Release Notes - Pharsight

Pharsight ® WinNonlin ® 5.3 

Release Notes 

December 2009 

Contents 

Overview ......................................................................................................................................... 1 

What’s new in Version 5.3.............................................................................................................. 1 

Defects corrected in Version 5.3 ..................................................................................................... 3 

Known IVIVC issues in Version 5.3 .............................................................................................. 4 

Known issues in Version 5.3 .......................................................................................................... 6 

Overview 

The WinNonlin ® 5.3 release addresses certain defects and enhancement requests that have been 

identified since the release of WinNonlin ® 5.2.1. 

What’s new in Version 5.3 

Document Manager in Pharsight Knowledgebase Server allows users to delete multiple 

items at once (QC 1270): In WinNonlin 5.3, users can delete multiple items at once in the PKS 

Document Manager. Previously, users were limited to deleting one item at a time. 

The Equation Manager in the Multi-Transform tool expands to match wide column 

headers and lengthy cell values (QC 1515): In previous versions of WinNonlin, it was 

sometimes difficult to use the Equation Manager because the grid view displayed fixed column 

widths which could result in the inability to see full column names or cell contents. The column 

widths of the grid displayed in the Equation Manager now match the column width or data 

values found in the selected worksheet, whichever is longer, up to approximately 64 characters. 

Annotation column cells in workbooks now wrap text (QC 1776): In WinNonlin 5.3, 

workbook annotation column cells wrap text so long descriptions are easier to read. Loading 

Revision 0 Page 1 of 16 December 2009

WinNonlin ® 5.3 Release Notes What’s new in Version 5.3 

workbooks created in earlier versions of WinNonlin will also display these Annotation columns 

with the new wrap text formatting. 

Validation and prediction grids are now saved as separate workbooks (QC 1850): To 

improve compatibility with PKS Reporter, the IVIVC Wizard in WinNonlin 5.3 creates two new 

workbooks using the output in the validation and prediction grids in the IVIVC Wizard. The new 

workbooks are called "Validation Errors.pwo" and "Prediction Errors.pwo." 

Descriptive Statistics and the Table Wizard have a new standard deviation option (QC 

2407): Users who need to use the 68-95-99.7 rule to calculate standard deviations now have the 

option to do so in WinNonlin 5.3. The Descriptive Statistics module and the Table Wizard now 

have a Number of S(tandard)D(deviations) option. Also, the Descriptive Statistics module 

creates new confidence interval output, which is listed in the User’s Guide. 

IVIVC Wizard creates two new plots during deconvolution process (QC 2429): In 

WinNonlin 5.3, the IVIVC Wizard creates two new deconvolution plots, "Fa-Avg" and "Fa-Avg 

By Profile." Fa-Avg is Fabs (subject * formulation) grouped by subject with Fabs_avg 

(formulation) overlaid vs. time, and sorted by formulation. Fa-Avg By Profile is Fabs grouped by 

formulation vs. time, and sorted by profile. 

NOTE: If a user selects a data set that is already deconvolved and averaged, then these plots are 

not created. 

The IVIVC Wizard creates a new plot during the correlation phase (QC 2431): In 

WinNonlin 5.3, the IVIVC Wizard creates a plot showing Fdis vs. Fabs grouped by formulation. 

This new plot is called "Corr Abs vs. Diss." 

IVIVC correlation may be validated using mean-observed data (QC 2432): WinNonlin 5.3 

provides the option to calculate IVIVC %PE_AUC and Cmax values during the validation and 

prediction phases using predicted vs. mean-observed concentration-time data where arithmetic 

means are generated directly from the user-supplied observed data. 

WinNonlin 5.3 supports Microsoft Windows Vista (QC 2557): WinNonlin now supports the 

32-bit version of Windows Vista. 

WinNonlin 5.3 supports Microsoft Office 2007 (QC 2574): WinNonlin now supports Office 

2007. 

WinNonlin 5.3 uses the same licensing system as Phoenix 1.x (QC 2576): Earlier versions of 

WinNonlin were using version 6.0 of the Sentinel license management system. WinNonlin 5.3 

has been upgraded to use the same version as Phoenix 1.x, namely 8.1.1, of this system. 

WinNonlin 5.3 supports Microsoft Windows 7 (QC 2578, 2582): WinNonlin now supports 

64-bit and 32-bit versions of Windows 7. 


WinNonlin ® 5.3 Release Notes Defects corrected in Version 5.3 

WinNonlin 5.3 supports increased character names for study data (QC 2579, 2580): To 

support upcoming PKS 4.1 compatibility, WinNonlin supports using 40 character analyte names, 

50 characters route names, and 100 character formulation names. Shorter names are still 

supported by WinNonlin accessing versions of PKS prior to 4.1. 

