CN Validation 1.1 (Full) CN 1.1 en Full CN Validation Criteria v1.1 with additional recommended criteria. File Quantity Statistics 6.17.326 File Size Statistics 6.17.326 Empty Chapters Statistics 6.17.19 The file folder must not be empty. 6.17.62 The file size limit should not be exceeded. 6.17.21 6.17.23 Unreferenced files are not allowed. 6.17.37 File type (file extension check) 6.17.9 6.17.44 The naming of files and folders must be correct. 6.17.34 m1 folder exists, and no files are placed. 6.17.37 6.17.220 util file folder exists and contained files must be correct. 6.17.8 6.17.46 6.17.47 6.17.55 6.17.51 6.17.58 No other files are allowed in sequence root folder 6.17.37 Sequence folder requirement 6.17.30 Sequence number 6.17.238 Index.xml file 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 File index.xml must be valid. 6.17.48 The file 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 Replaced or appended contents should not be identical to the previous files. 6.17.208 Leaf element: new, replaced or appended leaf elements must have a value for the cross reference (xlink:href). 6.17.27 Leaf element: deleted leaf element must have no value for the cross reference (xlink:href). 6.17.26 Leaf element: replaced, deleted and appended leaf elements must have a corresponding modified file. 6.17.13 Leaf element: all files provided in the initial sequence must be in operation ‘New’. 6.17.207 The modified file must exist. 6.17.14 Only relative paths can be used in reference. 6.17.29 'checksum-type' attribute 6.17.2 Check of MD5 checksum 6.17.7 Check of MD5 checksum for the backbone file 6.17.5 Requirements for the use of node extension 6.17.350 Naming rules of title of node extension 6.17.351 The leaf title must not be empty 6.17.25 The 'delete' leaf title must match the 'deleted' leaf title 6.17.306 No space is added at the beginning or end of the leaf title. 6.17.167 Element must have leaf. 6.17.204 m1 administrative information and prescribing information must exist. 6.17.211 Use of append 6.17.230 File should not be relocated. 6.17.82 Attribute-indications 6.17.176 Attribute-manufacturer 6.17.176 Attribute-substance 6.17.176 No space is added at the beginning or end of the attribute value. 6.17.177 Reference to content 6.17.24 Detect invalid life cycle pattern: Append operation causes branches 6.17.201 Detect invalid life cycle pattern: Delete operation causes branches 6.17.201 Detect invalid life cycle pattern: Replace operation causes branches 6.17.201 Detect invalid life cycle pattern: operation on deleted leaf element 6.17.200 Detect invalid life cycle pattern: Append operation on an appended leaf element 6.17.199 Detect invalid life cycle pattern: Append operation on the STF leaf element that is not the latest 6.17.210 The language attribute cannot be changed during the replacement operation 6.17.352 The regional xml file in Module 1 must exist. 6.17.39 The reference to the schema in cn-regional.xml is directed to the Schema provided in util folder. 6.17.52 The regional backbone file must be valid. 6.17.48 The current sequence must use a schema version that is no lower than that used in the previous sequence 6.17.66 The file referenced by the attribute of file reference (xlink:href) must exist. 6.17.28 Multiple operations on same document in same sequence are not allowed. 6.17.209 Replaced or appended contents should not be identical to the previous files. 6.17.208 Leaf element: new, replaced or appended leaf elements must have a value of file reference (xlink:href). 6.17.27 Leaf element: deleted leaf element must have no value of file reference (xlink:href). 6.17.26 Leaf element: replaced, deleted and appended leaf elements must have a corresponding modified file. 6.17.13 Leaf element: all files provided in the initial sequence must be in operation ‘New’. 6.17.207 'checksum-type' attribute 6.17.2 Check of MD5 checksum 6.17.7 Operation attribute for cover letter 6.17.181 Operation attribute for application form 6.17.181 Use of 'Node Extension' is not allowed. 6.17.168 The leaf title must not be empty. 6.17.25 The 'delete' leaf title must match the 'deleted' leaf title. 6.17.306 No space is added at the beginning or end of the leaf title. 6.17.167 There must be a leaf element under the element. 6.17.204 Application folder title 6.17.163 Sequence folder title 6.17.31 M1 folder directory structure 6.17.327 Reference to content 6.17.24 Detect invalid life cycle pattern: append operation causes branches 6.17.201 Detect invalid life cycle pattern: deletion operation causes branches 6.17.201 Detect invalid life cycle pattern: replacement operation causes branches 6.17.201 Detect invalid life cycle pattern: operation of the deleted leaf element 6.17.200 Detect invalid life cycle pattern: append operation to an appended leaf element 6.17.199 Use of append 6.17.230 The language attribute cannot be changed during the replacement operation 6.17.353 Envelope element: application number 6.17.105 Envelope element: application type 6.17.165 Envelope element: product type 6.17.311 Envelope element: original number 6.17.308 Envelope element: related sequence 6.17.104 6.17.203 Envelope element: regulatory activity type 6.17.312 Envelope element: sequence number 6.17.30 Envelope element: sequence type 6.17.193 Envelope element: sequence description 6.17.309 Envelope element: sequence correlation information 6.17.314 Value of correlation sequence 6.17.74 Value of correlation sequence 6.17.247 Envelope element at application level must remain unchanged 6.17.307 The type of regulatory activity must remain unchanged 6.17.310 Integrity validation of Module 1: Application type: New Drug Application Regulatory activity type: Original Application or New Indication Sequence type: Original 6.17.315 Integrity validation of Module 1: Application type: New Drug Application Regulatory activity type: Original Application or New Indication Sequence type: Original 6.17.316 Integrity validation of Module 1: Application type: Abbreviated New Drug Application Regulatory activity type: Original Application or New Indication Sequence type: Original 6.17.317 Integrity validation of Module 1: Application type: Abbreviated New Drug Application Regulatory activity type: Original Application or New Indication Sequence type: Original 6.17.318 Integrity validation of Module 1: Application type: Investigational New Drug Regulatory activity type: Original Application or New Indication and Drug Combination Sequence type: Original 6.17.319 Integrity validation of Module 1: Application type: Investigational New Drug Regulatory activity type: Original Application or New Indication and Drug Combination Sequence type: Original 6.17.320 Integrity validation of Module 1: Application type: Investigational New Drug Regulatory activity type: Development Safety Report Sequence type: Original 6.17.321 Integrity validation of Module 1: Application type: Investigational New Drug Regulatory activity type: Development Safety Report Sequence type: Original 6.17.322 Number of leaf elements contained in an element 6.17.323 Integrity validation of Module 1: Application type: Drug Substance Application Regulatory activity type: Original Application Sequence type: Original 6.17.313 Integrity validation of Module 1: Application type: Drug Substance Application Regulatory activity type: Original Application Sequence type: Original 6.17.324 STF file must be valid. 