, there is a growing need to better understand how immune safety decisions are made, what evidence informs them, and where NAMs already contribute. Mapping this decision landscape is a critical step toward shifting from fragmented, method-based discussions to a more integrated, decision-focused paradigm.

This workshop will convene experts from regulatory agencies, industry, and academia to examine the evolving role of NAMs in immune safety. Presentations will highlight regulatory perspectives, current applications, and real-world case studies, providing a foundation for collaborative discussions on barriers, gaps, and opportunities.

Workshop Purpose: The workshop aims to facilitate cross-sector dialogue on how NAMs can more effectively support immune safety decision-making throughout drug development and regulatory evaluation. Rather than focusing solely on individual technologies, discussions will center on how diverse evidence streams, spanning in vivo, in vitro, in silico, and clinical data, are integrated to evaluate immune safety risks. Participants will explore where NAMs are already informing decisions, where expectations diverge, and where key gaps remain.

Workshop Objectives

1.      Establish a shared understanding of the landscape: Review global regulatory perspectives on NAM adoption; Assess current use of NAMs in immune safety; Identify where NAMs already inform decisions

2.      Illustrate real-world application: Present case studies from industry and regulators; Highlight successes and implementation challenges; Examine differences across modalities and product classes

3.      Map the immune safety decision landscape: Identify key immune safety liabilities and decision points; Map evidence streams used to inform decisionsEvaluate current contributions of NAMs

4.      Assess confidence in current approaches: Identify areas of sufficient vs. limited confidence; Examine factors influencing confidence in NAM-derived evidence

5.      Identify and prioritize gaps: Highlight scientific, technical, and translational gaps; Assess regulatory and operational barriers; Prioritize gaps with the greatest near-term impact

6.      Inform future collaborative work: Identify opportunities for cross-sector collaboration; Define potential HESI ITC workstreams; Support development of a consensus publication