Users can save IVIVC projects to PKS when the IVIVC wizard is open (QC 2581): In 

WinNonlin 5.3, users can save IVIVC files to PKS, including the .ivc project file. Previously, 

users could not save IVIVC projects to PKS when the IVIVC wizard was open. Now users can 

save scenarios to and load scenarios from PKS with the wizard open. This allows users to save 

IVIVC projects to PKS without saving them to a local disk first, thereby maintaining FDA 21 

CFR Part 11 compliance by creating a complete audit history for IVIVC projects. 

Defects corrected in Version 5.3 

Missing values in a data set affected KS_pvalue in Descriptive Statistics (QC 2486): In 

previous versions of WinNonlin, if a user performed descriptive statistics on a data set that had 

no zero or negative values, and if missing values were added to the data set, then the KS_pvalues 

changed when the output worksheet was refreshed. This is corrected in WinNonlin 5.3. 

Previous versions of WinNonlin required manual inclusion of registry entries so SSL 

(Secure Sockets Layer) would work (QC 2519): To get SSL in WinNonlin versions 5.0 

through 5.2.1 to work properly, users had to update the registry settings for both httpstream3 and 

httpstream4. This problem is corrected in WinNonlin 5.3, so users no longer have to take extra 

steps to get SSL to work. 

WinNonlin froze when saving a PWO file (QC 2535): This problem could occur when using 

WinNonlin after installing a new print driver. WinNonlin 5.3 corrects the problem by forcing an 

update of the file TTF16.OCX when WinNonlin is installed. 

NOTE: If a computer has PKS Reporter installed and WinNonlin 5.3 is used to remove a preexisting 

version of WinNonlin but is not re-installed, PKS Reporter is rendered inoperative. To 

correct this, install WinNonlin 5.3 on the computer. 

Table Wizard incorrectly sorted text cross variables (QC 2537): If a column containing text 

was selected as a cross variable, the Table Wizard did not correctly create the table. This is 

corrected in WinNonlin 5.3. 

Numeric subject IDs were incorrectly sorted and plotted by the IVIVC Wizard (QC 2545, 

CRM 64300): In previous versions of WinNonlin, the IVIVC Wizard sorted numeric subject 

data as text, so subjects 01 and 11 would be displayed before 02. This is corrected in WinNonlin 

5.3. 


WinNonlin ® 5.3 Release Notes Known IVIVC issues in Version 5.3 

Certain table options are not retained when the input data set is changed (QC 2548): When 

users select all three group variable options in the Table Wizard, the option selections are not 

preserved when the input data set is changed and the table is refreshed. The first two options are 

available in the File menu in the Table Wizard. The third option is selected by clicking the page 

break (PB) button. The selections are now retained upon refreshing. 

The IVIVC Wizard no longer requires the dissolution model to be fit in order to predict PK 

values (QC 2570): Users can now select their own dissolution data worksheet in the Prediction 

tab. Users no longer have to fit the dissolution model to predict PK values. 

WinNonlin encryption updated so automation works with Japanese versions of Microsoft 

Windows (QC 2583): In previous versions of WinNonlin, people using AutoPilot on a computer 

running a Japanese version of Windows could not load scenarios from Pharsight Knowledgebase 

Server because of a password encryption error in WinNonlin. This is fixed in WinNonlin 5.3. 

PKS Save failure when run with automation (QC 2616): Under system heavy loads, 

WinNonlin may not be able to save successfully to PKS. The resulting error displayed by the 

automation application is “Failed to save scenario.” This issue has been corrected in WinNonlin 

5.3. 

Known IVIVC issues in Version 5.3 

Performance problem after saving or reloading an IVIVC project that was run up to Build 

Correlation (QC 1813): Clicking on Build Correlation immediately after loading a completed 

project creates a performance problem. WinNonlin® can take several minutes or more before 

getting through the step. 

Loo-Riegelman Rel_Fraction_Abs output chart displays in wrong scale (QC 1831): If you 

specify an AUCINF value, the Loo-Riegelman Rel_Fraction_Abs output chart displays in semilog 

scale, rather than in linear scale. 

IVIVC Wizard window remains on top of all open applications (QC 1890): If you want to 

work in other applications while leaving WinNonlin® running with the IVIVC Wizard active, it 

is suggested that you minimize the entire WinNonlin® parent application to hide the wizard 

dialog from your desktop. 

Levy’s chart source is marked as changed after generating UIR or Deconvolve (QC 1991): 

If you generate Levy Plots outside of the IVIVC Wizard, then use the wizard to generate UIR 

from the same dataset that was used to create the Levy Plots, after the UIR is generated the two 

Levy Plot output files change to pink and are marked as Source Changed. 


