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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.


Related in: MedlinePlus

Simcyp screen representing a PD link response unit: input from the previous unit can go through a Link transform model and then feed into either a growth/progression/turnover model, survival model or custom scripted model.
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Fig5: Simcyp screen representing a PD link response unit: input from the previous unit can go through a Link transform model and then feed into either a growth/progression/turnover model, survival model or custom scripted model.

Mentions: Two types of PD Response Unit have so far been implemented: the PD Basic Unit (Version 11) and the PD Link Unit (Version 12). Just one PD Basic Unit is all that is needed to represent elementary PD (such as a Hill model or Emax response) and a PBPK compartment providing a concentration or amount driving the response can be selected from a simple dropdown list; thus a specialist in metabolism or biopharmaceutical science does not need further training to add a quick preview of possible PD effects, consequent to some simulated PK interaction or a formulation change. Nevertheless, with a PD Link Unit attached, Simcyp extends the offered response models to include many indirect models via link models well known to pharmacometricians and PK/PD modellers, combining concepts from Generalized Linear Models (McCullagh and Nelder 1989), Survival Analysis (Kalbfleisch and Prentice 2002), empirical disease progression (Chan and Holford 2001) and “Indirect Physiological PK/PD” (Dayneka et al. 1993). Figure 5 shows the screen representing the PD Link Unit.Figure 5


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)

Simcyp screen representing a PD link response unit: input from the previous unit can go through a Link transform model and then feed into either a growth/progression/turnover model, survival model or custom scripted model.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig5: Simcyp screen representing a PD link response unit: input from the previous unit can go through a Link transform model and then feed into either a growth/progression/turnover model, survival model or custom scripted model.
Mentions: Two types of PD Response Unit have so far been implemented: the PD Basic Unit (Version 11) and the PD Link Unit (Version 12). Just one PD Basic Unit is all that is needed to represent elementary PD (such as a Hill model or Emax response) and a PBPK compartment providing a concentration or amount driving the response can be selected from a simple dropdown list; thus a specialist in metabolism or biopharmaceutical science does not need further training to add a quick preview of possible PD effects, consequent to some simulated PK interaction or a formulation change. Nevertheless, with a PD Link Unit attached, Simcyp extends the offered response models to include many indirect models via link models well known to pharmacometricians and PK/PD modellers, combining concepts from Generalized Linear Models (McCullagh and Nelder 1989), Survival Analysis (Kalbfleisch and Prentice 2002), empirical disease progression (Chan and Holford 2001) and “Indirect Physiological PK/PD” (Dayneka et al. 1993). Figure 5 shows the screen representing the PD Link Unit.Figure 5

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.


Related in: MedlinePlus