Global summit on regulatory science 2019 nanotechnology and nanoplastics : perspectives on nanotechnology and nanoplastics.
Date: 2020-07-09
Institutions: Joint Research Centre
Subjects: harmonisation of standards, nanotechnology, research method, research policy, research report

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This publication is a 
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Contact information 
Birgit Sokull-Kluettgen, European Commission, Joint Research Centre 
Anil K. Patri, U.S. Food and Drug Administration 
JRC-NANOTECHNOLOGY@ec.europa.eu  

EU Science Hub 
https://ec.europa.eu/jrc 

JRC120318 

EUR 30195 EN 

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ISBN 978-92-76-18435-5 

ISSN 1831-9424 

doi:10.2760/517689 

Luxembourg: Publications Office of the European Union, 2020 

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How  to  cite  this  report:  Allan  J.,  Sokull-Kluettgen  B.,  and  Patri  A.K.,  Gobal  Summit  on  Regulatory  Science  2019    Nanpotechnology  and 
Nanoplastics,  EUR  30195  EN,  Publications  Office  of  the  European  Union,  Luxembourg,  2020, 
ISBN  978-92-76-18435-5, 
doi:10.2760/517689, JRC120318. 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
JRC TECHNICAL REPORT 

Global Summit on Regulatory Science 2019 
Nanotechnology and Nanoplastics 

Perspectives on 
nanotechnology and 
nanoplastics 

Jacqueline E M Allan  

Birgit Sokull-Kluettgen  

Anil K Patri  

JRC120318 

2020 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Contents 

Foreword ...........................................................................................................................................................................................................................................................3 

Summary and Conclusions ................................................................................................................................................................................................................5 

1   Introduction ......................................................................................................................................................................................................................................... 11 

1.1 GSRS19 Programme Overview ................................................................................................................................................................................. 11 

1.2 Committees and Attendance ..................................................................................................................................................................................... 12 

2  Global regulatory science perspectives on nanotechnology and nanoplastics ........................................................................ 15 

3  Regulatory research needs for new and follow-on nanomedicines .................................................................................................. 23 

4  Safety assessment of Nanomaterials ......................................................................................................................................................................... 33 

5  Nanotechnology in the agri/food/feed sector ....................................................................................................................................................... 43 

6  Documentary standards and reference materials ............................................................................................................................................ 53 

7  Challenges concerning Nanoplastics ............................................................................................................................................................................ 63 

8  Poster session ................................................................................................................................................................................................................................... 71 

Annexes ........................................................................................................................................................................................................................................................... 79 

Annex 1. Agenda ............................................................................................................................................................................................................................. 80 

Annex 2. Biographies of speakers and session chairs ................................................................................................................................... 87 

Annex 3. List of participants ............................................................................................................................................................................................. 107 

1 

2 

Foreword 

The Global Summit on Regulatory Science (GSRS) is organised yearly by the Global Coalition 
for  Regulatory  Science  Research  (GCRSR).  This  international  coalition  was  established  in 
2013, with the aim of facilitating education, scientific training, and scientific exchanges in 
the field of regulatory science with an impact on public health. Partner organisations of the 
GCRSR come from Argentina (ANMAT), Australia / New Zealand (TGA/FSANZ), Brazil (ANVISA), 
Canada  (HC),  China  (CFDA),  European  Union  (EFSA,  EMA  &  JRC),  Japan  (MHLW  &  FSCJ), 
Republic of Korea (MFDS), Singapore (AVA), and the USA (FDA). 

The  2019  Global  Summit  on  Regulatory  Science  (GSRS19)  on  Nanotechnology  and 
Nanoplastics was co-
and the GCRSR, and hosted by the JRC at Ispra and Stresa (Italy), from 24-26 September 
2019.  The  GSRS19  attracted  almost  200  scientists  from  36  countries  around  the  world, 
representing regulatory agencies, academia and industry, to discuss global regulatory science 
perspectives  on  medical  products,  food,  and  standards  related  to  nanotechnology  with  a 
special session on emerging challenges with nanoplastics. This summit provided a venue for 
regulators,  policy  makers,  and  scientists  to  exchange  views  on  innovative  technologies, 
methods and regulatory assessments, as well as harmonising strategies to address emerging 
challenges via global collaborations.  

The organisers thank those that contributed to the success of the GSRS19, in particular, the 
invited speakers and poster presenters for their excellent scientific contributions, the session 
chairs and panellist for the fruitful discussions, and participants coming from all over the 
world that brought diverse perspectives of global importance. The organisers recognise the 
contributions  and  dedication  of  the  Scientific  Programme  Committee  and  the  immense 
amount of planning and hard work by the Local Organising Committee from the JRC in Ispra 
that contributed to the success of the summit. We also thank the professional and friendly 
staff from Hotel La Palma in Stresa (Italy) for their excellent hospitality. 

scheduled to be held 28-30 September 2020, at NIH Campus in Bethesda, Maryland, USA 
(more  information:  http://aralliance.org/gsrs/).  We  hope  to  see  you  at  this  summit  and 
contribute to its success. 

3 

4 

Summary and Conclusions 
The 2019 Global Summit on Regulatory Science (GSRS19) on Nanotechnology and Nanoplastics at 
Ispra and Stresa (Italy), 24-26 September 2019, was co-organised by the European Commission's 
Joint Research Centre (JRC) and the Global Coalition for Regulatory Science Research (GCRSR). The 
GSRS19  attracted  almost  200  scientists  from  around  the  world,  and  provided  a  platform  for 
interaction between those researching, producing and regulating nanomaterials, to exchange views 
and experiences on policies and practices in regulation, standards, definitions and methodologies for 
nanomaterials and nanoplastics.  

Global regulatory science perspectives on nanotechnology and nanoplastics 

 to enhance properties, reduce 
Nanotechnology is an area of product innovation that is developing 
 faster than regulatory 
consumption of materials, alleviate waste, and help the environment, etc. 
frameworks. Participants in GSRS19 stressed the importance of discussion, collaboration and mutual 
learning in regulatory science for nanotechnology. International and national forums are helping to 
bring stakeholders together in dialogues to address areas of shared interest and concern. Sharing of 
research  results  and  research  facilities  is  strengthening  the  science  base  for  regulation  of 
nanomaterials and nanotechnology-based products.  

The growing and diverse area of nanomaterials needs to have robust research and development, and 
appropriate, independent and rigorous regulation, with good linkages between the components of the 
system and partnerships between their actors   academia, industry and governments.  

Regulatory research needs for new and follow-on nanomedicines 

There is  a gradual increase in medical  products that utilize nanomaterial. In  addressing the many 
challenges of regulation and regulatory science to ensure that the nanomedicines that come onto the 
market  are  of  high  quality,  safe  and  efficacious,  the  importance  of  international  collaboration  on 
standards,  definitions,  reference  materials  and  regulations  was  stressed  many  times  during  the 
summit. A more holistic view of the benefits and potential risks, especially of complex nanomedicines, 
is needed and can be achieved if scientific and regulatory communities work more closely together. 
There  should  be  increased  efforts  to  ensure  that  testing  of  nanomaterials  and  nanomedicines  is 
rigorous, reproducible, and comparable between samples and situations, throughout the development 
pipeline.  Suitable  novel  tests  and  analysis  methods  must  be  developed  (and  be  complementary) 
specific to complex medical products if there is to be a robust regulation of nanomedicines and to 
update existing guidance, as applicable. Sharing of data and research methods and infrastructures 
will be an important part of this effort.  

Nanotechnology does not present a one-size-fits-all situation, there being many possible variants and 
associated  characteristics  of  any  single  type  of  material.  Only  by  working  together  can  the  vast 
potential  of  nanomedicines  be  realised  to  benefit  public  health,  not  least  by  ongoing  interface 
between developers and regulators, throughout the lifecycle of a product. The challenges are further 
compounded by the growing number of different types of novel materials with increased complexity, 
merging  nanotechnologies  with  other  emerging  technologies,  which  are  incorporated  into  novel 
medical  products.  Simplification  of  the  regulatory  system  is  being  sought,  including  approvals  of 
platform drugs and incorporating the use of novel methods for clinical trials, which should lead to 
reduction in the costs of bringing much needed nanomedicines to the patient.  

Safety assessment of Nanomaterials 

Many factors determine the safety of nanomaterials. Data is at the core of rigorous assessment of 
the risks of nanomaterials and their management. In a wide-ranging session on nanosafety, the main 
points  centred  on  the  complexity  of  nanosafety  assessment  and  the  difficulties  of  making  robust 
measurements across such a plethora of sizes and types of nanomaterials, with their many diverse 
characteristics and physical forms.  

5 

The assessment of nanosafety needs additional (and sometimes nano-specific) harmonised methods, 
standards and reference materials. International efforts are ongoing to address potential hazards of 
nanomaterials for health and the environment, but there is still much to achieve and understand. The 
importance  of  collaborations  was  stressed  and  continuing  communication  on  nanomaterials 
regulatory  science  research,  and  appropriate  harmonisation  of  legal  and  regulatory  structures. 
Collaborations  in  the  field  of  medicinal  products  was  identified  as  a  model  for  future  progress  in 
advanced nanomaterials. 

Nanotechnology in the agri/food/feed sector 

Nanotechnology has many potential agri/food/feed applications but the rapid growth in the number 
and  diversity  of  materials  will  increasingly  challenge  the  regulatory  system.  Potential  benefits  of 
using nanomaterials include safer products, lesser waste generation, leading to a cleaner environment 
and  better  quality  of  life.  The  current  risks  are  largely  unknown  as  data  is  either  lacking  or  not 
comparable, despite the high level of public funding given to research in the area over the last two 
decades.  Future  risks  are  unpredictable  as  nanotechnology  is  offering  a  plethora  of  complex  and 
diverse materials that are incorporated in additive and continuous manufacturing whose behaviour 
is, as yet, difficult even to model. The regulatory system also needs to be able to cope with the many 
new materials and potential applications that are on the horizon, in order to enable access to possible 
benefits  while  mitigating  risk.  In  some  cases,  the  area  of  agri/food/feed  faces  particularly  severe 
challenges  as  the  nanomaterials  have  a  biological  component,  similarly  in  this  regard  to 
pharmaceutical and medical applications. 

To address these challenges, communication is essential - on data and methods, on testing to ensure 
quality and comparability of results, on regulation and risk assessment - as is collaboration and the 
building of trust between stakeholder groups at national and international levels, within and across 
sectors. 

Documentary standards and reference materials 

There  are  many  complementary  efforts  in  documentary  standards  (such  as  OECD  and  ISO)  and 
reference materials but also a lack of international coordination, which give raise to some duplication. 
It was stressed that the OECD test guidelines are regulatory recognised methods used for the risk 
assessment  of  chemicals  and  the  OECD  is  currently  focussing  on  test  guidelines  targeting 
nanomaterials. There are deficiencies in inter-laboratory comparisons, and robust comparable results 
are  in short  supply. Lack  of reference  material  for  different  measurand  complicates this  situation 
further. Within the rapidly-developing domain of nanotechnology, it is particularly important that the 
work  on  reference  materials  and  standards  be  accelerated  through  better  communication  and 
collaboration. Actions need to be taken at multiple levels to develop and validate simple methods that 
can  be  easily  applied  by  industry.  To  make  progress  in  this  important  and  exacting  area,  it  was 
proposed to establish a standards interest group under the Global Coalition to better coordinate and 
communicate among regulatory science and regulation bodies.  

Challenges concerning nanoplastics 

Research into (micro- and) nanoplastics has started only recently and thus, there are many unresolved 
issues  of  terminology,  definitions,  sampling,  characterisation  and  the  assessment  of  hazard  and 
exposure  that,  in  combination,  make  it  difficult,  even  impossible,  to  evaluate  and  regulate  the 
potential risks of nanoplastics. While some information on microplastics is available, research data 
on nanoplastics is virtually non-existent. Coordinated effort is needed across all these areas in order 
to produce reference materials, robust standards, guidance and legislation. Since it is a global issue, 
such efforts can and should build upon the existing knowledge, lessons learned from nanomaterial, 
including  governmental  and 
and  with  existing  national  and 
intergovernmental bodies. A platform for information exchange on nano- and microplastics is needed, 
along  with  the  global  coordination  of  activities  on  methods,  documentary  and  reference  material 

international  mechanisms, 

6 

standards towards hazards, exposure and risk assessment to ascertain effects on environment and 
human health.  

Concluding remarks 

In  GSRS19,  it  was  stressed  that  increased  collaboration  is  needed  to  achieve  consensus  on 
terminology,  definitions,  sampling  and  characterisation  of  nanomaterials  and  the  assessment  of 
hazards and exposures. The challenges for regulators and scientists are further compounded by the 
growing number of different types of materials that contribute through their nano-size dimension.  

 between researchers on data 
Enhanced communication across all parts of the system is essential 
and methods, those undertaking testing to ensure quality and comparability of results, regulators and 
those being regulated.  

Increased  collaboration  between  stakeholder  groups  can  be  achieved  through,  for  example,  closer 
collaboration  between  agencies 
  at  international  level,  between  the  international  system  and 
national  systems,  across  different  domains  (food,  medical,  chemical,  etc.)  and  within  sectors. 
Achieving comparable datasets is a key global issue. A better structure for regulatory science can be 
created  by  developing  trust  between  individuals  and  organisations  through  data  transparency.  No 
matter what the approach or combination of approaches, the key to success will be the involvement 
of all stakeholders in creating a better, fit-for-purpose system.  

Report author: Jacqueline E M Allan1 

Editors: Birgit Sokull-Kluettgen and Anil K Patri 

1

7 

8 

9 

10 

1 Introduction 
The  Global  Summit  on  Regulatory  Science  2019  (GSRS19)  brought  together  scientists  from 
government,  industry,  and  academic  research  communities  from  around  the  world  to  address 
regulatory-research questions concerning nanotechnology and nanoplastics. It provided a platform 
for regulators, policy makers, and bench scientists to exchange views on innovative methodologies 
and  regulatory  assessments,  as  well  on  harmonising  strategies  on  regulatory  science  via  global 
collaboration. Nanotechnology research has an important role in enabling science-based regulatory 
decision-making across a wide range of scientific and technical disciplines by providing essential and 
fundamental background information. 

Nanomaterials offer a wide range of diverse functionalities due to their specific physical and chemical 
properties, which promote their use to meet the needs of a wide range of applications. They offer 
new avenues in diagnostics and therapeutics in healthcare, for example, and open up the opportunity 
to address previously unmet medical needs. They also find applications across food and agriculture, 
transport and logistics, energy and the built environment, etc. The number and variety of new and 
modified  nanomaterials  that  are  being  developed  and  the  range  of  applications  has  significantly 
increased over the last ten years. It is therefore of prime importance that regulatory science can keep 
pace  with  new  developments.  This  conference  provided  an  opportunity  for  the  regulatory  science 
community  to  consider  areas  including  regulatory  research  needs  for  nanomedicines,  safety 
assessments for nanomaterials, nanotechnology in the agri/food/feed sector and challenges in the 
domain  of  nanoplastics.  The  discussion  of  documentary  standards  and  reference  materials  was 
central to all areas. 

1.1 GSRS19 Programme Overview 

Focus of GSRS19 

The  Summit  focussed  on  knowledge  gaps  and  research  priorities  in  regulatory  science  in 
nanotechnology and nanoplastics. It also considered how these can be addressed and what platforms, 
mechanisms,  communities  of  practice,  and  networks  exist  (or  need  to  be  developed)  to  facilitate 
effective collaborations between international partners. 

Programme 

The first day of GSRS19 began with Welcome Remarks by the Global Coalition for Regulatory Science 

plenary  session  addressed  Global  regulatory  science  perspectives  on  nanotechnology  and 
nanoplastics with presentations both on national activities (for example, from the USA, Canada and 
Japan) and on the importance of collaboration and research in regulatory science.  

Parallel sessions took place on both days of the Global Summit. Each parallel session concluded with 
a  moderated  discussion  with  the  panel  of  the  speakers,  questions  from  the  audience  and 
brainstorming discussions on the session topic with panel and audience participation.  

The parallel sessions on the first day addressed the topics of Regulatory research needs for new and 
follow-on nanomedicines and Safety assessment of nanomaterials. The day concluded with a poster 
session and social dinner.  

The second day began with parallel sessions on Nanotechnology in the agri/food/feed sector and on 
Documentary standards and reference materials. The closing plenary session addressed Challenges 
concerning nanoplastics. 

11 

 
 
 
The programme for the two days is found in Annex 1, together with the biographies of speakers and 
session chairs (Annex 2), and the list of participants (Annex 3).  

The GSRS, including the social events, provided networking opportunities, and brought the community 
together to work towards greater common understanding of the topics  of the Global Summit and 
shared future goals. 

Satellite Visits 

The EC JRC offered the participants both training opportunities and laboratory visits at its Ispra site: 

  Hands-on  training  on  determining  size  distributions  of  nanomaterials  gave  participants  the 
opportunity to deepen their knowledge on how to measure nanoparticle size distributions using 
different  measurement  techniques  (such  as  single  particle  inductively  coupled  plasma  mass 
spectrometry, transmission electron microscopy, centrifugal particle sedimentation). Furthermore, 
the NanoDefiner e-tool, a decision support framework, was presented, and the participants could 
familiarise themselves with it. 

  There  was  an  introductory  course  on  the  Use  of  Reference  Materials  and  the  estimation  of 

measurement uncertainty.  

  Also visits to the EC JRC Nanobiotechnology Laboratory and ECVAM (EU Reference Laboratory for 
alternatives to animal testing) were offered, as was a tour to the EC JRC Visitors' Centre that 
included a presentation of EC JRC activities on Food Contact Materials. 

Satellite Meetings 

Apart from the excellent networking opportunities at the Global Summit, additional formal satellite 
meetings included:  

  A meeting of the Nanomedicines Working Group of the International Pharmaceutical Regulators 

Programme (IPRP),  

  The Annual Meeting of the European Food Safety Authority (EFSA) Nano Network; and  
  A Workshop on Standards for Regulatory Science of the ASTM International E56 Committee on 

Nanotechnology. 

1.2 Committees and Attendance 

Global Coalition for Regulatory Science Research (GCRSR) Co-Chairs 

William Slikker, U.S. Food and Drug Administration (FDA, USA)  

Marta Hugas, European Food Safety Authority (EFSA, EU) 

Scientific Programme Committee 

Anil K. Patri, U.S. Food and Drug Administration (FDA, USA) (Co-chair) 

Birgit Sokull-Kluettgen, European Commission Joint Research Centre (EC JRC, EU) (Co-chair)  

Susanne Bremer-Hoffmann, European Commission Joint Research Centre (EC JRC, EU)  

Marta Hugas, European Food Safety Authority (EFSA, EU) 

12 

 
  
 
 
 
 
Reinhilde Schoonjans, European Food Safety Authority (EFSA, EU) 

́rez de la Ossa, European Medicines Agency (EMA, EU) 

Michael Johnston, Health Canada (HC, Canada) 

Deborah Moir, Canadian Food Inspection Agency (CFIA, Canada) 

Neil Vary, Canadian Food Inspection Agency (CFIA, Canada) 

Nick Fletcher, Food Standards Australia New Zealand (FSANZ, Australia/New Zealand)  

Xingchao Geng, National Institute for Food and Drug Control (NIFDC, China)  

Attendance 

The  Global  Summit  attracted  around  200  participants  from  government  agencies,  industry,  and 
academia. Participants came from 36 countries representing wide geographical areas, including the 
USA,  Canada,  Argentina,  Chile,  China,  Japan,  Singapore,  Republic  of  Korea,  India,  Australia,  New 
Zealand,  and  Egypt,  as  well  as  from  many  EU  Member  States.  During  the  two  days  of  the Global 
Summit, there were over 50 presentations by invited speakers, five panel discussions and 28 poster 
presentations by scientists and students on the latest research related to the session topics.  

In  addition  to  the  two  days  of  the  Summit,  hands-on  training  on  determining  size  distribution  of 
nanomaterials was provided to 28 participants from 12 countries including EU Member States, Chile, 
India,  Mexico  and  Singapore.  An  introductory  course  on  the  use  of  reference  materials  and  the 
estimation of measurement uncertainty had 29 participants, and around 40 delegates visited the EC 
JRC facilities at Ispra. 

13 

 
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14 

2  Global regulatory science perspectives on nanotechnology 

and nanoplastics 

Co-chairs: Anil K. Patri (FDA, USA) and Birgit Sokull-Kluettgen (EC JRC, EU) 

Following a welcome to participants by both Session Co-chairs, Ms Birgit Sokull-Kluettgen explained 
that the goal of the Global Summit is to address the questions: 

  What needs to be accomplished and what are the research gaps and/or priorities in regulatory 

science in nanotechnology in the areas being discussed? and 

  How  can  these  priorities  be  addressed  (e.g.  through  platforms,  mechanisms,  communities  of 
practice,  and  networks  (existing,  or  that  need  to  be  developed))  to  facilitate  effective 
collaborations between international partners? 

Reflecting on this context for the Summit, opening remarks were made by  William  Slikker (FDA, 
USA) on behalf of the Global Coalition for Regulatory Science Research (GCRSR). The working groups 
of the Coalition cover nanotechnology as a topic as well as bioinformatics and emerging technologies, 
with a focus on regulatory priorities. The goal of the Coalition is to support research for regulatory 
science, which it achieves by facilitating education, scientific training, and scientific exchanges in the 
field of regulatory science with an impact on public health. The GCRSR sees nanotechnology as an 
area of significant expansion. The importance of learning from one another across the domains of 
regulatory science was stressed, as well as the importance of the topic of nanoplastics.  

2. 
Elke Anklam 
The JRC is a policy neutral body of the European Commission, one part of the institutional triangle of 
the European Union, a triangle consisting of the European Parliament, the Council of Europe and the 
European  Commission.  As  a  service  of  the  European  Commission  (EC),  the  JRC  is  responsible  for 
providing  both  a  science  and  knowledge  service,  supporting  EU  policies  with  independent  advice 
throughout  the  whole  policy  cycle.  This  encompass  knowledge  production  and  knowledge 
management.  

With six locations in five EU Member States (Italy, Belgium, Germany, the Netherlands and Spain), the 
JRC is responsible for 42 large scale research facilities that house 1,500 core research staff, half of 
its total workforce, across a broad range of science and technologies. The research staff of the JRC 
produce  over  1,400  scientific  publications  per  year,  with  83%  of  core  staff  possessing  a  doctoral 
degree. While the JRC started in the area of nuclear science, it works now on many themes, one of 
which is Health, Consumers and Reference Materials. The activities include production of reference 
materials  at 
in  support  of  EU  policy  on 
nanomaterials/nanotechnology, health technology, consumer products and micro- and nanoplastics 
in Ispra. 

(Belgium)  and  work 

the  JRC  Geel  site 

The JRC aims to support innovation in Europe in many ways, including through Open Access to JRC 
Research Infrastructures by external users3. Since the start of open access in June 2017, there have 
been 19 calls enabling such open access. These have resulted in 87 user institutions being involved 
across 24 countries in 58 projects (six having been completed), with 199 individual users. 

Anil K. Patri (FDA, USA) presented Nanotechnology regulatory science at US FDA
to  the  regulation  of  production  of  nanotechnology  is  to  accept  that  promise,  risk  and  uncertainty 
accompany  all  new  technologies.  Therefore,  the  FDA  took  the  decision  not  to  introduce  new 
regulations  for  nanomaterials,  believing  that  its  existing  framework  is  sufficient  to  regulate 
nanomaterials and products containing nanomaterials.  

2

3

15 

                                          
 
 
Horizon  scanning  and  internal  reviews  of  product  submissions  are  key  components  of  regulatory 
science research on nanotechnology at FDA. Nanotechnology Core Facilities provide laboratory testing 
capacity at FDA, enabling the development of testing methods and standards related to the safety 
assessment  of  products  that  contain  nanomaterials  or  otherwise  involve  nanotechnologies.  The 
CORES  (Collaborative  Opportunities  for  Research  Excellence  in  Science)  programme  has  been 
established  by  the  FDA  to  foster  collaborative  and  interdisciplinary  research  on  product 
characterisation and safety. FDA also has a programme to train staff to evaluate scientific data for 
regulatory applications involving nanotechnologies. The FDA conducts gap analyses and establishes 
collaborative research to address those gaps, the outcomes being used for staff training, guidance 
documents (particularly those to help industry4), and works with stakeholders on the development 
and recognition of standards.  

The  FDA  cooperates  with  other  US  government  departments  and  agencies  via  the  National 
Nanotechnology Initiative (NNI)5 and asks industry to seek a dialogue with it early in the development 
phase.  It  also  works  with  other  countries  bilaterally  on  nanotechnology  topics  including  capacity 
building, for example, through joint and collaborative workshops (e.g. with Health Canada, and with 
regulation organisations in India). 

The  FDA  collaborates  globally  on  regulatory  topics,  one  priority  being  the  question  of  how  to 
consistently characterise nanomaterials globally. It participates, for example, in ISO/TC 2296, ASTM 
E567 and similar groups to develop standards suitable for use by industry.  

The speaker identified progress in regulatory science in nanotechnology as including high levels of 
publication, however leading only, so far, to a low number of products being developed. There are 
many  reports  of  positive  findings  in  cancer  research  and  the  active  targeting  of  cancer  using 
nanotechnology-based agents, but, despite this vast effort, there is much still to be achieved to bring 
solutions to the point of their being a significant number of products on the market. On a positive 
note, the FDA is receiving increasing numbers of submissions of nanomaterial-containing products in 
this area, many being now in clinical trials and others having been approved for future drugs and 
devices.  

Marta Hugas (EFSA, EU, and Co-chair of GCRSR) spoke about The importance of collaboration and 
research in regulatory science. The European Food Safety Authority (EFSA)8, an independent agency 
of the EC, assesses risks associated with food and the feed chain. Its remit covers food and feed 
safety;  nutrition  (including  additives);  animal  health  and  welfare;  and  plant  protection  (including 
pesticides)  and  plant  health.  EFSA  provides  fit-for-purpose  scientific  advice  to  inform  policy  and 
regulation and their implementation for human and food/plant health. It also uses environmental risk 
assessments to explore the possible impact of the food chain on the biodiversity of plant and animal 
habitats.  

In close collaboration with national authorities and in open consultation with its stakeholders, EFSA 
provides  independent  and  transparent  scientific  advice  and  clear  communication  on  existing  and 
emerging risks associated with the food chain. It aims to provide, both for experts and for the general 
public, accurate and timely information on food safety issues, to raise awareness and explain the 
implications of scientific results.  

EFSA operates through a Scientific Committee and Panels composed of independent scientific experts 
who undertake scientific assessments and develop related assessment methodologies. Its ten Panels 
cover areas including contaminants in the food chain; food contact materials, enzymes and processing 
aids; and food additives and flavourings. To address the use of nanotechnologies and nanomaterials, 
it  established the  EFSA  Scientific  Network  for  Risk  Assessment  of  the use  of  Nanotechnologies in 

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Food and Feed9, to facilitate the exchange of information between EFSA and Member States, and for 
the prioritisation of risk assessment activities. It also has a Working Group on Nanotechnologies in 
Food and Feed.  

Mauro  Ferrari  (University  of  St.  Thomas,  USA  and  incoming  President  of  the  European  Research 
e 
Council) addressed The clinical translation of nanomedicines, with the sub-title of 

.  

The speaker highlighted many positive aspects of the clinical translation of nanomedicines. Regulation 
is an essential part of the process of product development and release to the market and must be 
considered as early a

use competitive know-how and intellectual property. Being wise about regulation is a key part of the 
mission of researchers and developers in nanomedicine as well as being their ethical responsibility to 
society.  

Basic  science  is  increasingly  a  part  of  all  stages  of  innovation  and  product  development  in 
nanomedicines, meaning that changes can be made at many points in the creation of a product. Every 
such  change  may  have  a  regulatory  implication  so  there  needs  to  be  clarity  in  drug  design  and 
production to ensure that the process can proceed. In science, change can be ongoing but, in product 
development, once the needs are met no further change should be made. 

Nanotechnology is the means to concentrate treatments and reduce the amount of harm done to 
other parts of the body than the target site. Recently, there have been many developments in the 
area  of  nanomedicines,  from  the  concerns  about  biodistribution  to  the  continuation  of  the  highly 
successful  National  Cancer  Institute  (NCI)10  of  the  National  Institutes  of  Health  (NIH)11  and  high 
visibility corporate setbacks in clinical trials. However, there has also been the emergence of fourteen 
new nanodrugs since 2005 and the emergence of new fields based on nanotechnology or enabled by 
it, such as RNAi therapeutics.  

Key to the future success of nanomedicines is the ability of researchers, industry and regulators to 
work together to bring potential products to the market. In this, establishing the right partnerships 
between the regulator and regulatory scientists is paramount.  

In addition to working on scientific aspects 
 such as the need to have nanomaterials that dissolve 
harmlessly in body, to be able to better concentrate a treatment in a specific location and to achieve 
sequential multiple actions of drugs using nanotechnology 
 there needs to be a greater focus on 
establishing teams to address the whole value chain, with regulatory aspects being dealt with on an 
ongoing basis and in parallel throughout research, development and deployment to markets. There is 
also a need for new, not-for-profit mechanisms to bring the research funded by taxpayers through 
development and to the wider population as new diagnostics and therapeutics to benefit everyone 
who needs them.  

Primal Silva (Canadian Food Inspection Agency, Canada) presented Current research and regulatory 
approach for nanomaterials and nanoplastics in Canada. Several Canadian departments and agencies 
work  to  ensure  safe  use  of  nanotechnology,  including  Health  Canada  (HC)12,  with  its  Healthy 
Environments  and  Consumer  Safety  Branch  (HECSB)13;  Environment  and  Climate  Change  Canada 
(ECCC)14;  Agriculture  and  Agri-Food  Canada  (AAFC)15;  and  the  Canadian  Food  Inspection  Agency 

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(CFIA)16. They adopt a regulatory focus in order to mitigate risk, building an inventory of nanomaterial 
products on the market, determining how nanomaterial products are used or consumed, considering 
lifecycle and exposure and assessing biological effects of specific nanomaterials. Health Canada and 
agement Plan (CMP) by taking any 

action on potentia

. 

The Canadian nanomaterial regulatory approach follows the OECD Council Recommendation on the 
Safety Testing and Assessment of Manufactured Nanomaterials17  18  to apply existing international 
and national chemical regulatory frameworks or  other management systems adapted to take into 
account  the  specific  properties  of  manufactured  nanomaterials
Canadian Environmental Protection Act (CEPA, 1999). The Canadian Food and Drugs Act19, Consumer 
Product Safety and Hazardous Products Act20, Pest Control Products Act21, Feeds Act22, Fertilisers Act23, 
and Health of Animals Act24 can also be applied as relevant to nanomaterials. Tools within the CMP 

Working Definition for Nanomaterials25. 

