The enhanced pre- and postnatal study for nonhuman primates: update and perspectives.

Area of Science:

• Pharmacology and Toxicology
• Developmental and Reproductive Toxicology
• Biopharmaceutical Preclinical Development

Background:

• New scientific knowledge and guideline changes (ICH M3(R2), ICH S6(R1)) necessitated updated preclinical study designs.
• Experiences from biopharmaceutical preclinical development drove the evolution of study designs.
• The enhanced pre- and postnatal (ePPND) study design is primarily for biopharmaceuticals, not traditional pharmaceuticals.

Purpose of the Study:

• To introduce and detail the enhanced pre- and postnatal (ePPND) study design.
• To explain how ePPND integrates embryofetal development (EFD) study elements into the postnatal phase.
• To highlight the relevance of ePPND for biopharmaceutical safety assessment, particularly monoclonal antibodies.

Main Methods:

• The ePPND design involves investigating key embryofetal development (EFD) elements in newborns and infants.
• Utilizes the cynomolgus monkey as the relevant nonhuman primate model.
• Incorporates recommendations from ICH S6(R1) guidelines for study conduct and parameters.

Main Results:

• The ePPND study design is presented as the preferred approach for monoclonal antibody development.
• ICH S6(R1) provides options for modified EFD and postnatal development (PPND) study concepts.
• Social housing was demonstrated as feasible for developmental toxicity studies in cynomolgus monkeys.

Conclusions:

• The ePPND design represents a significant advancement in preclinical safety testing for biopharmaceuticals.
• Compliance with ICH S6(R1) is essential for the proper conduct of ePPND studies.
• The cynomolgus monkey model is suitable for ePPND studies, with social housing being a viable option.