WinNonlin ® 5.3 Release Notes Known IVIVC issues in Version 5.3 

The IVIVC Wizard's Correlation tab and Validation grid do not clear when the input data 

are changed (QC 2016): If a user loads an IVIVC project that has been run through prediction, 

and then loads a project that has been run through validation, the Prediction tab of the IVIVC 

Wizard shows a blank first row in the Prediction grid, along with data loaded from the project 

that was run through prediction. Also, if the In-Vitro data set is modified after the In-Vitro tab is 

set up, the Validation grid in the Correlation tab still contains old data. The Validation and 

Prediction grids should be cleared when a new project is loaded, or when the source data 

changes, but they are not. The problem is that when a user makes changes in the IVIVC Wizard 

that clears either of these grids, and then undoes those changes, the Project Status indicator might 

change to green, but the grids are not re-populated in accordance with the changes. 

Possible freezing of the IVIVC Wizard when minimizing WinNonlin® or the wizard itself 

(QC 2180 & 2181): If WinNonlin® is minimized while the IVIVC Wizard is open or the IVIVC 

Wizard is minimized, the product can become unstable when the Windows Taskbar group for 

WinNonlin® is clicked to restore or maximize. This problem has only been noted when the 

Windows Taskbar option to group similar taskbar items is selected. 

Levy Plot dataset selection doesn't allow for worksheet selection (QC 2211): The 

workaround is to close the Levy Plots and reopen it. 

Saving an IVIVC project with a long filename causes Error 53 (QC 2292): If you have a 

(project name + filename + folder length) combination that nears 128 characters in length, saving 

an *.ivc project might cause an error. If this occurs, save the IVIVC project to a folder path that 

is shorter. 

Unable to load an IVIVC project when the project is moved to another directory and input 

files are not in same directory (QC 2393): Since IVIVC projects are based on WinNonlin® 

workspaces, it is highly suggested that input and output files for any IVIVC project be stored 

together in a unique directory. Doing so ensures that they may be easily moved around on your 

computer as a group if necessary and shared with your colleagues. Failure to do so may lead to 

errors occurring. 

An IVIVC project with a user-defined Tcutoff value fails in the prediction step (QC 2466): 

If a user enters a Tcutoff of 12 hours when fitting the Correlation, and then clicks the Predict PK 

button on the Prediction tab, the following error messages are displayed: 

• Duplicate time values of 12 found in a profile of data for the Input Function on profile: 

Function=1 

• Convolution failed due to all data profiles being invalid. 

The workaround is to use a custom model. 

IVIVC Prediction fails when formulations have different numbers of subjects (QC 2469): If 

the formulations and the mean formulations have a different number of subjects, an IVIVC 

project fails. 


WinNonlin ® 5.3 Release Notes Known issues in Version 5.3 

IVIVC validation fails when there are a different number of subjects in different studies 

and one study has only one subject (QC 2470): If a crossover study, for example, has multiple 

formulations and studies, and one study has a different number of subjects and one study has one 

subject, the validation process fails. The failure occurs when mean profiles are used for external 

validation. 

Entering reserved keywords into a custom model IVIVC causes errors in the IVIVC 

Wizard (QC 2471): If a custom IVIVC model uses the terms Tcut and Xcut instead of Tcutt and 

Xcutt, for example, the model fails, because Tcut and Xcut are reserved keywords. 

IVIVC error occurs in the prediction step when eleven formulations are used in a data set 

(QC 2489): An error is created in IVIVC when too many formulations are used in the prediction 

step. This causes the validation results to not match the prediction results. 

IVIVC does not work if the file DefaultNCAParameterNames.map is placed in the 

WinNonlin installation directory (QC 2502): This defect occurs because if Cmax or any AUC 

parameter is renamed, then the IVIVC Wizard cannot find the correct output columns in the 

NCA output in the Validation and Prediction steps. The workaround is to remove 

DefaultNCAParameterNames.map from the WinNonlin installation directory. 

The Prediction Dissolution Model should default to In-Vitro selection (QC 2503): The 

Dissolution Model selected in the In-Vitro tab of the IVIVC Wizard should be automatically 

selected as the Dissolution Model in the Prediction tab, but it is not. 

Known issues in Version 5.3 

Saved .lml files do not work correctly when used with a different workbook (QC 505): If a 

user creates a Bioequivalence project and saves it as an .lml file, and uses the .lml file with 

another workbook with the same column headers as the original workbook but in a different 

order, the Bioequivalence Model wizard references the columns by order, and not by header 

name. This causes the model to fail. 

If an .lml file is loaded by selecting Open in the File menu or by using the Open file button, 

the model settings are not correctly applied (QC 584): If a user loads an .lml file using either 

of the above methods, the settings in the Bioequivalence Model wizard are set to their defaults. 

However, the settings are correctly saved in the .lml file. The workaround is to open the .lml file 

using the Load or Previous Model buttons in the Bioequivalence Model wizard. The settings 

saved in the .lml file are correctly applied when the model file is loaded. 

Absolute error Bars revert to Relative error bars when a chart is reloaded (QC 797): If a 

user creates a chart and sets the error bars to Absolute, closes the Chart Wizard, and opens it 



again to edit the chart, the error bars setting changes to Relative. The only way around this is to 

select Absolute again. 