Comparability between the Canadian and US approaches to nanotechnology includes the similarity of 
their definitions of a nanomaterial and their shared activities on regulation via the Canada-United 
States Regulatory Cooperation Council (RCC) through its nanotechnology work plan. This highlights 
the importance of developing a common approach to prioritizing and conducting nanomaterial risk 
assessments and on data gathering to advance the understanding of exposure to nanomaterials. They 
are also working together on the development of a classification scheme for nanomaterials based on 
their chemical composition and unique properties. This scheme would allow for the identification of 
nanomaterials that behave differently from non-nanoscale forms to help prioritise risk assessments. 
The  RCC  is  also  working  on  the  creation  of  a  nanomaterials  use  matrix  to  identify  commercial 
nanomaterials that are in use. 

The  speaker  highlighted  the  importance  of  data  to  enable  the  assessment  of  the  risks  of 
nanomaterials and the management of any risks, data on composition and morphology, particle size 
and size distribution, electrical, mechanical and optical properties, surface-to-volume ratios, chemical 
reactivity, and agglomeration and aggregation properties. 

Collaboration was seen as very important in enabling the potential of nanotechnology to be realised 
through  safe  products.  Canadian  agencies  work  with  the  OECD  as  well  as  regulatory  agencies  in 
Europe  and  the  RCC  to  harmonise  approaches  to  safety  assessments  of  nanomaterials,  to  share 
information and to address challenges. It also works with stakeholders to foster research and promote 
the responsible development of nanomaterials. In the domain of standards, Canadian agencies work 
with  organisations  at  national,  multinational  and  global  levels  (ISO/TC229,  OECD)  to  harmonise 
approaches  to  safety  assessment,  and  to  share  information  on  products  and  labelling,  methods, 
definitions and terminology and standardised methods to characterise nanomaterials. 

The  US  National  Nanotechnology  Initiative  (NNI)26  is  Leveraging  advances  in  nanotechnology  and 
international collaboration to address emerging contaminants, as presented by Lisa Friedersdorf 
(National Nanotechnology Coordination Office (NNCO), USA).  

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The NNI is a collaborative effort of more than twenty US Departments and agencies27. It operates 
under  the  National  Science  and  Technology  Council  of  the  White  House  Office  of  Science  and 
Technology  Policy.  Executive  Office  of  the  President.  One  of  its  coordination  mechanisms,  the 
Subcommittee  on  Nanoscale  Science,  Engineering  and  Technology  (NSET)  has  a  Nanotechnology 
Environmental  and Health Implications (NEHI)28  Working Group co-ordinating  Federal research and 
development directed at understanding the environmental, health, and safety (EHS) implications of 
nanotechnology. With members including regulatory and research agencies, it focuses on the six core 
topics  of  nanomaterial  measurement  infrastructure;  human  exposure  assessment;  human  health; 
environment;  risk  assessment  and  risk  management;  informatics  and  modelling.  The  agencies 
involved in NEHI have developed guidance documents covering topics including worker safety and 
provide webinars on nanotechnology EHS. Information is disseminated by (approximately  monthly) 
webinars on topics such as Characterisation and Quantification of Engineered Nanomaterials: Drivers 
of NanoEHS Research; Nanotechnology-Related Standards; and Working Safely with Nanomaterials 
in the Laboratory. The webinars are archived on the nano.gov website29, together with resources for 
nanotechnology laboratory safety.30  

Collaboration  between  the  US  and  other  countries  include  the  RCC  mentioned  above  and  EU-US 
Nanotechnology Communities  of  Research  (CoRs),  which  are  scientist-led and globally  open  to all. 
Nanotechnology  CoR  EHS  topics  include  characterisation;  databases  and  computational  modelling; 
human and ecotoxicity; exposure through product life; risk assessment; and risk management and 
control.  Participants  work  together  on  co-authored  papers,  workshops  and  webinars.  There  are 
ongoing activities to build a CoR on nanomedicine based on growing existing collaborations.  

On nanoplastics, it was noted that there is an informal US Nanoplastics Interest Group of 15 agencies, 
interested in leveraging advances in nanotechnology, building on relationships and mechanisms for 
collaboration, and focussing on addressing current concerns and preventing future contamination.  

An  increasingly  important  approach  to  nanosafety  is  Safe  by  design:  creating  nanomaterials  of 
tomorrow to be safe for use and across their lifecycle from production to waste, or recycling and 
reuse, as presented by Carlos Eduardo Lima da Cunha (EC Directorate General for Research and 
Innovation,  EU).  Through  a  change  of  mind-set,  adopting  a  safe-by-design  approach,  the 
nanomaterials  of  tomorrow  can  have  the  required  advanced  properties  and  being  both  safe  and 
carbon neutral to support the circular economy and safety throughout the lifecycle of a product. Safe 
by design can be a means to drive innovation forward.  

In  the  EU  context,  support  mechanisms  include  Digital  Innovation  Hubs  and  Open  Innovation  Test 
Beds. With technical universities or research organisations at the core, Digital Innovation Hubs31 are 
one-stop-shops  for  companies  -  especially  SMEs,  start-ups  and  mid-caps  -  to  access  technology-
testing, financing advice, market intelligence and networking opportunities, supporting companies to 
achieve a digital transformation. Open Innovation Test Beds32 offer access to the physical facilities, 
capabilities and services need in the development, testing and upscaling of advanced materials in 
industrial environments, helping to bring them within the reach of companies. Open Innovation Test 
Beds (OITBs) upgrade existing (or support the setting of new) public and private test beds, pilot lines, 
and demonstrators to develop, test and upscale nanotechnologies and advanced materials for new 
innovative products and services in specific domains.  

The speaker noted that there are different mind-sets in the US and the EU around regulation and that 
the  EU  could  benefit  from  more  regulation  as  a  means  to  drive  innovation,  also  advocating  the 

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development  and  agreement  on  international  standardised  methods  to  characterise  particles  to 
support work on standards and support regulation.  

Haruhiro  Okuda  (National  Institutes  of  Health  Science  (NIHS),  Japan)  described  the  Progress  of 
regulatory science in Japan. Regulatory science in Japan focuses on achieving the best outcome for 
human health and society. Ja
aim to ensure the longest, good-quality life for its people. The healthcare policy of Japan aims to 
provide the best level of medical care in the world by promoting integrated medical R&D activities 
and by seamlessly transferring research outcomes into practical applications.  

Responsibility for regulation and regulatory science in the area lie with the Ministry of Health, Labour 
and  Welfare  (MHLW)33;  the  Pharmaceuticals  and  Medical  Devices  Agency  (PMDA)34;  the  National 
Institute of Health Sciences (NIHS)35; and the Agency for Medical Research and Development (AMED)36. 
Japan aims to lead the world in regulatory innovation based on regulatory science. Regulatory science 
is seen as a science to enable accurate assessment, evaluation and decision-making based on robust 
(scientific) evidence.  

The  PMDA  established  a  Regulatory  Science  Centre  in  2018,  one  of  its  roles  being  to  promote 
innovative  approaches  to  advanced  therapies  and  technologies.  Its  activities  include  the  horizon 
scanning  needed  to  enable  regulators  to  keep  pace  with  new  developments.  It  also  supports 
collaboration between university research institutes, medical institutions and the PDMA Science Board. 
It is also working towards actively using clinical trial data and real world data (electronic healthcare 
records). Patient information from hospital databases is being analysed to identify adverse events 
and  to  help  in  product  development  and  evaluation  in  large  populations  (e.g.  by  pharmaceutical 
companies and insurance companies).  

Research is at the core of all activities in the integrated system being created in Japan to support 
health and long life, with research on innovative pharma, medical devices and regenerative medical 
products, combined with research on regulatory fields, and on avoidance of dangers and on ensuring 
the quality and safety of food and lifestyle based on scientific evidence.  

In summary, in Japan, regulatory science research on cutting-edge pharmaceutical products has been 
intensified  by  the  Act  on  Promotion  of  Healthcare  Industries  and  Advancement  of  Healthcare 
Technologies  as  well  as  the  establishment  of  the  Agency  for  Medical  Research  and  Development. 
Reforms are being sought (by MHLW/PMDA) to develop a rational and efficient regulatory system, 
based on regulatory science, and a combination of horizon scanning and data mining are being used 
to inform new and better healthcare and healthcare products.  

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3  Regulatory research needs for new and follow-on 

nanomedicines 

́rez de la 

Ossa (EMA, EU) and Michael Johnston (Health Canada, CA) 

The parallel session on nanomedicines began with perspectives from the USA, India, the EU, Singapore 
and Norway, and concluded with industry views and a panel discussion. 

Katherine  Tyner  (FDA,  Office  of  Pharmaceutical  Quality,  USA)  presented  Regulatory  research 
supporting the development of drug products containing nanomaterials: A US-FDA perspective. 

At the FDA Centre for Drug Evaluation and Research (CDER), the focus is on ensuring that safe and 
effective drugs of high quality are available to improve the health of Americans. CDER regulatory 
science  programmes  operate  in  areas  including  applied  regulatory  science,  clinical  pharmacology, 
biomarkers,  clinical  trial  methodology,  drug  safety  monitoring,  generic  drugs  and  bioequivalence, 
manufacturing  innovation,  prescription  drug  advertising  and  risk  communication,  product  quality 
assessment and radioactive drug research. It also undertakes and leads activities to streamline the 
drug development process and ensure drugs are safe and effective. 

Approvals  sought  through  submissions  to  the  CDER  typically  fall  into  one  of  four  categories:  (1) 
Investigational  New  Drug  Applications  (INDA):  a  request  to  administer  an  investigational  drug  or 
biological product to humans; (2) New Drug Applications (NDA): approval for a new pharmaceutical 
for sale and marketing; (3) Biologic License Applications (BLA): comparable to NDA, but for biologics 
(e.g.  monoclonal  antibodies,  proteins);  and  (4)  Abbreviated  New  Drug  Applications  (ANDA):  the 
application for a US generic drug approval usually refers to generics. 

The drugs are evaluated37 by the CDER for safety, efficacy and quality. Submissions to the FDA of 
drug products in the above categories and containing nanomaterials have being rising significantly38 
from 5 to 15 a year in the 1990s, to between 15 and 25 a year since 2010, although this is partly 
driven by the rise in the number of submissions related to generic drugs.  

the  science  of  developing  new  tools,  standards,  and 

approaches to assess the safety, efficacy, quality, and performance of all FDA-regulated products
Regulatory science and research forms the foundation for risk-based evaluation of drug products, 
including review of drug product applications, inspection and surveillance, and standards and policy 
development. They affect all drug product areas: new drugs, generics, over-the-counter drugs and 
biotechnology products. In particular, for new technologies, foundational research contributes in the 
areas of quality and safety (e.g. different toxicity pathways may result from difference agglomeration 
structures). There is also a need for targeted research on issues and limitations, to support quality 
(e.g. in vitro  release testing for a given system)  and for safety  (e.g. macrophages are first line of 
defence against, e.g., listeria 
 but does their behaviour change if they are full of nanoparticles?). 
Finally, the presenter spoke about the need for standardisation and presented the FDA activities in 
the  area,  including  FDA  CDER  participation  at  the  Joint  Sub-committee  on  Nanotechnology  of  the 
United  States  Pharmacopeia  (USP),  the  ASTM  E56  Committee  on  Nanotechnology,  ISO/TC229 
Nanotechnologies and the OECD WPMN (Working Party on Manufactured Nanomaterials). Its goals 
are to prioritise nanotechnology standards based on FDA needs, assist in development of standards, 
and consolidate FDA comments for nanotechnology standards that are up for review.  

In  conclusion,  regulatory  science  in  the  USA  forms  the  foundation  of  science-based  regulatory 
decision-making and can be divided into phases that contribute from the basic understanding of a 
technology to the development of standards. Nanotechnology can serve as an example of how to 

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address  and  incorporate  a  new  technology  into  a  regulatory  setting.  Work  on  nanotechnology 
standards is long-term and additional nanotechnology-related areas need to be addressed, including 
medical devices and complex drugs (e.g. multi-stage drugs and drugs with highly complex structures).  

Amit K. Dinda (All India Institute of Medical Sciences (AIIMS)39, India) spoke about the Challenges in 
the development of an Indian guideline for nanopharmaceuticals. The market size for nanomedicine 
and nanodevices in India is small but high growth is predicted, with an expected market of up to USD 
2  billion  annually  by  2023.  Several  Indian  companies  have  developed  nanomedicines  that  are 
preclinical  development,  in  clinical  trials  or  marketed.  Indian  companies  have  invested  strongly  in 
nanopharmaceuticals  but  national  regulation  does  not  yet  fully  support  their  manufacture  and 
deployment.  

by  the  Indian  Government  in  2019  for  finished  formulation  nanopharmaceuticals  and  active 
altered 
dimensions, properties or phenomenon due to nanotechnology 40. The guidelines cover the scientific 
rationale for developing the nanopharmaceuticals and a comparison with existing drugs to show, via 
in vitro and in vivo studies, improved safety, efficacy, reduction in toxicity profile, reduction in required 
dose or frequency of administration, improvements for patients, cost benefit or other benefits.  

The  speaker  highlighted  the  challenges  in  developing  regulatory  guidelines  for  nanoformulations. 
There is the need to clearly define the critical attributes of the product, to undertake testing using 
many  different 
(immunological)  and 
pharmacological properties, to have available appropriate and validated in vitro and in vivo models, 
to  ensure  regulatory  alignment  (e.g.  across  potential  markets)  and  to  ensure  pharmacovigilance 
throughout the life cycle of the nanopharmaceuticals.  

to  establish  physicochemical,  biological 

techniques 

́rez de la Ossa (European Medicines Agency (EMA), EU) and Susanne Bremer-
Hoffmann  (EC  JRC,  EU)  presented  Nanomedicines:  EU  regulatory  experience,  challenges  and 
regulatory research work. The speakers highlighted that nanotechnology is still an emerging science 
with great potential in a wide range of applications including drug delivery, diagnostics, theranostics 
and regenerative medicine.  

́rez de la Ossa reported that in 2011 the EC published a Recommendation on the 
definition of nanomaterial41 with size as the critical factor (1-100 nm) although acknowledging that 
that upper limit of 100 nm is not scientifically justified across the whole range of nanomaterials. The 
special  circumstances  prevailing  in  the  pharmaceutical  sector
Committee on Emerging and Newly Identified Health Risks stated that the Recommendation should 
not  prejudice  the  use 
devices 42.  

The EMA operates a working definition of nanomedicines as medicinal products that are purposely 
designed systems for clinical applications and have at least one component at the nano-scale, leading 
to definable specific properties and characteristics providing clinical advantages, the nanotechnology 
offering specific benefits in, for example, dosage, drug targeting or reduced toxicity.  

The  nanomedicines  evaluated  by  EMA  include  liposomes  (Caelyx®,  Myocet),  iron  nanoparticles, 
nanocrystals,  albumin  nanoparticles  (Abraxane)  and  lipid  nanoparticles  but  there  are  many  other 

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types of systems under research43 44. It was hi
variety of 

The presenter provided an overview of the major deficiencies identified by EMA during the evaluation 
of marketing authorisation applications for nanomedicines. These pertained to insufficient product 
characterisation  (chemistry,  manufacturing  and  control  (CMC)),  inadequate  specifications  and 
pharmacokinetic studies for the so-
innovator product).  

The presenter also provided an overview of the support offered by EMA to developers to help them 
to  launch  safe  and  beneficial  products  onto  the  market.  This  includes  guidance  documents45  (i.e. 
reflection papers on liposomes, iron oxide nanoparticles, block copolymer micelles and nanoparticle 
coatings);  provision  of  scientific  advice46;  and  meetings  with  the  Innovation  Task  Force47,  a 
multidisciplinary group with scientific, regulatory and legal competences that works on coordination 
across the EMA and provides a forum to discuss scientific, legal and regulatory issues of emerging 
therapies and technologies with  applicants,  especially SMEs,  academics  and  researchers.  The  EMA 
also supports its stakeholders through policy (including the EMA Regulatory Science Research Strategy 
202548)  and  by  ongoing  liaison  on  nanomedicines  with  international  partners  including  the 
International  Pharmaceutical Regulators  Programme  (IPRP)49
Pharmaceuticals and Medical Devices Agency (PMDA)50. 

As  nanomedicines  are  complex,  attention  needs  to  be  paid  during  their  early  development  to  the 
critical 
nd  safety;  the  identification  of 
appropriate analytical characterisation methods; and ensuring that scale-up to a reproducible large-
scale  manufacturing  process  can  be  achieved.  To  support  developers  in  achieving  these,  they  are 
encouraged  to  remain  in  contact  with  the  EMA  from  the  early  stages  of  development  to  the 
applications for marketing authorisation. 

Continuing  the  joint  presentation,  Ms  Susanne  Bremer-Hoffmann  (EC  JRC,  EU)  highlighted  the 
activities of the European Commission's Joint Research Centre (JRC) in the field of Nanomedicine, 
which  aims  to  provides  researchers  with  a  transdisciplinary  testing  infrastructure  for  preclinical 
characterisation assays (physical, chemical,  in vitro and in vivo biological testing) of nanoparticles 
used  for  medical  applications.  The  JRC  offers  open  access  to  its  laboratory  infrastructure  to  both 
academia and SMEs (with 14 projects to date) and is a partner in European research consortia such 
as REFINE (H2020: Regulatory science  framework for Nano(bio)material-based medicinal products 
and devices)51 and EU-NCL (the EU Nanomedicine Characterisation Laboratory)52. The international 
policy  collaborations  of  the  JRC  in  this  field  include  contributing  to  the  IPRP  Working  Group  on 
Nanomedicines49 and bilateral collaboration with NIST. It also works with EU regulators (e.g. the EU 

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Innovation  Network,  EU-IN53)  and  contributes  to  work  on  standards,  interacting  with  international 
bodies including ISO, CEN and ASTM.  

As a partner of the REFINE consortium, the JRC, lead the tasks to identify and summarize current 
challenges  in  the  regulation  of  nanomedicines.  The  systematic  analysis  of  regulatory  documents, 
standards,  guidance  documents,  conference  and  workshop  reports  as  well  as  peer-reviewed 
publications is now available as a white paper aiming to guide research efforts including European 
projects in the field-. In particular, the lack of relevant and reliable methods/ tools for quality and 
safety  assessments  as  well  as  the  need  to  develop  new  approaches  supporting  the  regulation  of 
borderline  products  and  nanosimilars  were  identified  as  top  priorities  necessary  to  advance  the 
regulatory science of nanomedicines. The JRC is currently investing significant efforts in the review 
of existing methods that can deliver necessary information to regulate nanomedicines54. However, 
even  if  formal  standards  exist,  they  have  often  been  developed  for  a  different  category  of 
nanomedicines  or  nanomaterials  used  in  other  industrial  sectors.  Additional  efforts  are  needed  to 
assess their performance for the huge variety of nanomedicines. Other areas suffer from a complete 
absence of standardised methods. The evaluation of existing methods for their potential to become 
a formal standard is now crucial for progressing the field. Especially methods addressing information 
gaps such as i) effects on the blood and immune system; ii) the kinetic properties in biological media 
(including  drug  release  kinetics,  degradation  mechanisms  and  products  and  agglomeration, 
aggregation  and  adhesion  characteristics);  iii)  ADME  (absorption,  distribution,  metabolism  and 
excretion) and biodistribution; iv) surface properties; and vi) drug loading and release are needed. The 
challenge  of  an  international  acceptance  of  documentary  standards  deriving  from  various 
standardisation bodies that often differ in their composition, working modalities etc. requires more 
attention  in  particular  since  regulatory  acceptance  of  standards  is  often  laid  down  in  respective 
legislations. 

In conclusion, the speaker summarised priorities in regulatory science for nanomedicine as including: 
developing  a  better  evidence  base  for  priority  setting  for  standard  development  (e.g.  through 
collection of case studies from agencies) and agreeing a standardisation path that can be accepted 
by all agencies. These progressive steps can be supported through horizon scanning activities in order 
to detect quality and safety issues (e.g. using text mining of the burgeoning scientific literature) and 
work on the similarity of follow-on products. The Nanomedicines Working Group of the International 
Pharmaceutical Regulators Programme was identified as an appropriate mechanism to tackle these 
challenges.  

Matthias  G.  Wacker  (National  University,  Singapore)  presented  on  Translational  nanomedicine 
How to predict clinical performance?, focussing on the importance of ensuring that clinical data is 
complemented by laboratory-based information and, as necessary, animal testing. The work at his 
laboratory  at  the  University  of  Singapore  is  primarily  focussed  on  identifying  the  critical  quality 
attributes (CQAs) of the nanomedicines from the clinical data sets; determining which in vitro and in 
vivo  methods  can  provide  relevant  markers  for  clinical  performance.  Further,  he  is  developing  a 
toolbox  of  ways  to  reliably  characterise  the  CQAs,  and  explaining  pharmacokinetics  of  previous 
formulations and designing new ones with improved properties. Elimination of nanomedicines from 
blood circulation is a key area of activity of many research groups globally, because of the complexity 
of mechanisms involved in tissue accumulation and degradation. In this context, he highlighted the 
drug release rate as a key parameter to predict the clinical performance. For some formulations, drug 
release  testing  in  combination  with  particle  characterization  methods  can  also  be  applied  for 
determining and reducing the risks to the aquatic environment of drugs found in wastewater. This 
application is rarely explored and requires further research in the future. 

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Significant scientific challenges include the accurate prediction for the elimination of long-circulating 
liposomes (not even from  vivo studies); that even increasingly complex  in vitro models do not yet 
improve predictions of clinical performance; and that currently the data in the literature is very limited 
with  regard  to  characterisation  of  nanocarriers.  Overall,  a  more  holistic  view  on  the  benefits  and 
potential risks of nanomedicine will be achieved if scientific communities work more closely together.  

Sven Even Borgos (SINTEF55, Norway) stressed the importance of Joining transatlantic forces via 
the EU-US Communities of Research and the EU-NCL.  

The EU Nanomedicine Characterisation Laboratory (EU-NCL) is a decentralised institution composed 
of multiple European key reference laboratories combining diverse core competences and offering 
open  access  to  the  research  community,  including  companies.  The  EU-NCL  undertakes  trans-
disciplinary research on the development and clinical applications of nanotechnology, disseminating 
lessons-learned,  best  practices,  knowledge,  tools  and  methods  to  the  scientific  community  in  an 
environment  that  protects  any  proprietary  information.  Its  mission  is  to  perform  pre-clinical 
characterisation of nanomedicines, identify and characterise critical parameters of nanomaterials in 
biological systems and develop improved analytical methods. 

Through the EU-US Communities of Research (CoRs) and specifically the NanoEHS CoR, the EU-NCL 
is a partner in international collaboration efforts. The US equivalent of the EU-NCL is the US National 
56 (NCI-NCL). The reasoning for action 
on nanomedicines is that accelerated development of nanotechnology based innovative therapeutic 
and diagnostic products is needed to benefit patients across the globe. With the CoR, stakeholders 
from  academia,  government,  industry,  NGOs  and  third  parties  have  a  shared  platform  to  address 
health  and  safety  concerns  about  nanomaterials  for  medical  applications  and  to  collaboratively 
advance the field. There is no designated funding for the CoR, the communities being largely self-run 
with the European Technology Platform on Nanomedicine (ETPN)57 coordinating the participation of 
EU stakeholders and the US National Nanotechnology Coordination Office providing administrative 
support.  

The  focus  areas  of  the  NanoEHS  CoR  are  the  characterisation  of  nanomedicines  (including 
harmonizing standard operating procedures), standardisation of assays (with active engagement with 
ASTM, ISO and OECD), interaction with regulators on guidance and regulations in nanomedicine, and 
ongoing  activities  related  to  bringing  the  relevant  communities  together  on  nanosafety  (e.g. 
exchanges  on  methods  and  protocols  and  focusing  on  the  full  lifecycle  of  nanomedicines)  and 
cooperation with current H2020 research projects58. Overall, stakeholders need robust and relevant 
reference  materials  and  methods  that  are  sensitive  to  the  biologically  relevant  properties  of 
nanomaterials. The speaker advocated  independent, science-first structures (like NCI-NCL and  EU-
NCL) as  the  means to achieve these targets,  provided they have robust and effective links to the 
regulators. 

Pieter Cullis (National Centre of Excellence in Nanomedicines, Canada) presented the Nanomedicines 
. The research 
themes of the NMIN - targeted drug delivery, gene therapy and diagnostics 
 target the capacity of 
nanomedicines  to  improve  small  molecule  drugs  for  chemotherapy  and  enable  macromolecular 
genetic  drugs  for  gene  therapy.  Canada  has  long  been  at  the  forefront  in  the  development  of 
nanomedicines  for  chemotherapy  and  gene  therapy,  with  several  approved  drugs  developed/co-
developed in Canada to treat cancers (e.g. Myocet and Marqibo), macular degeneration (e.g. Visudyne) 
and fungal infections (e.g. Abelcet).  

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The history of gene therapies has been one of slow progress as viral vectors have limited capacity 
for delivering genetic information, are difficult to manufacture, provoke an immune response, may 
result in mutagenesis or viral transmission and can be extremely expensive, while non-viral vectors 
have none of these problems but have a history of poor transfection efficiency, have a history of 
being large, unstable systems, and can be toxic.  

Non-viral lipid nanoparticle systems are now starting to overcome these problems and are being used 
to enable gene therapies, former problems having been overcome. Applications include delivery of 
siRNA to silence pathological genes, mRNA to express therapeutic genes or gene editing techniques. 
The presentation focused on Onpattro, a non-viral lipid nanoparticle (LNP) formulation used to deliver 
siRNA into hepatocytes to treat Hereditary Amyloid Transthyretin (hATTR) Amyloidosis, which has been 
recently approved in the USA, EU and Canada. These nanoparticles facilitate the intracellular delivery 
of the siRNA and evade the uptake by immune cells. Once in the cell, the siRNA knocks down (silences) 
mutant59 and wild-type60 TTR production, while thus reducing the amount of unstable transthyretin in 
the  circulation  and  preventing  further  deposition  of  amyloid  fibrils.  The  low  circulation  levels  of 
transthyretin can promote amyloid plaque dissolution and promoting elimination from the body, which 
results in stabilisation of the patient and recovery from the toxicities seen in the heart and nervous 
systems. The Onpattro gene therapy approved by the US FDA in August 2018 - the first approval for 
this class of drug -  appears to only to halt the progression of the hereditary disease but also to 
reverse the accumulated damage. The key innovation is the encapsulation of the active components 
(siRNA) so that they reach their target inside hepatocytes. Gene therapies enabled by LNPs are now 
being developed to treat a wide variety of diseases and for vaccine applications. Research in the area 
is  gaining  significant  interest  from  large  pharmaceutical  companies.  However,  there  will  be  many 
regulatory  challenges,  particularly  where  drugs  are  individualised  to  patients  or  small  groups  of 
patients. It is of paramount importance that regulatory science and the regulatory system keep pace 
with such developments in nanomedicine.  

Jon de Vlieger (Lygature61) spoke of his not-for-
 experiences of Science-based 
regulations  for  non-biological  complex  drugs  (NBCDs),  nanomedicines  and  their  similars.  Lygature 
manages public-private partnerships for the development of new medical solutions for patients. Its 
five main areas of activity are neglected diseases, sharing resources, regulatory innovation, patient 
engagement  and  data  infrastructure.  Based  in  the  Netherlands,  it  brings  together  people  from 
academia, industry and society, in many different disciplines and organisations to pioneer solutions 
in medical technology and pharmacotherapy.  

The rise of bio- and nano-technologies has accelerated the development of complex medicines based, 
for example, on polynuclear ferric hydroxide carbohydrate complexes, glatiramoids and liposomes. 
Lygature has a working group62 on non-biological complex drugs (NBCDs), with the mission to ensure 
that  appropriate  science-based  approval  and  post-approval  standards  are  created  and  globally 
introduced  to  ensure  patient  safety  and  benefit.  NBCDs  are  used  to  treat  a  variety  of  medical 
conditions including cancer, auto-immune diseases, infectious diseases and anaemia.  

One complexity of NBCDs is that, while for small molecule drugs identical copies can be made, for 
NBCDs it is impossible to ensure identical copy versions. This affects the development of follow-on 
drugs and their evaluation for marketing authorisation63. In the case of NBCDs (and biologics), their 
characteristics are defined by the manufacturing process, resulting in heterogeneity. The complexity 
of the product may complicate the demonstration of therapeutic equivalency between the originator 
and the follow-on version. Evaluations may result in different outcomes and affect the decision to 

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approve or not approve directly or to approve only after clinical trial, which impacts patients, insurers 
and researchers. It has been reported that some nanosimilars have had different regulatory outcomes 
in different regions and some NBCDs have been approved through different pathways (generic vs 
hybrid)64. Such complexity leads to different regulatory approaches worldwide and even differences 
in  the  EU  from  one  follow-on  product  to  another.  At  present,  NBCDs  are  not  being  defined  as  a 
separate  product  class  and  there  therefore  no  specific  regulatory  pathway  for  NBCD  follow-on 
products exists65 66. The speaker presented a study showing the variation in the regulatory approaches 
for  NBCDs  and  their  follow-on  products  in  the  EU,  predominantly  relying  on  non-centralised 
procedures65 and suggested to make the centralised procedure mandatory for this product class to 
guarantee consistency in the scientific evaluation of follow-on products. 

The  main  regulatory  challenges  are  the  lack  of  standardisation  of  nomenclature,  test  methods  or 
characterisation,  which  can  lead  to  divergence  in  regulatory  approaches  globally.  This  could  be 
addressed  through  regulation,  legislation,  alignment  and  harmonisation  but,  no  matter  what  the 
approach or combination of approaches, the key to success will be the involvement of all stakeholders 
(scientists, regulators, standards bodies, industry, patient representatives, etc.) in creating a fit-for-
purpose system. 

Following  the  presentation,  the  audience  was  informed  about  the 
Mutual  Recognition  and  Decentralised  Procedures  -  human  (CMDh)67,  which  examines  questions 
relating  to  the  marketing  authorisation  of  human  medicines  under  evaluation  in  two  or  more  EU 
Member States under the mutual recognition or decentralised procedure to facilitate harmonisation 
in those procedures.  

̀s Pottier (Nanobiotix) presented work on NBTXR3, a first-in-class hafnium oxide nanoparticle 
radio-enhancer: Journey from concept to clinical application.  She highlighted  that discussions with 
regional  and  local  regulatory  authorities  were  essential  not  only  in  the  late  stages  of  product 
development  but  also  in  the  early  stages  and  throughout  the  process.  The  focus  should  be  on 
discussing and identifying all regulatory requirements for product designation and registration. Some 

As an example, NBTXR3 is classified as a medical device in the EU but as a drug in the US.  

Nanobiotix  has  learnt  that  collaboration  with  regulatory,  ethical  systems  and  clinicians  are  all 
essential in delivering its products to the market. In-depth collaboration among different scientific 
domains is also needed within Nanobiotix. Interactions with hospitals and clinicians are essential to 
explain  and  identify  medical  and  patient  needs.  The  speaker  identified  the  interactions  as  also 
providing for eventual modifications and improvements of the product. Having undertaken product 
development in a largely EU-centred environment, it will need to have a wider view on regulation, 
ethics and clinical aspects as its NBTXR3 moves into global product development. 

