EUROPEAN COMMISSION DIRECTORATE GENERAL JOINT RESEARCH CENTRE Directorate D - Institute for Reference Materials and Measurements

Key Briefing

on

JRC's Activities on Reference Materials

Max Planck (Nov. 1941): "An experiment is a question which science poses to nature, and a

measurement is the recording of nature’s answer"

JRC-IRMM: Confidence in Measurements®

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Table of Contents

1 Introduction .................................................................................................................................... 3

2 Reference materials: Concepts and terminology ........................................................................... 4

3 Reference Materials at JRC ............................................................................................................. 6

3.1 Brief history ............................................................................................................................. 6

3.1.1 The beginning .................................................................................................................. 6

3.1.2 Enlargement of CRM portfolio – from CBNM to JRC-IRMM ............................................ 6

3.1.3 Handover of BCR CRMs to JRC-IRMM ............................................................................. 7

3.1.4 The evolution from BCR to IRMM and ERM CRMs .......................................................... 8

3.2 The JRC as reference material producer ................................................................................. 8

3.2.1 RM development and production process ...................................................................... 8

3.2.2 Related quality management ........................................................................................ 10

3.2.3 Collaborators and partnerships for RM production ...................................................... 11

3.2.4 RM customers ............................................................................................................... 12

3.3 The JRC involvement in RM standardisation and coordination ............................................ 14

3.3.1 Participation in related international committees ........................................................ 14

3.3.2 Knowledge transfer activities on RMs provided by the JRC .......................................... 15

3.4 JRC reference material production infrastructure and resources ........................................ 16

3.4.1 Staff ............................................................................................................................... 16

3.4.2 Budget ........................................................................................................................... 17

3.4.3 Infrastructure and laboratories ..................................................................................... 18

4 The intervention logic for the JRC activities on reference materials ............................................ 20

4.1 Legal considerations ............................................................................................................. 20

4.2 Economic considerations ...................................................................................................... 21

4.3 Intervention logic for production of RMs by the JRC ............................................................ 22

5 Positioning of JRC's activities on reference materials .................................................................. 24

5.1 JRC’s priority setting for the RM activities ............................................................................ 24

5.2 Food & feed reference materials .......................................................................................... 26

5.3 Health related reference materials ....................................................................................... 29

5.4 Environmental reference materials ...................................................................................... 31

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5.5 Engineering reference materials ........................................................................................... 34

5.6 Nuclear reference materials ................................................................................................. 36

6 Outlook into JRC's activities on reference materials .................................................................... 38

Annex .................................................................................................................................................... 41

Table A1: Food & feed CRMs released by JRC-IRMM in 2006-2015 ......................................... 42

Table A2: Food & feed RMs (non-certified) released by JRC-IRMM in 2006-2015 ................... 46

Table A3: Health diagnostic CRMs released by JRC-IRMM in 2006-2015 ................................. 51

Table A4: Environmental CRMs released by JRC-IRMM in 2006-2015 ..................................... 52

Table A5: Environmental RMs (non-certified) released by JRC-IRMM in 2006-2015 ............... 53

Table A6: Engineering CRMs released by JRC-IRMM in 2006-2015 .......................................... 54

Table A7: Engineering RMs (non-certified) released by JRC-IRMM in 2006-2015 .................... 57

Table A8: Nuclear CRMs released by JRC-IRMM in 2006-2015 ................................................ 58

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1 Introduction

The European Commission's Joint Research Centre (JRC) has a well-established capability for the

development and production of reference materials. It started with the Central Bureau of Nuclear

Measurements (CBNM) as part of the Commission's tasks under the Euratom Treaty signed in 1957

The CBNM located in Geel, Belgium, officially started its work in 1960. It changed its name in 1993

into the JRC-Institute for Reference Materials and Measurements (IRMM).

In 1973, the European Commission established a Community Bureau of Reference (Bureau

Communautaire de Référence - BCR) with the mandate to organise interlaboratory studies and to

certify reference materials using existing laboratories in the Member States. The programme was

supported by activities carried out at various JRC Institutes (Ispra, Petten and Geel). From 1987-

2002, the BCR became part of the research framework programmes of the European Community. In

1995, the JRC-IRMM took over the full responsibility for the management of the certified reference

materials (CRMs) released by the BCR, i.e. their storage, distribution and stability monitoring after

certification and the renewal of exhausted certified reference materials. BCR-related activities

outside the JRC were completely stopped at the end of 2002 following the closure of the Standards,

Measurements & Testing (SMT) programme of DG RTD.

Since the 1970s the JRC's portfolio of reference materials was enlarged from the nuclear area to the

fields of environment, food and feed, health diagnostics and key enabling technologies (KETs) such

as bio- and nanotechnology. Today, the JRC-IRMM offers about 800 different materials, available

under the BCR®, IRMM and ERM®1 brands of which about 100 materials are for nuclear safeguards.

The JRC is currently establishing a long-term strategy, which requires substantiation and a regular

update of the rationale and vision for the various fields in which the JRC is active. For this purpose,

the JRC is evaluating its activities in the area of reference materials, also in line with the

recommendation of the Ex-post Framework Programme 7 Evaluation that the JRC should conduct

dedicated sectorial evaluations.

This document is providing corresponding background information, facts and figures on JRC's

reference material activities during 2006-2015.

1 ERM is the registered trademark for European Reference Materials

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2 Reference materials: Concepts and terminology

Reference materials (RMs) play a crucial role in establishment and dissemination of metrological

traceability and further quality assurance, such as method validation, laboratory-internal quality

control and proficiency tests2. RMs are of particular importance when it comes to the measurements

of complex matrices such as environmental, food or clinical samples, but also for the

characterisation of functional properties of advanced materials.

There exists a multitude of different terms for reference materials required for various parts of the

measurement process, such as measurement standard, laboratory standard, reference standard,

analytical standard, reference substance, standard material, quality control material, proficiency

testing material, laboratory control material, or calibration material. However, they are all based on

the same scientific-technical concepts. In recent years, international understanding, harmonisation

and cooperation on reference materials have advanced globally, mainly to allow for the recognition

of measurement results across borders and to reduce technical barriers to trade.

In fact, there is a close relation between the intended use of a reference material in a given

measurement procedure and the required material characteristics. In this context, it should be

noted that the term 'Reference Material' is both used as generic, i.e. a family name for different

groups of such materials, and as a label for a sub-group. The current conceptual approach as

described in ISO Guides 30, 31, 33 and 34 is summarised in the following Figure 1.

Figure 1: Family of reference materials (QA/QC = Quality Assurance / Quality Control)

2 Specific type of interlaboratory comparisons, also called round robins or comparative testing

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In the following, the definitions set for RMs by ISO Guide 30:2015 are listed:

• Reference material (RM): "material, sufficiently homogenous and stable with respect to one

or more specified properties, which has been established to be fit for its intended use in a

measurement process".

• Certified reference material (CRM): "reference material (RM) characterized by a

metrologically valid procedure for one or more specified properties, accompanied by an RM

certificate that provides the value of the specified property, its associated uncertainty, and a

statement of metrological traceability".

Consequently, CRMs are a sub-group of RMs which come with additional characteristics and

information (see figure above). This qualifies CRMs to be also used for calibration (provided that the

knowledge of the property value is sufficiently precise for the specific purpose) and for checking the

trueness of measurement results in method validation and quality control. In this briefing, the other

RM sub-group is referred to as 'non-certified RMs' for clarity purposes.

It has to be noted that there is still some confusion in the literature and other communications

about the terminology regarding RMs and their classification. A major reason is that various aspects

are often mixed. In dependence on the intended use reference materials can be classified according

to their:

• Role in the measurement process

- calibrant/calibration material

- quality control material

- proficiency testing material

• Composition

- pure substances (and their solutions)

- matrix materials (complex materials such as blood or sediments)

• Tested/certified property

- presence/absence of a material component (e.g., chemical element, isotope, chemical

compound, physical particles)

- identity of a material component (e.g., DNA sequence, specified microorganism)

- concentration of a material component

- functional material property (e.g., hardness, enzyme activity)

• Application sector, e.g.

- food analysis

- environmental analysis

- nuclear safeguards measurements

- engineered material characterisation

- health diagnostics

In the following chapters the fundamental classification into certified and non-certified RMs will be

used, and the focus of JRC's RM activities on selected application sectors will be explained.

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3 Reference Materials at JRC

3.1 Brief history

3.1.1 The beginning

The JRC's Central Bureau of Nuclear Measurements (CBNM) officially started its activities in 1960 on

the grounds of the Belgian communities of Mol and Geel. The focus of the CBNM was on nuclear

measurements, particularly on nuclear reference data to support nuclear energy production. In

performing such measurements, special samples with relevant nuclides were needed. These first

reference samples were prepared and certified based on the needs of the CBNM scientists, and

subsequently on specifications required by the scientific community worldwide.

Consequently, sophisticated RM production techniques were developed and moreover, metrological

measurement capabilities became established at the CBNM. During 1963 to 1969, about 17 000

samples with users from 12 countries were prepared and certified. These samples could be seen as

the precursors of certified RMs, as produced today following established international guidelines.

The CBNM's first non-nuclear RMs were designed to support the special Eurisotop3 programme for

international interlaboratory comparisons. These RMs – for the determination of the oxygen content

in non-ferrous metals - were released in 1973, just before the European Commission set up the

Bureau Communautaire de Référence (BCR) service, which was dedicated to the certification of RMs.

In 1974, the Eurisotop certificates were changed into BCR certificates.

Consequently, the CBNM relabelled its first CRMs as BCR CRMs and they were stored and distributed

on behalf of the BCR. The CBNM, together with other JRC-Institutes at the sites of Ispra (Italy) and

Petten (The Netherlands) became increasingly involved in the certification activities of the BCR.

3.1.2 Enlargement of CRM portfolio – from CBNM to JRC-IRMM

In 1984, it was decided that all BCR CRMs stored until then in other European institutions that

participated in the BCR programme were to be centralised in and distributed from the CBNM in

Geel. Moreover, it was planned that the CBNM was to become the European Commission's support

laboratory for the BCR activities, particularly for the preparation of special materials, their storage,

and distribution.

As a result, a building dedicated for this purpose was established at the JRC-Geel site in 1986.

Significant investments were made in both storage facilities and processing equipment (clean cells,

jet mills, freeze dryers, etc.). The equipment was financially supported by the BCR programme.

Subsequently, all BCR CRMs were transferred to the CBNM, making it the reference centre for BCR

CRM customers.

3 The Eurisotop Office was created in 1960 as a division of Euratom to promote the use of nuclear techniques

in industry.

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Meanwhile, the CBNM started the preparation of materials for environmental monitoring and food

analysis, on behalf of not only the BCR programme, but also on request of other Directorates

General (DGs) of the European Commission, such as DG Agriculture as well as for external

customers. Together with the preparation of CRMs , the in-house expertise in measurements was

increased. This paved the way for the widening of CBNM's activities, from a nuclear focus to a

horizontal measurement Institute that was also reflected in the change of name: from CBNM to JRC-

IRMM (Institute for Reference Materials and Measurements) in 1993.

3.1.3 Handover of BCR CRMs to JRC-IRMM

The initial BCR programme underwent a continuous process of name-changing; from BCR to

Measurement and Testing (MT) to Standard, Measurement and Testing (SMT), but will be called for

simplicity BCR in the following. As the preparation of CRMs is not a short-term project, the BCR,

hosted by DG Research could no longer carry out the responsibility of managing its CRMs. The need

to co-ordinate the BCR activities with other RM related programmes had been mentioned in the

evaluation report of the indirect action programme 1975-19784.

Meanwhile, as the JRC-IRMM was well equipped with appropriate facilities and competences, it took

over in 1995 the full responsibility for the management of the BCR CRMs, including storage,

distribution and stability monitoring. The agreement between DG Research and the JRC included

that the JRC-IRMM would also be responsible for certifying new BCR CRMs in replacement of those

exhausted. As a consequence, the JRC-IRMM developed not only its storage and processing facilities

further, but also advanced the BCR certification approaches further. Moreover, the distribution of

CRMs to customers worldwide was increased by the nomination of 'authorised distributors',

operating under strict control of the JRC-IRMM regarding their storage and distribution conditions

for the CRMs.

New CRMs developed by the JRC-IRMM aiming to support the implementation of EU policies were

labelled as IRMM CRMs. The JRC-IRMM continued to develop and provide nuclear reference

materials in close consultation, coordination and cooperation with EURATOM safeguards authorities

and some key international nuclear agencies, like the French Atomic Energy and Alternative Energies

Commission (CEA), the International Atomic Energy Agency (IAEA), the United States Department of

Energy (US-DOE), the New Brunswick Laboratory (NBL) in the US and others worldwide.

In 2002, the BCR programme stopped altogether and since 2003, the tasks of development,

production and distribution of CRMs assigned by the European Commission are performed only by

the JRC-IRMM.

4 Commission of the European Communities, Research Evaluation-Report No. 3, EUR 7422 EN/FR

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3.1.4 The evolution from BCR to IRMM and ERM CRMs

In 1996, the JRC-IRMM signed a collaboration agreement with the International Federation of

Clinical Chemistry and Laboratory Medicine (IFCC), stipulating the development and production of

joint IRMM/IFCC CRMs, a privilege which so far had been restricted to the World Health

Organisation (WHO). When the labelling of genetically modified organisms (GMOs) became a

political issue, the JRC-IRMM began developing reference materials for GMOs in 1997 and was the

first institute worldwide to prepare and release such CRMs.

In addition to the CRM portfolio extension, the JRC-IRMM became more actively involved in new

concepts for RM certification, such as the inclusion of measurement uncertainties in accordance

with the Guide for Expression of Uncertainty in Measurement (GUM)5 and the estimation of

uncertainties related to homogeneity and stability statements in the certification process. Today,

these concepts are used worldwide and are mirrored in various guides published by the ISO

Committee on Reference Materials (ISO/REMCO).

Because of the enormous need for well-characterised CRMs at the internationally established quality

level, the JRC-IRMM joined forces with two other well recognised RM producers in Europe: the

German Federal Institute for Materials Research and Testing (BAM) and LGC Ltd in the UK. In 2003, a

Memorandum of Understanding marking the birth of European Reference Materials (ERM®) was

signed between the partners. They agreed on technical guidelines for CRMs to carry the trademark

ERM and assuring high-quality CRMs, prepared following ISO Guide 34. This ERM co-operation is

open for new members fulfilling the criteria as published (www.erm-crm.org).