Applying a transformation to derived, or locked, workbook produces unexpected output 

(QC 807): If a user applies a transformation to a locked workbook, such as an NCA output 

workbook, and selects Adjacent as the destination area, WinNonlin® gives an error message that 

says "Locked cells cannot be modified." However, WinNonlin® still creates the column and 

places an entry in the first cell of the new column. The workaround is to save the locked 

workbook, close it, and open it; or select Dependencies in the File menu to detach the workbook, 

and then apply the transformation. 

Installation (QC 825): If WinNonlin® is installed locally using an Administrator account, then 

it is not always accessible by other local users. 

Changed column names are not updated during the refresh of chart (QC 826): If a 

worksheet is used to create a chart, and columns in the worksheet are renamed, and a user rightclicks 

the chart and selects Refresh, WinNonlin® gives an error message and the chart is not 

updated with the renamed columns. 

Users cannot delete excluded points if slopes have been cleared in NCA model 220 (QC 

1110): If the start and end times for a slope are specified and a time point is excluded, and then 

the start and end times are reset to zero, the excluded point cannot be cleared and WinNonlin® 

produces an error message. The workaround is that the excluded time points must be included 

before the start and end times are changed. 

Linear Mixed Effects Wizard’s Contrasts and Estimates grids show only one level of the 

first variable in four-way interaction (QC 1315): If an .lml file is created in WinNonlin® 

version 4.2 or lower and opened in WinNonlin® 5.0 or higher, an error message is displayed that 

states that "Too many estimate values found on file." This error message is displayed because 

more coefficients were saved in the .lml file because it was created with an older version of 

WinNonlin®, and in version 5.0 and higher the Estimates grid is too small to display all the 

coefficient values. This defect does not affect studies with two-way or three-way interactions. 

Performing Multi-Transform on a column in a results workbook can cause an error if the 

model is changed and Refresh is used (QC 1414): If a Multi-Transform is performed on an 

output worksheet such as Final Parameters, and the model is changed so new columns are added 

to the Final Parameters worksheet, selecting Refresh in the Multi-Transform output workbook 

fails because WinNonlin® does not know where to add the new column. 

LIB file overwritten (QC 1440): If you open a PMO file, save it as a LIB file, then resave it as 

a PMO file, a version of the LIB file is overwritten. 

License Unicode patch works for node license but not for floating licenses in certain cases 

(QC 1457): The Unicode patch, which addresses non-English ASCII characters in the machine 

name causing licensing issues, works for node licenses. However, it does not work if the license 



is floating, installed on a Floating License Server that has non-English characters in the ASCII 

name, and the WinNonlin® client machine uses that name as its host name. 

The workaround is to use the IP address of the license server instead of the DNS name. 

In an NCA model if the Y-variable, such as concentration, has a missing value at time 0 the 

carry-along information is not displayed at time 0 in the Summary Table worksheet (QC 

1525): Carry-along variables in an NCA model are not displayed in the Summary Table for time 

0 if the source data has a missing Y-value at time 0 or there is no observation at time 0 in the 

data set. For other time points the carry-along variables are displayed correctly. 

Refresh All option not working for Deconvolution (QC 1734): It does not record the 

Exclusions in the History Tab. 

Uninstalling WinNonlin (QC 1739): Uninstalling WinNonlin does not delete all files from the 

Pharsight/WinNonlin folder. 

Linear Mixed Effects in WinNonlin® is case-insensitive (QC 1790): The Linear Mixed 

Effects wizard in WinNonlin® cannot differentiate between upper and lower cases in input data 

sources. For example, if AA and aa are used as subject identifiers, only AA is shown in the 

output. The workaround is to not use lower and upper case to differentiate between variables 

values in a data set. 

PKS error message (QC 1922): When using WinNonlin® with PKS 3.0 and a dataset that has 

different Treatment Descriptions for the same Treatment, an error message might result. For 

example, if Treatment = A throughout the dataset, but the associated Treatment Descriptions are 

IV and Extravascular, an error message occurs. 

This issue does not occur when using WinNonlin with PKS versions 3.1 and later. 

Script error message is displayed when printing certain online help headings and subtopics 

(QC 1985): When selecting to print the selected heading and all subtopics, an Internet Explorer 

Script Error message is displayed. However, despite this error, help prints without any errors. 

Merge output includes excluded data (QC 2002): The merge output produces output that 

contains excluded rows and data from the original input workbooks. 

Modeling Error 10998 intermittently occurs when opening files directly from a .zip file (QC 

2035): Extracting the file from the zip file first and then opening it solves the issue at first, but if 

you try to re-open the file again from the zip file, the error occurs again. 

No units are carried through the NCA calculations when all concentrations are 0 (QC 2042, 

ONYX 49088): When running noncompartmental analyses for a profile where all concentrations 

for a subject are 0, a warning message is displayed that units might be wrong, Cmax is set to 0 

(which is correct), and all other parameters are reported as "missing" (which is also correct). All 



results (whether 0 or missing) are contained in the "non-transposed final parameters" sheet, but 

all units are missing. 

