Notice - Health Canada posts validation rules for submissions provided in the eCTD format

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Contact: eReview

Notice

November 13, 2007

Our file number: 07-126626-915

Health Canada is pleased to announce that the validation rules for submissions in the electronic Common Technical Document (eCTD) format have now been posted. These rules build on the information provided in the draft guidance document Guidance for Industry: Preparation of Drug Submissions in eCTD Format as well as specifications for the regional administrative module (Module1) of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 eCTD Backbone File. These validation rules are being posted to provide further information to stakeholders to assist in the preparation of drug submissions in eCTD format.

Health Canada uses LORENZ's docuBridge® Validator for the validation of submissions in the eCTD format. The docuBridge®Validator verifies and validates eCTDs based on configured check options and dynamic verification rules set in accordance to specified DTDs and various requirements published by the International Conference on Harmonization and other authorities. The resulting structured report provides a list of analysed items checked against the set requirements.

Please refer to the table below for the settings of Health Canada's Validation rules. The check options can be sorted into primary and secondary groups. The primary options are those that affect any eCTD and consist of four categories: General, PDF Analysis, Referenced Files, XML Files. The secondary options are based on regional requirements and include: ICH, Canada Module 1.

Although the software and profile may be updated without further notice, the current version used by Health Canada is:

• software: docuBridge® eCTD Validator 2.0 SP1 HF1
  
• profile: eCTD Validator - Profile HC-SC-2.0

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

Health Products and Food Branch
Therapeutic Products Directorate
Submission and Information Policy Division
101 Tunney’s Pasture Driveway
Finance Building A.L. 0201A1
Tunney’s Pasture
Ottawa, Ontario, K1A 0K9
e-mail: ereview@hc-sc.gc.ca

Health Canada eCTD Validation Rules eCTD Validator - Profile HC-SC-2.0

General

ID #	Rule Name	Rule Description	Severity
1	Empty Folders	Any empty folders in the application hierarchy?	Error
2	File and Folder Security	Any files or folder with restricted access permission? Can all folders and files be opened?	Error
3	File Size	Are there files which exceed the allowed maximum size of 100 MB?	Error
4	Processing	Unexpected program termination? Application folder structure correct? Problems opening xml files?	Error
5	Sequence Folder Requirements	Sequence number numeric? Sequence number 0000 for initial sequence? Highest sequence loaded?	Error
6	XML Backbone(s) identification	Do the index files have a known and configured version?	Error

