The European Nanomedicine Characterisation Laboratory

Susanne Bremer-HoffmannJoint Research CentreEuropean Commission

NMBP 14-2017 Regulatory Science Framework for assessment of risk benefit ration of Nanomedicines and Biomaterials

Thematic brokerage workshopsWorkshop 7: EU-U.S Cooperation

EU Brokerage Event on Kets in Horizon 2020Strasbourg, 1st October 2015

101/10/2015 - BE KETs Regulatory Science Framework for Nanomedicines and Biomaterials

Outline

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Some institutional information on our organisation and our skills and expertise

Introduction into a European transnational infrastructure in nanomedicine (funded by European Union’s Horizon 2020 research

and innovation program)

Regulatory Science Framework for Nanomedicines and Biomaterials

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Joint Research Centre

EUROPEAN COMMISSION

DIRECTORATESGENERAL

DIRECTORATESINSTITUTES

UNITS SCIENTIFIC UNITS

European Reference Laboratories,

Centres & Bureaus

JRC

Regulatory Science Framework for Nanomedicines and Biomaterials

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As the Commission's in-house science service, the Joint Research Centre's mission is to provide EU policies with independent, evidence-based scientific and technical support throughout the whole policy cycle.

Working in close cooperation with policy Directorates-General, the JRC addresses key societal challenges while stimulating innovation through developing new methods, tools and standards, and sharing its know-how with the Member States, the scientific community and international partners.

The Mission of the Joint Research Centre

Regulatory Science Framework for Nanomedicines and Biomaterials

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Science for a healthier life

Institute for Health and Consumer Protection

Regulatory Science Framework for Nanomedicines and Biomaterials

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● Alternatives to Animal Testing

● Food and Consumer Products

● Genetically Modified Organisms

● Public Health

● Nanotechnology

Policy Support Areas

Regulatory Science Framework for Nanomedicines and Biomaterials

Nanomaterials in food and consumer products

• Scientific and policy input for the development of the definition of nanomaterial (2011/696/EU, review in 2014)

Safety assessment of nanomaterials• bridge the gap: available scientific results vs. regulatory data needs• Standardized protocols for toxicity testing • OECD Working Party for Manufactured Nanomaterials

Provision of tools• Repository of Representative Nanomaterials for Testing• Databases on nanomaterial properties• Methods for detection and tracing• Validating of advanced analytical methods• Establishment of an infrastructure for the characterisation of

nanomedicines

Key activities

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State-of-the-art laboratories for analytical chemistry, toxicology, nanobiosciences and molecular biology

Facilities

Multidisciplinary team Regulatory Science Framework for Nanomedicines and Biomaterials

Technologies available for nanomedicine characterisation in the JRC

Methods  Dynamic light scattering DLSCentrifugal liquid sedimentation CLSField flow fractionation FFFPartical tracking analysis PTAAtomic force microscope AFMX-ray diffraction XRDSingle particle inductively coupled plasma-mass spectrometry ICP-MSSpecific surface area by nuclear magnetic resonance NMRHigh performance Liquid chromatography HPLCAnalytical ultracentrifugation AUCTransmission electron microscopy TEMScanning electron microscopy SEMScanning/transmission electron microscopy STEMAtomic force microscopy AFMFourier transform infrared spectroscopy FTIRGas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) GC/LC-MSUV-Visible Spectroscopy UVVISRaman spectroscopy

Competitive Research ProjectsPolicy Support – Strategic Research

MARINA Managing Risks of Nanomaterials

NANoREG A common European Approach to the Regulatory Testing of Nanomaterials

NANODEFINE Development of methods and standards supporting the implementation of the EC definition of nanomaterial (collaboration with IRMM)

NANOMILE Engineered nanomaterial mechanisms of interactions with living systems

SMART-Nano       Sensitive MeAsuRemenT, detection, and identification of engineered NANOparticles in complex matrices

EU-NCL European Nanomedicine Characterization Laboratory

10 Regulatory Science Framework for Nanomedicines and Biomaterials

Supporting the advancement of regulatory science in the area of nanomedicines by:

1. Providing technical/scientific expertise to policy makers, regulators and harmonisation/standardisation bodies e.g. International Pharmaceutical Regulators Forum by:

•Harmonisation of terminology and classification •Exchange and mapping of general Critical Quality Attributes in collaboration with the FDA and MHLW

2. Developing, optimising (of existing methods) and validating methods assessing quality and safety of products supporting the authorisation of urgently needed health care products

3. Investing in pre-standardisation and harmonisation efforts in nanotechnology

4. Partner in the EU-NCL project (Grant Agreement No 654190)

13 out of 16 national platforms presented their organisation incl. memberships as well as regional competences, national priorities and existing expertise/ infrastructures/ resources

Information exchange on the various funding policy initiatives and dialogues with the ministries and funding agencies about steps to be taken in order to improve R&D and translation of nanomedicine in the individual Member States

Sharing experiences on regulations in Europe as well as on the approval of clinical trials and authorisation of products

1st Workshop of the national nanomedicine platformsJune 2015

Regulatory Science Framework for Nanomedicines and Biomaterials

EU Nanomedicine Characterization Laboratory

(EU-NCL)

- the first European transnational infrastructure in nanomedicine-

On behalf of the consortium

European Union’s Horizon 2020 research and innovation program under grant agreement No 654190.

