Medicinal Products Registration EMEA/FDA/SWISSMEDIC - Ywesee

Medicinal ProductsRegistrationEMEA/FDA/SWISSMEDIC5 Novem ber, 2004Beat Schm idSWISSMEDICErlachstrasse 8CH-3000 Bern

Regulatory WorldEUUSA+ Others: EFTA(CH), Canada, Australia,WHOJapan

Regulatory World (2)Since 1990 = InternationalConference on Harm onisation (ICH)Requirem ents since 1990

International Conference onHarm onisation (2)Swissm edic im plem ents all ICH Guidelinesthat have reached step 5

International Conference onHarm onisation (3)Harm onisation of the Form at of theDossier Com m on TechnicalDocum ent (CTD)

Sum m ary ofProductCharacteristicsM odule1RegionalAdm inist rat iveInform at ion1 .1 ToC of M od 1 orove rall To, incl. M od 1CTDOverviewsandSum m ariesDataCTD ToC (M od 2 ,3 ,4 ,5 )2 .1CTD Int roduct ion2 .2NonclinicalOverviewClinicalQualiOverviewtOverally 2 .4 2 .5Sum m ary Nonclinical ClinicalSum m ary Sum m ary2 .3 2 .6 2 .7M odule 3 M odule 4 M odule 5Qualit y Nonclinical ClinicalSt udy St udyRe port s Report s4 .1 ToC3 .1 ToCforM od 3for M od45 .1 ToCforM od 5

Marketing AuthorisationProcedures• EU (EMEA)• CH (Swissm edic)• US (FDA)(NDA)-Marketing AuthorisationApplication (MAA)-MAA-New Drug Application

Marketing Authorisation ProcessDossierValida t ionScie nt ificAssessm e ntOpinion2 nd Scient ificAssessm entNot ificat ion ofPrim aryDecisonNot ificat ion ofDecison

Marketing AuthorisationProcedure US/FDA

The New Drug Developm ent Process:Steps from Test Tube to New Drug Application Reviewhttp://www.fda.gov/cder/handbook/

IND Review Processhttp://www.fda.gov/cder/handbook/

NDA Review Processhttp://www.fda.gov/cder/handbook/

Marketing AuthorisationProcedure EU/EMEA- Centralised Procedure- Mutual Recognition Procedure

Centralised Procedure (EMEA)Medicinal Products developed by m eans of:- rDNA technology- Expression of genes coding for proteins- Hybridom a and m onoclonal antibody m ethodsAs of 20 Novem ber 2005:New Active Substances for Specified TherapeuticAreas:- AIDS- Cancer- Neurodegenerative disorders- Diabetes- Orphan m edicinal products

Centralised procedure (EMEA)Presubm ission phaseRa pport eur/co-rapport eurappoint edCent ralised procedurest art s(Day 0 )Ra pport eur and co-ra pport eurassessm ent report s circulat ed on Day7 0 of procedureCom m ent s from ot herM e m berSt at es by Day 1 0 0CPM P agrees consolidat ed list ofquest ions t o applicant by Day 1 2 0Applicant responds within 6m onthsJP Griffin, J O‘Grady, The Regulation of Medical Products, BMJ Publishing Group 2003, p.60.

Centralised procedureJoint assessm ent of responses by rapport eurand co-rapport eur w it hin 3 0 days (Day 1 5 0of procedure)CPM P decides w het her ahearing is required onout st anding issues(Day 1 8 0 of procedure)CPM P final opinion (Day2 1 0 )Com m ission decisionaft er 9 0 daysCom m unit y aut horisat ionJP Griffin, J O‘Grady, The Regulation of Medical Products, BMJ Publishing Group 2003, p.60.

