PART I – FORMAT AND CONTENT OF APPLICATIONS
Since 1995, ICH has been striving to develop common agreed content and structure for the key data sections (SAFETY, QUALITY, and EFFICACY) of regulatory submissions for drug products, in order to reduce the workload and duplicated data gathering that was required to develop a new drug product for sale and supply in the USA, Europe, and Japan.
Up until the development of the CTD guidelines, all previous ICH guidelines had dealt with the data required for submission, and the way in which the data were presented to the regulatory authorities had not been addressed.
The development of the CTD guidelines was subject to much debate and took a considerable time to negotiate within the working groups. Finally, in June 2000 a working group of ICH published a Multidisciplinary Guidelines on the CTD at Step 2 (draft for comment) and a considerable step forward was made for this aspiration. The final version was published in November 2000, which represented rapid progression from Step 2 to Step 4 compared to the normal time period for promulgation of ICH guidelines.
The ICH CTD guideline has since been subject to a standardization update and was last issued as a series of smaller sub-guidelines on the sections relating to Quality, Safety and Efficacy in September 2022. Guidelines have also been progressed to implement the electronic CTD (eCTD).
The CTD guidelines are divided into the following segments:
- M4 Organization
- M4Q Quality (rapporteur: EU)
- M4S Safety (rapporteur: MHLW)
- M4e Efficacy (rapporteur: FDA)
- eCTD (rapporteur: FDA)
Questions and answer documents relating to each of these five areas have also been published and have been updated as experience has been gained.
Implementation of the CTD Guidelines
It has been possible to submit MAA applications in the EU in the CTD format since July 2001. In practice, however, very few companies used this format until it became mandatory in 2003. During this transitional phase it was possible to submit applications in ‘mixed’ format.
This approach became unacceptable from 1 July 2003, when it became mandatory for all new EU MAA applications to be presented in CTD format. Subsequent communication from the Commission clarified that this date applied only to centralized applications, due to the need for Member States to transpose the CTD requirements given in Directive 2003/63/EC of 25 June 2003 revising Annex 1 to Directive 2001/83/EC into national legislation. Member States were required to do this y 31 October 2003. Therefore, the CTD format became mandatory for national MAA applications and mutual recognition applications from this date.
After the implementation dates, a few circumstances remained where there were exceptions to the requirement to use the CTD format. The time allowances for permitted for these exceptions have now passed. Questions and answer guidance on specific requirements for different types of applications has been produced by the Commission.
The ICH eCTD specification guideline has also been adopted by the CHMP. The Electronic Submission Telematics Implementation Group (TIGes) is working on the implementation of the eCTD. With effect from June 2003, applicants have had the option of submitting an eCTD. The EMEA has indicated that the target date for all national competent authorities to be able to accept eCTD applications only (ie no paper) is January 2010. Already some countries will only accept eCTD applications eg CZ.
