US Validation 4.3 [DTD 3.3] (Full) US 4.3 en Full US Validation Criteria v4.3 [DTD 3.3] with additional recommended criteria. eCTD submission missing us-regional.xml file 6.17.39 Invalid leaf element operation 6.17.180 Application form and cover letter should be "New" 6.17.181 Extraneous leaf element path 6.17.26 Extraneous modified leaf element path 6.17.42 Leaf element path length exceeds maximum (230 characters) 6.17.35 Leaf element path contains invalid characters: backslash(\), colon(:), asterisk(*), question mark(?), less than(<), greater than(>), pipe(|), or space ( ) 6.17.29 More than one version of the us-regional.xml file exists 6.17.39 Missing required file 6.17.57 Required file checksum value in the util folder must match the expected checksum 6.17.8 6.17.46 6.17.47 6.17.55 Omitted leaf element path 6.17.27 Missing modified file 6.17.14 A leaf referenced in the modified-file element was not originally submitted to all applications in the grouped submission 6.17.179 Omitted leaf element modified file path 6.17.13 File name contains invalid characters: tilde(~), forward slash(/), backslash(\), colon(:), asterisk(*), question mark(?), single quote('), double quote(") less than(<), greater than(>), pipe(|), or space( ) 6.17.34 File name exceeds maximum length (64 characters) per eCTD specification 6.17.33 File size exceeds maximum limit (400 MB) per eCTD specification 6.17.21 Invalid file extension 6.17.44 Leaf element title leads or ends with a space 6.17.167 Omitted leaf element title 6.17.25 File does not contain a file extension 6.17.9 No leaf element for file 6.17.37 Non-required file exists 6.17.178 Folder contains no files or sub folders 6.17.62 No file for leaf element 6.17.28 Application Mismatch 6.17.99 Company name is missing 6.17.171 Application type is invalid 6.17.165 Application number does not match the folder name 6.17.163 Company name must remain constant 6.17.162 Promotional labeling and advertising regulatory contact is missing 6.17.161 Material-id exceeds 30 characters 6.17.160 2253 submission does not include Product Labeling 6.17.361 The only valid FDA Form to include in a 2253 submission is FDA Form 2253 6.17.362 Promotional Material Issue Date Format is incorrect 6.17.363 The submission-id referenced has not been received and/or processed 6.17.153 Issue-date attribute value is missing 6.17.149 Sequence number was previously submitted 6.17.32 Sequence number does not match the folder name 6.17.31 An older version of the DTD has been used after a submission to the application used a higher version. 6.17.65 6.17.66 us-regional.xml is not referencing the DTD and stylesheet at an approved valid location 6.17.128 A required attribute value in M1 is missing 6.17.127 Invalid M1 attribute value 6.17.126 A submission sub-type error occurred because this particular submission sub-type is only allowed once for each regulatory activity. 6.17.125 Submission-sub-type is invalid for submission-type 6.17.124 All grouped submission submission-sub-type values must be the same 6.17.123 For all sequences for a regulatory activity the submission type must be consistent, and the submission sub-type must be valid for the submission type. 6.17.261 The eCTD sequence number of the submission sub-type that starts a new regulatory activity and the submission id must match. 6.17.262 All grouped submission application-type values must be the same 6.17.122 All grouped submission submission-type values must be the same 6.17.121 Different sequence numbers are referenced for the same application number 6.17.120 Submission-type is invalid for application-type 6.17.119 Submission description exceeds 128 characters 6.17.118 No application element with application-containing-files value of “true” 6.17.117 More than one application-containing-files element has a value of "true" 6.17.116 Cross-reference-application-number must contain 6 numeric digits only 6.17.115 Supplement-effective-date-type attribute value is missing 6.17.114 Email address exceeds 64 characters 6.17.113 id element has changed 6.17.112 id element must contain 9 digits only 6.17.111 Invalid form type for eCTD location 6.17.110 Application number must contain 6 numeric digits only 6.17.105 Submission sequence number must contain 4 numeric digits only 6.17.30 Submission-id element must contain 4 numeric digits only 6.17.103 Misnamed form 6.17.100 Application number in form does not match application number in us-regional.xml 6.17.99 Multiple application forms present for the same application 6.17.97 Application form placed in wrong TOC location 6.17.95 Wrong application form 6.17.94 Fillable form not included 6.17.101 Attribute value leads or ends with a space 6.17.177 Required attribute value omitted in M2 - M5 6.17.176 An attribute appears multiple times in the stf.xml file 6.17.175 Extraneous attribute 6.17.174 Checksum value must match the actual checksum 6.17.5 6.17.7 Invalid checksum formatting in index-md5.txt. 6.17.6 Invalid checksum type 6.17.2 Omitted checksum value 6.17.3 Unexpected checksum value 6.17.4 Omitted DTD version in index.xml file 6.17.173 Omitted DTD version in us-regional.xml file 6.17.173 Unsupported DTD version in index.xml file 6.17.170 Unsupported DTD version in us-regional.xml file 6.17.170 Node-extension exists 6.17.168 Node-extension does not have a title 6.17.25 Node-extension title leads or ends with a space 6.17.167 Text data was truncated 6.17.164 A dataset named ts.xpt with information on study start date must be present for each study in 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 For SEND data, a DM dataset and define.xml must be submitted in module 4, sections 4.2.3.1, 4.2.3.2, 4.2.3.4 For SDTM data, a DM dataset and define.xml must be submitted 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. 