Missing values when Disable curve stripping is selected (QC 2162): If "Disable curve 

stripping" is selected before Baseline values are entered, missing values on the Final Parameters 

tab can occur. 

WinNonlin® and PKS GUI field names differ (QC 2235): In WinNonlin® the Dose attribute 

“Route” is displayed as Analytical Method, whereas PKS displays the same attribute as Route. In 

addition, the Treatment attribute in PKS is displayed as Treatment Code in WinNonlin®. 

Missing time points plotted incorrectly (QC 2237): Missing time points are plotted for 

Lambda Z as zero values. 

Model options default output option changes (QC 2252): If you change another global setting, 

defined in Tools > Options, the global setting for text output is changed to unselected. 

Workaround is to change the global settings by selecting the option for text output. 

Professional license error message (QC 2289): With a new installation of WinNonlin®, even 

with a Professional license installed, the error message, “You are using this product without a 

registered license,” is displayed when opening WinNonlin®. This message is displayed for the 

first 30 days after installation, during which time the 30-day trial license to the Enterprise edition 

is valid. 

Create study requires workaround when mapping time unit to a column (QC 2302): 

Workaround involves mapping time unit first. 

2316, CRM 49405 Special case where AUClast is reported as missing (QC 2316): For NCA 

models 200 and 202, if there is only one non-zero value and that value does not occur at dosing 

time, then AUCall is reported, but AUClast is missing even though it can be computed. The 

workaround is to obtain AUClast from the Summary Table worksheet. 

Superfluous error message in text output when another error occurs (QC 2349): When an 

error occurs in Modeling, an extra error message, Error 10161, Inadequate System Resources 

Available for this Problem, might also be displayed in the text output file. 

The Increment for Partial Derivatives entry field is not enabled correctly, so the default 

value is always used (QC 2351): If a user enters a different value in the Increment for Partial 

Derivatives entry field in the Settings tab of the Model Options dialog, and saves the model as a 

.pmo file, then partial derivatives reverts to its default value when the .pmo file is loaded. 

The workaround is to use the DINCREMENT command in ASCII model format. 

File open dialog does not default to file type of pre-populated filename (QC 2392): File open 

dialog defaults to last file type opened instead. 



Loading a saved Multi-transform causes information about worksheet to be lost (QC 2396): 

Worksheet name is lost. 

Users are not warned when non-refreshable actions are performed on derived output (QC 

2481): WinNonlin® does not warn users that when data exclusions and inclusions are performed 

on derived output, the changes are not preserved when the model that created the output is rerun. 

The workaround is to use Multi-Transform to exclude or include data in order to retain 

changes when the model is re-run. 

Study and scenario status is not displayed in the Pharsight® Knowledgebase Server 

Load from WNL dialog description window (QC 2493): Currently the only status message 

displayed in the description window is whether or not the study or scenario is locked. If the study 

or scenario is unlocked, there is no message stating such in the description window. 

NCA sparse sampling models are not correctly saved as .pmo files (QC 2523): If a sparse 

sampling model is run without being saved, then the output workbook does not contain any 

subject data. If the model contains sort variables it is saved correctly. If the model contains sort 

variables, then the output from a newly created model and the output from a saved .pmo file are 

the same. The defect occurs when no sort variable is selected in the model. 

An error occurs when table template 9 is selected and a user drags variables from one 

dataset to another (QC 2526): When a user selects table template 9, and attempts to drag 

variables from the DS1 - Cross Variables box to the DS2 - Variables box, an error occurs that 

prohibits the user from creating the table. 

Tables cannot display units in the output if the data set in focus does not have units (QC 

2529, 2530): Table templates 1 through 9 cannot display units in the output if the data set in 

focus does not have units. The workaround for table templates 1 through 8 is to make sure that 

the data set you want to use is in focus. There is no workaround for table template 9. 

Extra NCA parameters are generated in output when running a previously saved steadystate 

model (QC 2538, CRM 63147, 128333, 128613): The problem occurs when an NCA 

model is applied to a dataset, the steady-state option is set on the Dosing tab of the Model 

Properties dialog, and the model/data combination is saved as a PMO file or saved as a scenario 

to PKS. In these cases, when the PMO or scenario is reloaded into WinNonlin and executed, 

there are unexpected parameter values that will appear on the Final Parameters and Nontransposed 

Final Parameters worksheets of the derived output. In addition, accessing the Model 

Properties dialog after loading such a PMO or scenario will result in an error message box that 

states "Unable to load NCA preferred parameters. Invalid cell reference." 

Loading LML file at LinMix / Bioequivalence wizard can take a long time (QC 2542): 

WinNonlin allows users to load LML files from the LinMix / Bioequivalence dialog as a method 

to reuse the same model settings across various datasets. This process however can take a very 

long time if the LML file used has data embedded directly in the file. To work around the 



problem, open the LML file in a standard ASCII text editor, and remove the line that has the 

command "INFILE", and also remove all of the rows of data that follow the command. All other 

commands should be left intact. Save the changes and then the LML file is ready to be reused on 

other datasets without causing unnecessary processing delays. 

