JP Validation 1.0b (Full) JP 1.0b en Full JP Validation Criteria v1.0b with additional recommended criteria. Ensure that the 'checksum-type' attribute must have the value md5 or MD5 6.17.2 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 the 'checksum' of the index.xml file (calculated by validation tool) must match the checksum provided in the index-md5.txt file 6.17.5 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 Allow a user to validate the completeness and correctness of the folder(s) and file(s) transfer by regenerating the MD5 checksum of the file(s) and comparing it with the MD5 provided for the file ('checksum' attribute) in backbone (index and regional) xml files 6.17.7 Ensure that the checksum of the DTD for STFs provided in the util folder must match the checksum value provided by the agency 6.17.8 Ensure that all files must have one and only one file extension 6.17.9 Ensure that the bookmark pane is visible ('initial view' of the document is set to 'Bookmarks Panel and Page') when the pdf document contains bookmark(s) 6.17.10 Ensure that the bookmark pane is not visible ('initial view' of the document is set to 'Page Only’) when the pdf document does not contain bookmark(s) 6.17.11 Ensure that all PDF files open in "most recent view" (i.e. 'inherit zoom for bookmarks and links, 'default' in open dialog box (ICH eCTD Specs p7-4), and "Page Layout = Default" and "Magnification = Default") 6.17.12 Ensure that modified-file attribute is present and value for the attribute is provided (i.e. not empty string) when the leaf operation of the file is 'append', 'replace' or 'delete' 6.17.13 Ensure that the leaf referenced in 'modified-file' attribute exists (in the backbone xml file for the sequence number referenced in modified-file attribute and is present physically in the compile/import location) 6.17.14 Ensure that all hyperlinks and bookmarks in the submission documents are relative links (not absolute or rooted) 6.17.15 Ensure that 'Fast Web Access' is enabled for all PDF files in the submission 6.17.16 Ensure that there are no broken hyperlinks and/or bookmarks (internal, external - same sequence, across sequence, across application) in a PDF document in the submission 6.17.17 Ensure that pdf version number is valid (only 1.4 or 1.5 or 1.6 or 1.7) for all PDF documents in the submission 6.17.18 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 6.17.19 Ensure that value for ID attribute must start with a letter or underscore character 6.17.20 Ensure that file size does not exceed with the Default max value define for the region 6.17.21 Ensure 'title' attribute is present for every leaf(s) (regardless of the leaf operation) and/or node extension(s) and the value for the attribute is not empty 6.17.25 Ensure that the value for xlink:href (if present) must be blank when the value for operation attribute is 'delete' for the leaf 6.17.26 Ensure that xlink:href attribute is present and value for the attribute is provided when the value for operation attribute is 'new' or 'append' or 'replace' 6.17.27 Ensure that the xlink:href and/or modified-file attribute conforms to the eCTD standard (valid characters - no backslash '\', colon':', asterisk'*', question mark'?', less than'<', greater than'>', pipe' | ', or space ' ', file path relative to the backbone xml files and includes file name in the path) 6.17.29 Ensure that the Sequence Number contains four digits (i.e. numbers between 0000 to 9999) in the regional xml file and in the sequence folder 6.17.30 Ensure that the sequence Number (in each envelope) in regional backbone xml file (GC: sequence, ZA: ectd-sequence, CH:ectd-sequence, EU: sequence, AU: sequence-number, US: sequence-number, CA: sequence-number) must match the sequence folder name 6.17.31 Ensure that the same Sequence Number is not already used in the application (including folder name) 6.17.32 Ensure that for all leafs in the submission, file names (including extension) and/or folder names does not exceed 64 characters 6.17.33 Ensure that for all leafs in the submission, file names and/or folder names contains valid characters (only a-z, 0-9 and hyphen characters are allowed - must not contain tilde(~), forward slash(/), backslash(\), colon(:), asterisk(*), question mark(?), single quote('), double quote(") less than(<), greater than(>), pipe( | ), or space( )) 6.17.34 Ensure that the leaf element path does not exceed max number of character length allowed for that region 6.17.35 Ensure that there no unreferenced files in the submission (i.e. sequence folder only contains index.xml and index.md5.txt file, M1 to M5 does not have extra files, M1 folder does not contain any files) 6.17.37 Ensure that 'util' folder exists and is in the correct location (<sequence number>/util) 6.17.38 Ensure that one and only one index.xml and regional.xml files exist and are placed in the correct location (index: <app-id>\<seq-num>\index.xml and regional: <app-id>\<seq-num>\m1\<region>\ xx-regional.xml) 6.17.39 Ensure that there is no security setting or password protection (i.e. certificate security, owner password set or adobe policy server settings and All ‘restrictions’ should be ‘allowed’ when viewing Document Preferences-->Security settings) to access and open any files in the submission 6.17.40 Ensure that the syntax of the modified-file attribute is in accordance with the ICH 3.2 DTD version 6.17.41 Ensure that modified-file attribute is not present and/or value for the attribute is not provided when the leaf operation of