The enhanced pre- and postnatal development study for monoclonal antibodies

Area of Science:

• Pharmacology and Toxicology
• Developmental and Reproductive Toxicology

Background:

• New scientific knowledge and guideline changes (ICH M3(R2), ICH S6(R1)) necessitate updated preclinical study designs.
• Experiences from biopharmaceutical preclinical development drove the evolution of study designs.
• The enhanced pre- and postnatal development (ePPND) study is specifically for biopharmaceuticals, not conventional small molecule drugs.

Purpose of the Study:

• To adapt standard embryo-fetal development studies for evaluating drug effects in newborns and infants.
• To provide guidance on implementing the ePPND study design.
• To detail methods for assessing drug safety during the pre- and postnatal periods.

Main Methods:

• Utilizes the cynomolgus monkey as the relevant nonhuman primate model.
• Incorporates monitoring of menstrual cycles for timed pregnancies and ultrasound for pregnancy confirmation.
• Includes morphometric measurements, in vivo skeletal examination, and comprehensive infant evaluations.

Main Results:

• The ePPND design shifts key developmental assessments from the fetus to the newborn/infant.
• ICH S6(R1) guideline (reached step 5 in June 2011) provides detailed recommendations for ePPND studies.
• The study outlines specific protocols for infant assessments, including neurobehavioral and immune system evaluations.

Conclusions:

• The ePPND study design is a crucial adaptation for preclinical safety assessment of biopharmaceuticals.
• This approach addresses critical developmental windows post-conception.
• The cynomolgus monkey model and detailed evaluation parameters support robust safety assessments.