Release Notes GLOBALvalidator 3.0 SP3 - Extedo

CONFIDENTIAL - PROPRIETARYRelease Notes – GLOBALvalidator 3.0 SP3Document Date:03-May-2013Document Version: 1.0Status:Document ID:releasedReleaseNotes-GLOBALvalidator-3.0-SP3-1.0Document FilenameDocument SiteReleaseNotes-GLOBALvalidator-3.0-SP3.docxhttp://sharepoint/websites/RD/GLOBALvalidator/Approval:Name / Title Role Date SignatureLoïs BéguéProduct Implementation ManagerAuthorMichael GessertProduct ManagerApproverBarbara HeegProduct Quality ManagerApproverTemplate version: 4.0 Template release date: 16-Apr-2012 Page 1 of 27

CONFIDENTIAL - PROPRIETARYTable of Contents1 INTRODUCTION 32 VERSION 3.0 42.1 NEW FEATURES 42.2 FIXED ISSUES 52.3 VALIDATION SET SUMMARY 63 VERSION 3.0 HF 1 83.1 NEW FEATURES 83.2 FIXED ISSUES 83.3 VALIDATION SET SUMMARY 84 VERSION 3.0 HF 2 104.1 NEW FEATURES 104.2 FIXED ISSUES 104.3 VALIDATION SET SUMMARY 105 VERSION 3.0 SP 1 125.1 NEW FEATURES 125.2 FIXED ISSUES 135.3 VALIDATION SET SUMMARY 146 VERSION 3.0 SP 1 HF 1 166.1 NEW FEATURES 166.2 FIXED ISSUES 166.3 VALIDATION SET SUMMARY 167 VERSION 3.0 SP 1 HF 2 187.1 NEW FEATURES 187.2 FIXED ISSUES 187.3 VALIDATION SET SUMMARY 188 VERSION 3.0 SP 2 208.1 NEW FEATURES 208.2 FIXED ISSUES 218.3 VALIDATION SET SUMMARY 219 VERSION 3.0 SP 3 239.1 NEW FEATURES 239.2 FIXED ISSUES 249.3 VALIDATION SET SUMMARY 2510 KNOWN ISSUES 27Template version: 4.0 Template release date: 16-Apr-2012 Page 2 of 27

CONFIDENTIAL - PROPRIETARYFeature 23243: Turn on/off validation sets in GLOBALvalidatorThe list of validation sets visible to the user can be configured in a new options dialog.This feature requires a license and is not available in the free version (EURSvalidator).Feature 23252: Introduction of GLOBALvalidatorThe EXTEDO applications EURSvalidator and GECCO are combined into a new product GLOBALvalidator.Feature 23253: Licensing of GLOBALvalidatorA license key is required to enable enhanced features of GLOBALvalidator and additional validation sets.Basic validation sets are still available in the free version (EURSvalidator).The license key for GLOBALvalidator can be purchased from the EXTEDO homepage(www.extedo.com).Feature 23333: Enable copy in General Information and Error Details ViewsThe General Information and Error Details views offer a new button to copy the information into the clipboard.Feature 23391: Submission Level Tests should be included to Validation ReportThe General Information view and the validation reports list the number of failed submission level tests.2.2 Fixed IssuesIssue 22051: EU eCTD v3.1 Rule 13.03 errorIf the path to eu-regional xml contained uppercase letters like '/m1/EU/', the rule 13.03 reported a mismatchbetween sequence folder name and sequence stored in the envelope.Impact low, detectability high, detected in version 2.0.00.01Issue 22825: (CAS-05447-XFY9) eCTD v3.1 criterion 16.BP08 / NeeS v2.1 Criterion 03.BP06 incorrectThe eCTD v3.1 rule 16.BP08 and the NeeS v2.1 rule 03.BP06 should detect an incorrect initial view settingof a PDF file. Instead they detected an incorrect inherit zoom setting for bookmarks and hyperlinks inthe PDF file.Impact medium, detectability high, detected in version 2.0.00.08Issue 22903: (CAS-05503-5FJY) vNeeS could not be loaded to EURSvalidator/GLOBALvalidatorIn EURSvalidator/GLOBALvalidator the “open submission” operation was limited to four digit sequencefolders. The sequence folder of vNeeS submissions follows a different naming convention and could notbe opened.Impact medium, detectability high, detected in version 2.0.00.11Issue 22942: (CAS-05937-M0PN) NeeS v2.1 PDF tests are skippedEURSvalidator reported skipped PDF rule tests when a NeeS v2.1 validation set was used. The affectedvalidation sets were EU-NeeS and HR-NeeS.Impact high, detectability high, detected in version 2.0.00.11Issue 22949: Validation engine does not show error regarding fast web accessFor some PDF files EURSvalidator/GLOBALvalidator did not recognize that the “Fast Web View” optionwas missing. This issue occurred if a PDF document was modified after linearization.Template version: 4.0 Template release date: 16-Apr-2012 Page 5 of 27