Weighting options are lost if the Data Variables dialog is opened (QC 2544): If the Data 

Variables dialog is accessed for any model type in WinNonlin, the Weighting scheme will 

always revert back to the default setting of Uniform Weighting. The workaround is to set the 

Weighting scheme on the Model Options dialog after all Data Variables settings have been 

made. 

Table significant figures drop trailing zeroes in some instances (QC 2553, CRM 65517): 

Depending on the magnitude of the data processed and the precision requested, the Tables 

module might remove significant digits that are trailing zeros. 

WinNonlin crashes if a user creates a new workbook and selects Multi-transform (QC 

2585): If a user creates a new workbook and selects Multi-transform, WinNonlin displays an 

error message that states "Runtime Error '380' Improper Property value." At this point users can 

only click OK to close WinNonlin. 

In rare instances, profile data is excluded in the NCA Summary Table worksheet (QC 

2587, CRM 128348): When this error occurs, the profile data for the last time point for that 

particular profile is excluded in the Summary Table worksheet. In order for this highly 

infrequent defect to occur, the input data set must have excluded profiles. 

NOTE: this is likely to happen when there are exclusions and NO OBSERVATIONS AT TIME 

0. If the relative actual time is negative at relative nominal time 0, then WinNonlin throws out 

those points and generates a row for time 0. This means there are no corresponding carry alongs 

at time 0, thus the missing values. Therefore the sort keys are shown to be excluded in the 

Summary Table. 

Workaround: If users encounter this issue, they can use the Multi-Transform tool to remove the 

data to be excluded in a systematic and reproducible fashion. 

Users with a WinNonlin professional license and an AutoPilot PKS license can use 

AutoPilot to access Pharsight Knowledgebase Server (PKS) (QC 2588): Users must have a 

WinNonlin enterprise license to access PKS. However, users who have an AutoPilot PKS 

Edition network license and a WinNonlin professional local license can use AutoPilot to load 

scenarios from and save scenarios to PKS. However, users with this configuration cannot access 

PKS from within WinNonlin. 

User-defined Lambda_Z range not valid for a urine NCA model (QC 1876, CRM 48705): If 

a data set has a repeating decimal, such as .33333333, then the NCA urine model might not 

accept a user-defined Lambda_Z range. 



Unable to add a dosing column to a PKS study (QC 1982): In a PKS study, if you try to add 

actual dose data to the dosing information manually by adding dosing observation columns 

within the Dosing tab, the change is not recorded as a PKS Study change, but rather is recorded 

as a scenario change. 

Crossover design tool (QC 2270, CRM 49330): Crossover design analysis cannot be run on a 

dataset with more than 83 subjects. 

Exporting linear and logarithmic charts to a Microsoft Word document at the same time 

causes custom scaling values to revert to automatic (QC 636): If the Add log charts check 

box is selected in the Word Export Options dialog, and a custom Y-axis scale is used, the 

exported linear charts use the custom Y-axis values for the first linear chart only. All other linear 

charts revert to automatic scaling. The workaround is to export charts twice; once using a linear 

scale and once using a logarithmic scale. 

Emax PD models are not reparameterized to match drug-based parameters used in 

modern drug modeling textbooks (QC 776): The Emax parameter in WinNonlin is responsebased 

rather than drug-based. This usage does not reflect what is currently used in drug 

modeling, where Emax is the difference between the maximum effect and the baseline effect 

(E0), and the baseline effect is effect seen at C0. 

Some Summary Table results are missing if there is no value in the concentration column 

for time zero (QC 1251): The NCA Summary Table output is labeled as Missing in cells for 

subjects that are missing concentration data. WinNonlin inserts a zero value so AUC can be 

computed, which causes Missing to be inserted in cells in the Summary Table for the missing 

concentration value. 

Data exclusion errors occurs when the Window background color is set to anything other 

than white (QC 1318, 1319): If a user goes to the Display Properties dialog in Microsoft 

Windows, selects the Appearance tab, clicks on Advanced, and selects Window in the Item menu 

and changes the background color to any color but white, WinNonlin analysis wizards include 

any data that has been excluded. This defect occurs no matter how the data is excluded. This 

defect affects analysis functions such as Descriptive Statistics. The workaround is to open any 

folder in Windows and make sure the background color is white. If it is not, change it to white in 

the Display Properties dialog. 

Table templates 6 and 8 do not correctly handle crossover and ID variables that contain 

mixed text and numerical values (QC 1448): If the crossover variable contains mixed text and 

numerical values the crossover variable cells in the table are not centered, even if center 

alignment is specified. Also, the ID variable column is not correctly created if the source column 

contains a mix of text and numerical values. The ID variable column only displays integer 

values, even if decimal values are present. This defect only affects table templates 6 and 8. 

