Species selection for monoclonal antibody (mAb) nonclinical safety programs has long defaulted to non-human primates (NHPs) — and for good reasons. This reliance is now under pressure from multiple directions: ICH S6(R1)'s focus on demonstrable biological activity in species selection, the FDA Modernization Act 2.0's intent to broaden the accepted evidence base for nonclinical safety (including alternatives to animal studies), and growing agency and institutional emphasis on NHP reduction in drug development.
Transgenic and humanized mouse (huMouse) models have gained traction as a potential path forward — offering target engagement in a rodent system that may, in some cases, reduce or eliminate the need for large animal studies. The regulatory logic is attractive. The practical reality, however, is more complicated.
This session takes an honest look at both sides. Drawing on case study examples and a live cross-functional dialogue between a toxicologist and regulatory affairs lead, we will walk through a framework for evaluating huMouse model suitability — what characterization data regulators expect, how to construct a scientifically defensible species justification, and what current FDA guidance does and does not say about these models in the context of mAb safety packages. Equally important, we will examine where these models have real limitations: incomplete immune reconstitution, variable target expression fidelity, questions around toxicity translatability, and situations where a huMouse simply cannot carry the weight of a full safety program.
We will also address a question coming up more frequently in regulatory conversations: do huMouse models qualify as New Approach Methodologies (NAMs)? The short answer is no — they remain animal-based systems. But as FDA's Predictive Toxicology Roadmap and emerging NAMs frameworks continue to evolve, understanding how huMouse models complement rather than replace true NAMs has real implications for how sponsors frame nonclinical packages going forward.
The session is designed for a mixed audience. Early-stage regulatory professionals will leave with a practical characterization framework and a clearer understanding of what ICH S6(R1) requires in practice. Late-stage and senior regulatory professionals will engage with the strategic implications — including where guidance is silent, how agencies have responded to huMouse justifications in practice, and how to position these models across development stages. The goal throughout is the same: help attendees make better-informed decisions about when huMouse models strengthen a regulatory submission — and when they don't.
Audience Learning Level
Intermediate: Content is designed based upon the assumption that individuals have basic knowledge of the topic(s) and/or demonstrated competence related to the topic(s). Higher-level concepts are introduced during lectures; exercises requiring synthesis and/or application of concepts are incorporated into the activity.
Cancellations and Refunds
RAPS reserves the right to cancel this program at its sole discretion. RAPS will not be responsible for travel or other costs incurred due to cancellation. All cancellation requests must be submitted in writing to [email protected]. Cancellations will receive a full refund minus a 20% administrative fee. RAPS is unable to accept cancellations by phone.
Substitutions
Paid registration substitutions may be accepted with written approval from RAPS for requests received before the start of the event. To transfer a registration, email [email protected] with the event title, name of the original registrant and the contact information for the new attendee.
Questions
Contact the RAPS Support Center:
Call +1 301 770 2920, ext. 200 (8:30 am–5:30 pm EST, Monday–Friday) or email [email protected].
Speaker
Deven Dandekar PhD., DABT
