This concept paper addresses the need to update and revise the guidance available on the chemistry of 
the active substance. There are currently two approved guidelines on the subject; CPMP/QWP/130/96, 
Rev1 Note for guidance on the chemistry of new active substances and 3AQ5a, chemistry of the active 
substance. The former guideline was originally adopted in December 2003 and came into operation in 
February 2004 whilst the latter was adopted in October 1987 (which is over 25 years ago). It is felt 
appropriate to combine the two documents into a single guideline to provide better clarity for 
applicants. Additionally, since these documents were approved, there have been many changes in the 
regulatory requirements for example, introduction of the common technical document (CTD), changes 
to references to directives and guidelines and publication and approval of new guidance documents 
(e.g. ICH Q11, guideline on the limits of genotoxic impurities CPMP/SWP/5199/02, and guideline on 
the specification limits for residues of metal catalysts or metal reagents CPMP/SWP/QWP/4446/00 


The guidance documents therefore need to be combined and revised to be in line with all these 
changes and to facilitate the understanding of the applicant regarding the information required. 



Posted on the EMA website on 13 February 2014