Module 9 2021

22/03/2021

PD CONSIDERATIONS

Endpoint may not need to be validated but must be relevant + show clear dose/concentration response relationship Occasionally may replace clinical trial

Steep part of dose respons e curve

May need to test at several doses

Response Dose

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PD CLINICAL ENDPOINTS: EU Guidelines

In certain cases, PK/PD studies may be sufficient to debmonstrate clinical comparability, provided that the following conditions are met: ● An accepted surrogate marker exists ● If not accepted surrogate must be relevant to pharmacological action showing clear dose-response or a concentration-response relationship: a single or multiple dose-exposure-response study at two or more dose levels may be sufficient to waive a clinical efficacy study. ● In exceptional cases, the confirmatory clinical trial may be waived if physicochemical, structural and in vitro biological analyses and human PK studies together with a combination of PD markers that reflect the pharmacological action and concentration of the active substance, can provide robust evidence for biosimilar comparability.

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