What it checks. Checks the sequence folder structure for any empty folders (folders without any files or subfolders)

What it checks. Checks the sequence folder structure for any files or folders the user does not have access permission to.

What it checks. This rule's implementation checks for files that exceed the configured maximum size. Warning for PDF files between 150 MB and 200 MB. Warning for other file types larger than 100 MB (excluding SAS XPT).

What it checks. This rule's implementation checks for files that exceed the configured maximum size (Max. size: 200 MB for PDF, 1 GB for SAS XPT).

What it checks. Checks the sequence folder name. Furthermore the rule will report a finding if the sequence seems to be the initial sequence for the application but its name is not 0000

What it checks. The validated sequence is not the highest numbered sequence in the application. Higher numbered sequences exist.

How to fix it. Validate and submit sequences in order. Ensure the current sequence is the latest.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. Identifies all ICH and regional index files found in the sequence folder. Incorrect or invalid index files will be reported as errors.

What it checks. Identifies all STF files found in the sequence folder. Invalid STF files will be reported as errors. STF files with an incorrect name will be also reported as errors.

What it checks. Each subsequent transaction provided in the lifecycle of a dossier, must have a sequence number that is consecutively incremented by 1 number (for example 0000, 0001, 0002, 0003, and so on). Skipping numbers is not acceptable for sequence numbers. Validating a transaction with sequence number 0004 will report an error if sequence number 0003 does not exist (even if sequence 0004 does not have any reference to it).

What it checks. Word document will be reported as corrupted or password protected if one or more of the following situations occur: Document is corrupt or unreadable.Document has password protection.Document references an attached template located via http or https.Document is empty.Note: This rule applies only to Word version 2007 or later (.docx).

What it checks. A duplicate eCTD sequence has been detected. This sequence number has already been submitted.

How to fix it. Submit using a unique sequence number that has not been previously used.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. A PDF document will be reported as corrupt if one or more of the following situations occur: 1. The document cannot be opened because it is damaged. 2. The document appears to have 0 pages. 3. The document appears to be an application form, but the form content cannot be read. 4. The document contains additional data (more than 1024 characters) after the last %%EOF (End Of File). An example of situation number (3) could be a document appearing to have 1 page only and the page contains the text phrase Please wait... If this message is not eventually replaced by the proper contents of the document, your PDF viewer may not be able to display this type of document.

What it checks. Retrieves all non-relative bookmarks in PDF documents and prints the total count, including the broken ones.

What it checks. Retrieves all web link bookmarks and e-mail bookmarks in PDF documents and prints the total count.

What it checks. Retrieves all external bookmarks other than web links and e-mail links from PDF documents and prints the total count.

What it checks. Retrieves all inactive bookmarks in PDF documents and prints the total count.

What it checks. Retrieves all broken inter-application bookmarks in PDF documents and prints the total count.

What it checks. Retrieves all broken intra-application bookmarks in PDF documents and prints the total count.

What it checks. Retrieves all broken intra-sequence bookmarks from PDF documents and prints the total count.

What it checks. Retrieves all unknown bookmarks (links that could not be identified or contain JavaScript code) from PDF documents and prints the total count.

What it checks. Reports the number of bookmarks per document and the total number of bookmarks in the sequence.

What it checks. Retrieves all non-relative hyperlinks from PDF documents and prints the total count, including the broken ones.

What it checks. Retrieves all web links and e-mail links from PDF documents and prints the total count.

What it checks. Retrieves all external hyperlinks other than web links and e-mail links from PDF documents and prints the total count.

What it checks. Retrieves all inactive hyperlinks from PDF documents and prints the total count.

What it checks. Retrieves all broken inter-application hyperlinks from PDF documents and prints the total count.

What it checks. Retrieves all broken intra-application hyperlinks from PDF documents and prints the total count

What it checks. Retrieves all broken intra-sequence hyperlinks from PDF documents and prints the total count.

What it checks. Retrieves all unknown hyperlinks (links that could not be identified or contain JavaScript code) from PDF documents and prints the total count.