PDF Analysis

ID #	Rule Name	Rule Description	Severity
7	Bookmarks - Absolute (Rooted)	Retrieves all non-relative bookmarks from PDF documents and prints the total count. Note that broken bookmarks are also included in the counting.	Info
8	Bookmarks - Absolute (Rooted), broken	Retrieves all broken non-relative bookmarks from PDF documents and prints the total count.	Error
9	Bookmarks - External	Retrieves all external bookmarks (e.g. web links, e-mail links) from PDF documents and prints the total count.	Error
10	Bookmarks - Inactive	Retrieves all inactive bookmarks from PDF documents and prints the total count.	Error
11	Bookmarks - Inter Application	Retrieves all inter-application bookmarks from PDF documents and prints the total count. Note that broken or rooted bookmarks are also included in the counting.	Information
12	Bookmarks - Inter Application, broken	Retrieves all broken inter-application bookmarks from PDF documents and prints the total count.	Error
13	Bookmarks - Intra Application	Retrieves all intra-application bookmarks from PDF documents and prints the total count. Note that broken or rooted bookmarks are also included in the counting.	Information
14	Bookmarks - Intra Application, broken	Retrieves all broken intra-application hyperlinks from PDF documents and prints the total count.	Error
15	Bookmarks - Intra Sequence	Retrieves all intra-sequence bookmarks from PDF documents and prints the total count. Note that broken or rooted bookmarks are also included in the counting.	Information
16	Bookmarks - Intra Sequence, broken	Retrieves all broken intra-sequence bookmarks from PDF documents and prints the total count.	Error
17	Bookmarks - Other	Retrieves all unknown bookmarks (links that could not be identified) from PDF documents and prints the total count.	Information
18	Hyperlinks - Absolute (Rooted)	Retrieves all non-relative hyperlinks from PDF documents and prints the total count. Note that broken hyperlinks are also included in the counting.	Information
19	Hyperlinks - Absolute (Rooted), broken	Retrieves all broken non-relative hyperlinks from PDF documents and prints the total count.	Error
20	Hyperlinks - External	Retrieves all external hyperlinks (e.g. web links, e-mail links) from PDF documents and prints the total count.	Error
21	Hyperlinks - Inactive	Retrieves all inactive hyperlinks from PDF documents and prints the total count.	Error
22	Hyperlinks - Inter Application	Retrieves all inter-application hyperlinks from PDF documents and prints the total count. Note that broken or rooted hyperlinks are also included in the counting.	Information
23	Hyperlinks - Inter Application, broken	Retrieves all broken inter-application hyperlinks from PDF documents and prints the total count.	Error
24	Hyperlinks - Intra Application	Retrieves all intra-application hyperlinks from PDF documents and prints the total count. Note that broken or rooted hyperlinks are also included in the counting.	Information
25	Hyperlinks - Intra Application, broken	Retrieves all broken intra-application hyperlinks from PDF documents and prints the total count.	Error
26	Hyperlinks - Intra Sequence	Retrieves all intra-sequence hyperlinks from PDF documents and prints the total count. Note that broken or rooted hyperlinks are also included in the counting.	Information
27	Hyperlinks - Intra Sequence, broken	Retrieves all broken intra-sequence hyperlinks from PDF documents and prints the total count.	Error
28	Hyperlinks - Other	Retrieves all unknown hyperlinks (links that could not be identified) from PDF documents and prints the total count.	Information
29	PDF Optimization	Any PDF documents that are not optimized (not linearized)?	Ignore
30	PDF Protection	Any PDF documents with a password protection set?	Error
31	PDF version checking	Checks all PDF document versions against the list of forbidden versions (see the corresponding field on the Check Options tab).	Warning

Referenced Files

ID #	Rule Name	Rule Description	Severity
32	HREFs to targets outside application	The eCTDValidator checks for broken links in submission files. Hyperlinks targeting files outside the application will be identified.	Error
33	HREFs to targets outside sequence	The eCTDValidator checks for broken links in submission files. Hyperlinks targeting files outside sequence will be identified.	Error
34	Life Cycle Management Semantics	For leafs with operation "new", the eCTDValidator verifies that: modified file must not exist / title is given / href must exist. For leafs with operation "replace", the eCTDValidator verifies that: modified file must exist / title is given / href must exist. For leafs with operation "append", the eCTDValidator verifies that: modified file must exist / title is given / href must exist. For leafs with operation "delete", the eCTDValidator verifies that: modified file must exist / title is not required / href must not exist. The eCTDValidator verifies that for initial submissions all leafs have the operation "new". The eCTDValidator checks modified files in LCM: leaf in previous sequence must exist. It also verifies that when the attribute "modifiedfile" 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 eCTDValidator checks that all files referenced in the backbone exist.	Error
35	MD5 Checksum	The eCTDValidator regenerates the MD5 checksums for all referenced files and compares the checksums to the values provided in the backbone file.	Error
36	Naming Syntax	Checks the syntax all referenced file names (path length, illegal characters, etc.).	Error
37	Relative References	The eCTDValidator 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.	Error
38	Unreferenced Files	Searches for files not referenced in an index file (ICH, Regional or STF).	Error

XML Analysis

ID #	Rule Name	Rule Description	Severity
39	DTD Checksum (comparing content)	The DTDs and mod files found in the util/dtd folder will be compared to the corresponding DTDs and mod files located in the eCTDValidator's installation folder (subfolder DTDs). The comparison is performed byte for byte, ignoring white space.	Error
40	Existence of Node extensions	The eCTDValidator checks for "node-extension" elements being used and reports them as Warnings or Errors when found.	Ignore
41	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
42	Validate against delivered DTD	Performs XML validation for ICH Backbone and Regional backbones. Uses the DTD or Schema given in the application folder (util/dtd).	Error
43	Validate against specified DTD	Performs XML validation for ICH Backbone and Regionals backbones. Uses DTD or Schema given in the eCTDValidator's subfolder DTDs. Check does not depend on the version given in the index file. DTD/Schema to be used can be specified in validate.xml ("validateagainst").	Ignore
44	Validate against stored DTD	Performs XML validation for ICH Backbone and Regionals backbones. Uses DTD or Schema given in the eCTDValidator's subfolder DTDs. This check always uses the DTD/Schema according to the version in the index file.	Error

