The IVIVC object provides an organized environment in which to build and manipulate IVIVC models. The IVIVC object also estimates the UIR for one or more profiles given an IV (bolus), infusion, or oral formulation. The IVIVC object supports specification and running all or a subset of operations required to create an IVIVC model, validate it, and use it to make PK predictions.
Note that in vitro and in vivo data must be in separate datasets. Individual functions are specified and run in the separate panels and tabs of the IVIVC object.
The IVIVC object contains several sub-workflows or steps. These steps can be executed individually during the IVIVC modeling, i.e., it is not necessary to execute the entire object during the IVIVC modeling process. When an IVIVC object is executed, however, all IVIVC steps will run.
Note: If the data for a step is fed into the workflow (e.g., through a data link), executing the IVIVC step from the step’s properties panel will not execute the source feeder and can lead to a “lack of source” error. If this occurs, execute the full IVIVC workflow object to ensure that sources are executed prior to the IVIVC workflow validation.
In vitro data, in vivo data, and dosing data should be similarly scaled for a successful IVIVC (see the “IVIVC workflow example” for an example of a full IVIVC workflow). Phoenix IVIVC uses a two-stage Level A correlation, where deconvolution is followed by a linear correlation model representing a relationship between in vitro dissolution and in vivo input rate. The in vitro dissolution and in vivo input curves should be directly superimposable or be made superimposable by using a scaling factor (see FDA 1997 Guidance on IVIVC) or by changing units to convert data appropriately. For example, specifying in vivo dosing as a very large value will result in large input rates from deconvolution. If dissolution data is then given in small-scale numbers, Level A IVIVC may fail to produce accurate results due to numerical instabilities, particularly Convolution in the prediction stage may fail to produce non-zero concentrations. The dosing data in this case should be scaled by using larger units (e.g., convert ng to mg) in order for the input rates to be consistently scaled with the dissolution data.
Use one of the following to add the object to a Workflow:
Right-click menu for a Workflow object: New > IVIVC > IVIVC.
Main menu: Insert > IVIVC > IVIVC.
Right-click menu for a worksheet: Send To > IVIVC > IVIVC.
To view the object in its own window, select it in the Object Browser and double-click it or press ENTER. All instructions for setting up and execution are the same whether the object is viewed in its own window or in a Phoenix view.
This section contains the following topics:
InVitro setup
InVitro Formulation mapping panel
InVitro Estimates mapping panel
InVivo setup
Correlation Estimates mapping panel
Prediction setup
Prediction Dosing mapping panel
Prediction Estimates mapping panel
Legal Notice | Contact Certara
© Certara USA, Inc. All rights reserved.