3.2 The JRC as reference material producer

3.2.1 RM development and production process

The development and realisation of a new RM is a multistage process requiring a range of scientific-

technical and management competences. At JRC-IRMM each production of a (C)RM (non-certified

RM or certified RM) is managed as a separate project taking into account the main steps as

schematically shown in Figure 2.

5 ISO/IEC Guide 98-3 (1995) Uncertainty of measurement-part 3: guide to the expression of uncertainty in

measurement (GUM)

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Figure 2: RM development and production process at JRC-IRMM

After initial research to explore the required characteristics of a newly demanded RM, to identify

and develop techniques for homogenising and stabilising a potential starting material as well as

analytical methods to characterise the targeted material properties, it takes on average about 4

years from the planning to the release of the RM.

During the planning phase of a RM project the potential demand for this RM, the estimated costs

and the scientific-technical challenges are investigated. The staff members involved in a possible RM

project discuss in detail the design and specificities of each RM project. This planning phase may

involve feasibility studies to refine the planning. The project responsible summarises the information

in a Project Planning Form (PPF), which answers the most important questions, such as:

• In which type of analytical measurement shall the RM be used and what is it specific

function (e.g., quality control or calibration)? Is a certified reference material needed or can

a non-certified RM be used?

• What would be a suitable starting material for the RM (e.g., fish liver vs. whole fish vs. edible

part of a fish)? Are there any Intellectual Property Rights (IPRs) or personal data protection

needs (e.g., materials for clinical diagnostics) linked to the selected starting material? How

closely can or should the chosen starting material resemble a routine test sample?

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• What would be a suitable certified value (i.e. 1 % (m/m) GMO or 10 % (m/m)) taking into

account, e.g., threshold values in legislation?

• What is an acceptable uncertainty for a certified value, seen the repeatability of the routine

analytical techniques applied by the control laboratories (i.e., is it worthwhile and possible

to lower the uncertainty of the certified value)?

• How much time, staff and budget resources will be needed from the planning to the release

of the RM (what are the estimated costs for one unit of the RM)?

• Can measurement laboratories use other already available RMs? How many units of the RM

will most likely be needed per year and how many units should be produced (what is the

anticipated stability of the material)?

• What is the best processing technique to maintain the required characteristics of the RM?

Which impact does this have on the stability? What is a suitable containment for the RM?

What should be the size of an individual unit?

• Are there specific health and safety precautions which have to be taken into account (during

processing, characterisation, storage or shipment of the RM)?

With the approval of the project plan, a project responsible is assigned who coordinates the

necessary steps and actions in a RM project, from the sourcing of starting materials, via processing,

homogeneity and stability studies to the value assignment. The project responsible finally drafts the

documentation accompanying the RM after its release.

The documentation of the RM (certification report and certificate in case of a CRM, report and

material information sheet in case of a non-certified RM) is subjected to several internal and

external reviews. At least two JRC-IRMM experts, who are not involved in the specific RM project,

perform a comprehensive internal review.

The resulting draft is then reviewed by the corresponding Team Leader (the co-ordinator for the

scientific area concerned), the Quality Manager for ISO Guide 34 and in case of CRMs by a panel of

three external experts specialised for the parameters to be certified. Afterwards the revised draft is

reviewed and authorised for release by the JRC-IRMM co-ordinator for ISO Guide 34 activities. There

is an additional external review cycle by experts from the ERM partners in case of ERM branded

CRMs, concluded by the approval of the ERM Panel.

3.2.2 Related quality management

In order to fulfil its role as reference material producer the JRC-IRMM established a comprehensive

and transparent quality system according to the most advanced international standards. Since 2004

it is accredited to ISO Guide 34 which prescribes the required competences for RM producers (ISO

Guide 34:2009 - General requirements for the competence of reference material producers).

Analytical measurements performed in the frame of RM characterisation are carried out at JRC-

IRMM under ISO/IEC 17025 accreditation (ISO/IEC 17025:2005 - General requirements for the

competence of testing and calibration laboratories). Furthermore, the JRC-IRMM holds an

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accreditation as proficiency testing provider according to ISO/IEC 17043 (ISO/IEC 17043:2010 -

Conformity assessment - General requirements for proficiency testing). All staff involved in RM

activities is regularly trained on the corresponding procedures and qualified auditors of JRC-IRMM

perform annually the required internal audits. The follow-up is managed by JRC-IRMM's Quality

Group and the management. Besides the JRC-IRMM Quality Manager, who looks also to the

adherence to ISO/IEC 17025, there are appointed quality experts for technical issues of ISO Guide 34

and ISO/IEC 17043, respectively, as well as quality management co-ordinators at Head of Unit level

for the three standards.

JRC-IRMM's quality system is subject to regular audits of the Belgian accreditation body BELAC,

which has been employing international experts as technical auditors, as well as to the reviews of

the EURAMET Technical Committee on Quality.

3.2.3 Collaborators and partnerships for RM production

The (C)RM projects at JRC-IRMM are planned and executed mostly in form of JRC-led international

collaborative projects. They involve hundreds of expert laboratories all over the world which have

been on beforehand assessed for their scientific-technical competence for the envisaged task

according to the most recent international standards (ISO Guide 34, ISO/IEC 17025, ISO 15189 etc.).

As mentioned above, in 2003 the JRC has established a network of leading RM Producers in the EU

(ERM® – European Reference Material cooperation) for advancing the early-on coordination of RM

projects, sharing best practises and experiences and optimising the use of specialised competences.

Three major European reference materials producers, JRC-IRMM, BAM and LGC, have combined

forces to establish the ERM® brand. ERM® CRMs are materials which undergo uncompromising peer

evaluation and offer highest quality and reliability. They are distributed under the ERM® brand

which is a trademark owned by the European Union.

Moreover, the JRC-IRMM cooperates with other leading RM producers worldwide such as the US

National Institute for Standards and Technology (NIST), where a Co-operation Agreement was

established in 2007, the National Research Council (NRC) Canada, the Korea Research Institute of

Standards and Science (KRISS) and the National Measurement Institute of Australia (NMIA). These

strategic bilateral partnerships are used to avoid overlaps, exchange experiences and undertake

common (C)RM projects. They are also exploited periodically for getting access to complementary

capabilities.

A regular exchange of information on ongoing and just finalised (C)RM productions and production

experiences is also taking place at the annual meetings of the ISO Committee on Reference Materials

(ISO/REMCO), the Consultative Committee on Amount-of-Substance: Metrology in Chemistry and

Biology (CCQM) of the International Committee for Weights and Measures (CIPM), the Joint

Committee on Traceability in Laboratory Medicine (JCTLM), and the Versailles Project on Advanced

Materials and Standards (VAMAS), as well as at scientific conferences (e.g. BERM) and other publicly

open events.

In the nuclear field the main co-operations are laid down in respective cooperation agreements of

the European Commission or the JRC:

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• European Commission – IAEA Cooperative agreement from 1976; with a statement on

reinforcing cooperation between the IAEA and the European Commission in 2008;

• Collaboration Agreement CEA- JRC-IRMM for the development and production of a 243Am

CRM (2015-2018);

• Agreement between the US Department of Energy and the European Atomic Energy

Community represented by the European Commission in the field of Nuclear Material

Safeguards and Security Research and Development (2010); Action Sheet 43 for

Collaboration on CRM Development and Safeguards Measurement Quality Assurance;

• JRC framework sales contract with Japan Nuclear Fuel Limited (JNFL);

• JRC - Japan Atomic Energy Agency (JAEA) collaboration agreement in the field of Nuclear

Safeguards, Security and Non-Proliferation (1990).

3.2.4 RM customers

There are currently about 800 different CRMs available from JRC-IRMM (catalogue available at

https://ec.europa.eu/jrc/en/reference-materials/catalogue) of which about 21 000 units are

distributed per year by the JRC and its five authorised distributors. The latter distributed 60 % of the

samples in 2015. A summary on the number of distributed CRM units is provided in Figure 3.

Figure 3: Number of CRMs distributed by JRC-IRMM and its authorised distributors in 2006-2015

Figure 4 shows that the RM customers are located all over the world as illustrated by the

geographical distribution for the ones which have ordered CRMs directly from JRC-IRMM in 2015.

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Figure 4: Geographic location of customers who have ordered non-nuclear CRMs directly

from JRC-IRMM in 2015

Structured customer feedback is sought via regular customer satisfaction surveys, and the results

are considered in the planning and execution of RM activities.

In 2015, the largest number of distributed CRMs was for food/feed safety and quality control

including genetically modified organisms (GMOs), followed by healthcare diagnostics, engineering

(advanced) materials including nanomaterials and CRMs for environmental analysis.

Figure 5: Application fields for JRC-IRMM's CRMs distributed in 2015

Approximately 340 CRMs are currently distributed under the BCR brand, mostly originating from the

BCR and SMT programmes of the European Commission. About 255 materials are distributed under

the ERM brand and about 200 materials under the IRMM brand. The contribution of units from

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CRMs released since 2006 on the number of distributed CRM units was 58 % in 2015 as outlined in

Figure 6.

Figure 6: Legacy of CRMs distributed in 20156

More detailed information on the development and application sectors of JRC's RMs is given in the

Chapter 5.

3.3 The JRC involvement in RM standardisation and coordination

3.3.1 Participation in related international committees

As already mentioned in Chapter 3.1, the JRC-IRMM work on RMs is performed in collaboration with

institutions and scientific organisations worldwide. This concerns not only the development and

production of specific RMs, but also the advancement of a common understanding of underlying

scientific-technical concepts and approaches, as well as the development and agreement of

terminology and RM-related documentary standards.

Consequently, the JRC is represented on selected committees and working groups of relevant

international organisations. In recent years, the JRC has been increasingly requested as coordinator

and facilitator of discussions and consensus-building activities in such international communities.

These include not only international standardisation organisations such as ISO and CEN (European

Committee for Standardization) but also the Codex Alimentarius, AOAC International and the Clinical

and Laboratory Standards Institute (CLSI). Moreover, the JRC-IRMM is strongly interlinked with

6 CRMs released before 2003: mainly from BCR/SMT projects; 2003-2006: Transition period, where JRC-IRMM finalised

quite some BCR/SMT projects; since 2006: CRMs planned, developed and produced by JRC-IRMM

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metrology organisations (EURAMET and CIPM), pre-normative bodies such as the Versailles Project

on Advanced Materials and Standards (VAMAS) and the International Federation of Clinical

Chemistry and Laboratory Medicine (IFCC). In this frame, the JRC has also contributed to the shaping

of the strategies and work programmes of such international organisations in the areas of

metrology, standardisation, and pre-normative research.

An example is the JRC work in the ISO Committee on Reference Materials (ISO/REMCO). During the

period 2006-2015, the committee developed new international guides for reference materials and

revised all of its existing guides with major input from the JRC. Experts from JRC-IRMM acted as Vice

Chair (2006-2008), Chair (2009-2014), and convenors of ISO/REMCO working groups on 'competence

of RM producers', 'RM distribution and transport', and 'RMs for qualitative properties'. Since 2014, a

JRC-IRMM expert is chairing the Joint Working Group 43 of ISO/REMCO and the ISO Committee on

Conformity Assessment (CASCO) which is tasked with the transformation of ISO Guide 34:2009 into

an international standard ISO 17034. The JRC-IRMM also closely collaborates in the revision of

ISO/IEC 17025, e.g. for interlinking it with ISO 17034.

Moreover, the international harmonisation of RM-related concepts, as well as quality and

assessment criteria is included in JRC co-operations with:

− the European Committee for Standardisation (CEN);

− the European Directorate for the Quality of Medicines (EDQM);

− the International Atomic Energy Agency (IAEA);

− the Commission for the Establishment of Analytical Methods (CEA/CETAMA) that resides

within the French Atomic Energy and Alternative Energies Commission (CEA);

− the US-DOE- New Brunswick Laboratory (NBL);

− the Joint Committee on Traceability in Laboratory Medicine (JCTLM).

3.3.2 Knowledge transfer activities on RMs provided by the JRC

Since 2004, the JRC is organising a training course entitled 'Use of Reference Materials and the

Estimation of Measurement Uncertainty'. It is targeting laboratory managers and practitioners in

analytical laboratories, as well as auditors of accreditation bodies who need to assess the estimation

of measurement uncertainties and the correct selection and application of RMs. This course strongly

emphasises the practical application of theoretical concepts and each lecture is accompanied by

exercises in small groups supported by a trainer. During 2006-2015, there have been 283 external

participants from all over the world including regular attendance from the European Commission's

DG Energy (European Nuclear Safeguards) and EDQM (European Pharmacopeia).

The development and use of nuclear RMs is part of the ESARDA course syllabus on Nuclear

Safeguards and Non-Proliferation under quality control and confidence in analytical measurement

results7. Furthermore, training in the preparation of nuclear RMs is given by the JRC in cooperation

7 Nuclear Safeguards and Non-proliferation, Course Syllabus, Editor G. Janssens-Maenhout; Working Group on

Training and Knowledge Management Hosted by the Joint Research Centre, December 2008

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with EURATOM, the IAEA, CEA/CETAMA and the US-DOE under Joint Outreach and Training on

Nuclear Safeguards.

Major training and knowledge transfer activities on RMs were performed in the frame of a three-

year capacity building programme for Turkey by JRC-IRMM in 2009-2012. This included long-term

training stays of Turkish scientists in Geel, dedicated workshops and project planning support in

Turkey, as well as support for the establishment of RM production facilities and the corresponding

quality management system at the Turkish National Metrology Institute UME.

3.4 JRC reference material production infrastructure and resources

3.4.1 Staff

The scientific-technical staff working on RM activities at JRC-IRMM is multidisciplinary with

competencies in analytical chemistry and bioanalysis, biology, pharmacy, biochemistry,

microbiology, life sciences, food chemistry and technology, material sciences, engineering, physical

chemistry, radiochemistry and nuclear sciences. The already highly qualified JRC staff is further

internally trained on the most advanced knowledge on metrological aspects, RM production,

standardisation and corresponding quality management, hence, specific and cutting-edge education

and training that are not available externally. Moreover, a systematic training programme for

continuous improvements is designed and executed for all staff on an annual basis.

