TY - JOUR
KW - Monoclonal antibodies
KW - new approach methodologies
KW - Non-human primate toxicity
KW - Nonclinical safety assessment
KW - Regulatory toxicity
KW - Repeat-dose toxicity studies
AU - Yanning Hao
AU - Nakissa Sadrieh
AB - A retrospective analysis of nonclinical study reports submitted in regulatory packages of FDA-approved mAbs, excluding antibody–drug conjugates, was conducted. This analysis was limited to the period between January 2020 and April 2025. For highly target-specific mAbs, the incremental contribution of long-term animal studies to regulatory safety assessment was evaluated. FDA review documents were examined to assess study duration, species selection, and the regulatory relevance of toxicological findings to determine whether long-term in vivo studies submitted in Biologics License Applications (BLAs) identified new safety signals beyond those seen in shorter-term studies. Among the mAbs evaluated, long-term NHP toxicity studies were included in more than half of the development programs but rarely altered regulatory conclusions regarding human risk. Additional findings were predominantly attributable to known pharmacology or species-specific immunogenicity and generally did not affect no-observed-adverse-effect-level (NOAEL) determination, clinical trial design, or labeling. No long-term study in this analysis identified unanticipated off-target toxicities that fundamentally altered the overall safety assessment. These results are consistent with principles articulated in the FDA's 2025 Roadmap for Reducing Animal Testing in Preclinical Safety Studies and provide descriptive information relevant to recent draft FDA guidance on streamlined nonclinical safety studies for monospecific mAbs.
BT - Regulatory Toxicology and Pharmacology
DA - 2026-09-01
DO - 10.1016/j.yrtph.2026.106124
N2 - A retrospective analysis of nonclinical study reports submitted in regulatory packages of FDA-approved mAbs, excluding antibody–drug conjugates, was conducted. This analysis was limited to the period between January 2020 and April 2025. For highly target-specific mAbs, the incremental contribution of long-term animal studies to regulatory safety assessment was evaluated. FDA review documents were examined to assess study duration, species selection, and the regulatory relevance of toxicological findings to determine whether long-term in vivo studies submitted in Biologics License Applications (BLAs) identified new safety signals beyond those seen in shorter-term studies. Among the mAbs evaluated, long-term NHP toxicity studies were included in more than half of the development programs but rarely altered regulatory conclusions regarding human risk. Additional findings were predominantly attributable to known pharmacology or species-specific immunogenicity and generally did not affect no-observed-adverse-effect-level (NOAEL) determination, clinical trial design, or labeling. No long-term study in this analysis identified unanticipated off-target toxicities that fundamentally altered the overall safety assessment. These results are consistent with principles articulated in the FDA's 2025 Roadmap for Reducing Animal Testing in Preclinical Safety Studies and provide descriptive information relevant to recent draft FDA guidance on streamlined nonclinical safety studies for monospecific mAbs.
PY - 2026
EP - 106124
T2 - Regulatory Toxicology and Pharmacology
TI - FDA CDER analysis of non-human primate (NHP) data in monoclonal antibody (mAb) development to support the streamlining of nonclinical safety studies
UR - https://www.sciencedirect.com/science/article/pii/S0273230026000978
VL - 170
Y2 - 2026-05-11
SN - 0273-2300
ER -