CONFIDENTIAL - PROPRIETARYImpact low, detectability low, detected in version 2.0.00.11Issue 22962: (CAS-05567-RJ38) NeeS: Invalid links in ToC cause too many errors (rule 01.07)In the case that a ToC PDF file contained invalid hyperlinks (without a destination) EURSvalidator/GLOBALvalidatorskipped all other hyperlinks in the file and reported too many rule violations for EUNeeS 2.1 and HR NeeS 2.1 rule 01.07.Impact medium, detectability medium, detected in version 2.0.00.11Issue 22967: (CAS-05592-0YXZ) PDFs with bookmarks to named destinations are skippedIn some cases EURSvalidator/GLOBALvalidator could not resolve bookmarks to named destinations andskipped the affected documents. The problem affected the following rules:EU and HR eCTD v3.1: 16.BP03, 16.BP05, 16.BP06, 16.BP10 and 16.BP11 EU and HR NeeS v2.1:03.BP03, 03.BP04, 03.BP08Impact medium, detectability high, detected in version 2.0.00.11Issue 23083: EU eCTD v3.1 Rule 16.03 does not consider exceptionsAccording to EU eCTD v3.1 Rule 16.03 PDF files must not have any security restrictions. However, thesections m3/33-lit-ref, m4/43-lit-ref and m5/54-lit-ref are exempt from this rule. EURSvalidator/GLOBALvalidatordid not consider this exception. The same applied to EU NeeS v2.1 rule 03.03 andthe HR counterparts.Impact medium, detectability high, detected in version 2.0.00.11Issue 23658: EU NeeS v2.1 rule 01.05 ignores missing links to module ToCsThe EU NeeS v2.1 rule 01.05 did not check if the main ToC contains a link to each existing module ToC.A new fail message has been added: fail-01.05.04: Module TOCs are used, but the Main CTD TOC doesnot contain hyperlinks to all module TOCs. Missing hyperlinks: {0}. The issue also affects HR NeeS v2.1.Impact medium, detectability medium, detected in version 3.0.0.0005Issue 23855: (CAS-06205-512Y) Hyperlinks with target outside of the EU-NeeS 2.1 and HR-NeeS 2.1are not recognized (rule 03.BP02)The rule did not recognize a hyperlink with a target outside of the NeeS in the following case: The sequencefolder name in the hyperlink reference equals the current sequence folder name but the parentfolder name is different. E.g. the current sequence is located in abc\0000 and the hyperlink points to a filein ..\..\def\0000.Impact medium, detectability high, detected in version 2.0.00.11Issue 24031: Report rendering fails when validating EU DTD 1.3 submission with EU 3.1 rulesWhen an EU submission based on DTD 1.3 was validated using the EU-eCTD v 3.1 (DTD 1.4) validationset the creation of the report failed with an exception message. HR-eCTD v3.1 (DTD 1.4) was also affected.Impact high, detectability high, detected in version 3.0.0.00082.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified in this versionFDA-eCTD v1.0 (DTD 2.01) x x -Template version: 4.0 Template release date: 16-Apr-2012 Page 6 of 27

CONFIDENTIAL - PROPRIETARYFDA-eCTD v1.0 (DTD 2.01) FAST - x newFDA-eCTD v1.0 (DTD 2.01) -GECCO- x newFDA-eCTD v2.1 (DTD 2.01) - x newFDA-eCTD v2.1 (DTD 2.01) FAST - x newEU-eCTD v2.0 (DTD 1.2.1) - x xEU-eCTD v2.1 (DTD 1.3) - x xEU-eCTD v2.1 (DTD 1.4) - x xEU-eCTD v2.1 (DTD 1.4) –GECCO- x (only XML checks) newEU-eCTD v3.1 (DTD 1.4) x x xEU-eCTD v3.1 (DTD 1.4) FAST - x newCA-eCTD v1.0 (DTD 1.0) –GECCO- x (only XML checks) newCH-eCTD v1.0 (DTD 1.0/1.0.1) - x xCH-eCTD v1.1 (DTD 1.1) x x xCH-eCTD v1.1 (DTD 1.1) -GECCO- x (only XML checks) newHR-NeeS v1.0 - x -HR-NeeS v2.1 –Submission Only x x xHR-eCTD v2.1 (DTD 1.4) - x xHR-eCTD v3.1(DTD 1.4) x x xEU-NeeS v1.0 - x -EU-NeeS v2.1 –Submission Only x x xVMD-eNTA(immunological product) DTD 0.9VMD-eNTA(pharmaceutical product) DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)x x -x x -x x -x x -Template version: 4.0 Template release date: 16-Apr-2012 Page 7 of 27

CONFIDENTIAL - PROPRIETARY3 Version 3.0 HF 1StatusReleasedTested with Operating System: Windows 7Release Date 21-May-2012 Released By Karin AwaloffBuild 3.0.0.0023 Database version n/aDeliveryValidationComponentSetupIncludes a full setup with all fixes and features mentioned below.2.0.0.0015ValidationLibrary1.2.21.223.1 New FeaturesNone3.2 Fixed IssuesIssue 24058: (CAS-06524-X21S) Modified file that refers to current sequence is not detected by rule11.09 in EU eCTD v3.1EU eCTD v3.1 rule 11.09 did not detect if the modified-file reference of a leaf in index.xml referred to anotherleaf in the current submission. Also applies to HR eCTD v3.1.Impact medium, detectability medium, detected in version 2.0.00.11Issue 24681: (CAS-06787-0641) Error 11.09 is shown even if previous sequence is presentWhen the modified-file ID of a leaf is equal to the leaf ID the EU-eCTD v3.1 rule 11.09 incorrectly showedan error “Not all modified-file entries are pointing to a leaf”. Also applies to HR eCTD v3.1.Impact high, detectability medium, detected in version 3.0.0.00223.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified in this versionFDA-eCTD v1.0(DTD 2.01)FDA-eCTD v1.0(DTD 2.01) FASTFDA-eCTD v1.0(DTD 2.01) - GECCOFDA-eCTD v2.1(DTD 2.01)FDA-eCTD v2.1(DTD 2.01) FASTx x -- x -- x -- x -- x -EU-eCTD v2.0 - x -Template version: 4.0 Template release date: 16-Apr-2012 Page 8 of 27

CONFIDENTIAL - PROPRIETARY(DTD 1.2.1)EU-eCTD v2.1 (DTD 1.3) - x -EU-eCTD v2.1 (DTD 1.4) - x -EU-eCTD v2.1(DTD 1.4) - GECCO- x (only XML checks) -EU-eCTD v3.1 (DTD 1.4) x x xEU-eCTD v3.1(DTD 1.4) FASTCA-eCTD v1.0(DTD 1.0) - GECCOCH-eCTD v1.0(DTD 1.0/1.0.1)- x x- x (only XML checks) -- x -CH-eCTD v1.1 (DTD 1.1) x x -CH-eCTD v1.1(DTD 1.1) - GECCO- x (only XML checks) -HR-NeeS v1.0 - x -HR-NeeS v2.1 –Submission Onlyx x -HR-eCTD v2.1 (DTD 1.4) - x -HR-eCTD v3.1(DTD 1.4) x x xEU-NeeS v1.0 - x -EU-NeeS v2.1 –Submission OnlyVMD-eNTA(immunological product)DTD 0.9VMD-eNTA(pharmaceutical product)DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)x x -x x -x x -x x -x x -Template version: 4.0 Template release date: 16-Apr-2012 Page 9 of 27

