Spring Intro 2023

Mike Kelly

Exposure Response (PK/PD) Modelling

 In the early 2000’s the FDA initiated their Critical Path Initiative  They identified systematic failure within Drug Development Programs and reported that there needed to be a paradigm shift to improve the efficiency of clinical drug development ● Better compounds i.e. less failure later in development due to lack of efficacy, variability in response, inappropriate PK, poor absorption ● Reduced timelines  FDA propose utilization of model-based drug development to improve drug development and decision making including ● Exposure-response modeling (PK/PD) ● Disease modeling - relationship between patient characteristics, biomarkers and the time course of disease  Maximize and integrate data to support and improve decisions ● Selection and justification of dosing regimen ● Patient groups

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Clinical Application of Pharmacokinetics and Pharmacodynamics

Clinical Phase

Pharmacodynamics Pharmacokinetics

Phase 1 Safety

Yes Yes Yes

Yes Yes Yes

Tolerance

Phase II

Proof of concept

Dose finding

Yes

Yes

Phase III Pivotal trials

Efficacy/safety

Population PK

Phase IV Generic drugs

Possible

Yes Yes Yes

Biosimilars

Yes

Line extensions

Possible

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