An industry perspective on current QSP trends in drug development

Abstract

2023 marks the 10th anniversary of Natpara's submission to the US FDA, which led to the first recorded regulatory interaction where a decision was supported by Quantitative and Systems Pharmacology (QSP) simulations. It had taken about 5 years for the timid QSP discipline to emerge as an effective Model-Informed Drug Development (MIDD) tool with visible impact in the pharmaceutical industry. Since then, the presence of QSP in the regulatory environment has continued to increase, to the point that the Agency reported 60 QSP submissions in 2020 alone, representing ~ 4% of their annual IND submissions [1]. What sort of industry mindset has enabled QSP to reach this level of success? How does QSP fit within the MIDD paradigm? Does QSP mean the same to Discovery and to Clinical Development projects? How do 'platforms' compare to 'fit-for-purpose' QSP models in an industrial setting? Can QSP and empirical Pharmacokinetic-Pharmacodynamic (PKPD) modelling be complementary? What level of validation is required to inform drug development decisions? This article reflects on all these questions, in particular addressing those audiences with limited line-of-sight into the drug industry decision-making machinery.

Keywords: MID3; MIDD; QSP; Quantitative systems pharmacology.

Fig. 1

Comparison of the progression in the number of annual QSP publications (according to PubMed, updated from [13]) vs. regulatory submissions reported by the US FDA [11, 12]. The arrow marks the time of the first recorded QSP-based regulatory submission. If the growth in publications is indeed approaching a plateau (see text), and the annual growth rates of regulatory submissions stayed the same since 2020, then the QSP activity and impact in late stages of industry has potentially reached the public domain levels