Modelling and simulation (M&S) of clinical data, e.g. pharmacokinetic, pharmacodynamic
and clinical endpoints, is a useful approach for more efficient interpretation of
collected data and for extrapolation of knowledge to the entire target population.
This type of documentation is included in the majority of marketing authorization
applications for new medicinal products. This article summarizes the current status
of regulatory review with respect to the role of M&S in Europe from the perspective
of the Swedish Medical Products Agency. At present, regulatory bodies in Europe encourage
the application of the M&S approach during drug development. However, there is a lack
of consensus and transparent guidance documents. The main regulatory usage is in the
evaluation of dose choices in sub-populations and as support for the dosing regimen
in general. The regulatory review of conestat alfa illustrates how the dose recommendation
was revised during the approval procedure based on M&S information. A survey of marketing
authorization applications for new medicinal products approved in 2010 revealed that
the use of the information gained from M&S documentation varies with respect to both
regulatory review and the applicants' presentation of the data in the submitted dossier.
Increased utilization and broadened application of M&S is anticipated in pharmaceutical
development, where one area of focus is medicines for paediatric patients. Accordingly,
the regulatory agencies will need to increase their capability to assess and utilize
this type of information, and an interactive process among regulatory agencies is
warranted to provide more unified regulatory assessment and guidance. Moreover, applicants
are encouraged to expand on the usage of exposure-response models to map the systemic
exposure range that yields safe and efficacious treatment and to improve the presentation
of the gained knowledge in summary documents of the marketing authorization applications.