Regulatory Science Framework for assessment of risk-benefit ratio of Nanomedicines and BiomaterialsNMP14-2017

Our Mission

• To provide a trans-disciplinary testing infrastructure covering a comprehensive set of preclinical characterisation assays (physical, chemical, in-vitro and in-vivo biological testing) facilitating understanding of biodistribution, metabolism, pharmacokinetics, safety and immunological effects of Med-NPs.

• To foster the use and deployment of standard operating procedures (SOPs), benchmark materials, and quality management for the preclinical characterisation of Med-NPs.

• To promote inter-sectorial and inter-disciplinary communication among key drivers of innovation, especially between developers and regulatory agencieshttp://dev.eu-ncl.eu/

Regulatory Science Framework for Nanomedicines and Biomaterials

Who we are

Nano4Life 2015, Swansea, UKBiological in-vitro Biological in-vivo Quality

EU-NCL: a distributed infrastructure combining complementary expertise

Physico-chemistry

Our Objectives• To perform and standardize the pre-clinical characterization of nanomaterials intended for

medical therapies in Europe

• To accelerate translation of engineered nanoparticles for medicine applications to medicinal products

• To improve quality of data in IMP applications by using recognised and standardised methods

• To support product developer by addressing feedback of decision makers regarding nanospecific properties

• To identify and to characterize critical parameter related to nanomaterial interaction with biological systems

Nano4Life 2015, Swansea, UK

EU-NCL Concept

What will the EU-NCL offer

Nano4Life 2015, Swansea, UKRegulatory Science Framework for Nanomedicines and Biomaterials

How will EU-NCL work

Nano4Life 2015, Swansea, UKRegulatory Science Framework for Nanomedicines and Biomaterials

What can we provide• Access to a trans-disciplinary testing infrastructure allowing a detailed

nanocharacterisation; providing a final report on quality and safety of the tested material (→ First call for applications is expected for summer 2016)

• Standard operating procedures (SOPs) for the non-clinical characterisation of Med-NPs

• Knowledge base to be used by industry, regulators, product developer without reference to individual products (IP protection)

• To promote inter-sectorial and inter-disciplinary communication among key drivers of innovation, especially between nanomedicine developer and regulators

http://dev.eu-ncl.eu/ Regulatory Science Framework for Nanomedicines and Biomaterials

Contact detailsContact person Patrick BOISSEAU

Organisation MINATEC Campus

Adress 17 rue des martyrs, 38054 Grenoble , FRANCE

Phone nr

E-mail Patrick.boisseau@cea.fr

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Disclaimer: The opinions expressed in this presentation do not necessarily represent the official view of the European Commission

• Back-up slides

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Technologies available for nanomedicine characterisation in the JRC

Methods  Dynamic light scattering DLSCentrifugal liquid sedimentation CLSField flow fractionation FFFPartical tracking analysis PTAAtomic force microscope AFMX-ray diffraction XRDSingle particle inductively coupled plasma-mass spectrometry ICP-MS

Specific surface area by nuclear magnetic resonance NMRHigh performance Liquid chromatography HPLCAnalytical ultracentrifugation AUCTransmission electron microscopy TEMScanning electron microscopy SEMScanning/transmission electron microscopy STEMAtomic force microscopy AFMFourier transform infrared spectroscopy FTIRGas chromatography-mass spectrometry (GC/MS) and liquid chromatography-mass spectrometry (LC/MS) GC/LC-MS

UV-Visible Spectroscopy UVVISRaman spectroscopy

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EU Definition of NanomaterialsCommission Recommendation on the definition of nanomaterial (2011/696/EU, review in 2014)

• Scientific and policy input for the development of the definition

• Support to Commission services for the review of the definition scheduled for December 2014

• JRC Reference Reports

• Requirements for size measurement: capabilities of available methods

• Reliable and validated measurement methods

• Reference materials

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Principal customers:ENV, SANTE, GROW

Working Party for Manufactured Nanomaterials

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• Recommendation of the OECD Council on the Safety Testing and Assessment of Manufactured Nanomaterials

• Preparation, contribution, and chairing of Expert Workshops (Environmental Fate & Eco-Toxicology; Physical- Chemical Properties; Genotoxicity, Toxicokinetics, Categorisation, Read Across)

• 8 Test Guidelines or Guidance Documents project proposals to address specifically NMs

• Co-chairing of 3 Steering Groups

• "Testing Programme": JRC Reports on SiO2, TiO2, MWCNT, CeO2, ZnO Characterisation and Physico-Chemical Properties

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Regulatory challenges

• ‘Nanosimilars’ - evaluation of follow-on nanomedicine products– Step-wise comparability studies

• ‘Next generation’ nanomedicines– Advances in nanoscience leading to creation of more complex, hybrid structures– Wave of new pharmaceuticals, imaging agents

Unclear regulatory path– combination products – borderline products

Who we are (satellite labs)• University of Minho, PT• Adjuvatis, Lyon, FR• BIONAND, Malaga, SP• University of Bordeaux , FR• Brno University of

Technology, CZ• Charles University Prague, CZ• Ciber BBN, SP

Nano4Life 2015, Swansea, UK

• CyberNano, Nancy, FR• University Paris-Descartes, FR• FORTH Heraklion, GR• Institute of High Pressure

Physics , Warsaw, PL• INL, Braga, PT• RIVM, Bilthoven, NL• Swansea University, UK