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An agency of the European Union
The SME Office at the European Medicines Agency
Constantinos ZiogasSME Office, Stakeholder & Communication Division, European Medicines Agency
Open Info DayHorizon 2020 'Health, demographic change and wellbeing‘Brussels 22 November 2013
How can regulators proactively support drug development?
2
Development challenges - seeing through the eye of the customer
Issues: Solutions:
Perceived barriers to
engaging with regulators –
small companies, start-ups,
academic groups (main
developers of ‘advanced
therapies’)
Easy access through
‘SME Office’
Early support from
‘Innovation Task Force’
3
A proactive regulatory approach: “Be part of it and
shape it together.”
4
Incentives/Assistance to drug development
ITF Orphan
ScientificAdvice
AdvancedTherapiesPaediatricSME
5
Orphan DesignationTime
Knowledge
Medical Plausibility
Pos Benefit-Risk
Compliance with Ped Invest Plan
Marketing Authorisation (To)
(Clinical) Development
Scientific Advice
Benefit-Risk Mgt Plan
Paediatric Invest. Plan
Industry - Regulator interactions
ITF
6
Support to small & medium sized enterprises (SMEs)
7
Tailoring assistance for SMEs
To promote innovation & development of new medicinal products by SMEs
8
SME Office
• A single interface/’one-stop shop’
• SME assignment, public SME register
• Fee incentives, regulatory assistance, translations
• Facilitate communication
• News bulletins, SME User Guide
• Workshops
9
Assignment of SME Status
For applicants established in EEA
SME criteria defined in Recommendation 2003/361/EC:
Headcount < 250 and annual turnover not more than € 50 mil or balance sheet not more than € 43 mil
Submit information to show compliance with criteria
120
183223
185
229
354
622
0
100
200
300
400
500
600
700
2006 2007 2008 2009 2010 2011 2012
Assignment
10
Incentives for SMEs
* Medicines based on genes / cells / tissues
• Regulatory, administrative and procedural assistance • Fee reductions and deferrals• Certification of Quality/Non-clinical data for advanced therapy medicinal products*• Translation of product information
11
Fee Incentives for SMEs
90% reduction on :
• scientific advice• GMP, GLP, GCP, PhVig inspections• scientific services
100% ‘waiver’ on administrative services
For MAA, SME fee deferral
• orphan medicine: 100% waiver to 1st year post-licensing
• paediatric use marketing autorisation: 50% fee reduction
Conditional Fee Exemption
Subject to EMA scientific advice – payment only for positive
outcome12
Experience with SMEs 2006-2012
1098 companies assigned SME status
From 27 countries across EEA
41% micro, 38% small, 19% medium
Majority human, 44 vet, 66 human/vet & 154 service providers
Public register of companies launched in 2010
13
SME product pipeline – categories
Research/Discovery13%
Pharmaceutical development15%
Preclinical14%
Clinical exploratory12%
Clinical confirmatory9%
(Pre) Registration15%
Marketing22%
Therapeutics (84%), vaccines (7%), diagnostics/imaging (9%) Orphan medicines (20%) Nanotechnology (4%), pharmacogenomics/biomarkers (3%)
Product development stages:
14
Regulatory Assistance for SMEs
• Direct assistance:
• Queries dealt with by SME office e-mail/telecon
• Briefing meetings/telecon on regulatory strategy
• Published SME User Guide on regulatory procedures
• SME News bulletin
• Annual training/workshops tailored for SMEs
15
Scientific advice
16
http://www.emea.europa.eu/index/indexh1.htm
under Application Procedures
Scientific advice and ‘protocol assistance’
• EU advice on development &
agreement of future strategy
• Working party of CHMP
• Note: Protocol assistance is
scientific advice for orphan
designated products, and does not
only relate to clinical aspects.
