The electronic format is the expected format for submissions today and to be able to work more efficiently, the Medical Products Agency (MPA) strongly urges applicants to send all their submissions in electronic format. The EU e-submission formats – eCTD, NeeS, or VNeeS – should be used.
Information on each of the three formats can be found on the EMA website “eSubmission” (see link to the right). All strengths and formulations of a medicinal product should be managed in the same format.
In accordance with the EU eSubmission Roadmap the eCTD format is mandatory for applications for new medicinal products for human use in the decentralised procedure from 1 July 2015, for applications for new medicinal products for human use in the mutual recognition procedure from 1 January 2017 and all other types of applications within the mutual recognition procedure from 1 January 2018. The VNeeS format is mandatory for applications for new medicinal products for veterinary use in the decentralised procedure from 1 January 2016 and for all types of applications within the mutual recognition procedure from 1 January 2017.
For more information on the EU eSubmission Roadmap and the introduction of mandatory eCTD, VneeS, eAF and CESP, see the EMA eSubmission website.
Bookmarks for this page:
Technical requirements and validation
Guidance documents and other aids
Using the CESP
Using the eSubmission Gateway/Web Client
Switch from paper-based submission to e-submissions
Active Substance Master File
Five ways to send an electronic submission to the Medical Products Agency
- Using the CESP – recommended by the Medical Products Agency for all types of applications except those listed in paragraph 2
- Using the eSubmission Gateway/Web Client – only for submitting documentation for human medicinal products in the Centralised Procedure, as well as for PSUR documentation for all authorised medicinal products being assessed within the EU Single Assessment
- Using EudraLink - a complete eCTD, NeeS, or VNeeS will have to be zipped in order for the folder structure to remain
- Using email – can be used for submissions no larger than 20 MB. Aa complete eCTD, NeeS, or VNeeS will have to be zipped in order for the folder structure to remain
- Using CD/DVD -refrain from zipping the content
NOTE! Use only one of the above for each submission since duplicate submissions will cause the MPA unnecessary extra work.
Cover letter template
The Medical Products Agency recommends applicants to use the CMDh cover letter template for all submissions made for DCP/MRP (see link to the HMA website to the right). It is also recommended to use the template when submitting national applications to the Medical Products Agency.
The Medical Products Agency does not require an original signature or a scanned signature on neither the application form nor the cover letter. However, the applicant should always lock the electronic application with a so-called “signature” (see below).
Electronic application form
The electronic application form ( eAF) should be used for the application types that have one. The eAF should always be sent electronically, so even if other documentation is submitted in paper format the eAF must be attached electronically (on disc) .
Please note that the eAF should always be sent to us locked (with a so-called “signature”)
For more information about the eAF and how to lock the form, see the EMA webside on eAF (see link to the right).
All PDF files should normally, when possible, be created from electronic text documents (e.g. Word). To facilitate the assessment, applicants should ensure that all PDF files allow for text to be fully editable after copying, so that they can easily be used to create our assessment reports.
The product information (SmPC, PL, labelling) should always be included as Word copies (with tracked changes when applicable). For submissions in the national procedure and when Sweden acts as RMS in a DCP/MRP, Word copies of included Module 2 documents are greatly appreciated, as we frequently copy text and tables from these into our assessment reports.
The Word files should be placed outside the submission folder structure, in a separate folder named “xxxx-working documents”.
Technical requirements and validation
All electronic submissions (eCTD, NeeS and VneeS) must comply with current ICH and/or EU requirements and pass the technical validation performed by the Medical products Agency against current validation criteria (see links to the ICH and the EMA eSubmission website to the right).
All Pass/Fail criteria must be met for a submission to be accepted.
Guidance documents and other aids
Guidance and validation criteria documents for each format can be found on the EMA eSubmission website. In addition there is a separate guide for eCTD submissions in MRP and DCP: ”CMDh Best Practice guide on the use of eCTD in the MRP/DCP” (see link to the right).
If you need to build a NeeS manually, the Module 2-5 folder structure is available for download from the ICH website. The EU Module 1 folder structure can be downloaded from the Medical Products Agency website (see link to the right); note that this contains country and language folders only for Sweden and “common”. Consult the EU eCTD Module 1 specification for file and folder naming rules (the naming rules can also be found on a separate tab of the eCTD and NeeS validation criteria documents, available on the EMA eSubmission website).
The CMDh eCTD BPG (see link to the right) clarifies thatno eCTD sequence is required for the following national submission types:
- Change of MAH
- Change of local agent
- Dose dispensing
- Sunset Clause
- New mock-ups
- Legal status
- National notifications for a pack size in a CMS, which is already included in the core SmPC of the MRP dossier
- National notifications to remove/add an already approved indication, due to patent usage in a CMS
For all submission types above, documentation can be sent to the Medical Products Agency as PDF files without folder structure. They must still comply with the file level requirements – i.e. PDF 1.4, 1.5, 1.6 or 1.7 and no security settings. The Medical Products Agency accepts the same handling for NeeS and VNeeS dossiers.
Please note that national translations of product information should always be placed outside the eCTD/Nees folder structure - in a separate folder called "working documents" along with an application, or as separate Word files through email/EudraLink if it is a supplement to an ongoing case.
Using the CESP
The Medical Products Agency recommends applicants to use the common platform for submissions made to the EU agencies, the CESP. It can be used for electronic submissions for all procedures (MRP, DCP, national submissions and CP ). There is no nominal size limit for submissions (it has been tested for ›8 GB); to minimize bandwidth zipping is a requirement. As with other e-submissions to the MPA, only eCTD, NeeS, and VNeeS submissions are accepted via the CESP. It should not be used for electronic copies of submissions made for paper based dossiers; these copies should always come on CD/DVD together with the documentation on paper.