the file is 'new' 6.17.42 Ensure that there are no corrupted/unreadable files in the submission (meaning PDF files can be opened by ISO 32000-1 compliant software. Content is not invalid or the page count is not 0 or the encryption is not too strong) 6.17.43 Ensure that the files provided in the folders for Module 1 to 5 are in acceptable format for the region 6.17.44 Ensure that a valid ICH DTD exists in the util folder (i.e. checksum of the ICH dtd in util folder must match the published checksum of the DTD provided by the agency) of the compiled and/or imported submission 6.17.46 Ensure that a valid regional DTD (including mod files) and/or schema exists in the util folder (i.e. checksum of the regional dtd/schema and mod file in util folder must match the published checksum of the DTD provided by the agency) of the compiled and/or imported submission 6.17.47 Ensure that the backbone xml files (index, regional and STF) are well-formed (i.e. syntax is correct) and are valid as compared to the DTD / schema and/or attribute files versions provided in the 'util/dtd' folder of the compiled and/or imported submission 6.17.48 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) 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 the reference to the DTD or schema in the backbone xml files are directed to the DTD or schema provided in the util folder 6.17.52 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 xml backbone files are named correctly 6.17.56 Ensure that all required ICH and regional DTD (including .mod files) and/or Schema files referenced in the submission must exists in correct location (i.e. <app-id>\<seq-num>\util\dtd) and these files are named correctly 6.17.57 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 there no empty folders in the submission (i.e. folders without files or subfolders) 6.17.62 Ensure that all hyperlinks and bookmarks (internal, external, same sequence, across sequences and across applications) in the submission documents are set to inherit-zoom 6.17.63 Ensure that all files and folders in the submission are accessible to the user 6.17.64 Ensure that the ICH DTD versions used in the current sequence (sequence being tested) is equal to or higher than the DTD version used in the numerically preceding sequence of the application 6.17.65 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) 6.17.67 Ensure that the ICH DTD version used in the current sequence (sequence being tested) is equal to or lower than the DTD version used in the numerically succeeding sequence of the application 6.17.80 Ensure that for all leaves,except leaves within node extensions(and leaves in module 3.2.A for EU 3.0.2) within the same CTD section with an operation attribute value of replace, delete or append, the modified file must be present in the same eCTD section (same section heading and same metadata combination) of the dossier.Using the operation attribute 'delete' to remove content in sections which are no longer used, due to updates of the eCTD, should be exempt from this rule 6.17.82 Provide list of all documents in the submission containing annotation (other than links and bookmarks) 6.17.83 Ensure that all hyperlinks and bookmarks in the submission documents must not have multiple actions (e.g. opening two different pages) 6.17.85 Ensure that all hyperlinks and bookmarks (internal, external, same sequence, across sequences and across applications) in the submission documents are not inactive (without any action) 6.17.86 Ensure that all hyperlinks and bookmarks in the submission documents must not have unknown action (links that could not be identified or contain JavaScript code) and print total count 6.17.87 Ensure that all hyperlinks and bookmarks in the submission documents must not point to external destinations (other than web or email) 6.17.88 Ensure that all hyperlinks and bookmarks in the submission documents must not point to web address or email 6.17.89 Ensure that the link and/or bookmark destination does not point to a corrupt document 6.17.91 The system shall ensure that the links and/or bookmark in the submission documents point to an existing page and/or named destinations 6.17.92 Ensure that all documents in the submission are text searchable 6.17.93 Ensure that fonts referenced by the PDF documents in the submission are standard fonts and all non-standard fonts are fully embedded 6.17.102 Ensure that all stf files in the submission do not contain 'content-block' element 6.17.106 Ensure that 'property' element (if present) is listed before its sibling 'file-tag' element in all of the stf files of the submission 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 6.17.108 Ensure that child element 'title' is not provided in the doc-content of the STF files in the submission 6.17.109 Ensure that an STF xml file is referenced in a submission only once 6.17.129 Ensure that 'title' element (within 'study-identifier') is present and value for title is provided in the STF xml file 6.17.130 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) 6.17.131 Ensure that STFs (files named as ‘stf-xxxxxxxxx.xml’) in the submission contain study-id information (element and the value is not empty) and reference leafs 6.17.132 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 6.17.133 Ensure that one and only one doc-content file-tag is specified for each file referenced in the STFs. 6.17.134 Ensure that STF is only referenced in the sections of M4 and M5 allowed as per the STF specification 6.17.135 