Technical details for electronic applications
These guidelines describe the technical specifications that applicants must comply with when submitting electronic marketing authorisation applications, variations, etc. as well as supplemental information related to applications. They elaborate on the "Guidelines on submission of electronic applications".
When applicants submit electronic marketing authorisation applications, variations, etc. as well as supplemental information related to applications – see "Guidelines on submission of electronic applications" – the submitted documents must comply with the technical specifications below. This technical description has the same scope as described in the "Guidelines on submission of electronic applications" and uses the same terminology.
CDs and DVDs must be imprinted with the details as described in "Guidance for Industry on Providing Regulatory Information in Electronic Format: eCTD electronic Submissions" (see link in the box to the right), section 2.10.6. This also applies NeeS and VNeeS applications. In addition, the format concerned (eCTD, NeeS or VNeeS) must be specified, and the authorisation procedure applied (CP, DCP, MRP or NP) must appear from the CD or DVD, if this is not implicitly indicated by the procedure number.
The same details as well as the email address of the applicant's contact person must be stated in the cover letter. Further to NeeS/VNeeS submissions, we recommend that the paper version of the cover letter describe the total number of files and byte size of the electronic submission.
Use only labels that are designed specifically for CDs and DVDs.
Documents on CD/DVD must not be password-protected or otherwise encrypted. The documents must not be compressed (zipped), but must be immediately accessible.
Supplemental information and working documents submitted by email or via Eudralink (cf. "Guidelines on submission of electronic applications") must comply with the same requirements as documentation submitted on CD/DVD – including naming and format requirements. If the applicant submits more than one file by email or via Eudralink, the applicant must compress the attached files in a single archive file. Documentation in NeeS/VNeeS or eCTD format must be compressed in an archive file, which maintains the original folder structure.
At present, the Danish Medicines Agency accepts the following archive file formats:
- MS Windows' ZIP-compressed folder
At present, the Danish Medicines Agency does not accept the following archive file formats:
The list is updated regularly.
The documentation contained in the attached file is archived and assessed independently of the email/Eudralink message. Thus, the text contained in the subject and message fields only serves the purpose of identifying the case concerned and the relevant dossier. Documentation of relevance to the review process (including the cover letter) is to be included at an appropriate place in the folder structure.
Neither email, Eudralink message, archive file nor documents must be password-protected or otherwise encrypted.
The Danish Medicines Agency makes no guarantee that it can receive files larger than 40 MB. Email is generally considered an unsecure communications platform, and until receipt on our servers, the Danish Medicines Agency takes no responsibility for the protection of confidential information.
Eudralink messages must be set to the maximum expiry time (90 days).
Common European Submission Platform (CESP) is a system which allows applicants to submit application-related material to the participating European regulatory agencies. Distribution takes place via sFTP on the basis of a "delivery file" (XML file). For guidance on how to be set up as a user and how to use CESP, please see cesp.hma.eu.
Submissions made via CESP (cf. "Guidelines on submission of electronic applications") must comply with the same requirements that are established for documentation submitted on CD/DVD – including naming and format requirements. The documentation must not be compressed ("zipped") in formats other than those supported by CESP (see cesp.hma.eu).
The documentation contained in the CESP submission is archived and assessed independently of the delivery file. Thus, the text contained in the delivery file only serves the purpose of identifying the case concerned and the relevant dossier. Documentation of relevance to the review process (including the cover letter) is to be included at an appropriate place in the folder structure.
Documents in a CESP submission must not be password-protected or otherwise encrypted.
With the exception of working documents, only documentation in PDF format is generally accepted. We accept PDF version 1.4 and later versions.
Cover letter, application form and other key documents of the electronic documentation (cf. "TIGes/CMB Harmonised eCTD Guidance", Annex 2, Section A2-2) must be text-searchable, making it possible to copy short passages and searching for text. Any scanned documents must therefore be OCR'd. All other documents must, to the extent possible, be text-searchable. Furthermore, it must be possible to copy charts, tables, etc. contained in the documentation
Note that the Danish Medicines Agency does not require electronic documents to bear the applicant's signature. We therefore recommend applicants to generate electronic documents directly from the electronic text source, rather than scanning and OCR-processing the documents.
This applies to eCTD, NeeS and VNeeS.