16
Scope of scientific advice
• Scientific Advice can be provided on ANY scientific question
- Quality, non-clinical and clinical
• At any time point of the development
Early advice with subsequent follow-up is recommended
• Not only product specific Broad advice, Conditional approval/Exceptional circumstances
- On the eligibility or on proposed development
Qualification of biomarkers and other novel methodologies
Note: Clinical trial authorisation is handled at the national level
18
FAQs in Scientific Advice
Quality/CMC
• comparability, stability, etc.
Non-clinical• in vivo pharmacology for innovative products
• animal models for products with human specific targets, animal models mimicking the human disease, surrogate molecules
• carcinogenicity and reprotoxicity waivers, etc.
Clinical• PK/PD, dose-finding, interactions
• exploratory & pivotal trials: study endpoints, population, comparator, blinding, statistics (interim A, adaptive/seamless design), safety DB
19
Key features of scientific advice
• Optional (upon company request)
• Strictly confidential
• Robust
• Short procedures 40 to 70 days
•‘Pre-submission’ assistance
• Face-to-face meetings with scientific experts for 50% of advice
• Fee-related activity (significant fee waiver/reduction for orphan products/paediatrics/SMEs)
• Written responses adopted by the licensing Committee, sent to the
company ie. the ‘scientific advice letter’
20
Figures for scientific advice
308
322
356
339
65
66
76
74
81
263
214
80
140
196
67
71
86 23
32
57
63
67
0 50 100 150 200 250 300 350 400 450
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
Scientific Advice Protocol Assistance
20
Compliance with scientific advice is associated with positive MA outcome
21
Scientific advice and MA application outcome (2004-7; N=188)
Who requests SA?
Big pharma: 33%
Who complies with SA?
Company size is significantly associated with positive outcome of MA application: OR = 2.96 (95%CI: 1.92, 4.56)
Obtaining and complying with SA appears to be a predictor of outcome [compliant with SA vs. no-SA: OR 14.71, 95% CI 1.95; 111.2; non-compliant with SA vs. no-SA: OR 0.17, 95% CI 0.06; 0.47, p<0.0001)].
Regnstrom et al; Eur J Clin Pharmacol. 2010 Jan;66(1):39-48
Big pharma: 84% Medium pharma: 60% Small pharma: 25%
23
Innovation Task Force (ITF)
Multidisciplinary platform
for preparatory dialogue
and orientation on
innovative medicines,
technologies and methods
24
Purpose of Innovation Task Force (ITF):
• Provide a forum (soft landing zone) for innovation
• Complementary and preparatory to existing formal procedures
Tools:
Briefing meetings Scientific recommendations on classification Workshops (e.g. nano, stem-cell)
25
A platform for discussing a wide range of topics
Preclinical and in vitro models
Biomarker Qualification
Adaptive designs
“-omics”
Methodologies and Statistics
Epigenetics
Synthetic Biology
Nanopharmaceuticals
Borderline products
Advanced therapies
26
ITF briefing meetings
• Objective: facilitating the informal exchange of information and guidance in the development process, complementing and reinforcing existing formal procedures
• Scope: regulatory, technical and scientific issues arising from innovative medicines development, new technologies and borderline products
• Applicants: Consortia, Networks, Public/private partnerships, Learned societies, Pharmaceutical industry, Academia
• Free of charge
• Scientific discussions led by experts from the Agency network, working parties and committees
• For pharmacogenomics, with PG Working Party
27
‘Mutually benefitting’ dialogue
• Starting the regulatory dialogue with the Agency early
• Facilitating knowledge exchange on innovative strategies:
update on progress, address new science and questions to
regulators, understand concerns and prepare for solutions
• Providing orientation on regulatory science topics in drug
development
• Identify issue of particular interest to regulators in preparing
for formal procedures (e.g. biomarkers qualifications,
scientific advice, orphan medicines designation)
28
ITF briefing meetings
29
SMEs in ITF briefing meetings
30
Thank you for your attention
31