AU Validation 3.1 (Full) AU 3.1 en Full AU Validation Criteria v3.1 with additional recommended criteria. XML backbones identification 6.17.39 6.17.56 6.17.65 6.17.66 6.17.80 6.17.81 STF identification 6.17.214 Folders must not be empty 6.17.62 File size limits should not be exceeded 6.17.21 6.17.23 Unreferenced files are not allowed 6.17.37 File types (file extensions) check 6.17.9 6.17.44 File name syntax must be correct 6.17.33 6.17.34 6.17.35 Folder m1 exists and no files are placed there. 6.17.37 Folder util exists and contained files are correct 6.17.8 6.17.38 6.17.46 6.17.47 6.17.57 6.17.178 No other files are allowed in sequence root folder 6.17.37 Sequence folder requirements should be followed 6.17.30 6.17.32 6.17.213 File index.xml must exist 6.17.39 The reference to the DTD in index.xml is directed to the DTD provided in the util folder. 6.17.52 The index.xml file must be valid 6.17.48 The files referenced by the cross reference (xlink:href) must exist 6.17.28 Multiple operations on same document in same sequence are not allowed 6.17.209 Replace or append should not provide content identical to the previous file 6.17.208 Leaf operation attribute 6.17.13 6.17.26 6.17.27 6.17.42 6.17.207 Modified file existence 6.17.14 Only relative references are being used 6.17.29 References to targets outside application 6.17.206 References to targets outside sequence 6.17.205 Attribute checksum-type 6.17.2 MD5 Checksum 6.17.7 MD5 for Index file 6.17.5 Node Extension title must not be empty 6.17.25 Leaf title must not be empty 6.17.25 Element must have leaf 6.17.204 Attribute value checks 6.17.212 m1-administrative element must exist 6.17.211 File reuse 6.17.202 Use of Append 6.17.230 Constraints for sequence type Product Withdrawal 6.17.286 Requirements for submissions with sequence description Withdrawal 6.17.287 All individual references should be provided as separate files and uniquely identified 6.17.290 Detect invalid life cycle pattern: Append operations causing branches 6.17.201 Detect invalid life cycle pattern: Delete operations causing branches 6.17.201 Detect invalid life cycle pattern: Replace operations causing branches 6.17.201 Detect invalid life cycle pattern: Operation on deleted leaf content 6.17.200 Detect invalid life cycle pattern: Append on Append 6.17.199 Detect invalid life cycle pattern: Append operations not appending to most recent STF leaf 6.17.210 Module 1 (regional xml file) exists 6.17.39 The reference to the Schema in au-regional.xml is directed to the Schema provided in the util folder. 6.17.52 The regional backbone file must be valid. 6.17.48 The files referenced by the cross reference (xlink:href) must exist 6.17.28 Multiple operations on same document in same sequence are not allowed 6.17.209 Replace or append should not provide content identical to the previous file 6.17.208 Leaf operations 6.17.13 6.17.26 6.17.27 6.17.42 6.17.207 Modified file existence 6.17.14 Only relative references are being used 6.17.29 HREFs to targets outside application 6.17.206 HREFs to targets outside sequence 6.17.205 Attribute checksum-type 6.17.2 MD5 Checksum 6.17.7 Cover letter operation attribute 6.17.181 Node Extension title must not be empty 6.17.25 Leaf title must not be empty 6.17.25 Element must have leaf 6.17.204 Application folder name must match esub-id 6.17.163 Sequence folder name must match sequence number from backbone 6.17.31 Element related-sequence-number value 6.17.203 File reuse 6.17.202 Application form operation attribute 6.17.181 Foreign regulatory status operation 6.17.231 Risk management plan operation 6.17.232 Sequence type references in related-sequence-number 6.17.234 Lifecycle management tracking table operation 6.17.233 Use of Append 6.17.230 Lifecycle Operations in section 1.3 6.17.289 Constraints for sequence type Product Withdrawal 6.17.286 Constraints for sequence description Withdrawal 6.17.287 Detect invalid life cycle pattern: Append operations causing branches 6.17.201 Detect invalid life cycle pattern: Delete operations causing branches 6.17.201 Detect invalid life cycle pattern: Replace operations causing branches 6.17.201 Detect invalid life cycle pattern: Operation on deleted leaf content 6.17.200 Detect invalid life cycle pattern: Append on Append 6.17.199 Envelope: esub-id 6.17.198 Envelope: client-id 6.17.197 Envelope: aan 6.17.196 Envelope: product-name 6.17.195 Envelope: artg-number 6.17.194 Envelope: sequence-type 6.17.193 Envelope: sequence-type (version plausibility) 6.17.192 Envelope: sequence-description 6.17.191 Envelope: sequence-description (version plausibility) 6.17.190 Envelope: reg-activity-lead 6.17.189 Envelope: reg-activity-lead (version plausibility) 6.17.188 Envelope: Sequence type vs. Sequence Description 6.17.235 Envelope: submission-number 6.17.291 Envelope: submission-mode 6.17.292 Envelope: Submission number combinations 6.17.293 Envelope: email 6.17.294 Required documents 6.17.236 Expected documents 6.17.236 Possible documents 6.17.236 Check index reference 6.17.139 Check index reference (title match) 6.17.187 Content Blocks are not accepted 6.17.106 No backslash in xlink:href reference 6.17.186 Study Identifier category must not be empty 6.17.185 Study Identifier study-id must not be empty 6.17.132 Study Identifier title must not be empty 6.17.130 Categories and file tags 6.17.184 STF leaf elements must reference other STF leaf upon append 6.17.183 Category information must be provided for certain STFs 6.17.182 STF cannot reference another STF 6.17.141 STF files must reference at least one leaf 6.17.140 Study ID for STF must remain constant 6.17.138 Invalid STF TOC location 6.17.135 STF doc-content file tag count 6.17.134 Informational output about the number and total size of non E3 documents. 