Model-informed precision dosing (MIPD) has become synonymous with modern approaches forindividualizing drug therapy, in which the characteristics of each patient are considered as opposedto applying a one-size-fits-all alternative. This review provides a brief account of the currentknowledge, practices, and opinions on MIPD while defining an achievable vision for MIPDin clinical care based on available evidence.We begin with a historical perspective on variabilityin dose requirements and then discuss technical aspects of MIPD, including the need for clinicaldecision support tools, practical validation, and implementation of MIPD in health care.Wealso discuss novel ways to characterize patient variability beyond the common perceptions of geneticcontrol. Finally, we address current debates on MIPD from the perspectives of the new drugdevelopment, health-care economics, and drug regulations. ; QC 20201012
This summary workshop report highlights presentations and over-arching themes from an October 2011 workshop. Discussions focused on best practices in the application of biopharmaceutics in oral drug product development and evolving bioequivalence approaches. Best practices leverage biopharmaceutic data and other drug, formulation, and patient/disease data to identify drug development challenges in yielding a successfully performing product. Quality by design and product developability paradigms were discussed. Development tools include early development strategies to identify critical absorption factors and oral absorption modeling. An ongoing theme was the desire to comprehensively and systematically assess risk of product failure via the quality target product profile and root cause and risk analysis. However, a parallel need is reduced timelines and fewer resources. Several presentations discussed applying Biopharmaceutics Classification System (BCS) and in vitro–in vivo correlations in development and in post-development and discussed both resource savings and best scientific practices. The workshop also focused on evolving bioequivalence approaches, with emphasis on highly variable products (HVDP), as well as specialized modified-release products. In USA, two bioequivalence approaches for HVDP are the reference-scaled average bioequivalence approach and the two-stage group-sequential design. An adaptive sequential design approach is also acceptable in Canada. In European Union, two approaches for HVDP are a two-stage design and an approach to widen Cmax acceptance limits. For some specialized modified-release products, FDA now requests partial area under the curve. Rationale and limitations of such metrics were discussed (e.g., zolpidem and methylphenidate). A common theme was the benefit of the scientific and regulatory community developing, validating, and harmonizing newer bioequivalence methodologies (e.g., BCS-based waivers and HVDP trial designs).
