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Notice - Validation rules for regulatory transactions submitted to Health Canada in the electronic Common Technical Document (eCTD) format

December 1, 2016
Our file number: 16-114068-403

Validation rules for regulatory transactions provided to Health Canada in the electronic Common Technical Document (eCTD) format

Health Canada is pleased to announce the revised validation rules for regulatory transactions in the electronic Common Technical Document (eCTD) format. These revised validation rules (see table below) are being posted to provide further information to stakeholders to assist them in the preparation of regulatory transactions in eCTD format. The revised rules also build on the information provided in the Guidance Document: Preparation of Drug Regulatory Activities in Electronic Common Technical Document (eCTD) Format as well as specifications for the regional administrative module (Module1) of the eCTD standard defined in Guidance for Industry: Creation of the Canadian Module 1 Backbone (eCTD) and the International Conference on Harmonisation (ICH) Electronic Common Technical Document Specification (Version 3.2.2).

Since June 2016, Health Canada has been providing the Validation Reports only for regulatory transactions that failed validation. Sponsors are expected to validate their eCTD regulatory transactions and correct any warning(s) and error(s) before sending them to Health Canada.

Although the profile may be updated without further notice, as of January 1st, 2017, Health Canada will be validating regulatory transactions in eCTD format using the following version:

  • CA eCTD - Profile 4.2

Should you have any questions regarding the content of the notice, please contact:

E-mail: ereview@hc-sc.gc.ca

Health Canada eCTD Validation Rules
CA eCTD - Profile 4.2
ID # Rule Name Rule Description Severity
A - GENERAL
A01 Empty Folders Checks the sequence folder structure for any empty folders (folders without any files or subfolders). Error
A02 File and Folder Security  Checks the sequence folder structure for any files or folders the user does not have access permission to. Error
A03a File Size  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 files larger than 100 MB (excluding SAS XPT). Warning
A03b File Size  This rule's implementation checks for files that exceed the configured maximum size
(Max. size: 200 MB for PDF, 1 GB for SAS XPT).
Error
A05a Sequence Folder  Requirements 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. Error
A05b Higher sequences found Reports error if the validated sequence is not the highest in the application folder. Error
A06a XML Backbones Identification Identifies all ICH and regional index files found in the sequence folder. Incorrect or invalid index files will be reported as errors. Error
A06b STF Identification Identifies all STF files found in the sequence folder. Invalid STF files will be reported as errors. Error
A07 Sequence numbering 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).
Error
B - PDF ANALYSIS
B01 Corrupt or unreadable PDF documents 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 or the encryption is too strong.
  2. The document appears to have 0 pages.
  3. The document appears to be an application form, but the form content cannot be read.
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."

