Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Requirements for the presentation of data in Module 3 of the CTD for new drug products ***

Erika Piest (Abschlußjahr: 2002)

Since July 2001 the submission of New Drug Applications in the new CTD format is accepted by authorities of the ICH- regions, either as complete CTD-structures or else as mixed format applications on a case-by-case basis.

The new format will become mandatory from July 2003 onward in Europe and Japan, and although it is not strictly mandatory yet for the USA most companies aiming to submit applications in all three regions will therefore prepare their documentation in the CTD-format.

The basis for the agreement on a harmonized format was formed by the ongoing process of harmonization of requirements as to the content of the included data, issued in form of the harmonized tripartite ICH-Guidelines.

Although already relevant sections of the CTD appear to be harmonized as Guidelines have been agreed upon covering the sections in question there are still a lot of persistent difficulties when trying to compile dossiers acceptable in all three ICH-regions.

It was the aim of this master thesis to cover relevant and important sections of the Module 3 Quality with regard to the placing of the information in the CTD-structure, to discuss and clarify requirements concerning the content of data to be included with regard to currently updated Guidelines and also referencing these Guidelines, and it focuses especially on differences in the regional requirements of the respective authorities, causing the most complications when trying to compile .harmonized. dossiers.

The thesis is built up following the structure of the CTD, however not all parameters and sections are covered in the discussion.

Special emphasis is laid on the topics Impurities, Specifications, Development Pharmaceutics, Bioequivalence, Manufacturing and Stability Testing. The information presented was obtained by comparison of regional guidelines, information collected from work-shops and presentations as well as own experiences and experiences of colleagues.

As an appendix a tabular overview of the Module 3 is presented including Reference Guidelines for EU and US, requirements to contents of presented data, information on presentation of the documentation (single or multiple documents) and special requirements of EU and USA.

The table may be used as Check-List for CMC-documentation and may also be constantly updated as new information becomes available.

As a conclusion it has become clear that we are still far away from being able to submit a harmonized application as each region continues to keep its own pharmacopoeia and harmonization of pharmacopoeial methods is only slowly proceeding. The different structures of especially FDA and European authorities (centralized approach versus decentralized) also influence the requirements to the presented data.

All in all even though it is a very difficult and weary progress, the implementation of the CTD together with the continuous harmonization of guidelines and requirements will in time lead to a simplification of application procedures and to the saving of time and resources, and hereby contribute to a better and quicker availability of innovative drug products on the international market.