What it checks. Reports the number of hyperlinks per document and the total number of hyperlinks in the sequence.

What it checks. Finds PDF documents with password protection.

What it checks. Checks all PDF document versions against the list of allowed versions.

What it checks. Finds all documents with an owner password set, excluding Health Canada application forms regardless of their location and literature references in subfolders: 33-lit-ref, 43-lit-ref, 54-lit-ref.

What it checks. Finds all encrypted documents.

What it checks. For all bookmarks, the named destination or destination page will be verified.Non existing destinations will be reported (i.e. the destination file exists but the page does not).

What it checks. Finds all bookmarks with multiple actions assigned.

What it checks. For all hyperlinks, the named destination or destination page will be verified.Non existing destinations will be reported (i.e. the destination file exists but the page does not).

What it checks. Finds all hyperlinks with multiple actions assigned.

What it checks. This rule is configured to detect attachments and portfolio documents found in PDF documents.

What it checks. All bookmarks and hyperlinks should have a magnification setting of 'Inherit Zoom'. This rule performs the corresponding checks for bookmarks.

What it checks. All bookmarks and hyperlinks should have a magnification setting of 'Inherit Zoom'. This rule performs the corresponding checks for hyperlinks.

What it checks. Checks for PDF documents with an incorrect initial view. ICH eCTD Specification: Documents with bookmarks must show the bookmarks pane in their initial view. The Magnification and Page Layout should be set as 'default'.

What it checks. PDF documents with more than 10 pages must have bookmarks. Excluded from this check are literature references in sections 3.3, 4.3, and 5.4; the life cycle management table; and Health Canada application forms.

What it checks. Finds all documents where printing is not allowed.

What it checks. Finds all documents where copying the content is not allowed.

What it checks. This rule checks for PDF files that contain, dynamic content (e.g., audio, video or special effects), or 3D content. Health Canada application forms are excluded from this check regardless of their location.

What it checks. This rule checks for PDF files that contain JavaScript. Health Canada application forms are excluded from this check regardless of their location.

What it checks. The document appears to contain image-only, non-text-searchable content.

How to fix it. Ensure all PDF documents contain searchable text. Minimize the use of scanned documents.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. Checks for broken links in submission files. Hyperlinks targeting files outside the application will be identified.

What it checks. Checks for broken links in submission files. Hyperlinks targeting files outside sequence will be identified.

What it checks. This check option refers to the current sequence. It will perform a general verification of the leaf life cycle properties in this sequence only (no deep history scanning). For leaf elements with operation 'new', the eValidator verifies that: modified file must not exist / title is given / href must exist.For leaf elements with operation 'replace', the eValidator verifies that: modified file must exist / title is given / href must exist.For leaf elements with operation 'append', the eValidator verifies that: modified file must exist title is given href must exist.For leaf elements with operation 'delete', the eValidator verifies that: modified file must exist title is not required href must not exist.The eValidator verifies that for initial submissions all leaf elements have the operation 'new'.The eValidator checks modified files in LCM: leaf in previous sequence must exist. It also verifies that when the attribute 'modified-file' has been used for a leaf document then the referenced document exists in the previous submission. It is recognized that this attribute is invalid when used for submission sequence number 0000.The eValidator checks that all files referenced in the backbone exist.

What it checks. The eValidator regenerates the MD5 checksums for all referenced files and compares the checksums to the values provided in the backbone file.

What it checks. Checks the syntax of all referenced file names (path length, illegal characters, etc.). The maximum path length is 200 characters.

What it checks. The eValidator checks that only relative references (href and modified file) are used. Also, only forward slashes '/' are allowed (no backslashes). Do the file references in the index files (ICH, Regional, STF) use relative paths? Absolute (i.e. rooted) paths are not allowed.

What it checks. Searches for files not referenced in an index file (ICH, Regional or STF).

