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?

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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’

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A proactive regulatory approach: “Be part of it and

shape it together.”

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Incentives/Assistance to drug development

ITF Orphan

ScientificAdvice

AdvancedTherapiesPaediatricSME

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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

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Support to small & medium sized enterprises (SMEs)

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Tailoring assistance for SMEs

To promote innovation & development of new medicinal products by SMEs

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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

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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

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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

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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

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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:

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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

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Scientific advice

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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.

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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

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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

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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’

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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

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Compliance with scientific advice is associated with positive MA outcome

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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%

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Innovation Task Force (ITF)

Multidisciplinary platform

for preparatory dialogue

and orientation on

innovative medicines,

technologies and methods

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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)

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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

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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

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‘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)

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ITF briefing meetings

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SMEs in ITF briefing meetings

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Thank you for your attention

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