All About Regulatory Affairs - Granzer

1 All About Regulatory AffairsForum Heidelberg August 2010Dr. Ulrich of procedure When do we have a choice of procedure for a generic medicinal product? When the originator product was approved centrally New pharmaceutical forms with new features are no generics When it is a classical small molecule Independent of indication! When it fulfils the eligibility criteria for the centralized procedure Innovation Novel (new) technology3 MRP and DCPS cope4 Scope of MRP/DCP: New active substances (if not mandatory for the centralised procedure) Generic medicinal products to authorised reference medicinal products Informed consent Well established use (WEU.)

2 Bibliographic applications) line extensions to national authorisations known substances in new combination New indications/new pharmaceutical forms for known substances5 Article 17 of Directive 2001/83/EC 1..Applications for marketing authorizations in two or more member states in respect of the same medicinal product shall be submitted in accordance with Articles 27 to Where a Member State notes that another marketing authorization application for the same medicinal product is being examined in another Member State, the Member State concerned shall decline to assess the application and shall advise the applicant that Articles 27 to 39 apply.

3 6 Article 18 of Directive 2001/83/EC Where a Member State is informed in accordance with Article 8(3)(1) that another Member State has authorized a medicinal product which is the subject of a marketing authorization application in the Member State concerned, it shall reject the application unless it was submitted in compliance with Articles 27 to 39. Factors influencing the selection of procedure Marketing agreements Co-marketing: No of independent marketing authorizations No of Trade Names Co-promotion Only one Trade Name No of partners in the EU Markets, where the product shall be launchedMRP still a choice?

4 Single (national) approval first Followed by MR round(s)9 Application to first member stateAssessment reportincluding SPC, PIL First Authorization: RMS210 daysApplicant request on mutual recognition of first(reference) authorisationMutual Recognition ProcessObjections from CMSsBy day 50clarification and dialogue / point ofview of applicant (orally or writing)resolution of issuesAdditional National Authorization(s)35 daysNational evaluation and licencing processMutual Recognition Procedure90 days5 daysMR advantages and issues No slots necessary Freedom to chose the national authority Timelines can be negotiated on a national level Option to be faster than in DCP due to immediate start But: one single country first, loss of marketing opportunity for multinational companiesDCP - Slots The ProblemNo of procedures finished in 2008 MRP: Split by Member StateDCP.

5 Split by Member State15 EEA distribution of RMS rolesWhy bother with the Centralized Procedure?Decentralised Procedure1718 Application to all member statesRMS to start reviewCMSs send comments to RMS and Applicant Consultation between RMS, CMS and Applicant (5 days)PAR to CMSs and Applicant70 daysDay 105: Clock stop orpositive close of procedureRMS updates PrAR to prepare draft AR (DAR)Day 106: Submission of the responseRMS evaluation of the dossier: Preliminary Assessment Report(PAR)Decentralized Procedure30 daysPreparation of response document by applicant3 6 monthsDay 120: Consensus?

6 End of procedureDay 120: No consensus?Follow on process19 Day 120: Follow on processCMSs send comments to RMS and Applicant Consultation between RMS, CMS and Applicant (5 days)Day 145: CMSs send (final) comments on draft AR25 daysDay 150: Consensus?: Procedure is forwarded to the Coordination group for the Mutual Recogntionand the Decentralized Procedure (CMD) Day 180: CMD becomes involvedCMSs prepare response to Draft Assessment ReportDecentralized Procedure30 daysRMS prepares report on outstanding issues by Day 18030 daysDay 195: Discussion at CMD/Break out session End of procedureYes?

7 NO?Day 195: Discussion at CMD/Break out session Day 210: Mutual Approval?Referral to CMDD ecentralized ProcedureEnd of procedureGrant of national licenses within 30 daysYes?NO?Publication ofAssessment report on the internetDay 195: Discussion at CMD/Break out session Day 210: Mutual Approval?Referral to CMDD ecentralized ProcedureEnd of procedureGrant of national licenses within 30 daysYes?NO?: life becomes difficult!Publication ofAssessment report on the internet22 CMD(h)-Referral in DCP and MRPCMD-Referral - Trigger: Disagreementbetween MS concerned by the application at the end of MRP (Day 90) or DCP (Day 210) based on potential serious risk to public health What does this mean?

8 If all are positive: Case closed If all are negative but the applicant: CASE CLOSEDOne MS, the RMS, has to be positive to trigger a referral24 Day 0 RMS starts procedure: Draft LoQ to MSs for commentsDay 10final LoQ to the ApplicantDay~201st CMD-Meeting: Discussion of caseDay 25 Response from Applicant on LoQ 10 days for preparation of response (day 11 day 20) No new information Usually no new arguments Improvement of statements if possible Cooperation with RMS, if RMS is positive Cooperation with CMS, if at least one CMS is positive60 Days CMD-Procedure (CMD-SOP)Day 35 Updated AR of the RMS to CMDDay 45 MSs position on response to LoQDay~50 Discussions at 2nd CMD-Meeting.

9 Hearing of written commentsDay 60close of procedure with two options: consensus or referral to CHMP26 Withdrawal of Applications The applicant has the right to withdraw the application until the last day of the MRP or DCP. However, if the applicant has withdrawn the application from a MS because a potential serious risk to public health was raised by this MS, the application will be automatically forewarded for discussion to the CMD(h) A withdrawal will not help the applicant!27 Referrals to CHMP in 2007 (21 Procedures)ProductReason for Referral to CHMPCHMPV antasSafety & EfficacypositiveFentastad (5)

10 Bioequivalence, SPC, Quality, Non-clinicalNegative-RESimvastatin KrkaBioequivalencenegativeEformaxQuality , Safety & EfficacynegativeBicaluplex 150 mgSafety & Efficacy of an indicationpositiveXeominSafety & EfficacypositiveMenitorixSafety & EfficacypositiveCoxtralEfficacynegativeP ulairmaxQuality, Safety & EfficacynegativeOraceaSafety & EfficacypositiveRapinylSafety & EfficacypositiveAlvescoEfficacypositiveA torvastatin (4)BioequivalencewithdrawnSlots current situation UK: depends on indication, no clear guidance, ask S: slot days where requests for certain times are being accepted D: Slots in 2012 and 2013 NL: Working on system, but no quick slots DK: Already in 2012 Makes CP attractive?