Module 9 2021

22/03/2021

Preclinical testing of biologics Post-FIH Testing

ReproTox Study : • Used primarily to provide advice to accidentally pregnant woman on drug • If two species used in tox programme, typically uses rat. If single species, then uses primate • Assesses pre and post-natal development and developmental toxicities • Treatment of pregnant female primate from gestation D20 to natural birth • Dosing stops at birth but dam and pup assessed for 3-6 months post-birth • Assess infant key organ system development as defined by pharmacology and any other concerns arising during development of molecule • Design usually agreed at EOP2 meeting with FDA

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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Preclinical testing of biologics Post-FIH Testing

Genotoxicity : • Genotoxicity not relevant as proteins don’t normally interact directly with DNA • Concern may arise if the mAb interacts with proteins in DNA synthesis or maintenance but classic genotoxicity tests unlikely to be suitable • Should be considered if mAb is conjugated – linker? Carcinogenicity : • Specific studies rarely performed for mAbs or other biologics • Carcinogenicity Assessment Document (CAD) uses a weight of evidence approach based on MoA • Submitted to Health Authorities at EOP2 meetings • FDA approve; EMA acknowledge

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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