REGULATION (EC) No 1901/2006

of 12 December 2006on medicinal products for paediatric use

Article 45 and more…

Christer Backman

CMD(h) Sweden

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

DEADLINE TASKS WHO CMD(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

DEADLINE TASKS WHO CMD(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 YesJan 10 Symbol on all products

with paediatric indication

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.

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

Art. 45

How are NCAs and EMEA collecting data on MPs with paediatric use?

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

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.

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.

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

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

CMD(h) press release October 2007

Q&A

• http://hma.eu/99.html

• list of contact points ?

EMEA – paedstudies@emea.europe.eu

MPA – paediatric.studies@mpa.se

13 Q & A

• art 45 and 46 so far

• living document

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

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

Work flowOct-Jan

• Tables (line listings) with annexes to: paediatric.studies@mpa.se

• documents stored

• questions to appointed contact person (Lena Ahlström) – support from members of CMD(h) and PDCO

Work flowJan-Feb 2008

• Check of compliance (= check if all MAH submitted the information)

• remind MAHs

Work flowJan- April 2008

• receive the remaining detailed info (SPC) – 26 April

• store the new documents

• check of compliance

Work flowJan- …. 2008CMD(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

Work flowJan- …. 2008 rapporteurs appointed

• receive studies from MAHs – Registration Office

• studies to project manager

• assessment procedure ?

Procedure ??

• use/improve principles for current work sharing ?

• appointment of rapporteurs and co-rapporteurs ?

• important with appropriate competence, true work sharing and collaboration

Article 461. 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

Symbol art. 32

Survey Art 42

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

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.

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

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.

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.

Art 726 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)

Art 826 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)

Thank you for your attention

• Questions ?