Michael  Johnston  (Health  Canada,  Canada)  presented  The  IPRP  Nanomedicines  Working  Group: 
current  and  potential  future  activities.  The  International  Pharmaceutical  Regulators  Programme 
(IPRP)68  is  under  the  umbrella  of  the  International  Council  for  Harmonisation  of  Technical 

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Requirements for Pharmaceuticals for Human Use (ICH)69. The role of the IPRP is in identifying and 
addressing  emerging  issues  of  shared  interest  in  pharmaceutical  regulation,  sharing  regulatory 
perspectives  on  ICH  work,  discussing  challenges  and  promote  consistent  implementation  of  ICH 
guidelines, promoting greater convergence in regulatory approaches based on international standards 
and best practices, facilitating inter-agency collaboration, enhancing communications and supporting 
capacity building (e.g. training). Nanomedicines is the theme of one of its eight working groups70. 

The  membership  of  the  Nanomedicines  Working  Group71  (NWG)  includes  government  and  agency 
representatives  from  countries  in  the  Americas,  Asia,  Europe  and  Oceania.  Its  objectives  are  non-
confidential  information  sharing,  regulatory  harmonisation,  collaboration  between  international 
regulators  on  the  organisation  of  training,  and  outreach  to  communities  of  innovators  in 
nanomedicine  and  other  stakeholders.  Its  scope  covers  nanomedicines,  nanomaterials  in  drug 
products,  borderline  and  combination  products,  and  methodologies  used  during  development  and 
evaluation. Activities of the NWG have included Mapping Nanomedicine Terminology in the Regulatory 
Landscape and a Survey of liposome regulation among IPRP NM WG members. 

The  Nanomedicines  Working  Group  has  been  developing  a  framework  for  the  NWG  to  promote 
regulatory research collaboration between its members, given the increasing need for documentary 
test method standards and reference materials and the rapid advances in the field of nanomedicine. 
Many regulatory agencies are facing limitations in resources and collaboration can help them to jointly 
develop the necessary tools to support the efficient regulation of nanotechnology-enabled products, 
the NWG seeing itself as a suitable platform to facilitate those efforts. The first phase would be to 
generate,  distribute  to  members  and  keep  updated  an  inventory  of  research  laboratories/groups 
interested in participating in collaborative regulatory research projects. Follow-up activities would aim 
to ensure productive research collaborations and exchanges of good practice and training within the 
regulatory research community. 

Panel discussion  

The purpose of the panel discussion was to explore Regulatory research needs for new and follow-on 
nanomedicines,  in particular addressing the questions of gaps and priorities and how they can be 
addressed. Simplification, communication and standardisation of approaches were highlighted.  

The discussion initially focused on standardisation of research methods for nanomedicines and other 
complex  systems  with  the  parallel  development  of  suitable  analytical  methodologies.  The 
methodologies  being  used  are  highly  complex  and  not  always  comparable  between  different 
laboratories, resulting in a need for harmonisation in analytical procedures and in data requirements 
for nanomaterials.72 The panel also saw a need for reference materials and for theoretical modelling 
of nanomaterials to better understand their characteristics and behaviours, particularly in complex 
systems. Characterisation was identified as a somewhat neglected topic and one participant put the 
possibility of establishing an independent organisation to oversee characterisation of nanostructures 
forward. Participants highlighted the need for a way of defining critical quality attributes and methods 
to correlate physiological properties with biological effects. 

On clinical trials, it was noted that, for rare diseases there is a move away from standard double-
blind clinical trials to ones based on a small and select group. On this subject, reference was also 
made to the emergence of flexible and novel clinical trial designs and the US FDA 21st century cures73 

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and Drug Monetisation Act. The issue of  patient pressure was highlighted as potentially becoming 
extreme (including the rejection of placebos in clinical trials) and leading to the need to develop a 
different clinical trial structure. Concerns were expressed that the medicines are emerging but the 
regulatory processes are not.  

Platform approvals were seen as being an important regulatory innovation, involving approval of the 
development process for a drug platform (for example as used by some companies to manufacture 
synthetic peptides) that can be used differently for each patient.  

Access  to  clinical  data  and  the  ways  in  which  it  is  reported  was  found  to  be  not  sufficiently 
standardised and it was not always clear how much should be shared in a regulatory context. Benefits 
could result from increasing the analysis of clinical data and making it more available to the scientific 
community. However, the quality of some data was also questioned.  

It was noted that the regulator needs to understand the science that gives a specific nanomaterial its 
unique nature and the special attributes that make the product act as it does. In relation to this, it 
was seen that researchers want to interact with regulators while enabling the regulatory authorities 
to keep their independence.  

On the question of how to work better to address gaps and challenges, the importance of  sharing 
information and experiences was stressed. It was noted that some mistakes of the past twenty years 
74. For 
collaboration, the EU-US Communities of Research and the International Pharmaceutical Regulators 
Programme were seen as useful mechanisms.  

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4  Safety assessment of Nanomaterials 

Co-chairs: Peter Goering (FDA, USA) and Juan Riego Sintes (EC JRC, EU) 

The  session  focussed  on  the  fate  of  nanomaterials  in  the  environment  and  in  biomedical  and 
consumer  products,  and  the  efforts  of  some  US,  EU  and  international  agencies  and  organisations 
addressing nanomaterials as a potential hazard in the environment.  

Robert Burgess (EPA, USA) provided an Overview of ecological studies on the fate and effects of 
nanomaterials in the marine environment from the perspective of the US Environmental Protection 
Agency (EPA) and specifically from its Marine Research programme.  

Nanomaterials are found in an increasing number of products on the market and, inevitably, some of 
them, or their degradation products, make their way into the environment. Information is needed for 
risk assessment on the fate and effects of nanomaterials in the marine environment, particularly for 
economically important species. As the mission of the EPA includes protecting human health and the 
environment and ensuring safety of chemicals (including nanomaterials) in the marketplace, it has 
established a Nanomaterials Research Program within the EPA Office of Research and Development 
to support the scientific needs of EPA policy offices and regions. All the laboratories under the EPA 
Office  of  Research  and  Development  have  participated  in  this  research  programme.  The  National 
Health and Environmental Effects laboratory (NHEERL) conducts systems-based, effects research for 
sustainable  human  health  and  ecological  integrity,  which  includes  work  on  nanomaterials  and 
nano/microplastics. 

There are two main US environmental legislative acts that govern nanomaterials regulation and data 
collection:  the  Toxic  Substances  Control  Act  (TSCA)  and  the  Federal  Insecticide,  Fungicide,  and 
Rodenticide Act (FIFRA). Marine nanomaterials research performed by NHEERL is focussed on the fate 
of nanomaterials in marine systems and the effects of nanomaterials on the marine system (such as 
levels of toxicity and bioaccumulation). A specific study of five nanomaterials (nanoparticles of silver 
and  titania  as  well  as  graphene,  quantum  dots  and  SWCNTs  (Single-walled  carbon  nanotubes)) 
presented by the speaker showed that salinity is a key driver, with larger nanoparticles found where 
salinity is high, probably due to agglomeration effects. Dissolved salts affect nanomaterial stability 
in solution and affect their bioavailability and the environmental exposure levels. Overall, it seems 
that  large  agglomerated  nanoparticles  tend  to  settle  out  of  the  water  column  in  the  sediment, 
resulting in a low concern about toxicity from these particles in the marine ecosystem. However, toxic 
ions are seen to leak into water from some types of nanoparticles, resulting in adverse effects.  

There  is  still  only  limited  information  on  the  fate  and  effects  of  nanomaterials  in  the  marine 
environment.  Analytical  methods  to  isolate,  extract  and  identify  nanomaterials  from  the  marine 
ecosystem are still needed. The situation is complicated as manufactured nanomaterials (MNMs) are 
often  mixed  with  natural  materials,  making  it  difficult  to  assess  the  MNMs  present  in  the  marine 
environment compared to the quantity of naturally occurring nanomaterials. In addition, the toolbox 
for measuring adverse effects in the marine environment is limited and methods generally focus on 
acute toxicity, while sub-lethal toxicological methods are also needed. The expansion of community-
level method development and application will also help to strengthen the knowledge base for risk 
assessment on nanomaterials in the marine environment.  

Abdel Sumrein (ECHA, EU) explained the role of the European Chemicals Agency (ECHA) in  Safety 
assessment  of  nanomaterials  under  REACH.  Since  2007,  the  REACH  legislation  has  laid  down  the 
system  within  the  European  Union  for  registration,  evaluation,  authorisation  and  restriction  of 
chemicals, including nanomaterials. There are many important aspects of the system, for example, 
the registration of chemicals based on the information provided by companies, and the evaluation of 
those  chemicals  by  Member  States.  REACH  is  just  one  part  of  the  legislation  that  address  also 
nanomaterials as they may also fall under legislation for occupational safety, food packaging and 
biocides, for example.  

33 

In  2018,  the  annexes  of  REACH  were  amended with  the  introduction  of  nano-specific  information 
requirements  and  new  provisions  for  their  chemical  safety  assessment  and  downstream  user 
obligations75. ECHA is finalising guidance documents, tools and methods in support of the legal text 
amending REACH. Guidance relies on available (and ideally, standardised) methods that can be used 
to fulfil the requirements of the REACH regulation.  

The new REACH requirements affect substances that comprise nanoforms and, to date, 37 substance 
registration  dossiers  contain  information  on  nanoforms.  There  is  no  transition  phase  for  the 
implementation of the new requirements, even though fully harmonised or standardised test methods 
may not be available yet. Accordingly, the development of tests methods is of highest importance. 
ECHA relies on OECD76 as well as CEN77 and ISO78 working in this area, further development of test 
methods and standardised measurements being a key priority for the application of legislation to 
nanomaterials. ECHA will assess the incoming dossiers case by case to understand the robustness of 
the data included and its completeness. 

In  addition  to  its  regulatory  role,  ECHA  hosts  the  European  Union  Observatory  for  Nanomaterials 
(EUON)79 that aims to provide objective and reliable information to the public and others on innovation 
and safety aspects of nanomaterials on the EU market. 

Wim  de  Jong  (Scientific  Committee  on  Consumer  Safety  (SCCS)80,  EU)  spoke  about  the  Safety 
assessment  of  nanomaterials  as  ingredients  for  cosmetic  products,  remarking  that  the  general 
problem with nanomaterials is that the safety assessment lags behind products on the market. The 
use  of  nanomaterials  as  ingredients  (e.g.  colorants  or  UV  filters)  in  cosmetic  products  (such  as 
sunscreens  and  toothpastes)  is  specifically  covered  under  the  EU  Cosmetics  Regulation  (EC)  No 
1223/2009, which provides a high level of protection for human health. There are specific regulatory 
provisions  for  nanomaterials,  including  requirements  for  notification  to  the  authorities  six  months 
before  market  release,  labelling  and  the  possibility  of  referral  to  the  SCCS  if  safety  concerns  are 
identified. Concerns could relate to the crossing of membrane barriers in the body, accumulation and 
bio-persistence, for example.  

The SCCS has produced guidance notes, checklists and memoranda81 to improve safety and safety 
assessments. Despite the production of a memorandum on "Relevance, Adequacy and Quality of Data 
in  Safety  Dossiers  on  Nanomaterials"82,  there  are  no  complete  safety  dossiers  addressing 
nanomaterials so far. The SCCS itself has produced opinions on many nanomaterials evaluated as 
cosmetic  ingredients  for  various  applications,  including  zinc  oxide,  titania,  carbon  black,  silica, 
hydroxyapatite, styrene, acrylates and silver.  

The  example  of  nanoscale  titania  as  UV-filter  in  sunscreens,  the  most  common  application  in 
cosmetics,  was  presented.  The  information  provided  in  the  safety  dossier  and  evaluated  by  SCCS 
covered a selection of fifteen different materials from different manufacturers, the incomplete and 
patchy information provided by the companies complemented with literature searches by SCCS. The 
conclusion of the SCCS Opinion83 was that the use of the evaluated (nano)titania as a UV-filter in 
sunscreens, at a concentration up to 25 % w/w, can be considered to not pose any risk of adverse 
effects  in  humans  after  application  on  healthy,  intact  or  sunburnt  skin,  but  that  the  use  of 

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(nano)titania in spray products that might lead to consumer exposure to (nano)titania by inhalation 
cannot be considered safe. 

The highlighted challenges for risk assessment of cosmetic nano-ingredients were the uncertainties 
and  knowledge  gaps  with  regard  to  physicochemical  properties,  environmental  behaviour  and 
toxicological  effects.  It  was  noted  that  the  testing  included  in  dossiers  is  often  done  early  in  the 
product development process, and the material in the final product may be very different. The data 
therefore do not cover all three stages of the processing of the nanomaterials: as produced, as used, 
and  as  formulated.  In  addition,  for  group  submissions,  it  is  not  always  clear  whether  all  the 
nanomaterials  included  in  a  submission  are  the  same  material.  There  are  also  limitations  in  the 
validated methods for detection and characterisation of nanomaterials and for exposure assessment 
via dermal, inhalation and ingestion routes. Additional issues are emanating from the ban on animal 
testing of cosmetic ingredients in the EU. 

The  most  recent  revision  of  the  SCCS  Guidance  on  the  safety  assessment  of  nanomaterials  in 
cosmetics  was  published  in  201984.  It  focusses  on  safety  concerns  about  nanomaterials  that  are 
insoluble  or  poorly  soluble  and  bio-persistent,  the  need  for  high  quality  characterisation  of 
nanomaterials, risk assessment in case of the possibility of systemic exposure, and the use of non-
animal testing. The Guidance will take a weight of evidence approach, rather than a margin of safety 
approach given the absence of in vivo data and the limited number of validated or scientifically sound 
in  vitro  methods  for  nanomaterials.  The  presenter  identified  the  dossier  requirements  for 
nanomaterials  as  cosmetic  ingredients,  the  relevant  methods  available  for  their  testing  and  the 
elements  of  the  checklist  for  safety  evaluations.  The  available  replacement  methods  form  an 
important part of the toolbox for the safety assessment of nanomaterials in cosmetics.  

In summary, the main challenges for dossier evaluation of nanomaterials as cosmetic ingredients 
include the need for high quality characterisation, uncertainties about whether the material described 
and presented in the dossier is the same as material that was actually evaluated and tested, the need 
for risk assessment to take into account the possibility for internal exposure due to translocation of 
the nanomaterial, the need for non-animal testing methods, and the move to what needs to be a 
robust weight of evidence approach to safety assessment. 

The presentation of Kumiko Ogawa (National Institute of Health Sciences (NIHS), Japan) highlighted 
research  on  Size-dependent  toxicity  of  silver  nanoparticles.  Silver  nanoparticles  (AgNPs)  are 
commonly used in many kinds of consumer products, including food containers, textile fabrics, and 
cosmetics, due to their antimicrobial properties and they can exhibit different toxicity and distribution 
effects due to their size. The factors determining the level of toxicity (for a fixed weight of particles) 
include the number of particles, their diameter and their surface area.  

During experiments on mice with AgNPs of diameter 10nm, 60nm and 100nm, severe lesions were 
found in the livers of mice exposed to AgNP10 (10nm). When correcting for the surface area, in order 
to obtain exposure to the same total surface area for each particle size, it was determined that the 
degree of toxicity was not defined by the total surface area but by the size of particles, with only 
AgNP10 being significantly toxic to mice. Looking also at the distribution of the nanoparticles in the 
body, large amounts of AgNPs and ionic silver were observed in the liver of mice treated with 10 nm 
AgNPs. In order to have a clear picture of the risks of such AgNPs, work is needed with doses that 
relate  to  the  real  environment  (much  lower  than  were  used  in  this  research),  as  well  as  data  on 
excretion and accumulation of these nanomaterials.  

There are many routes for international cooperation on regulatory science, one of which was described 
by Ritu Nalubola (FDA - Europe Office, USA) who presented The FDA - Europe Office   Our role and 
how you can engage with us.  

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The goal of the FDA Europe Office85 (located in Brussels and Amsterdam) is to foster collaboration 
 regulatory 
authorities  in  Europe,  including  but  not  limited  to  the  EU,  and  much  of  Russia  and  central  Asia.  It 
supports  overall  regulatory  cooperation  between  the  US  and  EU,  focussing  on  policy  coherence, 
regulatory dialogue, policy analysis and strategic engagement. 

The main work areas of the Office in 2019 have been on the EU-US Mutual Recognition Agreement 
on  pharmaceutical  GMP  (Good  Manufacturing  Practice)  inspections,  Brexit,  emerging  technologies, 
antimicrobial resistance, collaboration with the European Medicines Agency (EMA) (one of its closest 
contacts), food (EFSA partnerships, assessments by the Centre for Food Safety and Applied Nutrition 
assessments, agencies for US government collaboration with other US government agencies on export 
certifications)  and  medical  devices.  Recent  accomplishments  include  the  implementation  of  the 
Mutual Recognition Agreement (MRA) between the USA and EU on pharmaceutical GMP inspections. 
This was the culmination of five years of close collaboration between FDA, EC, EMA and EU Member 
States, with FDA capability assessments of all 28 EU Member States being completed in July 2019 
to match the EU capability assessments of the FDA in 2017. The MRA means that the US and EU can 
itories, reducing the 
demand  on  resources  for  inspections  at  the  FDA  and  its  EU  equivalent,  the  European  Medicines 
Agency, allowing both sides to avoid duplication and reallocate resources towards inspection of drug 
manufacturing  facilities  with  potentially  higher  public  health  risks  across  the  globe.  There  is  the 
potential for extending the MRA also in the area of veterinary drugs.  

Ritu Nalubola also presented a recent publication comparing the drug marketing authorisations of the 
FDA and EMA. The authors found a high level of concordance (91-98%) in decisions on marketing 

conclusions about efficacy and based on review of the same or differing clinical data submissions. 

In  September  2019,  the  FDA  and  US  Department  of  Agriculture  (USDA)  launched  the  Seeds-for-
Sprouting Export Certification Programme re-opening US access to the EU market for the first time 
since  2012.  Under  the  programme,  it  is  verified  that  the  food  safety  management  systems  of 
exporters comply with EU requirements. The FDA, as the competent authority, provides oversight of 
the programme, while the US Department of Agriculture conducts the audits and issues the EU health 
certificate. 

In terms of future priorities, the FDA Europe Office will continue to encourage active international 
engagement, especially on emerging technologies on areas such as digital health, real-world data, 
genome editing (and gene drives86) and artificial intelligence, and to strengthen the cooperation with 
European counterparts on food safety (e.g. on whole genome sequencing for pathogen detection) and 
risk communication. Increased regulatory cooperation at international level on medical devices should 
also be a priority. Another important theme will be US/EU equivalence determination to resume trade 
in bivalve molluscan shellfish. Finally, the Office will be looking to leverage partnerships to help build 
stronger pharmaceutical regulatory systems in third countries. 

Peter Goering, (FDA, USA) presented a priority area for the FDA Centre for Devices and Radiological 
Health  (CDRH),  Nanotechnology  and  medical  devices:  A  regulatory  science  approach  involving 
research,  standards,  and  risk  assessment.  The  FDA  defines  regulatory  science  as 
developing  new  tools,  standards,  and  approaches  to  assess  the  safety,  efficacy,  quality,  and 
performance of all FDA-

thereby including medical devices.  

Medical  devices  are  very  varied  in  nature  and  find  real  and  potential  applications  in  areas  from 
cardiovascular and orthopaedic to gastro-urinary and ophthalmics. CDRH engineers and toxicologists 
are closely connected with the medical device technology and how devices are manufactured.  

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CDRH houses a Nanotechnology Regulatory Science Research Programme comprised of three pillars: 
physico-chemical  characterisation  methods,  in  vitro  and  in  vivo  models,  and  (toxicological)  risk 
assessment.  These  efforts  support  and  contribute  to  regulatory  review,  standards  and  guidance 
documents, and staff training and communication.  

Applications  to  CDRH  for  medical  devices  that  incorporate  nanotechnology  include  the  types  of 
applications  available  for  all  device  applications:  pre-submission  (enabling  developers  to  discuss 
products with FDA experts before submission and to ensure that testing is on the right track), pre-
market notification, pre-market approval, investigational device exemption and requests by device 
manufacturers to obtain FDA views on a device classification. The types of devices that incorporate 
nanotechnology include antimicrobial, dental, orthopaedic, neurological and combination devices, and 
in  vitro  diagnostics.  The  devices  use  various  nanomaterials,  including  silver,  zirconia,  titanium  and 
titanium, iron oxide, polymers, calcium compounds, gold and graphene. 

Challenges  and  opportunities  for  nanotechnology  research  in  the  medical  devices  arena  include 
determining the magnitude and rate of release into the body (where improved in vitro release test 
methods are needed) and whether any release and patient exposure results in adverse health impacts, 
(driving the need to continue to advance toxicology risk assessment approaches). Another issue is 
whether nanoparticles affect the accuracy and/or reliability of standard biocompatibility or toxicity 
test assays, such as for cytotoxicity and genotoxicity. Because of the vast number of sizes, shapes, 
and chemistries of nanomaterials, there is also a need to develop in vitro models (2D, 3D, organ on a 
chip, organoids) and in silico models in order to predict human responses and improve in vitro to in 
vivo extrapolations. 

Nadim  Akhtar  (AstraZeneca)  identified  some  key  CMC  (Chemistry  Manufacturing  and  Control) 
challenges of developing commercial nanomedicines and working with commercial nanoparticles for 
pharmaceuticals in terms of their characterisation, demonstration of bioequivalence, the use of  in 
silico  models  and  the  development  of  biopharmaceuticals.  Examples  of  nanoparticles  used  by  his 
company  include  polymeric  nanoparticles  encapsulating  drugs  that  are  released  through  diffusion 
(accurins)  and  polymer-conjugated  drugs  released  via 
In 
characterisation, it is often difficult to find both the right equipment and the expertise in the same 
place.  

linker  chemistry 

(dendrimers). 

It is important to understand the aggregation and solution behaviour of the nanoparticles in order to 
understand  their  behaviour  in  physiological  conditions.  This  is  critical  for  the  design  of  dendrimer 
drugs, where the active pharmaceutical ingredient and the dendrimer (nanoparticle) are covalently 
bound, and the release profile of the drug depends on the composition of the dendrimer, and on time.  

The drug release profile from encapsulated drugs (e.g. accurins) is more complex and takes place by 
diffusion. It can be modelled87 and the drug molecules in the centre of the nanoparticle are seen to 
disappear the slowest, as they have the furthest distance to travel to escape the nanoparticle. The 
size  of  the  nanoparticles  is  observed  to  affect  the  drug  release.  In  silico  simulations  are  used  to 
understand better the release behaviour and optimise it. Controlled release from a particle can change 
from the initial stages, where there should be a uniform concentration of the active component, to 
later  stages,  when  some  molecules  have  been  released  and  the  concentration  and  distribution  of 
drugs are different.  

Key challenges in biopharmaceutics were identified as including the need to deal with drug product 
changes  during  clinical  development  (e.g.  changes  of  manufacturing  site,  manufacturing  process 
and/or scale). For example, a change in one parameter can affect many different characteristics and 
fundamentally change the formulation under investigation. In these cases, a strong and scientifically 
sound  bridging  strategy  is  essential.  It  can  also  be  difficult  to  establish  parameters  around  the 

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biological end-points, to identify the critical quality attribute (CQA) with the potential to achieve  in 
vivo performance.  

In  summary,  robust  characterisation  methods  are  needed  to  enable  bioequivalence  to  be 
demonstrated;  there  needs  to  be  a  sound  understanding  of  the  impact  of  process  parameters  on 
product attributes; in vitro, in vivo correlations (IVIVCs) and biopharmaceutic bridging strategies are 
needed to secure flexibility for a complex product. 

The presentation of Jan Simak (FDA, USA) looked at the Investigation of blood and endothelial toxicity 
of engineered nanoparticles using a PAMAM (polyamidoamine) dendrimer model. The focus was on 
the  effects  of  nanomaterials  on  blood  platelets  and  the  cells  lining  arteries  and  veins  (vascular 
endothelial cells) and the question of what assays to use to predict any potential adverse effects. The 
speaker  presented  research  to  show  that  large  cationic  PAMAM  dendrimers  evidence  both 
proinflammatory and proapoptotic effects in endothelial cells and, at high dendrimer concentrations, 
these effects are accompanied by necrotic cytotoxicity. Size-charge modified PAMAM dendrimers may 
be a useful model for investigating in vitro toxicity of small (< 10 nm) nanoparticles, and some work 
on this was presented. 

Haemostasis (coagulation of blood within a damaged vessel e.g. in the healing of a wound) is  an 
integral part of the inflammatory response of the body involving blood platelets. The dendrimers used 
in the presented research had a specific size and a surface that could be modified. PAMAM dendrimers 
that  were  hydroxy-terminated,  carboxy-terminated  and  amine-terminated  were  tested  for  their 
potential to induce blood platelet aggregation. The assay was a very simple one involving the counting 
of platelets before and after treatment. With cationic dendrimers, it was found that there was blood 
platelet aggregation and fragmentation, the latter the outcome of probable disruption of the integrity 
of the platelet membrane. 

For vascular endothelial cells88, the effect of different size-charge modified PAMAM dendrimers on 
cell viability89  and LDH90 release (evidence of cell death) was  measured at  different doses.  It was 
found  that,  here  again,  cationic  dendrimers  have  adverse  effects  on  the  plasma  membrane  and 
mitochondrial membrane, inducing a release of extracellular vesicles. However, it was not clear either 
if the process was active (the cell trying to remove the dendrimers) or passive (cell death) nor whether 
the dendrimers were inside or outside the vesicles.  

Challenges  in  the  evaluation  of  the  effects  of  nanomaterials  on  blood  coagulation  and  the  main 
concerns for these assays were sample preparation, characterisation of the nanomaterial under test 
conditions (size distribution, particle aggregation, surface charge, etc.), the nanomaterial dosimetry 
(which should be based on surface area), the selection of assays for different purposes (e.g. screening 
and  mechanism  investigation),  and  the  need  for  standardisation  and  inter-laboratory  studies; 
obtaining healthy cells for the studies (given that the patients are severely ill) and dealing with the 

sample size t
vivo. 

in vitro and in 

Luis Velasquez Cumplido (I3CBSEK, Universidad SEK, Chile) presented an International review of 
micro  and  nanoplastic  regulations  in  marine  environments  and  their  potential  impact  on  Chilean 
aquaculture. Aquaculture is growing in quantity and diversity globally and the long coastline of Chile 
is  highly  productive  in  valued  fish  and  aquaculture  resources,  most  notably  in  the  south  of  Chile. 
However, there is widespread concern that, in parallel to the growth in aquaculture, there may be an 
increase  in  the  amount  of  plastic  litter  in  the  oceans  and  seas,  to  the  detriment  of  ecosystems, 
biodiversity and potentially human health, making microplastics and nanoplastics a multidisciplinary 

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global issue. Work is being undertaken by international organisations such as GESAMP91 (the Joint 
Group  of  Experts  on  the  Scientific  Aspects  of  Marine  Environmental  Protection)  and  the  Food  and 
Agriculture Organisation of the United Nations (FAO)92. 

Plastic  makes  up  80-85%  of  the  total  number  of  marine  litter  items,  measured  by  beach  counts. 
Although definitions may vary, it is generally agreed that microplastics include particles and fibres of 
plastic  measuring  less  than  5  mm,  including  nanoplastics  (less  than  0.1  microns).  Primary 
microplastics  are  intentionally  manufactured  (e.g.  pellets,  powders,  scrubbers),  while  secondary 
microplastics result from plastic material breakdown (e.g. of fishing gear, cages, buoys, boats and 
packaging).  Microplastics  tend  to  attract  persistent  and  bioaccumulative  contaminants  that  are 
present in the water, as well as living organisms (marine invertebrates, bacteria, fungi, viruses) that 
use them as a substrate. Such microplastics can enter the human food chain through the consumption 
of fish and seafood, particularly those eaten completely without the removal of their digestive tract 
(e.g. whitebait, crustaceans and molluscs).  

The Natural Language Processing (NLP)-based tool IRIS.AI was used to identify 382 research papers 
or patents related to plastics and microplastics legislation worldwide. These were grouped by themes 
including plastic, regulation, legislation, etc. Other terms that emerged includes  material, pollution, 
land-based, composite, management and policy. 

Solutions using circular economy models are being sought for the plastics issue, not least the recycling 
of materials and banning of plastic bags (Chile being the first South American country to instate a 
ban in 2018). In Chile, a form of  Extended Producer Responsibility has been proposed; putting the 
burden of recovery on producers of products, e.g. a producer of beverages bottled in plastic must 
recover  a  percentage  of  their  bottles  from  consumers  and  the  environment.  It  is  expected  that 
producers will be motivated to move to biodegradable materials rather than single-use, throwaway 
plastic, as recovery may be too expensive. In addition, they will hopefully be encouraged to design 
their  remaining  plastic  products  for  end-of-life  material  recovery  and  remanufacture,  as,  once 
producers recover their plastic product, they must deal with it in some way. Another aspect of plastics 
management in Chile is education and citizen science. For example, nearly 1000 school-children from 
39 schools on mainlan

́ficos de la Bastura  (Litter Scientists). 

Research to address the problem of microplastics and nanoplastics has been minimal thus far in Chile, 
but the speaker presented a plan for a project to generate a baseline of micro and nanoplastics in 
the marine environment and their levels in fish close to fish farming centres in the south of Chile. It 
was noted that standardised protocols and common units are needed. 

Panel discussion  

The panel discussion focused on gaps and priorities in Safety assessment of Nanomaterials, and how 
they can be addressed, beginning with a summary by one of the co-chairs (Peter Goering (FDA, USA)).  

Risk and safety assessment approaches for nanomaterials are still incomplete due to vast number of 
nanoparticle sizes, shapes, chemistries and surface functionalities. For risk assessment, the key needs 
are for robust exposure assessments, dose-response assessments, and in silico modelling and in vitro 
tests that can be extrapolated to in vivo/human (IVIVE). In risk assessment, current studies can be 
used to develop tolerable intake values for the clinically relevant routes of exposure (oral, inhalation, 
IV, dermal). For exposure assessments, the nanoparticle/ion release methods may not be sufficient. 
Determining the margin of safety remains difficult with the current trend of reducing the number of 
animal studies. In general, alternative (non-mammalian) methods, such as in vitro organoids, organ 
on a chip models and in vivo models (e.g., zebrafish, C. elegans) need to be further developed and 
incorporated into safety testing regimens. 

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Dosimetrics for nanomaterials were also discussed, including the metrics of mass, surface area and 
number, and how to use doses that are clinically realistic. It was asked whether more absorption, 
distribution,  metabolism,  and  excretion  (ADME)  work  is  needed,  e.g.,  looking  at  bio-persistence  in 
tissues  and  excretion  kinetics.  There  are  also  uncertainties  in  methods  for  physico-chemical 
characterisation (detection in cell culture media and biofluids). 