The staff of JRC-IRMM which has been involved in RM development and production activities is

summarised in the following table:

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Table 1: Number of JRC-IRMM staff involved in RM activities

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

non-nuclear RM activities

Permanent scientists8 19 20 22 21 21 20 21 20 21 20

Permanent technical

support staff8

24 26 24 23 20 20 23 22 20 22

Temporary staff

(mainly Postdoc scientists)

16 19 19 21 27 22 22 19 19 13

nuclear RM activities

Permanent scientists 2 2 2 2 1 1.5 2.5 2.5 2.5 2

Permanent technical

support staff 5 5 3.5 5 5 4.5 5 5 6 5

Temporary staff

(mainly Postdoc scientists) 0.5 1 1 0.5 0.5 1.5 2.5 2.5 3 2

It should be noted that the table includes 6 staff (1 scientist, 4 permanent technical/administrative

support staff, 1 temporary support staff), who are in charge of the storage, distribution and post-

certification monitoring for non-nuclear RMs, and that a reduction of 5 staff during 2016 is already

announced.

3.4.2 Budget

In addition to the staff costs, the budget for JRC-IRMM's activities on RMs is composed of three main

components:

− JRC institutional budget (so-called 'specific credits') from the Framework Programmes (FP)

on Research and Technology Development of the European Commission;

− JRC institutional budget (specific credits) from the EURATOM Programme;

− Additional income from the distribution of reference materials.

An overview on the RM-related specific credits from FP 7 and Horizon 2020, respectively, during

2006-2015 is provided in the following table.

8 Staff number given as 'head counts' and not as full time equivalents (FTE)

18

Table 2: Institutional JRC budget attributed to RM activities

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Specific credits/FP

(kEUR)

1850 2002 1761 1838 1971 2188 2200 2170 2200 2236

Specific credits/EURATOM

(kEUR)

252 242 270 464 590 530 350 363 363 364

The additional income generated by the distribution of CRMs is shown in Figure 7.

Figure 7: Additional income generated from the distribution of CRMs

Moreover, the JRC participated to a very limited extent in collaborative projects funded in the

context of the Framework Programmes (FP 7, Horizon 2020) or the Article 185 initiative 'European

Metrology Research Programme' (EMRP) which aimed, among other goals, also to study the

feasibility to develop a few selected new RMs. The RM-related additional income from those

projects was about EUR 1 million during 2006-2015.

3.4.3 Infrastructure and laboratories

The JRC's RM activities are carried out in state-of-the-art laboratory facilities including various

analytical laboratories (trace element analysis, organic analysis, nucleic acid analysis, protein

analysis, microbiological and pathogen analysis and engineering material analysis) and unique

processing facilities for the necessary manipulation and manufacturing of the wide range of liquid

and solid materials. A dedicated Reference Material Production Building hosts the majority of the

RM processing activities, and recent refurbishments of the nucleic acid analysis and organic analysis

laboratories have ensured that JRC's laboratory facilities are state-of-the-art.

The JRC laboratories focus on specific tasks for which either no external expert contractor can be

found (e.g. for specialised R&D tasks, new and/or unique processing procedures, certain high-

19

accuracy measurements), which are time-critical (e.g. processing controls) or which have to be

performed in-house because of contractual constraints (e.g. Intellectual Property Right (IPR) issues in

GMO CRM projects).

Overall, the vast majority of technical tasks for RM projects are currently outsourced, particularly the

sampling of the starting materials, most homogeneity and stability measurements, and

interlaboratory studies for RM characterisation. However, the limitations for outsourcing have

increased in recent years as, for instance, external pilot processing facilities were diminished in

various industrial branches, or external laboratories tend to deliver routine measurement services at

an insufficient performance level for RM projects. Therefore, the appropriate balance between own

and outsourced tasks has to be found for each RM project, taking into account the necessary quality

criteria for the final product with sufficient control over critical steps in the process and the

corresponding international standards for RM producers.

The development of nuclear CRMs is exclusively carried out in the JRC-IRMM's nuclear chemistry and

nuclear mass spectrometry laboratories. These nuclear -controlled area laboratories are providing,

together with a clean laboratory area, the necessary infrastructure to carry out in a safe and secure

manner actinide chemical separation, accurate weighing of actinides, mass spectrometric analysis of

actinide samples ranging from nuclear fuel material to the low environmental level, computerised

automated dispensing of actinide solutions, and production of actinide reference particles.

JRC-IRMM has a storage building dedicated to its reference materials. It has compartments and

equipment to store materials at temperatures from -70 oC to +18 oC at controlled humidity. Some

(C)RMs are even stored at -190 oC in special containers. The building also hosts the distribution

activities for non-nuclear RMs, which are shipped via contracted courier services. The nuclear CRMs

are separately stored in JRC-IRMM's nuclear zone and are distributed directly from the JRC-IRMM to

customers.

20

4 The intervention logic for the JRC activities on reference materials

4.1 Legal considerations

Standards and reliable measurements are essential to verify that products and services comply with

legislation that has been put in place to protect consumers, citizens and the environment by

minimising the exposure to risks and ensuring their safety. They are also of relevance for regulations

for preventing fraud and putting in place of conditions for trade and taxation require monitoring by

measurements.

The analysis of the EUR-LEX database of the European Union (EU) revealed that around 3500 EU

legislative acts make reference to standardisation, including 20 % of all Directives. The role of

standardisation shall also remain high on the policy agenda. In his Political Guidelines published in

July 2014, the President of the European Commission Juncker stated: "Jobs, growth and investment

will only return to Europe if we create the right regulatory environment and promote a climate of

entrepreneurship and job creation" and further "we should ensure that Europe maintains its global

leadership in strategic sectors with high-value jobs". To accelerate EU growth, industries need

framework conditions that provide them with the basis upon which to invest, to innovate and to

gain global market share in an increasingly competitive world. Standards are a cornerstone of these

conditions and are an integral part of Horizon 2020, the EU Framework Programme for Research and

Innovation.

It is widely accepted that roughly 50 % of legislation globally involves measurements that are often

technologically cutting-edge and in most cases comparative. Their correct application and

interpretation require state-of-the-art knowledge and equipment. This role is performed by the so-

called infrastructure technologies that provide, among others, quality assurance, production control

and market acceptance. RMs, being a member of the infrastructure-technology family, play a pivotal

role in assuring accuracy and traceability of measurement results, thus of their comparability. In this

case, RMs provide a bridge between the legal requirements and the market reality.

Although not explicitly mentioning the term 'RMs', the following articles relating to the Treaty on

Functioning of the European Union (TFEU)9 are a solid base for establishing a common European and

comparable measurement framework for the effective implementation and operation of the internal

market:

• Article 26: The Union shall adopt measures with the aim of establishing or ensuring the

functioning of the internal market.

• Article 114: […] adopt the measures for the approximation of the provisions laid down by

law […] which have as their object the establishment and functioning of the internal market.

• Article 179: […] the Union shall […] (enable) undertakings to exploit the internal market

potential to the full, […] (by) the definition of common standards […].

The importance of measurements in nuclear safety, security and safeguards was clearly recognised

and enshrined in Article 8 of the Euratom Treaty:

9 Consolidated version of the Treaty on the functioning of the European Union, OJ C326/47 (2012)

21

• […] It shall also ensure that a uniform nuclear terminology and a standard system of

measurements are established. It shall set up a central bureau for nuclear measurements10.

Moreover, Chapter VII of the Euratom Treaty tasks the European Commission with the control of all

civil fissile nuclear material in the European Union. The JRC-IRMM is responsible in fulfilling this legal

obligation in nuclear standards and measurements supporting Commission Regulation (Euratom)

302/2005 on the application of Euratom safeguards.

A strong regulatory push has been initiated by Regulation (EC) No 765/2008 setting out the

requirements for accreditation and market surveillance relating to the marketing of products:

• […] This Regulation provides a framework for the market surveillance of products to ensure

that those products fulfil requirements providing a high level of protection of public

interests, such as health and safety in general, health and safety at the workplace, the

protection of consumers, protection of the environment and security […]

• […] this Regulation on accreditation should apply to bodies carrying out conformity

assessments in both the regulated and the non-regulated areas. The issue at stake is the

quality of certificates and test reports […]

Therein, the need for using (C)RMs by control laboratories is mandated via their required

accreditation to international standards such as ISO/IEC 17025. Consequently, one of the JRC's key

competences listed in the Regulation establishing the EU Framework Programme for Research and

Innovation Horizon 202011 is RMs for supporting the implementation and monitoring of legal

requirements (see also Chapter 5).

4.2 Economic considerations

The basic economic logic behind public investment in R&D is market failure, especially on

infrastructure technologies. Private companies expect a certain return on investment which is

difficult to realise in a changing legal environment. Legislation is often technically complicated to

implement and changes sometimes relatively fast. For instance, environmental EU policy comprises

more than 500 legislative acts and includes pollution limits which are regularly updated.

Moreover, infrastructure technologies contribute to all three stages of economic activities (R&D,

production and commercialisation)12. As a result, they are broader in reach than market strategies of

companies. Consequently, there is a disincentive investing in them, as companies focus their efforts

on proprietary technologies (applied R&D).

10

As mentioned in Chapter 1, this led to the establishment of the CBNM now JRC-IRMM. 11

Annex II of Regulation (EU) No 1291/2013 establishing Horizon 2020 – the Framework Programme for

Research and Innovation, OJ C74E (2012) 12

Tassey, G., Modelling and Measuring the Economic Roles of Technology Infrastructure, NIST (2007)

22

A high technological risk and uncertainty is also closely linked to the development of new RMs which

hampers their marketing and commercialisation. Faced with long development time and lack of

significant cash flow during the process, private companies are reluctant to enter such a market. In

particular, the production of matrix RMs (representing real-life materials) requires substantial

interdisciplinary research and knowledge, from basic science and engineering to technologies. This

prevents making the production of specifically complex matrix based RMs a profitable business.

Furthermore, companies focus on the private rate of return (PRR) and infrastructure technologies

are best understood by social rate of return (SRR) – both rates being different in value and logic. In

general infrastructure technologies, supporting the economy, such as physical infrastructure (roads,

bridges, etc.), are seen as public goods which provide the framework for new and possibly disruptive

products, services and processes. They have the potential for a very high SRR and conversely, a low

PRR. A typical example are measurement standards (e.g., CRMs for calibration), which yield

significant benefits to society but are developed in a transparent process which cannot occur under

intellectual property (IP) protection. Therefore, a strong "free-rider" element occurs that

discourages private companies from investing adequately in developing infrastructure technology.

Consequently these technologies, and (C)RMs in particular, will predominantly be publicly funded.

4.3 Intervention logic for production of RMs by the JRC

The legal and economic constraints from the above clearly point to the need for public intervention

in the production of (C)RMs. The logical question then is why JRC-IRMM?

The JRC's RM activities draw on its competencies and infrastructure in analytical (measurement)

sciences applied in chemistry, biology and life sciences, material sciences and nuclear sciences.

Moreover, generic understanding of the international standardisation processes and quality

infrastructures is fundamental for translating policy and market needs into RM projects and RM

related deliverables with a high impact.

As outlined in Chapter 2, the JRC-IRMM steadily grew in its role of developing and producing RMs,

starting with nuclear RMs and covering to-date a broader range of materials. JRC's RM activities

respond to EU policy needs, covering wide areas such as environmental protection, industrial

competitiveness, food safety, consumer protection, citizen's health and nuclear security. These are

all shared competences between the EU and the Member States in which the subsidiarity principle

applies. It is hard to imagine a national body, maintaining a broad spectrum of knowledge and

infrastructure that addresses pan-European issues that mostly target the EU single market. The JRC-

IRMM, with its history of scientific excellence and second-to-none infrastructure, supports industrial

competitiveness, quality of life, safety and security in the EU by providing trustworthy measurement

standards and quality tools vital for technology development, innovation and market acceptance in

the frame of the EU single market.

23

The JRC demonstrated its ability to react efficiently to supranational crises (e.g. BSE) and to

effectively execute diverse CRM projects (e.g. a world leader in GMO CRMs, provider of crucial

healthcare biomarker CRMs, etc.). This enables the JRC to be a reliable partner of the European

Commission's policy DGs and international institutions and organisations. The considerations for

JRC's intervention in the area of RM development and production is visualised in Figure 8 and is

further outlined in Chapter 5.

Figure 8: JRC's reasoning for RM activities

24

5 Positioning of JRC's activities on reference materials

5.1 JRC’s priority setting for the RM activities

In positioning of the JRC as an internationally trusted and reliable provider of (C)RMs enabling and

supporting measurements required for the implementation and monitoring of EU policies, the

following aspects are (and should be further) applied:

• EU policy alignment - Alignment of JRC's RM activities with the tasks of the JRC, which are

derived from societal challenges and policy priorities of other Commission DGs.

• Legislation requiring RMs - Forecasting of required RM activities for the implementation and

monitoring of EU legislation. This takes into account the fact that demands for use of RMs

are often expressed in legislative documents in an indirect manner, e.g. via the prerequisite

for control laboratories or proficiency testing providers to be accredited according to ISO/IEC

17025 and ISO/IEC 17043, respectively, or to follow the principles of these standards.

• Avoiding duplication - Exploiting further the regular dialogues with other major RM

producers, in particular with institutes receiving public funding, to avoid duplication of

efforts as much as possible and to exchange best-practice information.

• Networking – Maintaining and strategically developing networks of external experts for

sharing knowledge on new developments, using complementary competences and

collaborating on RM projects.

Criteria for the selection and prioritisation of RM projects at JRC-IRMM are based on the needs,

requests, policy relevance and non-availability of an RM from other producers as outlined in Figure

9. The decision for a replacement of a highly demanded CRM is taken using the same selection and

prioritisation criteria as for other RM projects.

