What it checks. File is named ich-ectd-3-2.dtd

What it checks. In the folder /XXXX/util/dtd

What it checks. Currently acceptable versions are described in the current ICH eCTD Specification. (The checksum for the DTD in eCTD v3.2 (ich-ectd-3-2.dtd) shall match the published value)

What it checks. With reference to any transition guidance, going back to an earlier version is not allowed when a newer version has already been used for that eCTD. 'The sequence numerically preceding the incoming sequence in the eCTD lifecycle' refers to the highest numbered sequence that is numerically lower than the incoming sequence.The criterion should only be tested if there are sequences with lower sequence numbers present.

What it checks. This rule specifically tests in situations where sequences have been submitted out of order. 'The sequence numerically succeeding the incoming sequence in the eCTD lifecycle' refers to the lowest numbered sequence that is numerically higher than the incoming sequence. The criterion should only be tested if there are sequences with higher sequence numbers present.

What it checks. File is named ectd-2-0.xsl

What it checks. In the folder /XXXX/util/style

What it checks. For example, the checksum corresponding to the stylesheet from eCTD specification v3.2 (ectd-2-0.xsl) is 3a07a202455e954a2eb203c5bb443f77

What it checks. File is named eu-regional.dtd

What it checks. In the folder /XXXX/util/dtd

What it checks. Currently acceptable with reference to any transition guidance (Refer to http://esubmission.ema.europa.eu/eumodule1/index.htm). For example, the checksum for the DTD for EU m1 v3.1 is f8e473246d58499f9ffff8e51a32380d

What it checks. With reference to any transition guidance, going back to an earlier version is not allowed when a newer version has already been used for that eCTD. 'The sequence numerically preceding the incoming sequence in the eCTD lifecycle' refers to the highest numbered sequence that is numerically lower than the incoming sequence. For example if 0109 used DTD 1.4, 0110 was DTD 2.0, and 0111 is not present, then 0112 must be built in either DTD 2.0 or higher.The criterion should only be tested if there are sequences with lower sequence numbers present.

What it checks. This rule specifically tests in situations where sequences have been submitted out of order. 'The sequence numerically succeeding the incoming sequence in the eCTD lifecycle' refers to the lowest numbered sequence that is numerically higher than the incoming sequence. For example if 0010 used DTD 1.4, and 0012 was DTD 2.0, then 0011 must be built in either DTD 2.0 or 1.4. The criterion should only be tested if there are sequences with higher sequence numbers present

What it checks. File is named eu-leaf.mod

What it checks. In the folder /XXXX/util/dtd

What it checks. For example, the checksum for eu-leaf.mod from EU eCTD Module 1 v3.1 is 23B854174E61C68044B9F53C0009AF95

What it checks. File is named eu-envelope.mod

What it checks. In the folder /XXXX/util/dtd

What it checks. For example, the checksum for eu-envelope.mod from EU eCTD Module 1 v3.1 is cf059a8f48c68fe4ce9ad2947ab854ca

What it checks. File is named eu-regional.xsl

What it checks. In the folder /XXXX/util/style

What it checks. For example, the checksum for the stylesheet from EU eCTD Module 1 v3.1 is 474f3fe1fdadb31c74477793e060383d

What it checks. The root folder /XXXX

What it checks. File is named index.xml

What it checks. Well formed with respect to the rules of the XML specification

What it checks. Valid with respect to the ICH eCTD DTD file included in the util/dtd folder

What it checks. This is the ICH DTD in /XXXX/util/dtd, and tested for validity by rules 1.1 - 1.4. A valid reference means a URI - see http://www.w3.org/TR/xml/ and http://www.ietf.org/rfc/rfc3986.txt (version 2005 page 22, section 3.3)

What it checks. This is the ICH stylesheet in /XXXX/util/style and tested for validity by rules 2.1 - 2.3. A valid reference means a URI - see http://www.w3.org/TR/xml/ and http://www.ietf.org/rfc/rfc3986.txt (version 2005 page 22, section 3.3)

What it checks. The root folder /XXXX

What it checks. The file is named index-md5.txt

What it checks. The folder /XXXX/m1/eu

What it checks. File is named eu-regional.xml

What it checks. Well formed with respect to the rules of the XML specification

What it checks. Valid with respect to the EU Module 1 DTD file included in the util/dtd folder