On  environmental  fate  and  hazard  in  the  marine  environment,  it  was  asked  what  additional 
approaches are needed, if any, given that aggregation limits bioavailability and, for released ions, 
methods are already available. There may be a need for improved methods for solubility, degradation, 
and toxicity as well as methods for aquaculture and ocean capture assessment of nanomaterials, and 
microplastics and nanoplastics. It was noted that the EU and US FDA have a high concordance of 
regulatory decisions. 

Moving away from the marine environment, the question of exposure was raised for cosmetics, such 
as inhalation of powders that are spread on the skin. It was  noted that risk  assessment  concerns 
systemic  exposure,  not  local  exposure.  Indeed,  the  minor  modifications  to  the  product,  which  all 
manufacturers  make,  are  a  bigger  problem  when  it  comes  to  exposure  as  the  consequences  are 
unknown. Studies are not performed on each specific product, and there are no complete dossiers. In 
addition, testing is done at the early stages of product development but not on the final product. In 
the USA, no labelling of nanomaterial-containing products is required, but with powders in general 
both, the dermal and inhalation routes, are considered. 

On  EU-US  collaboration,  it  was  noted  that  the  disappearance  of  the  EU-NCL  (Nanomedicine 
Characterisation  Laboratory)  would  affect  collaboration  and  project-to-project  learning.  The  most 
value will be created by putting the resources in the right places (e.g., in developing relevant tools). 
The  importance  of  collaborations  and  common  understanding  was  raised.  It  was  noted  that  the 
difference between academic and regulatory science is that the latter must have a purpose beyond 
fundamental  knowledge  (e.g.  ensuring  safety).  A  common  purpose  also  helps  when  different 
institutions  and  organisations  collaborate.  Harmonisation  of  methodologies  (e.g.,  for  micro-  and 
nanoplastics),  documenting  regulatory  science  studies  and  the  use  of  round  robins  were  all 
highlighted as important future steps.  

On round robins, it was noted that they are valued collaborations. Additionally, in the NANoREG93 and 
NanoReg294 projects, there have been problems with the lack of reference nanomaterials that can 
serve  as  positive  or  negative  controls.  So  far,  reference  nanomaterials  exist  only  for  particle  size 
determination  and  are  not  easy  to  create  as  they  depend  on  extensive  datasets,  requiring 
commitment  from  testing  laboratories  from  all  over  the  world.  In  the  meanwhile,  representative 
nanomaterials are available from the JRC Nanomaterials Repository. Good quality (validated) data 
are needed and there have been some efforts made in Europe. The problem is the lack of harmonised 
protocols, standardised methods and templates for study data (to report the data and metadata). 
Notably,  the  JRC  hosts  a  collection  of  tools  and  templates  for  generating  and  reporting  data  for 
nanomaterials, the NANoREG toolbox. The application of FAIR (Findable, Accessible, Interoperable and 
Reusable) principles to data is seen as a step in the right direction. 

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41 

42 

5  Nanotechnology in the agri/food/feed sector 

Co-chairs: Primal Silva (CFIA, CA) and Reinhilde Schoonjans (EFSA, EU) 

The  session  provided  both  a  panoramic  view  of  the  current  state  of  nanotechnology  in  the 
agri/food/feed  sector  and  an  overview  of  high-potential  future  products,  also  considering  in  detail 
certain applications of nanotechnology and methods of analysis and characterisation.  

̀ze (EFSA, EU) gave a presentation on Nanomaterials in food and feed - Experience 

and perspective from the European Food Safety Authority. 

Nanomaterials are chemical substances according to EU legislation, and are regulated by REACH (EU 
Regulation 1907/2006). The EC 2011 recommendation95 on the definition of a nanomaterial seeks to 
provide a definition of the term nanomaterial across all EU legislation. The EC Regulation 2018/1881 
modifies the annexes of REACH to include nano-specific clarifications and requirements.  

Regarding nanotechnology in the food chain, which is governed by various food legislations, guidance 
from EFSA was made available in 2011 and updated in 201896. In the context of food, health and 
nanomaterials,  EFSA  both  prescribes  and  evaluates  the  adequacy  of  risk  assessments  in  of 
applications dossiers possibly comprising small particles, including particles in the nanosize. 

The application dossiers for nanoscale materials received by EFSA mainly concern the two areas of 
food contact materials and food additives, but also application for feed additives and novel foods 
have  been  received,  whereas  none  having  been  received  for  pesticides  so  far.  The  majority  of 
materials are substances (potentially) containing a fraction of nanoparticles within, for example, a 

unbound state or as an aggregate or as an agglomerate and where, for 50 % or more of the particles 
in the number size distribution, one or more external dimensions is in the size range 1 nm-

Risk assessments are needed for (engineered) nanomaterials in agri/food/feed applications and these 
are to be based on sound scientific knowledge and methodologies, to produce robust data. EFSA has 
issued scientific guidance for risk assessment (2011, updated 2018)96 and horizon scanning (2014). 
In  the  future,  EFSA  plans  to  provide  more  detailed  technical  guidance  on  physico-chemical 
characterisation. This will, inter alia, enable EFSA to provide criteria to establish the presence and to 
document the nano-fraction in a product. EFSA is also identifying and supporting key research areas 
to advance future risk assessments.  

It was noted that there is a scarcity of data specific and relevant for nanofractions. New products are 
subject to the current regulatory system, and need to be addressed as recommended in the nano-
specific guidance. However, there are products on the market that were released many years ago 
when no nano-specific guidance was available. The assessment of these products remains difficult 
with  respect  to  implementing  the  new  guidance  in  retrospect.  For  example,  for  novel  foods 
legislation97 has been in place since 2018 but, when such products come up for renewal, the processes 
to follow can be unclear. EFSA is developing its processes and learning on a case-by-case basis, the 
priority  being  that  the  applicant  has  to  demonstrate  the  safety  of  the  product.  EFSA  uses  its 
knowledge to assess the safety, with the scientific and technical aspects being accompanied by many 
legal discussions and frequent requests for additional information from EFSA to the applicants.  

EFSA is advising applicants to build multi-disciplinary teams of technicians, toxicologists, regulatory 
scientists  and  consultants  to  jointly  tackle  nano-specific  assessments  of  potential  risks  in 

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agri/food/feed  applications  of  nanotechnology.  At  present,  also  in  EFSA,  its  staff  and  experts  are 
learning by doing and trained to assess information related to nanomaterials and food. EFSA has a 
crosscutting working group providing expert advice to EFSA staff and panel experts for the topic. It 
works with stakeholders in Member States through the EFSA nano network and provides workshops 
on the implementation of its guidance materials. It also works with academia, both procuring research 
and as members of advisory boards of research consortia.  

Reinhilde  Schoonjans 

. The aim of the 
guidance is to give applicants and assessors the tools they need to prepare complete nanotechnology 
application dossiers and their review. The guidance covers areas such as novel foods, food contact 
materials, food and feed additives, and pesticides, and is intended in particular for risk assessors, risk 
managers and applicants. It was noted that hazard identification and characterisation must take into 
account that a nanomaterial may lose its nanoform as it goes through the body (e.g. the digestive 
tract), at which point the nano-specific guidance is no longer required and the conventional guidance 
according to the envisaged use is sufficient.  

Towards grouping of nanomaterials: lessons learnt and remaining challenges was presented by Frank 
Herzberg  (BfR,  Germany).  Nanomaterials  are  subject  to  many  regulatory  requirements  in  the  EU, 
including those for chemicals (REACH)98, novel foods99, food additives100, plastic food contact materials 
and active and intelligent food contact materials101, food information provision102, biocidal products103, 
plant  protection  products104  and  cosmetic  products105.  Nanomaterials  are  a  particular  regulatory 
challenge  because  they  can  be  synthesised  based  on  many  different  core  materials,  and 
nanomaterials of the same core chemistry can exist in many different forms (i.e. different shapes, 
surfaces, sizes). 

Grouping  of  substances  is  explicitly  mentioned  in  some  of  the  regulations  (e.g.  in  REACH  and  for 
biocidal  products)  and  the  use  of  data  from  structurally  related  substances  (read-across)106  is 
foreseen as a possibility. However, in the food sector (e.g. in novel foods and in food contact material), 
it  is  rarely  applied.  Some  regulations  also  contain  guidance  for  grouping  of  substances,  although 
REACH  is  the  only  one  of  those  mentioned  above  that  has  specific  guidance  for  the  grouping  of 
nanomaterials.  

Should  it  be  the  case  that  testing  does  not  seem  to  be  scientifically  needed,  there  are  additional 
challenges  inherent  in  grouping  nanomaterials,  and  structural  similarity  alone  does  not  suffice.  A 
grouping of nanomaterials may also include nanoforms of the same substance with different nano-
specific  physico-chemical  parameters  (e.g.  morphology  and/or  surface  chemistry).  Sets  of  similar 
nanoforms can be created, but boundary criteria need to be established.  

Specific hurdles to be overcome in putting nanomaterial grouping into practice include the very low 
number of case studies of nanomaterial grouping; the limited mechanistic information and limited 
reliable in vivo data; some specific data issues (the absence of systematic, comparative data sets, 
uncertainties  resulting  from  insufficient  data  quality  and  missing  benchmark  materials);  and 
difficulties  in  correlating  the  physico-chemical  properties  with  toxicity  (uncertainties  about  the 
relevant parameters and variations due to life cycle modifications, e.g. where the material changes 
during use, resulting in changes in its toxicological behaviour). 

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Various  initiatives  (e.g.  NANoREG107,  NanoReg2108,  ENPRA109  and  NanoTest110)  have  provided 
information that can be accessed in the database eNanoMapper111. Inevitably, the usefulness of the 
database is only as good as its content and it suffers from the low number of grouping case studies, 
comparability  issues,  and  the  other  issues  mentioned  above.  For  example,  the  NanoReg2  project 
assessed regulatory requirements for nanomaterials grouping in different EU chemicals legislations 
and  found  the  data  to  be  heterogeneous,  with  dosimetry  often  insufficiently  reported.  The  data 
curation needed to fill the gaps was very time-consuming and, where information was lacking (e.g. 
where positive controls or benchmark materials were missing), the data quality remained poor and 
not useable for comparison with other studies. The project also concluded that the choice of cell type, 
assays, and assay conditions is highly important and that the aggregation of individual study data 
needs to be improved.  

A new project funded by the German government112 is aiming to address some of the above issues 
for  polydisperse  materials  (e.g.  metal  powders  for  additive  manufacturing/  3D  printing),  materials 
with specific morphologies (e.g. fibres) and materials with mixed chemical composition (e.g. for laser 
cutting).  One  material  type  under  scrutiny  will  be  polymer  particles  as  intermediate  products  for 
additive manufacturing (microplastics and nanoplastics). The project, Innovative Materials and new 
production processes: Safety in Life Cycle and in industrial value chain (InnoMatLife), also aims to 
develop grouping principles for those materials 

The  speaker  concluded  by  highlighting  the  need  for  a  common  understanding  of  data  quality 
requirements;  to  achieve  broad  and  secure  data  access;  and  to  succeed  in  grouping  across  nano-
substances. The research gaps to attain these goals are in developing reliable comparative datasets; 
standardised  and  validated  methods;  mechanistic  and  long-term  information;  and  data  on  next-
generation  materials.  Standards,  particularly  the  work  of  ISO,  and  comparable  data  are  essential 
components of a robust regulatory system.  

Ralf  Greiner (Max  Rubner-Institute (MRI)113, Germany)  presented  Nano-sized delivery systems  for 
food  applications.  The  benefits  of  nanotechnology  in  food  ingredients  using  encapsulation  include 
improved  bioavailability  and/or  absorption;  masking  an  undesirable  taste  or  flavour;  achieving 
controlled release of the encapsulated ingredient (e.g. vitamins or minerals); protect the encapsulated 
ingredient  from  the  external  environment  (e.g.  protecting  it  from  heat,  acidity,  moisture);  and 
achieving controlled interaction between the encapsulated ingredient and the food matrix, etc.  

There are, however, many variables in nano-sized delivery systems. Some structures function well in 
water but are not necessarily transferable to other food matrices. The delivery systems need to be 
food grade and safe (or listed by the relevant regulatory authority), as well as compatible with the 
food matrix. There needs to be a proper formulation in order to ensure a good distribution of the 
active ingredient in the product, which can contribute to increased bioavailability. The materials must 
be  robust  enough  to  withstand  processing,  distribution,  handling  by  the  consumer,  etc.,  with  no 
negative effects, sensory or other. 

Release mechanisms of nano-sized delivery systems result in various processes of diffusion into the 
body.  There  is  degradation  by  digestive  enzymes  and  dispersal  triggered  by  changes  in  the  local 
environment (e.g. pH, temperature, moisture). The release of the encapsulated ingredient is dependent 
on  many  variables,  including  the  shape  and  dimensions  of  the  delivery  system;  its  chemical 
composition;  the  type  of  ingredient  and  its  diffusivity  and  solubility  in  the  encapsulant  and  the 

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environmental; the ingredient ratio in the delivery system and the external medium; the encapsulation 
load and the loading efficiency.  

While there are several products on sale, there is a strong motivation to develop optimal formulations, 
the aim being to include less of the ingredient and to rely on improved bioavailability. However, this 
is proving difficult, for example, in the case of iron fortification products. The goal is to mask the 
unpleasant iron taste and flavour, to deal with the instability of the formulations and problems of 
precipitation, and to produce an iron fortification that is mild on the stomach with sustained release, 
high absorption and bioavailability. Even products that are on the market114 have been seen to provide 
no significant improvement in iron absorption when incorporated in real food matrices compared with 
ferrous sulphate as a control.  

In concluding, the speaker noted that before nano-sized materials find widespread application in the 
food sector information on potential risks that may arise from their consumption must be available. 
An  important  issue  is  whether  the  nano-sized  material  is  digested  differently  from  its  individual 
component  building  blocks.  If  absorption  and  bioavailability  of  the  nutrients  can  be  improved, 
modifications may be needed in the accepted daily intakes for these materials in the nano-form. In 
vitro and in vivo experiments are necessary to study the efficacy of the delivery systems as well as 
potential adverse effects. 

Nanomaterials for reducing food-related waste was the subject of the presentation by Ken Bosnick 
(Nanotechnology Research Centre, National Research Council, Canada). The focus of the presentation 
was on food waste related to processing and at the consumer  stage.  Nanomaterials are used for 
example, in spoilage and pathogen sensing, and in the exploitation of renewable materials.  

North America wastes over 20% of the meat it produces. This is not only an economic loss due to the 
waste but also a pollutant as the meat is a producer of greenhouse gas emissions. Quality control 
measures result in the meat being discarded and spoilage-sensing devices are a better alternative. 
Early detection of biogenic amines can be exploited for improved quality assurance (QA) and lead to 
a reduction in food waste. For example, metal oxide semiconductor (MOS) gas sensing technologies 
could be exploited in portable meat spoilage sensing devices for use in the meat processing industry. 
The sensitivity of the sensors is enhanced by using nanomaterials as their nanostructured form offers 
a higher surface area per volume of sensing material. The geometry and composition of the materials 
can  be  optimised  to  improve  both  the  response  times  and  sensitivities.  Catalyst  particles  help  to 
overcome chemisorption barriers and reduce sensor-operating temperatures. Other materials being 
researched are silicon nanowires and other semiconductors, while heterostructures (e.g. ZnO / NiO) 
may offer even higher sensitivities. 

Nano-enabled  devices  are  also  being  developed  for  rapid,  sensitive  and  selective  detection  of 
bacterial (e.g. salmonella) and viral (Hepatitis C)) pathogens, which is pivotal to food safety and public 
health,  and  to  support  a  competitive  food  processing  industry.  Conventional  culture-based  assays 
suffer from being time consuming, costly and labour-intensive, but now nano-enabled biosensors are 
being developed to reduce the time needed from days to a few hours, thereby also reducing costs.  

The presenter also provided examples of nanocomposites for renewable food packaging, identifying 
a  potential  route  towards  making  renewable-derived  packaging  that  will  be  competitive  with 
petroleum-derived packaging. The issues of poor mechanical properties of renewable and degradable 
packaging  (compared  with  petroleum-based  materials,  i.e.  common  plastics)  can  be  overcome  by 
compounding compatibilised and pristine cellulose nanocrystals (CNCs) with polylactide and casting 
it into packaging films using a twin-screw extruder. 

Smart,  renewable  and  multifunctional  food  packaging  material  is  also  being  developed.  While 
blending cellulose nanocrystal (CNC) nanorods with renewable-derived packaging adds only passive 
reinforcement, smart functionality can be added to the CNC particles by synthesising designer hybrids 

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with active materials. This can, for example, lead to smart, renewable packaging that can sense meat 
spoilage, using zinc oxide nanoparticles as the means to optically-sense biogenic amines. 

In conclusion, nanotechnology can make a significant impact in reducing food and food-related waste, 
including  through  spoilage  sensing  devices  for  increased  quality  assurance,  pathogen  sensing  for 
rapid, point-of-control use, improving the competitiveness of renewable-derived packaging and, in the 

economic and environmental gain.  

́rie Fessard (ANSES, France) presented work on the Genotoxicity of aluminium nanoparticles. 
Key areas that need to be addressed through regulatory science are to obtain oral exposure data 
(there currently being mostly inhalation data); to extend the knowledge about the nanoforms used in 
agri/food/feed; and to establish validated methods adapted to nanomaterials. These will enable better 
identification  of  the  hazard,  if  any,  of  nanomaterials  in  food  and  feed  and  improve  related  risk 
assessments. Methods are needed to know more about material behaviour along the digestive tract 
(e.g. what modifications happen, what are the impacts of crossing the intestinal barrier). Other areas 
in which work on methodologies is needed is on the link between toxicity and accumulation, and the 
development of in vitro methods for testing repeated exposure. High throughput methods are needed, 
as many types of nanomaterials exist, although this may be helped by nanomaterial grouping if that 
can be robustly achieved. There is also an urgent need to understand why so many discrepancies are 
found in data that aims to (and ideally should) be comparable, e.g. in round robin testing in different 
labs. There have been projects to address this last issue but they have been of too short duration to 
come to robust conclusions.  

Aluminium was the chosen topic of the research, and the main subject of this presentation, as it is 
widely found in direct contact with food as a packaging and it occurs in food additives, flavourings 
and  processing  aids.  The  current  data  on  aluminium-containing  nanomaterials  is  limited  and 
insufficient. 

In the reported research on toxicity of different forms of aluminium (Al0, Al2O3) in rats, it was found 
that multiple testing methods were needed to establish whether the different forms of aluminium 
(Al0, Al2O3) behaved in the same way. These complementary methods included biokinetics modelling, 
liver  immunostaining  for  the  biomarker  gamma-H2Ax,  histopathology,  transmission  electron 
microscopy (TEM) of the liver and brain, and polymerase chain reaction (PCR) targeted analysis on 
key gene expression from brain and intestine. It was found that, in this investigation of behaviour 
along the digestive tract, in vitro results did not mimic what was seen in vivo. The nature of the link 
between genotoxicity and accumulation varies according to which organs and tissues are examined 
and at what point in time the analysis is undertaken, results that cannot yet be explained.  

Katrin Löschner (National Food Institute, Technical University of Denmark) presented work on the 
Analysis of inorganic nanoparticles in food and biological matrices. Physico-chemical characterisation 
is needed to determine whether the material is a nanomaterial, and should consequently be subject 
to a nano-specific risk assessment, for hazard identification and characterisation in matrices including 
water, feed, test media, biological tissues and fluids (and in the context of in vitro, in vivo, in silico 
and  ADME  studies);  and  for  exposure  assessments  (quantification  of  nanomaterial  in  food/feed, 
migration from food contact materials/FCMs) in various matrices (e.g. feed, food, food supplements, 
FCMs,  food  simulants).  Nanomaterial  characterisation  has  to  consider  a  number  of  parameters, 
including e.g. particle size, particle shape, elemental composition, crystal structure, surface charge, 
surface area, and agglomeration or aggregation state. There  are also extrinsic (media-dependent) 
properties to be considered such as physical and chemical stability of nanomaterials and coatings; 
solubility  in  relevant  media,  dispersibility  of  poorly  soluble  nanomaterials;  and  chemical 
reactivity/catalytic activity. Sample preparation for nanoparticles can also be very challenging115 and, 

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as a combination of analytical techniques must be used to fully characterise them, many different 
preparations may be required.  

The speaker finished by noting some general challenges, most significantly that there are no generic 
methods for nanomaterial characterisation. Methods need to be developed that are specific to certain 
nanoparticle/matrix combinations and sometimes even for specific nanoparticle characteristics (e.g. 
surface properties). There are few validated methods for nanoparticles in complex matrices and these 
have typically only been tested by a single laboratory. There are no certified reference materials with 
nanoparticles in a matrix. Suitable methods can be further developed if regulatory needs are better 
known, including the need for clarity on the definition of nanomaterials in, for example, food-labelling 
regulations. 

Nanopesticides  and  their  deliberate  application  in  agriculture  was  presented  by  Melanie  Kah 
(University of Auckland, New Zealand). There is a wide variety of different nano-enabled pesticides 
for  agriculture,  the  first  generation  including  metals  and  metal  oxides  and  the  second  generation 
being nanocarriers loaded with an active substance. The active substances can be, for example, an 
existing  substance such  as  a  pesticide  (and  the  nanopesticide is  therefore  a  reformulation),  novel 
nanopesticides (e.g. using pheromones or RNAi) or nature-inspired nanocarriers. The durability of a 
nanopesticide is how long it maintains the properties that are specific to its nano-size.  

The key driver for applying nanotechnology to develop new plant protection products is to address 
the weaknesses of existing products. Current pesticides can be improved through three main avenues: 
more efficient application of stable suspensions giving homogeneous coverage; reduced losses and 
transportation to non-target areas; and improved interactions with the host or with the target (e.g. 
improved uptake). Nano-pesticides can have  different size distribution or release rate, so adapted 
protocols  have  been  designed  to  measure  those  parameters  and  evaluate  how  they  can  be 
incorporated in current models used for conventional pesticides. The scientific and technical literature 
(peer review papers but also patents and websites) can be useful in identifying the most advanced 
nano-pesticides  and  to  evaluate  their  performance  relative  to  their  non-nano  equivalent.  The 
International  Union  of  Pure  and  Applied  Chemistry  (IUPAC)116  has  funded  workshops  looking  at 
establishing  guiding  principles  for  the  environment  and  human  health  risk  assessment,  and  their 
possible harmonisation.  

The speaker noted that there is a great variety of nano-enabled products with potential applications 
in agriculture, and some look very promising in being able to improve the efficiency of currently used 
pesticides. However, there is  a  disconnect  between the published  science  and  agricultural context. 
Durability criteria can be a very useful and pragmatic approach to determine the specific nano-specific 
and  pesticide  properties  of  the  new  products.  Measurement  approaches  are  currently  limited,  and 
more work is needed to characterise nano-pesticides over time after they are applied in the field.  

The  Observations  of  nano-agrochemicals  and  nanoplastics  in  food  and  agriculture  research  by 
Hongda  Chen  (National  Institute of Food  and  Agriculture,  Department  of  Agriculture,  USA)  began 
with an introduction to the work of the National Institute of Food and Agriculture (NIFA). Its remit is 
to invest in and advance agricultural research117,  118 and education and thereby to address societal 
challenges.  Topics  under  its  remit  include  nanoscale  delivery  of  agrochemicals,  the  benefits  of 
engineered  nanomaterials  in  crop  production,  sensors  and  detection  for  precision  agriculture  to 
environment,  health  and  safety  (EHS)  implications  of  nanoparticles,  economic,  legal  and  social 
implications (ELSI) of nanotechnology, and communication, education and public perception. Specific 
projects to improve the efficiency of nutrient use are underway on synchronising nutrient release with 
uptake  and  on  using  nanoscale  elements  to  suppress  plant  disease  and  increase  crop  yields. 
Researchers are also being funded for work on plant growth regulation, printable nano-based sensors 

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of pathogen residuals in fields, and the different behaviours of human body compared with control 
animals. Each project must demonstrate the benefits that could result from related developments in 
agriculture  and  food.  Potential  benefits  range  from  high  priority  (and  therefore  more  likely  to  be 
funded) such as reduced pesticides for/in foods, lower amounts of harmful bacteria and less illness 
from food, to lower priority (and less likely to be funded) such as changed taste (making vegetables 
taste like chocolate) and altering the colour of foods. 

Research gaps in food safety are in material characterisation methods (qualitative and quantitative, 
standards, etc.) and in risk characterisation (hazard and exposure). A specific issue is the ingestion by 
marine life of microplastics and nanoplastics, the impact and their fate in the environment, and how 
they are transformed under various food processing technologies. 

The speaker summarised that, for nanotechnology in agricultural and food, the most promising areas 
of  development  are  in  food  and  nutrition  security,  there  being  currently  no  real-life  applications. 
Development is ongoing and it is expected that, if there is clear evidence of the benefits, consumers 
will accept nanotechnology in foods. Key issues that need to be addressed to ensure food and feed 
safety  in  the  future  application  of  nanotechnology  are  regulation  and  the  harmonisation  of 
international dialogue. 

  an  exploration,  as  an 
Agnes  Oomen  (RIVM,  The  Netherlands)  presented  Nanobiotechnology 
is  no  clear  definition  of  bionanotechnology119  or 
example  of  advance  materials.  There 
nanobiotechnology,  but  there  is  a  high  pace  of  scientific  developments  and  a  convergence  of 

to design and develop complex structures at the nanoscale for a specific functionality (e.g. the so-
called DNA-origami120, RNA-origami and designed protein structures) potentially in combination with 
nanomaterials. 

Dealing with these complex and advanced systems is difficult and brings new challenges. What is 
important is being able to identify what applications are possible, whether there will be associated 
risks,  which  regulatory  frameworks  are  expected  to  be  applied,  and  if  risks  will  be  covered  by 
regulatory frameworks. 

Looking  more  closely  at  the  specific  types  of  bionano,  DNA-origami  is  a  self-assembly  of  DNA-
molecules, usually a long DNA-strand to which smaller DNA-strands attach at pre-determined sites 
to form the desired 2D or 3D structure and size (typically 25-150 nm) onto which molecules and 
nanomaterials can be coupled at the surface. Open-source computer programmes are being used to 
design the DNA-origami structures, with a steep decrease in production costs (from USD 200 to USD 
0.2 per mg) and sales of commercial kits with the necessary building blocks. There is at least one 
company  that  produces  customised  structures121,  although  large-scale  production  is  still  difficult. 
Potential application areas of DNA-origami include tailored encapsulation structures (until now mostly 
for cancer medication but with agri/food/feed potential), molecular tools and nanoreactors for the 
fabrication of nanomaterials, building bio-mimicking systems, sensors and nano devices/robots. These 
could also potentially be expanded into areas such as DNA for data storage122.  

RNA-origami  is  similar  to,  albeit  lagging  behind,  DNA-origami.  It  could  be  used  to  make  larger 
quantities and offers additional possibilities to link substances. Protein-origami would enable larger 
3D-structures compared to DNA- and RNA-origami. 

The  potential  risks  are  not  known  yet,  given  the  relatively  unknown  kinetic  behaviour  of  bionano 
structures  (mainly  based  on  information  on  DNA-origami),  with  there  being  no  information  on  its 
uptake by the body. In vitro it is seen to be taken up by the cells, although its degradation path and 

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products  remain  unclear.  Hazards  include  that  such  foreign  DNA,  RNA  and  protein  will  evoke  an 
immune  response,  although  that  could  be  the  desired  trait  for  the  future  design  of  adjuvants  for 
vaccines. There may also be integration of small DNA-fragments in the DNA. RNA-origami fragments 
(degradation products) may interfere with naturally occurring RNA in the cell and thereby affect gene 
regulation  and  protein  production  of  the  cell.  Protein  structures  may  lead  to  protein  aggregation. 
Overall, there are many knowledge gaps that need to be resolved for these new forms of materials.  

The  relevant  regulations  will  be  those  dependent  on  the  product  type  (e.g.  food  or  cosmetics  or 
pharmaceuticals), as well as for chemicals in general (REACH). The genetically modified organisms 
(GMO) regulation is not applicable as there is no intention to change the DNA of an organism. An 
important issue for the application of regulations such as REACH is that it is unclear to what category 
a  bionano  structure  belongs,  as  it  could  be  considered  a  chemical  substance,  a  nanomaterial,  a 
UVCB123, or a mixture, for example. Under REACH, notification is only required when the market volume 
is over 1000 kg (1 tonne) per annum and production volumes of bionano structures is expected to be 
low as they are highly specific and tailored. They may thus remain unobserved under the legislation. 
In terms of toxicity, it is not clear that the existing tests are suitable for these new bionano materials, 
and there is currently no specific test regime in place for RNA interference and protein aggregation. 

It was concluded that technological development is moving towards manipulability at the nanoscale, 
with these developments in bionanotechnology representing only some examples. From a regulatory 
and policy perspective, the applications are at an early stage and not yet on the market, with the 
research being currently technologically oriented, without much considerations on potential risks or 
safety or potential adverse effects. As the field develops, both risks and benefits should be taken into 
account. For now, the applicable legal frameworks are generic and do not consider the specificities of 
these new materials and their potential impacts.  

Safe-by-design  could  be  an  appropriate  approach  for  these  new  materials,  starting  early  in  the 
innovation  process  and  balancing  safety  and  functionality,  taking  into  account  the  safety  issues 
mentioned here. Key steps will include dialogue with stakeholders in a trusted environment and to 
ensure regulatory preparedness. 

Panel discussion  

The panel discussion focused on the actions needed to progress in the safe use of nanotechnology in 
agri/food/feed applications, addressing the questions of gaps and priorities. It was noted that, when 
nanotechnology is used in different sectors (e.g. medical versus food), research, regulatory science 
and regulation must reflect the application area and cannot be generic. Validated and standardised 
methods are needed in research and for regulatory purposes, there being few generic methods for 
nanomaterial characterisation.  

In EHS and regulatory science, concerns were expressed about data comparability. It was proposed 
that  public  funding  should  be  of  longer  duration  in  Europe  in  order  to  retain  the  expertise  on  a 
thematic and experimental area and to develop the research further, thereby ensuring that methods 
would be better developed and to be able to conduct round robin tests over a significant time period. 
There  were  also  concerns  that,  although  databases  have  been  created,  the  quality  of  the  content 
depends on the information provider. Databases are also left to decay at the end of the project if 
there is no follow-up action, similarly with the many websites created during research projects, e.g. 
under the EU Framework Programmes. A common database infrastructure was proposed, bringing 
together  information  based  on  end-points  rather  than  materials  and  provided  that  industry 
proprietary information could be protected. 

The discussion moved to the topic of how the regulatory agencies, the research community and risk 
assessment specialists can work together. The regulatory environments differ between countries so 
early  exchanges  of  information  and  collaborations  are  essential.  In  each  regime,  it  is  essential  to 
know the regulatory data needs in order to undertake relevant studies. Guidance is already provided 

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through, for example, EFSA for agri/food/feed, but industry often struggles to find the time to locate 
and  read  the  information  that  is  available.  To  help  address  this  issue,  there  are  specific  EFSA 
mechanisms for SMEs to provide pre-submission advice, measures that are to be expanded in the 
future  to  enable  extensive  discussions  before  a  dossier  is  submitted,  similar  to  what  happens  in 
Australia  and  New  Zealand.  On  communication  between  regulatory  science  and  industries,  a  one-
stop-shop for information was proposed for responsible industry, especially SMEs, to be easily able 
to find information about relevant data-gathering methods.  