6.17.216 PDF documents must be readable 6.17.43 Bookmarks must be relative 6.17.15 Bookmarks with web or email destinations 6.17.89 Bookmarks to other external destinations (not web or email) are not allowed 6.17.88 Bookmarks with unknown actions are not allowed 6.17.87 Bookmarks must not be inactive 6.17.86 Bookmarks must not be broken 6.17.17 Bookmarks must not have multiple actions 6.17.85 Bookmarks must 'Inherit Zoom' 6.17.63 Hyperlinks must be relative 6.17.15 Hyperlinks with web or email destinations 6.17.89 Hyperlinks to other external destinations (not web or email) are not allowed 6.17.88 Hyperlinks with unknown actions are not allowed 6.17.87 Hyperlinks must not be inactive 6.17.86 Hyperlinks must not be broken 6.17.17 Hyperlinks must not have multiple actions 6.17.85 Hyperlinks must 'Inherit Zoom' 6.17.63 PDF version must be correct 6.17.18 PDF documents with attachments are not allowed 6.17.84 PDF documents with annotations 6.17.83 PDF documents should not have any security settings 6.17.40 PDF initial view must be correct 6.17.10 6.17.11 6.17.12 PDF documents must not be password protected 6.17.40 PDF should have 'Fast Web Access' active 6.17.16 Documents with more than 10 pages should have bookmarks. 6.17.281 Ensure that 'checksum' attribute is present and value for the attribute is provided (i.e. not empty string) when 'operation' attribute for the leaf(s) is 'new', 'append' or 'replace'. 6.17.3 Ensure that 'checksum' attribute value is not provided when 'operation' attribute for the leaf(s) is 'delete'. 6.17.4 Ensure that invalid formatting is not provided for 'checksum' in index-md5.txt (32 characters are not specified for the MD5 checksum, or included trailing spaces or carriage returns). 6.17.6 Ensure that all lowest level heading elements included in the submission (index and regional xml file - section, node extension and/or nested node extensions) must contain one leaf. The system shall include in the message the lowest level section name where no leaf child nodes are provided in the xml backbone files (index and regional). 6.17.19 Ensure that value for ID attribute must start with a letter or underscore character. The system shall include in the message the name of the file where leaf id does not starts with a letter or an underscore in the xml backbone files (index and regional). 6.17.20 Ensure there is no reference leaf(s) point to a file (outside of the eCTD lifecycle) across application (xlink:href points to a different application). The system shall include in the message name of the file where xlink:href (application id in the xlink:href does not match with current application) points to different application. 6.17.24 Ensure that the syntax of the modified-file attribute is in accordance with the ICH 3.2 DTD version. The system shall include in the message the title or name of the file where modified-file attribute does not contain correct syntax (i.e. modified- file="../0001/index.xml#a1234567"). 6.17.41 Ensure that the names of all files and folders in the submission corresponds to the ICH and/or regional agency defined folder structure and file names (i.e. extra subfolders should be reported, 'rp' or 'ap' suffix in file names of the ASMF submission shall be ignored by the validation). The system shall include in the message name and/or title of the file or folder which does not conform to agency defined structure and/or name. 6.17.49 Ensure that the reference to the stylesheet in the backbone xml files are directed to the stylesheet provided in the util folder. 6.17.51 Ensure that one and only one index-md5.txt file exists and is placed in the correct location (i.e. <app-id>\<seq-num>\index-md5.txt). 6.17.53 Ensure that index MD5 txt file is named correctly (i.e. index-md5.txt). 6.17.54 Ensure that a valid ICH, regional and STF stylesheet exists in the util folder (i.e. checksum of the ICH and regional stylesheets in util folder must match the published checksum of the stylesheet provided by the agency) of the compiled and/or imported submission. 6.17.55 Ensure that ICH and regional stylesheet files exist in correct location (i.e. <app-id>\<seq-num>\util\style) and are named correctly. 6.17.58 Ensure that all files and folders in the submission are accessible to the user. The system shall include in the message title of the file and/or folder that is not accessible to the user 6.17.64 Ensure that all hyperlinks and bookmarks between two PDFs must be configured as specified in ISO 32000-1:2008 (link path must not contain back slash, only forward slash is allowed, links must not be made with Java script code). The system shall include in the message the name of the file containing hyperlinks and/or bookmarks that are not according to the ISO 32000-1:2008 specification. 6.17.67 Ensure that the hyperlinks and/or bookmarks in the submission documents does not target document outside current eCTD application. 