Figure 9: Criteria for selection and prioritisation of RMs to be developed by the JRC

25

Today, as a consequence of the EU policy needs and the worldwide RM supply activities, the JRC

focuses to a large extent on the design, development and provision of complex (so-called 'matrix')

RMs. This means that naturally occurring biological or environmental materials or man-made

products (e.g., foodstuff, advanced materials) of complex composition/structure are mainly used as

starting materials. They often demand the development and application of highly project-specific

metrological concepts for establishing traceability of certified values as well as advanced

technological capabilities for further material processing. The JRC’s projects for entirely new RMs

focus on scientifically cutting-edge materials with newly certified value/matrix combinations and

material properties closely and feasibly match real-world samples tested in routine control

laboratories. Priority is given to those scientific-technical developments which require

interdisciplinary competences and approaches as this has proven to allow exploiting synergies and

maximizing the JRC's impact as well as saving staff resources.

The other major drivers of JRC's RM activities are located within and outside the European

Commission. Several services in the policy DGs are cooperating with the JRC in the formulation

phase of new EU legislation, whereas most requests are derived from the technical implementation

stage or after detecting compliance problems with existing EU regulations.

More major drivers of RM activities are networks of official control laboratories in the Member

States, such as the National Reference Laboratories (NRLs) co-ordinated by a EU-Reference

Laboratory (EURL), Network Laboratories in nuclear safeguards and security, EU Agencies,

standardisation and accreditation bodies, and needs of EU market participants in complying with EU

regulations (e.g. inventors of Genetically Modified Organisms (GMO), In-Vitro-Diagnostics (IVD)

industry).

The JRC-IRMM aims to serve these bodies in situations where RMs are not available from other

reliable sources. Consequently, close information exchange and cooperation with European

standardisation, metrology and accreditation organisations, including their global counterparts as

well as application sector-specific organisations are crucial. To optimise its services and prioritise its

RM activities, JRC-IRMM explores the strategies of its customers and collaborators, engages in

regular pro-active dialogues with them, has discussions with international bodies and networks on

future needs, runs dedicated customer surveys, and implements the results thereof. During the last

years, about 30 newly produced CRMs were released annually by the JRC as shown in Figure 10:

26

Figure 10: Number of CRMs finalised and released in 2006- 2015 by the JRC

5.2 Food & feed reference materials

The intervention logic for the development and production of RMs for food and feed is summarised

in Figure 11.

Figure 11: Intervention logic for food and feed RMs

Food and feed legislation

Regulation (EC) No 882/2004 demands that official controls are carried out by the Member States to

check compliance of food and feed, following the provisions of the related EU laws. Furthermore, it

establishes European Union Reference Laboratories (EURLs), which shall provide (reference)

methods to the National Reference Laboratories (NRLs) and check the measurement capabilities of

the NRLs by organising proficiency tests on a regular basis. Official food and feed control laboratories

0

10

20

30

40

50

60

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

Nu

mb

er

of

ne

w m

ate

ria

ls r

ele

ase

d

YearNon-nuclear materials Nuclear materials

Mandate (EC) No 882/2004 Official control, EURLs, NRLs (EC) No 1981/2006 Accreditation to ISO/IEC 17025 and ISO/IEC 17043: use of RMs e.g. (EC) No 1829/2003, (EC) No 619/2011: RM availability mandatory

Deliverables RMs for proficiency testing of laboratories RMs for method developments in CEN standardisation and EU projects (C)RMs for implementation of EU legislation

Impact Enabling implement-ation of EU legislation Setting up reliable measurement systems for operationally defined parameters Enabling & proving measurement capabilities of Member States' laboratories Enabling standardised methods (CEN, ISO) Ensuring food/feed quality and safety

Activities Development and production of (C)RMs Underpinning research Method development & validation for RM processing and characterisation Distribution of (C)RMs User guidance & training Standardisation

27

shall be accredited according to ISO/IEC 17025:2005, which demands the use of (certified) reference

materials for calibration and quality assurance.

EU legislation related to the methods of sampling and analysis of certain contaminants in food and

feed specifically requires the use of CRMs, where available. It concerns especially mycotoxins

(Regulation (EC) No 401/2006), dioxins and dioxin-like PCBs (Regulation (EC) No 1883/2006), and

lead, cadmium, mercury, inorganic tin, 3-monochlor-propanediol and polycyclic aromatic

hydrocarbons (Regulation (EC) No 333/2007).

Wines produced in the EU have an important market share in the global market and their quality is

of prime importance to maintain their reputation. To check whether sugar has been added to

fermenting must and/or wine has been watered, the International Organisation of Vine and Wine

(OIV) validated methods based on isotopic measurements of wine ethanol and wine water. The OIV

method for measuring the 13C/12C ratio of wine ethanol by isotope ratio mass spectrometry

mandates the use of CRMs (namely BCR-656 Wine alcohol, BCR-657 Glucose, CRM-660

Hydroalcoholic solution); the method for the determination of the deuterium distribution in ethanol

by nuclear magnetic resonance requires the use of the CRMs BCR-123 (Ethanol) and STA-003

(Tetramethylurea). The use of those OIV methods for the official control of wine in the EU is

obligatory (Regulation (EC) No 2676/90).

At the global level the Procedural Manual of the FAO/WHO Codex Alimentarius, which details the

rules on methods of analysis to be fulfilled for settling disputes, also requires the use of CRMs,

where available, for checking trueness of an analytical method.

GMO legislation

EU legislation regulates the placing on the market of food and feed which consists of, contains, or is

produced from genetically modified organisms (GMOs). These items are referred to as genetically

modified (GM) food and feed and require authorisation. According to Regulation (EC) No 1829/2003

food and feed products need to be labelled if they contain more than 0.9 % of GMOs. The EC

Recommendation (EC) No 787/2004/EC focussing on sampling and detection of GMOs in food and

feed had suggested to expressing measurements results in DNA copy number ratios. Since the

implementation of Regulation (EC) No 619/2011, a feed may contain 0.1 (m/m) % of a GMO for

which an authorisation process is pending, or for which authorisation in the EU has expired.

Furthermore, this regulation clarified in 2011 that measurement results should be expressed in GMO

mass fractions.

The authorisation of GM food and feed for the EU market requires explicitly the availability of GMO

RMs. They are needed for calibration and quality control of GMO measurements in the

implementation of the GMO labelling thresholds. JRC-IRMM developed and released the worldwide

first GMO CRMs based on gravimetrically prepared mixtures, certified for their GMO mass fraction.

As the EU Recommendation mentioned above had for some years suggested the need to express

GMO measurement results in DNA copy number ratios, JRC-IRMM developed a scientific concept for

implementing this different measurement unit in GMO quantification. For this purpose several GMO

CRMs were additionally characterised and certified for their DNA copy number ratio and specific

separate CRMs, based on designed DNA fragments, which were developed and released for the

28

calibration of the measurements. While the legal interpretation of GMO labelling thresholds

reverted to mass fractions, also the concept of suitable sets of GMO CRMs was also developed

further by JRC-IRMM and accepted internationally. Today, a pure GMO CRM is used by many

laboratories for calibration and different mixtures of GMO blank and GMO pure materials, certified

for their GMO mass fraction, primarily serve the implementation of (EC) No 619/2011 and (EC) No

1829/2003.

The biological species which are authorised in the EU as food and feed products increase constantly.

While the first GMOs were maize and soya, JRC-IRMM had to invest in the development of

processing techniques for other challenging species, such as sugar beet and potato (high sugar and

starch content, respectively) or cotton seed and rapeseed (high fat content). Besides these

challenges for the processing of GMO starting materials, the type of CRMs was in some cases

adjusted to the sampling and analysis techniques applied. For instance, the control of the correct

labelling of sugar is carried out on the sugar beets and not on the final food product. A similar

situation exists for potatoes. Therefore, instead of mixtures, a blank material and a pure GMO CRM

have been produced, thus focussing the characterisation and certification on the GMO identity.

During the period 2006-2015, JRC-IRMM has distributed on average about 7000 units of GMO CRMs

annually. The larger fraction of these CRMs is used in Europe (Figure 12), but a considerable amount

is also used in third countries to facilitate trade with the EU. So far JRC-IRMM developed and

released about half of the various GMO CRMs required for the EU market authorisation of a GMO

event as food or feed product.

Figure 12: Geographic distribution of customers ordering GMO CRMs from JRC-IRMM

An overview of all certified and non-certified food and feed reference materials which have been

released by JRC-IRMM in 2006-2015 is provided in Tables A1 and A2 in the Annex.

It should be noted that there are several unique RMs among the ones listed in the annexed Table A2.

For example the BSE RMs, which had been developed based on a concept created in co-operation

29

with Nobel Laureat S. Prusiner, were provided for the quality control of BSE testing by the

corresponding official control laboratories in the EU Member States.

5.3 Health related reference materials

The intervention logic for the development and production of RMs for health diagnostics is

summarised in Figure 13.

Figure 13: Intervention logic for health related RMs

The societal and economic challenges and consequences of citizen's health and healthcare are

tremendous. Improving the reliability of medical diagnostics has impacts on the efficiency of

diagnosis, therapy (improved medical guidelines, personalised medicine, pharmacokinetic/genetic

assessment of new and existing drugs) and the economy of healthcare systems. Moreover, it is

increasingly recognised that the majority of data from biomedical studies cannot be qualified as

'reproducible'. In fact, the quality of rapidly developing diagnostics techniques, particularly in

molecular biology, has so far not been sufficiently addressed. Reliable and thus comparable medical

measurement data are required for assessing the performance and limitations of current and new

diagnostic methods under realistic conditions. Corresponding standardisation efforts are of benefit

to patients, industry and society.

Therefore, EU Directive 98/79/EC on in-vitro diagnostic (IVD) medical devices demands that "[…] the

traceability of values assigned to calibrators and/or control materials must be assured through

Mandate

Directive 98/79/EC: Traceability to be established with CRMs EU Programme for Research and Innovation Horizon 2020

Deliverables

CRMs for implementation of EU legislation CRMs as globally recognised (JCTLM) calibrants of higher order Documentary standards as EU harmonised standards

Impact

Enabling implement-ation of EU legislation Setting up reliable measurement systems for health biomarkers Enabling IVD manufacturers to establish traceability for IVDs Enabling comparable health diagnostics data worldwide Saving healthcare costs and enabling medication developments

Activities

Development and production of CRMs Underpinning research Method development & validation for RM processing and characterisation Distribution of CRMs User guidance & training Standardisation

30

available reference measurement procedures and/or available reference materials of a higher order

[…]".

As already mentioned in Chapter 2, the JRC is closely co-operating with the International Federation

of Clinical Chemistry and Laboratory Medicine (IFCC) and is involved in international bodies aiming at

the establishment and maintenance of reliable and sustainable reference measurement systems for

health diagnostics. These are for IVDs in particular the International Organization for Standardization

(via ISO TC 212) and the Joint Committee on Traceability in Laboratory Medicine (JCTLM), which

operates under the umbrella of the IFCC, the International Laboratory Accreditation Corporation

(ILAC) and the International Bureau for Weights and Measures (BIPM). The health-related CRM

activities of the JRC are performed, thanks to its independence from commercial or specific national

interests and by an institution which can offer innovative and harmonised solutions for the EU single

market.

In 2006-2015, the development, production and distribution of CRMs for health diagnostics were

focused on ensuring the continuous availability of globally accepted and used biomarkers as well as

the realisation of new CRMs for the calibration and/or quality control of further biomarker

measurements. A prominent example of the first group is the CRM ERM-DA470k/IFCC, which is a

second-generation development of a CRM that has been successfully used by the major IVD

manufacturers worldwide as 'gold standard' for the calibration of their IVD kits and in measuring a

range of proteins in routine blood testing of patients since 1993. The newcomer group of CRM

includes world-first materials for human genetic testing of a prothrombin mutation (IRMM/IFCC-

490-492) and the first serum protein CRM (ERM-DA476/IFCC) for the calibration of measurements of

anti-myeloperoxidase immunoglobulin G antibodies, a marker for several autoimmune diseases.

Another highlight after solving some scientific-technical challenges was the release of a set of 6

calibrators (ERM-AD623a-f) allowing clinical laboratories to monitor precisely the efficacy of medical

therapies in patients suffering from a type of leukaemia representing about 15–20 % of all cases of

adult leukaemia in Western populations. This new CRM set is an essential tool to correctly assess the

human response to leukaemia treatment and to ensure the early detection of a relapse of individual

patients.

International acceptance of the new CRMs has been ensured, following compliance with the

principles of ISO Guide 34:2009, compliance with the EC mandated standards ISO 15194 and ISO

17511 and successful reviews and listing by the JCTLM.

An overview on all certified reference materials for health diagnostics which have been released by

JRC-IRMM in 2006-2015 is provided in Table A3 in the Annex.

The global character of IVD manufacturing and the influence of the EU IVD Directive on

corresponding CRM demands can be seen in Figure 14 below and by the more than 4000 CRM units

distributed annually on average during 2006-2015.

31

Figure 14: Geographic distribution of customers ordering health diagnostics CRMs from JRC-IRMM

5.4 Environmental reference materials

The intervention logic for the development and production of RMs for environmental analysis is

summarised in Figure 15.

Figure 15: Intervention logic environmental RMs

Environmental protection is an important cornerstone of sustainable growth, which is one of the

three priorities of Europe 2020. It includes the monitoring of the status of the environment as well

as of possible pollutions sources. Ensuring confidence in environmental information is one important

Mandate

Directives 2000/60/EC & 2008/105/EC & 2013/39/EC & 2009/90/EC Directive 2008/50/EC Regulation (EC) 765/2008 EU Programme for Research and Innovation Horizon 2020

Deliverables

CRMs for implementation of EU legislation RMs for proficiency testing of laboratories RMs for method developments in CEN standardisation and EU projects

Impact

Enabling implement-ation of EU legislation Enabling & proving measurement capabilities of MS laboratories Ensuring EU quality standards thereby supporting a common market in services Facilitating environmental monitoring efficacy

Enabling standardised methods (CEN)

Activities

Development and production of (C)RMs Underpinning research Method development & validation for RM processing and characterisation Distribution of (C)RMs User guidance & training Standardisation

32

objective defined in the Commission Communication on improving the delivery of benefits from EU

environment measures (COM (2012) 95 final). Environmental protection expenditure is estimated to

account for a 1.82 % of the gross domestic product in the EU or EUR 439 per capita (Environmental

statistics and accounts in Europe 2010 Edition, Eurostat 2010), while the costs of non-

implementation of current legislation are estimated at about EUR 50 billion. On the other hand, the

full implementation of the EU waste legislation alone is estimated to contain net costs, which are

EUR 72 billion lower than in the case of non-implementation (COM (2012) 95 final). Reliable

measurements help to decide how to spend money most efficiently in this field.

