Current state and prospects of biotechnology in Central and Eastern European countries. Part I: Visegrad countries (CZ, H, PL, SK)

Abstract

Innovation is a key determinant of sustainable growth. Biotechnology (BT) is one such industry that has witnessed a revolution in innovative ideas leading to the founding of many new companies based on providing products, solutions and services, stretching from the food industry to environmental remediation, and new medicines. BT holds much promise for the development of national and local economies, however, this requires a strategic approach involving actors within government, industry, and academia working in concert to maximize this potential. This first article reviews the current “state of play” in the field of BT within the Central Eastern European (CEE) countries. For the purposes of this article, CEE refers to the countries of Czech Republic, Hungary, Poland, and Slovakia (the so-called Visegrad – V4 countries). We examine the components that support the creation and development of a BT sector in CEE and also highlight the barriers to these objectives. Clearly setting priorities for the countries’ policy agenda, as well as
the alignment of Smart Specialization Strategy will help to focus efforts. Recent investments in R&D infrastructure within CEE have been substantial, but conditions will need to be optimized to harness these largely European investments for effective use towards SME high-tech development.
ARTICLE HISTORY
Received 15 April 2018
Revised 27 July 2018
Accepted 30 August 2018
KEYWORDS
Biotechnology (BT); Central
Eastern Europe (CEE);
Visegrad countries (V4);
Smart Specialization
Strategy (RIS3); higher
education; public financing
science; venture capital
Introduction

Full text

Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=ibty20
Critical Reviews in Biotechnology
ISSN: 0738-8551 (Print) 1549-7801 (Online) Journal homepage: http://www.tandfonline.com/loi/ibty20
Current state and prospects of biotechnology in
Central and Eastern European countries. Part I:
Visegrad countries (CZ, H, PL, SK)
Markus Dettenhofer, Miroslav Ondrejovič, Viktória Vásáry, Pawel Kaszycki,
Tomasz Twardowski, Stanislav Stuchlík, Ján Turňa, Munis Dundar, Kevan M.
A. Gartland & Stanislav Miertuš
To cite this article: Markus Dettenhofer, Miroslav Ondrejovič, Viktória Vásáry, Pawel Kaszycki,
Tomasz Twardowski, Stanislav Stuchlík, Ján Turňa, Munis Dundar, Kevan M. A. Gartland &
Stanislav Miertuš (2018): Current state and prospects of biotechnology in Central and Eastern
European countries. Part I: Visegrad countries (CZ, H, PL, SK), Critical Reviews in Biotechnology,
DOI: 10.1080/07388551.2018.1523131
To link to this article: https://doi.org/10.1080/07388551.2018.1523131
Published online: 29 Oct 2018.
Submit your article to this journal
View Crossmark data

REVIEW ARTICLE
Current state and prospects of biotechnology in Central and Eastern
European countries. Part I: Visegrad countries (CZ, H, PL, SK)
Markus Dettenhofer
a
, Miroslav Ondrejovi
c
b
, Vikt
oria V
as
ary
c
, Pawel Kaszycki
d
, Tomasz Twardowski
e
,
Stanislav Stuchl