The ID variable used in the Table Wizard cannot contain more than 12 digits in a cell (QC 

1873): If the column selected as the ID variable in the Table Wizard contains more than 12 digits 



in a cell, WinNonlin treats the numbers as non-numeric, which compromises the table's 

accuracy. The workaround is to not use more than 12 digits in a column that is used as the ID 

variable in the Table Wizard, because WinNonlin does not support more than 12 significant 

digits or decimal places. 

Significant figures and decimal places are not presented consistently in table results and 

.pwo files due to trailing zeros being incorrectly truncated (QC 2046, ONYX 49092): If a 

user sets the number of significant digits to three in the Table Wizard, some values are shown 

with only two significant digits because any trailing zeros are truncated in the output. This defect 

also affects output .pwo files. 

Confidence interval value in table automation Visual Basic file must be specified, or it is set 

to zero (QC 2415): If the table creation process is automated, and table.ConfidenceInterval is 

not defined in the Visual Basic file, then the table's confidence interval defaults to zero. The 

workaround is to set table.ConfidenceInterval to equal the desired confidence interval value. 

The mouse operations are not recorded in the History worksheet (QC 2417): The "drag 

down" and "drag and drop" mouse operations are not recorded in the History worksheet in 

WinNonlin. 

Selecting the Show formulas check box does not show formulas in worksheet cells (QC 

2418): If a user selects Options in the Tools menu, selects the Workbooks tab, and selects the 

Show formulas check box, WinNonlin does not show the formulas in worksheet cells. Only the 

values are displayed. 

Parameter output information for an NCA model with steady state dosing is not retained in 

.pmo files (QC 2421): If an NCA model with steady state dosing is saved as a .pmo file, when 

the .pmo file is reopened and the model is run, all possible output parameters are included in the 

results. The workaround is to open the .pmo file and select Model Options in the Model menu. 

This action forces WinNonlin to check the specified model options before the model is run. 

RANDOM statement in bioequivalence .lml model file is not properly loaded when the 

model file is opened (QC 2456): If a user loads an .lml file that uses the RANDOM statement, 

the random effects are not properly loaded when the file is opened. The workaround is to start 

the Bioequivalence wizard, select Parallel/Other, and then click Load. Load the parallel study 

model file that has a variance structure. The model loads and runs as expected. 

If multiple sort levels and dependent variables are selected in the Linear Mixed Effects 

Wizard, the LSM Differences worksheet only shows the first row of results (QC 2465): If a 

Linear Mixed Effects model contains multiple sort levels and dependent variables, then the LSM 

(Least Squares Means) Differences worksheet only shows the first row of results. The 

workaround is to go to the text output and get the LSM Differences for the missing rows. 

Table template 9 cannot be detached, reattached, and refreshed (QC 2472): If a table is 

created using template 9, and a user right-clicks the table and selects Detach, and then selects 



Re-attach, WinNonlin gives two error messages and the table disappears and cannot be 

recovered. 

Linear Mixed Effects Wizard crashes when stress testing is done using very long string 

values (QC 2478): If a user decides to perform stress tests on WinNonlin's Linear Mixed Effects 

engine, then any test data sets cannot contain very long string values. 

Table Wizard incorrectly rounds decimal places in individual data before calculating 

summary statistics (QC 2479): The Table creation function in WinNonlin only accurately 

supports 10 significant digits or decimal places. If any values used in table creation contain more 

than 10 significant digits or decimal places, then the extra digits or decimals places are truncated 

before summary statistics are calculated. For example, if there is a value where the integral 

portion is 4 digits, the decimal places are only accurate to 6 digits, and if the integral portion is 7 

digits, the decimal places are only accurate to 3 digits. 

Pharsight ® Knowledgebase Server scenarios with multi-transformed workbooks from 

which NCA models are derived might cause an error in PK Automation projects (QC 

2480): In some cases, the sort keys of the multi-transformed data set do not match the sort keys 

in the derived NCA model. When the model is saved locally, WinNonlin is unable to reset the 

sort keys of the data set so the model cannot run. Attempting to use the model with the data set in 

an automation project gives the following error message: 

An error has occurred in the application. 

Failed to Load Scenario via scripting. 

The workaround is as follows: 

• Open the model in WinNonlin. 

• Open the data variables for the model and click OK. 

• Click on the Model workbook and select Sort in the WinNonlin Tools menu. This shows 

the sort keys for the workbook. They should match what is in the model. If they do not 

match, then change the workbook sort keys to match the model sort keys. 

• Click OK. 

• The NCA output workbooks turn pink. Refresh them or re-run the model. 

• After a successful modeling run, save the scenario back into the Pharsight 

Knowledgebase Server, In the WinNonlin File menu, select Save or Save As. 

