1. Paediatric Worksharing CMDh participation Work-sharing in Art 45 and 46 procedures Experiences in Art 29 procedures Presidency meeting 29 September 2011 Truus Janse-de Hoog Matthias Sennwitz (statistics)

2. Content of presentation Overview of work-sharing procedure Progress so far Art 29 procedures Conclusions

3. Importance Work-sharing procedure Most of the medicinal products on the market are used off label in children Local recommendations for paediatric use-not always evidence based Work-sharing procedures in EU give overall assessment of available paediatric data in dossiers of these medicinal products Many products out of data exclusivity, no longer under patent- MAHs not interested to start new studies

4. Paediatric Regulation Art 45 and 46- a reminder Paediatric studies already completed, by the date of entry into force for authorised products to be submitted by the MA holder to the competent authority(CA) by 26 January 2008 (Art 45(1)) Any other MA holder-sponsored studies to be submitted by the CA within six months of completion (Art 46) - whether or not part of an agreed paediatric investigation plan (PIP) - whether or not MA holder intends to apply for a paediatric indication CAs may update the SmPC and PIL and may vary the MA CAs shall exchange information regarding the studies submitted and, as apropiate, their implications for any MAs concerned. EMA to coordinate the exchange of information

5. What had to be done? Joint CMDh/EMA subgroup established-agreed template for submission of list of studies, actual studies submitted at start of Work-sharing procedure EMA responsibility to collate information from all MA holders in all MS - Approximately 18.000 line listings - around 1000 substances (chemical only) - average of 5 documents per active but some duplication

6. What have we achieved so far? Art 45 So far 12 waves have started since Q4 2008 205 active substances, most MS involved in assessment Number of PARs published: 67 Recommendations on SmPC’s published in Excel sheet; these include also the former HMA Work-sharing procedure Art 46 Assessed on an ongoing basis 208 studies up to September 2011 Number of PARs published: 25

7. Status Art. 45 procedures (Status: August 2011)

8. CMDh priorities in assessment Oncology Psychiatry Pulmonary conditions Antibiotics Neonatology (where possible) The list of off-patented products (EMEA/226983/2008) Furthermore: Requests for priority received from MS Availability of assessors at national level All MSs are invited to forward lists of products for priority assessment

9. Article 45 – waves 1- 11 Updated on 11 April 2011

10. Article 46* Worksharing per Number of Studies until end of March 2011 * Art. 46 Rapporteurs appointed by the CMDh Secretariat according to the BPG Art. 46 Updated on 11 April 2011

11. Impact of Work-sharing procedures Art45 67 assessment reports published - ‘new’ paediatric indications: 7 - revision for clarity or consistency: 32 - Safety information added: 3 - study information added: 8 - no change: 17 However - if assessment report is not published, no information available in the public domain on the outcome of the assessment - MAH’s are not very interested to update their SmPCs and PLs - implementation can be complicated because of disharmonised national product information and difference national practice

12. Practical experiences Identified issues by assessors Incomplete dossiers, old study reports of variable quality Missing literature Lack of information or analysis about known extensive off-label use No complete overview on European situation No recommendations for SmPC Lack of analysis/literature by MAH

13. Art 29 of Regulation (EC)1901/2006 Applicable to non-centrally authorised products Scientific assessment done by the CHMP Short timetable (60 days) Assessment limited to the specific aspects of the SmPC to be varied MSs have to issue compliance statement at national level afterwards

14. CHMP opinions adopted for Art 29 procedures Cozaar Arimidex Diovan Sortis

15. First experiences Scope of assessment and EC decision is limited RMS needs to check all existing SmPCs and assess whether there was full compliance with the PIP MSs not always aware on the need to issue compliance statement at national level within 30 days to allow MAHs to get the reward Confusion about responsibility for Risk Management Plan National Patent offices confused about national statements and conclusions assessment reports

16. Proposals for improvement CMDh Guidance document “Recommendations for implementation of Commission decisions following Art 29 of Paed. Regulation’ updated Several meetings with Patent offices to explain procedure Use of standard statement by NCAs very much appreciated by patent offices In conclusion of CHMP assessment report reference to full/partial compliance PIP No Risk management plan (RMP) approved by CHMP, recommendations on how to adopt RMP should be implemented at national level

17. Conclusions Assessment of paediatric data of products already on the market is in the interest of Public Health (relevant for Art 45, 46 and Art 29 procedures) Outcome of assessment is published on CMDh website- available for Health professionals and patients National agencies should inform health professionals about the procedures and outcome of assessments Work sharing procedures Art 45 and 46 well established- but long proces EU assessment is focussed on relevant information for prescribers Implementation of outcome of assessment needs more attention