The developmental toxicity testing of biologics

Area of Science:

• Pharmacology and Toxicology
• Drug Development
• Preclinical Research

Background:

• Biologic drugs possess distinct characteristics compared to small molecules, offering significant benefits to both drug developers and patients.
• Preclinical drug development necessitates careful consideration of developmental toxicity testing requirements and optimal timing.

Purpose of the Study:

• To evaluate the selection criteria for appropriate animal test systems in preclinical developmental toxicity testing for biologic drugs.
• To propose an optimized study design for developmental toxicity testing when nonhuman primates are the most relevant species.

Main Methods:

• Comparative analysis of biologic drugs versus small molecules in drug development.
• Assessment of pharmacodynamic cross-reactivity in potential animal test systems.
• Evaluation of conventional rodent/non-rodent species versus nonhuman primates for functional relevance.
• Consideration of extended study designs, such as the extended one-year repeat-dose nonclinical toxicity study (ePPND), for nonhuman primate studies.

Main Results:

• The choice of test system is critical for accurate developmental toxicity assessment, requiring pharmacodynamic activity comparable to humans.
• While conventional species may suffice, nonhuman primates are often the only relevant models for certain biologic drugs.
• The extended nonclinical toxicity study (ePPND) is proposed as the default study design when nonhuman primates are utilized.

Conclusions:

• Utilizing relevant species, such as nonhuman primates with an ePPND design, ensures appropriate toxicity screening for biologic drugs.
• This approach effectively balances the need for comprehensive safety evaluation with the goal of reducing overall animal usage in preclinical development.