The CESP is reached via the HMA CESP web page (see link to the right). In order to use the CESP, you must first register on the CESP web page. The portal includes a self-service feature, which requires each company to assign one administrator, who in turn assigns and manages user accounts to other people in the organization. Note that there is a separate form to use for registration of the administrator, accessible via the same link on the CESP website. The Medical Products Agency recommends all new users of the CESP to participate in the free webinars offered regularly.
The Medical Products Agency would like to emphasize the importance of not submitting duplicate documentation. If documentation is resent the comments field should always be used to clarify why the documentation is being sent again including a reference to the previous CESP-submission.
If the documentation for an MRP product is only to be sent to one specific CMS the RMS "zz" should be specified, in order to avoid the RMS receiving a copy of the documentation.
Using the eSubmission Gateway/Web Client
Any submission of documentation for human medicinal products in the Centralised Procedure, as well as PSUR documentation assessed within the EU Single Assessment, should be made only via the eSubmission Gateway/Web Client. Any such submission sent to the Medical Products Agency in any other way will be discarded – we will fetch the documentation from the Common Repository/PSUR Repository.
For information on the eSubmission Gateway/Web Client, consult the EMA website (see link to the right).
EudraLink is a secure file transfer solution provided by the EMA. To use the service you must first register for a EudraLink account through the EMA website. Individual files must not exceed 200 Mb, but otherwise there are no size restrictions. Any submission containing folders (e.g. eCTD, NeeS and VneeS) must be zipped in order for it to reach the recipient(s) in the intended structure.
Ensure that all submissions have an expiry date of at least 30 days.
When sending documentation on CD/DVD, the Medical Products Agency need only one copy of each disc. Discs must be clearly labeled in accordance with current EU e-submission guidelines. If multiple submissions for a product are made at the same time, these should preferably be contained on one single disc. Each submission must still have a separate folder structure, and the disc should be labeled with all submissions it contains.
You can find additional information on various practical aspects with submissions on the page “Practical guidance for submissions” (see link to the right).
Switch from paper-based submissions to e-submissions
The Medical Products Agency encourages applicants to make all submissions in electronic format, even for dossiers initially submitted on paper (a so called paper-based dossier).
Any dossier format change from paper to eCTD, NeeS, or VNeeS must be made in conjunction with the submission of a variation renewal application, PSUR or other new regulatory activity. Alternatively, a switch can be made at any point in the dossier lifecycle by submitting a “baseline” dossier (see below).Unless otherwise agreed, any dossier format switch is assumed to apply for all strengths and formulations of a medicinal product sharing the same trade name. Thus, even if the submission initiating the format switch only concerns some of all dossiers with the trade name, they will all be encompassed by the switch.
A technical validation of the submission will be made. If the submission does not pass this validation, the Medical Products Agency will request a technically revised submission. All future submissions made will be expected to be in the same format (or later upgraded from NeeS to eCTD).
When switching submission format from paper to one of the EU e-submission formats, there is no requirement for reformatting any documentation previously submitted only on paper. However, to facilitate assessment the Medical Products Agency recommends that dossiers that are switched to eCTD format start the lifecycle with a collection of all currently valid Module 3 documents as a so-called “baseline”. This reformatted documentation should be sent as a unique sequence (normally 0000), with the cover letter clarifying that the contents have been previously assessed and that the only change made is the dossier format.
A baseline can also be submitted later in the dossier lifecycle, adding valid documentation that hasn’t yet been submitted in eCTD format. Here too, the documentation must be sent as a unique sequence (with the next available sequence number in the lifecycle), together with a clarification in the cover letter that no new information is included, but only the format is changed. Please consult the EU Harmonised technical eCTD guidance for further information on Baseline submissions (see link to the EMA eSubmission website to the right).
Documentation for a paper-based dossier should be submitted electronically. The EU e-submission formats are strongly recommended, but until further notice the MPA will accept other electronic formats. These should be structured in a logical fashion, based on the CTD/NtA structure, and all files should preferably be in PDF 1.4 or higher.
The applicants are expected to switch paper-based dossiers to an EU e-submission format (eCTD , Nees , VNeeS ) as soon as possible. For products handled in MRP there are set dates for mandatory eCTD and VNeeS.
Active Substance Master File (ASMF)
The Medical Products Agency also prefers ASMF documentation from the ASMF holder in electronic format. The technical requirements for electronic medicinal product documentation (see above) apply to ASMF documentation as well. Any electronic ASMF documentation submission will be technically validated, with revisions requested if the submission does not comply with the requirements. Once the electronic submission is found to be in compliance with the EU e-submission technical validation criteria, the ASMF holder will be informed that the Medical Products Agency will expect all future submission for the ASMF dossier in the same format.
As clarified by the current EU guidance documents, the format of the ASMF dossier does not need to be the same as the format of any medicinal product dossier referencing the ASMF. The contents of the Applicant’s Part must still be identical, but the format may differ.
For more information on ASMF submissions in eCTD format, please consult the “Practical guidelines on the Use of the eCTD Format for ASMFs for Active Substance Master File Holders and Marketing Authorisation Holders” guidance document on the EMA eSubmission website. This guidance document is generally applicable to ASMF NeeS submissions as well, though certain technical details will differ. Note that this document is due for an update, and that some of the requirements from the validation criteria documents for eCTD/NeeS submissions supersede parts of the ASMF guidance document.