The ICH CTD (Common Technical Document is a structure, format and set of requirements for application dossiers for the registration of medicinal therapeutics (pharmaceuticals, biologics and ATMPs). It is widely used across the US, Europe, Japan and many other countries. Many regulatory affairs professionals are familiar with the CTD triangle which provides a simple structure to a very complex application dossier.

We interviewed our regulatory affairs trainer, Sophie Nageotte, to discuss the CTD. She explains what it is in simple terms and provides some insight into the most challenging areas such as module 3 of the CTD (CMC quality module).

 

Could you give us a quick summary of the ICH CTD (Common Technical Document. What is it in Regulatory Affairs?

First of all, the CTD is a registration dossier, so it is to get your marketing authorisation application. As for this registration dossier, it is built around three very critical notions. First, you have the efficacy part, which is demonstrated with the clinical studies. Second, you have the safety of your drug, which is discussed in the non-clinical and clinical studies. Finally, you have the quality part, which is also a very critical one which is about the manufacture and the control of your drug product and drug substance at the manufacturing site.

When you are registering your product, you must demonstrate to the health authority by the data that you’ve collected and presented in this marketing authorisation dossier, the CTD, that the medicine is effective to treat and to prevent the disease concerned. You also need to demonstrate that it is safe for the patient and that the risk/benefit balance is appropriate. Finally, you must demonstrate the quality of your product is adequately controlled and guaranteed. There are several formats around the world that are used to submit this kind of data and the one that is applicable in Europe, but also in the ICH region is the CTD, the common technical document.

 

I know the CTD is made up of modules, could you give us a little bit of detail about each of those?

This is how we usually display or represent the CTD, the CTD triangle (see video below). You can see at the base of the pyramid we have the main modules of the CTD. We have module 3, quality, where you will describe all the operations you perform on your product and on your Active Pharmaceutical Ingredient (API), the manufacture, and the control. Within 4 which are the non-clinical study reports. This is where you will provide all the results on your non-clinical studies, on your safety studies such as toxicology. And then there is module 5, which is where you provide the clinical study reports. These are the studies that you conducted on people demonstrating the efficacy of your product.

Modules 4 and 5 are the full reports, so they are a bit difficult for an evaluator to comprehend when starting to evaluate a dossier. This is why in the CTD you have a second story called module 2, which is about summarising the modules 3, 4, and 5. For module 3 it’s just a basic summary, called the Quality Overall Summary (QOS). However for modules 4 (non-clinical) and module 5 (clinical) data, module 2 is really essential because this is where you have an overview and summary. Within module 2 you will present the results and how you interpreted the results of your study. This is also where you will explain why you chose the study design in relation to your indication etc. In my opinion, module 2 is where an evaluator would begin reading if they wanted to assess the safety and the efficacy of your product.

Finally, you have the peak of the triangle, which is called module 1. It is generally not considered part of the CTD in the sense that it’s where you provide the regional information, and you may have different sections, different format according to the region, and this is also where you provide data such as pharmacovigilance system, product information, and patient information leaflets in each respective language.

 

Is there anything that people should keep in mind when they’re working on the CTD?

Yes, this is actually what I’m talking about in this slide (see video below). The CTD is a harmonisation of format so it means that you will have the structure of the dossier that is the same everywhere. You will find the same chapter names, chapter titles, but the content inside the chapters and the titles can still be different between the three ICH regions, because the CTD gives no information about the content of the dossier. It does not indicate which studies to conduct or which data to collect to get an approval by authorities. For this kind of content, you need to refer to the guidelines or to the regional legislation, and where ICH guidelines exist you should not expect any difference in content, but you still have some specificities. For example, within the European CTD you need to take into account European guidelines so you need to refer to the European pharmacopoeia not the US pharmacopoeia or BP. You need to follow the guidelines on BSE, TSE and if your API is covered by a CP, this is where you can provide the European certificate of suitability or using the active substance master file procedure. So, keep in mind that it’s a harmonisation of format not a harmonisation of content.

 

What would you say is the most challenging module within the CTD to put together or manage?

I would say the quality parts because that is the area that is the most difficult to manage during the life cycle of the product, after approval. People sometimes think that once you get the registration of your product this is the end of regulatory activities. However, for quality (module 3) this is just the beginning. You have a legal requirement to consider all technological progress and to apply state of the art methods to your manufacture, for your analytical control. It is a requirement to always look for production changes to improve manufacturing and control of your product, so it means that you always need to optimise your quality part and to make changes throughout the life cycle. This part of the CTD is a challenging one because it’s always moving and evolving.

 

Watch the interview below:

 

Sophie teaches on the following courses:

Understanding EU Regulatory Affairs

 

To view all our regulatory affairs courses follow the link below.

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