ık
f,g
,J

an Tur
na
f,g
, Munis Dundar
h
, Kevan M. A. Gartland
i
and Stanislav Miertu
s
b,j
a
CEITEC –Central European Institute of Technology, Masaryk University, Brno, Czech Republic;
b
Faculty of Natural Sciences,
Department of Biotechnology, University of SS. Cyril and Methodius in Trnava, Trnava, Slovakia;
c
Research Institute of Agricultural
Economics, Budapest, Hungary;
d
Faculty of Horticulture, Department of Biochemistry, Institute of Plant Biology and Biotechnology,
University of Agriculture in Krakow, Krakow, Poland;
e
Department of Protein Biosynthesis, Institute of Bioorganic Chemistry, Polish
Academy of Sciences, Poznan, Poland;
f
Faculty of Natural Sciences, Department of Molecular Biology, Comenius University, Bratislava,
Slovakia;
g
Science Park, Comenius University, Bratislava, Slovakia;
h
Department of Medical Genetics, Erciyes University, Kayseri, Turkey;
i
Life Sciences, Glasgow Caledonian University, Glasgow, UK;
j
International Centre for Applied Research and Sustainable Technology,
Bratislava, Slovakia
ABSTRACT
Innovation is a key determinant of sustainable growth. Biotechnology (BT) is one such industry
that has witnessed a revolution in innovative ideas leading to the founding of many new compa-
nies based on providing products, solutions and services, stretching from the food industry to
environmental remediation, and new medicines. BT holds much promise for the development of
national and local economies, however, this requires a strategic approach involving actors within
government, industry, and academia working in concert to maximize this potential. This first art-
icle reviews the current “state of play”in the field of BT within the Central Eastern European
(CEE) countries. For the purposes of this article, CEE refers to the countries of Czech Republic,
Hungary, Poland, and Slovakia (the so-called Visegrad –V4 countries). We examine the compo-
nents that support the creation and development of a BT sector in CEE and also highlight the
barriers to these objectives. Clearly setting priorities for the countries’policy agenda, as well as
the alignment of Smart Specialization Strategy will help to focus efforts. Recent investments in
R&D infrastructure within CEE have been substantial, but conditions will need to be optimized to
harness these largely European investments for effective use towards SME high-tech
development.
ARTICLE HISTORY
Received 15 April 2018
Revised 27 July 2018
Accepted 30 August 2018
KEYWORDS
Biotechnology (BT); Central
Eastern Europe (CEE);
Visegrad countries (V4);
Smart Specialization
Strategy (RIS3); higher
education; public financing
science; venture capital
Introduction
Biotechnology is a key sector of research and innov-
ation, which could substantially contribute to the
development of high-tech industries, progress, and
the well-being of society. The European Commission
(EC) has launched the RIS3 program (Research and
Innovation Smart Specialization Strategy) [1]. This
innovative approach promotes the efficient and tar-
geted use of public investment in research and
innovation to enable countries and regions to capital-
ize on their strengths and create new competitive
advantages. As BT is a RIS3 priority in many
European countries, surveying the potential for fur-
ther development of BT is essential and it is directly
related to the evaluation of the potential and pro-
gress in areas of higher education, research, and
entrepreneurship. Therefore, we have focused on the
present survey and critical evaluation of these BT
areas in the region of CEE, which is playing an
increasing role in Europe and worldwide. Because of
the limited space of review papers, we have chosen
typical countries of the region and have divided it
into two papers. The first is focused on Central
Europe (so-called V4 countries, Czech Republic (CZ),
Hungary (H), Poland (PL), Slovakia (SK)) and the
second paper is focused on selected new and pre-
accession EU countries, namely Croatia (CRO),
Romania (RO), Bosnia and Herzegovina (B&H) and
Serbia (SRB). These selected eight countries are a rep-
resentative sample of the whole CEE region and
account for a population of almost 100 million inhab-
itants with a cumulative GDP of $1,260 Bn.
CONTACT Stanislav Miertu
sstanislav.miertus@ucm.sk, icarst.miertus@libero.it Faculty of Natural Sciences, Department of Biotechnology, University
of SS. Cyril and Methodius in Trnava, Nam. J. Herdu 2, 917 01 Trnava, Slovakia; Markus Dettenhofer markus.dettenhofer@ceitec.cz CEITEC –
Central European Institute of Technology, Masaryk University,

Zerot

ınovo n
am. 9, 60177 Brno, Czech Republic
ß2018 Informa UK Limited, trading as Taylor & Francis Group
CRITICAL REVIEWS IN BIOTECHNOLOGY
https://doi.org/10.1080/07388551.2018.1523131

