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The simcyp population based simulator: architecture, implementation, and quality assurance.

Jamei M, Marciniak S, Edwards D, Wragg K, Feng K, Barnett A, Rostami-Hodjegan A - In Silico Pharmacol (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.

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.

No MeSH data available.


The chronology of expansion of the Simulator features from 2001–2013 under the Simcyp Consortium guidance. The development started with static metabolic drug-drug interaction calculations then dynamic drug-drug interaction models followed by whole body PBPK and so on.
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Fig1: The chronology of expansion of the Simulator features from 2001–2013 under the Simcyp Consortium guidance. The development started with static metabolic drug-drug interaction calculations then dynamic drug-drug interaction models followed by whole body PBPK and so on.

Mentions: Since its inception the Simcyp Simulator has been developed in conjunction with a Consortium of major pharmaceutical companies, who share pre-competitive information and provide guidance on the addition of further capabilities and features. The usage and functionality of the Simulator is further enhanced by collaborations with drug regulatory bodies and academic centres of excellence worldwide. Every year a new version of the Simulator with new features is released. A rough chronological order of the development of models and databases within the Simulator is shown in Figure 1. The Simulator development started with simple static drug-drug interaction calculations (“Static CYP DDI” section of Figure 1). This was expanded to dynamic models and the minimal PBPK model that was subsequently expanded to full PBPK models. The recent developments include handling of therapeutic proteins, the ability to add custom PD scripts and to model time-variant physiology in paediatric population as the subjects grow and in pregnant women over the duration of pregnancy.Figure 1


The simcyp population based simulator: architecture, implementation, and quality assurance.

Jamei M, Marciniak S, Edwards D, Wragg K, Feng K, Barnett A, Rostami-Hodjegan A - In Silico Pharmacol (2013)

The chronology of expansion of the Simulator features from 2001–2013 under the Simcyp Consortium guidance. The development started with static metabolic drug-drug interaction calculations then dynamic drug-drug interaction models followed by whole body PBPK and so on.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230310&req=5

Fig1: The chronology of expansion of the Simulator features from 2001–2013 under the Simcyp Consortium guidance. The development started with static metabolic drug-drug interaction calculations then dynamic drug-drug interaction models followed by whole body PBPK and so on.
Mentions: Since its inception the Simcyp Simulator has been developed in conjunction with a Consortium of major pharmaceutical companies, who share pre-competitive information and provide guidance on the addition of further capabilities and features. The usage and functionality of the Simulator is further enhanced by collaborations with drug regulatory bodies and academic centres of excellence worldwide. Every year a new version of the Simulator with new features is released. A rough chronological order of the development of models and databases within the Simulator is shown in Figure 1. The Simulator development started with simple static drug-drug interaction calculations (“Static CYP DDI” section of Figure 1). This was expanded to dynamic models and the minimal PBPK model that was subsequently expanded to full PBPK models. The recent developments include handling of therapeutic proteins, the ability to add custom PD scripts and to model time-variant physiology in paediatric population as the subjects grow and in pregnant women over the duration of pregnancy.Figure 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Simcyp Limited (a Certara Company), Blades Enterprise Centre, John Street, Sheffield, S2 4SU UK.

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.

No MeSH data available.