Regulatory Focus™ > News Articles > What's a 'New' Drug in the EU? EMA Explains

What's a 'New' Drug in the EU? EMA Explains

Posted 27 April 2015 | By Michael Mezher 

What's a 'New' Drug in the EU? EMA Explains

When is a chemical entity considered a new active substance (NAS)? The European Medicines Agency (EMA) answers that question and provides clarification on the type of information required to demonstrate that a substance qualifies for NAS status in a draft reflection paper published Friday.


Obtaining NAS status is important for drug makers, as products granted NAS status benefit from a full 10 years of protection against generic competition.

However, to ensure companies do not take advantage of the incentives offered by EMA, companies benefiting from these incentives must either show that:

  • their product contains a "chemical active substance that is not previously authorized" and is
    "not related to any other authorised substances"
  • demonstrate that the entity "differs significantly" in safety or efficacy.

Products that do not qualify for NAS status are considered to fall under the existing period of exclusivity of the previously authorized product under Article 10 of Directive 2001/83/EC, which states:

"The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy. In such cases, additional information providing proof of the safety and/or efficacy of the various salts, esters, or derivatives of an authorised active substance must be supplied by the applicant."

EMA Guidance

The reflection paper published by EMA is intended to provide guidance to applicants on the elements to consider when qualifying an active substance as a NAS.

The document provides considerations for isomers, mixtures of isomers, complexes, derivatives, esters and ethers, salts and solid state forms of chemical entities, and provides examples of when a chemical structure could generally be considered for NAS status.

For instance, in the case of complexes, EMA gives two examples to demonstrate whether a chemical structure would qualify for NAS status.

In the first example, a complex that is "intended to release an active substance that is entrapped by the complex" by breaking down in the body would not be considered for NAS status unless significant differences in safety and/or efficacy are established.

However, complexes that are "intended to remain intact in the body ... because they do not dissociate[,] the therapeutic moieties are presumed to be different and could be considered as NAS." In the second case, EMA says applicants may need to provide evidence that the complex does not dissociate.

Documentation Required

Companies looking to claim NAS status for an active substance are advised to provide documentation demonstrating whether the substance is related to a previously authorized substance by including a "comparison of the structural substance/features … for any structurally related already authorised substances."

Substances that are structurally related to already authorized medicine must provide documentation demonstrating that the new substance is significantly different in terms of safety and/or efficacy. Companies are also encouraged to request scientific advice from EMA to determine the type of evidence necessary to substantiate such claims.


EMA Reflection Paper

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