Directive 2000/60/EC (the Water Framework Directive, WFD) plus amending Directives 2008/105/EC

and 2013/39/EC stipulate the need to monitor priority hazardous substances in surface waters and

biota to ensure a good water status in the EU. Directive 2009/90/EC, which lays down technical

specifications for chemical analysis and monitoring of the water status, demands that "[…] technical

operations to ensure the quality and comparability of analytical results should adopt internationally

accepted quality management system practices. As a consequence, the practices set out in EN

ISO/IEC 17025 are appropriate. It is appropriate to ensure that laboratories performing chemical

analysis demonstrate their competence through their participation in internationally or nationally

recognised proficiency testing programmes, as well as their use of available reference materials […]".

Moreover this Directive requests that "[…] Member States shall ensure that laboratories or parties

contracted by laboratories demonstrate their competences in analysing relevant physico-chemical or

chemical measurands by […] analysis of available reference materials that are representative of

collected samples which contain appropriate levels of concentrations in relation to relevant

environmental quality standards […]".

Therefore, the JRC is regularly performing gap analyses regarding the availability of RMs for the

implementation of the Water Framework Directive and the other EU environmental legislation

covering the surface, ground and marine waters13. Based on that, JRC-IRMM participated in a project

of the European Metrology Research Programme (EMRP) and developed non-certified RMs (Table

A5) for investigating new analytical methods for selected priority pollutants in whole surface water.

Moreover, such RMs were also provided to CEN for establishing standardised methods for water

monitoring. Also a range of CRMs for the quality assurance of environmental water monitoring were

finalised and released in the reporting period.

For achieving an appropriate environmental status of air the Directive 2008/50/EC on ambient air

quality and cleaner air for Europe demands that "[…] to ensure accuracy of measurements and

compliance with the data quality objectives […], the appropriate competent authorities shall ensure

that the national laboratories […] are accredited according to EN/ISO 17025 […]". Consequently, DG

Environment requested JRC-IRMM to develop the missing CRMs to assess the performance of

analytical methods and control laboratories for particulate matter suspended in air (PM10). Two new

CRMs have been developed and produced to match the requirements of the Directive regarding the

type of matrix including the particle size and the nature and content of certified analytes. These

CRMs ERM-CZ100 and ERM-CZ120 have been made available for quality assurance of the analysis of

selected elements and polycyclic aromatic hydrocarbons (PAHs) in PM10 and for method validation

purposes including trueness estimation.

13

Ricci et al., Trends in Analytical Chemistry 76 (2016) 194-202

33

The EU-wide trend towards accreditation of laboratories involved in environmental monitoring has

been supported by the development and distribution of a range of environmental CRMs. They are

required to demonstrate the analytical competences of the control laboratories and the traceability

of their measurement results. Therefore, about 2000 corresponding CRMs were distributed annually

on average and the geographic origin of their customers is shown in Figure 16.

Figure 16: Geographic distribution of customers ordering environmental CRMs from JRC-IRMM

Tables A4 and A5 in the Annex provide an overview on all certified and non-certified environmental

reference materials which have been released by JRC-IRMM in 2006-2015.

34

5.5 Engineering reference materials

The intervention logic for the development and production of JRC's engineered RMs is summarised

in Figure 17.

Figure 17: Intervention logic for engineering RMs

The availability of (C)RMs as measurement standards and quality benchmarks for functional

properties of advanced materials, industrial products and fuels is important for supporting the

competitiveness of European industry and for the required compliance controls with EU legislation.

JRC's RM activities in the broad field of the so-called engineering materials have, in the period 2006-

2015 been focused on:

− the sustainable provision of CRMs for testing of impact resistance (in support of Regulation

(EU) 305/2011 and Directives 1997/23/EC and 2009/105/EC);

− the development and production of CRMs to support the implementation of Directive

2011/65/EU on the restriction of the use of certain hazardous substances in electrical and

electronic equipment ('RoHS Directive') and the Waste Electric and Electronic Equipment

Directive 2012/19/EU;

− the development and production of fuel & biofuel CRMs enabling the implementation of

Directive 2009/30/EC on fuel specifications and supporting Directive 2009/28/EC on the

promotion of renewable energy;

− the development of non-certified and certified RMs for reliable and comparable

measurements of the size of nanoparticles thus enabling the implementation of the

Commission Recommendation COM (2011)696 on the definition of the term 'nanomaterial'.

In 2005 JRC-IRMM started an activity on developing concepts for reference materials envisaged for

use in the field of nanotechnology. It was realised that this emerging field of technology was, and

still is, associated with some measurement challenges, to which JRC-IRMM could contribute by

Mandate

Directive 2009/30/EC on fuel specifications Directive 2011/65/EU on the restriction of hazardous substances Regulation (EU) 305/2011 and Directives 1997/23/EC & 2009/105/EC Regulation (EC) 765/2008 EU Programme for Research and Innovation Horizon 2020

Deliverables

CRMs for implementation of EU legislation RMs for method developments RMs for proficiency testing of laboratories RMs for internal quality control Documentary standards (ISO)

Impact

Enabling implement-ation of EU legislation Reducing non-fiscal barriers to trade Setting up reliable measurement systems for operationally defined parameters Enabling & proving

measurement capabilities of Member States' laboratories Enabling standardised methods (CEN, ISO)

Activities

Development and production of (C)RMs Underpinning research Method development & validation for RM processing and characterisation Distribution of (C)RMs User guidance & training Standardisation

35

transferring it experience with measurements, quality assurance of measurements and RM

development from other areas of expertise. In 2008 JRC-IRMM successfully finalised IRMM-304, a

non-certified RM for silica nanoparticles in solution. This was a first step that allowed JRC-IRMM, as

well as laboratories required for characterisation studies on candidate CRMs, to gain the necessary

experience with various size measurement methods and procedures. In 2010 JRC-IRMM could

release its first CRM for nanoparticle sizing, ERM-FD100. In the following year, IRMM-304 was

upgraded to a CRM (ERM-FD304) by using newly available measurement results. Moreover, the first

CRM with a bimodal size distribution of silica nanoparticles has been developed and produced (ERM-

FD102). These CRMs (see Table A6) are applied for quality control of particle size measurements. To

enable the development and performance assessment of new measurement methods for

nanoparticles in more complex materials such as foodstuff, a range of non-certified RMs have been

designed and produced for some EU projects (see Table A7).

The influence of EU legislation on manufacturing and product control activities of industry located

outside the EU but exporting a significant part of their goods into the EU can also be seen for specific

cases from RM customer demands. For instance, JRC's CRMs which enable the quality control of

measurements results required to demonstrate compliance of manufactured electrical and

electronic equipment with the 'RoHS Directive' 2011/65/EU have been ordered (about 700-800 units

per year) mainly by customers in Asia (see Figure 18) as their products have the largest share on the

EU market.

Figure 18: Geographic distribution of customers ordering CRMs supporting the implementation of

the RoHS Directive from JRC-IRMM

36

5.6 Nuclear reference materials

The intervention logic for the development and production of JRC's nuclear CRMs is summarised in

Figure 19.

Figure 19: Intervention logic for nuclear RMs

Chapter VII of the Euratom Treaty holds the European Commission (EC) responsible for the control

of all civil fissile nuclear material in the EU. Therefore, the production of nuclear RMs is embedded in

the Euratom Treaty and JRC-IRMM is responsible for fulfilling this legal obligation in nuclear

standards and measurements by developing and producing nuclear CRMs. Nuclear CRMs as provided

by the JRC are an indispensable metrological tool for nuclear industry and safeguard laboratories to

meet the requirements for accountancy measurements in compliance with The International Target

Values for Measurement Uncertainties in Safeguarding Nuclear Materials – ITVs-2010.

Nuclear safeguards conclusions are based to a large extent on comparison of measurement results

between operator and safeguards laboratories. In nuclear forensics, characteristic parameters (also

referred to as "signatures") are used for re-establishing the history of nuclear material found out of

regulatory control. Signatures can either be "predictive" (i.e. self-explaining) or "comparative" in

nature. The latter require external data of known nuclear material for supporting data

interpretation. In either case, accurate measurement results are required to be performed with a

validated method and expressed as a measured quantity value with uncertainty and traceability.

Today, the JRC is developing and producing its nuclear CRMs primarily on demand of DG Energy for

Euratom safeguards and for the safeguards authorities of the International Atomic Energy Agency

(IAEA). The work of the latter is performed in the framework of the EC Cooperative Support

Programme to IAEA (EC SP)14,15. Therefore, the JRC has invested enormous effort in the development

of new CRMs and the provision of other quality assurance tools (namely interlaboratory

14

http://publications.jrc.ec.europa.eu/repository/handle/JRC93746 15

https://www.iaea.org/safeguards/symposium/2014/home/eproceedings/sg2014-slides/000088.pdf

Mandate

Euratom Treaty (2012/C327/01)

Commission Regulation (Euratom) 302/2005 on the application of Euratom safeguards

EU CBRN Action Plan (2010/2114(INI))

Deliverables

CRMs for implementation of EU legislation Documentary standards CRMs for proficiency testing of laboratories for nuclear safeguards and security

Impact

Supporting European and international Safeguards authorities

with nuclear CRMs and quality assurance tools for the implementation of Chapter VII of the Euratom Treaty, the Non-proliferation Treaty, the Additional Protocol ((INFCIRC/153 corrected, INFCIRC/540), and the CBRN Action Plan

Activities Development of nuclear CRMs Standardisation Underpinning research Method development and evaluation Interlaboratory Comparisons REIMEP/NUSIMEP Distribution of CRMs User guidance and training courses (ESARDA, IAEA..)

37

comparisons), particularly for 'age-dating' of uranium and plutonium samples and for isotopic

fingerprinting. Moreover, JRC's nuclear CRMs are applied by users worldwide operating uranium-

enrichment facilities, fuel-fabrication, nuclear-power-generation and reprocessing plants. They are

also required by holders of small stocks of fissile materials for industrial, research or medical

purposes. JRC's nuclear CRMs are also used to assess the radioactivity measurement systems of EU

Member States.

Priority setting for the nuclear CRM development and production occurs at three levels:

• at JRC and partner DG level via the definition and assessment of the annual JRC Work

Programme, regularly monitored via respective task sheets;

• at the level of international/governmental organisations via mechanisms laid down in the

respective support programmes and/or cooperation agreements. Priorities for support to

the IAEA are set in line with the priorities as defined in the IAEA Department of Safeguards

Long-Term Research & Development Plan, 2012-2023 (STR–375). The Joint Steering

Committee meeting between the US Department of Energy (DOE) and Euratom represented

by the European Commission is held on an annual basis. During this meeting action items

are defined and their status reviewed and priorities set. It further ensures coordination

between JRC-IRMM and the US New Brunswick Laboratory (NBL) on nuclear reference

material development and provision of interlaboratory comparisons;

• at international level and with industry via regular technical meetings and dedicated

workshops using the existing platforms of exchange and cooperation between the

safeguards; security, operators; research; and metrology communities of the European

Safeguards Research and Development Association (ESARDA), the US Institute for Nuclear

Material Management (INMM) and the French Commission d'Etablissement des Methodes

d'Analyse (CETAMA).

38

6 Outlook into JRC's activities on reference materials

The JRC-IRMM has a proven track record in the field of RM development and production. It should

be stressed that new demands and challenges regarding new RMs constantly emerge, leading to the

legitimate question of, which directions the JRC should take in the future.

RMs are a very specific niche product whose benefits are fully understood by professionals such as

analytical chemists or laboratory technicians, though this may not be the case with policy makers

and ordinary citizens. Nevertheless, RMs have significant economic and social impacts, albeit most of

the times, indirectly. Two specific examples easily highlight the importance of the RMs:

• lives saved or prolonged (social impact) by improved medical treatment with the help of a

CRM for leukaemia monitoring (ERM-AD623) that helps determine when to exactly

administer a drug and when not;

• sound company management and control of competitive trading prices (economic impact)

by testing refined copper on the market with the help of copper CRMs (ERM-EB074 & 75), as

the price of copper, is established as a function of the impurity levels in the product.

Because of the nature of RMs, as an infrastructure technology, companies lack a strong incentive to

enter the market of RM production.

If development and production of RMs were to be suspended or downsized at the JRC, the void

might not be filled by the private sector or potentially by national RM producers. The former seeks

to maximise profits (hardly achievable for the vast majority of RMs) and the latter follow legitimate

specific national interests and priorities. Nevertheless, accurate measurement results, and thus the

need for (C)RMs, are in high demand in many fields and even projected to increase further. This is

elaborated in more detail in the following.

Health diagnostics

Health is a crucial and booming sphere in light of the ageing population and the spread of non-

communicable and rare diseases. A straightforward example is Alzheimer's disease, which global

cost is estimated at $604 billion – that means 1% of the world GDP (as a comparison: cancer costs

$895 billion annually and heart disease – $753 billion)16! Moreover, people affected by Alzheimer's

disease are projected to increase from 44 million in 2013 to 135 million in 2050, thus placing a heavy

burden on public finances and the social fabric. The JRC-IRMM is currently developing a CRM to

allow standardisation and to facilitate better treatment of Alzheimer disease – a daunting task with

considerable socio-economic impact.

Furthermore, personalised medical treatment and the subsequent spread of medical devices will

considerably increase the need for CRMs of higher order as already stipulated by the EU IVD

Directive17. The JRC's collaboration with the IFCC is an excellent forum to increase further pre-

normative research in the area and to address these standardisation challenges. Allergens, on the

16

M. Prince et al., Alzheimer's Disease International (ADI), London, UK 2013. 17

Directive 98/79/EC of the European Parliament and of the Council

39

other hand are also an emerging threat requiring accurate measurement results for decision-making

and are preferably to be standardised with CRMs (cross-cutting with the food area).