The documentation submitted must comply with the specifications laid down by ICH, EMA and CMD. Some of the requirements established in these specifications can be checked automatically and are established in the common-European validation criteria (see box to the right).
The technical structure of human electronic applications (excluding working documents) are validated according to these common-European validation rules. The Danish Medicines Agency uses EURSvalidator.
Note that after validation, some tools store a validation report in the folder containing the electronic submission. This extra document is enough to render a submission technically invalid. Validation reports should be placed in the "workingdocuments" folder or left out altogether.
At present, the Danish Medicines Agency has not fully implemented a validation tool for veterinary electronic submissions. The Danish Medicines Agency therefore reserves the right during a regulatory activity to refuse the submitted documentation, either fully or partially, if it proves incompatible with our systems and processes.
The Danish Medicines Agency may choose to accept an application that does not fully comply with all criteria.
Prior to submission, the Danish Medicines Agency strongly recommends applicants to perform a technical validation of the documentation against the current common-European validation rules. Normally, the validation software – including EURSvalidator – is provided free of charge.
When the eCTD format is used for the first time (and exceptional conversions of the eCTD dossier), we encourage applicants to submit a baseline submission for the product, which contains the full or partial dossier updated with all previously submitted documentation. In this connection, we will approach the requirement for text searchable files pragmatically since we expect that any scanned documentation will be exchanged for text searchable files at a later stage in accordance with applicable standards. In general, we encourage applicants to submit a baseline submission covering the part of the dossier which the current application concerns.
A baseline application is submitted in one (or several) independent sequence(s) without changes to the previously submitted documentation and is accompanied by a signed declaration stating that the documentation contained in the sequence(s) specifically referred to is identical to the previously submitted documentation and that any omissions do not render the submitted documentation misleading.
There is no obligation to submit a baseline submission, and the lack of a baseline submission will not delay the review process, but it will facilitate the handling and assessment process of the Danish Medicines Agency if a baseline is submitted. Missing eCTD sequences in the Danish Medicines Agency's archives could also result in non-technically valid sequences when a replace-operation is performed.
We would prefer to receive a full baseline dossier, but a conversion of parts of the dossier (particularly the currently relevant ones) is preferred to receiving none at all. Non-converted parts of the dossier can be submitted in future baseline submissions. We prefer to receive text-searchable files. If it is not possible to generate files from a text-based electronic source or to OCR process scanned documents, we do, however, accept non-OCR'd files in baseline submissions.
For medicinal products that have already been converted to eCTD, all previous eCTD sequences will serve as a baseline submission provided that these accumulated sequences correspond to the dossier as it appears pursuant to previously submitted applications. Electronic documentation submitted in addition to paper documentation (including documentation received before 1 January 2010) as well as documentation that has not been submitted according to the Danish Medicines Agency's guidelines will not be used as a baseline submission.
Applicants are welcome to contact the Danish Medicines Agency for information on which sequences we have archived in eCTD format.
The Danish Medicines Agency must handle and archive documentation differently depending on its format. Therefore, we wish to minimise the number of formats within the same product family and to minimise the number of switches between formats during the product's life cycle.
Since particularly the switch between eCTD and other formats is administratively burdensome, we only accept transition to eCTD. The transition to eCTD processing must be made for the entire product family (same SpN / D.Sp.No.). After a transition has been made to eCTD, previously submitted regulatory activities (new marketing authorisation, variation, renewal, etc.) can be completed in the previous format, but any submissions relating to subsequent applications must be in eCTD format.
Just before, or in connection with, the first eCTD submission, the applicant completes, signs and submits a confirmation, stating that the applicant understands our requirements for format transition and acknowledges that future applications must be submitted in the eCTD format. This applies both to a change in format and the submission of a new marketing authorisation application in eCTD. The confirmation must be submitted on paper, bearing a wet signature or via CESP. Please find a link in the right-hand box (Confirmation for eCTD submissions).
Instead of submitting the "Confirmation for eCTD submissions", the applicant may use the latest version of the CMDh's cover letter template and put a tick mark in "We confirm that all future submissions for this specific product will be submitted in this same format".
Because of the Danish Medicines Agency's electronic archives, we request applicants to describe to the Danish Medicines Agency the structure applied on their dossiers and to follow this structure consistently, so that documentation which affect several dossiers is submitted in separate sequences and so that documentation is not repeated within the same dossier.