EU Paediatric Regulation - 1901/2006 & 1902/2006

In November 2001, the European Commission organised a “brainstorming” meeting with representatives of Member States and research-based industry. This was followed by the release of a public consultation paper in February 2002 on “Better Medicines for Children – proposed regulatory actions in paediatric medicinal products”. This paper represented one of the first steps of the Commission to address the problem. A reflection paper followed incorporating the comments received in June 2002. Over sixty sets of comments were received from interested parties and these were taken into account when drafting the proposal for the Paediatric Regulation.
In March 2004, the European Commission consulted on a draft Regulation on medicinal products for paediatric use. On 29 September 2004, the EU Commission released the first proposal for a Regulation on Medicinal Products for Paediatric Use together with an explanatory memorandum, the Extended Impact Assessment and a “questions and answers” document. Following the plenary vote of the European Parliament on the Commission’s proposal on 7 September 2005, the Commission has responded to the parliamentary amendments in the form of a modified proposal. Finally it was adopted by the European Parliament and the Council on 12 December 2006.
The Council of Health Ministers reached political agreement on 9 December 2006. The proposal for a Regulation on Medicinal Products for Paediatric Use went into a second reading in the European Parliament.
On 27 December 2006 the Paediatric Regulation – Regulation (EC) No 1901/2006 as well as the amending Regulation (Regulation (EC) No 1902/2006) – were published in the Official Journal of the European Union. Both entered into force on 26 January 2007.

Features of Paediatric Regulation:

• Establishment of Paediatric Committee (PDCO) with in the EMEA
• 5 paediatric sub-populations

• Paediatric Investigational Plan (PIP) requirement for; new MAAs, new indications,
• Approved products covered by IP
• Products not covered by patents
• Timing of PIPs
• Rewards and Incentives for the industry
• Provision for Waivers and Deferrals

PIP:

Paediatric Investigation Plan (PIP) = A research and development programme aimed at ensuring that the necessary data are generated determining the conditions in which a medicinal product may be authorised to treat the paediatric population.

Sponsors must possess a complaint PIP when applying for marketing approval of unauthorised drugs, or when applying for approval of new indications, pharmaceutical forms, or routes of administration for currently authorised drugs. The default situation is that a Marketing Authorisation Application should now include findings from the paediatric population.

EU PIP should include

• Measures to assess quality, safety and efficacy
• Timing of investigations 
• 5 subpopulations of children
• Formulation development
• For approved products; literature evidence and cross-referral

The requirement for new medicines:

• Marketing Authorisation Application (MAA) considered valid only if it includes one of the following:

• Results of all studies performed and details of all information collected in compliance with an agreed PIP

• A product‐specific waiver or a class waiver

• A deferral

• The PIP also to be included in the application
• The documents submitted to cover all subsets of the paediatric population

Medicinal Products subject to the requirement:

• Authorised medicinal products protected either by a Supplementary protection certificate (SPC) or a patent which qualifies for the granting of the SPC
• New medicinal products (not authorised)
• Medicinal products already authorised

• Applications for authorisation of new indications, new pharmaceutical forms, and new routes of administration

• Requirement covers both the existing and the new indications, pharmaceutical forms and routes of administration

Requirement excludes Marketing Authorisation Application (MAA) for:

• Generics or similar biological medicinal products
• Medicinal products authorised through the well‐established medicinal use procedure
• Homeopathic medicinal products and traditional herbal medicinal products authorised through the simplified registration procedures

EU PIP Waivers:

• If products or class is likely to be in-effective or unsafe in children
• Disease or condition only occurs in adults
• Product does not present a significant benefit over existing products
• Can be issued for one or more paediatric populations or for one or more indications

EU PIP Deferrals:

• When it is appropriate to conduct studies in adults before initiating studies in children because of safety concerns
• When studies in children may take longer than in adults
• May be requested at the same time as the PIP is submitted
• May be requested for specific paediatric populations on technical grounds – formulation development

Incentives/rewards for Industry:

• Paediatric scientific advice: free of charge
• PDCO assessments: free of charge
• Registered products with an SPC: 6 month extension of SPC (Supplementary Protection Certificate)
• Orphan products : Additional 2 years market exclusivity from 10 -12 years
• New type of marketing authorisation, the Paediatric Use Marketing Authorisation (PUMA), which allows ten‐years of data protection for innovation (new studies) on off‐patent products

Reference:

1. EMA: Paediatric Medicines

2. EMA: Report to the European Commission On companies and products that have benefited from any of the rewards and incentives in the Paediatric Regulation and on the companies that have failed to comply with any of the obligations in this Regulation, covering the year 2011