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.

Introductory Chapter: The Modern-Day Drug Discovery

“…The observed data/evidence obtained during the developmental phase does not necessarily answer all the questions; thus the scope of MIDD is largely expanded with analysis of RWD to generate real-world evidence (RWE) to resolve these unanswered questions. Although RWD is obtained under less-controlled settings requiring proper interpretation of the findings, it should be considered as an attractive tool appealing for MIDD [42].…”

Iberoamerican Pharmacometrics Network Congress 2018 Report: Fostering Modeling and Simulation Approaches for Drug Development and Regulatory and Clinical Applications in Latin America

“…Pharmacometrics and systems pharmacology have emerged in the developed world and were established as new paradigms in drug discovery and development. Model‐informed decisions are proved to reduce economic costs and favor ethics, focusing on optimizing clinical trial designs as well as on extracting the meaningful and relevant information from the data, far beyond statistically significant P values . The application of this quantitative framework for dose optimization and therapeutic innovation is on its way to change the rationale in which drugs are used in the clinical setting.…”

“…Model-informed decisions are proved to reduce economic costs and favor ethics, focusing on optimizing clinical trial designs as well as on extracting the meaningful and relevant information from the data, far beyond statistically significant P values. [1][2][3][4] The application of this quantitative framework for dose optimization and therapeutic innovation is on its way to change the rationale in which drugs are used in the clinical setting. As stated before by Pillai et al, 5 for the developing world these approaches represent an "opportunity to bring modern methods into play" and thus push forward the development of drugs, therapeutic strategies, and basic research in pharmacology and pharmaceutical innovation in our countries.…”

MID3: Mission Impossible or Model‐Informed Drug Discovery and Development? Point‐Counterpoint Discussions on Key Challenges

“…Reviews of the literature and standard practice across organizations have generally affirmed the documented standards, acknowledged the modest improvements in organizational awareness, and set expectations for future wider use and impact, and have also highlighted areas for further improvement. 8 There have been significant developments in the regulatory domain, with model-informed drug development (MIDD) being formally noted in the Prescription Drug User Fee Act VI, highlighting model-informed decisions made in the areas of extrapolation and dose optimization, inference about efficacy, clinical trial design, and informing policy. 9 Additionally, the US Food and Drug Administration (FDA) has implemented a new Model-Informed Drug Development Paired Meeting Pilot Program.…”