CONFIDENTIAL - PROPRIETARY4 Version 3.0 HF 2StatusReleasedTested with Operating System: Windows 7Release Date 05-Jun-2012 Released By Karin AwaloffBuild 3.0.0.2000 Database version n/aDeliveryValidationComponentSetupIncludes a full setup with all fixes and features mentioned below.2.0.0.0016ValidationLibrary1.2.21.234.1 New FeaturesNone4.2 Fixed IssuesIssue 24814: Autoselect should select FDA 1.0 criteriaThe autodetect feature selected the new FDA v2.1 validation rules for FDA eCTD submissions. As theseare not yet effective the old FDA v1.0 rules should be selected instead.Impact low, detectability medium, detected in version 3.0.0.0023Issue 24827: GECCO reports are invalidAlthough the validation was successful the reports for GECCO validation sets showed an invalid resultand the message:"The number of documents presented does not match the number of validated documents. Please contactyour next EXTEDO representative.".Impact high, detectability high, detected in version 3.0.0.00234.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified in this versionFDA-eCTD v1.0(DTD 2.01)FDA-eCTD v1.0(DTD 2.01) FASTFDA-eCTD v1.0(DTD 2.01) - GECCOFDA-eCTD v2.1(DTD 2.01)x x -- x x- x x- x -FDA-eCTD v2.1 - x xTemplate version: 4.0 Template release date: 16-Apr-2012 Page 10 of 27

CONFIDENTIAL - PROPRIETARY(DTD 2.01) FASTEU-eCTD v2.0(DTD 1.2.1)- x -EU-eCTD v2.1 (DTD 1.3) - x -EU-eCTD v2.1 (DTD 1.4) - x -EU-eCTD v2.1(DTD 1.4) - GECCO- x (only XML checks) xEU-eCTD v3.1 (DTD 1.4) x x -EU-eCTD v3.1(DTD 1.4) FASTCA-eCTD v1.0(DTD 1.0) - GECCOCH-eCTD v1.0(DTD 1.0/1.0.1)- x -- x (only XML checks) x- x -CH-eCTD v1.1 (DTD 1.1) x x -CH-eCTD v1.1(DTD 1.1) - GECCO- x (only XML checks) xHR-NeeS v1.0 - x -HR-NeeS v2.1 –Submission Onlyx x -HR-eCTD v2.1 (DTD 1.4) - x -HR-eCTD v3.1(DTD 1.4) x x -EU-NeeS v1.0 - x -EU-NeeS v2.1 –Submission OnlyVMD-eNTA(immunological product)DTD 0.9VMD-eNTA(pharmaceutical product)DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)x x -x x -x x -x x -x x -Template version: 4.0 Template release date: 16-Apr-2012 Page 11 of 27

CONFIDENTIAL - PROPRIETARY5 Version 3.0 SP 1StatusReleasedTested with Operating System: Windows 7Release Date 31-Aug-2012 Released By Karin AwaloffBuild 3.0.1.0005 Database version n/aDeliverySetupIncludes a full setup with all fixes and features mentioned below.ValidationValidation2.0.0.0021ComponentLibrary1.2.21.275.1 New FeaturesFeature 17660: Configurable Report Filename and file location (e.g. close to submission)There are new options available to configure the path and file name.In the “Report Settings” tab of “Options” dialog the user can choose:Report patho Save reports within the dossier folderooSave reports within the user specific document folderSave reports in user defined pathReport file nameo Standard file name “ValidationReport__.pdf”oUser defined file name. Possible place holders are:• : Name of dossier folder.• : Name of sequence folder.• : Current date in format YYYYMMDD.• : Current time in format HHMM.The report options list in the toolbar does not display the option if the reports are stored in dossier folderdue to its replacement with the new options.This feature requires a license and is not available in the free version (EURSvalidator).Feature 22645: ‘Browse for Folder’ window with extra field for pathThe dialog to select a submission folder has been extended with a text field where a submission path canbe typed in or copied into.This feature requires a license and is not available in the free version (EURSvalidator).Feature 23617: Add upgrade hints for GLOBALvalidatorThe toolbar has been extended with a new “upgrade” icon. User may get a dialog with a link to theGLOBALvalidator web store.This feature is only available in the free version (EURSvalidator).Feature 25230: EU-eCTD 4.1 Validation SetEMA published a new EU eCTD validation set which is now supported by EV/GV.Template version: 4.0 Template release date: 16-Apr-2012 Page 12 of 27