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 lifecycle stf must have the same study-id as the original stf (referenced by the modified-file) 6.17.138 Ensure that files referenced by an STF exist in the submission/application (referenced by index.xml) 6.17.139 Ensure that STF file must reference at least one leaf element 6.17.140 Ensure that an STF file does not reference another STF file 6.17.141 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 valid STF DTD version (e.g. version = "STF Version 2.2") is listed in the index.xml file for stf leaf element 6.17.144 Ensure that STF DTD version in stf xml file (i.e. dtd-version = "2.2") must match the stf dtd version specified for the stf leaf in index.xml file (i.e. version = "STF Version 2.2") 6.17.145 Ensure that STF DTD version (e.g. dtd-version = "2.2") is specified in the STF XML file 6.17.146 Ensure that STF DTD version (e.g. version = "STF Version 2.2") is specified in the index.xml file for stf leaf element 6.17.147 Ensure that stf xml file is not cumulative information 6.17.148 Ensure that leaf 'title' and/or 'keyword' (if present) are no longer than 512 characters 6.17.164 Ensure that 'title' element of the 'leaf' and/or 'node-extension' does not begins or ends with a 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 extra attributes (i.e. 'manufacturer' attribute is referenced in m4 or m5 section, or 'species' attribute is referenced in m5 STF) are not specified in the xml backbone files 6.17.174 Ensure that an attribute is not referenced multiple times in an STF (i.e. two ‘type-of-control ‘) 6.17.175 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 6.17.177 Ensure that non-required files are not present in the util folder (i.e. submission does not have an stf or leaf but the stylesheet and dtd files are present in the util folder) 6.17.178 Ensure that operation attribute is present and valid value ('new', 'append', 'replace' or 'delete') for the attribute is provided 6.17.180 Ensure that 'category' information must be provided for STFs in following sections: • 4.2.3.1 Single dose toxicity section contains 'species' and 'route-of-admin'. • 4.2.3.2 Repeat dose toxicity section contains 'species', 'route-of-admin', and 'duration' (if applicable). • 4.2.3.4.1 Long term [carcinogenicity] studies contain 'species'. • 5.3.5.1 Study reports of controlled clinical studies pertinent to the claimed indication contain 'type-of-control’. 6.17.182 Ensure that 'modified-file' of lifecycle stf must point to a stf (e.g. not a pdf document) 6.17.183 Ensure that 'file-tag' values and 'category' values are valid as per the 'valid-values.xml' file referenced by the submission 6.17.184 Ensure that value for study-identifier/category element must not be empty 6.17.185 Ensure that 'xlink:href' attribute of a leaf referenced in an STF must exists and must not contain backslashes 6.17.186 Ensure that the titles from the doc-content elements (if present) must match the corresponding leaf title values in the ICH backbone 6.17.187 Ensure that 'append' operation is not applied on an existing lifecycle 'append' leaf (E.g. Detect invalid life cycle pattern: sequence 0001 appends a document in sequence 0000, sequence 0002 append operation leads to the append in 0001.) 6.17.199 Ensure that leaf lifecycle operation ('append', 'replace' or 'delete') is not applied to a lifecycle 'delete' leaf (E.g. sequence 0001 deletes a document in sequence 0000, sequence 0002 any life cycle operation leads to the already deleted leaf in 0001.) 6.17.200 Ensure that a leaf is not lifecycled ('append', 'replace' or 'delete') by more than one leaf to cause branching (i.e. scenario where a append/replace/delete operation is being applied on a leaf, which has already been replaced by another leaf. E.g. sequence 0001 replaces a document in sequence 0000, sequence 0002 append operation leads to the already replaced leaf in 0000.) 6.17.201 Ensure multiple lifecycle operations on same document in same sequence are not allowed (E.g. sequence 0001 includes two lifecylce operations referencing the same leaf in sequence 0000.) 6.17.209 Ensure that most recent stf (stf that was lifecycled last instead of previous or original stf) is lifecycled 6.17.210 Ensure attribute (if present i.e. indication, excipient, dosage-form, manufacturer, product-name, substance etc.) value must not be empty string 6.17.212 Ensure that the sequence being validated is the highest sequence in the application 6.17.217 Ensure that 'm1' folder must exist in the submission 6.17.220 Ensure that 'submission-type' attribute is present and valid value for the attribute is provided (from the list of values provided in the DTD) 6.17.228 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 Demographic (DM) dataset and define.xml for Standard for Exchange of Nonclinical Data (SEND) data must be submitted in module 4, sections 4.2.3.1, 4.2.3.2, 4.2.3.4 6.17.257 Ensure that Demographic (DM) dataset and define.xml for Study Data Tabulation Model (SDTM) data or ADaM Subject level analysis dataset (ADSL) dataset and define.xml for Analysis Data Model (ADaM) must be submitted 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 6.17.258 Ensure that only one dataset of each type (filename configured) referenced in an STF is marked as 'new' operation Note: This is applicable for : Module 4 : section 4.2.3.1, 4.2.3.2, 4.2.3.4 Module 5: section 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 6.17.259 Ensure PDF documents with more than 10 pages must have bookmarks 6.17.281