Czech Republic
The Czech Republic, with its population of 10.6 Mn.
(2017), is classified as a moderate innovator based on
its RD&I (research, development, and innovation) out-
puts according to the European Commission [2], which
is at a similar level to its CEE neighbors. The 2015 level
of expenditure on R&D amounted to 1.9% of GDP, com-
pared with an EU average of 2.0%, and 12.5 personnel
per 1000 full-time employees were working primarily in
R&D [3]. The Czech Republic has a long tradition in the
industrial sectors including, machinery, electronics, and
energy. Prior to the communist period, the country was
very industrialized with a concentration of businesses in
Czechoslovakia and also in the Czech lands under the
Hapsburg monarchy. From the period of 1989 onwards,
private enterprises have been established, however,
with a slow transition to recapture an innovative cap-
acity driven by R&D. Higher education has been trad-
itionally strong in the Czech Republic, especially in the
fields of engineering, chemistry, and physics, and lat-
terly, life sciences have been given new emphasis.
Recent changes to the Czech National Policy on RD&I
emphasized efforts to optimize the management and
financing of science to support more frontier research
results and the involvement of innovative enterprises in
R&D. The key industries to support were identified as
the digital economy or ICT, automotive, aviation, and
rail transportation, as well as BT and nanotechnol-
ogy [4].
BT in the Czech Republic
The focus of this review will cover BT, which in its strict-
est sense refers to products, services or processes utiliz-
ing, and/or being derived from living systems. This will
narrow the scope of activities to be highlighted within
the Czech Republic, as the chemical and pharmaceut-
ical industry will not encompass this field. Nevertheless,
we could not exclude the work of the chemist Antonin
Holy, who was a pioneer in the invention of nucleic
acid analogs for use as viral disease inhibitors of HIV-1
and Hepatitis B. Holy’s work led to licensing agreements
with the US-based pharmaceutical company, Gilead
Sciences, with several compounds being successfully
approved for clinical use.
At present, activities in the fields of BT are evolving
and do not have the same long-standing tradition as in
the chemical industry. Research both at the academic
level and in private companies within the Czech
Republic covers the range of activities. This includes
green BT (plant and microorganisms for agriculture),
advances in traditional yellow (food) BT (fermentation
within the beer industry), and white (industrial) BT
enzyme-based bio-catalysis of industrial processes
and environmental remediation, as well as red field BT
(biomedicine and diagnostics in both for human and
animal health).
One of the most promising areas of advancement is
the development of vaccines and immunomodulation
with both being employed for the treatment of cancers
and the prevention of infectious diseases. There is an
alignment of some academic research with for-profit
companies, but the biotech company, Sotio, has deve-
loped a platform for cancer treatment with several late-
stage clinical trials on-going [5]. Assisted reproduction
using in vitro fertilization (IVF) is another strong discip-
line of clinically oriented enterprises with more than 30
companies, which together, places the Czech Republic
is in a leading position globally [6]. Within the diagnos-
tic area, R&D in the field of antibody generation and
characterization for the purpose of diagnostic kit pro-
duction continues. However, the move from the aca-
demic laboratory and reagent market, to companion
diagnostics is still in its early stages. The Czech Republic
has developed a strong position within the field of
nanotechnology, and in combining with this biologic-
ally based nanostructure, such as hyaluronic acid and
its derivatives and companies are investing in new
areas of wound dressing and matrices for medical
application.
Priority and smart specialization strategy in BT
The Smart Specialization Strategy (RIS3) concept has
been introduced as a new framework for regional and
national stakeholders to work collaboratively to identify
areas of competitive advantage compared with other
EU regions [2]. This has enabled countries, such as the
Czech Republic, not only to identify but also to priori-
tize the national innovation directions, which should be
followed by support actions, such as policies and pro-
grams. Turning to BT, the field of innovative medicinal
products for both human and animal use is highlighted
in the RIS3 as a single focus. In particular, targeted ther-
apeutics using carrier systems consisting of macromol-
ecular complexes or nanotechnology-based scaffolds
for formulations including novel or generic drugs are
considered. Advanced cell therapies and regenerative
medicine, with the use of stem-cell technologies, are
prioritized, as are therapeutic and preventative vac-
cines. Progress in personalized medicine has witnessed
a growing demand, and thus in vitro diagnostics, utiliz-
ing molecular-based technologies and improved imag-
ing methodologies are emphasized. These efforts
2 M. DETTENHOFER ET AL.