Marketing AuthorisationProcedureSw iss Agency for Therapeut ic Product sSince Ja nuary 2 0 0 2

Responsibilities ofSwissm edic• Swissm edic is responsible for the evaluationof the benefit/risk relationship- NOT Price (l‘OFAS)- NOT Reim bursem ent (l‘OFAS)• No treaties with other Agencies (FDA, EMEA)about m utual recognition of the evaluationand MA:Swissm edic has to evaluate the dossier onits own

Responsibilities of Swissm edic(2)The law on Therapeutic Products Art. 13 on m edicinalproducts and procedures authorized in foreigncountries states:“ If a m edicinal product or procedure is alreadyauthorized in a country having equivalent m edicinalproduct control, the results of tests (of the otherAgency) carried out for this purpose shall be takeninto account.”Many countries take into consideration Swissm edicdecisions

Divisions w it h M A processNon-prescript ion M edicine s, Biological M e dicine sM edical De vice s and Est ablishm e nt sand Laborat orie sPre script ion M e dicine s, Ve t erinaryM e dicines and Pharm acovigilanceVaccine s andBlood Product sBiot echnologyM edicinesPrescript ionM edicines ATC IPrescript ionM edicines ATC IICom plem e nt ary andHerbal M edicine sVet erinary M edicineNon-pre script ionM edicinesTOXICOLOGY

Review ProcessDivisionm eet ingBuilding ofcase t eamRegulatoryQualityPreclinicalClinicalIndividualre viewPeerreviewM e dicine sExpertCom m it t eem e e t ing( Divisionm e et ing)Final opinionandDecision let t e r

ReviewTim elines2 w eeks2 w eeksAdm inist rat ive checkBuilding ofcase t eamIndividualand PeerReview9 w eeks9 w eeksDivisionm ee t ingM edicines ExpertCom m it t ee m eet ing5 w eeks Approval/deficiency let t er(~ 2 0 0 days)

Negat ive opinionDeficiencylet t er3 0DaysResponseNoYesReject ion3 0anyt imDayse1 2 0Appeal New M AA DaysAddit ionalDat a/Response t oDeficienciesSubm ission ofDossier for„ Second loop“W it hdraw al oft he M AAM AA closed

„ Secondloop“1 2 0 DaysNoAdm inist rat ive checkO.K.YesRe view2 0 0 DaysOpinionPosit ive:Approval let t erNegat ive:Deficiency let t erW it hdraw a lof t he M AA3 0DaysReject ion( Reasons asde scribe d in t hede ficie ncy let t e r)3 0DaysAppeal

2 w eeks2 w eeks9 w eeks9 w eeksSwitzerlandAdm inist rat ive checkBuilding ofcase t eamIndividualand PeerRe viewDivisionm eet ingM edicines ExpertCom m it t ee m ee t ing5 w eeks Approva l/deficiency let t er(~ 2 0 0 days)Centralised procedure (EMEPre subm ission phaseRa pport eur/co-rapport eurappoint edCent ra lised procedurest art s(Day 0 )Rapport eur and co-rapport eurasse ssm ent report s circulat ed on Day7 0 of procedureCom m ent s from ot herM e m berSt at es by Day 1 0 0CPM P agrees consolida t ed list ofquest ions t o applicant by Day 1 2 0Applicantresponds within 6m onthsJP Griffin, J O‘Grady, The Regulation of Medical Product

SwitzerlandPosit ive:Approvallet t erResolut ion of m inordeficiencies (e.g.Qua lit y),Sm PC m odificat ions,Condit ionsAppealM a rket ingAut horisat ion90 Days(Applicant)NoAppea l90 Days(Swissm edic)Centralised procedure(EMEAJoint assessm ent of re sponses by rapport eurand co-ra pport eur w it hin 3 0 days (Day 1 5 0of procedure)CPM P decides w het her ahearing is required onout st anding issues(Day 1 8 0 of procedure)CPM P final opinion (Day2 1 0 )Com m ission decisionaft er 9 0 daysCom m unit y aut horisat ionJP Griffin, J O‘Grady, The Regulation of Medical Produc

Average AnnualApplicationsEM EASw issm edicFDA2 52 42 6Per year for New Act ive Subst ancesTim e Period: 1 9 9 7 – 2 0 0 1

Differences between Swissm edicFDAUSACH

Differences Between Swissm edicEMEA/FDA• Decision based on the subm itteddossier.No „ consolidated list of questions“before prim ary opinion. No „ rolling• review“ Only m inor deficiencies can be dealtwith during the review processShort review tim es forapplications of high qualityInconvenience for incom plete orprem ature dossiers