6.17.257 6.17.258 For each study in 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, no more than one dataset of the same name should be submitted as new 6.17.259 eCTD element does not contain any leaf elements 6.17.19 Cumulative STF files are not allowed 6.17.148 The correct STF file-tags must be used for all standardized datasets and corresponding define.xml files in 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 6.17.256 Omitted STF DTD version in leaf element 6.17.147 Omitted STF DTD version in STF XML file 6.17.146 STF DTD version must match the XML file 6.17.145 Unsupported STF DTD version in leaf element 6.17.144 Unsupported STF DTD version in STF XML file 6.17.143 A file has been submitted in a study section without providing an STF file. STFs are not required for 4.3 Literature references, 5.2 Tabular listings, 5.4 Literature references and 5.3.6 Postmarketing reports 6.17.142 STF cannot reference another STF 6.17.141 STF does not relate to any leaf elements 6.17.140 STF relates to a non-existent leaf element 6.17.139 Study ID for STF must remain constant 6.17.138 Invalid STF file extension 6.17.137 Invalid STF file name 6.17.136 Invalid STF TOC location 6.17.135 Omitted STF doc-content file tag 6.17.134 Multiple STF doc-content file tags 6.17.134 STF XML title and leaf element title do not match 6.17.133 Invalid STF XML file 6.17.132 STF XML file is missing 6.17.131 The study title for the STF is missing 6.17.130 The same STF XML is referenced more than once. 6.17.129 STF doc-content title used 6.17.109 The element 'file-tag' preceded the element 'property' 6.17.107 Use of content-block is not recommended 6.17.106 Failed to process PDF contents 6.17.43 Non standard font (not embedded) 6.17.102 PDF security used 6.17.40 PDF version of document is incorrect 6.17.18 PDF does not have 'Fast Web Access' active 6.17.16 PDF opening settings not optimal 6.17.10 6.17.11 6.17.12 Document has password protection 6.17.40 Document has annotations, only PDFs in module 1, section 1.15 are permitted to have annotations. 6.17.83 Document contains no text 6.17.93 Broken bookmark 6.17.17 Corrupt bookmark 6.17.91 Bookmark has non-existent named destination or page 6.17.92 Multiple action bookmark 6.17.85 External bookmark 6.17.89 Inactive bookmark 6.17.86 Non-relative bookmark 6.17.15 Bookmark does not 'Inherit Zoom' 6.17.63 Broken hyperlink 6.17.17 Corrupt link 6.17.91 Link has non-existent named destination or page 6.17.92 Multiple action hyperlink 6.17.85 External hyperlink 6.17.89 Inactive hyperlink 6.17.86 Non-relative hyperlink 6.17.15 Link does not 'Inherit Zoom' 6.17.63 XML didn't pass validation with the schema (DTD) and attribute files 6.17.48 Ensure that value for ID attribute must start with a letter or underscore character 6.17.20 Allow users to configure file size limit for special file types (i.e. xpt). For all other file types (where configuration is not specified), default max file size value in the 'Check for File Size' field shall be used for validation 6.17.23 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) 6.17.24 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 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 ICH and regional xml backbone files are named correctly 6.17.56 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 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) 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 Ensure that all pdf documents in the submission must not have any attachments 6.17.84 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 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 '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 same xlink:href is not referenced more than once in the backbone xml files 6.17.202 Ensure that all element in the submission backbone xml files must have leaf child nodes 6.17.204 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 that only operation 'new' is used for all leafs in the initial sequence of the application 6.17.207 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 Identify and report all invalid STF files. STF files with an incorrect name will be also reported. 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 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 regional folder exists inside M1 and it must not contain any subfolders 6.17.222 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 PDF documents with more than 10 pages must have bookmark 6.17.281