Regulatory pathways to new medicines · Regulatory pathways to new medicines, T. Humphreys,...
Transcript of Regulatory pathways to new medicines · Regulatory pathways to new medicines, T. Humphreys,...
An agency of the European Union
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
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Post Nov 2005 Three European Systems
Centralised Procedure (via EMA)
Mutual Recognition procedure
Decentralised Procedure
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Auto-immune disease and Other immune dysfunctions
Viral diseases
AIDS Cancer Neurodegenerative disorder
Diabetes
-Recombinant DNA technology
-Controlled gene expression
-Monoclonal AB ATMP
Orphan Med Prod NAS / “known” AS
Reg. 726/2004
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
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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
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Assembling your Marketing Authorisation Application
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All Marketing Authorisation applications must demonstrate
the same standard of
100% QSE
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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. 10 (c) Informed Consent
Art. 10 (a) Well Established Use 100% bibliographic
Art. 10 (b) Fixed Combination Dose
forms > 0% - < 100% Non
clinical / clinical studies
Generic / Biosimilar Pharma
Art. 10 (1) Classic “generic”
Bioequivalence +/- biowaiver
Art 10 (3) Complex “generic”
> 0% - < 100% Non clinical / clinical studies
Art. 10 (4) Biosimilars
“Comparability” QSE data package
Trends in EU marketing authorisation applications 1995-2012
0
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
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Centralised Procedure Overview
D 80 Rap AR ------- Co-Rap
AR
D 115 Peer
Review Telecon
START
Assessment
Rap
Co-Rap
D -180
D 121 Response
Submission
D 120 Joint LoQ
Clock Stop (3 – 6 m) App R/cR
Assess Teams
D 121 Response
Submission
D 150 Joint
Response AR
D 180 LoOI
Clock Stop
(1-3 m)
D 181 Oral Expl
D 210 Opinion
Consensus Simple
Majority
CHMP
Comments
CHMP
Comments
SAG / WP consultation
Inspections GMP / GCP
Primary Evaluation
Secondary Evaluation Decision Making
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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 of science and therapies, accelerated assessment procedures should be set up, reserved for medicinal products of major therapeutic interest, and procedures for obtaining temporary authorisations subject to certain annually reviewable conditions.
Soliris Isentress VPRIV Pumarix Zytiga Incivo
Victrelis Kalydeco
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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
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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
15
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
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CHMP Voting Rules
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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
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CHMP Outcomes 2012 - 2013
0
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
42
8 8
3 35
2 2
57 8
5
1
1
1
2
1
1
1
1
1 11
1
1
1
1
11
1
1
13
4
6
1
6
1
Neg Re ex
W/d
Neg Maj
Pos Maj
Neg Con
Pos Con
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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 ?
Phase I Phase II Phase III Phase IV
Conventional development NOT possible (too rare):
Conventional development possible:
Surrogate endpoint confirmation of benefit
proved benefit
Exceptional circumstances
Full MA
Cond. approval Full MA
MA under EC
Phase I Phase II Phase III Phase IV
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Conditional Approval
100
Adequate Data
Time
+ve CHMP opinion
“normal” MA
+ve CHMP opinion
Exceptional Circumstances
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Exceptional Circumstances 2006 – 2012
Metabolism
Elaprase
Vedrop
Orphacol
Glybera
Nervous System
Zenas
Vyndaqec
Anti-Infectives
Daronix
Focetria
Pandemrix
Celvapan
PIV – H5N1(X2)
Foclivia
Pumarix
Oncology
Evoltra
Atriance
Yondelis
Ceplene
Arcalyst
Ilaris
Blood
Atryn
Hormonal
Increlex
3
5
3
7
2 1 1
0
2
4
6
8
2006 2007 2008 2009 2010 2011 2012
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Conditional Approval 2006 – 2012
Oncology
Sutent Orph
Vectibix
Tyverb
Arzerra
Votrient Orph
Votubia Orph
Caprelsa
Xalcori
Adcentris
Pixuvri
Anti-Infective
Prezista
Isentress
Intelence
Cayston
Arepanrix
Humenza
CNS / NDD
Diacomit Orph
Fampyra
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Real access to products?
Member 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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• 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 on draft CAT opinion
• 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
Imatinib Accord Imatinib
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