Module 9 2021

22/03/2021

Preclinical testing of biologics Assessing Clinical Risk

Calculate the Therapeutic Index – No magic correct number!

Proceed into Clinical Studies (with clinical monitoring)

Yes

No

STOP (or reassess therapeutic dose?)

Increasing Doses Planned in Human

Toxicity observed in nonclinical studies

Larger TI

Lowest NOAEL from any study

Drug X

Smaller TI

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

Chronic Repeat Dose Toxicity Study : • Longest duration toxicity study is 26 weeks dosing (supports lifetime dosing) • Timing triggered by clinical dosing duration – could be very early or very late • Assessment s generally mimic those for the first FIH-enabling tox study but also allows focus on potential or known toxicities • Uses sexually mature males and females to allow assessment of potential impact on fertility • Menstrual cycling and hormone monitoring • Testicular & sperm evaluation (weight, size, sperm motility, morphology etc)

Preclinical testing of Biologics – March 22 nd 2021

The Organisation for Professionals in Regulatory Affairs

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