Regulatory pathways to new medicines EU 28: science, medicines, - PowerPoint PPT Presentation

Regulatory pathways to new medicines EU 28: science, medicines, health – a regulatory system fit for the future 6 – 7 May 2013, Dubrovnik, Croatia Presented by: Tony Humphreys Head of Regulatory, Procedural and Scientific Committee Support Patient Health Protection An agency of the European Union

Post Nov 2005 Three European Systems Centralised Mutual Decentralised Procedure Recognition Procedure ( via EMA) procedure 1 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Mandatory Scope of Centralised Procedure Auto-im m une disease and Other immune dysfunctions Neurodegenerative Cancer AI DS disorder Viral - Recom binant DNA technology diseases Diabetes - Controlled gene expression Orphan Med Prod - Monoclonal AB NAS / “know n” AS ATMP Reg. 7 2 6 / 2 0 0 4 2 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Optional Scope of Centralised Procedure Art. 3(2) of Regulation (EC) No 726/2004 Art. 3(2)(a) Art. 3(2)(b) Significant Innovation Interest of New Active Patients at Substances -Therapeutic Community &/or OR Level Scientific &/or Technical 3 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

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Committees Co-ordination T-36/48 T-36/12 T-24/12 T-12 MO T 0 MO MO MO Orphan MAA Regulatory Changes Scientific Adv. MAA Evaluation Designation Protocol assist. Presub. Filing Strategy MA + PhV + Paed Req . CHMP COMP CHMP CHMP CAT PRAC CHMP COMP PRAC CAT SAWP PDCO SAGs Launch CAT PDCO PDCO WPs Pre-submission phase Evaluation Post Authorisation 6 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Assembling your Marketing Authorisation Application All Marketing Authorisation applications must demonstrate the same standard of 1 0 0 QSE % 7 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Applicants “choice” of legal basis Generic / Innovator All Pharma Biosimilar pharma Pharma Art. 1 0 ( 1 ) Art. 1 0 ( c) Classic “generic” Art. 8 ( 3 ) “Full” Informed Consent Bioequivalence + / - 100% non clinical / biowaiver clinical studies Art 1 0 ( 3 ) Art. 1 0 ( a) Complex “generic” Well Established Use > 0% - < 100% Non 100% bibliographic clinical / clinical studies Art. 8 ( 3 ) “Mixed” > 0% - < 100% Non clinical / clinical Art. 1 0 ( b) Art. 1 0 ( 4 ) studies Fixed Combination Dose Biosimilars forms 100% balance “Comparability” QSE > 0% - < 100% Non bibliography data package clinical / clinical studies 8 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Trends in EU marketing authorisation applications 1995-2012 60 50 40 30 20 10 0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Orphan Other (biosimilar, generic, WHO, WEU etc) Non-orphan Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 9

Centralised Procedure Overview D -1 8 0 Rap D 8 0 D 1 1 5 S D 1 2 0 D 1 2 1 Rap AR Peer T CHMP Joint Response Assessm ent ------- Review A Com m ents Submission LoQ Co-Rap R Telecon Co-Rap T Clock Stop AR ( 3 – 6 m ) App R/ cR Primary Evaluation Assess Team s SAG / WP consultation Decision Secondary Evaluation Making D 1 5 0 D 1 2 1 D 1 8 1 Joint D 1 8 0 D 2 1 0 CHMP Response Oral Response Com m ents LoOI Opinion Submission Expl AR Clock Consensus Stop Sim ple Inspections GMP / GCP ( 1 -3 m ) Majority 10 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Accelerated Assessment – Regulation 726 / 2004 Art. 33 In order to meet, in particular, the legitimate expectations of patients and to take account of the increasingly rapid progress of science and therapies, accelerated assessm ent procedures should be set up, reserved for medicinal products of major therapeutic interest, and procedures for obtaining tem porary authorisations subject to certain annually reviewable conditions. Soliris Isentress VPRIV Pumarix Zytiga Incivo Victrelis Kalydeco 11 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