should be supported by research to uncover new prog-
nostic and diagnostic biomarkers, as well as research in
medical devices to enhance noninvasive imaging.
Connected to nanotechnological advances, the focus
should include using nanotextiles and hydrogels for
medical applications such as wound-healing, release
formulation of antiseptics, and protective barriers
against infectious agents or allergens [7].
In the area of BT related to energy, priority is given
to bio-based solutions to alternative energy sources,
which include biomass, production of biofuels, and
microorganisms. These are seen as “eco-innovations,”
which include using bio-modification processes to man-
age waste to create energy [8].
Education in BT
The Czech system of higher education conducts pro-
grams within universities throughout the country and
offers a wide range of subjects to study, up to the doc-
toral level. Higher educational learning is offered with-
out charge if administered in the Czech language. In
addition, new English language-based degrees are
being offered by universities, usually for a fee. Several
programs are offered in the broad area of BTs (for detail
see Table 1). In addition, many universities offer classes
in BT, such as the Charles University in Prague, the
Faculty of Pharmacy, the Brno University of Technology
Faculty of Chemistry, and the Palacky University in
Olomouc Department of Botany. However, only a lim-
ited number of Czech universities offer full programs in
these subjects. Universities additionally offer courses in
biochemistry and molecular biology, but these pro-
grams are not specifically targeted to BT as a discipline
translating basic and theoretical studies, with the imple-
mentation of this training for their societal or industrial
utilization.
Research in BT
Several organizations that are either faculties or depart-
ments within universities in the Czech Republic, or are
institutes of Czech Academy of Sciences (CAS) are
engaged in research in different areas of BT (selected
recognized institutions and their research areas are
listed in Table 2).
Enterprises and companies in performing R&I
in BT
The largest number of BT companies operate within the
segment relevant to medical and veterinary activities,
referred to as red BT. Although major foreign BT com-
panies have some presence in the Czech Republic,
much of their activities do not include R&D, but rather
focus on regional sales and marketing. With red BT of
Czech origin, several target the area of diagnostics for
animal and/or human health, utilizing technologies reli-
ant on DNA or protein-based techniques (Erban
Lachema, Generi Biotech, BioVendor, Protean,
GenTrend, Exbio). A relatively more mature set of com-
panies include those focused on animal vaccines, with
Bioveta and Dyntex having a large portfolio of prod-
ucts. Two companies, Sotio, and AB Check, have pro-
gressed into later-stage clinical trials for the treatment
of cancers [5]. Both companies have unique technology
platforms, which have enabled the development of
treatment options for multiple indications. Regarding
environmental BT companies, the Nafigate Corporation
has developed an environmentally friendly alternative
to plastic packaging, which has been awarded the Frost
& Sullivan prize for the best innovation in 2015 (see
Table 3 for the extended list of companies).
Funding support schemes for BT
The funding system within the Czech Republic consists
of several different agencies and ministries which fund
RD&I as a whole. However, much of the funding has
been segregated to either categories of basic research,
on the one hand, through the Ministry of Education
Youth and Sports, and the Czech Science Foundation,
or on the other hand, applied research through the
Ministry of Industry and Trade (MIT). Grants are admin-
istered through MIT to promote SME projects, in the
areas of industrial research, engineering, and technol-
ogy development. An additional government body, the
Technological Agency of the Czech Republic (TACR),
which was established in 2011, became one of the prin-
cipal funders for R&D projects. TACR supports applica-
tion-based research, which serves at the level of
experimental development and bridging fundamental
research to bring it closer to market.
Financial support other than the Czech grant system
includes the European Investment Bank, which has
established a mechanism for local banks to administer
loans to small- and medium-sized enterprises (SMEs) in
the Czech Republic under very favorable terms.
Through this scheme, loans are made based on an
evaluation of the business case and are intended to
stimulate SMEs to bring their products or services to
market. The Czech Republic is transitioning towards a
more R&D intensive economy. Accordingly, investors
who have accumulated wealth from other more
CRITICAL REVIEWS IN BIOTECHNOLOGY 3

traditional sectors are particularly developing invest-
ment funds in the IT sector, but also in the area of BT.
RSJ Securities are interested in a wide range of projects
in IT and BT, including in the field of applied life scien-
ces for human health and longevity. The PPF Group has
a very diverse portfolio, which includes telecommunica-
tions, banking, real estate, insurance, and agriculture
sectors, and is a major investor in Sotio, which has been
mentioned earlier.
Regulatory environment
Regarding agricultural BT, the Czech Republic ratified
the Cartagena Protocol in September 2003, and the
Table 1. Listing of BT programs in the V4 countries offering accredited degrees.
Organization Program title Degree Program specializations
Czech Republic University of Chemistry and
Technology, Prague
Biochemistry and Biotechnology MSc/PhD Microbiology, biochemistry, bioengineering,
biotechnologies, and food science
Czech Technical University
in Prague
Bio-Medical and
Clinical Technology
MSc Biomedical engineering, systematic integra-
tion of processes in health service,
instruments, and methods for
biomedicine
Technical University of Ostrava Biomedical Engineering MSc Medical instrument engineering, signals,
and image processing
Masaryk University Special Biology BSc/MSc Microbiology and molecular biotechnology
Mendel University Molecular Biology and
Biotechnology
BSc/MSc/PhD Plant and animal genetics, molecular
biotechnology
University of Southern Bohemia,