Furthermore, the document has no valid XFA XML data.
Error
B02 Bookmarks - Absolute (Rooted) Retrieves all non-relative bookmarks in PDF documents and prints the total count, including the broken ones. Error
B03a Bookmark - External (www, e-mail) Retrieves all web link bookmarks and e-mail bookmarks in PDF documents and prints the total count. Error
B03b Bookmarks - External (other) Retrieves all external bookmarks other than web links and e-mail links from PDF documents and prints the total count Error
B04  Bookmarks - Inactive Retrieves all inactive bookmarks in PDF documents and prints the total count. Error
B06 Bookmarks - Inter Application, broken Retrieves all broken inter-application bookmarks in PDF documents and prints the total count. Error
B08 Bookmarks - Intra Application, broken Retrieves all broken intra-application bookmarks in PDF documents and prints the total count. Error
B10 Bookmarks - Intra Sequence, broken Retrieves all broken intra-sequence bookmarks from PDF documents and prints the total count. Error
B11  Bookmarks - Other Retrieves all unknown bookmarks (links that could not be identified) from PDF documents and prints the total count. Warning
B12 Bookmarks - Count Reports the number of bookmarks per document and the total number of bookmarks in the sequence Information
B13 Hyperlinks - Absolute (Rooted) Retrieves all non-relative hyperlinks from PDF documents and prints the total count, including the broken ones. Error
B14a Hyperlinks - External (www, e-mail) Retrieves all web links and e-mail links from PDF documents and prints the total count. Error
B14b Hyperlinks - External (other) Retrieves all external hyperlinks other than web links and e-mail links from PDF documents and prints the total count. Error
B15  Hyperlinks - Inactive Retrieves all inactive hyperlinks from PDF documents and prints the total count. Error
B17 Hyperlinks - Inter Application, broken Retrieves all broken inter-application hyperlinks from PDF documents and prints the total count. Error
B19 Hyperlinks - Intra Application, broken Retrieves all broken intra-application hyperlinks from PDF documents and prints the total count. Error
B21 Hyperlinks - Intra Sequence, broken Retrieves all broken intra-sequence hyperlinks from PDF documents and prints the total count. Error
B22  Hyperlinks - Other Retrieves all unknown hyperlinks (links that could not be identified) from PDF documents and prints the total count. Warning
B23  Hyperlinks - Count Reports the number of hyperlinks per document and the total number of hyperlinks in the sequence Information
B24 PDF Protection Finds PDF documents with password protection Error
B25 PDF version checking Checks all PDF document versions against the list of allowed versions. Warning
B32 PDF Protection: Owner password Finds all documents with an owner password set. Error
B33  PDF Protection: Encrypted Finds all encrypted documents. Information
B35 Bookmarks - deep destination check 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).
Error
B36 Bookmarks - multi action Finds all bookmarks with multiple actions assigned Error
B37 Hyperlinks - deep destination check 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).
Error
B38 Hyperlinks - multi action Finds all hyperlinks with multiple actions assigned Error
B40 PDF documents with attachments are not allowed This check examines PDF documents and reports all documents having any attachments. Error
B41 Bookmark does not 'Inherit Zoom" All bookmarks and hyperlinks should have a magnification setting of "Inherit Zoom". This rule performs the corresponding checks for bookmarks. Warning
B42 Link does not 'Inherit Zoom' All bookmarks and hyperlinks should have a magnification setting of "Inherit Zoom". This rule performs the corresponding checks for hyperlinks. Warning
B43 PDF Initial View 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". Warning
B44 PDF documents with more than 10 pages must have bookmarks 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. Warning
C - REFERENCED FILES
C01 HREFs to targets outside application Checks for broken links in submission files. Error
Hyperlinks targeting files outside the application will be identified.
C02 HREFs to targets outside sequence Checks for broken links in submission files. Information
Hyperlinks targeting files outside sequence will be identified.
C03 Life Cycle Management Semantics 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). Error
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.
C04 MD5 Checksum The eValidator regenerates the MD5 checksums for all referenced files and compares the checksums to the values provided in the backbone file. Error
C05 Naming Syntax Checks the syntax all referenced file names (path length, illegal characters, etc.). The maximum path length is 180 characters. Revised Error
C06 Relative References The eValidator checks that only relative references (href and modified file) are used. Also, only forward slashes "/" are allowed (no backslashes). Error
Do the file references in the index files (ICH, Regional, STF) use relative paths? Absolute (i.e. rooted) paths are not allowed.
C07 Unreferenced Files Searches for files not referenced in an index file (ICH, Regional or STF). Error
D - XML ANALYSIS
D01 DTD/Schema Checksums Rule compares the checksums of the DTD and schema against the following checksums: Error
ich-ectd-3-2.dtd: 1d6f631cc6b6357f0f4fe378e5f79a27
ca-regional-2-2-.xsd: ff564d6e69adebd9a9b4f274e65cf5f1
xml.xsd: 382b0a4f7529d2c5f7b0af0aa713b0a5
xlink.xsd: 52d1a3b8596e4fb61d3ec1cde24be16a
ich-stf-v2-2.dtd: 0972c10a4dadf3df5d2f41b2026a4a5c
D02 Existence of Node extensions The eValidator checks for "node-extension" elements being used and reports them for informational purposes. Information
D03 MD5 for Index files MD5 checksums for index files will be calculated and compared against the MD5 checksums provided in the MD5 text files. Error
D04 Validate against delivered DTD Performs XML validation for ICH Backbone and Regional backbones. Error
Uses the DTD or Schema given in the sequence number folder (util/dtd).
F - CA REGIONAL 2.2
F01 All files should have one and only one file extension Checks if referenced files have exactly one file extension. Error
F03 Element must have leaf Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'. Error
F04 The folder m1\ca must exist. The sequence folder must have a subfolder m1 with a subfolder ca. Error
F05 No subfolders in ca-subfolder The folder m1\ca must not have any subfolders. Warning
F06 Leaf title must not be empty For operations other than 'delete', all leafs must have a 'title' child. The title must be present. Error
F07 Module 1 (regional xml file) exists The regional backbone ca-regional.xml file must exist in folder m1\ca. Error
F08 Application folder name must match dossier-identifier The element value for the dossier-identifier must match the name of the parent folder of the sequence folder.  And the dossier-identifier must start with the letter e or s. Error
F09 Element sequence-description Refer to the CA M1 guidance document for the list of valid values for the sequence-description element. Error
F10 Cover letter operation attribute Cover letter should have 'new' operation attribute Warning
