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!

Document Management

For my first ‘real’ post I thought I should approach the subject of document management, and more specifically, document management systems (DMS). The importance of effective document management can’t be overstated in founding and maintaining an efficient, well ordered and audit ready Regulatory department. DMSs such as SCORE or Documentum’ FirstDoc are powerful tools which primarily act as a repository for your company’s documents. But they can do so much more than this. They are designed to: interact with publishing software, enable document workflows, archive documents, provide audit trails…there are too many features to list here!  

So, what do I mean by ‘effective document management’? Well, from my experience working in a number of systems and seeing first hand the nightmares that substandard document management can cause, I would simmer it down to the following question:

                “Although I can find and use this document, could my
                                    successor or theirs…!?”

 At the lowest, most practical level, this really is the most important question to ask – everything else for now can wait. The ability to find and use documents efficiently underpins everything good document management practice is all about. Hours can be wasted searching for important documents in a DMS which, inevitably, were authored by someone no longer at the company and need to be located for an important Variation or possibly even worse, for audit purposes. I know, because I’ve been there.

I’ll address some of the usual pitfalls below…

• Are your colleagues even using the system?

If one thing’s for sure it’s this – if your documents aren’t even in your DMS, nobody will be able to find them within it. That’s a fairly obvious statement of fact. I’ve had people send me documents by email, or even on a portable hard drive in order to avoid having to upload important submission documents into a DMS [I’ll come to this again later]. This means that should anyone else need to cover for me, or replace me and my colleague on a permanent basis, it would be as if the document had never existed. Vanished for all eternity. A DMS can be an expensive tool, it’s probably a good idea to use it.

• How are you naming your documents?

The most important piece of metadata associated with a document is, of course, its name. It’s the most obvious way of differentiating between documents in any folder, but more than that, it should be used to tell you what the document actually is. Document names such as “Document 1” or “Appendix 2” give you very little idea about what you’re going to see when you open it up. A good naming convention could contain some or all of the following:

CTD Number or name: 1.2 Application Form

Product and/or INN name: Wonderdrug (amazingsubstance)
The date it was drafted: 03 June 2011

Simple things like naming conventions can dramatically reduce the time spent searching for documents.

• How are you organising your documents?

One of the most important features of any DMS is its folder structure. A typical DMS will file all of your products into so called ‘Cabinets’ but then the way in which folders are arranged below this level is mostly up to you. It’s a good idea to keep documents from different lines completely separate. Clinical, Nonclinical, CMC…etc. should all have their own areas of the DMS in which to operate. Within these areas it would be a good idea to use a folder hierarchy to keep documents separate. Break the structure down into a low level; for example a folder for each CTD section. Finding a file in a folder containing 5 documents is much easier than finding a file in a folder containing 500. It’s much easier to navigate a well designed folder structure than search through pages and pages of files.

• Are your staff well trained with access to well drafted user guides?

Keeping your staff trained, with access to well drafted training guides is absolutely critical to maintaining high standards of document management. A brand new DMS can be a daunting prospect for document authors, so make sure that they have the confidence to use it, and the ability to find help when they need it. If they don’t have this, they’ll either make mistakes or avoid using the system altogether (and who could blame them?). Remember, the DMS is only as useful as you make it.

 

These are but a few of the issues to consider when thinking about and implementing a DMS; I’ve only addressed a small number. If you need any advice on finding the right DMS for your company, or need help establishing processes please do get in touch with us via our website www.apexregulatory.co.uk and we’d be glad to help you take those all important next steps.

First Post!

Welcome to our blog! Apex Regulatory specialise in all things to do with Regulatory Operations. We'll use this blog from time to time to share updates and helpful snippets which will hopefully shed some light on our world. eCTD creation, document formatting and best practice for document storage - a few of the topics you can expect us to explain and (hopefully) help you with.

We do offer a professional publishing and consultancy service, so if this is something you require please have a look at our website (http://www.apexregulatory.co.uk/) and feel free to get in touch!

Apex