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SAG / Working Party Constellation Pharmacogenomics Biosimilars SAG Urology diagnostics Biostatistics SAG Radiopharmaceuticals CVS Blood Prod SAG Respiratory SAG QWP * CVS Patients & Neurology Consumers Cardiovascular SAG CNS HIV / CHMP Vaccines Antiviral BWP * SAG Sci Adv Rheumatology Gastroenterology Psychiatry SWP * Immunology Geriatrics SAG Infectious Diabetes Pharmacokinetics * 1 / MS Diseases SAG representation Oncology Oncology 13 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Scientific Advisory Groups: input To deliver independent recommendation to specific questions SAG  Cardiovascular Provides answers to Rapporteur / CVS issues each question Co-Rapporteur:  Anti-infectives present the issue and S  Diabetes / If no consensus: provide additional Endocrinology majority views information on the A  Diagnostics recorded together dossier  HIV / Viral with any divergent Diseases position in document G  Neurology “SAG answers and  Oncology comments to the  Psychiatry CHMP” Possible hearing from  Vaccines applicant Position is reflected in CHMP Assessment Report 14 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Scientific Advisory Groups (SAGs) 2006 - 2013 Vaccines; 2 Diagnostics; 6 Psychiatry; 1 Neurology; 8 Oncology; 39 Anti-infectives; 10 HIV / Viral diseases; 12 Central Nervous Cardiovascular; 18 system; 14 Diabetes / Encrinology; 16 15 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

CHMP Voting Rules 32 members eligible Norway and Iceland Abstention! to vote recorded separately (27 MS/ NCAs + 5 co-opted) Quorum = Voting Simple Majority: 17 to sustain a positive or negative opinion No pre-determined MS position CHMP capacity scientific member, hence vote personal / individual 16 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

CHMP Outcomes 2012 - 2013 16 Neg Re ex 14 6 12 W/d 10 1 Neg Maj 6 2 1 1 1 8 1 4 Pos Maj 1 1 6 1 3 1 1 1 1 1 8 8 8 8 Neg Con 4 1 1 1 1 1 7 1 5 1 1 5 5 4 2 3 3 Pos Con 2 2 2 1 0 Jan Feb March April May June July Sept Oct Nov Dec Jan Feb March April 17 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Drug development and data criteria for different type of opinions / centralised MA Full MA  Conventional development possible: proved benefit Cond. approval Full MA confirmation Surrogate endpoint of benefit Phase II Phase II Phase III Phase III Phase I Phase I Phase IV Phase IV Full MA ?  Conventional development NOT possible (too rare): MA under EC Exceptional circumstances 18 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Conditional Approval +ve CHMP opinion “normal” MA 100 +ve CHMP Adequate opinion Data Exceptional Circumstances Time 19 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Exceptional Circumstances 2006 – 2012 8 7 6 5 4 3 3 Anti-I nfectives Metabolism 2 2 1 1 Daronix Elaprase 0 2006 2007 2008 2009 2010 2011 2012 Focetria Vedrop Pandemrix Orphacol Oncology Celvapan Glybera Evoltra Blood PIV – H5N1(X2) Atriance Atryn Nervous Foclivia Yondelis System Pumarix Ceplene Horm onal Zenas Arcalyst Increlex Vyndaqec Ilaris 202 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 20 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 020

Conditional Approval 2006 – 2012 Oncology Sutent Orph Anti-I nfective Vectibix Prezista Tyverb Isentress Arzerra Intelence Votrient Orph Cayston Votubia Orph CNS / NDD Arepanrix Caprelsa Diacomit Orph Humenza Xalcori Fampyra Adcentris Pixuvri 21 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Real access to products? Mem ber States 22 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Article 1 “The provisions of this Regulation shall not affect the powers of Member States’ authorities as regards setting the prices of medicinal products or their inclusion in the scope of the national health system or social security schemes on the basis of health, economic and social conditions. In particular, Member States shall be free to choose from the particulars shown in the marketing authorisation those therapeutic indications and pack sizes which will be covered by their security bodies.” 23 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013