What it checks. Rule compares the checksums of the DTD and schema against the following checksums: ich-ectd-3-2.dtd: 1d6f631cc6b6357f0f4fe378e5f79a27;ca-regional-2-2.xsd: ff564d6e69adebd9a9b4f274e65cf5f1;xml.xsd: 382b0a4f7529d2c5f7b0af0aa713b0a5;xlink.xsd: 52d1a3b8596e4fb61d3ec1cde24be16a;ich-stf-v2-2.dtd: 0972c10a4dadf3df5d2f41b2026a4a5c

What it checks. The eValidator checks for 'node-extension' elements being used and reports them for informational purposes.

What it checks. MD5 checksums for index files will be calculated and compared against the MD5 checksums provided in the MD5 text files (not case sensitive).

What it checks. Performs XML validation for ICH Backbone and Regional backbones.Uses the DTD or Schema given in the sequence number folder (util/dtd).

What it checks. Checks if referenced files have exactly one file extension.

What it checks. Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'.

What it checks. The sequence folder must have a subfolder m1 with a subfolder ca.

What it checks. The folder m1\ca must not have any subfolders.

What it checks. For operations other than 'delete', all leafs must have a 'title' child. The title must be present.

What it checks. The regional backbone ca-regional.xml file must exist in folder m1\ca.

What it checks. The element value for the dossier-identifier must match the name of the parent folder of the sequence folder. And the dossier-identifier must be lowercase 'e' followed by 6 digits

What it checks. Refer to the CA M1 guidance document for the list of valid values for the sequence-description element.

What it checks. Cover letter should have 'new' operation attribute.

What it checks. Checks for documents in the regional backbone, which are used as modified-file more than once.

What it checks. Checks for file reuse scenarios (Same values for xlink:href used multiple times in the regional backbone for this sequence).

What it checks. When replacing content, the new content should be different from the previous content. This check does not apply to image files provided in module 1.

What it checks. Valid file extensions include:Documents:.pdf,.doc,.docx,.xls,.xlsx,.wpd,.ppt,.pptx, Images:.png,.gif,.svg,.jpg,.jpeg,.tif,.tiff,.bmp, Audio/Video:.wav,.mp3,.mp4,.wmv,.mov,.mpg,.mpeg, Coding Language:.xml, Data:.dat,.inf,.txt.

What it checks. Detect invalid life cycle pattern: Delete operations causing branches.

What it checks. Detect invalid life cycle pattern: Replace operations causing branches.

What it checks. Detect invalid life cycle pattern: Operation on deleted leaf content.

What it checks. The value of the sequence-number element must match the sequence folder name.

What it checks. The operation attribute for this leaf element must be 'new' when provided for the first time, and 'replace'/ 'delete' whenever referenced again as part of a subsequent transaction.

What it checks. Element values product-name and applicant must not be empty.

What it checks. Cover letter should not have more than three pages.

What it checks. Node extensions in module 1 backbone (ca-regional.xml) are not allowed, except in 1.2.6 Authorization for Sharing Information heading, 1.2.7 International Information heading, and 1.6.1 Comparative bioavailability Information heading.The validator checks all headings and subheadings in the Canadian regional backbone (ca-regional.xml). It generates an error when there is (are) node extension(s) found in any subheadings other than those mentioned above This rule does not apply to leaves with operation 'delete'

What it checks. Node extensions are expected in section 1.2.7 International Information heading.Note: There is a mixture of node extensions and leaves allowed in the 1.2.7 International Information heading. A warning is generated when there is a (are) leaf (leaves) added under this heading. The warning serves the purpose to notify the user to manually verify the leaves added under this heading. Requirements are outlined below and will result in failure of the transaction if not followed:When provided, the International Status document and the Foreign review attestation must be added as leaves directly under 1.2.7 subheading. Any other foreign agency (such as FDA,. EMA) related documents must be provided using node extensions This rule does not apply to leaves with operation 'delete'

What it checks. For node extensions, the title child must be present (value must be present).

What it checks. The use of operation 'append' is not allowed in module 1.