Food

Food is an important topic, not only for the European consumers who spent about 15% of their

household income on food and drinks in 2011, but also for the food industry, which is the largest

employer in Europe's manufacturing sector, accounting for 4.5 million people (14% of the

workforce)18. Due to the complexity of the global supply chain and differences in the food safety

requirements worldwide, foodborne illnesses may easily occur, thereby posing a significant

economic and public health burden. Among the consequences are; higher healthcare expenses,

product recalls, with its associated costs and complex epidemiological tracking studies. Food

matrices are especially challenging to be analysed in search of hazardous substances and possible

adulterants. Therefore, the use of control materials, such as (C)RMs, is essential and in line with the

EU's "farm-to-fork" principle. Besides food and feed safety, the prevention of food fraud is a priority

for EU policy makers. Therefore, food control authorities need to consistently develop new

methodologies, as well as adapt existing ones to detect fraud and to ensure the authenticity of food

products, which is important for protecting fundamental rights of consumers. The strong attitudes of

Europeans towards food and the economic importance of the sector are also an important aspect of

the current TTIP discussions. Maintaining high food standards require reliable measurements and

mutual trust in their results. If the JRC, with its extensive accumulated expertise, would step aside,

the consequences could be significant, given its goal of ensuring improved food control in protecting

consumers and businesses.

Environment

The environment is an area where the EU prides itself for setting up the global benchmark for quality

and sustainability. For instance, road dust is responsible for 33 % of air pollution. The JRC plays a

significant role by coordinating the European Air Quality Reference Laboratories network (AQUILA)

to which the JRC-IRMM contributes with RMs, thereby improving the quality assurance of the

measurements. JRC's CRMs on polycyclic aromatic hydrocarbons (PAHs) and selected heavy metals

in a PM10-like dust are pivotal for accurate air quality measurements. The importance is highlighted,

for instance, by the willingness of OECD citizens to pay $1.7 trillion19 to pre-empt possible deaths

from bad air quality. The EU is also a home to the most comprehensive piece of legislation

concerning water quality – the Water Framework Directive (WFD)20. The Directive and its Daughter

Directives call for the stringent monitoring of 45 priority pollutants and their uniform measurement

and quantification across the EU is best achieved with appropriate CRMs. However, many CRMs are

still missing which presents a great possibility for future research and developments resulting in

improved environmental protection.

18

FoodDrinkEurope – "2013-2014 Data & Trends of the European food and drink industry" 19

OECD, The Cost of Air Pollution, 2014 20

Directive 2000/60/EC of the European Parliament and of the Council establishing a framework for the

Community action in the field of water policy

40

Engineering

Engineering is a key driver of employment and economic growth and has a substantial demand for

accurate measurements supported by CRMs. Of particular interest is the emerging field of

nanotechnology and its numerous applications, ranging from computing to cosmetics and from

pharmaceuticals to construction materials. The nanotechnology market was valued at $26 billion in

2015 and is projected to increase to $76 billion in 202021. As a result, human exposure to

nanomaterials is becoming ubiquitous and logically raises the issue of better understanding their

properties, also related to safety and health. JRC-IRMM released the first silica nanoparticle CRM as

a benchmark for a widely used product, thus facilitating the comparability of measurement results

and promoting innovation. However, more building blocks are needed in a field with vast

opportunities and unknowns, which requires informed decisions on substantial investments in

infrastructure and human capital.

Nuclear safeguards

Safeguards authorities, nuclear industry, laboratories and research institutes worldwide use the JRC

nuclear CRMs, quality tools and services for accurate measurements of samples from all stages of

the nuclear fuel cycle and for environmental sample analysis. The Euratom Treaty endows the

European Commission with full responsibility for the implementation of safeguards in the EU. At the

international level, the IAEA is in charge of safeguards. Close interactions between the European

Union, its Member States and the IAEA, as well as the relevant authorities in the US, will define

future needs and guide related developments. There are, besides the JRC-IRMM, only two other

main nuclear RM providers. It is not expected that this number will increase in the future. Therefore,

the European Commission must ensure that the European and international safeguards community

can also count in the future on appropriate quality assurance tools. To this end, the JRC has to

guarantee that its role in the field of nuclear CRMs can be fulfilled. Obviously, the nuclear CRM

production should be as in the past, prioritised and duplication has to be avoided. This is pursued via

the close networking and transparent priority setting as outlined before.

Overall Summary

The examples above illustrate the need for (C)RMs in evidence-based policy making, in particular for

the implementation and monitoring of legislation in various sectors. Related RM activities require

significant investments in human capital, infrastructure and time as well as demonstrated

competence and reputation.

Although most of the above are already present at the JRC, further efforts are required to address

future needs in the health, food, environment and engineering sectors, but not only limited to them.

In the best case scenario, these challenges will be dealt with simultaneously. However, given the

current economic situation, precedence should be given to the most burning issues aligned with the

political priorities of the European Commission.

21

ReportLinker, Nanotechnology Market Outlook 2020.

41

Annex

42

Table A1: Food & feed CRMs released by JRC-IRMM in 2006-2015

Material code Matrix Certified property

IRMM-447 Genomic DNA of Listeria Monocytogenes

Identity

IRMM-449 Genomic DNA of Escherichia coli

Identity

ERM-BF423a Maize (GMO) MIR604 maize mass fraction

ERM-BF423b Maize (GMO) MIR604 maize mass fraction

ERM-BF423c Maize (GMO) MIR604 maize mass fraction

ERM-BF423d Maize (GMO) MIR604 maize mass fraction

ERM-BF421a Potato (GMO) EH92-527-1 potato mass fraction

ERM-BF421b Potato (GMO) EH92-527-1 potato mass fraction

ERM-BF419a Sugar beet (GMO) H7-1 sugar beet mass fraction

ERM-BF419b Cotton seed (GMO) H7-1 sugar beet mass fraction

ERM-BF422a Cotton seed (GMO) 281-24-236 x 3006-210-23 cotton seed mass fraction

ERM-BF422b Cotton seed (GMO) 281-24-236 x 3006-210-23 cotton seed mass fraction

ERM-BF422c Cotton seed (GMO) 281-24-236 x 3006-210-23 cotton mass seed fraction

ERM-BF422d Cotton seed (GMO) 281-24-236 x 3006-210-23 cotton seed mass fraction

ERM-BF424a Maize (GMO) 59122 maize mass fraction

ERM-BF424b Maize (GMO) 59122 maize mass fraction

ERM-BF424c Maize (GMO) 59122 maize mass fraction

ERM-BF424d Maize (GMO) 59122 maize mass fraction

IRMM-315 4-Deoxynivalenol in acetonitrile

4-Deoxynivalenol mass fraction

IRMM-316 Nivalenol in acetonitrile Nivalenol mass fraction

BCR-162R Soya-maize oil blend Fatty acid methyl ester (FAME) mass fractions

ERM-AC057 Aflatoxin B1 in acetonitrile Aflatoxin mass fraction

ERM-AC058 Aflatoxin B2 in acetonitrile Aflatoxin mass fraction

ERM-AC059 Aflatoxin G1 in acetonitrile Aflatoxin mass fraction

ERM-AC060 Aflatoxin G2 in acetonitrile Aflatoxin mass fraction

ERM-AD413 Plasmid DNA (GMO) MON 810 maize copy number ratio

ERM-BD273 Toasted bread Acrylamide mass fraction

ERM-BF413d Maize (GMO) MON 810 maize copy number ratio (addition of a certified value to an existing CRM)

ERM-BF420a Maize (GMO) 3272 maize mass fraction

ERM-BF420b Maize (GMO) 3272 maize mass fraction

ERM-BF420c Maize (GMO) 3272 maize mass fraction

ERM-BF425a Soya (GMO) 356043 GAT soya mass fraction

ERM-BF425b 356043 GAT soya (GMO) 356043 GAT soya mass fraction

ERM-BF425c 356043 GAT soya (GMO) 356043 GAT soya mass fraction

ERM-BF425d 356043 GAT soya (GMO) 356043 GAT soya mass fraction

ERM-BF426a Soya (GMO) 305423 OH soya mass fraction

ERM-BF426b Soya (GMO) 305423 OH soya mass fraction

ERM-BF426c Soya (GMO) 305423 OH soya mass fraction

ERM-BF426d Soya (GMO) 305423 OH soya mass fraction

IRMM-425 Tetramethylurea D/H ratio (Masterbatch)

43

Material code Matrix Certified property

IRMM-448 Genomic DNA of Campylobacter jejuni

Identity

IRMM/IFCC466 Glycated haemoglobin (HbA1c)

Purity

IRMM/IFCC467 Haemoglobin (HbA0) Purity

IRMM-804 Rice flour Trace element mass fraction

BCR-263R Peanut meal Aflatoxin mass fraction

BCR-380R Whole milk powder Crude protein, fat, lactose, ash mass fraction

BCR-385R Peanut butter Aflatoxin mass fraction

BCR-401R Peanut butter Aflatoxin mass fraction

BCR-685 Skim milk powder Crude protein, fat, lactose, ash mass fraction

ERM-BB124 Pork muscle Nitroimidazole mass fraction

ERM-BF410ak Soya (GMO) Roundup-ready soya

ERM-BF410bk Soya (GMO) Roundup-ready soya

ERM-BF410dk Soya (GMO) Roundup-ready soya

ERM-BF410gk Soya (GMO) Roundup-ready soya

IRMM-311 Genomic DNA of Bacillus licheniformis DSM 5749

Fragment length in the size interval 50 - 90 kb

IRMM-312 Genomic DNA of Bacillus subtilis DSM 5750

Fragment length in the size interval 15 - 97 kb

IRMM-351 Bioball Colony forming units of Escherichia Coli per sphere

IRMM-352 Bioball Colony forming units of Salmonella Enteriditis per sphere

STA-003k Tetramethylurea D/H ratio

ERM-BE376 Compound feedingstuff Aflatoxin mass fraction

ERM-BF413ak Maize (GMO) MON 810 maize mass fraction

ERM-BF413ck Maize (GMO) MON 810 maize mass fraction

ERM-BF413ek Maize (GMO) MON 810 maize mass fraction and copy number ratio

ERM-BF413gk Maize (GMO) MON 810 maize mass fraction

ERM-BF427a Maize (GMO) 98140 maize mass fraction

ERM-BF427b Maize (GMO) 98140 maize mass fraction

ERM-BF427c Maize (GMO) 98140 maize mass fraction

ERM-BF427d Maize (GMO) 98140 maize mass fraction

ERM-BF428a Cotton seed (GMO) GHB119 cotton seed mass fraction

ERM-BF428b Cotton seed (GMO) GHB119 cotton seed mass fraction

ERM-BF428c Cotton seed (GMO) GHB119 cotton seed mass fraction

IRMM-354 Bioball Colony forming units of Candida albicans per sphere

IRMM-355 Bioball Colony forming units of Enterococcus faecalis per sphere

ERM-BB130 Pork muscle Chloramphenicol (CAP) mass fraction

ERM-BB384 Pork muscle Proximate mass fraction

ERM-BC381 Rye flour Proximate mass fraction

ERM-BC382 Wheat flour Proximate mass fraction

ERM-BE375 Animal feed Aflatoxin mass fraction

ERM-BF429a Cotton seed (GMO) T30-40 cotton seed mass fraction

ERM-BF429b Cotton seed (GMO) T30-40 cotton seed mass fraction

ERM-BF429c Cotton seed (GMO) T30-40 cotton seed mass fraction

ERM-AD415 Plasmid DNA (GMO) NK603 maize copy number ratio

44

Material code Matrix Certified property

ERM-AD425 Plasmid DNA (GMO) 356043 soya copy number ratio

ERM-AD427 Plasmid DNA (GMO) 98140 maize copy number ratio

ERM-BB386 Bovine urine Stilbene mass fraction

ERM-BB389 Bovine urine Stilbene mass fraction

ERM-BB492 Milk powder Oxytetracycline (OTC) mass fraction

ERM-BB493 Milk powder Oxytetracycline (OTC) mass fraction

ERM-BD600 Milk Powder Vitamin mass fraction

ERM-BF415e Maize (GMO) NK603 maize copy number ratio (addition of a certified value to an existing CRM)

ERM-BF425c Soya (GMO) 356043 soya copy number ratio (addition of a certified value to an existing CRM)

ERM-BF427c Maize (GMO) 98140 maize copy number ratio (addition of a certified value to an existing CRM)

ERM-BF430a Potato (GMO) AM04-1020 potato mass fraction

ERM-BF430b Potato (GMO) AM04-1020 potato mass fraction

ERM-BF430c Potato (GMO) AM04-1020 potato mass fraction

ERM-BF430d Potato (GMO) AM04-1020 potato mass fraction

ERM-BF430e Potato (GMO) AM04-1020 potato mass fraction

ERM-BB184 Bovine muscle Trace elements mass fraction

ERM-BB186 Pig kidney Trace elements mass fraction

ERM-BF431a Potato (GMO) AV43-6-G7 potato mass fraction

ERM-BF431b Potato (GMO) AV43-6-G7 potato mass fraction

ERM-BF431c Potato (GMO) AV43-6-G7 potato mass fraction

ERM-BF431d Potato (GMO) AV43-6-G7 potato mass fraction

ERM-BF431e Potato (GMO) AV43-6-G7 potato mass fraction

ERM-BF432a Soya (GMO) DAS-68416-4 soya mass fraction

ERM-BF432b Soya (GMO) DAS-68416-4 soya mass fraction

ERM-BF432c Soya (GMO) DAS-68416-4 soya mass fraction

ERM-BF432d Soya (GMO) DAS-68416-4 soya mass fraction

ERM-BF433a Maize (GMO) DAS-40278-9 maize mass fraction

ERM-BF433b Maize (GMO) DAS-40278-9 maize mass fraction

ERM-BF433c Maize (GMO) DAS-40278-9 maize mass fraction

ERM-BF433d Maize (GMO) DAS-40278-9 maize mass fraction

ERM-BC211 Rice As species

ERM-BD150 Milk powder Trace and essential element mass fraction

ERM-BD151 Milk powder Trace and essential element mass fraction

ERM-BF434a Rapeseed (GMO) 73496 rapeseed mass fraction

ERM-BF434b Rapeseed (GMO) 73496 rapeseed mass fraction

ERM-BF434c Rapeseed (GMO) 73496 rapeseed mass fraction

ERM-BF434d Rapeseed (GMO) 73496 rapeseed mass fraction

ERM-BF434e Rapeseed (GMO) 73496 rapeseed mass fraction

ERM-BF436a Soya (GMO) DAS-44406-6 soya mass fraction

ERM-BF436b Soya (GMO) DAS-44406-6 soya mass fraction

ERM-BF436c Soya (GMO) DAS-44406-6 soya mass fraction

ERM-BF436d Soya (GMO) DAS-44406-6 soya mass fraction

ERM-BF436e Soya (GMO) DAS-44406-6 soya mass fraction

45

Material code Matrix Certified property

STA-003m Tetramethylurea D/H ratio

ERM-BF437a Soya (GMO) DAS-81419-2 soya mass fraction

ERM-BF437b Soya (GMO) DAS-81419-2 soya mass fraction

ERM-BF437c Soya (GMO) DAS-81419-2 soya mass fraction

ERM-BF437d Soya (GMO) DAS-81419-2 soya mass fraction

ERM-BC717 Maize two additional values for DON and NIV

ERM-BF435a Potato (GMO) PH05-026-0048 potato identity

ERM-BF435b Potato (GMO) PH05-026-0048 potato identity

ERM-AD442k DNA in buffer lambda DNA mass concentration

ERM-BF438a Maize (GMO) VCO-Ø18195 maize mass fraction

ERM-BF438b Maize (GMO) VCO-Ø18195 maize mass fraction

ERM-BF438c Maize (GMO) VCO-Ø18195 maize mass fraction

ERM-BF438d Maize (GMO) VCO-Ø18195 maize mass fraction

ERM-BF439a Maize (GMO) DP- ØØ1441-3 maize mass fraction

ERM-BF439b Maize (GMO) DP- ØØ1441-3 maize mass fraction

ERM-BF439c Maize (GMO) DP- ØØ1441-3 maize mass fraction

ERM-BF439d Maize (GMO) DP- ØØ1441-3 maize mass fraction

ERM-BF439e Maize (GMO) DP- ØØ1441-3 maize mass fraction

46

Table A2: Food & feed RMs (non-certified) released by JRC-IRMM in 2006-2015

Material code Matrix Property of interest Purpose of material

QCM-GHa500 BSE GENERIC HOMOGENATE (1:10 positive/negative dilution)

