The concept of eSubmission and the use of electronic format of files were first introduced by pharmaceutical companies in coordination with the EMA and “pioneer” National Competent Authorities, under the auspices of International Conference on Harmonisation (ICH). ICH has agreed on certain rules and requirements for a structured submission of electronic files. The aim of eSubmission is focused on the minimisation of paper use during the exchange of information between applicants and National Competent Authorities and facilitation of business process.
The idea was welcomed by the European Commission, which consequently formed the Telematics Implementation Group for electronic submission (TIGes) to facilitate and enable implementation of ICH specifications for electronic submission in Europe. TIGes is operating under the control and coordination of the Telematics Management Committee with the following defined tasks:
What is a Submission?
To ensure improved responsibilities and accountability
To facilitate communication between the different parties involved – Member States, EMA and the Commission
- To ensure the appropriate involvement of interested third parties
- To prevent unnecessary duplication of work
- To ensure a suitable fit between the available resources, the final users’ needs and the technical achievements
- TIGes consists of members of National Competent Authorities and representatives from industry.
A submission refers to a specific set of information on a product that is transmitted to the Agency for regulatory action (i.e. review, approval and issuing a licence). This set of information could be part of an application from the interested party (e.g. pharmaceutical company) or information requested by the agencies. It could also be safety information such as Periodic Safety Update Reports, not necessarily leading to a regulatory action.
An application refers to a set of documents submitted for the approval of a new medicinal product, or a variation or renewal of the marketing authorisation with specific changes to the approved information for that product.
An application may consist of several individual submissions or sequences, which should be viewed together as part of an incremental process (even though they may be received non-consecutively).
An Application follows a path of an initial submission followed by a cycle of reviews and responses until approval for a marketing authorisation or its variation or its renewal. Except for the first submission of a product, a submission is always based on a previous submission for the same product.
What is an eSubmission?
An electronic Submission (or eSubmission) is a set of registration files submitted in electronic form during an approval or variation or renewal procedure (Centralised, National, Mutual, Decentralised). It could be a set of files (Portable Document Format (.pdf), Microsoft® Word files (.doc) or Rich Text Format (.rtf) and picture files like jpeg, or png, etc.) usually submitted in folders according to the current paper CTD guidance or files structured and organised according to the specifications for eCTD. Other structures or formats can be accepted according to various requirements. A NeeS (Non eCTD electronic Submission) or other type of non eCTD compliant submission differs from an electronic Common Technical Document (eCTD) as it does not contain an XML backbone or MD5 checksum as defined by the ICH (http://estri.ich.org/) – it is merely a collection of electronic files either as a “bunch” of files or organised in folders.
eSubmission could include:
- Modules 1-5 or part of them in electronic form. The most common format of files is Acrobat’s pdf for Modules 3-5 and MS Word for Modules 1-2.
- Applicant’s responses.
- Product information (SPC, PL, labelling, outer and inner package).
The media normally used for an eSubmission is a CD. Alternatively an email could be used if the size of files permits or through Agencies’ portal.
An eSubmission includes the term eCTD.
An eCTD is the electronic submission of registration files that are organized according to the version 3.2 of the ICH eCTD specifications and the current version of the EU Module 1 specifications. In other words, an eCTD is the submission of (mostly) PDF leaf documents, stored in the eCTD directory structure, crucially accessed through the XML backbone (index.xml) and with the files integrity guaranteed by the MD5 Checksum.