Table Wizard refreshes cause incorrect formatting or table creation failure when two or 

more tables are created from the same data set (QC 2482, CRM 65100, 61552): If two tables 

are created using the same data set and the data set is changed, then refreshing the tables causes 

the tables to become incorrectly formatted, or the refresh fails to create a new table. The 

workaround is to close the Table Wizard before selecting to refresh the tables. 

WinNonlin can lose the scenario hierarchy in the Pharsight Knowledgebase Server Load 

dialog (QC 2484): If a user logs in to the Pharsight Knowledgebase Server, selects a study that 

has multiple daughter scenarios, loads the study, and clicks Cancel in the Select the fields for the 

Observation worksheet dialog, the study's scenario hierarchy is flattened. 



Saving a workspace should automatically save a copy of the loaded workbook in the same 

folder but it does not (QC 2487): If a user saves a workspace, then WinNonlin should 

automatically save a copy of the loaded workbook in the same directory. However, WinNonlin 

saves a pointer to the data and not the actual data in the workspace, which causes confusion for 

users when they try to share work. The workaround is to place a copy of the data in the same 

directory as the workspace file, or warn other users that the workspace file contains a pointer to 

the data and not the actual data. 

Manual edits to a chart previously saved in the Pharsight Knowledgebase Server do not 

persist when the chart is saved back into the Pharsight Knowledgebase Server (QC 2488): 

If a user makes changes to the X-axis or Y-axis labels of a chart using the Chart Designer, for 

example, the chart is displayed correctly in WinNonlin, even after the chart is saved to and 

loaded from the Pharsight Knowledgebase Server. However, when the same chart is inserted into 

PKS Reporter using either the Insert Multiple PKS Images or the Insert PKS Tag operations, the 

chart defaults to the labels used before the user changes were made. This defect also affects other 

chart attributes modified in the Chart Designer. 

Changing the Data Variables selections in NCA model 220 resets Slope 2 to Best Fit (QC 

2499): This defect occurs when a user specifies the start and end times for Slope 2 in NCA 

model 220, and then changes the selections made in the Data Variables dialog. After the changes 

are made in the Data Variables dialog, Slope 2 is switched back to Best Fit instead of using the 

user-specified values. 

A problem reading the dosing worksheet prevents any analysis in an NCA Constant 

Infusion model (QC 2504): The dosing sheet for a mixed matrix (plasma and urine) study is not 

initially read correctly by WinNonlin, even if a matrix is excluded. The result is that a single 

failed profile prevents the other profiles from being analyzed. The workaround is to choose to 

not default to PKS dosing by selecting the Dosing Data Variables dialog in the Model menu. 

This allows the user to select a different dosing data worksheet. Clear the No Source check box 

and then select the dosing data from another worksheet. A user can then enter dosing data 

manually, or select a transformed dosing data worksheet as the source. 

Missing values are not grayed out in the NCA Final Parameters and Summary Table 

worksheets (QC 2505): Missing values are not grayed out in the NCA Final Parameters and 

Summary Table worksheets, and there are inconsistencies in how the worksheets display some 

missing values. For example, a missing value in the Final Parameters worksheet is sometimes 

displayed as a zero in the Summary Table worksheet. 

Certain values in the terminal phase of the Nonparametric Superposition Wizard should 

not permit superposition but the analysis completes anyway (QC 2506): If a user selects the 

Define terminal phase check box and enters a limited range of values so that the terminal phase 

contains only one point, the terminal phase cannot be determined. However, the Nonparametric 

Superposition Wizard runs anyway. 



If WinNonlin saves a study or data set to the Pharsight® Knowledgebase Server that 

contains units that WinNonlin cannot process, two critical errors occur (QC 2509, CRM 

62202): If a user chooses to save a study or data set that contains certain units, then the study or 

data set cannot be loaded from the Pharsight Knowledgebase Server and the Pharsight 

Knowledgebase Server Web interface crashes. The two most frequently occurring units that 

cause this error are μ (micro) and m 2 (meters squared). This defect affects any study or data set 

that contains characters that are not in the Oracle Database character set. There are two 

workarounds. The first is to go into the Oracle Database and replace the units using SQL 

statements. The second is to not use characters that Oracle does not support. 

Descriptive Statistics counts excluded data as missing (QC 2515): The Descriptive Statistics 

Wizard should simply leave the excluded rows and cells out of its computations, but it does not. 

Dosing and initial parameter values are not retained in ASCII model with differential 

equations, function variables, and unused data (QC 2522): Dosing and initial parameter 

values are not retained in an ASCII model that contains differential equations and function 

variables, when there are more levels in the Function column than there are NFUNs specified in 

the model. When the Dosing tab is closed and reopened or if a user runs the model, the dosing 

values are all reset to zero. The same happens with initial estimates and bounds. The 

workaround is to delete or exclude all the rows in the dataset that have a value of 2 in the 

Function column, so CONS and PARMS are retained as expected. Similarly, altering the model 

to state NFUN 2, and making FUNCTION 2 do something like F=F, allows the model to run 

fine.

Release Notes - Pharsight

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