Mass fraction of BSE positive brain BSE testing – quality control

QCM-tgMB-147 BSE TRANSGENIC MOUSE BRAIN (147 days) Mass fraction of BSE positive brain BSE testing –

quality control

QCM-tgMB-220 BSE TRANSGENIC MOUSE BRAIN (220 days) Mass fraction of BSE positive brain BSE testing –

quality control

QCM-tgMB-98 BSE TRANSGENIC MOUSE BRAIN (98 days)

Mass fraction of BSE positive brain BSE testing – quality control

CRL-MYC_2007_04 Standard solution acetonitrile Aflatoxins Support EURL /

PT CRL-MYC_2007_05 Standard solution Ochratoxin Support EURL /

PT CRL-MYC_2008_06

Standard solution Deoxynivanenol Support EURL / PT

CRL-MYC_2008 Standard solution Fuominisin Support EURL / PT

CRL-MYC_2009 Standard solution T2 HT2 standard Support EURL / PT

EURL-MYC_2010_a

Standard solution HAc and ACN

Ochratoxin Support EURL / PT

EURL-MYC_2010_b

Standard solution HAc and ACN Ochratoxin Support EURL /

PT EURL-MYC_2010_c

Standard solution HAc and ACN Ochratoxin Support EURL /

PT EURL-MYC_2010_d

Standard solution HAc and ACN Ochratoxin Support EURL /

PT EURL-MYC_2010_e

Standard solution HAc and ACN Ochratoxin Support EURL /

PT

EURL-MYC_2011 Standard solution K2Cr2O7 Support EURL / PT

EURL-MYC_2011 Standard solution in toluene / ACN Aflatoxin B Support EURL /

PT

EURL-MYC_2011 Standard solution HAc and ACN Ochratoxin Support EURL /

PT

EURL-MYC_2012 Standard solution Ochratoxin Support EURL / PT

EURL-MYC_2013 Coconut Aflatoxins Support EURL / PT

EUR-MYC_2015a Nutmeg Ochrataoxin Support EURL / PT

EUR-MYC_2015b Nutmeg Ochrataoxin Support EURL / PT

CRL-PAH-2006_01 Acetonitrile standard Polycyclic aromatic hydrocarbons, PAH Support EURL /

PT CRL-PAH_2007_02a Acetonitrile standard Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

CRL-PAH-2007_03 Edible oil

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

CRL-PAH_2008 Standard solution Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

CRL-PAH_2009_05

Standard in toluene cyclohexane

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

CRL-PAH_2009_05

Mineral oil in solvent Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

CRL-PAH_2009_06 Standard solution Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

CRL-PAH_2009_07 Olive oil / ACN Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

47

Material code Matrix Property of interest Purpose of material

CRL-PAH_2009_08 Olive oil Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2010_a

Standard solution PT infant formula

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_b

Standard solution PT infant formula

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_c

Standard solution PT infant formula

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_d

Standard solution PT infant formula

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_e

Standard solution PT infant formula

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_f

Standard solution, PT olive oil

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_g

Standard solution, PT olive oil

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_h

Standard solution, PT olive oil

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_i

Standard solution, PT olive oil

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2010_j

Standard solution, PT olive oil

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2011-07a

ACN solution food supplement

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2011-07b

ACN solution food supplement

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2011-07c

Toluene solution food supplement

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2011-07d

Toluene solution food supplement

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2011-08

Standard solution toluene / cyclohexane

Polycyclic aromatic hydrocarbons, PAH, 15+1

Support EURL / PT

EURL-PAH_2011-09a ACN / oil Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2011-09b Toluene / oil Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2011-09c Oil Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2012a Standard solution, ACN Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2012b Standard solution, toluene Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2012c Standard solution, toluene Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2012d Standard solution, toluene Polycyclic aromatic hydrocarbons, PAH,

15+1 Support EURL / PT

EURL-PAH_2013 Olive oil 4 PAHs EURL / PT

EURL-PAH_2013 Standard solution, ACN / toluene PAHs, (15+1) EURL / PT

EURL-PAH_2014_1 wine phtalates EURL / PT

EURL- wine phtalates EURL / PT

48

Material code Matrix Property of interest Purpose of material

PAH_2014_2

EURL-PAH_2014_3 wine phtalates EURL / PT

EURL-PAH_2014_4 wine phtalates EURL / PT

EURL-PAH_2014_5

Iso-octane phtalates EURL / PT

EURL-PAH_2014_6 Iso-octane phtalates EURL / PT

EURL-PAH_2014a Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014b

Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014c Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014d Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014e Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014f Pork fat in solvent Boar taint EURL / PT EURL-PAH_2014g

Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014h Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014i Pork fat in solvent Boar taint EURL / PT

EURL-PAH_2014 Fish oil PAHs, 15+1 EURL / PT

IMEP-102_2007 Acidified standard solutions Pb, Cd, Hg in mineral water EURL / PT

IMEP-103_2007 Fish feed Pb, Cd, Hg in fish feed EURL / PT

IMEP-104_2008 Lobster hepatopancreas Cd, Pb, Hg, methyl-Hg ,As EURL / PT

IMEP-105_2008 Mineral mix Cd, Pb, Hg and extractable Cd and Pb EURL / PT HM-EURL_IMEP-106_2009

Green tea Pb, Hg, Cd, As EURL / PT

HM-EURL_IMEP-107_2009 Rice Astot and inorganic As EURL / PT

HM-EURL_IMEP-109_2009 Dogfish liver tissue Pb, Hg, Cd, As EURL / PT

HM-EURL_IMEP-110_2010

Spinach leaves Pb, Hg, Cd, As EURL / PT

HM-EURL_IMEP-111_2010 Mineral feed Pb, Hg, Cd, As EURL / PT

HM-EURL_IMEP-112_2011 Wheat Astot and inorganic As EURL / PT

HM-EURL_IMEP-113_2011

Baby food ,soya milk Cd and Pb EURL / PT

IMEP-114_2012 Feed premix Pb, Hg, Cd, As and Sn EURL / PT HM-EURL_IMEP-115a_2012

Dogfish liver tissue Methyl mercury EURL / PT

HM-EURL_IMEP-115b_2012 Lobster hepatopancreas Methyl mercury EURL / PT

HM-EURL_IMEP-115c_2012 Oyster tissue Methyl mercury EURL / PT

HM-EURL_IMEP-115d_2012

Mussel tissue Methyl mercury EURL / PT

HM-EURL_IMEP-115e_2012 Tuna fish Methyl mercury EURL / PT

HM-EURL_IMEP-116_2013 Mushroom Cd, Pb, As, Hg and Sn EURL / PT

49

Material code Matrix Property of interest Purpose of material

HM-EURL_IMEP-117_2013 Feed premix Cd, Pb, As, Hg EURL / PT

HM-EURL_IMEP-118_2013

Canned vegetables (peas) Cd, As, Pb, Sn EURL / PT

HM-EURL_IMEP-119_2014 Alfalfa Cd, Pb, As EURL / PT

HM-EURL_HM-20_2015 Dark chocolate

Cd, Pb EURL / PT

HM-EURL_IMEP-121_2015 Kaolinitic clay Cd, Pb, As, Hg EURL / PT

IMEP-25_1_2009 Soft drinking water Bromate Support to CEN

IMEP-25_2_2009 Hard drinking water Bromate Support to CEN

IMEP-25_3_2009 Mineral water Bromate Support to CEN

IMEP-25_4_2009 Swimming pool water Bromate Support to CEN

IMEP-25_5_2009 Raw water Bromate Support to CEN

IMEP-25_6_2009 Blank Bromate Support to CEN

IMEP-25_7_2009 Standard solution Bromate Support to CEN

IMEP-32_1_2011 Fish feed blank Inorganic As Support to CEN

IMEP-32_2_2011 Fish feed spiked Inorganic As Support to CEN

IMEP-32_3_2011 Fish meal blank Inorganic As Support to CEN

IMEP-32_4_2011 Fish meal spiked Inorganic As Support to CEN

IMEP-32_5_2011 Fish fillets spiked Inorganic As Support to CEN

IMEP-32_6_2011 Fish meal spiked Inorganic As Support to CEN

IMEP-32_7_2011 Fish meal blank Inorganic As Support to CEN

IMEP-35_2012 Lipstick Pb EURL / PT

IMEP-41a_2014 Rice Inorganic As Support to CEN

IMEP-41b_2014 Wheat Inorganic As Support to CEN

IMEP-41c_2014 Mussel Inorganic As Support to CEN

IMEP-41d_2014 Cabbage Inorganic As Support to CEN

IMEP-41e_2014 Mushroom Inorganic As Support to CEN

IMEP-41f_2014 Seaweed Inorganic As Support to CEN

IMEP-41g_2014 Fish Inorganic As Support to CEN

IMEP-41h_2014 Rice Inorganic As Support to CEN

50

Material code Matrix Property of interest Purpose of material

IMEP-42_2015 Fish PFOA EURL / PT

REM_A_2012 Fresh water (mineral) Radionuclides PT / intercomparison

REM_B_2012 Fresh water (mineral) Radionuclides PT / intercomparison

REM_C_2012 Fresh water Radionuclides PT / intercomparison

SAFEED-PAP_A_2008 Animal feed Meat and bone meal (rests of PAP) EU project

SAFEED-PAP

SAFEED-PAP_B_2008 Animal feed Meat and bone meal (rests of PAP) EU project

SAFEED-PAP SAFEED-PAP_C_2008 Animal feed Meat and bone meal (rests of PAP) EU project

SAFEED-PAP SAFEED-PAP_D_2008 Animal feed Meat and bone meal (rests of PAP) EU project

SAFEED-PAP

IRMM-AD482 Plasmid DNA in buffer Ruminant DNA copy number concentration

Support to EURL / method validation

IRMM-AD483 Plasmid DNA in buffer Porcine DNA copy number concentration Support to EURL / method validation

CT-01/2010 GMO powder NK603 maize Support to EURL / PT

CT-02/2010 GMO powder MON 810 maize Support to EURL / PT

CT 01/2013 GMO powder 98140 maize Support to EURL / PT

CT 02/2013 GMO powder 356043 soybean Support to EURL / PT

CT 01/2014 GMO powder NK603 maize Support to EURL / PT

CT 02/2014 GMO powder DAS 40278-9 maize Support to EURL / PT

CT 01/2015 GMO powder 356043 soybean Support to EURL / PT

CT 02/2015 GMO powder DAS-81419-2 soybean and 68416-4 soybean

Support to EURL / PT

CT 01/2016 GMO powder DAS 40278-9 maize Support to EURL / PT

51

Table A3: Health diagnostic CRMs released by JRC-IRMM in 2006-2015

Material code Matrix Certified property

IRMM-468 Thyroxine (T4) Purity

IRMM-469 Triiodothyronine (T3) Purity

BCR-348R Human serum Progesteron mass fraction

IRMM/IFCC-490 Plasmid DNA preparation Identity for prothrombin wild type (homozygous)

IRMM/IFCC-491 Plasmid DNA preparation Identity for prothrombin mutation (homozygous)

IRMM/IFCC-492 Plasmid DNA preparation Identity for prothrombin mutation (heterozygous)

IRMM-435 Pharmaceutical glass Leachable alkali metal

ERM-DA470k/IFCC

Human serum Serum proteins

ERM-AD457/IFCC Enzyme preparation Aspartate transaminase activity

ERM-DA472/IFCC Human serum C-reactive protein (CRP) mass fraction

ERM-DA471/IFCC Human serum Cystatin C mass fraction

ERM-DA474 Human Serum C-reactive protein (CRP) mass fraction

ERM-AD623a Plasmid in buffer BCR-ABL copy number concentration

ERM-AD623b Plasmid in buffer BCR-ABL copy number concentration

ERM-AD623c Plasmid in buffer BCR-ABL copy number concentration

ERM-AD623d Plasmid in buffer BCR-ABL copy number concentration

ERM-AD623e Plasmid in buffer BCR-ABL copy number concentration

ERM-AD623f Plasmid in buffer BCR-ABL copy number concentration

ERM-DB001 Human hair Trace elements mass fraction

ERM-DA470k Human serum B2M mass fraction (addition of a certified value to an existing CRM)