F11 Multiple operations on same document in same sequence Checks for documents in the regional backbone, which are used as modified-file more than once. Error
F12 File reuse Checks for file reuse scenarios (Same values for xlink:href used multiple times in the regional backbone for this sequence) Information
F14 Replace or append should not provide identical content to the previous file When replacing or appending content, the new content should be different from the previous content. Error
F15 Invalid file extension Valid file extensions include: pdf, .doc, .docx, .xls, .xlsx, .wpd, .ppt, .pptx, .xml, .dat, .inf, .txt, .jpg, .png, .gif, .svg, .wav, .mp3, .mp4, .wmv, .jpg, .jpeg Revised Warning
F16 Detect invalid life cycle:  Append Detect invalid life cycle pattern: Append operations causing branches Error
F17 Detect invalid life cycle: Delete Detect invalid life cycle pattern: Delete operations causing branches Error
F18 Detect invalid life cycle: Replace Detect invalid life cycle pattern: Replace operations causing branches Error
F19 Detect invalid life cycle: Delete Detect invalid life cycle pattern: Operation on deleted leaf content Error
F20 Detect invalid life cycle: Append Detect invalid life cycle pattern: Append on Append Warning
F21 Element sequence-number The value of the sequence-number element must match the sequence folder name. Error
F22 Operation for Life Cycle Management Table The operation for this leaf must be 'replace' (or 'delete' if applicable) in sequences other than the initial one. In every sequence, a new version of that document must be submitted. Error
F23 Product Name and Applicant Element values ôproduct-nameö and ôapplicantö must not be empty. New Error
G - ICH BACKBONE 3.2
G01 All files should have one and only one file extension Checks if referenced files have exactly one file extension. Error
G02 Attribute checksum-type The checksum-type attribute must have the value md5 or MD5. Error
G03 Attribute dosage form Checks if the attribute value is present. Error
G04 Attribute excipient Checks if the attribute value is present. Error
G05 Attribute Indication Checks if the attribute value is present. Error
G06 Attribute Manufacturer Checks if the attribute value is present. Error
G07 Attribute Product-Name Checks if the attribute value is present. Error
G08 Attribute Substance Checks if the attribute value is present. Error
G09 Element must have leaf Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'. Error
G10 File index.xml exists The index.xml file must be present Error
G11 File index-md5.txt exists The MD5 checksum file index-md5.txt must be present. Error
G12 Folder m1 exists The m1 folder must be present. Error
G13 Folder util exists The util folder must be present Error
G14 Leaf title must not be empty For operations other than 'delete', all leafs must have a 'title' child. The title must be present. Error
G15 m1-administrative element must exist The element m1-administrative-information-and-prescribing information must be present. Error
G16 No other files in m1 The m1 folder must not have any other files in addition to the files explicitly allowed. Error
G17 No other files in root The root folder (sequence number folder) must not have any other files in addition to the files explicitly allowed. Error
G18 Node Extension title must not be empty For node extensions, the title child must be present (value must be present). Error
G19 Regional backbone(s) referenced operations Regional backone(s) referenced (ca-regional.xml) should have 'new' operation attribute. Warning
G20 Multiple operations on same document in same sequence Checks for documents in the ICH backbone, which are used as modified-file more than once. Error
G21 File reuse Checks for file reuse scenarios (Same values for xlink:href used multiple times in the regional backbone for this sequence) Information
G22 Invalid file extension Valid file extensions include: .pdf, .doc, .docx, .xls, .xlsx, .wpd, .ppt, .pptx, .xml, dat .inf, .txt, .jpg, .png, .gif, .svg, .sas, .xpt, .xsl, .dtd, .xsd, .wav, .mp3, .mp4, .wmv, .jpg, .jpeg Revised Warning
G23 Replace or append should not provide identical content to the previous file When replacing or appending content, the new content should be different from the previous content. Error
G24 Leaf count under a node 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". Revised Error
G25 Detect invalid life cycle: Append Detect invalid life cycle pattern: Append operations causing branches Error
G26 Detect invalid life cycle:  Append Detect invalid life cycle pattern: Append operations not appending to most recent STF leaf Error
G27 Detect invalid life cycle: Delete Detect invalid life cycle pattern: Delete operations causing branches Error
G28 Detect invalid life cycle: Replace Detect invalid life cycle pattern: Replace operations causing branches Error
G29 Detect invalid life cycle: Delete Detect invalid life cycle pattern: Operation on deleted leaf content Error
G30 Detect invalid life cycle: Append Detect invalid life cycle pattern: Append on Append Warning
G31 Strength in dosage form attribute 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. Error
G32 Do not relocate content 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.
Error
H - STF 2.2
H01 Check Index Reference Verifies that the href target exists and has the correct value. Error
H02 Check Index Reference (title - match) Verifies that the href target exists and matches the title value. Warning
H03 Content Block are not accepted Reports any used content-block element. Warning
H04 No backslash in HREF Verifies that href values do not contain backslashes. Error
H05 Study Identifier category must not be empty The value of the study-identifier/category element must not be empty. Warning
H06 Study Identifier study-ID must not be empty The value of the study-identifier/study-id element must not be empty. Warning
H07 Study Identifier title must not be empty The value of the study-identifier/title element must not be empty. Warning
H08 Categories and file tags Checks file tag values and category values against definitions in valid-values.xml file Warning
H09 STF leaf element must reference other STF leaf upon append STF leaf element must reference other STF leaf upon append. Error
Such leaf elements must not reference PDF files as modified files.
H10 Category information must be provided for certain STFs Category information must be provided for certain STFs Warning
H12 STF cannot reference another STF Leaf references in STFs must always target content files, not STFs. Warning
H13 STF does not relate to any leaf elements STF files must reference at least one leaf. Warning
H14 Study ID for STF must remain constant The STF study IDs must not change in the application lice cycle. Warning
H15 Invalid STF TOC location STFs should only be associated with certain headings under Modules 4 or 5. Warning
H16 STF doc-content file tag count There should be one and only one file tag for each doc-content. Warning
H19 Case Report Form(s) structure in 5.3.7 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. Error
H20 Use Study Tagging Files or Node Extensions 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".
Error