1. REGULATION (EC) No 1901/2006 of 12 December 2006 on medicinal products for paediatric use Article 45 and more… Christer Backman CMD(h) Sweden

2. Paediatric regulation A number of tasks require effective liaison between EMEA, Commission and Member States Uncertainties in estimated workload: close monitoring needed Diversity in tasks including new tasks for EMEA (e.g network) Impact on resources for both EMEA and Member States Impact on budget

3. DEADLINETASKSWHOCMD(h) involvement 26 jan 07 Define submissions of existing studies NCA Yes 5 Sept 07 Comments on network strategy MS Sept 07 – Jan 08 Adoption of Management Board MB Members 26 Oct 07 Determine penalties for infringing the regulation MS End of 07 Identify all products authorised at national level with a paediatric indication (symbol) NCA Yes End of 07 Start survey of all paediatric uses (to be completed by end of 08) MS Yes

4. DEADLINETASKSWHOCMD(h) involvement 26 jan 08 Report to Commission on inventory of national incentives MS 26 jan 08 Report to EMEA on companies benefiting from or breaching the legislation NCA/MS Yes 26 jan 08 Complete collection of existing studies in children for assessment NCA Yes Jan 08 Check of compliance RMS Yes (procedure) 26 July 08 validation NCA Yes Jan 10 Symbol on all products with paediatric indication

5. Article 45 By 26 January 2008, any paediatric studies already completed, by the date of entry into force, in respect of products authorised in the Community shall be submitted by the marketing authorisation holder for assessment to the competent authority. The competent authority may update the summary of product characteristics and package leaflet, and may vary the marketing authorisation accordingly. Competent authorities shall exchange information regarding the studies submitted and, as appropriate, their implications for any marketing authorisations concerned. The Agency shall coordinate the exchange of information.

6. Art.45 Existing studies MAH responsibility to send list of studies deadline 26 January 2008 deadline 26 April 2008 NCA shall assess amendments to SPC or MA exchange information EMEA coordinate

7. Art. 45 How are NCAs and EMEA collecting data on MPs with paediatric use?

8. CMD(h) web http://hma.eu/cmdh.html Paediatric DataAssessment Guidance paper Template line listing sample line listing Annex I – MAH declaration Annex II – products already authorised for paediatric use Q and A

12. Annex I – MAH declaration Subject: Declaration concerning paediatric studies already submitted to the NCAs, (Art. 45) We [MAH] confirm that all products authorised in [EU-Member- State/Community] are listed in the table submitted to the NCA, independent of whether paediatric use is granted or not and/or paediatric studies are available, already submitted or have yet to be submitted. We further confirm to the best of our knowledge, that all paediatric studies available have been submitted already. These products are indicated in the template (“Studies already submitted” indicated with YES). These studies are available on request by the National Competent Authority within 3 days at the latest.

14. Guidance concerning submission of inf. about MPs as requested by the Paed. Reg.  The template with the Annex I and the Annex II if applicable has to be sent to each NCA (copy EMEA) in electronic format only where the MP is authorised.  Therefore the NCAs will dedicate a mailbox or e- mail address. A list of these addresses for each NCA will be published on the CMD-h website.  Each MAH has to fill in the template for all their national approved MPs (including MRP and DCP) subdivided for each MS in English language.

15. Deadlines 26 Jan 2008 –For the line listing and the Annex I & II, –but 26 April 2008 –For annex II Deadline only in connection with Art.45, there is no deadline in the Regulation concerning all the other addition paediatric information

16. At national level Content of the guidance and timelines should be identical Update the national website –Link to the CMD- website –Translation of the guidance? –Additional information and explanation? Exchange of information between the NCA and the MAHs

17. CMD(h) press release October 2007

18. Q&A http://hma.eu/99.html list of contact points ? EMEA – paedstudies@emea.europe.eupaedstudies@emea.europe.eu MPA – paediatric.studies@mpa.se

19. 13 Q & A art 45 and 46 so far living document

20. How to comply and organise ? Art. 45 Information and templates etc on EMEA, CMD(h) and national website 1 November – work shop for industry in Sweden internal education and information

21. How to comply and organise ? Art. 45 Involves CMD(h) member PDCO member Registration Office Department of Preclinical and clinical assessment Department of Clinical trials Regulatory Administration

22. Work flow Oct-Jan Tables (line listings) with annexes to: paediatric.studies@mpa.se paediatric.studies@mpa.se documents stored questions to appointed contact person (Lena Ahlström) – support from members of CMD(h) and PDCO

23. Work flow Jan-Feb 2008 Check of compliance (= check if all MAH submitted the information) remind MAHs

24. Work flow Jan- April 2008 receive the remaining detailed info (SPC) – 26 April store the new documents check of compliance

25. Work flow Jan- …. 2008 CMD(h) members responsibility initiate internal discussions on SE rapporteurships Agree with EMEA/CMD(h) on rapporteurships Director of operations responsibility Internally appoint project teams for assessment of studies coordinate with purely national products

26. Work flow Jan- …. 2008 rapporteurs appointed receive studies from MAHs – Registration Office studies to project manager assessment procedure ?