What it checks. This is the EU Regional DTD in /XXXX/util/dtd, and tested for validity by rules 3.1-3.5. A valid reference means a URI - see http://www.w3.org/TR/xml/ and http://www.ietf.org/rfc/rfc3986.txt (version 2005 page 22, section 3.3)

What it checks. This is the stylesheet in /XXXX/util/style, and tested for validity by rules 6.1-6.3. A valid reference means a URI - see http://www.w3.org/TR/xml/ and http://www.ietf.org/rfc/rfc3986.txt (version 2005 page 22, section 3.3)

What it checks. This criterion will test whether the UUID is well formed

What it checks. This rule checks that the UUID is correct and the sequence is being loaded into the correct eCTD Application

What it checks. The UUID is unique for each Dossier and is identical with the most recent sequence sent.

What it checks. Note that this value is not case sensitive

What it checks. Note that if the content file is in an earlier sequence within the same eCTD application then the checksum can only be regenerated if access to this file is available.The MD5 checksum is not case sensitive

What it checks. The value for the cross reference (xlink:href) should be valid, and not contain any illegal characters. (Legal characters are lower case characters a-z, digits 0-9 and hyphens, as documented in the ICH eCTD specification). A valid reference means a URI - see http://www.w3.org/TR/xml/ and http://www.ietf.org/rfc/rfc3986.txt (version 2005 page 22, section 3.3).

What it checks. The attribute does not need to be included, or can be declared but with a null value

What it checks. The link within the XML leaf element is valid, i.e. the target exists

What it checks. Note - it is recommended that the tracking table is always provided with the operation attribute of 'new', due to national sequences in MRP/DCP

What it checks. The attribute does not need to be included, or can be declared but with a null value

What it checks. This test applies to all procedures.'common', 'ema', or 'edqm' are not considered to be country specific attributes.However, in common MRP/DCP sequences, replacing previously submitted national content also in other modules can result in a fail according to this criterion in other member states. Therefore, unless a technical solution to prevent this from occurring is available in the eCTD Building tool, applicants should avoid replacing, deleting or appending to content submitted in national sequences (other than the first national phase before MRP), and vice versa.

What it checks. Same CTD section' refers to the position in the table of contents. Sections are defined by the CTD and also by attributes in the eCTD. For example, applicants cannot replace content in the application form section with revised content that is being provided in the cover letter section. eCTD attributes also create applicant defined sections. For example, each 'substance' or 'manufacturer' attribute in m3-2-s-drug-substance, or 'product-name' attribute in m3-2-p-drug-product will create a new CTD section, and lifecycle between these sections is also not allowed. For further details refer to Section 2.9.6 on page 13 of the Harmonised Technical Guidance for eCTD Submissions in the EU.Due to inconsistency between tools how attributes are handled in the past, attributes in module 3.2.A should be allowed to be edited or not automatically copied. To avoid unnecessary errors these modules are exempt as well

What it checks. ID must be unique within each sequence

What it checks. Documents can be replaced or deleted just once.The modified file must not have been subject to another replace or delete operation in any of the available sequences

What it checks. In common MRP/DCP sequences, replacing previously submitted national content can result in a fail according to this criterion in other member states. Therefore, unless a technical solution to prevent this from occurring is available in the eCTD Building tool, applicants should avoid replacing, deleting or appending to content submitted in national sequences (other than the first national phase before MRP), and vice versa. 'common', 'ema', or 'edqm' are not considered to be country specific attributes

What it checks. The definition of 'same CTD section' is as in criterion 11.10. If the node extension is not in the same section the criterion 11.10 still applies

What it checks. The problem is with attributes in the XML that define re-useable sections. Hyphens or spaces at the beginning or end of a attribute name are not allowed

What it checks. i.e. numbers between 0000 and 9999

What it checks. This should be 'ema'

What it checks. The country attribute value must not be 'ema' or 'common' or 'edqm'

What it checks. The country attribute value must not be 'ema' or 'common' or 'edqm'

What it checks. This should be 'edqm'. It is expected to use 'centralised' as the procedure type (see criterion 14.9)

What it checks. Even if no content is specific to that country there must still be an EU envelope for each country receiving an MRP/DCP/NP submission. However, note that there is not a test for this scenario. For CP submissions, there must only be 'ema' or 'common' leaf attribute and a corresponding 'ema' envelope (see 14.1).This rule should not apply to documents in country specific leaves with 'delete' operation attributes. Refer to 14BP3

