EMA proposes new guideline on model-informed drug development
The European Medicines Agency (EMA) is planning to issue a draft guideline on the reporting and evaluation of new mechanistic models to encourage their broader use in model informed drug development (MIDD), according to a concept paper published on Friday.EMA said the new guideline will incorporate advancements in the field and that current guidance on MIDD is lacking; the sole guidance in his area is the guideline on physiologically based pharmacokinetic (PBPK) modelling and simulation which was adopted by EMA’s Committee for Medicinal Products (CHMP) in 2018.
The forthcoming guideline will cover a comprehensive range of modeling such as PBPK, physiologically based biopharmaceutics (PBBM), and quantitative systems pharmacology (QSP) models.
A PBPK model is a mathematical model that simulates the concentration of a drug in tissues and blood over time by measuring the rate at which the drug is absorbed into the body while a PBBM model is a subset of PBPK models that quantifies the relationship between drug product quality attributes and the clinically relevant limits specified for their quality control. QSP models are used to illustrate how therapeutic interventions impact a disease.
EMA stated that mechanistic models are being used more frequently throughout all stages of drug research and development. These models support comparability assessments between different formulations and manufacturing processes, assist in dose selection, inform study design, evaluate benefit-risk assessments, and contribute to labeling decisions.
Yet the key metrics and components for assessing mechanistic models are unclear, which leads to their underuse in drug development.
The paper states that “the inherent complexity of the mechanistic models as well as the type of data and methodologies used for their development and evaluation, mandate specific considerations for regulatory assessment and reporting compared to more empirical models, such as population pharmacokinetics, pharmacokinetic-pharmacodynamic and exposure-response models.”
The forthcoming guideline will discuss the different types and objectives of mechanistic models, applying the MIDD evidence assessment framework on mechanistic models, quantifying uncertainty, model structure and identifiability, regulatory requirements for data quality and relevance, developing and evaluating the model, and best practices for reporting results of mechanistic modelling.
The International Council for Harmonization (ICH) issued draft guidance in November 2024 that addressed several areas of MIDD, including population pharmacokinetics, PBPK, dose-exposure-response, and model-based meta-analysis. (RELATED: ICH releases draft GCP annex, MIDD guideline, Regulatory Focus 18 November 2024)
The deadline for commenting is 31 May 2025, and EMA is seeking input from other regulators. The agency plans to complete the draft guideline sometime in 2026.
Concept paper
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