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6  Documentary standards and reference materials 

Co-chairs: Debra Kaiser (NIST, USA) and Andrea Held (EC JRC, EU) 

The session focussed on the challenges of regulation of nanomaterials and the development and use 
of  standards  for  manufactured  nanomaterials,  of  creating  reliable  reference  materials  across  the 
wide variety of current and future nanotechnology-enabled materials and their applications, and on 
efforts to establish internationally accepted standards and test guidelines within those contexts.  

Debra Kaiser (National Institute of Standards and Technology (NIST), USA) opened the session with 
a  presentation  on  the  topic  of  Nanotechnology  standards:  Progress  on  GSRS16  needs  and  ASTM 
International Committee E56. The technical sessions of GSRS16124 covered the topics of advances in 
nanotechnology-derived  drug  products  liposomal  drug  products,  targeted  nanomaterials  for 
biomedical applications, advances in nanotechnology-derived medical devices, nanomaterials in food 
and food contact materials and nanomaterials in personal care products. Regulatory science research 
and  standards  needs  that  were  prioritised  by  participants  were  reference  materials,  guidance 
documents and documentary standards, and it was on the last of these that the speaker focussed.  

From GSRS16, it was concluded that, for regulation, documentary standards are needed for physico-
chemical characterisation (identification and quantitation of nanomaterials, critical quality attributes 
such as size and surface properties, and common methods), in vitro characterisation (interaction of 
nanomaterials with the immune system, drug loading and release from drug delivery systems) and 
other considerations such as materials that are already widely used (e.g. liposomes) and biologically-
relevant media (e.g. tissue and blood). ASTM E56 standards125 are addressing these regulatory needs 
identified at the GSRS16, albeit with most standards being work in progress (12 to 18 months being 
needed  to  draft  an  ASTM  standards  document)  and  most  test  methods  requiring  interlaboratory 
studies. ASTM E56 welcomes any individual or organisation wishing to participate in the development 
of nanotechnology and nanomaterial standards.  

ASTM co-ordinates with other standardisation organisations to avoid duplication. However, as ASTM 
work is proposed by individual members from, for example, a company or regulatory agency, it can 
be difficult to avoid duplication if that organisation proposes a standard, even if a similar activity is 
already  ongoing  in  ISO  or  OECD,  organisations  where  proposals  come  from  a  country.  During 
discussions  after  the  presentation,  as  ASTM  and  other  organisations  including  ISO  were  open  to 
further  strengthening  of  co-ordination  (especially  at  management  levels  and  via  a  formal 
mechanism), it was agreed that a co-ordination and information exchange group would be initiated 
by  the  organisers  of  the  GSRS19  Summit.  The  Chairman126  of  International  Organisation  for 
Standardization Technical Committee 229 (ISO/TC 229) stated that ISO works with, and welcomes, 
official  liaisons  and  expressed  his  availability  for  explanation,  discussion  and,  in  general,  more 
information on liaising with ISO/TC 229.  

The  European  Pharmacopeia  is  the  preferred  European  reference  for  standards  in  the  field  of 
medicine / pharmaceuticals and standards from other organisations are not automatically recognised. 
However, in cases in which there are no standards from the Pharmacopeia, standards from bodies 
such as ISO are preferred over no standards. It was noted that the USA Pharmacopeia has a section 
that works on nano-related issues, on which the U.S. FDA is represented. 

One of the complexities of using reference materials, as explained by Andrea Held (EC JRC, EU) in 
her  presentation  on  Reference  materials  supporting  legislation,  is  that  a  single  material  can  be  a 
certified  reference  material  (CRM)  for  one  property,  a  non-certified  reference  material  (RM)  for 
another property and a representative test material (RTM) for a third property. In reality, many of 

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those who require CRMs, will accept RMs and RTMs as temporary solutions. The reliable measurement 
of  size  and  shape  parameters  of  (nano)particles  is  crucial  for  the  implementation  of  regulations 
regarding nanomaterials and for their toxicology assessment. RMs and RTMs can play a crucial role 
in ensuring the reliability of such measurement results. In the legislative context, measurements must 
be  based  on  reliable  methods  (to  CEN  or  ISO  standards,  for  example)  with  well-characterised 
materials (RTMs, RMs) used for method development and implementation. RMs and CRMs are needed 
for quality assurance to ensure that measurement results in legal context are comparable and correct 
(for laboratory accreditation and method validation).  

EC JRC CRMs for nanoparticles are available with certified values of particle size (e.g. spherical silica 
particles in suspension), shape (e.g. TiO2 nanorods in suspension), and surface area (powders). There 
will soon also be CRMs for surface charge (density) analysis and industrially relevant nanoparticles 
with  a  broad  particle  size  distribution  (powders).  EC  JRC  RTMs  have  been  produced  in  support  of 
various activities including the work of the OECD Working Party on Manufactured Nanomaterials and 
projects, for example, NanoChOp and NanoDefine. They are available through the JRC Nanomaterials 
Repository127.  CRMs  are  also  available  from  other  providers,  including  BAM128  (DE),  PTB  (DE),  NIST 
(USA), NMIJ (JP), NCNST (CN) and from commercial producers. RMs and RTMs are also available from 
NIST (USA), from commercial producers and in the context of specific research projects129, with time-
limited availability130.  

A survey conducted by the JRC aimed to help establish priorities for nanoscale CRMs, RMs and RTMs.131 
It identified that RMs and RTMs are needed to support policy in many sectors including food and food 
contact  materials,  chemicals,  cosmetics,  medicines  and  biocides,  and  for  toxicology  and  eco-
toxicology  work.  Relevant  properties  sought  from  respondents  that  are  already  partly  covered  by 
reference  material  producers  are:  size  (distribution),  surface  properties  (including  area),  biological 
(toxicological) properties, chemical composition and shape. Those also sought but not yet in the JRC 
work programme include concentration in a matrix; aggregation, agglomeration and structure; particle 
number  (concentration),  solubility  and  stability,  dispersibility  and  dustiness.  The  types  of 
nanomaterials sought by respondents and available from RM producers include TiO2, silica and other 
oxides, silver and other metals, and carbon-based materials such as carbon nanotubes and graphene. 
Also sought and under development by the JRC are (C)RMs for complex matrices, such as food and 
cosmetics. It was noted that the need for (C)RMs for medicine and medicinal products seem to be 
underrepresented, although the survey was shared as widely as possible via EU Commission channels 
(e.g. standardisation committees and industry associations).  

Mar Gonzalez (Environment Health and Safety Division, Environment Directorate, Organisation for 
Economic Cooperation and Development (OECD)) presented OECD work supporting the regulation of 
nanomaterials132.  The  OECD  Council  Recommendation  on  Nanomaterials  (Sept.  2013)  chose  to 

exposure assessment methods and risk assessment approaches. Driven by regulatory needs, the aim 

humans  and  the  environment,  to  gain  efficiency  in  chemicals  management  by  developing  and 

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harmonising testing and assessment methodologies, and to avoid duplication of resources used by 
governments and industries. It does not cover pharmaceuticals133.  

Legally binding on OECD member countries and other adherents, the Mutual Acceptance of Data in 
the Assessment of Chemicals (MAD) is for industrial chemicals, pharmaceuticals, pesticides, biocides, 
food and feed additives and cosmetics. It reduces duplication of testing (saving an estimated EUR 
350 million annually) and the use of animals, and lowers trade barriers. The OECD Test Guidelines 
are  covered  by  MAD  and  aim  to  meet  the  regulatory  needs  of  member  countries  regarding  data 
requirements, while addressing animal welfare issues, and improving the cost-effectiveness of test 
methods.  

At the international level, scientific and regulatory acceptance of a Test Guideline can be helped by 
having  a  clear  regulatory  context  across  several  countries,  knowing  the  regulatory  requirements 
before undertaking data collection (assays). An OECD Test Guideline can be developed and published 
within a two-year period, but some have taken up to 10 years to finalise. To facilitate the process, 
there should be  early discussions between method developers and regulators, and  all stakeholder 
need to adopt an issue solving attitude. There needs to be clarity about the intended use of the assay 
or  battery  of  assays  and  their  purposes  e.g.  for  priority  setting,  hazard  identification,  or  risk 
assessment. The assay needs to be broadly available and accessible. Scientific acceptance can be 
fostered by having clarity of experimental data and of the applicability domain covered. There also 
needs to be clarity and transparency of the protocol, sufficient characterisation of the test system 
and  the  guarantee  that  the  protocol  will  be  maintained  over  time.  Clear  data  prediction  and 
interpretation models are needed as well as fit-for-purpose validation processes. The data needs to 
be available in the public domain. 

The  challenges  for  regulation  of  nanomaterials  include  risk  assessment  approaches  and  their 
harmonisation,  methods  for  exposure  assessment,  dosimetry  of  nanomaterials,  physico-chemical 
characterisation,  and  finding  alternative  methods  (e.g.  for  non-animal  testing).  The  importance  of 
breaking out of regulatory silos was highlighted. Other challenges are achieving policy coherence and 
regulatory convergence, and how to integrate the new approach of safe-by-design. Progress can only 
be made with consensus and willing, and change takes time. Although the need (for risk assessment, 
regulatory advances) is immediate, even Test Guidelines take time. In parallel, clear definitions are 
needed for existing and new nanomaterials, including those based on converging technologies such 
as biotechnology and nanotechnology.  

On  standards  for  nanomaterials,  the  OECD  mostly  works  with  ISO  (International  Organization  for 
Standardization), the next presentation being by Denis Koltsov (ISO/TC229, Nanotechnologies) who 
spoke on Nanotechnology standards for industry, regulators and other stakeholders.  

Since  the  2000s,  the  development  of  nanotechnology  has  led  to  an  enormous  investment  in 
nanomaterials production. Although the original hype has been somewhat tempered, it is still forecast 
that the market for manufactured nanomaterials will reach up to USD 100 billion by 2025. ISO is 
engaged  in  the  development  of  standards  for  nanomaterials  under  its  technical  committee 
ISO/TC229. An ISO standard is a documentary standard that represents the current best practice and 
consensus  of  all stakeholders  (countries and organisations).  Standards  facilitate  compatibility  and 
comparison of products, materials and services and, in the case of safety standards for products, 
facilitate consumer acceptance. While it may at first seem costly to comply with a standard, they 
save businesses time and money. 

The  development  process  for  standards  begins  with  a  draft  developed  at  national  level  through 
consultation with all stakeholders and accepted as best practice at national level, through a process 
that varies in duration from one month to one year. The next step is an ISO Draft Document that is 
commented on by all ISO members and accepted by ISO experts (typically taking two to four years). 

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The final ISO International Document is approved by ISO, accepted by ISO members and becomes a 
global reference.  ISO/TC229 aims through this process to contact as wide a stakeholder  group as 
possible to avoid redundant and duplicated work. 

ISO/TC 229 Nanotechnologies was founded in 2005 and has a membership of 33 participating and 
19  observing  countries.  It  has  developed  61  standards  and  related  informative  documents  (about 
one-third  of  the  61  are  Technical  Reports),  and  37134  are  under  development135.  The  scope  of 
ISO/TC229  is  standardisation  in  the  field  of  nanotechnologies  that  includes  either  or  both  of  the 
following: (1) Understanding and control of matter and processes at the nanoscale, typically, but not 
exclusively, below 100 nanometres in one or more dimensions where the onset of size-dependent 
phenomena usually enables novel applications; (2) Utilising the properties of nanoscale materials that 
differ  from  the  properties  of  individual  atoms,  molecules,  and  bulk  matter,  to  create  improved 
materials, devices and systems that exploit these new properties. 

Specific  tasks  include  developing  standards  for:  terminology  and  nomenclature;  metrology  and 
instrumentation, including specifications for reference materials; test methodologies; modelling and 
simulation; and science-based health, safety, and environmental practices. 

ISO/TC229 liaises and has agreements with a number of other international committees working on 
nanomaterials  including  the  OECD  Working  Party  on  Manufactured  Nanomaterials  (WPMN), 
CEN/TC352,  IEC/TC113136  and  ASTM  E56.  In  addition  to a  nanotechnology  liaison  and  coordination 
group (NLCG) and a sustainability, consumer and societal dimensions group (SCASD), ISO/TC229 has 
five  Working  Groups:  terminology  and  nomenclature  (5);  measurement  and  characterisation  (21); 
health, safety and environment (11); material specifications (13); and products and applications (2), 
the  number  in  parentheses  being  the  number  of  standards  and  informative  documents  under 
development by each group (January 2018). While Working Groups are typically led by one country 
or  organisation,  ISO/TC229  also  uses  a  system  of  study  groups  to  explore  areas  needing 
standardisation work, but too big for one country to lead. While most ISO TCs are vertical and address 
one file, ISO/TC229 is horizontal and therefore is more wide ranging than other TCs.  

It  was  noted  that  standards  are  the  consolidation  of  well-established  knowledge  and  their 
development is funded by the developer, so standardisation is usually not a primary way of sharing 
new  research  information.  However,  inter-laboratory  studies  can  be  undertaken  within  publicly 
financed research projects (e.g. under the Versailles Project on Advanced Materials and Standards 
(VAMAS)137) and contribute to the information used in the final development of a standard.  

Bryant  C  Nelson  (National  Institute  of  Standards  and  Technology  (NIST),  USA)  presented  some 
Challenges in standardising in vitro assays for the evaluation of nano-enabled drug products. The two 
key criteria for in vitro assays to support regulatory decision-making are relevance (the ability of a 
test method to measure or predict an effect/target of interest as well as the regulatory need, and 
incorporating fit-for-purpose) and reliability (the extent of reproducibility of results from a test within 
(intra-)  and  among  (inter-)  laboratories  over  time,  when  performed  using  the  same  standardised 
protocol or process (SOP)).  

Some major challenges in test methods and documentary standards for in vitro assays include that 
high-quality  test  methods  are  difficult,  time  consuming  and  costly  to  develop,  while  even  what  is 
considered high quality may suffer from a variability of source data. There is also a critical shortage 
of pre-competitive test methods and documentary standards compared to the increasing number of 
drug product submissions containing nanomaterials and limited availability and application of in vitro 

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assay  measurement  assurance  frameworks.  The  shortage  of  test  methods  and  standards  affects 
characterisation of quality attributes and manufacturing efficiency. Transferability of in vitro assays 
is also difficult. For example, many in vitro 
comparisons.  

Measurement assurance frameworks should be more widespread as they are important for ensuring 
measurement  confidence  in  the  results  from  in  vitro,  as  well  as  other,  assays.  To  achieve 
measurement  assurance  for  test  methods,  NIST  is,  inter  alia,  comprehensively  identifying  and 
evaluating  the  sources  of  variability;  carefully  designing  its  experiments  to  avoid  variations; 
establishing  robust  in-process  controls;  performing  interlaboratory  comparisons;  and  developing 
reference materials for traceability. 

Normative and pre-normative activities for nanomaterials measurement and characterisation  were 
presented  by  Charles  Clifford  (National  Physical  Laboratory  (NPL),  United  Kingdom).  Industrial 
developments in nanomaterials are leading to the production of both high volume, low cost and highly 
specialised  materials.  The  former  (high  volume,  low  cost  materials)  present  a  situation  where 
production volume can outstrip application need and there is competition to sell at the lowest price, 
which may lead to poor quality materials. Standards are essential for their quality assurance. The 
latter (highly specialised materials) have properties tailored to each application and highly specific 
properties  such  as  surface  functionalisation,  size  and  shape.  As  seen  in  previous  presentations  at 
GSRS19, standards are also needed for these novel materials. 

The  Surface  Technology  Group  of  the  NPL  works  on  unique  reference  materials,  interlaboratory 
studies and documentary standards. It engages via VAMAS to provide input to the work on surface 
chemical analysis, nanoparticle populations, graphene and Raman spectroscopy, that then feeds into 
the international bodies ISO/TC229 and CEN/TC352. For example, NPL has contributed to VAMAS work 
on nanoparticle number concentration, the aim being to achieve comparability and reproducibility of 
the measurement of number concentration of nanoparticles138, and to disseminate best practice for 
sample preparation and measurement. This VAMAS project involved 53 institutions mainly in Europe 
(over 75%), including National Metrology Institutes (NMIs), companies, research organisations, and 
academia, and resulted in 73 submitted measurement reports. Such collaborative international work 
can make a significant contribution in the development of standards  of industrial importance and 
that are based on valid and repeatable results.  

There is a clear opportunity to improve standards and regulatory science by testing and validating 
methods using VAMAS interlaboratory studies. In addition to good quality and reproducible data, there 
needs  to  be  greater  clarity  in  terminology  for  standards,  and  the  development  of  specific 
measurement  methods,  including  methods  for  specific  materials.  Overlapping  standards  from 
different organisations should be avoided.  

There  are  more  than  100  medical  device  applications  containing  nanomaterials  or  related  to 
nanotechnology in China. In his talk on Standards and evaluations of nanomedical devices in China, 
Liming  Xie  (National  Centre  for  NanoScience  and  Technology  (NCNST),  China)  provided  specific 
examples of how the medical regulations applicable to certain materials have changed over time in 
China.  

One example was that of medical devices containing nano-silver. In 2006, such devices were assigned 
as  Class  III  medical  products.  In  2009,  there  was  an  initial  discussion  on  the  standards  and 
experimental  supporting  information  (characterisation  and  clinical  evaluation)  needed  for  product 
registration.  In  2010,  there  was  a  subsequent  discussion  on  more  details  for  product  registration. 
Finally, in 2015, it was decided that products containing nanosilver in the form of a solution or gel 
would not be considered as medical devices but should be categorised as drugs.  

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Chinese organisations work with bodies such as ISO as a means to fully support the development, 
characterisation and regulation of medical devices and drug containing nanomaterials. This includes 
work  on  guidance  (characterisation  and  bio-evaluation),  technical  standards  (standardisation  of 
current methods and development of new methods), reference materials and fundamental research 
(e.g.  looking  at  the  molecular  mechanism  of  the  biological  effect  of  certain  nanomaterials). 
Collaborations across China have the common goal of creating a national top-level characterisation 
and evaluation platform for nanomedical devices (later also for nanodrugs). One such collaboration 
is between the NCNCT and the National Institutes for Food and Drug Control (NIFDC) (including the 
NCNST-NIFDC  Joint  Laboratory  for  Measurement  and  Evaluation  of  Nanomaterials  in  Medical 
Applications) and the Centre for Medical Device Evaluation (CMDE)139. The tasks being undertaken are 
fundamental research on bio-effects of medical nanomaterials, development of national standards 
and reference materials, and certified characterisation and evaluation of medical devices containing 
nanotechnology. 

Guidance and standards are both needed in regulation, and work on national standards in nano-and 
biotechnology  is  being  undertaken  by  SAC140/TC279  (National  Technical  Committee  279  on 
Nanotechnology)),  which  has  developed  standards  for  applications  of  silver  nanomaterials,  gold 
nanoparticles  and  carbon-based  nanomaterials.  More  than  40  technical  protocols  have  been 
developed  (14  for  physico-chemical,  26  for  in  vitro  biological  effects  and  4  for  in  vivo  biological 
effects) and some of these protocols can be applied to other nanomaterials. 

In  the  future,  it  is  planned  to  continue  close  cooperation  with  the  National  Medical  Products 
Administration  (NMPA)  (formerly  known  as  the  Chinese  FDA),  on  guidance,  standards,  reference 
materials,  characterisation  and  bio-effect  evaluations.  There  will  be  a  joint  platform  between  the 
NMPA and the Chinese Academy of Sciences (CAS) on regulatory science for innovative medicines. 
More international collaboration is planned on standards, characterisation and other key issues of 
regulatory  science.  As  there  are  many  documents  only  in  Mandarin,  it  could  be  beneficial  for 
international cooperation to translate them into English and send them, for example, to ISO. It was 
noted that as NCNST is a non-profit organisation, its reference materials can be sent outside China 
at no cost. 

ective generic 
drugs available to the American public, implementing standards based on the best available science 
and the results of the regulatory science research. Wenlei Jiang (FDA, USA) gave a brief overview of 
diverse FDA-approved nanotechnology drug products and introduced the concept of product-specific 
guidance to support generic nanotechnology product development in her presentation on Regulating 
generic nanotechnology drug products: Guidances and standards. Approved nanomaterial-containing 
products  are  based  on  liposomes,  inorganic  nanoparticles,  protein  nanoparticles,  polymer 
nanoparticles, emulsions, lipid complexes, nanotubes, nanocrystals and micelles. These products are 
used to combat diseases such as cancer, anaemia, macular degeneration and others. 

141,  provides  pre-
submission scientific advice on equivalence standards, consults and reviews complex scientific issues 
and ensures therapeutic equivalence of approved generic drug
respective reference listed drugs (RLDs), generally with the same active ingredient(s), conditions of 
use,  route  of  administration,  dosage  form,  strength  and  (with  certain  permissible  differences) 
labelling, and are therefore bioequivalent.  

In the development of standards for nanotechnology, the speaker identified steps from identification 
of  a  need,  stakeholder  engagement,  assay  development,  and  validation,  to  the  identification  of 
experts to undertake reviews, the iterative process to address all comments, and the final standard 
ready for interlaboratory studies. The Nanotechnology Standards Database is hosted by the American 

139

140

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58 

                                          
 
 
 
National  Standards  Institute  (ANSI)  and  contains  published  and  government  documents,  and 
documents under development. Major gaps in standards for nanomedicines were identified in a recent 
paper, which includes methods, guidance, reference materials and the evaluation of the suitability 
and recognition of standards developed in other sectors.54 

On characterisation methods for standards development, the speaker highlighted that most methods 
are highly product-specific and multiple different methods have been developed by different labs. 
Advanced analytical methods are not always the most readily available ones. In summary, it was seen 
that  documentary  standards  are  complementary  to  product-specific  guidance  for  generic 
nanotechnology  drug  product  development  and  to  support  generic  nanotechnology  drug  product 
development and review, there is a need to continue developing product-specific guidance, to promote 
harmonisation  of  assessment  criteria,  and  to  support  characterisation  method  development  into 
standards. 

Shan  Zou  (National  Research  Council  (NRC),  Canada)  presented  work  on  the  Characterisation  of 
nanomaterials and their cytotoxicity assessment. Significant advances in nanometrology, the science 
of  measurement  at  the  nanoscale,  are  crucial  for  the  continued  development  of  nanotechnology-
based  consumer  products.  The  NRC  works  to  enable  a  better  understanding  and  adoption  of  new 
nanomaterials through advanced characterisation methods and the development of standards and 
certified reference materials (CRMs). 

New and integrated measurement approaches with higher spatial resolution, accuracy and sensitivity 
are essential to fully characterise nanomaterials. NMIs142 are developing traceable instrumentation 
and  measurement  techniques  for  calibration  as  well  as  standards  and  reference  materials  and 
suitable  models  for  uncertainty  evaluation.  They  are  also  conducting  international  measurement 
comparisons via inter-laboratory comparisons to demonstrate repeatability and reproducibility. The 
or drawback in many 

143. 

Many questions have been raised about the potential impact of nanomaterials on human health and 
the environment. New measurement methods combined with the monitoring of toxic responses using 
cellular  model  and  assay  systems  are  expected  to  provide  insights  for  the  risk  assessment  of 
nanomaterials.  The  NRC  is  looking  at  the  new  area  of  nanocarbon  metrology  and  developing 
quantitative metrological assessment protocols for the characterisation of nanotubes and graphene 
related  materials.  A  Special  Interest  Group  (SIG)  of  NRC  Metrology  and  Canadian  companies  is 
facilitating the development of standards for graphene made by exfoliation methods. There are also 
many Canadian contributions to international standards activities (IEC/TC113, ISO/TC229, ASTM E56) 
and links to worldwide nanoscale measurements and nanomaterial metrology efforts.  

Panel discussion  

The discussion focused on the research gaps and/or priorities in regulatory science in test guidelines, 
documentary standards and reference materials for nanotechnology and how these can be addressed.  

One area needing more work in standards development is methods for liposomes. ASTM E56 has one 
published standard on liposomes and four standard test methods being developed. ISO/TC 229 has 
ideas on standardisation for measuring liposomes, but this field is challenging as there is still much 
research being done. It was noted that ISO/TC 229 and ASTM both use metrology checklists to identify 
the relevance and maturity of proposals for standardisation before initiating any work.  

While  there  are  standardisation  documents  based  on  the  use  of  specific  instrument  types  and 
techniques, properties of nanomaterials are method-defined and may be better served by standards 
that encompass the entire method, starting with the sample preparation, choice of instrument and 
reference materials. This would remedy the frequent need to use a combination of standards to obtain 

142

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the  desired  result.  Full  standards  also  require  interlaboratory  comparisons  to  confirm  the 
transferability of the method. It was noted that ASTM uses a specific template for reporting research 
t  the  US 
Pharmacopeia proposes to develop both general standards and product-specific ones with detailed 
testing conditions.  

As there is a legal requirement to reduce animal testing in the EU (and it is banned for cosmetics), 
harmonisation, via the OECD to ensure regulatory uptake, and standardisation for in vitro methods is 
urgently  required.  Communication  across  regulatory  silos  (e.g.  different  pieces  of  legislation)  and 
exchange  of  knowledge  could  help  to  promote  in  vitro  testing.  Such  communication  has  been 

-

project EU project Gov4Nano also provides an opportunity in its event for risk assessors to discuss 
risk assessment for nanomaterials.  

The question of having an efficient process for overall standardisation was raised. It was noted that 
the  OECD  does  not  develop  standards,  but  rather  Test  Guidelines  for  regulatory  testing  that  are 
applicable  to  "all"  chemicals  or  "all"  nanomaterials,  not  to  specific  ones.  When  needed,  OECD  Test 
Guidelines refer to, for example, ISO standards, which are either applied as such or adapted in order 
to implement specific steps. ISO and ASTM representatives recognised that there is some duplication 
of standards between the two standardisation bodies.  

To utilise evident synergies, it was proposed to set up a working group to look into the co-ordination 
of  documents  under  development  and  to  identify  priority  areas  (e.g.  standards  on  liposomes, 
nanomaterial toxicity) and gaps that could be jointly addressed. The Global Coalition could have a role 
as  a  facilitator  of  communication  among  different  standardisation  bodies,  which  tend  to  have 
different  priorities  and  business  models.  Another  suggestion  was  to  collaborate  on  laboratory 
activities related to standardisation, for example in inter-laboratory validation, similarly to what has 
been done by the USA and EU Nanomedicine Characterisation Laboratories. During the discussion, it 
was also pointed out that nanoscience is still in the development phase: thus some well-established 
(i.e. fully developed and validated) methods ready to be standardised are not available yet.  

It  was  further  remarked  that  industry  needs  simple  measurement  technologies  and  methods. 
Therefore, any advanced laboratory methodology is probably better suited to the validation of such 
simple methods, rather than to being used directly by industry.  

A  GCRSR  Standards  Group  was  proposed  to  improve  communication  specifically  on  international 
standards,  with  membership  to  include  GCRSR,  ISO,  ASTM,  CEN,  OECD,  etc.  The  panel  discussion 
concluded with a call for volunteers willing to contribute to the proposed group. 

60 

 
 
 
7  Challenges concerning Nanoplastics 

Co-chairs: Anil K. Patri (FDA, USA) and Arnd Hoeveler (EC JRC, EU) 

The  final  plenary  session  addressed  the  challenges  of  nanoplastics  such  as  definitions, 
characterisation and measurement, and highlighted some current scientific and regulatory activities.  

Based on the SAPEA144 report145 Nanna B. Hartmann (DTU, Denmark) discussed Risks of micro- and 
nanoplastics to humans and the environment. In this regard, terminology is of critical importance is 
terminology as, without a shared understanding it is difficult to clearly categorise plastic debris and 
create a framework to tackle environmental problems resulting from plastics, including nanoplastics. 
The aim should be the establishment of a clear nomenclature and research to provide a scientific 
foundation for discussions about harmonised regulatory definitions and mitigation policies for plastic 
debris.  

In a recent publication Hartmann et al.146 
heavily  modified  natural  polymers  as  an  essential  ingredient  that,  when  present  in  natural 
environments without fulfilling an intended function, are solid and insolubl
can be further categorised according to size, including sub-micron and nanoplastics (i.e. 1-1000 nm), 
shape, colour, and origin.  

There  is  currently  no  adequate  analytical  methodology  to  detect  and  characterise  nanoplastics. 
Although the presence of nanoplastics in nature is generally considered highly plausible, there is still 
little or no information on their presence in freshwater, soil or the atmosphere, in biota, drinking water 
exposure to microplastics in the laboratory has a significant, 
negative effect on food consumption, growth, reproduction and survival, once effect thresholds are 
exceeded
marine biota, molluscs and copepods. Nanoplastics and very small microplastics can pass biological 
barriers such as the gut epithelium. However, the studies used much higher concentrations of plastics 
than  those  currently  reported  in  the  environment,  or  very  small  microplastics  for  which  limited 
exposure  data  exists,  or  spherical  particles  not  representative  of  real-world  particles,  or  were 
conducted using relatively short exposure times. Thus, the studies may not apply to the situation in 
the natural environment.  

It is as yet unclear whether nano- and microplastics cause chemical toxicity in marine organisms147 
and  whether  such  plastics  may  present  an attributable risk  to  human  health  when they  enter  the 
food-chain148
mental  exposure  (in  terms  of 
concentrations, sizes, shapes, polymer types, weathering states) and exposure in lab-based studies, 
making risk assessment theoretical and not reliable. To close this gap, improved analytical methods 
and sampling procedures are needed to enable the production of reliable data on concentrations and 
properties of nano- and microplastics in the environment.  

Plastics contain not only polymers but also small organic chemicals (additives, residual monomers, 
polymerisation  aids)  that  can  leach  out  once  nano-  and  microplastics  are  released  into  the 
environment. At the same time, the plastic material can take up other hydrophobic organic chemicals 
(HOCs) from the environment. Laboratory studies indicate that HOCs can be transferred from plastics 
to  tissues  of  various  organisms,  but  evidence  is  weak  to  support  the  occurrence  of  ecologically 

144

145

146

147

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significant adverse effects on aquatic life because of exposure to microplastics. In addition, there are 
many other (direct) ways of uptake of chemicals, from food, prey or ambient water, which likely far 
exceed the uptake of chemicals via plastics. 

In  summary,  current  evidence  of  ecotoxicological  effects  of  microplastics  is  limited.  However,  if 
environmental emission rates remain unchanged, ecological risks of microplastics may be widespread 
within a century. More (quantitative and qualitative) information is needed  on environmental (and 
human)  exposure  to  nanoplastics,  enabled  by  improved  and  harmonised  measurement  methods. 
While  there  is  ongoing  work  to  improve  analytical  methods  for  microplastics,  new  (and  multiple) 
methods  are  required  for  the  analysis  of  nanoplastics.  This  must  be  complemented  with  the 
production of relevant hazard data and a better understanding of the potential modes of toxicity for 
different sizes, shapes and types of nano- and microplastics.  