6.17.69 count (keep track during validation) of all of the hyperlinks and the bookmarks with following criteria and list the result in the process log at the end of the compile and/or import process. - Non-Relative Hyperlinks - Non-Relative Bookmarks - Web link and email hyperlinks - Web links and email bookmarks - External Hyperlinks (excluding web links and emails) - External Bookmarks (excluding web links and emails) - Unknown Action Hyperlinks - Unknown Action Bookmarks - Inactive Hyperlinks - Inactive Bookmarks - Broken Hyperlinks (separate count for inter-application, intra-application and intra-sequence) - Broken Bookmarks (separate count for inter-application, intra-application and intra-sequence) - Number of bookmarks per document - Total number of bookmarks in the submission - Number of hyperlinks per document - Total number of hyperlinks in the submission 6.17.90 Ensure that the link and/or bookmark destination does not point to a corrupt document. The system shall include in the message the name/title of the file (including page number) containing hyperlinks and/or bookmarks that points to corrupt document. 6.17.91 Ensure that the links and/or bookmark in the submission documents point to an existing page and/or named destinations. The system shall include in the message the name/title of the file (including page number) containing hyperlinks and/or bookmarks that point to non-existing page and/or named destinations. 6.17.92 Ensure that 'property' element (if present) is listed before its sibling 'file-tag' element in all of the stf files of the submission. Message shall include the STF file name /title and reference leaf in the STF where 'property' element is listed after 'file-tag'. 6.17.107 Ensure that 'property' element is present in all of the stf files in the submission created with STF DTD v2.0 only. Message shall include the STF file name /title where 'property' element is missing in STF (DTD v2.0). 6.17.108 Ensure that child element 'title' is not provided in the doc-content of the STF files in the submission. Message shall include the STF file name /title and reference to the doc-content element where title is provided. 6.17.109 Ensure that an STF xml file is referenced in a submission only once. Message shall include the file name /title and the sections where stf is referenced. 6.17.129 Ensure that STF files are not missing in the submission (i.e. xlink:href contains ‘stf-xxxxxxxx.xml’ but system is not able to locate the file). Message shall include the STF file name and the location of the stf in the submission. 6.17.131 Ensure that STF title (within study-identifier element) in the stf xml file matches with the leaf title for the stf in the index.xml file. Message shall include the file name/title of the stf which does not match with leaf title. 6.17.133 Ensure that STF’s in the submission are named correctly based on the naming convention i.e. ‘STF-<study-id>.xml’. 6.17.136 Ensure that STFs in the submission have valid file extension (file extension is not missing and it is .xml). 6.17.137 Ensure that files in study sections are referenced by an STF. 6.17.142 Ensure that valid STF DTD version (e.g. dtd-version = "2.2") is referenced in the STF XML file. 6.17.143 Ensure that 'title' element of the 'leaf' and/or 'node-extension' does not begins or ends with a space. The system shall include in the message name/title of the node extension where title begins or ends with space. 6.17.167 Ensure that valid/supported 'dtd-version' is referenced in the ICH and regional backbone xml files. 6.17.170 Ensure that 'dtd-version' is referenced in the ICH and regional backbone xml files. 6.17.173 Ensure that required attributes (e.g. 'indication' in the section 5.3.5 element or 'type of control' in the STF XML file for a study in section 5.3.5.1) are present in the back bone xmls (index and regional) and in the heading element of STF XML file(s). 6.17.176 Ensure that attribute (i.e. substance, company-name, species) values in ICH, regional and/or STF backbone files does not begins or ends with a space. The system shall include in the message attribute and value that begins or ends with space. 6.17.177 Ensure that operation attribute is present and valid value ('new', 'append', 'replace' or 'delete') for the attribute is provided. The system shall include in the message the name of the file where operation attribute is not present and/or valid value is not provided. 6.17.180 Ensure that the sequence being validated is the highest sequence in the application. 6.17.217 Ensure that the reference for the regional xml backbone file in index.xml must have operation attribute value 'new'. 6.17.219 Ensure that 'm1' folder must exist in the submission. 6.17.220 Ensure that there is a stylesheet declaration in backbone xml files (index, regional and STF). 6.17.229 Ensure that the sequence numbers in an application are increased incrementally (The sequence number related to the life cycle should increase incrementally with each subsequent submission, for example 0000, 0001, 0002 etc. (the increase should occur in chronological order). 6.17.238 Ensure that TS.xpt is present in STF for module 4, sections 4.2.3.1, 4.2.3.2, 4.2.3.4 and in module 5, sections 5.3.1.1, 5.3.1.2, 5.3.3.1, 5.3.3.2, 5.3.3.3, 5.3.3.4, 5.3.4, 5.3.5.1, 5.3.5.2 6.17.255 Ensure that for each dataset (filename configured) type there is only one leaf referenced in an STF is of operation type 'new'. 6.17.259