29/30 September 2021
A chemical structure with a therapeutic moiety for which no authorisation dossier has been submitted so far and which is - from a chemical structure point of view - not related to any other authorised substances is per se a "NAS" (New Active Substance). But what about a physiologically active molecule present for example in different salts or esters? In which cases do the different derivatives of an effective substance have the NAS status?
The EMA provides clarification to these questions in a new Reflection Paper which was published on 19 January this year. The document entitled "Reflection paper on the chemical structure and properties criteria to be considered for the evaluation of new active substance (NAS) status of chemical substances" describes the criteria according to which isomers, mixtures of isomers, complexes, derivatives, esters, ethers, salts and other solid forms of physiologically active molecules can be classified as "NAS ". If an applicant claims the NAS status of a substance to the regulatory authority in the centralised (CP) or decentralised procedure (MRP/DCP), the authority will first check whether the claim is justified. Afterwards - in case of a positive decision - the usual review of the application dossier will be performed.
The applicant can refer to the criteria described in this Reflection Paper to substantiate his/ her claim of a NAS status. In general, the evidence has to be brought for the derivative in question that it differs significantly in properties with regard to efficacy and /or safety from the already approved active substance.
The scope of this Reflection Papers covers neither biological and biotechnological active substances nor active substances to be included in radiopharmaceuticals.