Cesk
e Bud
ejovice
Agricultural, Animal
Biotechnology
BSc/MSc/PhD Agriculture, biomass, plant engineering,
animal biotechnology
Hungary Szent Istv
an University Agricultural Biotechnology MSc/PhD Plant biotechnology, animal biotechnology
University of Pannonia Agricultural Biotechnology MSc/PhD Plant biotechnology
Szechenyi Istvan University Agricultural Biotechnology MSc/PhD Plant and animal biotechnology
University of P
ecs Biotechnology Pharmacy MSc/PhD Medical biotechnology, pharmaceutical
biotechnology
Pazmany Peter Catholic University Medical Biotechnology MSc/PhD Applied bioinformatics, molecular
biotechnology
Budapest University of
Technology and Economics
Biochemical Engineering BSc/MSc/PhD Applied biotechnology, health care, food
quality control, environmen-
tal protection
University of Debrecen Biotechnology MSc/PhD Pharmaceutical biotechnology, medicinal
biotechnology, environmental biotech-
nology, agricultural biotechnology,
entrepreneurship in biotechnology
Semmelweis University Pharmacy MSc/PhD Pharmaceutical biotechnology
University of Szeged Pharmacy MSc/PhD Pharmaceutical biotechnology
Poland Jagiellonian University in Krakow Biotechnology; Molecular
biotechnology
BSc/MSc/PhD Biotechnology; Biochemistry
University of Gdansk Biotechnology BSc/MSc/PhD Biochemistry; Biology; Biotechnology;
Microbiology; Environmental protection
University of Wrocław Biotechnology BSc/MSc/PhD Bioinformatics; Molecular biology; Medical
biology; Biotechnology of proteins and
peptides; Molecular microbiology
University of Warsaw Biotechnology BSc/MSc/PhD Biotechnology; Biology
Wrocław University of
Environmental and
Life Sciences
Biotechnology Eng/MSc/PhD Food biotechnology; Biotechnology
Adam Mickiewicz University
in Pozna
n
Biotechnology BSc/MSc/PhD Biotechnology; Biochemistry
Lodz University of Technology Biotechnology Eng/MSc/PhD Molecular biotechnology; Food biotechnol-
ogy; Fermentation technology and tech-
nical microbiology
Pozna
n University of Life Sciences Biotechnology Eng/MSc/PhD Biotechnology
Gda
nsk University of Technology Biotechnology Eng/MSc/PhD Molecular biotechnology; Biotechnology of
drugs; Technology, biotechnology, and
food analysis
University of Lodz Biotechnology BSc/MSc/PhD Medical biotechnology, Microbiological bio-
technology, Plant biotechnology;
Microbiology, Biotechnology and
Experimental Biology; Molecular
Genetics, Cytogenetics, and Biophysics
Slovakia Slovak University of Technology
in Bratislava
Biotechnology BSc/MSc/PhD Microbial, enzyme, industrial and medicinal
biotechnology
Comenius University in Bratislava Biotechnology BSc/MSc/PhD Molecular and medicinal biotechnology
University of SS. Cyril and
Methodius in Trnava
Biotechnology BSc/MSc Microbial, plant and medicinal
biotechnology
Slovak University of Agriculture
in Nitra
Agro-biotechnology BSc/MSc/PhD Microbiology and animal biotechnology
4 M. DETTENHOFER ET AL.

Table 2. Listing of academic and research organizations in the V4 countries performing BT-related research.
Organization Research areas
Czech Republic Institute of Biotechnology, CAS, Vestec Structural biology, protein engineering, cell pathology, molecu-
lar therapy
Institute of Microbiology, CAS, Prague Cellular and molecular microbiology, genetics and physiology of micro-
organisms and resistance to antibiotics, production of microbial
metabolites
Institute of Organic Chemistry and Biochemistry,
CAS, Prague
Organic chemistry, biochemistry, focused on medical and environmen-
tal applications, anti-viral discovery, protease inhibitors,
drug discovery
Institute of Experimental Medicine, CAS, Prague Cell biology, developmental biology, neurobiology, developmental toxi-
cology and teratology, molecular epidemiology, pharmacology,
immunopharmacology, cancer, stem cells
Institute of Molecular Genetics, CAS, Prague Genetics, epigenetics, signal transduction, cell and developmental biol-
ogy, immunology, transcriptional regulation, RNA biology
Institute of Molecular and Translational Medicine, Palacky
University, Olomouc
Human infectious diseases and cancer, drug screening, develop medi-
cines, medical devices, and diagnostics
Department of Biomedical Engineering, Brno University
of Technology
Analysis of biomedical signals and images, biomedical electronics, bio-
informatics, technology in medicine, genomics, and proteomics
Institute of Food Science and Biotechnology, Brno University
of Technology
Biofuels production from waste substrates, applied microbiology,
photocatalysis, food analysis
Food and Biochemical Technology, University of Chemistry
and Technology, Prague
Fermentation processes, bioengineering, biotechnological in the food,
pharmaceutical, chemical industries; and bioremediation of polluted
environments
RECETOX –Research Centre for Toxic Compounds in the
Environment, Masaryk University, Brno
Organic pollutants, polar organic compounds, toxic metals, and natural
toxins, enzymatic catalysis, and development of protein and cellular
biocatalysts for environmental, chemical and biomedical applications
Faculty of Science, University of South Bohemia,