Julien Gigault (CR-CNRS, France) also addressed the topic of Nanoplastics in the real world: source, 
presence and environmental fate. To establish the scale of the potential problem, sources were quoted 
which estimate that while in 2015 alone eight million metric tonnes of waste plastic ended up in the 
oceans, the fate of 99% of the material is unknown. Mention was made of a nanoplastics consortium, 
which is seeking to develop analytical methodologies to characterise nanoplastics and to develop a 
model for investigating the fate and impact of nanoplastics. 

As a starting point, nanoplastics were defined as any plastic from 1 nm up to 1000 nm in size existing 
as single particle or in homo- and/or hetero-aggregate form, resulting from the degradation of bulk 
or macroscopic plastic objects. Nanoplastics are difficult to detect. A consequence of their origin from 
degradation of a variety of plastic objects is that they are highly poly-dispersed in physical properties 
and heterogeneous in composition. Nanoplastics may present colloidal properties in aqueous media 
and thus may remain suspended in aqueous systems. A dedicated analytical strategy was developed 
and revealed the need for models, based on structure, shape, surface, composition, etc., in order to 
calibrate methods and for use in experimental studies. 

While  the  oceans  are  typically  considered  the  principle  environmental  compartment  contaminated 
with microplastics and nanoplastics, large amounts of plastic waste have also been buried in soils 
and left to decay for many years, thus forming a source of plastic particulates which may be carried 
by ground water into the aquatic environment. Such plastic-contaminated soils represent a source of 
naturally generated microplastics. A detailed case study was presented in which the analysis methods 
and results obtained from plastic-containing soil samples were described. Soil leachates have been 
found  to  contain  polyethylene  (PE),  naphthalene,  styrene  and  toluene.  It  was  noted  that  although 
styrene may come from plastics, it is also a pyrolysis product of natural organic matter.  

Nanoplastics are found to be highly mobile in soil and the organic matter present seems to have a 
strong influence on the fate of the plastic debris. Additives may increase transportation efficiency 
while increasing size and asymmetrical shape may be linked to increasing deposition. Shape also has 
an impact on the manner of the deposition. It is necessary to employ multiple methods for detection 
and characterisation, and  methods for  microplastics may not be sufficient to detect and  measure 
nanoplastics.  The  speaker  cautioned  against  extrapolation  from  one  nanomaterial  (a  specific 
nanoplastic) being a potential hazard to all nanomaterials (all nanoplastics) being dangerous. Proper 
communication  is  particularly  important  if  the  public  is  to  be  well  informed  and  if  a  balanced 
understanding of the benefits and risks of applications of nanotechnology is to be achieved. 

In addition, categorisation of all nanomaterials based on one nanomaterial should be avoided and 
caution  is  needed  in  comparing  nanomaterials  with  other  materials.  In  his  presentation:  Detecting 
nanoplastics in the environment: adapting existing methods from nanotechnology, Souhail Al-Abed 
(EPA, USA) emphasised that it is unlikely that a regulation designed for microplastics, for example, 
will  be  applicable  to  nanoplastics.  He  raised  issues  of  terminology  and  comparability  of  data, 
particularly for nanoparticles, and round robin testing. Comparing micro- to nanoplastics, it has been 
found that nanoplastics are physically less likely to settle than microplastics and they will typically 
be transported over longer distances than larger plastics. Nanoplastics are more likely to enter the 

64 

food  chain  and  to  bioaccumulate.  They  have  a  larger  surface  area  than  microplastics,  facilitating 
faster leaching of additives and greater adsorption of metals and organic pollutants. Overall, better 
extraction methods are needed if work on nanoparticles is to be undertaken, including the avoidance 
of issues of contamination. Current characterisation methods, such as dynamic light scattering (DLS), 
nanoparticle  tracking  analysis  (NTA),  and  electron  microscopy  (TEM/SEM),  all  provide  information 
about size and possibly shape, but are not able to differentiate between diverse polymers. Improved 
and emerging techniques include pyrolysis-GC/MS; atomic force microscopy - infrared spectroscopy 
(AFM-IR); and cloud point extraction (CPE). 

The  dilemma  of  environmental  analyses  is  that  it  is  not  possible  to  develop  a  detection  method 
without  an  adequate  extraction  method  that  eliminates  interferences  e.g.  by  non-plastic 
nanomaterials. At the same time, it is not possible to develop an adequate extraction method without 
a viable detection method to confirm analyte recovery and removal efficiency for interferences. Thus, 
it would help to establish reference materials for nanoplastics (e.g. polymer nanospheres) and to use 
such materials to test the efficiency of existing extraction methods for nanoplastics and to improve 
extraction methods with new filters, flotation media, settling times, etc. This could be a long iterative 
process and, indeed, may only be suited to near-spherical nanoplastic particles.  

In addition, the speaker proposed a new abbreviation for nanoplastics (NPls) to avoid confusion with 
the  abbreviation  for  nanoparticles  (NPs).  He  encouraged  the  idea  of  defining  the  size  range  for 
  1000  nm.  Even  in  studies  that  focus  on  microplastics,  standards  for 
nanoplastics  as  being  1 
nanoplastics  should  be  included  in  evaluating  extraction  and  detection  efficiencies.  Existing 
microplastics techniques need to be adapted for nanoplastics 
 either by coupling them with other 
techniques (AFM-IR) or by pre-treatment to aggregate the nanoplastics (CPE). Collective regulatory 
actions should include achieving established and verified methodologies for extraction, detection and 
characterisation of nanoplastics alongside microplastics. 

Douglas Gilliland (EC JRC, EU) considered the question of What can the analytics of nanomaterials 
bring to the detection of nanoplastics? In his introduction, the speaker outlined the commonly-used 
classification of nano- and micro-plastic particles based on their origin - either primary particles that 
have been manufactured at the micro- or nano-scale (e.g. for inks, paints, cosmetics and abrasives) 
or secondary particles resulting from the breakdown of plastics from bulk materials as a result of 
being subjected to wear that is mechanical, chemical or light-induced.  

Subsequently, when considering whether existing nanoparticle analytical methods could be used for 
nano-  and  microplastics,  an  important  issue,  which  was  highlighted,  was  that  many  engineered 
nanomaterials are inorganic in nature and thus more easily distinguished/identified in the presence 
of  a  background  organic  matrix  materials  via  elemental  detection  methods  such  as  ICP-MS 
(inductively coupled plasma mass spectrometry). In contrast, micro- and nano-plastic being mostly 
composed of the same elements (carbon, oxygen, hydrogen, nitrogen) as natural organic materials 
are more difficult to unambiguously identify and quantify. It was highlighted that some established 
analytical methods such micro-Raman and micro-FTIR can be effective for identifying microplastics 
although there is a need for further development and, above all, harmonisation and standardisation. 
For the smaller-sized nanoplastics, these methods are not effective and, in agreement with previous 
speakers, it was reiterated that there is a need for new methods to assess their presence, identity 
(including shape) and quantity in complex matrices such food, water and environmental samples. A 
number  of  existing  methods  for  characterising  engineered  nanomaterials  were  described  and 
consideration  given  to  their  potential  use  in  the  analysis  of  nano-  and  microplastics.  The  speaker 
presented  several  examples  of  studies  into  potentially  applicable  techniques  for  nanoplastic 
fractionation, sizing and chemical analysis including the specific instrumentation (such as electron 
microscopy (SEM)) that fall into this category.  

In  concluding,  the speaker  noted  that  the study of  sub-10  micron plastic  particles  presents  major 
challenges particularly if particle identification is required. Nanoplastics analysis methods can benefit 
from selected methods used for engineered nanomaterials. Key challenges that remain to be resolved 
include  sample  extraction,  concentration  and  handling  (avoiding  contamination),  and  improving 

65 

sensitivity and specificity. It is essential that there be a clear definition of the information required 

be a driver for the development of new analytical technologies for nanoplastics, given the common 
use of organic based nanomaterials in diagnostic and therapeutic health applications.  

Iseult  Lynch 
presentation on Harmonising detection, quantification and impact assessment of micro/nanoplastics 
in freshwater environmental hotspots. The project entails a large group of microplastics researchers 
sampling 100 rivers worldwide using the same inexpensive sampling device to capture small plastic 
particles.  Sampling  takes  place,  for  example,  in  different  climate  situations  (e.g.  before  and  after 
monsoon) and locations (e.g. up- and down-stream of wastewater treatment plants). The project aims 
to create a global database of plastic materials found in rivers and gathered using the same sampling 
technique. First, the focus is on optimising the methods for mesoplastics (increasing sensitivity and 
reducing  or  ideally  eliminating  contamination)  before  applying  them  to  microplastics.  Once  the 
techniques are effective in the laboratory, they will be tested for real-world applicability on unknown 
plastics (e.g. collected on a beach).  

The  speaker  identified  the  need  for  harmonisation  of  methods  and  for  more  robust  method 
development and testing. There is also a need to understand the effects, if any, of exposure to the 
plastics themselves and to any co-pollutants that they may have acquired (e.g. contaminants), and to 
move from observational and descriptive to hypothesis-driven research. The current research gaps 
and  priorities  in  regulatory  science  related  to  nanoplastics  highlighted  by  the  speaker  included 
methods  for  the  isolation  of  nano-fractions;  robust,  high  throughput  methods  for  detection  and 

assessment, co-transport, biomagnification etc., and hazard testing in accumulation hot spots.  

The first results of the RealRiskNano Project149 were presented by Ted Henry (Heriot-Watt University, 
UK)  in  Distinguishing  the  realistic  environmental  risks  of  nanoplastics  by  investigating  fate  and 
toxicology  in  real-world  scenarios.  Considering  that  some  microbes  form  agglomerates  with 
nanoplastics,  the  project  aims  to  evaluate  their  formation  and  their  presence  in  environmental 
locations,  evaluate  their  toxicology  and  biological  effects,  and  investigate  the  sorption  of  co-
contaminants. Sorption and bioavailability are investigated by measuring changes in biomarker gene 
expression.  

Looking  at  microplastics,  it  was  found  that  ingestion  occurs  in  biota,  but  absorption  is  low  and 
depuration is rapid. Any reduction in sorption and bioavailability depends on the context. The effects 
in  mesocosm  organisms  are  minimal  even  at  very  high  concentrations.  Human  exposure  to 
microplastics via consumption of seafood is low compared to other sources. For example, the uptake 
of  microplastics  from  eating  contaminated  mussels  is  estimated  to  be  less  than  the  microplastic 
contamination from the dust falling onto the plate during the meal.  

It was concluded that more work needs to be done to determine the extent to which nanoplastics are 
formed in the environment and to see where those particles accumulate. The relationship between 
the morphology, behaviour and impact of the particles needs to be clarified, looking, for example, at 
whether  some  shapes  of  nanoplastics  (e.g.  fibres)  are  particularly  problematic.  The  speaker 
emphasised that achieving a circular economy for plastics is challenging and that there is a need to 
work  globally  and  across  disciplines  to  address  the  challenges,  including  incorporating  plastic 
recycle/reuse into product design. 

Alfonso Lampen (BfR, Germany) gave a presentation on Micro- and nanoplastics in food: oral uptake, 
toxicology and initial aspects of risk assessment. There have been reports of the occurrence of plastics 

149

66 

                                          
 
in a variety of food products including bivalves150, salt151 and mineral water152. The plastics can come 
from  plastic  wrapping,  bottles  and  tubes,  but  also  from  manufacturing  processes.  Although 
microplastics occur in food, there is no harmonised definition of microplastics (in terms of size and 
morphology)  and  no  appropriate  methods  of  quantification.  Since  risk  depends  on  the  potential 
hazard, the exposure and the uptake, there is insufficient data to make a clear risk assessment in 
such  cases.  Despite  that,  recent  research153  has  reported  that  the  contamination  of  foodstuffs  by 
micro-  and  nano-plastic  particles  released  spontaneously  from  packaging  materials  seems  rather 
unlikely. 

In general, the skin, when intact, is a good barrier against chemicals and other agents that are, for 
example, carried by cosmetics. Uptake from foodstuff tend to be small and plastics have been found 
to persist the digestive process (saliva, digestion enzymes, etc.) in humans. Human digestion fluids 
are not able to degrade or change plastic materials.  

In  summary,  microplastics  can  accumulate in  the  environment  and  reach  the  food chain  but  their 
uptake from nutrition, their bioavailability and the toxicological mechanisms are not fully understood. 
Further research is needed concerning material characterisation, detection and cellular uptake and 
effects, even though, according to the current understanding, the risk to consumers is low.  

Sylvain Bintein (EC DG ENV, EU) presented the Proposal of ECHA (the European Chemicals Agency) 
for  a  restriction  of  intentionally-added  microplastics  and  nanoplastics.154 155  The  concerns156  about 
microplastics and nanoplastics derives from them being easily ingested due to their small size. They 
can enter into the food chain when being mistaken for food, e.g. by suspension feeders. Laboratory 
studies have reported a variety of adverse effects including toxicity. The materials tend to fragment 
into smaller and smaller particles and are resistant to (bio)degradation, leading to a potential long-
term, irreversible accumulation in the environment. 

ECHA has concluded that the release of intentionally added microplastics can pose a risk that is not 
adequately  controlled.  At  the  same  time,  it  is  acknowledged  that  the  current  data  provides  an 
incomplete picture of the situation. There are several risk assessment approaches being implemented 
under REACH:  threshold-based  (PEC/PNEC)157  and  non-threshold-based  (PBT/vPvB)158  approaches. A 
case-by-case  approach  is  also  an  option.  However,  a  significant  issue  is  the  lack  of  a  consistent 

to small solid particles composed of synthetic polymers that are non-degradable, a less than 5mm 
size criterion being often used.  

The  proposed  restriction  of  intentionally  added  microplastics  and  nanoplastics  includes  different 

natural/biodegradable  polymers  and  uses  without  foreseeable  micro-plastic  release);  (c)  labelling 
obligations (for uses where microplastic release can be minimised with instructions for use); and (d) 
mandatory  reporting  requirements  (of  identity,  description  of  use,  tonnage,  releases).  Outside  the 
scope of the ECHA restriction would be materials that occur in nature and have not been chemically 
modified, or materials that are (bio)degradable. Other proposed derogations from the ban (that would 
be  subject  to  labelling  and/or  reporting)  include  microplastics  used  at  industrial  sites,  used  in 

150

151

152

153

154

155

156

157

158

67 

                                          
 
 
 
 
   
 
 
 
 
medicinal  products  for  human/veterinary  use,  contained  throughout  their  life-cycle  (e.g.  in  a  solid 
matrix)  or  permanently  modified  at  the  point  of  use  so  they  are  no  longer  considered  as  being 
microplastics (e.g. coatings, films). 

Public  consultation  on  the  proposed  restriction  ended  in  September  2019.  Following  scrutiny  by 
-economic  analysis  (SEAC),  the  final 
Committee opinions will be sent to the Commission for decision-making in summer/autumn 2020. 
Any resulting restriction could potentially enter into force in summer 2021. 

The presenter noted that research is needed on toxicological effects of nano- and microplastics as 
well as their impacts on the terrestrial environment. Test methods need to be robust and applicable 
to polymers including nano- and microplastics in order to serve the needs of enforcement and proper 
implementation of the proposed restrictions.  

Panel discussion  

Some plastic items in the ocean are up to fifty years old, younger plastic items being mainly present 
along  the  coastline.  The  importance  of  a  circular  economy  was  stressed,  moving  away  from  an 
unsustainable, throwaway culture to one that avoids plastic entering the environment. One speaker 
suggested designing plastic articles such that they automatically degrade (totally) after use or/and 
making  them  suitable  for  a  circular  use  approach  and  recycling.  While  much  of  the  discussion  on 
nanomaterials,  such  as  nanoplastics,  is  around  how  to  regulate  them  as  chemicals,  an  effort  to 
transfer,  or  at  least  share,  the  focus  with  safe-by-design  could  produce  significant  benefits.  The 

(bio)degradable plastics. 

Much of the discussion focused on the importance of communication, cooperation and networking 
between actors. The US National Nanotechnology Initiative, a collaboration mechanism across USA 
government  departments  and  agencies  was  seen  as  a  model  for  (nationally)  determining  roles, 
deployment of resources and interaction methods. It was proposed that the EU-US Nanotechnology 
Communities  of  Research  could  expand  beyond  those  two  regions  as  a  platform  for  information 
exchange.  In  the  specific  area  of  regulatory  science,  the  Global  Coalition  on  Regulatory  Science 
Research (GCRSR) already has engagement from ten countries and the EU.  

Consideration is being given to the establishment of a European platform of experts coordinated by 
the JRC that would look at methods, standards, definitions and their harmonisation. The JRC already 
undertakes some activities where the effort could be enlarged to an international scale.  

68 

 
 
 
 
 
8  Poster session 
There were 28 poster presentations by scientists and students on the latest research related to the 
session topics.  

The  work  presented  included  research  to  understand  the  fate  and  effects  of  nanomaterials  in 
organisms and the environment, and on the characterisation and quantification of nanomaterials and 
nanoplastics.  Others  considered  risk  assessment  and  mitigation,  metrology  and  issues  of  data 
completeness.  On  the  topics  of  regulation,  work  was  presented  on  regulatory  preparedness  for 
nanomaterials and the implementation of the EC recommendation on the definition of nanomaterial. 
Many  nanomaterials  were  considered  in  the  poster  presentations,  including  nanoplastics  but  also 
carbon nanotube nanocomposites, titanium dioxide and other oxides, and iron-based nano-colloids. 
Examples of applications presented included polymer additives in 3D printing, antimicrobial agents, 
food grade nanomaterials and nanomedicines.  

A full list of poster presentations is provided below 

. 

Poster title, Authors, Affiliation 

Aquatic environmental risk assessment of chitosan/silver, copper and carbon 
nanotube nanocomposites as antimicrobial agents 

Nermeen M. Abu-Elala1, Huda O. Abu Bakr2, Marwa S. Khattab3, Samah H. Mohamed4, 
Maha A. El-hadye, Rehab A. Ghandour5, Rania E. Morsi6,7 

1 Department of Fish Diseases and Management, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt 
2 Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt 
3 Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt 
4 Department of Immunology, Animal Health Research Institute, Dokki, Giza, Egypt 
5 Department of Fish Diseases, Animal Health Research Institute, Dokki, Giza, Egypt 
6 Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt 
7 Analysis and Evaluation Department, Egyptian Petroleum Research Institute, Nasr City, Cairo, Egypt 
8 EPRI-Nanotechnology Center, Egyptian Petroleum Research Institute, Nasr City, Cairo, Egypt

VOC emissions influenced by polymer additives in 3D printing 

Souhail R. Al-Abed1 and Phillip M. Potter2, Farhana Hassan3, and Slawomir Lominicki3 

1 National Risk Management Research Laboratory, Office of Research and Development, United States Environmental 

Protection Agency, Ohio, USA 

2 Oak Ridge Institute for Science and Education, United States Environmental Protection Agency, Ohio, USA 
3 Department of Environmental Sciences, Louisiana State University, Baton Rouge, Louisiana, USA 

Application of enhanced darkfield hyperspectral microscopy for visualization of 
nanoparticles in histological tissue samples 

Trine Berthing, Alicja Mortensen, Ulla Vogel 

National Research Centre for Working Environment, Copenhagen, Denmark

71 

Poster title, Authors, Affiliation 

Combination of 47Ti and 48Ti for the determination of highly polydisperse TiO2 
particle size distributions by spICP MS 

Guillaume Bucher and François Auger 

Service Commun des Laboratoires, Pessac, France

Assessing nanomaterial physicochemical data completeness in existing 
databases 

Daniele Comandella1, Stefania Gottardo1, Iria Maria Rio-Echevarria1,2, Hubert Rauscher1* 

1 European Commission, Joint Research Centre (JRC), Ispra, Italy 
2 Present address: European Commission, Research Executive Agency, Brussels, Belgium 
* Corresponding author

Nanotechnology for the treatment of iron deficiency anemia: the case of 
parenteral iron-based nano-colloidal products 

Tiziana Di Francesco, Beat Flühmann 

Vifor Pharma Management Ltd., Glattbrugg, Switzerland 

Nanoplastics: an emerging pollutant. Preparation of models and analytical 
strategy for the determination of their physicochemical and environmental 
behavior 

Hind El Hadri1,2, Laurence Pessoni1, Cyril Cugnet1, Julien Gigault3, Cloé Veclin1, Elise 
Deniau1, Bruno Grassl1, Stéphanie Reynaud1 

1 IPREM (UPPA/CNRS), Pau, France 
2 Cordouan Technologies, Pessac, France 
3 Géosciences (Univ Rennes/CNRS), Rennes, France

Characterisation and Quantification of Nanoparticles in Food Grade Titanium 
Dioxide and in their Related Food Products 

Otmar Geiss1, Jessica Ponti1, Chiara Senaldi1, Ivana Bianchi1, Dora Mehn1, Josefa Barrero1, 
Douglas Gilliland1, Reinhard Matissek2, Elke Anklam1 

1 European Commission, Joint Research Centre (JRC), Ispra, Italy 
2 Lebensmittelchemisches Institut des Bundesverbandes der Deutschen Süßwarenindustrie, Cologne, Germany

72 

Poster title, Authors, Affiliation 

Advancing the regulatory science for nanomedicines through a systematic 
review of the scientific literature 

Blanka Halamoda-Kenzaoui, Antonio Puertas Gallardo, Susanne Bremer-Hoffmann 

European Commission, Joint Research Centre (JRC), Ispra, Italy

Bridging Communities in the Field of Nanomedicine 

Blanka Halamoda-Kenzaoui, Susanne Bremer-Hoffmann 

European Commission, Joint Research Centre (JRC), Ispra, Italy

Epigenetic Action of Titanium Dioxide Nanoparticles in Human Cells 

George J. Hammons, Marta Pogribna, Nathan Koonce, Beverly Word, Anil K. Patri, and 
Beverly D. Lyn-Cook 

FDA/National Center for Toxicological Research, Jefferson, USA 

Open science-open source precision medicine platform to support chronic 
kidney disease screeening modernization efforts worldwide 

Kimberly Harding1, Michael Volynsky2, Tesfaye Mersha3, Susanne Nicholas4, David R. 
Williams5, Robert M. Mayberry6, Jonathan Medverd7, Nicholas Polys8, Walter Magnussen9, 
Andrew Casertano10 

1 Monarch Innovation Partners, Inc., Rockville, MD, USA 
2 InfoPro Systems Inc., Rockville, MD, USA 
3

4 David Geffen School of Medicine at UCLA, Division of Nephrology, Los Angeles, USA 
5 Harvard T.H. Chan School of Public Health, Boston, MA, USA 
6 Morehouse School of Medicine, Health Disparities Center of Excellence, Atlanta, GA, USA 
7 University of Washington Medicine, Dept. of Radiology, Seattle, WA, USA 
8 Virginia Tech, Blacksburg, Visionarium Lab, VA, USA 
9 Texas A&M University, Internet 2 Technology Evaluation Center, TX, USA 
10 University of Maryland, iSchool, College Park, Maryland, USA

73 

Poster title, Authors, Affiliation 

How could all that stuff be in my blank!? 

Kay T. Ho1, Michaela A. Cashman2, Stephen Russo3 and Robert M. Burgess1 

1 US Environmental Protection Agency, Office of Research and Development, Atlantic Ecology Division, Narragansett, 

USA 

2 Oak Ridge Institute for Science and Education, US Environmental Protection Agency, Office of Research and 

Development, Atlantic Ecology Division, Narragansett, USA 

3 General Dynamics Electric Boat, North Kingstown, USA 

Regulatory Preparedness for nanomaterials and other innovative materials 

A. Paula K. Jantunen1, Agnieszka Mech1, Kirsten Rasmussen1, Juan Riego Sintes1, Stefania 
Gottardo1, Cornelle Noorlander2, Lya Soeteman-Hernandez2, Adrienne J.A.M. Sips2, 
Monique Groenewold2, Susan Dekkers2 

1 European Commission, Joint Research Centre (JRC), Ispra, Italy 
2 National Institute for Public Health and the Environment (RIVM), Centre for Safety of Substances and Products, 

Bilthoven, the Netherlands

Migration and toxic potential of silver nanoparticles in feminine hygiene 
products: characterization and in vivo rodent studies 

Nathan A. Koonce, Ammu Mathew, Ioana-Mihaela Popescu, Suman Ghorai, Julian E. A. 
Leakey and Anil K. Patri 

National Center for Toxicological Research, Office of Scientific Coordination - Nanotechnology Core Facility, Jefferson, 
USA

Characterization and quantification of nanoplastic in the environment: 
possibilities and limitations of Py-GCMS 

Corentin Le Juge1, Julien Gigault2 

1 Laboratoire Géosciences Rennes, France 
2 CNRS-Université de Rennes, France

Centrifugal field flow fractionation in analysis of nano- and microplastics 

Dora Méhn1, Giacomo Milan2, Marco Pallavera2, Douglas Gilliland1 

1 European Commission, Joint Research Centre (JRC), Ispra, Italy 
2 EOS srl, Milano, Italy

74 

Poster title, Authors, Affiliation 

Development of Nano tools for localized activation in radiation induced 
combinatory cancer treatment 

Rao Papineni1,2*, Sunil Krishnan3, Ajayan Pulickel4, and Onur Sahin2,3 

1 KUMC, Kansas 
2 PACT & Health LLC, Connecticut 
3 Mayo Clinic, Florida 
4 Rice University, Texas

Developing Methodologies for the Detection and Clean-up of Workplace Spills 
Containing Engineered Nanomaterials 

Viridiana Perez, Irene Andreu, Tony Ngo, Cameron Hodgins, Matthew W. Bilton, Kelly E.C. 
Cadieux, Michael T.Y. Paul, Tania C. Hidalgo Castillo, Clifton Bright Davies, Byron D. Gates 

Department of Chemistry, Simon Fraser University, Canada

Stabilization of Nanoplastic with Terrestrial and Marine Organic Matter - 
Implications for the fate of an emerging contaminant 

Alice Pradel, Séléna Ferreres, Julien Gigault 

Univ Rennes, CNRS, Géosciences Rennes, Rennes, France

Risk assessment and mitigation of the presence of engineered nanomaterials in 
Atlantic aquaculture: NANOCULTURE 

Monica Quarato, Laura Rodriguez-Lorenzo and Begoña Espiña 

Water Quality Group, Water4Enviroment Unit, Department of Life Sciences, International Iberian Nanotechnology 
Laboratory-INL, Braga, Portugal

Towards the implementation of the EC recommendation on the definition of 
nanomaterial 

Hubert Rauscher* and Agnieszka Mech 

European Commission, Joint Research Centre (JRC), Ispra, Italy 
* Corresponding author

75 

Poster title, Authors, Affiliation 

Zebrafish embryotoxicity of commercial nanomaterials used in the plastic 
industry 

Marisa P. Sárria1, Ivone Pinheiro1, Ana Vieira1, Cristiana Cunha1,2, Ana Vilas-Boas1,2, Laura 
Rodriguez-Lorenzo1, Andreia Gomes2, Begoña Espiña1* 

1 INL - International Iberian Nanotechnology Laboratory, Braga, Portugal 
2 University of Minho, Braga, Portugal 
* Corresponding author

Environmental risk assessment of medical products   ready for assessment of 
nano-scaled active ingredients? 

Kathrin Schwirn, Silvia Berkner, and Doris Völker 

German Environment Agency (UBA), Dessau-Rosslau, Germany

Nanoparticle analysis in consumer products 

Miguel Spuch-Calvar1, Alke Fink1,2, Barbara Rothen-Rutishauser1 

1 BioNanomaterials Group, Adolphe Merkle Institute, Fribourg, Switzerland 
2 Department of Chemistry, University of Fribourg, Fribourg, Switzerland

From research to harmonized testing: the case study of the hydrophobicity of 
nanomaterials 

Andrea Valsesia, Stefania Gottardo, Cloé Desmet, Pascal Colpo, Douglas Gilliland, Juan 
Riego Sintes 

European Commission, Joint Research Centre (JRC), Ispra, Italy

Physicochemical characterisation of several types of the E171 food additive 

Eveline Verleysen, Marina Ledecq, Sandra De Vos, Isaac Ojea Jimenez, Frédéric Brassinne, 
Nadia Waegeneers, Jan Mast 

Sciensano, Brussels, Belgium

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Poster title, Authors, Affiliation 

Determination of nanoplastics presence in contaminated soil: new 
considerations 

Aurélie Wahl, Mélanie Davranche, Julien Gigault 

Université de Rennes 1/CNRS, Géosciences Rennes, Rennes, France

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Nadim Akhtar 

Nadim Akhtar has a PhD degree in chemistry from Manchester and has been working 
for AstraZeneca since 2005. During this time Nadim has worked across different fields 
including    separation  science,  New  modalities  (proteins,  peptides,  nucleic  acids  and 
nanomedicines)  and    Predictive  Science  supporting  both  drug  substance  and  drug 
product  activities.  Nadim  currently  sits  in  the  Global  Product  Development  and  has 
worked in the nanomedicine area for a number of years, focusing on both early and 
late stage portfolio. Nadim has been involved with  several regulatory filing involving 
small molecules, oligonucleotides and nanomedicines. 

Souhail Al-Abed 

Dr. Souhail Al-Abed is a research chemist at the U.S. Environmental Protection Agency 
(EPA). His research activities include fate and risk evaluation of nanomaterials used in 
consumer  products  and  the  understanding  of  many  challenging  environmental 
problems from nano and micro plastics. He authored and coauthored more than 110 
peer-review  journal  articles  and  five  book  chapters.  He  is  a  Fellow  of  the  American 
Chemical Society (ACS) and Chair-Elect of the ACS Division of Environmental Chemistry. 
He is member of Working Party on Manufactured Nanomaterials (WPMN) at the OECD 
and  member  of  American  Geophysical  Union  in  the  Hydrology  section  and  serves  in 
many national and international research committees. 

Elke Anklam 

Elke Anklam is a chemist, with specialisation in food, organic and radiation chemistry. 
After obtaining her PhD from the University Hamburg (Germany), she worked in various 
European Research Institutions and was a Teaching Professor at the Applied University 
of Fulda (Germany). 

(EC-JRC).    Since  2006,  she  has  a  Director  position  in  the  JRC.  At  present,  she  is  the 
Director of the JRC-Geel  site and Director of JRC Directorate F: Health, Consumers & 
Reference Material, located at the  JRC-Geel and JRC-Ispra site. 

Sylvain Bintein 

For  the  past  15  years,  Dr.  Sylvain  Bintein  has  been  employed  at  the  European 
Commission  as  Team  Leader  of  the  team  dealing  with  regulation  for  registration, 
evaluation, authorisation and  restriction of Chemicals (REACH) and  the classification, 
labelling  and  packaging  of  chemicals  (CLP)  in  the  Directorate  General  for  the 
environment. He has a PhD in environmental toxicology and he is an engineer from the 
French National School for Water and Environmental Engineering. For several years, he 
was a member of the Scientific Committee to the Stockholm Convention on POPs, and 
of the Chemicals Management Plan Science Committee of the Government of Canada. 