6.17.48 Check the index reference. 6.17.186 'content-block' element is not recommended. 6.17.106 File reference must not use backslash. 6.17.186 The category element of study identifier can’t be empty. 6.17.185 Study ID of the study identifier can’t be empty. 6.17.132 The title of the study identifier must match the leaf title of the leaf element 6.17.133 Tag attribute and category element value 6.17.184 STF append operation 6.17.183 Category information must be provided for STF 6.17.182 STF can’t reference another STF. 6.17.141 STF file must reference at least one leaf element. 6.17.140 'study-id' of STF must remain consistent. 6.17.138 Invalid STF Table of Content position 6.17.135 STF 'doc-content' file-tag count 6.17.134 Section 5.3.7 Case Report Form structure 6.17.284 Use of STF. 6.17.325 STF file tags must be correctly used for relevant files in clinical trial database 6.17.354 Correct datasets and data definition files are essential for clinical trial data from the applicant 6.17.355 Databases submitted for the same study shall feature different names 6.17.356 PDF file must be eligible to read. 6.17.43 The bookmark must direct to the relative path. 6.17.15 The bookmark with a webpage or an email destination or other external links. 6.17.88 6.17.89 The bookmark with unknown action is not allowed. 6.17.87 The bookmark must not be inactive. 6.17.86 The bookmark must not be broken. 6.17.17 The bookmark must not have multiple actions. 6.17.85 The bookmark attribute must be ’Inherit Zoom’. 6.17.63 Hypertext links should use relative paths 6.17.15 Webpage or email or other external links’ hypertext links 6.17.88 6.17.89 The hypertext links with unknown actions should not be used 6.17.87 Hypertext links should not be inactive 6.17.86 The hypertext link should not be broken 6.17.17 The hypertext links should not have multiple actions 6.17.85 The hypertext links attribute should be ’Inherit Zoom’ 6.17.63 PDF version should be correct. 6.17.18 The PDF document with attachments is not allowed. 6.17.84 Annotated PDF document 6.17.83 PDF files cannot have any security settings 6.17.40 PDF initial view should be correct. 6.17.10 6.17.12 PDF document must not have password protection. 6.17.40 PDF should have 'Fast Web Access' active. 6.17.16 The document consisting of more than 5 pages should have bookmarks. 6.17.281 Restriction in PDF contents 6.17.305 PDF Content should be searchable 6.17.93 If non-standard fonts are used, they should be embedded in PDF files. 6.17.102 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 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 value for ID attribute must start with a letter or underscore character. 6.17.20 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 the leaf element path does not exceed max number of character length allowed for that region 6.17.35 Ensure that 'util' folder exists and is in the correct location (<sequence number>/util) 6.17.38 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 the names of all files and folders in the submission corresponds to the ICH and/or regional agency defined folder structure and file names. 6.17.49 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 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 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 hyperlinks and/or bookmarks in the submission documents does not target document outside current eCTD application. 6.17.69 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 the regional 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. 6.17.81 Print the count of all of the hyperlinks and the bookmarks with following criteria: - 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 6.17.91 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 application form is submitted in the correct location of the TOC. 6.17.95 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 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 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 referenced by an STF exist in the submission/application (referenced by index.xml). 6.17.139 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 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 extraneous 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 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 the titles from the doc-content elements (if present) must match the corresponding leaf title values in the ICH backbone. 6.17.187 Ensure same xlink:href is not referenced more than once in the backbone xml files 6.17.202 Ensure that xlink:href attribute in backbone xml files does not point to leaf outside current sequence. 6.17.205 Ensure that 'xlink:href' attribute in backbone xml files does not point to leaf outside application. 6.17.206 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 initial sequence of the application must be '0000'. 6.17.213 Print the listing of all STFs in the submission. 6.17.214 Report following information about the STFs in the submission (number and total size of non E3 documents). [Non E3 study files] Total size (KB): -- Number of 16.3 files: -- (value is determined by keeping count of ICH file tags in STF) Number of US files: -- (value is determined by keeping count of US file tags in STF) Number of JP files: -- (value is determined by keeping count of JP file tags in STF) 6.17.216 Ensure that the sequence being validated is the highest sequence in the application 6.17.217 Print the list of all encrypted documents in the submission. 6.17.218 Ensure that the reference for the regional xml backbone file in index.xml must have operation attribute value 'new'. 6.17.219 Ensure that there is a stylesheet declaration in backbone xml files (index, regional and STF). 6.17.229 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 Ensure ICH attributes must not contain leading or trailing spaces, nor start or end with hyphens. 6.17.297 Ensure that two leaf elements should not have the same leaf ID 6.17.298 Ensure 'Cover Letter' is required for CN region 6.17.399