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Issue of Interpretation

Uncertainties in the Paediatric Regulation need addressing to achieve improved child health

books_hammer The Paediatric Regulation (1901/2006) has been in force since January 26 2007. Its primary objective is very noble: to improve the health of children across the European Union. However, as with all legislation, the interpretation of the Regulation raises numerous issues, in particular with respect to the rewards and incentives offered. This is not surprising given the commercial effect of the rewards.

The key provisions for new products are outlined in Table 1.

For off-patent products, the Regulation provides for a Paediatric Use Marketing Authorisation (PUMA). PUMA will cover the paediatric indication and formulation. The reward for a PUMA is the same 8+2 data protection regime as provided for in Article 10.1 of Directive 2001/83 – amended.

In each of the above cases, the paediatric studies must be completed in accordance with an agreed paediatric investigation plan (PIP). The PIP plan is submitted early on in the overall product development – no later than the completion of relevant human pharmacokinetic studies in adults – to the Paediatric Committee of the EMEA.

The PIP should detail the proposed studies and timings to support the paediatric use. The studies must cover all age groups and all necessary age-related formulations. It is possible to apply for a waiver for a specific age group or a specific indication (if there are multiple indications) and also for a deferral, postponing the start date of the studies for a specified period of time. Waivers and deferrals must be scientifically justified.

The Paediatric Regulation is very strict in its requirement for compliance with an agreed PIP. If the studies are not compliant then the application for a marketing authorisation (MA) will be invalid. On the other hand, if the results of the paediatric studies are negative, the MA application will still be valid but the summary of product characteristics (SmPC) must contain a statement to that effect. It is hoped that this will reduce the number of off-label prescriptions for children. This is in line with one of the objectives of the Regulation – to ensure that the paediatric medicines are of high quality and have been appropriately authorised for paediatric use.

SPC extension
One of the most controversial issues in the new paediatric regime is the reward of 6-month supplementary protection certificate (SPC) extension. In some cases, depending on the member state, there has been a grant of either a negative or a zero-term SPC, from which the 6-month extension is calculated. The effect of this has been to give protection under an SPC where none existed before.

The approach taken by the UK Intellectual Property Office (IPO) is demonstrated by its decision in a case involving Merck's Sitagliptin (BL O/108/08; April 14 2008). Merck applied for an SPC under the Paediatric Regulation and obtained its first MA in the EU for Sitagliptin on March 21 2007. The date of the application for the patent was July 5 2002. Under Article 13(1) and (2) of the SPC Regulation (1768/92), because the difference between the date of first MA and the date of application of the patent was 4 years and 8.5 months, no SPC could be granted. If an SPC were granted in such a situation, it would have a negative duration of three and a half months and, as such, the SPC would expire before the basic patent expires.

Nevertheless, the IPO took the view that an SPC would be granted where it would impact on the monopoly and granted Merck a negative duration SPC, which it then extended by 6 months under the Paediatric Regulation. This stretched Merck's monopoly to September 20 2022 adding 2.5 months protection past the normal expiry of the patent, which would have been July 5, 2022.

Merck unsuccessfully appealed this decision with a view to persuading the IPO to grant a zero term SPC. Had Merck succeeded, their monopoly would have been extended by 6 months from the date of the patent expiry (January 5 2023). The IPO refused to round up a negative duration SPC to a zero term SPC.

The EC does not agree with the IPO's approach. In any event, different member states have approached the SPC extension reward differently, leading to a lack of harmonisation of SPC protection across Europe.

With respect to Merck's product Sitagliptin, for example:
• Netherlands – granted a negative term SPC
• Portugal, Slovenia and Germany - refused Merck's SPC application based on a zero or negative duration
• Greece – granted a zero term SPC, thus extending Merck's monopoly in Greece until January 5 2023.

This uncertainty needs to be resolved promptly as it concerns both innovator and generics companies alike. It may be that the best resolution is to modify the Regulation in order to clarify whether an SPC extension should be granted in the absence of a positive term SPC. It will be interesting to see how this issue unfolds over the next few years and whether an acceptable compromise can be reached between the stakeholders.

An interesting point is that the SPC Regulation itself is silent on the issue of negative or zero term SPCs. In contrast Article 36(4) of the Paediatric Regulation states:

"Paragraphs 1,2 and 3 [providing for the 6-month SPC extension] shall apply to products that are protected by a supplementary protection certificate under Regulation (EEC) No 1768/92, or a patent which qualifies for the granting of a supplementary protection certificate..."

What does 'qualifies' mean here? Does it mean a product that qualifies for an SPC regardless of whether it is a negative or zero term SPC or does it mean a product that qualifies for a positive term SPC only?

Until this issue is resolved, the incentive to conduct paediatric studies remains uncertain. If there is no reward, there will be no activity, and this would be contrary to the objectives of the Paediatric Regulation.

Table 1: New Products

Unauthorised (Article 7)
Authorised (Article 8)
Applies from
July 26 2008
January 26 2009
Submit results of studies and information required in the previously agreed PIP, with the application for MA
- unless a deferral or a waiver has been granted
Submit results of studies and information required in the previously agreed PIP, with the application for MA for new indications, new formulation or new routes of administration
- unless a deferral or a waiver has been granted
Reward (Article 36)
6-month extension of SPC
Conditions (Article 36)
• statement in the MA stating that the PIP has been complied with
• product has been authorised in all member states
• results of the studies under PIP are reflected in the SmPC – and if appropriate in the package leafle

MA delay
In a recent case (BL O/035/09; dated February 6 2009), Merck filed an application for an SPC extension for its caspofungin product (Cancidas) under the Paediatric Regulation. Merck had yet to receive its updated MA containing the compliance statement, as required by the SPC Regulation – Article 8(1)(d)(i). It submitted the positive opinion from the Paediatric Committee confirming that Merck had complied with the agreed PIP as evidence to support the grant of the SPC extension. Both the Examiner and the Hearing Officer took the view that a positive opinion from the Paediatric Committee was insufficient, and that an updated MA containing a compliance statement was necessary for the SPC extension. This was regardless of the fact that the delay by the competent authority in issuing the updated MA was beyond Merck's control. The company was given a period of time in which to rectify this irregularity.

Merck had concerns about the impact of the delay on its need make an application for an SPC extension prior to expiry of its original granted SPC as required by the SPC Regulation – Article 7(4) & (5) of the SPC Regulation.

In the first five years after the Paediatric Regulation entering into force, the application must be lodged 6 months before the SPC expires and, thereafter, it must be lodged 2 years before the SPC expires. The Hearing Officer took the view that the SPC reward is not based on just completing an agreed PIP, but it is also based on making sure that information regarding the paediatric use is made available by including this information in the MA and the SmPC.

The issue of delay by a competent authority in updating the MA should be addressed. It would be harsh to deny an SPC extension to an applicant that complies with the agreed PIP, but through no fault of its own, is unable to provide the updated MA within the time limit for applying for the SPC extension. This could undermine the objectives the Regulation.

In order to ensure that the paediatric regime, as prescribed by the Paediatric Regulation is a well oiled machine, all the issues raised need to be addressed promptly. Only by ensuring this can the objectives of the Regulation be achieved.

The Author
Dipti Dashore is senior associate at Taylor Wessing LLP
To comment on this article, email

11th June 2009


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