Model-Informed Drug Discovery and Development: Current Industry Good Practice and Regulatory Expectations and Future Perspectives

Abstract

Good practices around model-informed drug discovery and development (MID3) aim to improve the implementation, standardization, and acceptance of these approaches within drug development and regulatory review. A survey targeted to clinical pharmacology and pharmacometric colleagues across industry, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA) was conducted to understand current and future roles of MID3. The documented standards were generally affirmed as a "good match" to current industry practice and regulatory expectations, with some identified gaps that are discussed. All have seen at least a "modest" step forward in MID3 implementation associated with greater organizational awareness and share the expectation for a future wider use and impact. The priority within organizations was identified as a limitation with respect to the future of MID3. Finally, potential solutions, including a global overarching MID3 regulatory guideline, to facilitate greater acceptance by industry and regulatory decision makers are discussed.

Figure 1

Overview of six aspects ((a) practice, (b) implementation, (c) impact, (d) approaches, (e) organizational priority, and (f) enablers/disablers) that were covered in the questionnaire in support of the American Conference on Pharmacometrics 8 symposium session on “Model‐Informed Drug Discovery and Development (MID3): Industry Good Practice, Regulatory Expectations, and Technical Gaps.” References to the specific questions and the result tables and figures are provided. R&D, research and development.

Figure 2

Industry response to Q8 (aspect d): To what extent do the following themes feature in the of strategic plans in your organization? In this overview, the percentage of strategic plans that reference each of the application themes is shown as distribution across the 18 responding companies responding to this question. Compared with other areas, most companies focus on pharmacokinetics in their Model‐Informed Drug Discovery and Development strategic plans.

Figure 3

Response to Q12 (aspect d): How are the different approaches viewed with respect to being a solution with respect to making research and development (R&D) and/or regulatory review more efficient? Each modeling approach is assessed with respect to maturity of the methodology and the potential to increase the R&D efficiency. ¹The US Food and Drug Administration (FDA) actual textual response on systems pharmacology was: “this is a growing methodology whose exact potential is unknown at this time and the EMA share this viewpoint.” EMA, European Medicines Agency; PK/PD, pharmacokinetic/pharmacodynamic.

Figure 4

Graphical representation of disablers and enablers to growth in future impact of Model‐Informed Drug Discovery and Development (MID3; aspect f). Left: Q14, What disablers are most likely to hamper the growth in the degree of impact on MID3 on decision making over the next 5 years? Right: Q15, What enablers are most likely to aid the growth in the degree of impact of MID3 on decision making over the next 5 years? EMA, European Medicines Agency; FDA, US Food and Drug Administration; R&D, research and development.