27. Procedure ?? use/improve principles for current work sharing ? appointment of rapporteurs and co- rapporteurs ? important with appropriate competence, true work sharing and collaboration

28. Article 46 1. Any other marketing authorisation holder-sponsored studies which involve the use in the paediatric population of a medicinal product covered by a marketing authorisation, whether or not they are conducted in compliance with an agreed paediatric investigation plan, shall be submitted to the competent authority within six months of completion of the studies concerned. 2. Paragraph 1 shall apply independent of whether or not the marketing authorisation holder intends to apply for a marketing authorisation of a paediatric indication. 3. The competent authority may update the summary of product characteristics and package leaflet, and may vary the marketing authorisation accordingly. 4. Competent authorities shall exchange information regarding the studies submitted and, as appropriate, their implications for any marketing authorisations concerned. 5. The Agency shall coordinate the exchange of information

30. Symbol art. 32

31. Survey Art 42

32. Art. 50 penalties Commission shall publish a list of the companies that have failed to comply with any of the obligations in the regulation NCA shall provide this information

33. Current BPG for work sharing procedure in the assessment of paediatric data FLOW-CHART PAEDIATRIC ASSESSMENT PROCEDURE –Actions by rapporteur/co-rapporteur - 10 Working days Validate the application rapporteur and co-rapporteur decide on timetable Day 0 Rapporteur informs applicant and MSs of start date and timetable –Circulate timetable via MRFG mailbox By Day 70 Rapporteur and co-rapporteur circulate preliminary paediatric assessment report (PPdAR) to MSs via MRFG mailbox –By Day 85 Receive contribution from other MSs for inclusion in final PdAR or supplementary information request; rapporteur and co-rapporteur prepare together list of questions. Rapporteur writes initial version, send it to co-rapporteur for comments. By Day 89 Rapporteur sends one request for supplementary information as appropriate (clock stop) »Rapporteur informs MSs of request to Applicant Consider response from Applicant. Rapporteur assesses the response to the issues raised (except for the questions of the co-rapporteur. Co-rapporteur assesses their own questions). Discussions and agreement of the rapporteur and co-rapporteur on the final PdAR. Rapporteur takes the lead in the discussion with MSs and considers whether a break out may be needed. Timetable set (as before) for a breakout to be possible at Day 105. Rapporteur contacts EMEA (CMD(h)) secretariat if needed to book a room.

34. Public assessment reports - paediatric no specific obligation in Paediatric Regulation art 21 in 2001/83 is applicable ”The assessment report shall be updated whenever new information becomes available” Transparency needed

35. BPG By Day 90 (Clock on) Rapporteur circulates finalised PdAR to MSs with draft decision and give the MSs a set timeframe to respond for deciding whether a breakout has to take place. –Around Day 105 Hold break-out meeting (when needed) preferably to coincide with CMD(h) meeting, in case discussion is required between Member States to come to harmonised decision –By Day 115 Receive confirmation from MSs of acceptance/non-acceptance of PdAR decision. Rapporteur discusses with co-rapporteur and with MSs if needed By Day 120 Rapporteur finalises the procedure and notifies MSs and applicant of final position. Rapporteur request the MAH to submit a Type II variation (or extension of application if appropriate) to implement the proposal and amend the marketing authorisation as necessary BPG EU Work sharing procedure in the assessment of paediatric Data Rev. 3, March 2007 Page 4/7 By Day 180 Rapporteur prepares public paediatric assessment report in accordance with standard procedure agreed in MRFG. The public assessment report will be published on CMD(h) website. In the exceptional situation where no agreement can be achieved between the Member States following discussions in this procedure: For products approved in the MRP discussions can continue in the following Type II variation (or extension of application if appropriate). For nationally approved products it is a national decision how to update the SPC.

36. BPG current work sharing procedure As the aim of the procedure is to make the paediatric data available for the health care professionals it has been agreed to prepare a public assessment report after finalisation of the procedure. The public assessment report (PaedPAR) will be published on Heads of Medicines Agencies website. National agencies are advised to create hyperlinks to this website.

37. Art 7 26 July 2008 – need a decision from PDCO in the application New applications all procedures include a decision from PDCO re: PIP not generics/hybrid/biosimilars (art. 10) not WEU (art. 10a) not homeopathics (art. 16) not traditional herbals (art. 16a)

38. Art 8 26 Jan 2009 art. 7 is applicable for products still under protection new indications new pharmaceutical forms new routes of administration not generics/hybrid/biosimilars (art. 10) not WEU (art. 10a) not homeopathics (art. 16) not traditional herbals (art. 16a)

39. Thank you for your attention Questions ?