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

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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

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 1

Post Nov 2005 Three European Systems

Centralised Procedure ( via EMA) Mutual Recognition procedure Decentralised Procedure

2

Auto-im m une disease and Other immune dysfunctions Viral diseases

AI DS

Cancer

Neurodegenerative

disorder

Diabetes

• Recom binant DNA

technology

• Controlled gene

expression

• Monoclonal AB

ATMP

Orphan Med Prod NAS / “know n” AS

• Reg. 7 2 6 / 2 0 0 4

Mandatory Scope of Centralised Procedure

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

New Active Substances Significant Innovation

• Therapeutic

&/or Scientific &/or Technical Interest of Patients at Community Level

• Art. 3(2)(a)
• Art. 3(2)(b)

OR

• Art. 3(2) of Regulation (EC) No 726/2004

Optional Scope of Centralised Procedure

3 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 4

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 5

T-36/48 MO T-36/12 MO T-24/12 MO T-12 MO T 0

Committees Co-ordination

Pre-submission phase

CHMP COMP CAT PRAC PDCO CHMP SAWP CHMP PRAC CAT

Post Authorisation Evaluation

Launch

CHMP

Orphan

Designation + Paed Req. Scientific Adv. Protocol assist.

MAA Presub. Regulatory Filing Strategy MAA Evaluation Changes MA + PhV

COMP PDCO PDCO SAGs WPs CAT

6 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Assembling your Marketing Authorisation Application

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 7

All Marketing Authorisation applications must demonstrate the same standard of

1 0 0 %

QSE

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 8

Applicants “choice” of legal basis Innovator pharma

• Art. 8 ( 3 ) “Full”

100% non clinical / clinical studies

• Art. 8 ( 3 ) “Mixed”

> 0% - < 100% Non clinical / clinical studies 100% balance bibliography

All Pharma

• Art. 1 0 ( c)

Informed Consent

• Art. 1 0 ( a)

Well Established Use 100% bibliographic

• Art. 1 0 ( b)

Fixed Combination Dose forms > 0% - < 100% Non clinical / clinical studies

Generic / Biosimilar Pharma

• Art. 1 0 ( 1 )

Classic “generic” Bioequivalence + / - biowaiver Art 1 0 ( 3 ) Complex “generic” > 0% - < 100% Non clinical / clinical studies

• Art. 1 0 ( 4 )

Biosimilars “Comparability” QSE data package

Trends in EU marketing authorisation applications 1995-2012

10 20 30 40 50 60

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

10

Centralised Procedure Overview

D 8 0 Rap AR

• Co-Rap

AR D 1 1 5 Peer Review Telecon

S T A R T

Assessm ent

Rap Co-Rap

D

• 1 8 0

D 1 2 1 Response Submission

D 1 2 0 Joint LoQ

Clock Stop ( 3 – 6 m ) App R/ cR Assess Team s

D 1 2 1 Response Submission D 1 5 0 Joint Response AR D 1 8 0 LoOI

Clock Stop ( 1 -3 m )

D 1 8 1 Oral Expl D 2 1 0 Opinion

Consensus Sim ple Majority

CHMP Com m ents CHMP Com m ents

SAG / WP consultation Inspections GMP / GCP

Primary Evaluation Secondary Evaluation Decision Making

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

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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

• f 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

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

12 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 13

SAG / Working Party Constellation

CHMP

QWP* SWP* BWP* Sci Adv Patients & Consumers

Biosimilars Biostatistics Blood Prod CNS Rheumatology Immunology Infectious Diseases Oncology Pharmacokinetics Pharmacogenomics Geriatrics Cardiovascular Vaccines Gastroenterology Respiratory Urology Radiopharmaceuticals

* 1 / MS representation

SAG diagnostics SAG CVS SAG Neurology SAG Psychiatry SAG HIV / Antiviral SAG Oncology SAG CVS SAG Diabetes

