Pharmaceuticals for paediatric use

Mauro Turrini

Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use (hereinafter, “the Paediatric Regulation”) is intended to tackle the problems resulting from the absence of suitably adapted medicinal products for the paediatric population (including inadequate dosage information, non-availability to the paediatric population of therapeutic advances, suitable formulations and routes of administration as well as use of magistral or officinal formulations to treat the paediatric population).

In particular, the Paediatric Regulation introduces the requirement to include information about paediatric studies in the Marketing Authorisation (MA) application. This requirement, already mandatory for new medicinal products as from 26^th of July 2008, will start soon to be compulsory also for previously authorised medicinal products covered by a supplementary protection certificate (SPC) or a patent, which qualifies for the granting of the SPC (as from 26 January 2009).

According to Articles 7 and 8 of the Paediatric Regulation, all applications for a new MA, as well as all applications for variation and/or line extension of medicinal products covered by a SPC or a patent (which qualifies for the granting of the SPC), submitted, respectively, after the 26 July 2008 and 26 January 2009, will be regarded as valid only if they include, in addition to the particulars and documents already required by previous pharmaceutical legislation, the results of all studies performed and details of all information collected in compliance with an agreed Paediatric Investigation Plan (PIP). This obligation does not apply in cases where the Applicant can provide a decision issued by the EMEA granting a: i) product-specific waiver; ii) class waiver or; iii) deferral¹.

To compensate the new requirement above, Title V of the Paediatric Regulation provides for a number of rewards for the Applicants.

In this regard, Article 36 of the Paediatric Regulation provides that, for applications under Articles 7 or 8, which include the results of all studies conducted in compliance with an agreed PIP, the holder of the patent or SPC shall be entitled to a six-month extension of the period referred to in Articles 13(1) and 13(2) of Regulation (EEC) No 1768/92. Such a reward also applies in those cases where completion of the agreed PIP failed to lead to the authorisation of a paediatric indication, but “the results of the studies conducted are reflected in the summary of product characteristics and, if appropriate, in the package leaflet of the medicinal product concerned”.

This 6 month extension reward however will not apply in cases where:

• the centralized, mutual recognition, decentralized (and purely national) procedures have been used and the product has not been authorised in all Member States;
• the product, although protected by an SPC or under a patent which qualifies for the granting of the SPC, is designated as orphan medicinal product pursuant to Regulation (EC) No 141/2000;
• the product, following an application under Article 8 of the Paediatric Regulation, obtained a one-year extension of the period of marketing protection for the new paediatric indication².

Moreover, additional rewards are provided in cases of orphan medicinal products as well as Paediatric Use Marketing Authorisations (PUMA). In particular:

• In relation to orphan medicinal products, Article 37 of the Paediatric Regulation provides that in case of successful applications including the results of all studies conducted in compliance with an agreed PIP, the ten-year period of data exclusivity (i.e. see Article 8(1) of Regulation (EC) No 141/2000) shall be extended to twelve years;
• In relation to PUMAs, Article 38 of the Paediatric Regulation provides that in cases where a PUMA is granted (irrespective of the registration procedure followed), the data and marketing protection exclusivity periods provided by EU legislation shall apply³.

Finally, we refer to guidance recently provided by the EMEA which, in order to ensure compliance with the new requirement provided by the legislation, has published on its website a procedural advice document describing the procedures for the operation of: i) validation of MA applications and extension/variation applications; and ii) the compliance check with an agreed PIP.

For further information, please refer to http://www.emea.europa.eu/htms/human/paediatrics/compliance.htm

(1) As to the rationale for these exclusions, please see Recital 4 of the Regulation, according to which the objective pursued by the Regulation should be achieves without subjecting the paediatric population to unnecessary clinical trials(i.e. waivers) and without delaying the authorisasion of medicinal products for other age population (deferral).

(2) See article 14 (11) of Regulation (EC) N° 726/2004 or Article 10 (1), fourth subparagraph, of Directive 2001/83/EC ("significant clinical benefit in comparision with exsisting therapies")

(3) See Article 14(11) of Regulation (EC) N° 726/2004 as well as article 10(1) of Directive 2001/83/EC