Active substance

An active substance is any substance or mixture of substances intended to be used in the manufacture of a medicinal product and which, in that product, becomes the component exerting a pharmacological, immunological or metabolic action with a view to restoring, correcting or modifying physiological functions or making a medical diagnosis. Its definition was introduced into Directive 2001/83/EC by Directive 2011/62/EU on falsified medicines. It distinguishes the active substance from the excipient and underpins both the manufacturing regime and the identification of the protected product.

Manufacture and import of active substances

A manufacturer of medicinal products may only use active substances manufactured in accordance with the good manufacturing practice applicable to such substances. Manufacturers, importers and distributors of active substances established in the Union must register with the competent authority of their Member State, in France the ANSM. Since Directive 2011/62/EU, an active substance imported from a third country must in principle be accompanied by a written confirmation from the authority of that country attesting that its manufacturing standards are at least equivalent to those of the Union, except for countries recognised as offering that level of equivalence. The marketing authorisation holder remains responsible for the quality of the substance it uses and must audit its suppliers.

Identity of the active substance and regulatory protection

For the purposes of the generics regime, the different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance are considered to be the same active substance, unless they differ significantly in properties with regard to safety or efficacy. An applicant relying on a difference must demonstrate it. The question determines whether new active substance status is granted and, consequently, whether a new period of regulatory data protection begins. It also sheds light on lifecycle strategies based on a new salt or an isolated enantiomer, often discussed under the heading of evergreening.

The active substance and the supplementary protection certificate

Regulation (EC) No 469/2009 protects the active ingredient, understood as the active substance or combination of active substances of a medicinal product. The Court of Justice of the European Union holds that a substance with no therapeutic effect of its own, such as an adjuvant, is not an active ingredient and cannot, alone or in combination with an active ingredient, found a supplementary protection certificate. The notion of active substance, regulatory in origin, thus becomes a decisive criterion for the supplementary protection of the patent.

Key points

The active substance is the component of the medicinal product that produces its effect, as opposed to the excipients. Its identity determines the generics regime, new active substance status and the subject matter of the supplementary protection certificate. Before building a strategy on a new salt, isomer or combination, it should be checked whether the authority will treat it as a distinct substance and whether the patent relied on actually covers the active ingredient of the authorised medicinal product.

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This glossary entry is general in scope and does not constitute legal advice.

Dhenne Avocats acts in pharmaceutical patent disputes and on the medicines regulatory questions that accompany them, from the marketing authorisation to the supplementary protection certificate.

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