CONFIDENTIAL - PROPRIETARYAutoselect has been updated to select this new validation set for EU M1 DTD 1.4.This feature is available in both versions (EURSvalidator + GLOBALvalidator).Feature 25231: GCC-eCTD 1.0 Validation SetThe Gulf Countries published a new GCC eCTD validation set which is now supported by GV.Autoselect has been extended to select this new validation set for GCC M1 DTD 1.0.This feature requires a license and is not available in the free version (EURSvalidator).Feature 25232: GCC: KSA-NeeS 1.0 Validation SetThe Kingdom of Saudi Arabia published a new KSA-NeeS validation set which is now supported by GV.Autoselect has been extended to select this new validation set for KSA-NeeS (see also feature 25241).This feature requires a license and is not available in the free version (EURSvalidator).Feature 25233: EU-NeeS 3.0 Validation SetEMA published a new EU NeeS validation set which is now supported by EV/GV.Autoselect has been extended to select this new validation set for EU-NeeS (see also feature 25241).This feature is available in both versions (EURSvalidator + GLOBALvalidator).Feature 25241: Enhance autoselector to detect NeeS and vNeeS submissionsAutoselect has been extended to find also a NeeS-Submission: EU-NeeS, HR-NeeS, KSA-NeeS.The NeeS-Submission must follow these requirements to be detected:There must be the file ctd-toc.pdf stored in the submission folder.There must be a folder /m1/xx/10-cover (xx must be eu or gc) with the correct named cover letterdocument (CC-cover-VAR.pdf).Depending on the region code in folder path (xx is eu or gc) and the country code in cover letter file name(CC) the correct validation set (EU-NeeS 3.0, HR-NeeS 2.1, KSA-NeeS 1.0) can be selected for the submission.Examples: /m1/eu/10-cover/de-cover.pdf EU NeeS 3.0 /m1/eu/10-cover/hr-cover.pdf HR NeeS 2.1 /m1/eu/10-cover/common-cover.pdf EU NeeS 3.0 /m1/gc/10-cover/common-cover.pdf KSA NeeS 1.0 /m1/gc/10-cover/sa-cover.pdf KSA NeeS 1.05.2 Fixed IssuesIssue 22825: (CAS-05447-XFY9) eCTD v3.1 criterion 16.BP08 / NeeS v2.1 Criterion 03.BP06 incorrectEURSvalidator doesn’t properly check for eCTD v3.1 criterion 16.BP8/NeeS v2.1 Criterion 3.BP6 [PDFDocument Properties for the Inital View are set for "Page Layout = Default" and "Magnification = Default"].It doesn’t detect an error when pdfs have incorrect Initial View settings.Impact medium, detectability medium, detected in version 2.0.00.08Issue 24367: FDA 2.1 rule 5005 allows some non-standard fontsThe FDA 2.1 rule 5005 identifies some non-standard fonts as standard fonts, e.g. font names starting withbut not equal to "Arial". A more exact check is required.Impact medium, detectability medium, detected in version 3.0.00.16Template version: 4.0 Template release date: 16-Apr-2012 Page 13 of 27

CONFIDENTIAL - PROPRIETARYIssue 24468: Rule B10 is only displayed when DMF or PMF are emptyCH-eCTD v1.1 rule B10 (envelope attributes check) does not check whether the specified values for DMFnumber and PMF number are valid. A rule violation is only reported if one of the values is missing.Impact medium, detectability medium, detected in version 2.0.00.11Issue 24920: (CAS-07063-VSJJ) Fast Web View not recognized in some casesDuring EU NeeS v2.1 validation we receive warnings regarding the missing Fast Web View for all documentsincluded to one submission. But the preferences of the documents show the Fast Web View active.Impact medium, detectability medium, detected in version 3.0.00.23Issue 25064: Rule B05 (Swiss) Handling PDF/A and PDF/X documents as being invalidAccording to the Swissmedic Q+A document this PDF types are not allowed and should be named.Impact medium, detectability medium, detected in version 3.0.00.235.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified in this versionFDA-eCTD v1.0(DTD 2.01)FDA-eCTD v1.0(DTD 2.01) FASTFDA-eCTD v1.0(DTD 2.01) - GECCOFDA-eCTD v2.1(DTD 2.01)FDA-eCTD v2.1(DTD 2.01) FASTEU-eCTD v2.0(DTD 1.2.1)- x Changed: GV only- x -- x -- x x- x -- x xEU-eCTD v2.1 (DTD 1.3) - x xEU-eCTD v2.1 (DTD 1.4) - x xEU-eCTD v2.1(DTD 1.4) - GECCO- x (only XML checks) -EU-eCTD v3.1 (DTD 1.4) x x xEU-eCTD v3.1(DTD 1.4) FAST- x -EU-eCTD v4.1 (DTD 1.4) x x newCA-eCTD v1.0(DTD 1.0) - GECCOCH-eCTD v1.0(DTD 1.0/1.0.1)- x (only XML checks) -- x xCH-eCTD v1.1 (DTD 1.1) x x xCH-eCTD v1.1 - x (only XML checks) -Template version: 4.0 Template release date: 16-Apr-2012 Page 14 of 27

CONFIDENTIAL - PROPRIETARY(DTD 1.1) - GECCOHR-NeeS v1.0 - x -HR-NeeS v2.1 –Submission Onlyx x xHR-eCTD v2.1 (DTD 1.4) - x xHR-eCTD v3.1 (DTD 1.4) x x xGCC-eCTD v1.0 (DTD1.0)- x newEU-NeeS v1.0 - x -EU-NeeS v2.1 –Submission Onlyx x xEU-NeeS v3.0 x x newKSA-NeeS v1.0 - x newVMD-eNTA(immunological product)DTD 0.9VMD-eNTA(pharmaceutical product)DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)- x Changed: GV only- x Changed: GV only- x Changed: GV only- x Changed: GV onlyTemplate version: 4.0 Template release date: 16-Apr-2012 Page 15 of 27