Cesk
e Bud
ejovice
Wide range of biology fields including ecology, whole organism stud-
ies, parasites, plants, animal development
CEITEC –Central European Institute of Technology, Brno Life science and material science focus, high-tech experimental instru-
mentation, open-access facilities, international orientation
BIOCEV –Biotechnology and Biomedicine Center of the
Academy of Sciences and Charles University, Vestec
Therapeutic strategies, early diagnostics, biologically active agents
including chemotherapeutics, protein engineering
International Clinical Research Center (FNUSA-ICRC), Brno Research in disease mechanism and treatment of neurologic and car-
diac indications
Hungary Agricultural Institute, Centre for Agricultural Research,
Hungarian Academy of Sciences
Ongoing projects include an analysis of the agroecological equilibrium,
the preservation, and expansion of genetic variability, the produc-
tion of raw materials for healthy nutrition, the development of dur-
able stress resistance, and improvements in seed safety to meet the
requirements of sustainable development.
Institute for Veterinary Medical Research, Centre for
Agricultural Research, Hungarian Academy of Sciences
Virology –Bacteriology –Parasitology
Its fundamental purpose is basic research for gaining better knowledge
on pathogens (viruses, bacteria, parasites) with significance in veter-
inary medicine. Another principal task is to prepare the practical
implementation of the results, as well as to develop effective diag-
nostic methods, vaccines, and defensive strategies against diseases.
Plant Protection Institute –Department of Biotechnology,
Centre for Agricultural Research, Hungarian Academy
of Sciences
The main task of the department is the application of biotechnological
methods in basic and applied pest management research. Research
activities are focused on biotechnology-driven control of plant dis-
eases caused by phytoplasmas and bacteria, the role of reactive
oxygen species and programmed cell death in plant disease resist-
ance, and phytoremediation studies.
Institute of Experimental Medicine, Hungarian Academy
of Sciences
Pharmacology Cellular and Network Neurobiology, Molecular and
Developmental Neuroscience
Biological Research Centre, Szeged, Hungarian Academy
of Sciences
Biophysics, Biochemistry. Genetics, Plant Biology
The research topics include several fields of molecular and cell biology
from the industrial utilization of bacteria through controlled
improvement of cultivated plants to the problems of human health
and environmental protection.
Research Centre for Natural Sciences, Hungarian Academy
of Sciences
Enzymology –Structural biological basic research is directed toward
understanding physiological and pathophysiological processes on
the scale of molecules and cells. Research topics are continuously
extended from structural biology toward system biology to reveal
complex biological processes by the utilization of advances in pro-
teomics and bioinformatics.
Poland International Institute of Molecular and Cell Biology in
Warsaw (IIMCB)
Subordinate to the Polish Academy of Sciences (PAS). High-quality
(“HR Excellence in Research”logo) research in molecular biomedi-
cine to implement modern biotechnology: structural biology, bio-
informatics, computer modeling, molecular and cell biology,
neurobiology, cancer biology, and developmental genomics; devel-
opment of advanced research tools: equipment, experimental mod-
els and knowledge of modern research methods and technologies
Nencki Institute of Experimental Biology, PAS
(continued)
CRITICAL REVIEWS IN BIOTECHNOLOGY 5

