Can different salts of the same active ingredient be essentially similar?

Background
SmithKline Beecham ("SKB") challenged the approval of two generic versions of its antidepressant Seroxat. Seroxat, manufactured by SKB consists of paroxetine hydrochloride hemihydrate. Two generic manufacturers, Synthon and Genthon (collectively referred to as "S&G"), obtained approval under the abridged procedure from the Danish medicines agency of their generic version of Seroxat, which contain another paroxetine salt, known as paroxetine mesylate.

Under the abridged procedure a generic manufacturer may apply for marketing authorisation in respect of its generic version of the original product, relying on the regulatory data supplied by the originator company in respect of the original product. For the generic manufacturer to use the abridged procedure the protection period for the regulatory data in respect of the original product must have expired, and the generic manufacturer must demonstrate that the generic product is "essentially similar" to the original product.

S&G made an abridged application relying partly on data relating to the safety and efficacy of SKB's Seroxat. SKB challenged this abridged application on two grounds. The first challenge was that paroxetine hydrochloride hemihydrate could not be viewed as "essentially similar" to paroxetine mesylate. Secondly, SKB argued that S&G's product could not be essentially similar to SKB's product because S&G had had to submit additional pharmacological and toxicological data in respect of their abridged application to demonstrate essential similarity.

SKB commenced proceedings in the Danish court, which in turn referred two questions to the ECJ. The questions revolved around whether a product could be approved using the abridged procedure when it comprised a different salt from the originator product and whether the abridged procedure could be used where the generic applicant submitted extra data to show that the generic product was essentially similar to the original product.

The AG's opinion

The AG considered that two medicinal products, which share the same therapeutic moiety, but differ as to the identity of the salt associated with that therapeutic moiety can be regarded as essentially similar for the purposes of abridged authorisations for medicinal products. In response to the question regarding the submission of extra data the AG added that there was no general rule against submitted additional data in the abridged procedure, and that extra data might sometimes be needed to show essential similarity.

The opinion of the AG is persuasive but not binding on the ECJ, however given the provisions of the new Directive it is likely to be followed by the Court.

Changes to European legislation

Existing community legislation relating to abridged authorisations has already been amended and follows the same principles of the AG's opinion. Both Directive 2003/63/EC (which is already in force) and the proposed Directive 2004/27/EC (which is to be brought into force no later than 30th October 2005) have provisions that different salt of the same active ingredient can be essentially similar and allow a second applicant to rely on regulatory data of the first applicant in relation to a different salt form of the active ingredient, once any legal protection relating to that data has expired.

To view the Directive 2003/63/EC please click here.

To view the proposed Directive 2004/27/EC please click here.

For further information please contact Zelda Pickup on +44 (0)207 367 2043, [email protected], or Andrew Whitworth on +44 (0)207 367 2043 or at [email protected]