CONFIDENTIAL - PROPRIETARY6 Version 3.0 SP 1 HF 1StatusReleasedTested with Operating System: Windows 7Release Date 11-Sep-2012 Released By Maren MüllerBuild 3.0.1.1000 Database version n/aDeliveryValidationComponentSetupIncludes a full setup with all fixes and features mentioned below.2.0.0.0021ValidationLibrary1.2.21.286.1 New FeaturesNone6.2 Fixed IssuesIssue 25525: (CAS-07739-B1ZH) Issue with check for validation criterion 14.02 in EU eCTD 4.1If the procedure is centralised and the eCTD contains one envelope for EMA, the GLOBALvalidatorshows the error 14.02 during validation with EU eCTD v4.1.Impact high, detectability high, detected in version 3.0.1.0005Issue 25527: (CAS-07736-XMD3) EURSvalidator/Global validator: website link warning in EU v4.1Weblinks and emails are allowed, but EURS/GLOBALvalidator shows rule 16.B10 warning anyway in newvalidation set EU v4.1. This check is also in 2 other validation sets: EU-NeeS 3.0 (Rule 03.BP09) andGCC-eCTD 1.0 (Rule 16.BP10).Impact medium, detectability medium, detected in version 3.0.1.0005Issue 25534: (CAS-07751-1R4F) Error in new validation tool for CH specificationsWhen checking a Swiss application, the new validation tool 3.0 SP1 Build 5 showed a "B" criteria error forPDF version. This is a side effect of solution for SP1: Issue 25064 “Rule B05 (Swiss) Handling PDF/A andPDF/X documents as being invalid”. The additional check for PDF/A and PDF/X also has been triggeredfor documents with an empty conformance level, but the details about a detected PDF/A or PDF/X havenot been displayed in this case.Impact medium, detectability medium, detected in version 3.0.1.00056.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified in thisversionFDA-eCTD v1.0 (DTD 2.01) - x -FDA-eCTD v1.0 (DTD 2.01) FAST - x -Template version: 4.0 Template release date: 16-Apr-2012 Page 16 of 27

CONFIDENTIAL - PROPRIETARYFDA-eCTD v1.0 (DTD 2.01) - GECCO - x -FDA-eCTD v2.1 (DTD 2.01) - x -FDA-eCTD v2.1 (DTD 2.01) FAST - x -EU-eCTD v2.0 (DTD 1.2.1) - x -EU-eCTD v2.1 (DTD 1.3) - x -EU-eCTD v2.1 (DTD 1.4) - x -EU-eCTD v2.1 (DTD 1.4) - GECCO - x (only XML checks) -EU-eCTD v3.1 (DTD 1.4) x x -EU-eCTD v3.1 (DTD 1.4) FAST - x -EU-eCTD v4.1 (DTD 1.4) x x xCA-eCTD v1.0 (DTD 1.0) - GECCO - x (only XML checks) -CH-eCTD v1.0 (DTD 1.0/1.0.1) - x -CH-eCTD v1.1 (DTD 1.1) x x xCH-eCTD v1.1 (DTD 1.1) - GECCO - x (only XML checks) -HR-NeeS v1.0 - x -HR-NeeS v2.1 –Submission Only x x -HR-eCTD v2.1 (DTD 1.4) - x -HR-eCTD v3.1 (DTD 1.4) x x -GCC-eCTD v1.0 (DTD 1.0) - x xEU-NeeS v1.0 - x -EU-NeeS v2.1 –Submission Only x x -EU-NeeS v3.0 x x xKSA-NeeS v1.0 - x -VMD-eNTA(immunological product) DTD 0.9VMD-eNTA(pharmaceutical product) DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)- x -- x -- x -- x -Template version: 4.0 Template release date: 16-Apr-2012 Page 17 of 27

CONFIDENTIAL - PROPRIETARY7 Version 3.0 SP 1 HF 2StatusReleasedTested with Operating System: Windows 7Release Date 16-Oct-2012 Released By Karin AwaloffBuild 3.0.1.2000 Database version n/aDeliverySetupIncludes a full setup with all fixes and features mentioned below.ValidationValidation2.0.0.0022ComponentLibrary1.2.21.307.1 New FeaturesNone7.2 Fixed IssuesIssue 25556: Validating GCC Submissions does not allow to view envelope dataAfter opening an eCTD submission (EU, CH, …), the envelope details are displayed in GUI. But for GCCeCTDthese details are not displayed.Impact low, detectability high, detected in version 3.0.1.1000Issue 25786: EU NeeS 3.0 Rule 02.10 shall accept subfolder in m4In module 4 at least one level of subfolders should be accepted.Impact high, detectability high, detected in version 3.0.1.10007.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified in this versionFDA-eCTD v1.0(DTD 2.01)FDA-eCTD v1.0(DTD 2.01) FASTFDA-eCTD v1.0(DTD 2.01) - GECCOFDA-eCTD v2.1(DTD 2.01)FDA-eCTD v2.1(DTD 2.01) FASTEU-eCTD v2.0(DTD 1.2.1)- x -- x -- x -- x -- x -- x -EU-eCTD v2.1 (DTD 1.3) - x -Template version: 4.0 Template release date: 16-Apr-2012 Page 18 of 27

CONFIDENTIAL - PROPRIETARYEU-eCTD v2.1 (DTD 1.4) - x -EU-eCTD v2.1(DTD 1.4) - GECCO- x (only XML checks) -EU-eCTD v3.1 (DTD 1.4) x x -EU-eCTD v3.1(DTD 1.4) FAST- x -EU-eCTD v4.1 (DTD 1.4) x x -CA-eCTD v1.0(DTD 1.0) - GECCOCH-eCTD v1.0(DTD 1.0/1.0.1)- x (only XML checks) -- x -CH-eCTD v1.1 (DTD 1.1) x x -CH-eCTD v1.1(DTD 1.1) - GECCO- x (only XML checks) -HR-NeeS v1.0 - x -HR-NeeS v2.1 –Submission Onlyx x -HR-eCTD v2.1 (DTD 1.4) - x -HR-eCTD v3.1 (DTD 1.4) x x -GCC-eCTD v1.0 (DTD1.0)- x -EU-NeeS v1.0 - x -EU-NeeS v2.1 –Submission Onlyx x -EU-NeeS v3.0 x x xKSA-NeeS v1.0 - x -VMD-eNTA(immunological product)DTD 0.9VMD-eNTA(pharmaceutical product)DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)- x -- x -- x -- x -Template version: 4.0 Template release date: 16-Apr-2012 Page 19 of 27

