Integrating Regulatory Writing and Modeling and Simulation into the Drug Development Process

As the adoption of modeling and simulation for drug development expands, so too does the need to integrate it into the documentation submitted to regulatory agencies. Model-informed drug development (MIDD) includes physiologically-based pharmacokinetic (PBPK) and pharmacokinetic-pharmacodynamic (PK/PD) modeling. This methodology is emerging as not just an internal decision-making aid to reduce expenses and time, but also as an ethical imperative to optimize the number of subjects exposed to newly tested therapies.

The use of MIDD to bridge traditional studies with robust modeling that integrates prior knowledge has led to improved predictions, rationale, and justification for formulation, dosing, and study design decisions. There are also recent examples of regulatory agencies accepting it in place of clinical trials for some drug-drug interactions (Shepard et al. 2015) and thorough QT studies (Polak et al, 2015), thus reducing the number of subjects exposed to investigational treatments. Indeed, using MIDD to avoid performing a clinical study can easily save six months to a year and $500K to $1M. There is growing confidence among health authorities that MIDD strengthens traditional approaches by enabling more comprehensive evaluation, minimizing the need for certain studies, and, ultimately, lower risks to patients. This trend has been confirmed through numerous regulatory guidance documents (US Food and Drug Administration, 2012) and publications (Sinha et al. 2014).