What it checks. Refer to EU m1 specification. When submitting a first submission initialising a regulatory activity or proving a reformatted application, the related sequence attribute should be populated with the same number of that current sequence.Due to some inconsistencies of implementation the criterion is now be considered as P/F

What it checks. Refer to EU m1 specification. When submitting additional lifecycle sequences within an ongoing regulatory activity, the related sequence attribute should be populated with the number of the sequence that started this regulatory activity.Due to some inconsistencies of implementation the criterion is now be considered as P/F

What it checks. It is the intent to assure the INN data field is completed. It is strongly recommended to re-use the active ingredient name as of the application form. Separation of multiple names by colon

What it checks. The procedure type should be 'centralised' for EDQM

What it checks. Even if no content is specific to that country there must still be an EU envelope for each country receiving an MRP/DCP/NP submission. If there is a need for removal of earlier content that has erroneously been attributed to a particular country in the leaf metadata without provision of a corresponding envelope entry, then this BP error should be ignored

What it checks. This is the optional element for a high-level submission number, either a 'worksharing' number, or the high-level submission number to be used when grouping Type IA variations for multiple marketing authorisations. Refer to EU m1 Specification and validation criteria 14BP7 and 14BP8

What it checks. This is the optional element for a high-level submission number, either a 'worksharing' number, or the high-level submission number to be used when grouping Type IA variations for multiple marketing authorisations. Therefore, it should not be provided if the mode is not set to 'grouping' or 'worksharing'. Refer to EU m1 Specification

What it checks. Refer to the Acceptable file formats for EU Module 1

What it checks. Refer to the Acceptable file formats for EU Module 1

What it checks. Counting starts from the first digit of the sequence number in the sequence number folder name, and includes the filename

What it checks. Lower case characters a-z, digits 0-9 and hyphens are allowed (as documented in the ICH eCTD specification). This test should only be applied to the file names in the file system, for checks on the XML see test 11.4.

What it checks. Lower case characters a-z, digits 0-9 and hyphens are allowed (as documented in the ICH eCTD specification). This test should only be applied to the folder names in the file system, for checks on the XML see test 11.4.

What it checks. Including all subfolders within the m1-m5 folders but excluding 'util' folder and subfolders

What it checks. The folder is: /XXXX/m1/eu/10-cover/ema (for CP) /XXXX/m1/eu/10-cover/common (for MRP/DCP) /XXXX/m1/eu/10-cover/cc ('cc' being the actual country code for NP) There is no tracking table for EDQM submissions

What it checks. File is named common-tracking-var.pdf ('common' is the appropriate value for 'cc' in MRP/DCP) File is named ema-tracking-var.pdf ('ema' is the appropriate value for 'cc' in CP) File is named cc-tracking-var.pdf ('cc' being the actual country code for NP) Note that the use of XML format for the Tracking table is not acceptable, since there is no longer a valid EU standard to use for this format. There is no tracking table for EDQM submissions

What it checks. Any deviation should always be reported by the validating tool. Files larger than 500 MB should be avoided due to potential archiving issues and to make the assessment easier.

What it checks. Any deviation, including additional subfolders, should always be reported by the validating tool.Although navigation of an eCTD is typically carried out via the XML backbone, it is also helpful if the underlying files and folders follow the ICH and EU naming guidance

What it checks. Any deviation should always be reported by the validating tool.Note that the components of the file names in italics in Appendix 4 of the ICH eCTD specification are to be specified by the applicant (i.e. this is variable text).The potential presence of STF files in m4 or m5 should not be tested.Although navigation of an eCTD is typically carried out via the XML backbone, it is also helpful if the underlying files and folders follow the ICH and EU naming guidance

What it checks. This criterion will check whether the country codes are used consistently

What it checks. This criterion will check whether the country codes are used consistently

What it checks. Any deviation should always be reported by the validating tool. Video files larger than 1GB should be avoided due to potential archiving issues and to make the assessment easier.