CA Regional 1.0

ID #	Rule Name	Rule Description	Severity
45	Adherence to Naming Convention	Checks if the naming conventions for this backbone/regional are followed	Ignore
46	All files should have one and only one file extension	Checks if referenced files have exactly one file extension.	Error
47	Attribute Check-sum Type	The checksum-type attribute must have the value md5 or MD5.	Error
48	Attribute Submission Type	Checks if the submission-type attribute is present.	Error
49	Cover letter operation attribute	Cover letter should have 'new' operation attribute	Warning
50	Element 3011 form = {en/fr}	Check that the 3011 form is named hc-sc-3011-en.pdf in the English version, or hc-sc-3011-fr.pdf in the French version.	Warning
51	Element applicant	Checks if the attribute value is present.	Warning
52	Element must have leafs	Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'.	Error
53	Element product-name	Checks if the attribute value is present.	Warning
54	Element related-sequence-number format	The value of the sequence-number element must consist of 4 digits.	Ignore
55	Element related-sequence-number value	The numeric value of the related-sequence-number element must be lower than the sequence number being validated.	Ignore
56	Element sequence- number	The value of the sequence-number element must match the sequence folder name.	Error
57	Element sequence-number format	The value of the sequence-number element must consist of 4 digits.	Error
58	Element submission-date	The value of the submission-date element must be given in format YYYY-MM-DD	Error
59	Element submission-identifier format	The value of the application-identifier element must start with an e, followed by 6 digits.	Error
60	Element submission-identifier value	The value of the application-identifier element must match the application folder name.	Error
61	Folder m1\ca exists	The folder m1\ca must exist.	Error
62	Leaf title must not be empty	For operations other than 'delete', all leafs must have a 'title' child. The title must be present.	Error
63	Module 1 (regional xml file) exists	The regional backbone ca-regional.xml file must exist in folder m1\ca.	Error

ICH Backbone - 3.00

ID #	Rule Name	Rule Description	Severity
64	Adherence to Naming Convention	Checks if the naming conventions for this backbone/regional are followed	Ignore
65	All files should have one and only one file extension	Checks if referenced files have exactly one file extension.	Error
66	Attribute checksum type	The checksum-type attribute must have the value md5 or MD5.	Error
67	Attribute DosageForm	Checks if the attribute value is present.	Error
68	Attribute Excipient	Checks if the attribute value is present.	Error
69	Attribute Indication	Checks if the attribute value is present.	Error
70	Attribute Product-Name	Checks if the attribute value is present.	Error
71	Attribute Substance	Checks if the attribute value is present.	Error
72	Element must have leafs	Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'.	Error
73	File index.xml exists	The index.xml file must be present.	Error
74	File index-md5.txt exists	The MD5 checksum file index-md5.txt must be present.	Error
75	Folder m1 exists	The m1 folder must be present.	Error
76	Folder m2 exists	The m2 folder may exist.	Ignore
77	Folder m3 exists	The m3 folder may exist.	Ignore
78	Folder m4 exists	The m4 folder may exist.	Ignore
79	Folder m5 exists	The m5 folder may exist.	Ignore
80	Folder util exists	The util folder must exist.	Error
81	Leaf title must not be empty	For operations other than 'delete', all leafs must have a 'title' child. The title must be present.	Error
82	No other files in root	The root folder (the application root) must not have any other files in addition to the files explicitly allowed by the rules above.	Error
83	Node Extension title must not be empty	For node extensions, the title child must be present (value must be present).	Error
84	Regional backbone(s) referenced	All regional backbone files must be referenced.	Error

