title: The simcyp population based simulator: architecture, implementation, and quality assurance.
abstract: Developing a user-friendly platform that can handle a vast number of complex physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) models both for conventional small molecules and larger biologic drugs is a substantial challenge. Over the last decade the Simcyp Population Based Simulator has gained popularity in major pharmaceutical companies (70% of top 40 - in term of R&D spending). Under the Simcyp Consortium guidance, it has evolved from a simple drug-drug interaction tool to a sophisticated and comprehensive Model Based Drug Development (MBDD) platform that covers a broad range of applications spanning from early drug discovery to late drug development. This article provides an update on the latest architectural and implementation developments within the Simulator. Interconnection between peripheral modules, the dynamic model building process and compound and population data handling are all described. The Simcyp Data Management (SDM) system, which contains the system and drug databases, can help with implementing quality standards by seamless integration and tracking of any changes. This also helps with internal approval procedures, validation and auto-testing of the new implemented models and algorithms, an area of high interest to regulatory bodies.
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.
authors.forename: Masoud
authors.initials: M
authors.lastname: Jamei
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Marciniak
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.
authors.forename: Duncan
authors.initials: D
authors.lastname: Edwards
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.
authors.forename: Kris
authors.initials: K
authors.lastname: Wragg
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.
authors.forename: Kairui
authors.initials: K
authors.lastname: Feng
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.
authors.forename: Adrian
authors.initials: A
authors.lastname: Barnett
authors.affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK ; Centre of Applied Pharmacokinetic Research, the School of Pharmacy and Pharmaceutical Sciences, the University of Manchester, Manchester, UK.
authors.forename: Amin
authors.initials: A
authors.lastname: Rostami-Hodjegan
keywords: ADME; Model based drug development; Pharmacodynamics; Pharmacokinetics; Physiologically-based pharmacokinetic; Simcyp