Table 2. Continued.
Organization Research areas
Basic high-leveled (“HR Excellence in Research”logo) research in bio-
logical sciences; Departments of Cell Biology, Biochemistry,
Molecular and Cellular Neurobiology, Neurophysiology, Neurobiology
Center and other units
Institute of Biochemistry and Biophysics, PAS EU Center of Excellence in Molecular Biotechnology; microbial and
yeast molecular genetics, mutagenesis and DNA repair, plant
molecular biology, structural biology and bioinformatics; specialized,
state-of-the-art Laboratories (Bioinformatics, DNA sequencing,
Proteomics, Biological NMR, Bank of Biological Materials)
National Research Institute of Animal Production in
Krak
ow-Balice
The largest institute in the agricultural sector; R&D related to the
breeding of farm animals and the entirety of animal production
issues; accomplishments in the field of genetics, cytogenetics, repro-
ductive biotechnology, and molecular biology
Institute of Bioorganic Chemistry, PAS Multi-faceted interdisciplinary activities (“HR Excellence in Research”
logo) comprising chemistry, biology and informatics: research in bio-
organic chemistry, biochemistry, molecular biology, systems biology,
synthetic biology, and bioinformatics
Plant Breeding and Acclimatization Institute (IHAR) –
National Research Institute
The largest Polish research center in the multidisciplinary area of crop
improvement, biotechnology, germplasm conservation, and
enhancement
Institute of Plant Protection –National Research Institute Research aimed at plant protection and development of efficient con-
trol means against pests, to promote sustainable agriculture
in Poland
Faculty of Biotechnology of Wrocław University Member of the consortium Wrocław Centre for Biotechnology; biotech-
nology, biochemistry, bioinformatics, microbiology, immunology, vir-
ology, cell biology, and plant physiology (13 departments, 2
laboratories)
Intercollegiate Faculty of Biotechnology of the University of
Gdansk and Medical University of Gdansk
Unique institution created by two universities; the interdisciplinary
character of research and teaching (European Centre of Excellence
in Molecular Biomedicine) by combining biomedical and bio-
molecular issues and their applications in biotechnology for health
and life quality
Faculty of Biochemistry, Biophysics and Biotechnology of the
Jagiellonian University
Leading academic institution in Poland with well-established inter-
national collaboration, the highest original research articles score in
Poland (Nature Index, 2016). Focuses: modern biology, contempor-
ary biochemical, biophysical and biotechnological aspects of bio-
logical objects ranging from the molecular level through the cellular
and up to the level of whole animal and plant organisms (17
departments/laboratories)
Faculty of Biology of the Adam Mickiewicz University Biological Sciences, studies from the level of molecular organization of
life (molecular biology and genetics, biochemistry and bioenergetics)
through cellular, both pro- and eukaryotic (microbiology, cell biol-
ogy, cytology, and plant and animal histology), up to the systemic
organism and supra-organism levels (4 research institutes)
Faculty of Biotechnology and Food Sciences of the Lodz
University of Technology
Applied, interdisciplinary research on biotechnology, bioeconomy,
environmental sciences, food and nutrition, fermentation and tech-
nology of cosmetics (4 research institutes)
International Hereditary Cancer Center of the Pomeranian
Medical University in Szczecin
Centre of Excellence led by Prof. Jan Lubi
nski, advanced research and
achievements in hereditary cancer; involved in large international
projects, coordinating 2 large-scale EC grants
Prof. Wacław Da˛browski Institute of Agricultural and Food
Biotechnology
R&D in food technology, obtainment of novel products, sustainable
technologies for agricultural and food industry, fermentation, fruit
and vegetable, milling, baking and pastry, food concentrate and
stimulant, spirit and fodder industries, storage of cereal grains,
microbial strains in biotechnological processes, food safety,
research support
Institute of Biotechnology and Antibiotics (IBA) A state-owned R&D organization, focusing on scientific research in bio-
technology, development and implementation of antibiotic technol-
ogy and other biologically active substances; pharmaceutical
biotechnology (genetic engineering, genome diagnostics, monoclo-
nal antibodies, production of biologically active compounds, the
chemistry of therapeutic compounds)
Slovakia Slovak Academy of Science (SAS) Institute of Chemistry,
Polymer Institute
Enzyme and glycobiotechnology, preparation of materials and compo-
sites for biotechnology and biomedicine.
SAS, Institute of Molecular Biology, Institute of Molecular
Physiology and Genetics, Institute of Neuroimmunology
Clarification of structural, functional, and evolutionary properties of
proteins, issues of gene regulation, regulation of cellular transport
systems in the healthy organism, as well as in neurodegenerative
and psychiatric diseases, cardiac diseases and in multidrug resist-
ance of neoplastic cells and nervous tissue and central ner-
vous system
(continued)
6 M. DETTENHOFER ET AL.

Ministry of the Environment is the oversight authority
related to biosafety. Packaged food and feed must be
labeled with “contains GMO,”if the products contain
genetically modified ingredients. The Czech Republic
allows for the field trials of genetically modified crops,
unlike most EU member states. The Ministry of
Agriculture covers the domain of risks related to crops
and feed, as well as animal health matters, and spon-
sors relevant research. The Ministry of Health has over-
sight of human health risks, with the governing body
for medicines, medical devices, and pharmaceuticals
being the State Institute for Drug Control (S

