lang tran (iom) · biorima has received funding from the european union’shorizon 2020 research...

BIORIMA has received funding from the European Union’s Horizon 2020 research and

innovation programme under grant agreement No 760928

RRI Case 2 from nanomedicine NMBP-12-2017 BIORIMA:

Development of a reliable methodology for better risk management of engineered biomaterials in Advanced Therapy Medicinal Products and/or

Medical Devices

Lang Tran (IOM)

BIORIMA has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 760928

BIORIMA - AIMSBIORIMA aims to develop an Integrated Risk Management (IRM) framework for NBM used in AdvancedTherapy Medicinal products (ATMP) and Medical Devices (MD).

The BIORIMA IRM framework is a structure upon which the validated tools and methods for materials,exposure, hazard and risk identification/assessment and management are allocated plus a rationale forselecting and using them to manage and reduce the risk for specific NBM used in ATMP and MD.

The BIORIMA IRM framework will be• Robust and readily applicable to past and current generations of NBM.• Flexible, in its modular construction, which can easily integrate new scientific results.• Beyond the state of the art for NBM safety by providing an encompassing and consistent framework

applicable to both NBM and ENM.

The BIORIMA IRM framework will consist of:• Validated methodologies and tools to identify the potential Exposure and Hazard posed by NBM to

humans and the environment.• Validated methodologies for an Intelligent Testing Strategy (ITS).• A Tiered Risk Assessment (TRA) for NBM used in ATMP and MD;• Risk Management strategies and systems for evaluating, monitoring and reducing the risks of NBM.

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BIORIMA FRAMEWORK

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Progression to the creation of the NBM Framework

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BIORIMA and WP Structure

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NANOPOWDER

NANOSOL

FREE: short nanostructural order

SCAFFOLD

LINKED to a MATRIX: long nanostructural order

Nano-forms(1-100 nm)

FIBERS

RODS, TUBES

PARTICLES

PASTE

Biomaterials(MD, ATMP, COMBINED)

WP2- Nanobiomaterials


WP3 Objectives

• Identify release and exposure scenarios for NBM

• Develop standardized methods for release measurements from NBM over the entire life cycle

• Develop exposure monitoring systems to address all steps in life cycle

• Assessment of environmental fate and exposure

• Development of methods for evaluating NBM release from implants


Summary of Work performed in Task 3.1

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• We have now a better understanding of the releaseroutes and exposure situations in critical steps in thelife cycle

• Underlaying mechanisms of release and exposurebeing characterized

• Tailored decision trees to support risk assessmentbased on release / exposure pathways

BIORIMA has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 760928Confidential 9

T3.5 Methods for assessing the release of NBM from implants into the body due to fracture/fatigue/tear• Task leader LEEDS, partners ITENE, CEA, IUTA, RSCI• Study the release of NBM from products during

the use phase• 2 classes of implants investigated:

– Knee and hip implants developed in FP7 NMP LongLifeJoints

– Scaffolds with minerals, e.g. hydroxyapatite

• Wear and biological effect testing based on new or existing ISO standards


WP4 Objectives

• Robust, inter-laboratory validated test methods for identification of potential adverse health effects ofmedicinal products and medical devices as well astest schemes to assess possible environmental effects

• Methods should be relevant for the intended use of the medical products or devices – taking into accountthe nature and duration of the contact of the NBMs (e.g. implantable devices versus acute administration)


Test materials

www.electrospinning.co.uk

• New materials – newchallenges: WP4 will evaluate the potential hazard of a panel of NBMs (refer to WP2) for human health and theenvironment – and wewill "test the tests" toaddress whether existingprotocols are applicableto NBMs (e.g., scaffolds)

http://www.electrospinning.co.uk/


WP4 Environmental Effects

• Ultimately “all” is released in the

environment, EoL

• All material´s life cycle stages

Folsomia candida

Cells

Fish

Eisenia fetida

Enhytraeus sp.

Microbial

Cells


WP5 Objectives

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To develop a human health and environmental Risk Assessment (RA) strategies for NBM used in ATMP and MD, based on Integrated Approaches to

Testing and Assessment (IATA) involving experimental and modelling tools for assessment of both hazard and exposure

To develop a strategy for Risk Management (RM) of NBM involving tools/methods for i) monitoring and controlling risks in occupational and environmental settings, ii) management of accidental risks including explosion and massive release, and iii) risk reduction/safety-by-design (SbD)

To combine the RA and the RM strategies into the BIORIMA Risk Management Framework (RMF) for NBM used in ATMP and MD

To establish the rationale for using the RMF by different stakeholders as the basis for developing a web-based Decision Support System (DSS) for risk management of NBM


WP5 tiered approach

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1. Conceptual RM framework based on contributions from Tasks

5.1-5.3 and delivered as a White Paper (M15) (in progress)

2. IATA structured as decision trees generated by Task 5.1; The

IATA decision trees are intended to guide users through

selecting the right tools for risk assessment of NBMs according

to regulatory requirements and will be delivered as a Guidance

Document (M36) (in progress)

3. Web-based DSS implementing the decision trees + risk

management functionalities in user-friendly manner (M48)


Conceptual RM framework – White Paper

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Conclusions

• BIORIMA – Mid Term in June 2019

• BIORIMA – First Stakeholder Meeting –Valencia November 2018.

• BIORIMA – Training Schools in Venice (2018 and 2019 and forthcoming -2020 )

• Input to OECD

• Input to Nano-governance projects

lang tran (iom) · biorima has received funding from the european union’shorizon 2020 research...

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