Talking R&D: eCTD challenges
pharmafile | October 6, 2010 | Feature | Manufacturing and Production, Research and Development |Â Â Talking R&D, eCTD, eCTD submissionsÂ
The eCTD was of course developed by the ICH (International Conference on Harmonisation) Expert Working Group to make it easier, more structured and more readily understandable to transfer regulatory information.
A noble idea and a great starting point, but has it all been worth it?
And just what is it like working with the eCTD on a daily basis? The eCTD does have a steep learning curve as does the use of eCTD software.
It is practically impossible to generate an eCTD without specialist software, I have based my comments on using proprietary software.
An eCTD is broken down into four sections I will take each of the four sections in turn.
Folder Structure
Firstly, eCTD uses a hierarchical structure to folders and is easily managed and familiar.
Because of its universal standard eCTD, is easy to review in a basic way (web browser and acrobat reader) both of which are free software. Logical and easy, a great start! Reviewing is the only part of the eCTD that does not require complicated and/or expensive software.
Contents
The contents mirror that of the old paper CTD so the format is familiar, files are simply placed in the appropriate position in the folder structure. The first minor problem occurs when a file is not immediately available in electronic format. This means it must be scanned and converted into an electronic format, however this does not make it readily searchable, something the electronically rendered PDF file is.
OCR can be used to find text in scanned files but is not 100% accurate and is prone to error.
Including bookmarks and hyperlinks can be done automatically at the time of PDF creation but in the case of scanned documents it’s not available.
All of this leads to changing working practices to be completely ‘electronic’.
Because life cycle management (LCM) requirements ensure the dossier is always current, this allows the latest information to be viewed quickly. Dossiers can be re-used and adapted for other regions or countries. Also compilation can be done as documents are available; there is no need to wait for the whole dossier to be ready.
Whilst the eCTD is now the standard, some of the EU competent authorities have varied their timing for its implementation, with some still requiring paper submissions.
Because the eCTD specifications give specific requirements for PDF documents (fonts embedded, PDF1.4 etc.) documents that have been generated without these requirements being met mean extensive rework.
Once a dossier is in eCTD it has to be maintained as an eCTD, this can mean that for simple variations more work is required than previously as the eCTD sequence has to be generated. Another practical issue is that the eCTD does not have a mechanism to reject a submission. If a variation is made and rejected then the documents changed in that variation still appear to be current in the eCTD – effectively you cannot undo an eCTD sequence.
The eCTD’s complexity means that problems, no matter how they were caused, can be difficult to understand and resolve.
The XML backbone
Fear of the eCTD remains relatively common – this is largely caused by the emphasis that was placed on XML files at introduction. These are frightening to anyone who just uses a computer and does not work in IT.
However it can be simplified by thinking of it as a catalogue of the submission contents. Basically it is a list of the contents and the status and location of each file. When viewed like this it is not only simple but almost a pleasure to work with, as long as you are using specific eCTD software.
Study tagging files (FDA only)
These are XML files once again that provide information on clinical and non clinical studies that are presented in certain sections of the dossier. Having started this opinion piece by mentioning the ICH this does not present as harmonised an approach as one might wish for. In practical terms it can create problems for companies working with and submitting to authorities in both Europe and the US.
In addition there are several regional differences that have to be handled and make life more difficult for the end user, some of these stem from the old differences in the CTD and some because of the way different authorities choose to interpret the rules.
Michael Reynolds is head of sales and marketing at APCER. For more information visit: www.apcpharma.co.uk
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