What it checks. PDF 1.3 or earlier is not acceptable for technical reasons. No exceptions will be made. For example, if a literature reference is received in PDF 1.3 or earlier, then the applicant must provide it in PDF 1.4, 1.5, 1.6 or 1.7, even if this means copying the full text into a new document or even getting a paper copy and scanning it.Further guidance is provided about the best ways to check the PDF version in the comment to rule 16.BP1

What it checks. This includes passwords, certificate security, or adobe policy server settings. This test should not be used to test for corrupted files, instead see 16.4

What it checks. All 'restrictions' should be 'allowed' when viewing the Document Preferences > Security settings. This includes any of the following document restrictions: printing, changing the document, document assembly, content copying, content copying for accessibility, page extraction, filling of form fields, signing, creation of template pages. Specific security settings of files in m1.0 and m1.2 are tested in criterion 16.4

What it checks. These limited security settings are allowable for the application form, because they are necessary for the functioning of the eAF and similar forms such as e.g the PAM form

What it checks. This can be achieved by opening a PDF file in software which is compliant to ISO 32000-1; if the file opens without error, the PDF file is considered to be conformant. Absence of detection of conformance means corrupted PDF

What it checks. For easier identification of the PLM Portal web-based eAFs vs the interactive pdf eAF, the following details may help; For the eAFs generated from the PLM Portal that have not been altered further by any other tool, in the document properties the name of the application is: PDF generator and the author is 'European Medicines Agency'. For the interactive pdf eAF the name is 'Designer 6.5'. The PLM Portal eAF version number starts with 2.x and for the interactive pdf the version number starts with 1.x. The check on FHIR XML attachment is not applicable for the interactive pdf eAFs. The interactive pdf eAF must not contain any additional attachments.

What it checks. In the document properties the name of author for the interactive pdf eAF the name is 'Designer 6.5'. The interactive pdf the version number starts with 1.x and for the PLM Portal eAF version number starts with 2.x. The check on FHIR XML attachment is not applicable for the interactive pdf eAFs. The interactive pdf eAF must not contain any additional attachments.

What it checks. For PDF files with apparent versions of 1.3 or earlier, the version information should be taken from the first eight characters from the first line of the header in the file. For versions 1.4 and higher, the version should be taken from the document catalogue dictionary, if present. If both the header information and the catalogue information are present, then the document catalogue dictionary information takes precedent, see PDF 32000-1:2008 specification, chapter 7.5.2 for further details.Only the PDF versions specified are recommended by ICH. This test is important due to archiving and also that PDF files can be correctly opened and read by assessors

What it checks. Only links that open in the same software application are tested. Other links (e.g. web links and e-mail addresses) are not considered to link to essential content and should not be tested.If this BP criterion is not met, the assessor might not be able to conveniently find the relevant documents and read the submission as intended by the applicant

What it checks. Only links that open in the same software application are tested. Other links (e.g. web links and e-mail addresses) are not considered to link to essential content and should not be tested.If this BP criterion is not met, the assessor might not be able to conveniently find the relevant documents and read the submission as intended by the applicant

What it checks. Using 'inherit zoom' ensures that assessors do not need to spend time repeatedly setting the view when using the links for navigation to new documents

What it checks. The use of 'Fast Web View' helps ensure optimum performance of the review system.However, e.g. PAM form and eAF PDF files are exempt from this rule as they cannot be provided as fast web view version

What it checks. Setting page layout and magnification to default allows the assessor to set his/her own preferences to define how the PDF is displayed, rather than the settings being taken from each individual PDF file

What it checks. Relative links and bookmarks will continue to work when the submission is copied and loaded into new a environment at the agency side. Absolute (rooted) links and bookmarks will not

What it checks. Fulfilling this BP criterion make it more convenient for the assessor in knowing there are bookmarks without opening the pane

What it checks. Fulfilling this BP criterion makes it more convenient for the assessor in knowing there are no bookmarks without opening the pane to check

What it checks. Consult the PDF specifications as in ISO 32000-1:2008 for section 7.11.2.3 on how the paths need to be written in PDF. The paths cannot contain back slashes, only forward slashes. See also 12.6.4.3 for the remote goto action. The link to another PDF cannot be made with javascript code in the PDF. Please note, not all PDF tools display the path for the link with forward slashes. However, the presence of a backslash in a link as displayed in a PDF viewer or editor does not necessarily mean that the link is NOT according to the ISO specifications. Therefore, tests for backslashes must be performed in eCTD validation software.This BP criterion is important because links who are not according to section 7.11.2.3 may not work on certain devices, such as non-Windows operating systems or tablets

What it checks. This rule will check whether the Document Properties>Description of the PDF for SmPC, Labelling and Package Leaflet documents is completed (Title, Author, Subject, Keywords).