What it checks. Checks if referenced files have exactly one file extension.

What it checks. The checksum-type attribute must have the value md5 or MD5.

What it checks. Checks if the attribute value is present.

What it checks. Checks if the attribute value is present.

What it checks. Checks if the attribute value is present.

What it checks. Checks if the attribute value is present. Applicable only to sections where this attribute is mandatory, otherwise reported as warning.

What it checks. Checks if the attribute value is present.

What it checks. Checks if the attribute value is present. Applicable only to sections where this attribute is mandatory, otherwise reported as warning.

What it checks. Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'.

What it checks. The index.xml file must be present.

What it checks. The MD5 checksum file index-md5.txt must be present.

What it checks. The m1 folder must be present.

What it checks. The util folder must be present.

What it checks. For operations other than 'delete', all leafs must have a 'title' child. The title must be present.

What it checks. The element m1-administrative-information-and-prescribing information must be present.

What it checks. The m1 folder must not have any other files in addition to the files explicitly allowed.

What it checks. The root folder (sequence number folder) must not have any other files in addition to the files explicitly allowed.

What it checks. For node extensions, the title child must be present (value must be present).

What it checks. Regional backbone(s) referenced (ca-regional.xml) should have 'new' operation attribute.

What it checks. Checks for documents in the ICH backbone, which are used as modified-file more than once.

What it checks. Checks for file reuse scenarios (Same values for xlink:href used multiple times in the regional backbone for this sequence).

What it checks. Valid file extensions include: Documents:.pdf,.doc,.docx,.xls,.xlsx,.wpd,.ppt,.pptx,Images:.png,.gif,.svg,.jpg,.jpeg,.tif,.tiff,.bmp,Audio/Video:.wav,.mp3,.mp4,.wmv,.mov,.mpg,.mpeg,Coding Language:.xml,.xsl,.xsd,.dtd,Data, Modeling and Simulation:.dat,.inf,.txt,.sas,.xpt .wksz,.wksx,.wks (SimCyp workspace files, Pharmaceutical Drugs only) .sdax,.edpdp,.wsp,.epr,.pnf,.psf (Consistency Lot Release Testing Activities, Biologic Drugs only)

What it checks. When replacing or appending content, the new content should be different from the previous content.

What it checks. The number of leaves directly under a single node must not exceed 1000. This rule applies only to module 5 when using node extensions and only to leaves with operation attribute 'new'.

What it checks. Detect invalid life cycle pattern: Append operations causing branches.

What it checks. Detect invalid life cycle pattern: Append operations not appending to most recent STF leaf.

What it checks. Detect invalid life cycle pattern: Delete operations causing branches.

What it checks. Detect invalid life cycle pattern: Replace operations causing branches.

What it checks. Detect invalid life cycle pattern: Operation on deleted leaf content.

What it checks. Detect invalid life cycle pattern: Append on Append.

What it checks. Do not provide strength values in the dosage form attribute in sections 2.3.P, 3.2.P, 3.2.A.1, or 3.2.A.2. Any numeric value found in these attribute values will be reported as an error. If the strength value was already present in a previous sequence, the rule will not report an error for the current sequence

What it checks. This applies to leaf elements in the ICH sections modules 2-5.When revisions are sent to a regulatory authority, the new leaf element should be submitted in the same location in the backbone as the leaf element being appended, replaced or deleted.

What it checks. This check will examine the SAS XPT dataset files (XPORT). Files that are corrupt or compressed will be reported as Error. For details about the technical specifications, please refer to the FDA study data technical conformance guide.

What it checks. Leaf elements in 3.2.R Regional Information heading must be provided using node extensions. PDF files are not allowed as leaf elements directly under 3.2.R Regional Information heading. Acceptable titles of the node extensions are:3.2.R.1 Production Documentation, 3.2.R.2 Medical Devices,3.2.R.3 Lot Release Documentation,3.2.R.4 Yearly Biologic Product Report,3.2.R.5 Assessment of Similarity,3.2.R.6 On Site Evaluation,3.2.R.7 Other Regional Information,3.2.R.8 Product Lifecycle Management Information,Warning will be reported if the naming of the title is not followed.