88 

Sven Even Borgos 

Sven Even Borgos (n. 1976) is a biophysicist at SINTEF (Norway) with a PhD in molecular 
genetics, and has for the last decade specialized in advanced analytical chemistry 
  of  nanoparticulate systems.  He  is  assay group 
often  based  on  mass  spectrometry 
leader  of  chemical  characterization  in  the  European  Nanomedicine  Characterisation 
laboratory  (EUNCL),  work  package  leader  for  assessment  of  improved  nanomedicine 
characterization technologies in EUNCL, and work  package leader for the integration of 
regulatory  needs  with  available  characterization  technologies  in  the  REFINE  project, 
which  aims  to  contribute  a  regulatory  science  framework  for  the  risk-benefit 
assessment of nanobiomaterial-based medicinal products and medical devices. 

Ken Bosnick 

Dr. Ken Bosnick leads the Nanomaterial Depositions and Characterizations Team at the 

research interests center on inorganic nanomaterial depositions and their applications. 
Key  ongoing  projects  include  developing  methods  for  fabricating  sinterable  hybrid 
ceramic structures for applications in armour, exploiting conformal metal coatings for 
energy  harvesting,  and  synthesizing  semiconductor  nanostructures  for  gas  sensing 
applications. He has a keen interest in exploiting nanomaterials to tackle waste issues 
in the food sector, which will form the basis for his talk at GSRS19. 

Susanne Bremer-Hoffmann 

Dr. rer nat Susanne Bremer-Hoffmann, obtained her PhD from the Charite University 
Hospital  Berlin/D  for  her  work  on  T-cell  reactions  against  autologous  leukemia  cells. 
After post-doctoral  research at the Federal Institute for Risk Assessment in Germany, 
S.  Bremer  contributed  to  the    establishment  of  the  Centre  for  the  Validation  of 
Alternative  Methods  (EURL-
Research Centre JRC in 1995. She coordinated EURL-
reproductive toxicity including the validation and regulatory acceptance of in vitro tests 
assessing endocrine disrupters. Her research activities focussed on the development of 
in vitro toxicity tests based on murine/ human embryonic and induced pluripotent stem 
cells.  She  participated  in  several  European  and  international  research  projects, 
published more than  100 scientific manuscripts and contributed to various European 
and international expert groups e.g. at the OECD and the IPRP nanomedicine working 
group relevant for the implementation of  European legislation. 

89 

 
Robert Burgess 

Dr.  Robert  M  Burgess  has  been  a  Research  Physical  Scientist  with  the  United  States 
Environmental  Protection  Agency  (U.S.  EPA)  Office  of  Research  and  Development  in 
Narragansett, Rhode Island, USA for 27 years. His research focuses on understanding 
the  bioavailability  of  organic  and  metal  contaminants,  including  nanomaterials  and 
micro-  and  nanoplastics,  in  the  marine  environment.    This  work  supports  the 
development  of  informed  environmental  regulations.  He  has  contributed  to  the 
authorship of over 100 peer-reviewed papers related to ecotoxicity and ecological risk 

duate School 

of Oceanography. 

Hongda Chen 

Dr.  Hongda  Chen  is  a  National  Program  Leader  at  National  Institute  of  Food  and 
Agriculture  (NIFA),  USDA.  He  provides  the  leadership  for  nanoscale  science,  and 
nanotechnology for agriculture and food systems. He also leads the national portfolio 
of  engineering  for  research,  education  and  extension  in  food  manufacturing 
technologies, and value-added products. Dr. Chen received his Ph.D. in engineering from 
University of California, Davis. He was a professor of food engineering at University of 
Vermont.  Dr.  Chen  is  an  elected  Fellow  of  Institute  of  Food  Technologists  (IFT), 
International  Academy  of  Food  Science  and  Technology  (IAFoST)  of  IUFoST,  and 
American Society of Agricultural and Biological Engineers (ASABE). 

Charles Clifford 

Charles Clifford is a senior research scientist in the Surface Technology Group at the 

experience in international standardisation. He is UK head of delegation to ISO/TC229 
(nanotechnologies), CEN TC 352 (European nanotechnologies) and IEC TC113 (electro 
technical nanotechnologies). He is also UK secretary to ISO TC201 (surface chemical 
analysis).  He  leads  and  participates  in  collaborative  projects  with  a  focus  on 
nanomaterials and analysis at the nanoscale. He has a background in scanning probe 
microscopy. 

Pieter Cullis 

Pieter R. Cullis, Ph.D. FRSC, FNAI (USA), is Scientific Director & CEO of the NanoMedicines 
ntre of Excellence in nanomedicines, based at 
the University of British Columbia. Dr. Cullis and co-workers have been responsible for 
fundamental  advances  in  the  design  and  development  of  nanomedicines  employing 
lipid nanoparticle (LNP) technology for cancer therapies and gene therapies. This work 
has contributed to four drugs that have been approved by regulatory agencies in the 
U.S. and Europe. Dr. Cullis was elected a Fellow of the Royal Society of Canada in 2004 
and  was  also  awarded  the  Prix  Galien,  Can
pharmaceutical R&D, in 2011. 

90 

Wim H. de Jong 

Wim  H.  De  Jong,  DVM,  PhD  graduated  as  veterinarian  at  Utrecht  University,  the 
Netherlands in 1978 and is registered as specialist in Experimental Pathobiology, and 
Toxicological  Pathology.    His  research  involved  the  safety  evaluation  and  risk 
assessment  of  xenobiotics,  medical  devices  and  nanomaterials,  and  development  of 
alternative testing methods. He published more than 170 publications in peer reviewed 
international journals and books. He previously was employed by the National Institute 
for  Public  Health  and  the  Environment  (RIVM),  Bilthoven,  the  Netherlands.    He  was 
member of ISO TC 194/CEN TC 206 Biological and clinical evaluation of medical devices, 
ISO TC 229 Nanotechnology, SCHENIR, and working groups of the SCCS and EFSA. He is 
member of SCHEER and the SCCS working group on nanomaterials. He is member of 
the editorial board and reviewer for several scientific journals. 

Guilhem de Sèze 

Guilhem de Sèze joined the European Food Safety Authority (EFSA) in 2016 as Head of 
the Scientific Evaluation of Regulated Products Department. From 2008, he worked for 
the European  Chemicals Agency in Helsinki, where in 2011 he became a Head of Unit, 
first  for  Substance    Identification  and  Data  Sharing,  and  then  for  Evaluation.  Before 
this, Guilhem worked in the field of hazardous chemicals management in academia and 
in the chemical industry. He holds a PhD in chemical engineering from Louisiana State 
University. 

Jon de Vlieger 

Jon  de  Vlieger  obtained  his  doctoral  degree  in  bio  analytical  chemistry  from  the  VU 
University in Amsterdam. In 2011 he joined Lygature (former Top Institute Pharma), an 
independent not-for-profit organization based in the Netherlands. Lygature catalyzes 
the  development  of  new  medical  solutions  by  driving  public-private  collaboration 
between  academia,  industry,  and  society.  Dr.  de  Vlieger  coordinates  several 
international  public  private  partnerships,  including  the  Non  Biological  Complex  Drugs 
Working  Group,  an  international  network  of  scientific  and  clinical  experts  from 
academia,  industry  and  regulatory  bodies,  with  expertise  in  many  aspects  of  the 
development and evaluation of NBCDs and nanomedicines. He is a co-editor of the book 
on NBCDs in the AAPS Advances in the Pharmaceutical Sciences Series and is co-author 
on a series of key-papers on the  topic of regulatory challenges for NBCDs. 

91 

 
 
 
 
 
 
 
 
 
 
 
Amit K. Dinda 

Professor Amit K. Dinda is Head of Renal & Transplant Pathology at All India Institute 
of Medical Sciences, New Delhi. His research interests include experimental pathology, 
cancer, regulatory science, regenerative and nanomedicine. He has published more than 
350  research  articles,  edited  4  books,  written  14  chapters,  filed  12  patents.  He  is 
secretary  of  Indian  Society  of  Nanomedicine,  former  Vice  President  of  Electron 
Microscopy  Society  of  India,  Society  of  Tissue  Engineering  &  Regenerative  Medicine 
(India). He is an assessor for NABL (Laboratory Accreditation), GLP & GCP systems. He 
is an advisor for developing regulatory guidelines in India in the areas of Nanomedicine, 
Nanotechnology based agricultural and food products. 

Mauro Ferrari 

Mauro  Ferrari,  Ph.D.  trained  in  mathematics,  mechanical  engineering,  medicine,  and 
business.  He  served  in  tenured  faculty  and  academic  leadership  positions  at  UC 
Berkeley, Ohio State, the  National Cancer Institute of the USA, the University of Texas 
Medical School and MD Anderson  Cancer Centre   Houston, Houston Methodist Hospital 
(Executive  Vice  President)  and  Research    Institute  (President  and  CEO),  Weill  Cornell 
Medical College, and the University of St Thomas  Houston. An academic entrepreneur 
with several companies established around his research, Dr. Ferrari has served on the 
Board  of  Arrowhead  Pharmaceuticals  (NASDAQ:ARWR)  since  2010.    Currently  the 
President Designate of the European Research Council, he will begin serving his term 
on January 1, 2020. 

Valérie Fessard 

Dr  FESSARD  Valérie  is  a  toxicologist  working  for  ANSES  (France)  as  the  head  of  the 

logy 

recruited to develop assays for testing the genotoxicity of contaminants especially the 
comet assay (both in vitro and in vivo) and the in vitro micronucleus assay. Promoting 
the 3R rules, she wishes to improve in vitro toxicology testing using high throughput 
approaches and 3D cell models. She has a long standing experience in the toxicity of 
marine and freshwater toxins, nanomaterials and mixtures. She has been involved in 
several  European  projects  and  coordinated  recently  a  French/German  project  on  the 
toxicity of metallic nanoparticles. 

Lisa E. Friedersdorf 

Dr. Lisa Friedersdorf is the Director of the National Nanotechnology Coordination Office. 
She has been involved in nanotechnology for over twenty-five years, with a particular 
interest  in  advancing  technology  commercialization  through  university-industry-
government collaboration. She is a strong advocate for science, technology, engineering, 
and mathematics (STEM) education, and has over two decades of experience teaching 
at both the university and high school levels. Lisa earned her PhD and MSE in Materials 
Science  and  Engineering  from  the  Johns  Hopkins  University  and  BS  in  Mechanical 
Engineering from the University of Central Florida. 

92 

 
 
 
 
 
 
 
Julien Gigault 

Julien Gigault dedicated his research to the development of analytical strategies and 
experimental  protocols  for  determining  the  source,  fate  and  impact  of  nanoscale 
materials  in  the  environment.    After  his  PhD  in  Pau  (2011)  focused  on  the 
characterization of carbon nanotubes and fullerenes, he has continued at NIST under 
the supervision of Vincent A. Hackley by developing analytical approach to characterize 
inorganic nanoparticles (Gold and Silver nanoparticles) in an environmental and health 
context. Since 2014, he is a permanent CNRS researcher (government) and his main 
interests are the anthropogenic nanoparticles in the environment such as nanoplastics. 
He is author and co-author of 40 papers in international journals. He has also supervised 
and  coordinated  more  than  6  national  and  international  projects  on  nanoplastics 
involving 28 researchers in Europe. 

Douglas Gilliland 

Douglas Gilliland was awarded a PhD degree in applied chemistry from the University 
of Strathclyde, Glasgow in 1993 after which he joined JRC as a post-doctoral fellow 
before becoming a full staff member in 1997. Previous activities with JRC have included 
studies  of  corrosion  in  gas  turbines  and  implantable  medical  devices  using 
electrochemical, surface analytical (XPS and ToF-SIMS) and radiotracers methods. More 
recently he has gained experience in the synthesis of a wide range of nanomaterials 
becoming  responsible  for  scientific  activities  for  the  detection  and  physicochemical 
characterization of nanostructured materials and nanoparticles. Currently is expanding 
these research activities into the area of analytics for micro and nanoplastics. 

Peter L. Goering 

Dr. Goering is a Research Toxicologist and serves as Deputy Director; Division of Biology, 
Chemistry, and Materials Science; Office of Science and Engineering Laboratories; CDRH; 

associated  with  the  evaluation  of  nanomaterial  characterization  and  toxicity  for 
biocompatibility testing and predicting health risks. He currently serves as CDRH liaison 
to  the  ASTM  E56  standards  committee  on  Nanotechnology:  Physical,  Chemical,  and 
Toxicological Properties. He received his PhD from the Kansas University Medical School. 
Dr. Goering has co-authored over 100 peer-reviewed publications and book chapters, is 
a  Diplomate  of  the  American  Board  of  Toxicology,  and  a  Fellow  of  Academy  of 
Toxicological Sciences. He served as President of the Society of Toxicology in 2015-16. 

93 

 
 
 
 
 
 
 
 
 
 
 
Mar Gonzalez 

Mar  Gonzalez  joined  the  Organisation  for  Economic  Co-operation  and  Development 
(OECD) in 2004 to work in its Environment, Health and Safety Division. Over the years, 
she has had a number of responsibilities under the heading of safety/ risk assessment 
and international harmonisation in the regulation of chemicals and products of modern 
biotechnology.  Since  she  joined  OECD,  she  has  been  involved  in  various  technical 
programmes  covering  biosafety,  the  safety  of  novel  foods  and  feeds  and  chemical 
accidents  prevention,  preparedness  and  response.    She  was  involved  in  the 
establishment  of  the  programme  on  Nanosafety  in  2006  and  has  since  been 
responsible  for  the  implementation  of  its  programme  of  work,  which  includes  the 
development  of  tools  for  assessing  the  hazards  of  nanomaterials  such  as  the 
development of OECD Test Guidelines and guidance documents. From 2010 to 2018, 
she became responsible for the outreach work on chemicals, as well as reviewing the 
legal frameworks of non-OECD countries seeking a partnership at OECD. Mar has a BA 
in  Physical  Anthropology,  a  Master  degree  in  Biotechnology  and  Ethics  from  the 
University of Sheffield, UK and a Diploma on Biosafety. 

Ralf Greiner 

Ralf is Head of the Department of Food Technology and Bioprocess Engineering and 
Deputy  to  the  President  of  the  Max  Rubner-Institut  (MRI),  Karlsruhe,  Germany.  His 
research  is  focused  on  studying  and  modelling  conventional  and  new  processing 
technologies,  as  well  as  on  food  nanotechnology  and  food  application  of  enzymes 
especially phytases. His research activities resulted in about 180 original papers in peer-
reviewed  journals,  55  book  chapters  and  355  abstracts  or  short  papers  in  congress 
proceedings.  Ralf  is  a  representative  of  MRI  in  several  international  and  national 
associations on food technology, food control and food nanotechnology.  In addition, he 
is Editor for Food Control (Europe and South America). 

Nanna B. Hartmann 

Nanna B. Hartmann is a senior researcher at the Technical University of Denmark (DTU 
Environmental). She focuses her research on ecotoxicology and method development 
for testing of nanomaterials and microplastics in aquatic systems. Through her research 
she has a thorough experience in investigating the fate and effects of nanomaterials 
and microplastics in environmental and technical systems. She has extensive experience 
in working on the interface between science and regulation. She has been involved in 
the development of OECD test guideline development as well as providing expert advice 
to  the  European  C
micro- and nanoplastics. 

94 

 
 
 
 
 
 
 
 
 
 
Andrea Held 

Andrea Held holds a degree in chemistry from the University Dortmund, Germany. After 
obtaining her PhD, she started her career at the Joint Research Centre of the European 
Commission,  initially  providing  reference  measurements  on  samples  for  laboratory 
intercomparisons  and  organising  such  intercomparisons,  touching  also  on  nuclear 
measurements.  Her  main  focus  today  is  on  the  development  of  reference  materials 
supporting EU legislation, covering a broad range from food contaminants and priority 
pollutants in environmental matrices to advanced materials, nanomaterials and most 
recently also microplastics. 

Ted Henry 

Ted Henry is a Professor of Environmental Toxicology in the Institute of Life and Earth 
Sciences at Heriot-Watt University, Edinburgh, UK. He received a Bachelor of Arts (1992) 
from the  University of California Santa Barbara, a Master of Science (1998) at Auburn 
University  (AL,    USA),  and  PhD  at  Auburn  University  (2002).  For  over  15  years  his 
research  program  has  been  supported  (NERC,  US  EPA,  US  NSF,  EU  FP7,  and 
Horizon2020) to investigate the ecotoxicology of anthropogenic particles (engineered 
nanomaterials,  nanoplastics,  and  microplastics).  He  is  the  PI  of  the  current  NERC 
Highlights project RealRiskNano (NE/N006526/1) focused on the formation, fate, and 
environmentally relevant effects of nanoplastic microorganism agglomerates in marine 
ecosystems. 

Dolores Hernán Pérez de la Ossa 

Dolores  obtained  a  Pharmacy  degree  and  a  European  PhD  in  Pharmaceutical 
Technology from the Complutense University, Madrid, Spain conducting research stays 
at  USA  Virginia  Commonwealth  University-School  of  Medicine  and  the  Institute  of 
Biomolecular  Chemistry  of  the  Italian  National  Research  Council.  Her  main  area  of 
research was the development and in vitro and in vivo characterization of micro and 
nanoparticles for cannabinoid administration. 

She  joined  the  Quality  Office  of  the  European  Medicines  Agency  in  London  in  2010. 
Since  then  she  has  been  Product  Team  Leader/Quality  Specialist  for  numerous 
medicinal  products  applications  and  supported  the  development  of  several  scientific 
guidelines. Since 2012 she also acts as Scientific Secretary of the Quality Working Party 
Core  Team  (QWP  CT)  and  provides  scientific  support  to  the  EMA  PAT  team.  She 
represents EMA at the IPRP nanomedicines working group, ICH Q13 EWG and ASTM E55. 

95 

 
 
 
 
 
 
 
 
 
 
 
Frank Herzberg 

Dr. Herzberg studied Biology at the Free University of Berlin and made his Ph.D. on cell 
adhesion  molecules  in  amphibian  development. His  post-doc  research  at  the  Charité 
focused on the role of integrins in tumour development and metastasis. At BfR, he has 
been working on risk assessment of chemicals under REACH and on toxicological and 
regulatory aspects of nanomaterials. Dr.  Herzberg is a regular member of the Working 
Party of Manufactured Nanomaterials (WPMN) at OECD as well as the Nanomaterial 
Expert  Group  (NMEG)  at  ECHA  and  has  been  actively  involved  in  test  guideline  and 
REACH adaptation to accommodate nanomaterials. 

Arnd Hoeveler 

Arnd  Hoeveler  received  his  PhD  from  the  Institute  of  Genetics  at  the  University  of 
Cologne. He was awarded a full Professorship in Biochemistry and Molecular Biology in 
France. He served several positions in France before joining the Research Directorate at 
the European Commission in 1996. 

Between 2001 and 2006 he served as Head of Unit, covering Infectious Diseases, and 
led several European programmes dealing with HIV/AIDS, Malaria and Tuberculosis. In 

Health  Biotechnology  programme,  dealing  with  Diagnostics,  Regenerative  Medicine, 
Animal Replacement Strategies, Child Health, and the Innovative Medicine Initiative. 

Since October 2017 he is Head of the Consumer Products Safety Unit of the European 
Commission Joint Research Centre dealing with Medical Devices, Micro-Nano plastics 
and Nanobiotechnology. 

He  is  a  board  member  of  the  European  Federation  of  Immunological  Societies  and 
serves on several International Advisory Boards. 

Marta Hugas 

Dr Marta Hugas is serving as Chief Scientist at the European Food Safety Authority. This 

focal point on scientific matters and facilitating the understanding of science; fostering 
scientific  cooperation  as  well  as  leveraging  connections  and  networks  for  promoting 

several  positions:  Head  of  Biological  Hazards  Unit  (BIOHAZ),  Head  of  the  Risk 
Assessment and Scientific Assistance Department a.i. (RASA) and Head of the Biological 
Hazards and Contaminants Unit (BIOCONTAM). 

Marta holds a BSc in biological sciences, an MSc in genetics and microbial biotechnology 
and a PhD in food microbiology. Prior to joining EFSA, she worked for the Institute for 
Food and Agricultural Research and Technology (IRTA) in Spain, where she was Head of 
the  Food  Microbiology  and  Biotechnology  Unit  and  led  a  research  group  on  applied 
research on meat and food safety. From 1992 to 2004 she was an Associate Professor 

development of starter and bio protective cultures, probiotics for the safety of poultry 
meat,  emerging  preservation  technologies  as  well  as  risk  assessment  of  biological 
hazards. Dr Hugas has extensively published papers and book chapters. 

96 

 
 
 
 
Wenlei Jiang 

Dr. Wenlei Jiang currently serves as Senior Science Advisor in the Office of Research 
and  Standards  (ORS)/Office  of  Generic  Drugs  (OGD)/Center  for  Drug  Evaluation  and 
Research (CDER)/US FDA.  She has been championing regulatory research in the areas 
of  generic  nanomaterials,  narrow  therapeutic  index  drugs,  and  modified  release 
products to support review standards development and ensure post-market drug safety 
and efficacy. Currently she is leading efforts in complex drug product classification and 
research, and promoting global bioequivalence harmonization.  She also serves as Chair 
at  Product Quality Research Institute (PQRI) Biopharmaceutical  Technical Committee. 
Prior to joining FDA, she was at Novartis Pharmaceutical Corporation and she received 
her  PhD  in  Pharmaceutics  and  Pharmaceutical  Chemistry  from  The  Ohio  State 
University. 

Michael Johnston 

Dr.  Michael  Johnston  completed  his  graduate  studies  at  the  University  of  British 
Columbia  in  2006  which  focused  on  regulated  drug  release  from  liposomal  based 
nanoscale  drug  delivery  systems.  Since  2007,  Dr.  Johnston  has  been  with  Health 
Canada  where  he  heads  the  nanomedicine  laboratory  continuing  his  research  on 
nanoscale drug delivery systems, nanoscale vaccine adjuvants and therapeutic protein 
aggregates.  Dr.  Johnston  also  heads  the  Health  Products  and  Food  Branches 
nanotechnology  working  group  within  Health  Canada,  Co-chairs  the  International 
Pharmaceutical Regulators Forum Nanomecidines working group and is a member of 

Melanie Kah 

Melanie completed her PhD on the fate of ionisable pesticides at the University of York 
(UK).  After a couple of years at the UK Food and Environmental Research Agency (FERA), 
Melanie joined the University of Vienna (Austria). Her research on the risk assessment 
of nanopesticides is a good illustration of the multidisciplinary approaches developed 
in  her  group  to  deal  with  complex  contaminants  in  the  environment.  Melanie  was 
Distinguished  Visitor  at  the  CSIRO  in  2018  (Adelaide,  Australia)  before  joining  the 
University of Auckland (New Zealand) in January 2019. 

Debra Kaiser 

Dr. Debra Kaiser is currently a Senior Advisor in the Office of Data and Informatics at 

nanotechnology  documenta
Technical Committee E56 on Nanotechnology.  Her previous positions at NIST included 
Technical Director of the Nanotechnology Environment, Health, and Safety Program and 
Chief  of the  Ceramics  Division. She chaired  the committee that  developed  the  2014 
National  Nanotechnology  Initiative  Strategic  Plan  and  has  led  activities  in  the  US 
Federal  interagency  Nanotechnology  Environment  and  Health  Implications  Working 
Group. 

97 

 
 
 
 
 
 
 
 
Denis Koltsov 

Dr Denis Koltsov was born in Moscow in 1976, graduated from Cambridge University in 
1998 and obtained his PhD in nanotechnology in 2003 from the same university. He 
worked  as  a  research  associate  in  Cambridge  Nanoscience  Centre  before  taking  up 
lecturing position at Lancaster University in 2005 where he led nanotechnology work 
and  outreach  services  till  2009.  Dr  Koltsov  is  now  running  his  own  nanotechnology 
consulting practice (BREC Solutions limited) that focuses on technical, regulatory and 
standardisation issues nanotechnology innovation. Dr Koltsov is the author of several 
patents,  numerous  publications  and  confidential  reports  to  stakeholders.  He  is  a 
recognised authority in nanotechnology standardisation, innovation and current market, 
regulatory and policy trends. Dr Koltsov is an expert representing industry on BSI, ISO, 
IEC  and  CEN  expert  committees.  Dr  Koltsov  developed  and  published  a  number  of 
international nanotechnology standards and currently holds the chairman position for 
the  ISO  TC229  (Nanotechnologies).  He  has  conducted  a  number  of  industry-led 
consultations in nanotechnology sector and reported to relevant regulatory authorities. 
Dr Koltsov was/is a board member on large EU projects such as NanoDefine, NanoReg2, 
Gracious  and  international  organisations  such  as  National  Graphene  Association.  He 
advises  small  startups  as  well  as  multinationals,  international  organisations  and 
governments.  

Alfonso Lampen 

Study  Biochemistry  (University  of  Göttingen)  and  Veterinary  Medicine,  PhD.  in 
Biochemistry  and  Pharmacology  (University  Hannover  and  Veterinary  University  of 
Hannover). Extra Professor for Food Toxicology at the Veterinary University of Hannover. 
He  is  Head  of  the  Department  Food  Safety  at  the  German  Federal  Institute  for  Risk 
Assessment  (BfR).  Research  topics  are  the  gastrointestinal  barrier  and  the  mode  of 
action of relevant compounds after oral uptake in food toxicology. 

Carlos Eduardo Lima da Cunha 

He recently joined the European Commission after over 3 years working in chemical risk 
assessment  and  biotechnology  innovation  in  San  Francisco,  CA,  USA.  Before  that  he 
concluded  his  doctorate  studies  in  biochemistry  and  biophysics  at  the  Max  Planck 
Institute for  Biophysical Chemistry in  Germany,  where he worked on single-molecule 
protein  synthesis  characterisation.  It  was  there  that  he  was  first  introduced  to 
nanoparticles.  At  the  European  Commission,  he  combine  his  scientific  background  in 
problem  solving  with  risk  assessment  approaches  and  strategic  analysis  to  tackle 
European issues at a policy level. Currently, his focus is to bring safer nanotechnology-
containing products to European citizens, while promoting innovation. 

98 

 
 
 
 
 
 
 
 
 
 
Iseult Lynch 

Professor  Iseult  Lynch  is  the  Chair  of  Environmental  Nanosciences  of  the  at  the 
University    of  Birmingham,  theme  leader 
Environmental  Pollution    Solutions  research  theme,  and  Coordinator  of  the  H2020 
NanoCommons research infrastructure  for nanosafety. She is an Associate Editor for 
Environmental Science: Nano, Her research focuses on the environmental interactions 
of  nanoparticles  and  nanostructured  surfaces,  and  micro  and  nanoplastics,  with 
biological entities from macromolecules to organisms. She has a very broad overview 
of  all  aspects  of  nanomaterials  /  nanoplastics  safety  assessment  and  the  data 
requirements  for  risk  assessment,  and  on  the  need  for  harmonisation  and 
standardisation of methods and approaches. 

Katrin Löschner 

Katrin  Löschner  is  Senior  Researcher  at  the  National  Food  Institute  at  the  Technical 
University of Denmark. She obtained her PhD in Material Sciences at the Martin Luther 
University Halle-Wittenberg in Germany in 2008. Afterwards she moved to  Denmark 
and  combined,  as  a  Postdoc,  her  knowledge  on  materials  with  analytical  (food) 
chemistry. Her expertise is the analysis of nanoparticles in food and biological matrices 
with  specific  focus  on  techniques  based  on  inductively  coupled  plasma-mass 
spectrometry (ICP-MS) and the challenges related to sample preparation.  Katrin has 
been involved in several EU-funded (NanoLyse, NanoDefine, NanoSolutions, PATROLS) 
and national research projects. Since 2016, she is the Danish representative in EFSA´s 
Scientific  Network  of  Nanotechnologies.  She  is  active  as  an  expert  for  the  field  of 
(nano)particle  characterization in the EC´s H2020 Reference Material Review Panel and 
as technical expert for  the JRC. 

Ritu Nalubola 

Dr. Ritu Nalubola is the new Director of the FDA Europe Office. Prior to taking on this 
role in July 2018, she served as a Senior Policy Advisor in the Off
Office of the Commissioner. She has advised senior leadership at FDA, the Department 
of Health and Human  Services, and other U.S. government agencies on complex and 
cross-cutting policy issues,  including those related to nanotechnology, biotechnology 
and genome editing, food safety,  international standards, and trade-related matters. 

conjunction  with  the  broader  U.S.  government,  to  modernize  the  federal  regulatory 

across several Offices and Centers at FDA. She joined the agency after completing post-
doctoral  work  with  the  Johns  Hopkins  University  and  later  the  U.S.  Agency  for 
International Development setting up international public health programs. 

99 

 
 
 
 
 
 
 
 
 
Bryant C. Nelson 

Bryant is a staff research chemist at the National Institute of Standards and Technology 
(NIST) in the Material Measurement Laboratory (Gaithersburg, Maryland, USA). He was 
educated at the University of Texas at Austin, B.Sc., Chemistry, and the University of 
Massachusetts  at  Amherst,  Ph.D.,  and  Analytical  Chemistry  and  completed  his 
postdoctoral training as an NRC research fellow at NIST in Analytical Chemistry (clinical 
mass  spectrometry)  in  1997.  Bryant  became  a  permanent  staff  member  at  NIST  in 
2003. Since 2009, he has led research projects primarily focused on characterizing the 
toxicological  and  biological  effects  of  engineered  nanomaterials  and  is  currently  the 
NIST Nanomedicine Measurement Assurance Project Leader in which his focus is on the 
development  of  international  standards  and  test  methods  for  nano-enabled  medical 
products  and  devices.  He  is  a  member  of  the  Analytical  Chemistry  Division  of  the 
American Chemical Society, ASTM International and Sigma Xi. He has authored over 80 
peer-reviewed  publications  and  2  book  chapters.  He  has  given  over  75  oral 
presentations  domestically  and  internationally  and  is  a  past  Sigma  Xi  Distinguished 
Lecturer (2015   2017). He was awarded the NIST Outstanding Mentor Award in 2017. 
He is Past President of the NIST Chapter of Sigma Xi (2008   2009) and Past Associate 
Editor of the Journal of Environmental Quality (2011   2014). He is the Chair of ASTM 
International E56.08   Nano-Enabled Medical Products and a Councillor to the American 
Chemical Society representing the Analytical Chemistry Division. 

Kumiko Ogawa 

Dr.  Kumiko  Ogawa  graduated  (1988)  and  received  Ph.D.  (1993)  from  Nagoya  City 
University Medical School, then continued research as a postdoctoral research associate 
in  Pathology  and  Microbiology,  University  of  Nebraska  Medical  Center  (1993-1996). 
After serving in Experimental Pathology and Tumor Biology, Nagoya City University and 
Nagoya Higashi Municipal Hospital, she joined Division of Pathology, National Institute 
of Health Sciences (2009). She is a board-certified specialist of Japanese Society of 
Pathology and Japanese Society of Toxicologic Pathology. Her research interest includes 
toxicological pathology and carcinogenesis. She has been an expert committee member 
of the Food Safety committee in Japan and several evaluation committees for chemical 
safety in Japanese government. 