ICH Backbone - 3.2

ID #	Rule Name	Rule Description	Severity
85	Adherence to Naming Convention	Checks if the naming conventions for this backbone/regional are followed	Ignore
86	All files should have one and only one file extension	Checks if referenced files have exactly one file extension.	Error
87	Attribute checksum-type	The checksum-type attribute must have the value md5 or MD5.	Error
88	Attribute dosage form	Checks if the attribute value is present.	Error
89	Attribute excipient	Checks if the attribute value is present.	Error
90	Attribute Indication	Checks if the attribute value is present.	Error
91	Attribute Manufacturer	Checks if the attribute value is present.	Error
92	Attribute Product-Name	Checks if the attribute value is present.	Error
93	Attribute Substance	Checks if the attribute value is present.	Error
94	Element must have leafs	Checks for elements not having any leaf child nodes. This only affects elements with a name that starts with 'm'.	Error
95	File index.xml exists	The index.xml file must be present	Error
96	File index.md5.txt exists	The MD5 checksum file index-md5.txt must be present.	Error
97	Folder m1 exists	The m1 folder must be present.	Error
98	Folder m2 exists	The m2 folder must be present.	Ignore
99	Folder m3 exists	The m3 folder must be present.	Ignore
100	Folder m4 exists	The m4 folder must be present.	Ignore
101	Folder m5 exists	The m5 folder must be present.	Ignore
102	Folder util exists	The util folder must be present	Error
103	Leaf title must not be empty	For operations other than 'delete', all leafs must have a 'title' child. The title must be present.	Error
104	m1-administrative element must exist	The element m1-administrative-information-and-prescribing information must be present.	Error
105	No other files in m1	The m1 folder must not have any other files in addition to the files explicitly allowed by the rules above.	Error
106	No other files in root	The root folder (the application root) must not have any other files in addition to the files explicitly allowed by the rules above. .	Error
107	Node Extension title must not be empty	For node extensions, the title child must be present (value must be present).	Error
108	Regional backbone(s) referenced	All regional backbone files must be referenced.	Error
109	Regional backbone(s) referenced operations	Regional backone(s) referenced (ca-regional.xml) should have 'new' operation attribute.	Warning

STF - 2.0

ID #	Rule Name	Rule Description	Severity
110	Adherence to Naming Convention	Checks if the naming conventions for this backbone/regional are followed	Ignore
111	All files should have one and only one file extension	Checks if referenced files have exactly one file extension.	Error
112	Check Index Reference	Verifies that the href target exists and has the correct value.	Warning
113	Check Index Reference (title - match)	Verifies that the href target exists and matches the title value.	Warning
114	Content-Block block title must not be empty	The value of the content-block/block-title elements must not be empty.	Warning
115	Document content (file-tag, info type:FDA)	Verifies that the file-tag name value is one of these (for info-type fda):data-tabulation-dataset,data-tabulation-data-definition,data-listing-dataset,data-listing-data-definition, analysis-dataset, analysis-program, analysis-data-definition, annotated-crf, ecg, image,subject-profile,safety-report,antibacterial, special-pathogen,antiviral,iss,ise,pm-description	Warning
116	Document content (file-tag, info type:ICH-e3)	Verifies that the file-tag name value is one of these (for info-type iche3):legacy-study-report,synopsis,study-report-body,protocol-or-amendment,sample-case-report-form, iec-erb-consent-form-list,list-description-investigator-site,signatures-investigators,list-patients-with-batches,randomisations-scheme, randomisations-scheme, audit-certificates-report,statistical-methods-interim-analysis-plan, inter-laboratory-standardisation-methods-quality-assurance,publications-based-on-study,publications-referenced-in-report,discontinued-patients,protocol-deviations,patients-excluded-from-efficacy-analysis,demographic-data,compliance-and-drug-concentration-data, individual-efficacy-response-data,adverse-event-listings,listing-individual-laboratory-measurements-by-patient, case-report-forms	Warning
117	Document identifier (duration)	Verifies that the duration value (for info-type fda) is one of these: short, medium, long.	Warning
118	Document identifier (route of administration, info-type: FDA))	Verifies that the route-of-admin value (for info-type ich-e3) is other	Warning
119	Document identifier (route of administration, info-type: ICH-e3)	Verifies that the route-of-admin value is one of these: oral intravenous, intramuscular, intraperitoneal, subcutaneous, inhalation, topical	Warning
120	Document identifier (species)	Verifies that the species value (for info-type ich-e3) is one of these: mouse, rat, other-rodent, rabbit, dog, nonhuman-primate, other-nonrodent-mammal, nonmammal	Warning
121	Document identifier (type of control)	Verifies that the type-of-control value (for info-type ich-e3) is one of these: placebo, no-treatment-control, dose-response-without-placebo, active-control-without-placebo external-control	Warning
122	Document identifier category must not be empty	The value of the document-identifier/category element must not be empty.	Warning
123	Document identifier doc-id must not be empty	The value of the document-identifier/doc-id element must not be empty.	Warning
124	Document identifier title must not be empty	The value of the document-identifier/title element must not be empty.	Warning
125	No backslash in HREF	Verifies that href values do not contain backslashes.	Warning

