Preparing Documents for Submission

The preparation of documents for submission in CTD format can be a time consuming and arduous task. Your document authors should be well aware of the restrictions and requirements for such documents, and take care to ensure that their output remains compliant.

Some of the considerations to bear in mind are:

1. Is the document formatted correctly?

Best practice guidelines exist which regulate such things as the size and type of font used, the size of page margins, the use of headers and footers, page sizes, etc… When your documents are reviewed, are these guidelines taken into consideration as well as the document content itself?

2. Does the document follow the correct granularity guidelines?

Whilst there is flexibility regarding the granularity of documents in some CTD sections, in others there is not. Documents submitted in eCTD format cannot simply be submitted wherever and however you like – it may fail technical validation if you’re not careful. Even where there is flexibility, you should consider which is the best level of granularity to submit documents, bearing in mind eCTD lifecycle considerations. With existing eCTD applications this will largely depend upon how documents have been submitted in previous sequences. Replacing a high-level CTD document with a low level document will mean that some sections are lost from the current view.

3. Where should the document be linked?

Much of the time, the document author will have a better idea of where a document should contain a link to another document or section in order to facilitate its review. Where the document referenced was submitted in a previous lifecycle, would it be obvious to your eCTD compiler that this is the case? Consider changing the colour of text to blue in the source document to make the lives of your eCTD publishers a little easier.

There are many more considerations than those outlined above; however some of these provide common examples of how the use of document templates can greatly reduce the time it takes to create and publish documents for use in submissions. How can templates help you?

• All formatting (font size, style, margins, heading styles etc…) can be preloaded into the template. This would remove the need to format individual documents before, during or possibly even after authoring; greatly reducing the time it takes to create them, ensuring that they’re completely compliant whilst maintaining a professional and standardised style across all CTD sections and eCTD lifecyles.

• Automatic bookmarking using heading styles. It is possible to set up your templates in such a way that when converted to PDF, multilevel bookmarks are automatically generated. This can save hours when publishing submissions.

• Consistent and compliant granularity. If CTD templates are used, there will be no worrying about inconsistency of granularity when documents are authored.

If you’d like to know more about the preparation of CTD templates, and how they can benefit your authors, Apex would be happy to help. After consultation, Apex will even be able to create them for you. Please get in touch with us via our website: www.apexregulatory.co.uk. We’re also on Twitter, and LinkedIn!

How to file eCTD in MRP/DCP - One decision already made?

When filing a new eCTD using the Mutual Recognition or Decentralised Procedure, you need to be aware of the following question:

“When an application refers to multiple strengths or dosage forms, should I create one eCTD covering ALL strengths and dosage forms, or should I create one eCTD for EACH?”

This is no concern under the centralised procedure, where one eCTD will be submitted to cover all dosage forms and strengths: i.e. there’s no room for discretion.The advantages and disadvantages of both approaches are discussed in the TIGes guidance, but can be summarised as follows:

One eCTD for all forms/strengths:

Advantages
-                Common documentation, including Clinical, Nonclinical and some Quality data is provided only once.
-                Only one eCTD needs to be published (less publishing required, easier to control…etc.).

Disadvantages
-          The overall application will contain a greater number of sequences than if the eCTD is split (i.e. one sequence added per change to each and any of the forms/strengths).
-          Where some countries apply only for certain strengths, it can become confusing when tracking which countries are involved in any individual lifecycle.

One eCTD per form/strength

Advantages
-          Fewer sequences per eCTD application.
-          No confusion about which countries are involved in any individual application update.

Disadvantages
-          Common data is duplicated across different applications
-          More overall eCTD lifecycles to create and maintain (more publishing time required)

 However, following a recent publication by the Slovakian NCA (kindly Tweeted by Exalon), it’s clear that the discretionary nature of the above methods of application isn’t quite as clear cut as it may seem:

              “for each registration number in Slovakia (for each strength, each pharmaceutical form), or procedural number (MRP, DCP) to which the application relates [it] is necessary to create a separate directory…”    [emphasis my own]

Clearly there is a need either:

-          For the approved TIGes guidance to be updated, or
-          For all NCAs to understand that either filing approach is allowable.

If you’d like to know more about eCTD, please feel free to contact us via our website: www.apexregulatory.co.uk; our number’s at the top of the page, or use our Contact Form.
Also, find us on Twitter or LinkedIn!