Haruhiro Okuda 

Dr. Haruhiro Okuda is Director-General of National Institute of Health Sciences (NIHS).  
After obtaining Ph.D degree in medicinal chemistry from University of Tokyo, he joined 
the Pharmaceuticals and Medical Devices Evaluation Centre, the predecessor of PMDA, 
and was engaged in review of new drug approval application. From 2002 to 2018, he 
worked for NIHS, and served as Head of Division of Organic Chemistry, Head of Division 
of Drugs and Deputy Director-General. He worked to harmonize regulation on quality of 
chemical  drugs  for  over  10  years  as  a  member  of  ICH.  He  also  works  to  harmonize 
Pharmacopoeias of Japan, EU, and the USA as a PDG (Pharmacopoeia Discussion Group) 
member. 

100 

 
 
 
 
 
 
Agnes Oomen 

Dr. Agnes G. Oomen is a senior scientist and project leader at the National Institute for 
Public Health and the Environment (RIVM) in the Netherlands. She works at the interface 
between science and policy, leading and participating in national and European projects 
on e.g. the health risks, toxicokinetics and grouping and read-across of nanomaterials. 
She is an active member of the EFSA cross-cutting Working Group on Nanotechnologies 
and  acts  as  an  ad-hoc  expert  in  several  international  expert,  working  and  network 
groups.  She  initiated  and  was  part  of  a  project  team  exploring  the  scale  of 
developments of certain bionano-materials, and considering potential effects and the 
applicability of legal frameworks. 

Anil K. Patri 

Dr. Anil Patri serves as the lead for Nanotechnology coordination at the US Food and 
Drug Administration (US FDA). His laboratory is very active in nanotechnology regulatory 
science research to understand material characteristics, their safety and efficacy. Dr. 
Patri serves on the U.S. National Nanotechnology Initiative (NNI) NSET Subcommittee 
and NEHI working group for US government inter-agency coordination. He is as member 
of  ISO  TC229  and  serves  on  the  executive  committee  of  ASTM  E56  to  facilitate 
standards development. Dr. Patri serves as the US Co-chair for US-EU Communities of 
Research (CoR) on Nanomedicine and Characterization. 

Prior  to  joining  FDA  in  2014,  Dr.  Patri  served  as  the  Deputy  Director  of  the 
Nanotechnology Characterization Laboratory (NCL) at the Frederick National Laboratory 
for Cancer Research. In a decade-long tenure at NCL, he assisted collaborators from 
industry and academia in preclinical development of drug products for cancer utilizing 
nanotechnology,  many  currently  in  clinical  trials.    From  2006-2014,  he  served  as  a 
guest scientist at the National Institute of Standards and  Technology (NIST) and co-
developed  nominal  10nm,  30nm,  and  60  nm  colloidal  gold  reference    material 
standards.  Dr.  Patri  developed  nanotechnology-based  targeted  drug  delivery  and 
imaging agents until 2004 at the University of Michigan Medical School. He is a co-
author of 65 publications, served on editorial, advisory, and scientific review panels. 

Dr. Patri obtained his B.Sc., from Osmania University, M.Sc., in Chemistry from Aligarh 
Muslim  University  in  India,  Ph.D.  in  Chemistry  from  the  University  of  South  Florida 
followed by a post-doctoral training at the University of Michigan. He worked at Astra 
Zeneca and as a lecturer in Chemistry prior to graduate school. 

Agnès Pottier 

Agnès Pottier is VP, Global Head Discovery & New Venture within Nanobiotix. She joined 
the  company  in  2007  and  has  been  actively  involved  in  the  Discovery,  Intellectual 
Property and Non-Clinical Research activities, supporting the development of its first-
in-class radioenhancer NBTXR3. She is co-inventors of more than 15 patent applications 
families in the field of nanomedicine. Agnès hold a diploma from Engineering School 
ENSC  (Toulouse,  France)  and  a  PhD  in  Inorganic  Chemistry  from  University  Paris  VI 
(Paris, France). 

101 

 
 
 
 
Juan Riego Sintes 

Juan  Riego  Sintes  has  a  Degree  on  General  and  Organic  Chemistry,  PhD  in  Organic 
Chemistry,  MSc  in  Toxicology  and  MSc  in  Environmental  Chemistry  and  Engineering. 
Research on heterogeneous catalysis using supported reagents, molecular recognition 

Research Centre European Chemicals Bureau (ECB) Test Methods area. From 2005 leads 

Methods  for  chemicals,  chairs  the  EU  National  Coordinators  Group  for  TMs  and 
represents the Commission in the OECD Test Guidelines Programme (WNT). He chairs 
the  Steering  Group  on  Testing  and  Assessment  of  the  OECD  Working  Party  of 
Manufactured Nanomaterials (WPMN). Led/contributed several key deliverables of the 
lementation 
Projects  (RIPs)  and  REACH  Implementation  Projects  on  Nanomaterials  RIP-oNs  and 
many research projects.  Extensive experience in chairing and  managing international 
projects and experts groups in the interface between science and policy. 

Reinhilde Schoonjans 

Dr.  Reinhilde  Schoonjans  is  a  risk  assessment  scientist  at  the  European  Food  Safety 
Authority.  Her current mandate from the European Commission is to develop a technical 
guidance for establishing the presence of small particles at the nanoscale in products 
used  to  the  agri/food/feed  chain.  She  also  coordinates  the  expert  group  on 
nanomaterials in agri/food/feed products that developed the Scientific Guidance for risk 
assessment and she chairs the Nano Network with EU Member States delegates. Other 
topics  of  expertise  include  Synthetic  Biology  developments,  the  cloning  of  farmed 
animals,  biodiversity-related  protection  goals  for  environmental  risk  assessment, 
epigenetics  and  risk  assessment  of  genetically  modified  organisms.  She  previously 
worked on hazard criteria for endocrine disruption. Reinhilde Schoonjans is a Molecular 
Biologist holding a PhD from the University of Ghent, where she performed research on 
bispecific  antibodies  for  cancer  immunotherapy.  In  October  2005  she  qualified  as 
European Patent Attorney for the European Patent Office in Munich. 

Primal Silva 

Dr. Primal Silva. BVSc, PhD, is a veterinarian and a scientist. He obtained his PhD from 
the University of Sydney, Australia, in 1987 and conducted his post-doctoral studies at 
McMaster University and at the Ontario Veterinary College, University of Guelph. From 
1991-1993, he worked as an  Assistant Professor at the University of Guelph before 
joining the Federal Public Service in 1993  where he has held several positions with 
increasing responsibilities. Dr. Silva is currently the Chief Science Operating Officer in 
the Science Branch of the Canadian Food Inspection Agency. He is also a contributing 
member to numerous committees and working groups at domestic and international 
levels including the Scientific Advisory Body of OECD. 

102 

 
 
 
 
 
 
 
Jan Simak 

Dr. Simak is a representative of the Center for Biologics Evaluation and Research (CBER) 
in  the  FDA  Nanotechnology  Taskforce.  Dr.  Simak  is  a  Principal  Investigator  of  the 
research program on toxicity of engineered and biologic nano/microparticles in blood. 
Dr.  Simak  also  serves  as  a  scientific  lead  reviewer  of  cellular  blood  products  and 
transfusion devices. Dr. Simak received his Ph.D. in Biochemistry in 1992 at the Institute 
of Hematology and Blood Transfusion / UCT in Prague, Czech Republic. In 1992   2000, 
he served as Assistant Professor/PI at the 1st Faculty of Medicine, Charles University in 
Prague, and at the Neonatal Intensive Care, Institute for the Care of Mother and Child 
in Prague. Dr. Simak joined CBER FDA in February 2000. 

William Slikker 

Dr.  William  Slikker,  Jr.  received  his  Ph.D.  in  pharmacology  and  toxicology  from  the 
University  of  California  at  Davis.  Dr.  Slikker  holds  adjunct  professorships  in  the 
Department of Pediatrics, as well as the Department of Pharmacology and Toxicology 
at  the  University  of  Arkansas  for  Medical  Sciences.  He  has  held  committee 
chairmanships  or  elected  offices  in  several  scientific  societies  including  serving  as 
president  of  the  Teratology  Society,  the  Academy  of  Toxicological  Sciences  and  the 
Society  of  Toxicology.  Dr.  Slikker  is  also  theco-founder  and  past  president  of  the 
MidSouth Computational Biology and Bioinformatics Society. Currently Dr. Slikker is the 

Toxicological Research (NCTR). 

Birgit Sokull-Kluettgen 

Birgit Sokull-Kluettgen, who has a PhD in Natural Sciences (Biology), is the Deputy Head 

Centre (JRC) in Ispra (Italy). Joining the European Commission in 1995, Birgit worked 
for  many  years  on  the  scientific/technical  support  to  the  conception,  development, 
implementation and monitoring of EU legislation on chemicals. For a long time Birgit is 
involved in research and policy support projects on safety assessment of nanomaterials. 
Furthermore, she coordinates the JRC work on the impact and sustainability of plastics. 
She  is  particularly  interested  in  linking  science  to  policy  needs  in  order  to  provide 
circumspect  opinions  for  a better  regulation  to  the  European  Commission  and  to  EU 
Agencies. 

Abdel Sumrein 

Abdelqader Sumrein is a Scientific Officer at the European Chemicals Agency (ECHA), 
where he has been working since 2009. He works in the Data Availability Unit, where 
he acts as the product manager for the European Union Observatory for Nanomaterials 
(EUON). He has a MSc. Degree in Applied toxicology from the University of Surrey. Prior 
to joining ECHA, he was a graduate student in the Mirkin lab at Northwestern University 
working on the synthesis and applications of coordination polymer nanomaterials. He 

103 

 
 
 
 
 
 
 
 
Katherine Tyner 

Dr. Katherine Tyner is the Associate Director of Science in the Immediate Office of the 
Office of Pharmaceutical Quality (OPQ), Center for Drug Evaluation and Research at the 
United States Food and Drug Administration (FDA). As Associate Director, Dr. Tyner leads 
the  OPQ  Science  Staff  in  coordinating  the  intersection  between  science,  review,  and 
policy in OPQ as well as facilitating interactions between other CDER offices and FDA 
Centers. She received her PhD in Chemistry from Cornell University and joined the Food 
and Drug Administration in 2007 as a chemist specializing in nanotechnology. While at 
the FDA, Dr. Tyner has investigated the quality, safety, and efficacy of complex drug 
products including drug products containing nanomaterials, and she currently leads the 
CDER  nanotechnology  working  group  and  is  active  in  other  CDER  and  FDA 
nanotechnology initiatives. Dr. Tyner is the author of multiple book chapters and journal 
articles  concerning  the  appropriate  characterization  and  biological  impact  of 
nanoparticle therapeutics and other complex products. 

Luis Velasquez Cumplido 

With 25 years related to research, development and innovation, mainly in biomedicine, 
bionanotechnology, toxicology and pharmacology. In the last 5 years (2013-2018), has 
participated in the publication of more than 30  ISI manuscripts, filed 5 patents with 
three already granted. His work has more than 1000 bibliographic citations, with an h 
index of 17 and i10 of 36. He has been invited to participate in the working groups of 
the World Health Organization (WHO) and as an advisor on science and technology in 
the future commission of the Chilean Senate. 

In  Chile  his  scientific  work  has  been  financed  by  practically  all  the  instruments  of 
individual nature (CONICYT, FONDEF; CORFO, etc) and group (Basal centers, MECESUP, 
Rings etc). At international level it has been financed by the Wellcome Trust, Rocfeller 
Foundation,  Erst  Shering  Foundation.  For  his  scientific  work  he  was  named  as  the 
lighthouse of nanotechnology in Chile in the Nanofuture  Ligth house network of the 
European economic community. 

In  his  career,  he  has  directed  undergraduate  and  graduate  theses,  the  postdoctoral 
degree of 3 academics. Finally, he has been invited to present seminars in numerous 
countries and I have presented works in more than 100 congresses. He is a reviewer of 
numerous national and international ISI journals and  he is invited to review national 
and international projects such as the CNRS, France. 

104 

 
 
 
 
 
 
 
 
 
 
 
Matthias Wacker 

Matthias  G.  Wacker  is  Associate  Professor  in  the  Department  of  Pharmacy  of  the 
National  University  of  Singapore  (NUS).  Initially,  he  studied  Pharmacy  at  Goethe 
University  in  Frankfurt  (Germany)  where  he  obtained  his  doctoral  degree  in 
pharmaceutical  technology.  As  a  post-doc  and  group  leader  he  has  joined  Jennifer 
Dressman  and  Jörg  Kreuter  in  the  Institute  of  Pharmaceutical  Technology,  Goethe 

Pharmaceutical Technology and Nanosciences of the Fraunhofer-Institute for Molecular 
Biology  and  Applied  Ecology  in  Frankfurt  led  by  Gerd  Geisslinger.  Since  2012,  he  is 
scientific advisor to the editors of the Journal of Pharmaceutical Sciences and, in 2019, 
joined  the  editorial  board  of  the  European  Journal  of  Pharmaceutics  and 
Biopharmaceutics. Further, has was editing selected issues for the Beilstein Journal of 
Nanotechnology and Frontiers in Chemistry.  In recognition of his research excellence, 
he  was  honored  with  the  Eudragit®  Best  Paper  Award  (2014)  and  the  Phoenix 
Pharmaceutics Science Award (2017). In 2019, he was appointed as a member of the 
expert panel on New Advancements in In Vitro Performance Testing of the United States 
Pharmacopoeia. He has published and lectured extensively and organized symposia on 
various aspects of nanotechnology. 

Liming Xie 

Dr.  Liming  Xie  is  currently  a  professor  of  physical  chemistry  at  National  Center  for 
Nanoscience and Technology (NCNST), Beijing, China. He received his PhD degree from 
Peking  University  in  2009.  He  visited  Massachusetts  Institute  of  Technology  during 
2007 to 2008. He did postdoctoral research at Stanford University from 2009 to 2012 
and after that he joined NCNST. 

characterizations  and  biological  effect  evaluations  of  nanomaterials  toward  medical 
applications. He is the co-director of NCNST-NIFDC Joint Laboratory for Measurement 

Excellent Young 

Shan Zou 

Dr.  Shan  Zou  is  a  Senior  Research  Officer  and  Team  Leader  of  the  Nanoscale 
Measurement Discipline at the Metrology Research Centre, National Research Council 
Canada (NRC). She obtained her PhD from University of Twente, The Netherlands and 
joined NRC in 2007. She is the Secretary for ASTM International E56 Nanotechnology 
Committee and Secretary of the Canadian National Committee for IUPAC. She is also 
the member of BIPM-CCQM Cell Analysis Working Group. Her research interests include 
molecular-level visualization, sensing, and manipulation of engineered nanomaterials 
using  integrated  multimodal  techniques.  Recently  she  has  focused  on  cellular 
mechanical responses to drug and nanomaterials treatments, as well as their toxicity 
and risk assessment. 

105 

 
 
 
 
 
 
 
 
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Last Name 

First Name 

Organisation 

AKHTAR 

AL-ABED 

Nadim 

Souhail 

ALLAN 

Jaqueline 

ANASTASIO 

Yesica 

ANGELOV 

ANKLAM 

Angel 

Elke 

AstraZeneca Macclesfield, UK 

Environmental Protection Agency-EPA, USA 

Joint Institute for Innovation Policy (JIIP), 
Belgium 

ANMAT-Administración Nacional de 
Medicamentos, Alimentos y Tecnología  Médica, 
Argentina 

University of Food Technologies, Bulgaria 

European Commission, JRC, EU 

BACONNIER 

Simon 

CEA, France 

BAHRKE 

Susanne 

EDQM, Council of Europe 

BARAT BAVIERA 

Jose Manuel 

Universitat Politècnica de València, Spain 

BARONE 

BARRERO 

Flavia 

Josefa 

Istituto Superiore di Sanità, Italy 

European Commission, JRC, EU 

BARTHELEMY 

Eric 

EFSA, EU 

BASTOS 

Maria 

Faculty of Pharmacy, University of Porto, 
Portugal 

BELZ 

BEMRAH 

BIANCHI 

BINTEIN 

Susanne 

European Commission, JRC, EU 

Nawel 

Ivana 

Sylvain 

Anses, France 

European Commission, JRC, EU 

European Commission, DG ENV, EU 

BORCHARD 

Gerrit 

University of Geneva, Switzerland 

BORGOS 

Sven Even 

BOSNICK 

Ken 

SINTEF Industry, Dept. of Biotechnology  and 
Nanomedicine, Norway 

National Research Council Canada, 
Nanotechnology Research Center, Canada 

BRAS 

BREMER 

BUCHER 

Rafael 

Mars Wrigley, USA 

Susanne 

European Commission, JRC, EU 

Guillaume 

Service Commun des Laboratoires, France 

BURGESS 

Robert 

EPA, USA 

108 

Last Name 

First Name 

Organisation 

CALZOLAI 

CAPUTO 

Luigi 

Fanny 

CARLANDER 

David 

CASTENMILLER 

Jacqueline 

CECCONE 

CELLA 

CHALFIN 

CHAN SHEOT 

Giacomo 

Claudia 

Kate 

Harn 

European Commission, JRC, EU 

CEA Grenoble, France 

Nanotechnology Industries Association  (NIA), 
Belgium 

Netherlands Food and Consumer Product  Safety 
Authority (NVWA), Netherlands 

European Commission, JRC, EU 

European Commission, JRC, EU 

ASTM International, USA 

Singapore Food Agency, Singapore 

CHEN 

Hongda 

USDA, USA 

CHITTOFRATI 

Alba 

Solvay Specialty Polymers - R&D - Analytics  and 
Material Characterisation Dept, Italy 

CLIFFORD 

COLPO 

CROSS 

CUBADDA 

CULLIS 

Charles 

Pascal 

Richard 

National Physical Laboratory, UK 

European Commission, JRC, EU 

Centre for Ecology and Hydrology, UK 

Francesco 

Istituto Superiore di Sanità, Italy 

Pieter 

University of British Columbia, Canada 

DE JONG 

Wilhelmus 

Scientific Committee on Consumer Safety 
(SCCS), EU 

DE SEZE 

Guilhem 

EFSA, EU 

DE VLIEGER 

DESMET 

Jon 

Cloe 

Lygature - NBCD Working Group, Netherlands 

European Commission, JRC, EU 

DI FRANCESCO 

Tiziana 

Vifor Pharma Management Ltd, Switzerland 

DILCHEVA 

Valeriya 

Institute of Experimental Morphology, Bulgarian 
Academy of Sciences, Bulgaria 

DINDA 

Amit Kumar 

All India Institute of Medical Sciences, India 

EL HADRI 

Hind 

IPREM, France 

EL MINIAWY 

Hala 

Faculty of Veterinary Medicine, Cairo  University, 
Egypt 

109 

Last Name 

First Name 

Organisation 

ERDEN 

Dicle 

ESPINA 

FELEZ 

FERRARI 

FESSARD 

FIELD 

Begona 

Marta 

Mauro 

ValéRie 

Anne 

Pamukkale University, Faculty of Technology, 
Turkey 

International Iberian Nanotechnology  Laboratory 
(INL), Portugal 

Tolsa SA, Spain 

University of St. Thomas (UST), USA 

ANSES, France 

Therapeutic Goods Administration, 
Commonwealth Department of Health,  Australia 

FLÜHMANN 

Beat 

Vifor Pharma Ltd, Switzerland 

FORMANEK 

Florian 

HORIBA, France 

FRIEDERSDORF 

Lisa 

National Nanotechnology Coordination  Office, 
USA 

FRIESE 

Dagmar 

Federal Ministry of Health, Germany 

FUMAGALLI 

Francesco 

European Commission, JRC, EU 

GALLOCCHIO 

Federica 

Istituto Zooprofilattico Sperimentale delle 
Venezie, Italy 

GE 

GEERS 

Guanglu 

National Center for Nanoscience and  Technology, 
China 

Christoph 

Adolphe Merkle Institute, Switzerland 

GEERTSMA 

Robert 

RIVM - National Institute for Public Health  and 
the Environment, Netherlands 

GEISS 

GENG 

GIGAULT 

GILLILAND 

GIORIA 

GOERING 

GOLJA 

Otmar 

European Commission, JRC, EU 

Xingchao 

Julien 

Douglas 

Sabrina 

Peter 

Viviana 

National Institutes for Food and Drug Control 
(NIFDC), China 

CNRS Géosciences Rennes, France 

European Commission, JRC, EU 

European Commission, JRC, EU 

FDA, USA 

National Institute of Public Health, Slovenia 

GONZALEZ 

Mar 

OECD 

110 

Last Name 

First Name 

Organisation 

GOTCHEVA 

Velitchka 

University of Food Technologies, Bulgaria 

GOTTARDO 

Stefania 

European Commission, JRC, EU 

GOYAL 

GREINER 

HALAMODA 
KENZAOUI 

Aditya Sandeep 

Evora University, Portugal 

Ralf 

Max Rubner-Institut, Germany 

Blanka 

European Commission, JRC, EU 

HAMMONS 

George 

FDA / National Center for Toxicological  Research 
(NCTR), USA 

HARDING 

Kimberly 

Monarch Innovation Partners, Inc., USA 

HARTMANN 

Nanna Bloch 

Technical University of Denmark (DTU),  Denmark 

HELD 

HELLMER 

HENRY 

HERNAN PEREZ 
DE LA OSSA 

Andrea 

Lena 

European Commission, JRC, EU 

Swedish Chemicals Agency, Sweden 

Theodore 

Heriot-Watt University, UK 

Dolores 

EMA, EU 

HERZBERG 

Frank 

Bundesinstitut für Risikobewertung (BfR), 
Germany 

HO 

HOEVELER 

HUGAS 

ISLES 

IWASE 

Kay 

Arnd 

Marta 

Mike 

Ryo 

EPA, USA 

European Commission, JRC, EU 

EFSA, EU 

Alliance for Safe Online Pharmacy, UK 

Ministry of Health, Labour and Welfare,  Japan 

JANTUNEN 

Anna Paula 

European Commission, JRC, EU 

JIANG 

JOHNSTON 

KAH 

Michaela 

Wenlei 

Michael 

Melanie 

KAISER 

Debra 

Ministry of Agriculture of the Czech  Republic, 
Czech Republic 

FDA, USA 

Health Canada, Canada 

University of Auckland, New Zealand 

National Institute of Standards and  Technology 
(NIST), USA 

111 

 
Last Name 

First Name 

Organisation 

KASEMETS 

Kaja 

KAWANISHI 

Toru 

KESTENS 

KHATTAB 

KOBE 

KOIVISTO 

KOLTSOV 

KOONCE 

Vikram 

Marwa 

Andrej 

Pertti 

Denis 

Nathan 

National Institute of Chemical Physics and 
Biophysics, Estonia 

Food Safety Commission, Cabinet Office, 
Government of Japan, Japan 

European Commission, JRC, EU 

Cairo University, Egypt 

European Commission, DG ENV, EU 

Finnish Food Authority, Finland 

BREC Solutions Limited, UK 

FDA / NCTR, USA 

KOSTADINOVA 

Dessislava 

KOYAMA 

Kazuo 

Bulgarian Academy of Sciences - Institute of 
Optical Materials and Technologies "Acad.  Jordan 
Malinowski", Bulgaria 

Food Safety Commission, Cabinet Office, 
Government of Japan, Japan 

LA SPINA 

Rita 

European Commission, JRC, EU 

LAMPEN 

Alfonso 

LETTIERI 

LEYENS 

LIGUORI 

Teresa 

Lada 

Biase 

German Federal Institute for Risk  Assessment 
(BfR), Germany 

European Commission, JRC, EU 

Swissmedic, Switzerland 

EcamRicert - ECSIN Lab., Italy 

LIMA DA CUNHA  Carlos Eduardo 

European Commission, DG RTD, EU 

LLORENS-
CHIRALT 

LOPEZ 

LOUATI 

LYNCH 

Dorelia 

European Commission, JRC, EU 

Raquel 

AIMPLAS, Spain 

Isabel 

Claudia 

Iseult 

IMDEA WATER, Spain 

FDA Europe Office, USA 

University of Birmingham, UK 

LÖFFLER 

Beat 

European Foundation for Clinical  Nanomedicine, 
Switzerland 

LÖSCHNER 

Katrin 

Technical University of Denmark (DTU),  Denmark 

112 

 
Last Name 

First Name 

Organisation 

MANIKAS 

Rizos-Georgios 

European Commission, DG GROW, EU 

MANTOVAN 

Etienne 

EcamRicert, Italy 

MAO 

Zhenbin 

National Medical Products Administration 
(NMPA), China 

MARTÍNEZ 
HERNÁNDEZ 

Virtudes 

IMDEA Water Institute, Spain 

MAST 

Jan 

Sciensano, Belgium 

MATHISEN 

Gro Haarklou 

MAZZILIS 

Denis 

Norwegian Scientific Committee for Food  and 
Environment, Norway 

Agenzia Regionale per la protezione 
dell'ambiente Regione Friuli Venezia Giulia,  Italy 

MECH 

Agnieszka 

European Commission, JRC, EU 

MERCIER-BONIN  Muriel 

INRA, France 

MIKEC 

Darko 

Croatian Agency for  Agriculture and Food, 
Croatia 

MILOSEVIC 

Ana 

Empa, Switzerland 

MINELLI 

Caterina 

National Physical Laboratory, UK 

MORESSA 

Alessandra 

MORTENSEN 

Alicja 

Istituto Zooprofilattico Sperimentale delle 
Venezie, Italy 

National Research Centre for Working 
Environment, Denmark 

MÜNCHBACH 

Miriam 

Jungbunzlauer, Germany 

NAKAE 

Dóra 

Hiroki 

European Commission, JRC, EU 

JMAC Japan bio Measurement & Analysis 
Consortium, Japan 

NALUBOLA 

Ritu 

NELSON 

OGAWA 

OKUDA 

OOMEN 

PAPINENI 

Bryant 

Kumiko 

FDA, USA 

NIST, USA 

National Institute of Health Sciences, Japan 

Haruhiro 

National Institute of Health Sciences, Japan 

Agnes 

RIVM, Netherlands 

Lakshmana Rao 
Venkata 

University of Kansas Medical Center, USA 

113 

 
Last Name 

First Name 

Organisation 

PATRI 

PEREZ 

Anil K. 

FDA, USA 

Viridiana 

Simon Fraser University, Canada 

PETKOVA 

Svetlozara 

PICCOLI 

Elisa 

POPOVICI 

Georgeta 

Institute of Experimental Morphology, Bulgarian 
Academy of Sciences, Bulgaria 

Agenzia Regionale per la Protezione 
dell'Ambiente Friuli Venezia Giulia, Italy 

National Sanitary Veterinary and Food  Safety 
Authority, Romania 

POTTIER 

PRADEL 

Agnès 

Alice 

Nanobiotix, France 

Geosciences Rennes, France 

QUARATO 

Monica 

International Iberian Nanotechnology  Laboratory 
(INL), Portugal 

RASMUSSEN 

Kirsten 

European Commission, JRC, EU 

RAUSCHER 

Hubert 

European Commission, JRC, EU 

RIEGO SINTES 

Juan 

European Commission, JRC, EU 

RINCON RINCON  Ana Maria 

EFSA, EU 

RODRIGUEZ-
LORENZO 

ROSCH 

ROSSI 

Laura 

Micheline 

International Iberian Nanotechnology  Laboratory 
(INL), Portugal 

Ministère de la Santé - Direction de la santé 
- Division de la sécurité alimentaire,  Luxembourg 

Andrea M 

Istituto Nazionale di  Ricerca Metrologica,  Italy 

RÖSSLEIN 

Matthias 

Empa, Switzerland 

SABORIDO 

Mariano 

ANMAT-Administración Nacional de 
Medicamentos, Alimentos y Tecnología  Médica, 
Argentina 

SCHOONJANS 

Reinhilde 

EFSA, EU 

SCHWIRN 

Kathrin 

German Environment Agency (UBA),  Germany 

SCOTT-
FORDSMAND 

SENALDI 

SHARMA 

Janeck James 

Aarhus University, Denmark 

Chiara 

Supriya 

European Commission, JRC, EU 

Health Canada, Canada 

114 

Last Name 

First Name 

Organisation 

SILVA 

SIMAK 

Primal 

Canadian Food Inspection Agency, Canada 

Jan 

Center for Biologics Evaluation and  Research, 
U.S. Food and Drug  Administration, USA 

SIMEONOV 

Anton 

SIMON 

Peter 

NIH - National Center for Advancing 
Translational Sciences, Bulgaria 

Faculty of Chemical and Food Technology,  Slovak 
University of Technology in  Bratislava, Slovakia 

SLIKKER 

William 

FDA/NCTR, USA 

SMITH 

Ben 

SOKULL-
KLUETTGEN 

SOME 

Birgit 

Daniel 

Agency for Science, Technology &  Research, 
Singapore 

European Commission, JRC, EU 

Wyatt Technology, USA 

SPUCH-CALVAR  Miguel 

Adolphe Merkle Insititute, Switzerland 

STAMENITIS 

Stamatios 

MARS GmbH, Germany 

SUMREIN 

Abdelqader 

ECHA, EU 

TARAZONA 

TAY GENG 

Jose 

Yu 

THAKKAR 

Shraddha 

THÜRMER 

René 

EFSA, EU 

Singapore Food Agency, Singapore 

National Center for Toxicological Research,  US 
Food and Drug Administration, USA 

BfArM - Federal Institute for Drugs and  Medical 
Devices, Germany 

TONG 

TYNER 

Weida 

FDA/NCTR, USA 

Katherine 

FDA, Center for Drug Evaluation and  Research, 
Office of Pharmaceutical Quality,  USA 

VALSESIA 

Andrea 

European Commission, JRC, EU 

VELASQUEZ 
CUMPLIDO 

VETTORI 

VLADOV 

WACKER 

Luis 

Maria 

Ivelin 

Universidad SEK Chile, Chile 

EFSA, EU 

Institute of Experimental Morphology, Bulgarian 
Academy of Sciences, Bulgaria 

Matthias 

National University of Singapore, Singapore 

115 

Last Name 

First Name 

Organisation 

WIENCEK 

WYSER 

XENAKIS 

Justin 

Yves 

FDA/NCTR, USA 

Société des produits Nestlé, Switzerland 

Aristotelis 

National Hellenic Research Foundation,  Greece 

XIE 

Liming 

National Center for Nanoscience and  Technology, 
China 

YANG 

ZENTAI 

ZHANG 

ZOU 

Jun Young 

National Institute of Food and Drug Safety 
Evaluation, South Korea 

Andrea 

National Food Chain Safety Office, Hungary 

Hezhan 

National Institutes for Food and Drug Control 
(NIFDC), China 

Shan 

National Research Council Canada, Canada 

116 

 
 
 
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doi:10.2760/517689 

ISBN 978-92-76-18435-5