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 14

Scientific Advisory Groups: input

SAG CVS

S A G

• Cardiovascular

issues

• Anti-infectives
• Diabetes /

Endocrinology

• Diagnostics
• HIV / Viral

Diseases

• Neurology
• Oncology
• Psychiatry
• Vaccines

To deliver independent recommendation to specific questions

Rapporteur / Co-Rapporteur: present the issue and provide additional information on the dossier Possible hearing from applicant Provides answers to each question If no consensus: majority views recorded together with any divergent position in document “SAG answers and comments to the CHMP” Position is reflected in CHMP Assessment Report

Scientific Advisory Groups (SAGs) 2006 - 2013

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Oncology; 39 Cardiovascular; 18 Diabetes / Encrinology; 16 Central Nervous system; 14 HIV / Viral diseases; 12 Anti-infectives; 10 Neurology; 8 Diagnostics; 6 Vaccines; 2 Psychiatry; 1

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

CHMP Voting Rules

16

32 members eligible to vote (27 MS/ NCAs + 5 co-opted) Norway and Iceland recorded separately Abstention! Voting Simple Majority: 17 to sustain a positive or negative opinion Quorum = No pre-determined MS position CHMP capacity scientific member, hence vote personal / individual

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

CHMP Outcomes 2012 - 2013

2 4 6 8 10 12 14 16 Jan Feb March April May June July Sept Oct Nov Dec Jan Feb March April

1 8 4 2 8 8 3 3 5 2 2 5 7 8 5 1 1 1 2 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 3 4 6 1 6 1 Neg Re ex W/d Neg Maj Pos Maj Neg Con Pos Con

17 Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

Drug development and data criteria for different type of

• pinions / centralised MA

Full MA ?

Phase I Phase II Phase III Phase IV

• Conventional development NOT possible (too rare):
• Conventional development possible:

Surrogate endpoint confirmation

• f benefit

proved benefit Exceptional circumstances Full MA

• Cond. approval

Full MA MA under EC

Phase I Phase II Phase III Phase IV

18

Conditional Approval

100 Adequate Data Time +ve CHMP

• pinion

“normal” MA +ve CHMP

• pinion

Exceptional Circumstances

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Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 202 020

Exceptional Circumstances 2006 – 2012

Metabolism Elaprase Vedrop Orphacol Glybera Nervous System Zenas Vyndaqec Anti-I nfectives Daronix Focetria Pandemrix Celvapan PIV – H5N1(X2) Foclivia Pumarix Oncology Evoltra Atriance Yondelis Ceplene Arcalyst Ilaris Blood Atryn Horm onal Increlex

3 5 3 7 2 1 1 2 4 6 8 2006 2007 2008 2009 2010 2011 2012

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21

Conditional Approval 2006 – 2012

Oncology Sutent Orph Vectibix Tyverb Arzerra Votrient Orph Votubia Orph Caprelsa Xalcori Adcentris Pixuvri Anti-I nfective Prezista Isentress Intelence Cayston Arepanrix Humenza CNS / NDD Diacomit Orph Fampyra

Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013

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Real access to products?

Mem ber States

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.”

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Regulatory pathways to new medicines, T. Humphreys, Dubrovnik, 6 - 7 May 2013 24

• First treatment

pseudobulbar affect (uncontrolled emotional expression)

• CHMP opinion:

+ ve by consensus

• Eligibility:

significant therapeutic innovation

• Legal basis:
• Art. 10(6)
• Transdermal

formulation for patients with difficulty swallowing tablets

• CHMP Opinion:

+ ve by majority

• Eligibility:

significant innovation / patient interest

• Legal basis:
• Art. 10(3)
• First combined

tissue engineered medicine in EU

• CHMP Opinion:

+ ve by consensus based

• n draft CAT
• pinion
• Eligibility:

ATMP

• Legal basis:
• Art. 8(3)
• Generic of Glivec

= CML adults and paediatrics

• CHMP Opinion:

+ ve by consensus

• Eligibility: Art.

3(3) Generic CAP

• Legal basis:
• Art. 10(1)

Neudexta

dextromethorphan hydrobromide + quinidine sulphate

Sancuso

Granisetron PONV

MACI

Matrix induced antologous chondrocyte implantation

I m atinib Accord

Imatinib

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