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Interview : Bernard Orlandini speaks about pharmacometrics and MBDD

PhinC Development published an interview of Bernard Orlandini, managing director, in the LifeScience e-novation newletter. Topic: "Pharmacometrics and Model-Based Drug Development (MBDD): two solid assets in Research and Development"

View the LifeScience e-novation newsletter.

 

  • In a few words, what are pharmacometrics and MBDD?


Pharmacometrics assemble all quantitative approaches to improve knowledge of studied compounds in clinical pharmacology.
Model-Based Drug Development (MBDD) is the integration of these approaches within the development process to build models that help to manage drug development. Hence, the term MBDD reflects an integrative, iterative and cross-cutting approach.

  • How did pharmacometrics and MBDD become integrated in drug development?


We can explain the development of this discipline by major inputs from biostatistics during the last two decades (Bayesian methods, simulations, optimization algorithms…), and by the development of modeling/simulation and database tools that contain more and more molecular, physiologic, pharmacokinetic, pharmacologic and physiopathologic models.
Furthermore, the radical shift of “big pharmas” practices in early stages, the rise of biotechnologies and the new regulatory requirements compel to optimize and valorize early drug development.

  • When can pharmacometrics intervene in drug development?


Henceforth, we are far beyond the only frame of pharmacokinetic analysis, or dose-exposure-response standards.
Initially, PK/PD population analysis was widely used in phases II & III clinical studies to make assessments when experimental data are difficult to collect (inaccessible population, overdose, sparse critical evaluation, lack of information on drug exposure).
Modeling & Simulation is presently more and more implemented from pre-clinical stages to optimize a lead, to forecast and consolidate results thanks to the emergence of new methods like PBPK modeling.

  • According to you, did the use of pharmacometrics become a key success factor in innovative drug development?


Yes, because this approach responds:
- to the structural change of the drug development process that has become less sequential (step by step) and more translational and integrated;

- to the need for reducing the risk of failure in clinical development and maximizing the probability of detecting target signs as early as possible;

- to time saving requirements by targeting more narrowly the need for animal experiments, and by optimizing clinical study design;

- properly to repositioning or reformulation questions.

  • Considering the increasingly demanding regulatory requirements for medicines, how can drug development based on pharmacometric simulation be an asset?


The FDA and the EMA actively encourage these approaches; this is certified by many initiatives and publications (e.g. The FDA “critical path” initiative).
I will add that health authorities are increasingly stringent with empirical justifications. Hence, it is essential for regulatory submissions to provide quantitative justification for rationalizing the development plan (study design, criteria of assessment, dosage…).
And finally, from an ethical point of view, the efficient use of Modeling and Simulation can help to reduce drug exposure as much as possible (using targeted animal experiments and optimized study designs).