Upcoming Events

Signature Webinar–Part 1: Integrating NAMs into Weight of Evidence Frameworks for Nonclinical Assess

Part 1: Integrating NAMs into Weight of Evidence Frameworks for Nonclinical Assessment

SPEAKERS: Jacintha Shenton, PhD, and Laralynne Przybyla, PhD

Advances in science and technology are creating unprecedented opportunities to strengthen nonclinical assessment by initiating science-based weight-of-evidence (WoE) frameworks earlier in nonclinical development and through the integration of new approach methodologies (NAMs). This webinar will explore how a disease area- and modality-agnostic WoE framework can support more informed nonclinical and regulatory decision-making while enabling the broader application of NAMs, where scientifically appropriate. The framework integrates multiple lines of evidence, including public-domain knowledge, in silico and in vitro studies, NAMs with defined contexts of use, and in vivo studies, to support an integrated, science-based approach to nonclinical testing.

The webinar will highlight the multidisciplinary partnerships required to implement this vision, bringing together nonclinical scientists, experts in in silico and in vitro technologies, and regulatory scientists. These new ways of working have the potential to strengthen scientific and regulatory decision-making, improve the efficiency and human relevance of nonclinical development, and increase confidence in science-based nonclinical strategies.

Within the context of this framework, the webinar will focus on the role of NAMs in nonclinical assessment, examining how they are being integrated today and how their applications are expected to expand as scientific knowledge and technology continue to advance. Examples will include human cell-based assays, microphysiological systems, ex vivo tissues, and computational models, illustrating how clearly defined contexts of use enable these approaches to strengthen overall WoE assessments. Key scientific and regulatory considerations for broader NAM adoption will also be discussed, including establishing scientific validity, data quality and standardization, transparent communication of limitations, reusable data infrastructure, and continued engagement with regulatory agencies through meaningful use cases.

Part 2: Weight of Evidence Approaches for DART Assessments of Oligonucleotides: Current Reality and Future Considerations

This webinar will focus on the regulatory expectations regarding the developmental and reproductive toxicity (DART) assessment of oligonucleotide-based therapeutics (ONTs) as reflected in current guidance documents, highlighting some of the challenges in conducting these studies, and the potential for using weight-of-evidence assessments in lieu of animal studies for some, or all, DART endpoints. The 2021 PMDA guideline and 2024 draft FDA guidance on the nonclinical safety assessment of oligonucleotides both refer to ICH S5(R3) regarding expectations for DART assessment. While S5(R3) does support the use of WoE in DART assessment, this is generally in the context of establishing human risk (obviating the need to conduct one or more in vivo assessments), not in supporting a conclusion of low or negligible human risk. ONTs, however, have attributes that could conceivably allow for greater use of WoE assessments in establishing negligible risk for DART in some instances, potentially reducing or eliminating the need for product-specific DART assessments. This webinar will discuss these attributes and potential scenarios that would benefit from an ONT-specific application of WoE to the DART assessment.