Module 9 2024

03/09/2024

First-in-Human Studies -Preclinical Considerations

• Species Selection • Relevant species need to express the desired epitope and have similar tissue-cross reactivity profile as human tissues • Transgenic animals and homologous proteins • Activity • In vitro assays can assist to evaluate effects related to clinical activity, can be useful to predict in vivo activity, in particular sensitivity to the product • Pharmacokinetics(PK)/Pharmacodynamics (PD) • Determination of the no observed adverse event level (NOAEL) • Safety Pharmacology/Toxicology/Immunogenicity • Any target organ toxicity that may require monitoring in the clinical trial • Formation of anti-drug antibodies (ADAs) and correlation with pharmacological/toxicological changes

The Organisation for Professionals in Regulatory Affairs

ICH S6 (R1) – preclinical safety evaluation of biotechnology-derived pharmaceuticals ICH M3 (R2) – nonclinical safety studies for the conduct of human clinical trials and marketing authorisation for pharmaceuticals

9

PK/PD Modelling

E max

C max

AUC

EC 50

E 0

T max

The Organisation for Professionals in Regulatory Affairs

10

5