ERM-DA476/IFCC Human serum anti-MPO IgG mass fraction

52

Table A4: Environmental CRMs released by JRC-IRMM in 2006-2015

Material code Matrix Certified property

ERM-CA615 Groundwater Trace element mass fraction

ERM-CA616 Groundwater Major element mass fraction

ERM-CA713 Waste water Trace elements mass fraction

IRMM-428 Water Polyfluorinated alkyl substances (PFAS) mass fraction

ERM-CA408 Simulated rainwater Major element mass fraction

ERM-AC213 Pure solution Polycyclic aromatic hydrocarbon (PAH) mass fraction

ERM-CZ100 PM10-like dust Polycyclic aromatic hydrocarbon (PAH) mass fraction

ERM-CZ120 PM10-like dust Trace element mass fraction

BCR-277R Estuarine sediment Trace element mass fraction

BCR-280R Lake sediment Trace element mass fraction

BCR-320R Channel sediment Trace element mass fraction

BCR-176R Fly ash Trace element mass fraction

IRMM-540R Oxide glass U mass fraction

IRMM-541 Oxide glass U mass fraction

IRMM-007/1-6 64Zn in 0.5 M HNO3 Isotope amount content

IRMM-3702 64Zn in 1 M HNO3 Isotope amount content

IRMM-643 32S in 2.8 M HNO3 Isotope amount content

IRMM-644 32S in 3.2 M HNO3 Isotope amount content

IRMM-645 32S in 2.8 M HNO3 Isotope amount content

IRMM-646 34S in 2.8 M HNO3 Isotope amount content

IRMM-651 64Zn in 0.5 M HNO3 Isotope amount content

IRMM-652 64Zn enriched in 0.5 M HNO3 Isotope amount content

IRMM-653 67Zn in 0.5 M HNO3 Isotope amount content

IRMM-654 68Zn in 0.5 M HNO3 Isotope amount content

ERM-BB350 Fish oil Polychlorinated biphenyl (PCB) mass fraction

ERM-CC141 Loam soil Trace element mass fraction

ERM-CD281 Rye grass Trace element mass fraction

ERM-BB422 Fish Trace elements mass fraction

ERM-CC141 Sediment Hg mass fraction (addition of a certified value to an existing CRM)

ERM-CE278k Mussel tissue Trace elements mass fraction

ERM-CD200 Bladderwrack Trace element mass fraction

ERM-EF001 Biodiesel Fuel parameters according to EN 14214:2012

IRMM-426 Wild berries Radionuclide activity concentration

IRMM-427 Pike-Perch Polyfluorinated alkyl substances (PFAS) mass fraction

53

Table A5: Environmental RMs (non-certified) released by JRC-IRMM in 2006-2015

Material code Matrix Property of interest Purpose of material

IMEP-40_2014 Seawater Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Zn EURL / PT

EMRP-ENV08_2014 Whole water Polybrominated biphenyl ethers, PBDE EMRP project

ENV08 EMRP-ENV08_2014 Whole water Polycyclic aromatic hydrocarbons, PAH

EMRP project ENV08

EMRP-ENV08_2014 Whole water Tributyl tin, PAH EMRP project

ENV08 EMRP-ENV08_2014

Model (suspended) Particulate matter, sediment PBDEs EMRP project

ENV08 EMRP-ENV08_2014

Model (suspended) Particulate matter, soil PAHs

EMRP project ENV08

EMRP-ENV08_2014

Model (suspended) Particulate matter, sediment TBT EMRP project

ENV08 EMRP-ENV08_2014 Humic acid solution, HA Technical grade HA solution EMRP project

ENV08 EMRP-ENV08_2014 Whole water PBDEs

CEN method standardisation

EMRP-ENV08_2014 Whole water PAHs CEN method

standardisation EMRP-ENV08_2014 Whole water TBT CEN method

standardisation

IAEA 375 Soil Radionuclides Material for intercomparison

54

Table A6: Engineering CRMs released by JRC-IRMM in 2006-2015

Material code Matrix Certified property

ERM-FD100 Silica in suspension Nanoparticle size

ERM-FD102 Silica in suspension Nanoparticle size

ERM-FD304 Silica in suspension Nanoparticle size

ERM-EC680k Polyethylene Trace element mass fraction

ERM-EC681k Polyethylene Trace element mass fraction

ERM-EC590 Polyethylene Brominated flame retardant mass fraction

ERM-EC591 Polypropylene Brominated flame retardant mass fraction

ERM-EF211 Petrol S mass fraction

IRMM-018a Silicon dioxide Si isotope ratios

BCR-261T Ta2O5 on Ta Areal density of oxygen atoms, oxide thickness ratio

ERM-FA013at Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013ax Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016at Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016av Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415k Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415l Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415m Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415n Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415o Steel Impact toughness according to ISO-148 (Charpy test)

IRMM-521R Ni foil Co mass fraction

BCR-724A Glass ceramic Thermal conductivity, thermal diffusivity

BCR-724B Glass ceramic Thermal conductivity, thermal diffusivity

BCR-724C Glass ceramic Thermal conductivity, thermal diffusivity

BCR-724D Glass ceramic Thermal conductivity, thermal diffusivity

ERM-FA013az Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bb Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA014p Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA015u Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016aw Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016az Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013ba Steel Impact toughness according to ISO-148 (Charpy test) (master batch 30 J)

ERM-FA013bb Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bc Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bd Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA015v Steel Impact toughness according to ISO-148 (Charpy test) (Master batch 80 J)

ERM-FA016ax Steel Impact toughness according to ISO-148 (Charpy test) (Master batch 120 J)

ERM-FA016ay Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016ba Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415p Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415r Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013be Steel Impact toughness according to ISO-148 (Charpy test)

55

ERM-FA013bf Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA014q Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA015w Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016bb Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016bc Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415t Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013ay Steel Impact toughness according to ISO-148 (Charpy test) (master batch 30 J)

ERM-FA013bg Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bh Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA015x Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA015y Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415u Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bi Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bj Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016be Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415s Steel Impact toughness according to ISO-148 (Charpy test) (master batch 150 J)

ERM-FA415v Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415w Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FC395k Diesel Cold filter plugging point (CFPP), Cloud point (CP)

ERM-EF411 Hard coal Proximates and trace element mass fraction

ERM-EF412 Brown Coal Proximates and trace element mass fraction

ERM-EF413 Furnace coke Proximates and trace element mass fraction

ERM-FA013bk Steel Impact toughness at 0 °C according to ISO-148 (Charpy test)

ERM-FA013bl Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bs Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bt Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016bf Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA016bg Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415aa Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415w Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415z Steel Impact toughness according to ISO-148 (Charpy test)

IRMM-471 Cementite Carbon mass fraction

BCR-089 TiAl6V4 Trace element mass fraction (addition of certified values to an existing CRM)

ERM-EB530A Al Au mass fraction (calibrant for k0-INAA)

ERM-EB530B Al Au mass fraction (calibrant for k0-INAA)

ERM-EB530C Al Au mass fraction (calibrant for k0-INAA)

ERM-FA013bm Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bn Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA015ab Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415ab Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415ac Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415ad Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA415ae Steel Impact toughness according to ISO-148 (Charpy test)

ERM-EB074A Electrolytic Cu Trace element mass fraction

56

ERM-EB074B Electrolytic Cu Trace element mass fraction

ERM-EB074C Electrolytic Cu Trace element mass fraction

ERM-EB075A Electrolytic Cu with added impurities

Trace element mass fraction

ERM-EB075B Electrolytic Cu with added impurities

Trace element mass fraction

ERM-EB075C Electrolytic Cu with added impurities

Trace element mass fraction

ERM-FA013bu Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bv Steel Impact toughness according to ISO-148 (Charpy test)

ERM-FA013bw Steel Impact toughness according to ISO-148 (Charpy test)

57

Table A7: Engineering RMs (non-certified) released by JRC-IRMM in 2006-2015

Material code Matrix Property of interest Purpose of material

IRMM-304 Silica in suspension Nanoparticle size Quality control, method developments

IRMM-310 Poly(ethyleneterephthalate) Brominated flame retardant mass fraction Quality control

IMEP-22 Petrol Sulfur Intercomparisons

Nanolyse_2011 Aqueous solution nano Ag low EU project Nanolyse

Nanolyse_2011 Aqueous solution nano Ag high EU project Nanolyse

Nanolyse_2011 Aqueous solution Silica low EU project Nanolyse

Nanolyse_2011 Aqueous solution Silica high EU project Nanolyse

Nanolyse_2011 Rapeseed oil Fullerenes, C60 (low) EU project Nanolyse

Nanolyse_2011 Rapeseed oil Fullerenes, C60 (high) EU project Nanolyse

Nanolyse_2011 Tomato soup Silica low EU project Nanolyse

Nanolyse_2011 Tomato soup Silica high EU project Nanolyse

Nanolyse_2012 Chicken paste nano Ag low EU project Nanolyse

Nanolyse_2012 Chicken paste nano Ag high EU project Nanolyse

Nanolyse_2012 Aquarius nano gelatine (low) EU project Nanolyse

Nanolyse_2012 Aquarius nano gelatine (high) EU project Nanolyse

Nanolyse_2012 Aquarius + ethanol nano gelatine (low) EU project Nanolyse

Nanolyse_2012 Aquarius + ethanol nano gelatine (high) EU project Nanolyse

Nanochop_01-2013 Aqueous solution Colloidal silica EU project Nanochop

Nanochop_02_2013 Aqueous solution Non-aminated silica EU project Nanochop

Nanochop_03_2013 Aqueous solution Quantum dots EU project Nanochop

IRMM-380_2014 Pigment Pigment yellow 83 EU project Nanochop

IRMM-381_2014 Fine chemical Barium sulfate EU project Nanodefine

IRMM-382_2014 Nanomaterial Carbon nanotubes EU project Nanodefine

IRMM-383_2014 Nanomaterial Nano steel EU project Nanodefine

IRMM-384_2014 Fine chemical (salt) Calcium carbonate EU project Nanodefine

IRMM-385_2014 Clay Kaolin EU project Nanodefine

IRMM-386_2014 Pigment Pigment yellow 83 opaque EU project Nanodefine

IRMM-387_2014 Fine chemical (salt) NM-220 Barium sulfate EU project Nanodefine

IRMM-388_2014 Fine chemical (oxide) TiO2 K2360 EU project Nanodefine

IRMM-389_2014 Polymer Amino methacrylate copolymer EU project Nanodefine

Nanodefine_2014 Polymer Nanopolymer mono-modal EU project Nanodefine

Nanodefine_2014 Polymer Nanopolymer tri-modal EU project Nanodefine

Nanodefine_2014 Polymer Silica tri-modal EU project Nanodefine

BIOREMA_1_2009 Biodiesel, B100 Numerous properties in fuel EU project Biorema

BIOREMA_2_2009 Biodiesel, B100 Numerous properties in fuel EU project Biorema

BIOREMA_3_2009 Biodiesel, B100 Numerous properties in fuel EU project Biorema

Quovadis_2006 Acid digest Heavy metals EU project Quovadis

58

Table A8: Nuclear CRMs released by JRC-IRMM in 2006-2015

Material code Matrix Certified property

IRMM-074 series 1 M HNO3 U-233/U-235 ratio,U-233/U-238 ratio, U-235/U-238 ratio

IRMM-1027i dried nitrate in CAB U-235, U-238 and Pu-239 amount content, U and Pu isotope amount ratios, mass

IRMM-075 series 1 M HNO3 U-236/U-238 ratio

IRMM-081a 5 M HNO3 Pu-239 amount content, Pu isotope amount ratios

IRMM-086 5 M HNO3 Pu-239 amount content, Pu isotope amount ratios

IRMM-1027j dried nitrate in CAB U-235, U-238 and Pu-239 amount content, U and Pu isotope amount ratios, mass

IRMM-3183 1 M HNO3 U isotope amount ratios

IRMM-3184 1 M HNO3 U isotope amount ratios

IRMM-3185 1 M HNO3 U isotope amount ratios

IRMM-3186 1 M HNO3 U isotope amount ratios

IRMM-3187 1 M HNO3 U isotope amount ratios

IRMM-1027k dried nitrate in CAB U-235, U-238 and Pu-239 amount content, U and Pu isotope amount ratios, mass

IRMM-3100 1 M HNO3 U isotope amount ratios

IRMM-3102 1 M HNO3 U isotope amount ratios

IRMM-3636 1 M HNO3 U-236, U-233 amount content, U isotope amount ratios

IRMM-3636a 1 M HNO3 U-236, U-233 amount content, U isotope amount ratios

IRMM-3636b 1 M HNO3 U-236, U-233 amount content, U isotope amount ratios

IRMM-3660 1 M HNO3 U-236 amount content, U isotope amunt ratios

IRMM-3660a 1 M HNO3 U-236 amount content, U isotope amunt ratios

IRMM-3660b 1 M HNO3 U-236 amount content, U isotope amunt ratios

IRMM-1027m dried nitrate in CAB U-235, U-238 and Pu-239 amount content, U and Pu isotope amount ratios, mass

IRMM-046b 5 M HNO3 U-233 and Pu-242 amount content, U and Pu isotope amount ratios

IRMM-1027n dried nitrate in CAB U-235, U-238 and Pu-239 amount content, U and Pu isotope amount ratios, mass

IRMM-3100a 1 M HNO3 U isotope amount ratios

IRMM-049d 5 M HNO3 Pu-242 amount content, Pu isotope amount ratios

IRMM-1027L dried nitrate in CAB U-235, U-238 and Pu-239 amount content, U and Pu isotope amount ratios, mass

IRMM-1027o dried nitrate in CAB U-235, U-238 and Pu-239 mass per vial, U and Pu isotope amount ratios

IRMM-019 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-020 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-021 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-022 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-023 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-024 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

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Material code Matrix Certified property

IRMM-025 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-026 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-027 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-028 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-029 UF6 U isotope amount ratios, U amount fractions, U mass fraction, U molar mass

IRMM-046c 5 M HNO3 U-233 and Pu-242 amount content, U and Pu isotope amount ratios

IRMM-1027p dried nitrate in CAB U-235, U-238 and Pu-239 mass per vial, U and Pu isotope amount ratios

IRMM-1000a dried nitrate production date (via 234U/230Th chronometer)

IRMM-1000b dried nitrate production date (via 234U/230Th chronometer)

IRMM-1027q dried nitrate in CAB U-235, U-238 and Pu-239 mass per vial, U and Pu isotope amount ratios