硝子体内バイオセラピューティックの開発における動物使用削減の機会

A retrospective analysis of 15 intravitreal biotherapeutic programs was conducted to identify strategies for reducing animal use in ocular drug development. Three main opportunities were found: (1) reconsidering the necessity of chronic toxicology studies, (2) omitting studies or groups involving systemic routes of administration, and (3) reducing or removing recovery groups. Twelve programs included both ≤13-week and ≥26-week repeat dose intravitreal studies, enabling direct comparison of outcomes. Chronic studies did not reveal new clinically relevant toxicities beyond those identified in shorter studies. The primary difference was a higher incidence and severity of anti-drug antibody-associated late-onset ocular inflammation in chronic studies, sometimes resulting in secondary tissue damage and premature euthanasia, but without affecting human risk assessment or clinical monitoring. Systemic exposure margins were generally sufficient with intravitreal dosing alone, suggesting that additional systemic studies are often unnecessary. Recovery of findings could frequently be predicted using a weight-of-evidence approach, supporting the reduction or removal of recovery groups. Overall, the analysis demonstrates that streamlined development programs and study designs can support regulatory decision-making for ocular biotherapeutics, reducing animal usage without compromising patient safety. These recommendations align with current regulatory trends and emphasize the importance of scientific rationale in nonclinical study design.