NAS: new active substance
A new active substance (NAS) is a substance not previously authorised in an EU medicine, whose first product starts a new protection period.
The definition comes from Annex I to Chapter 1 of Volume 2A of the Notice to Applicants, which the CHMP applies through its reflection paper on the chemical structure and properties criteria to be considered for the evaluation of new active substance status. A chemical, biological or radiopharmaceutical substance is new if it has not previously been authorised as a medicinal product in the Union. A salt, ester, isomer, mixture of isomers, complex or derivative of an authorised substance can also qualify, but only where it differs significantly in properties with regard to safety or efficacy, which the applicant has to demonstrate with data. For a biological substance, a difference in molecular structure, nature of the source material or manufacturing process can support the claim.
NAS status matters because of the global marketing authorisation. A product containing a new active substance begins a new global marketing authorisation and therefore a new period of data exclusivity and market protection, whereas a new salt of a known substance without a significant difference belongs to the existing authorisation and inherits its protection dates. In the centralised procedure the CHMP states in its opinion whether the substance is new, and the EPAR records the decision. The applicant claims the status in the application form and supports it in the quality and clinical overviews.
The question also affects eligibility for the centralised procedure, because a new active substance for one of the therapeutic areas in the Annex to Regulation (EC) No 726/2004 must use the centralised route, and products containing any new active substance may use it at the applicant's choice.
What goes wrong: applicants who assume a new salt or a new enantiomer automatically restarts protection, then discover during assessment that the authority treats it as the same substance; claims supported only by physicochemical differences without evidence that they change safety or efficacy; and generic companies that rely on the exclusivity of the first authorisation when the originator holds a later NAS decision for a related substance. The status is determined once, at the first authorisation, so a decision taken in a national procedure can shape centralised assessments years later.
Under the new pharma package (not yet in force), a qualifying new active substance that meets conditions on comparator trials and early EU filing is one of the routes to an extra year of market protection; see exclusivity changes.
Used in
Before fixing generic entry dates, check whether a substance's first authorisation started a new protection period in the loss-of-exclusivity workflow.
Related terms
- GMA: global marketing authorisationThe global marketing authorisation (GMA) groups an initial authorisation with its later strengths, forms and extensions, so exclusivity runs once for all.
- Data exclusivity: regulatory data protectionData exclusivity is the eight years after a reference product's first EU authorisation in which generics cannot rely on its preclinical and clinical data.
- Centralised procedure: single EU marketing authorisation via EMAThe centralised procedure grants one marketing authorisation valid across the EU and EEA after a single EMA assessment and a Commission decision.
- Reference product: reference medicinal productThe reference medicinal product is the product, authorised in the EU on a full dossier, whose data a generic or hybrid application relies on.
- EPAR: European public assessment reportA European public assessment report (EPAR) is EMA's published account of how a centrally authorised medicine was assessed and why it was approved.
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