CONFIDENTIAL - PROPRIETARY8 Version 3.0 SP 2StatusReleasedTested with Operating System: Windows 7Release Date 22-Feb-2013 Released By Karin AwaloffBuild 3.0.2.0008 Database version n/aDeliveryValidationComponentSetupIncludes a full setup with all fixes and features mentioned below.2.0.0.0025ValidationLibrary1.2.21.388.1 New FeaturesFeature 25327: EU-PDF BP v1.0 (eCTD v4.1) Validation SetBased on PDF rules of EU-eCTD v4.1 this validation set provides a validation for PDF files only. The validationset can be selected for any submission (eCTD, NeeS) containing PDF documents using the validationsets drop down list before starting the validation. It will not be selected by the Autoselect functionality.This feature requires a license and is not available in the free version (EURSvalidator).Feature 25970: MCC-eCTD v1.0 (DTD 1.0) Validation SetSouth Africa plans to introduce eCTD at MCC. The validation sets were built by EXTEDO in 2012.The MCC validation rules are inherited from Swissmedic Validation sets adapted for MCC. The severity ofthe validation criteria are based on pass/fail and best practice (EU validation).Autoselect has been extended to select this new validation set for MCC DTD 1.0.This feature requires a license and is not available in the free version (EURSvalidator).Feature 25971: CA-eCTD v1.0 (DTD 1.0) Validation SetCanada published in 2007 a CA eCTD validation rule set version 1.0.This validation set covers the current “old” Canadian M1 DTD v1.0 (published 2007-11), but without theSTF-2.0-Checks. Some ignore/information checks are excluded too: Rules 11, 13, 15, 17, 22, 24, 26, 28,43 and 45.Autoselect has been extended to select this new validation set for CA DTD 1.0.This feature requires a license and is not available in the free version (EURSvalidator).Feature 25972: CA-eCTD v1.0 (Schema 2.2) Validation SetCanada plans to introduce a new Module 1 (Schema 2.2) on 1st April 2013.This validation set covers the new Canadian M1 schema v2.2 (published 2012-07) and the old CA validationset (published 2007-11), but without the STF-2.0-Checks. Some ignore/information checks are excludedtoo: Rules 11, 13, 15, 17, 22, 24, 26, 28, 43 and 45.This validation set is an interim solution for Canadian M1 until HCSC CA will publish new validation criteria.Here, the “old” validation sets for a DTD are adapted to the new Schema approach. There is no officialdocumentation available describing the adapted sets.Autoselect has been extended to select this new validation set for the new Canadian M1 schema v2.2.This feature requires a license and is not available in the free version (EURSvalidator).Template version: 4.0 Template release date: 16-Apr-2012 Page 20 of 27

CONFIDENTIAL - PROPRIETARYFeature 26423: GCC-eCTD M1v1.2 (DTD 1.0 NEW) v2.1 Validation SetGCC provided an update of their M1 (v1.2) including new validation sets. The first eCTD validation setv1.0 was built by EXTEDO.The GCC validation rules are inherited from EMA Validation sets. The severity of the validation criteriaare based on pass/fail and best practice (EU validation).The former GCC v1.0 validation sets do not cover any file and folder checks. These checks are now included.Autoselect has been extended to select this new validation set for the new GCC DTD 1.0.This feature requires a license and is not available in the free version (EURSvalidator).Feature 26424: KSA-NeeS M1v1.2 (DTD 1.0 NEW) v2.1 Validation SetGCC provided an update of their M1 (v1.2) including new validation sets. The first NeeS validation setv1.0 was built by SFA (official release).The KSA-NeeS validation rules are inherited from EMA Validation sets. The severity of the validationcriteria are based on pass/fail and best practice (EU validation).Autoselect has been updated to select this new validation set for KSA-NeeS instead of the first v1.0.This feature requires a license and is not available in the free version (EURSvalidator).8.2 Fixed IssuesIssue 26126: Misleading error messageWhen loading submissions, a misleading error message appeared if no index.xml or ctd-toc.pdf was presentin the submission folder. This message was now enhanced. In addition, a check for the gtoc.pdf filefor vNeeS is now included.Impact low, detectability medium, detected in version 3.0.1.2000Issue 26402: EU 4.1/NeeS 3.0 rule 16.BP6/03.BP05 ignore wrong initial view settingIf the initial view settings of a document are: Page Layout: Single Page, Magnification: Default, the pagelayout did not lead to a warning. But the correct Setting would be: Page Layout: Default, Magnification:Default (Default value for both).Impact medium, detectability medium, detected in version 3.0.1.2000Issue 26605: Wrong Checksum Error in EU v4.1The rule for the comparison of the checksum stored in index files against the recalculated checksum forthe referenced files shall not report an error, if the checksum difference is only the uppercase/lowercaseof letters A – F. Example: 01234a3e and 01234A3E shall be handled as the same value.Impact medium, detectability medium, detected in version 3.0.1.20008.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set Name EURSvalidator GLOBALvalidator Modified inthis versionFDA-eCTD v1.0 (DTD 2.01) - x -FDA-eCTD v1.0 (DTD 2.01) FAST - x -FDA-eCTD v1.0 (DTD 2.01) - GECCO - x -FDA-eCTD v2.1 (DTD 2.01) - x xFDA-eCTD v2.1 (DTD 2.01) FAST - x xEU-eCTD v2.0 (DTD 1.2.1) - x xTemplate version: 4.0 Template release date: 16-Apr-2012 Page 21 of 27