What it checks. Verifies that the href target exists and has the correct value.

What it checks. Verifies that the href target exists and matches the title value.

What it checks. Reports any used content-block element.

What it checks. Verifies that href values do not contain backslashes

What it checks. The value of the study-identifier/category element must not be empty.

What it checks. The value of the study-identifier/study-id element must not be empty.

What it checks. The value of the study-identifier/title element must not be empty.

What it checks. Checks file tag values and category values against definitions in valid-values.xml file. Accepting values as defined in valid-values.xml v6.

What it checks. STF leaf element must reference other STF leaf upon append.Such leaf elements must not reference PDF files as modified files.

What it checks. Category information must be provided for certain STFs.

What it checks. Leaf references in STFs must always target content files, not STFs

What it checks. STF files must reference at least one leaf.

What it checks. The STF study IDs must not change in the application life cycle.

What it checks. STFs should only be associated with certain headings under Modules 4 or 5.

What it checks. There should be one and only one file tag for each doc-content.

What it checks. If Study Tagging Files are used in the current sequence being validated, the node 5.3.7 must not be used. The Case Report Forms must be referenced from the Study Tagging Files. The previous sequences in the same dossier will not be checked.

What it checks. Leaf elements in module 4 (except those in subsection 4.3), with an operation attribute 'new', can use either node extensions, STFs or may be placed directly under the TOC sections.Leaf elements in subsections 5.3.1, 5.3.2, 5.3.3, 5.3.4, 5.3.5, and 5.3.7, with an operation attribute 'new', can use only node extensions or STFs.Although both node extensions and STFs are acceptable for study reports, only one or the other approach should be used consistently throughout the lifecycle of a leaf. Also, in a specific sequence all leaf elements should use the same approach.Note: Previous sequences in the same dossier will not be checked, and neither will leaf elements with operation attributes other than 'new'.

What it checks. The STF DTD version declared in the STF XML file is not a valid or supported version.

How to fix it. Use a supported STF DTD version in your STF XML files.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. A damaged or unreadable XML file (RT, PI, or MF) has been detected in the submission.

How to fix it. Resubmit with a valid, well-formed XML file.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. An RT or MF XML file that was present in a previous sequence is missing from this sequence.

How to fix it. Include the RT or MF XML file if it was present in a previous sequence.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. RT, PI, or MF XML files must be placed in the 1.2.1 Application Forms node.

How to fix it. Place all RT, PI, and MF XML files under the 1.2.1 Application Forms node.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. A 3011 Submission Application form must not be present alongside an RT XML file.

How to fix it. Remove the 3011 form when an RT XML file is included in the submission.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. The 1.2.1 Application Forms node must only contain RT, PI, or MF XML files. Multiple RT or MF files of the same type are not permitted.

How to fix it. Ensure only permitted XML file types are in the 1.2.1 node and remove duplicates.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. The Dossier ID field in the RT or MF XML file must match the top-level dossier folder name.

How to fix it. Ensure the Dossier ID in the XML matches the top-level folder name of the dossier.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. The first occurrence of the RT or MF XML file must use operation attribute 'new'. Subsequent occurrences must use 'replace'.

How to fix it. Set operation to 'new' for initial submission and 'replace' for subsequent sequences.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. The Dossier ID must follow the naming convention: lowercase 'e' followed by 6 digits.

How to fix it. Ensure the Dossier ID follows the format e######.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. Element values for "product_name" and "company_id" must not be empty.

How to fix it. Populate the product_name and company_id fields in the RT/MF XML file.

Reference. Health Canada eCTD Validation Criteria v5.3

What it checks. The software_version in the RT or MF XML file must be a version accepted by Health Canada.

How to fix it. Update the software_version field to a version accepted by Health Canada.

Reference. Health Canada eCTD Validation Criteria v5.3