STF - 2.2

ID #	Rule Name	Rule Description	Severity
126	Adherence to Naming Convention	Checks if the naming conventions for this backbone/regional are followed	Ignore
127	All files should have one and only one file extension	Checks if referenced files have exactly one file extension.	Error
128	Check Index Reference	Verifies that the href target exists and has the correct value.	Warning
129	Check Index Reference (title - match)	Verifies that the href target exists and matches the title value.	Warning
130	Content Block are not accepted	Reports any used content-block element.	Warning
131	Content-block block-title must not be empty	The value of the content-block/block-title elements must not be empty.	Warning
132	Document content (file-tag, info type:ich	Verifies that the file-tag name value is one of these (for info-type ich): pre-clinical-study-report, legacy-clinical-study-report, synopsis, study-report-body, protocol-or-amendment, sample-case-report-form, iec-irb-consent-form-list, list-description-investigator-site, signatures-investigators, list-patients-with-batches randomisations-scheme, audit-certificates-report, statistical-methods-interim-analysis-plan inter-laboratory-standardisation-methods-quality-assurance, publications-based-on-study publications-referenced-in-report, discontinued-patients, protocol-deviations, patients-excluded-from-efficacy-analysis, demographic-data compliance-and-drug-concentration-data, individual-efficacy-response-data adverse-event-listings, listing-individual-laboratory-measurements-by patient, case-report-forms, available-on-request	Warning
133	Document content (file-tag, info type:jp)	Verifies that the file-tag name value is one of these (for info-type jp): complete-patient-list, serious-adverse-event-patient-list, adverse-event-patient-list abnormal-lab-values-patient-list	Warning
134	Document content (file-tag, info-type:us)	Verifies that the file-tag name value (for info-type us) is one of these: data-tabulation-dataset, data-tabulation-data-definition, data-listing-dataset, data-listing-data-definition, analysis-dataset, analysis-program, analysis-data-definition annotated-crf, ecg, image, subject-profiles, safety-report, antibacterial, special-pathogen antiviral, iss, ise, pm-description, nonclinical-data, individual-subject-data-listing	Warning
135	No backslash in HREF	Verifies that href values do not contain backslashes.	Warning
136	Study Identifier (duration)	Verifies that the duration value (for info-type us) is one of these: short, medium, long	Warning
137	Study Identifer (route of admin)	Verifies that the route-of-admin (for info-type ich) value is one of these: oral, intravenous, intramuscular, intraperitoneal, subcutaneous, inhalation, topical, other	Warning
138	Study Identifer (species)	Verifies that the species (for info-type ich) value is one of these: mouse, rat, hamster, other-rodent, rabbit, dog, non-human-primate, other-non-rode, non-mammals	Warning
139	Study Identifer (type-of-control)	Verifies that the type-of-control (for info-type ich) value is one of these: placebo, no-treatment, dose-response-without-placebo, active-control-without-placebo, external	Warning
140	Study Identifier category must not be empty	The value of the study-identifier/category element must not be empty.	Warning
141	Study Identifier study-ID must not be empty	The value of the study-identifier/study-id element must not be empty.	Warning
142	Study Identifier title must not be empty	The value of the study-identifier/title element must not be empty.	Warning