CONFIDENTIAL - PROPRIETARYEU-eCTD v2.1 (DTD 1.3) - x xEU-eCTD v2.1 (DTD 1.4) - x xEU-eCTD v2.1 (DTD 1.4) - GECCO - x (only XML checks) -EU-eCTD v3.1 (DTD 1.4) x x xEU-eCTD v3.1 (DTD 1.4) FAST - x xEU-eCTD v4.1 (DTD 1.4) x x xEU-PDF BP v1.0 (eCTD v4.1) - x NewCA-eCTD v1.0 (DTD 1.0) - x NewCA-eCTD v1.0 (Schema 2.2) - x NewCA-eCTD v1.0 (DTD 1.0) - GECCO - x (only XML checks) -CH-eCTD v1.0 (DTD 1.0/1.0.1) - x xCH-eCTD v1.1 (DTD 1.1) x x xCH-eCTD v1.1 (DTD 1.1) - GECCO - x (only XML checks) -HR-NeeS v1.0 - x -HR-NeeS v2.1 -Submission Only x x xHR-eCTD v2.1 (DTD 1.4) - x xHR-eCTD v3.1 (DTD 1.4) x x xMCC-eCTD v1.0 (DTD 1.0) - x NewGCC-eCTD v1.0 (DTD 1.0) - x xGCC-eCTD v2.1 (DTD 1.0 NEW) - x NewEU-NeeS v1.0 - x -EU-NeeS v2.1 -Submission Only x x xEU-NeeS v3.0 x x xKSA-NeeS v1.0 - x -KSA-NeeS v2.1 - x NewVMD-eNTA(immunological product) DTD 0.9VMD-eNTA(pharmaceutical product) DTD 0.9vNeeS 1.0(immunological product)vNeeS 1.0(pharmaceutical product)- x -- x -- x -- x -Template version: 4.0 Template release date: 16-Apr-2012 Page 22 of 27

CONFIDENTIAL - PROPRIETARY9 Version 3.0 SP 3StatusReleasedTested with Operating System: Windows 7, Windows 8Release Date 03-Mai-2013 Released By Loïs BéguéBuild 3.0.3.0007 Database version n/aDeliverySetupIncludes a full setup with all fixes and features mentioned below.ValidationComponent2.0.0.0029ValidationLibrary1.2.22.049.1 New FeaturesFeature 26135: Support for Windows 8 and Windows Server 2012GLOBALvalidator should be able to run under Windows 8. This feature ensures the installation and executionon above mentioned Windows versions is working as desired.This feature is available for both licensed and non-licensed users of GLOBALvalidator.Feature 26551: New M1 (m1v1.2) and validation criteria for CH valid from July 1, 2013The new Switzerland standard DTD 1.2 has been published officially by end of March 2013, is recommendedfrom 1st July 2013 and will be mandatory from 1st Jan 2014Autoselect has been extended to select this new validation set.This feature is available for both licensed and non-licensed users of GLOBALvalidator.Feature 26692: EU-eCTD v4.1 Fast Validation SetFor EU-eCTD v3.1 there is a fast validation set available, containing all rules except the PDF checks.A similar fast validation set should be created for EU-eCTD v4.1.This feature requires a GLOBALvalidator license and is not available in the free version (EURSvalidator).Feature 26694:.Additional Validation Set Version Identifier for ReportAgencies reported that a change in the library version requires an update of the EURSvalidator. In casesthe validation set of the respective region is not covered by a change the update means additional workload without any business effect.Validation sets are reported with their library number (example: 1.2.21.38), which is associated with theDLL version number and the common folder name for the library version. This is updated for all validationsets with each build of validation library. An individual setting for selected validation sets is not possible.This feature requires a GLOBALvalidator license and is not available in the free version (EURSvalidator).Feature 26704: Validation Set Pre-Selection on First SetupThe options dialog contains a checkbox list of all validation sets to be visible in the list. Per default on firstsetup all validation sets were checked on. From now on, only the newest versions of the validation setsshall be checked on first setup. The other validation sets must not be selected.This feature requires a GLOBALvalidator license and is not available in the free version (EURSvalidator).Template version: 4.0 Template release date: 16-Apr-2012 Page 23 of 27

CONFIDENTIAL - PROPRIETARYFeature 26839: Support of M1 EU DTD v2.0 Val.Crit. v5.0 for eCTDThe new M1 is becoming effective on 1st Sept. 2013.Autoselect has been extended to select this new validation set.This feature is available for both licensed and non-licensed users of GLOBALvalidator.Feature 26964: Support of M1 EU DTD v2.0 Val.Crit. v4.0 for NEESThe new M1 is becoming effective on 1st Sept. 2013Autoselect has been extended to select this new validation set.This feature is available for both licensed and non-licensed users of GLOBALvalidator.Feature 26966: FDA: Support of FDA DTD 2.01 Val. Crit. 2.1 with valid-values 3.0The new FDA validation sets becoming effective from 30th April 2013 undergo additional adaption. Thevalid values version 3.0 must be utilized for the compliance check instead of the version 2.2.The validation sets for valid value 2.2 have been renamed, now mentioning “vv2.2”.Autoselect has been extended to select this new validation set.This feature is available for both licensed and non-licensed users of GLOBALvalidator.9.2 Fixed IssuesIssue 26830: Rule [5005] Fails: Although correctly embedded, some Subset-Fonts are not recognizedRelated Set: FDA-eCTD v2.1Description: PDFs must embed non-standard fonts. Though, even if a subset font is correctly embedded,the rule 5005 is sometimes broken.Impact low, detectability low, detected in version 3.0.2.0008Issue 26858: Unhandled exception when opening file located in unmapped network driveRelated Set: NoneDescription: Unhandled exception shown in case opening a document which is stored on an unmappednetwork drive.Impact low, detectability medium, detected in version 3.0.3.0002Issue 26861: Exception shown when opening settings while logged in as another userRelated Set: NoneDescription: Exception was shown several times when opening the Application settings under another(standard) user.Impact low, detectability low, detected in version 3.0.3.0001Issue 26877: Create a Digital Signature for GLOBALvalidator to run on Windows 8 / Win Server 2012Related Set: noneDescription: Windows 8 software compliance: application should have a digital signatureImpact low, detectability low, detected in version 3.0.3.0002Issue 26879: missing application form shows "wrong application" errorRelated Set: FDA-eCTD v2.1Description: FDA v2.1 submission without application form leads to an invalid result. Besides Warning no.5033 (An application without an application form has been submitted...) -Medium-, the additional Error no.5038 (A wrong application form based on the application type has been submitted,...) -High- is shown.But only no. 5033 should be displayed in the report.Impact medium, detectability medium, detected in version 3.0.3.0003Template version: 4.0 Template release date: 16-Apr-2012 Page 24 of 27

