Modelling and simulation: questions and answers

The European Medicines Agency's (EMA) provides an overview of its position on specific issues related to modelling and simulation in the form of questions and answers (Q&As).

Users should read the Q&As in conjunction with the relevant scientific guidelines.

The Committee for Medicinal Products for Human Use (CHMP) and the Paediatric Committee (PDCO) may seek the input of the Methodology Working Party (MWP) to address specific questions in relation to modelling and simulation.

The date after each question refers to when it was first published.


Model-based approaches for approval of alternative dosing regimens and routes of administration of (anti PD-1 and PD-L1) monoclonal antibodies

Recently, various posology changes for monoclonal antibodies such as change from body weight-based to flat dosing, change in dosing interval or in route of administration (and related formulation) relying on Model Informed Drug Development (MIDD) approaches have been issued as type II variations or line extensions. Moreover, there have been repeated requests directed to the scientific advice working party regarding the acceptability of model-based approaches for approval of new routes of administration (and related formulations) and posology of (approved) monoclonal antibodies. In particular, there have been several requests relating to anti-PD-1/PD-L1 monoclonal antibodies (mAbs). The purpose of this Q&A is to provide clarity on the acceptability of such approaches. The focus is on anti-PD-1/PD-L1 mAbs but the general principle applies to other mAbs as well.

The questions-and answers below address situations when modelling and simulations of pharmacokinetics (PK) and dose-exposure-response (D-E-R) relationships for efficacy and safety with or without additional clinical studies, can be acceptable to support such changes.


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