CONFIDENTIAL - PROPRIETARYIssue 26887: Wrong PDF version does not show a warningRelated Set: CH eCTD v1.1 / 1.2Description: Some PDF documents may contain the wrong version number in their meta data.Impact medium, detectability low, detected in version 3.0.2.0008Issue 26963: Inappropriate recognition of standard fonts while validating PDFs within FDA submissionsRelated Set: FDA-eCTD v2.1Description: The PDF standard defines 14 default fonts, that do not need to be embedded in documents(Helvetica, Courier,…). The FDA standard defines similar but not identical fonts (Arial, Courier,…).Impact medium, detectability medium, detected in version 3.0.2.0008Issue 27021: Problems with FDA validationRelated Set: FDA-eCTD v2.1Description: There’s no differentiation between "356h" and "1571" within check for application number inus-regional.Impact medium, detectability medium, detected in version 3.0.2.0008Issue 27038: Rules [5102] and [5202] are skipped even if the hyperlinks and bookmarks are validRelated Set: FDA-eCTD v2.1Description: The PDF links/bookmarks to named destinations are not checked: skipped. The customercannot check if the links are ok or not.Impact medium, detectability low, detected in version 3.0.2.00089.3 Validation Set SummaryThe following table provides a summary of the available validation sets (x) in the free version (EURSvalidator)and the licensed version of GLOBALvalidator. The last column indicates whether the validation sethas been modified in this version because of bug fixes or enhancements.Validation Set NameEURSvalidatorGLOBALvalidatorModifiedin thisversionFDA-eCTD v1.0 (DTD 2.01) - x -FDA-eCTD v1.0 (DTD 2.01) FAST - x -FDA-eCTD v1.0 (DTD 2.01) - GECCO - x -FDA-eCTD v2.1 (DTD 2.01, vv2.2) - x xFDA-eCTD v2.1 (DTD 2.01, vv2.2) FAST - x xFDA-eCTD v2.1 (DTD 2.01, vv3.0) - x NewFDA-eCTD v2.1 (DTD 2.01, vv3.0) FAST - x NewEU-eCTD v2.0 (DTD 1.2.1) - x -EU-eCTD v2.1 (DTD 1.3) - x -EU-eCTD v2.1 (DTD 1.4) - x -EU-eCTD v2.1 (DTD 1.4) - GECCO - x (only XML checks) -EU-eCTD v3.1 (DTD 1.4) - x -EU-eCTD v3.1 (DTD 1.4) FAST - x -EU-eCTD v4.1 (DTD 1.4) x x -Template version: 4.0 Template release date: 16-Apr-2012 Page 25 of 27

CONFIDENTIAL - PROPRIETARYEU-eCTD v4.1 (DTD 1.4) FAST - x NewEU-eCTD v5.0 (DTD 2.0) x x NewEU-PDF BP v1.0 (eCTD v4.1) - x -CA-eCTD v1.0 (DTD 1.0) - x -CA-eCTD v1.0 (Schema 2.2) - x -CA-eCTD v1.0 (DTD 1.0) - GECCO - x (only XML checks) -CH-eCTD v1.0 (DTD 1.0/1.0.1) - x -CH-eCTD v1.1 (DTD 1.1) x x xCH-eCTD v1.1 (DTD 1.1) - GECCO - x (only XML checks) -CH-eCTD v1.2 (DTD 1.2) x x NewHR-NeeS v1.0 - x -HR-NeeS v2.1 -Submission Only x x -HR-eCTD v2.1 (DTD 1.4) - x -HR-eCTD v3.1 (DTD 1.4) x x -MCC-eCTD v1.0 (DTD 1.0) - x -GCC-eCTD v1.0 (DTD 1.0) - x -GCC-eCTD v2.1 (DTD 1.0 NEW) - x -EU-NeeS v1.0 - x -EU-NeeS v2.1 -Submission Only - x -EU-NeeS v3.0 x x -EU-NeeS v4.0 x x NewKSA-NeeS v1.0 - x -KSA-NeeS v2.1 - x -VMD-eNTA (immunological product) DTD 0.9 - x -VMD-eNTA (pharmaceutical product) DTD 0.9 - x -vNeeS 1.0 (immunological product) - x -vNeeS 1.0 (pharmaceutical product) - x -Template version: 4.0 Template release date: 16-Apr-2012 Page 26 of 27

CONFIDENTIAL - PROPRIETARY10 Known IssuesIssue 24356: Multiple function calls within a test case may drop some error messagesIf a single testcase is to call a single (internal) check function repeatedly, then only the errors producedby the last call may be exposed. Prior calls in the test case may not expose any error: only the last failedfunction call shows its error.Impact low, detectability low, detected in version 3.0.0.0015Issue 26862: Adding dossiers (submissions) quickly in a row returns sometimes a .NET exceptionSometimes, when adding dossiers quickly to the UI using drag & drop, a .NET exception is returned.Impact low, detectability low, detected in version 3.0.3.0001Issue 26987: Issue Absolute Path GLOBAL Validator v3.0 SP2 Build 8Absolute Paths may sometimes not be detected in some PDF documents. The utilized 3 rd Party Component“iText library” may not load all hyperlinks of a document due to the unusual format of some metadata. The check function does not identify these “absolute path” links then.Impact: medium, detectability: medium, detected in version: 3.0.2.0008Issue 26993: Change the version of the KSA-NeeS 2.1 to KSA-NeeS 1.2 (see the report attached)Request from Authority. Change the version of the KSA-NeeS 2.1 to KSA-NeeS 1.2.It’s a typo issue.Impact low, detectability low, detected in version 3.0.2.0000Issue 27166: CH - Capital letter in galenic form does not show an errorIf there´s a capital letter in the folder name of the galenic form, the application does not show an errorbut should give error no. A11.Impact medium, detectability low, detected in version 3.0.3.0006Template version: 4.0 Template release date: 16-Apr-2012 Page 27 of 27