UKL).
Brief critical evaluation of the current situation of
BT and future prospects
The Czech Republic has developed a reasonably sound
foundation in the area of research related to medical
and veterinary biology, which would align with the
national priorities highlighted. The main challenge
going forward will be to overcome the barrier between
frontier research and the commercialization of BT
advances. The significant lack of larger companies
within the BT sector in the Czech Republic, creates two
key obstacles; first, the relative absence of personnel
who have advanced Technology Readiness Level (TRL)
experience or are working closer to the market, and
second, the options for licensing or buy-out partners
are not within close proximity.
The remedy for this would be to incorporate more
educational training programs which align with Czech
BT priorities. Furthermore, mechanisms to improve the
risk appetite, first, for potential entrepreneurs, and
second, for the investment community to take a long-
term view, can help to overcome these barriers. As
more players populate the local landscape, a critical
mass of talented biotech specialists could be devel-
oped, which should fill in the gaps to the currently frag-
mented sector.
Hungary
Development of BT in Hungary
As a quintessential modern technology, BT is deep-
rooted in Hungary. The origin of the term
“biotechnology”is considered by some to have been
utilized by the Hungarian agricultural engineer, Karl
Ereky. His forgotten and later rediscovered classic work
“Biotechnologie,”helped define this new discipline, and
was published in Berlin in 1919 [9–12]. Modern BT was
introduced through the Biological Research Center of
the Hungarian Academy of Sciences in the early 1970s.
By the 1980s, a state development program supported
BT research, fostering it as an independent sector after
Table 2. Continued.
Organization Research areas
Biomedicinal centrum SAS –Institute of Virology, Cancer
Research Institute
Virology, molecular biology, oncology, physiology and pathophysiology,
immunophenotyping, molecular-genetic diagnostics of cancer pre-
disposition, molecular mechanisms of DNA repair pathways and
mesenchymal stem cells
National Agricultural and Food Centre Research Institute of
Plant Production in Pie
st
'any, Research Institute for
Animal Production in Nitra, Food Research Institute
in Bratislava
Plant molecular biotechnology studies of crops, biochemistry, genetics,
embryology, food microbiology, genetics, food science, and technol-
ogy, including hygiene and sanitation of the food industry facilities
Science Park of the Comenius University in Bratislava Biomedicine, biotechnology, enviro-medicine, bioinformatics, relevant
ecological innovations. Collaboration with several private companies
in area of up-to-date genome research and bioinformatics (e. g.
Geneton, s.r.o. –non-invasive prenatal diagnostics “Trisomy Test”)
and also in IT research in the area of biosensors.
Medical University Science Park in Ko
sice Concentration of scientific potential and experimental infrastructure in
the field of medicine, biology, biochemistry, biophysics, informatics
and bioengineering; integration of biomedical research and the
transfer of research results into medical practice in the field of pre-
vention, diagnosis and treatment; application of scientific knowledge
in clinical practice, public health, education and biotechnology.
Martin Biomedicine Centre (BioMed Martin) Molecular medicine, neurosciences, oncology, respirology
AgroBioTech Research Centre in Nitra Agrobiology, food technology, biotechnology, bioeconomy,
applied ecology
Centre for the Research and Development of
Immunologically Active Substances
Immunology, molecular medicine, biotechnology
University Science Park STU Bratislava Materials research, chemistry, food, industrial biotechnologies, environ-
ment, safety and reliability of buildings, materials research, research
of nanostructures, analysis of samples for physics, chemistry, geol-
ogy, biology and medicine, using transmission electron microscopy
with cold cathode and resolution of 78 pm, and Auger spectrometer
with the Schottky cathode
CRITICAL REVIEWS IN BIOTECHNOLOGY 7

Table 3. Listing of BT companies in the V4.
Company Specialization
Czech Republic Sotio Advanced cell immunotherapy R&D using activated dendritic cells; Phase 3 trials for
prostate cancerwww.sotio.com
AB Check Human antibody technologies; Phase 2 trials for lymphomas, owned by Affimed
http://abcheck.eu
Contipro Sales and formulation of Hyaluronic Acid for use in wound-healing, cosmetics, and veterin-
ary productswww.contipro.com
Bioveta Sales of a wide range of animal products, and some bacterial lysates for humans
www.bioveta.eu/en
Dyntec Vaccine R&D, and sales of bacterial and viral lysates
www.dyntec.cz
Biopharm Distribution of veterinary products and vaccine R&D
www.bri.cz/en
Erban Lachema Analysis of urine, blood chemistry, microbiology, immunology, etc.
www.erbalachema.com
Generi Biotech Services for genetic, oncology, and microbiologic diseases
http://www.generi-biotech.com/
generi-biotech-en/
BioVendor Developing and manufacturing in vitro diagnostic and for-research-use immunoassays, anti-
bodies, and recombinant proteinswww.biovendor.com
Protean Antibody, enzymes, transcription factor, custom protein production; services for diagnosis in
stomatology and tick-borne diseaseswww.protean.bio/en
GenTrend Services for diagnosis in stomatology and tick-borne diseases
www.gentrend.cz/en
Exbio Antibody sales for laboratory use and diagnostics development
www.exbio.cz/
Bio Agens Research and
Development –BARD
Over the counter formulations of the microorganism Pythium oligandrum used to treat
pathogenic surface fungi
www.pythium.eu/
Nafigate Corporation Hydal biotechnology –biodegradable polymer derived from cooking oil waste, for use in
applications such as food packagingwww.nafigate.com/en/
LentiKat’s Biotechnologies Applications in wastewater treatment, distilleries, and chemicals for food and pharmaceut-
ical supplementswww.lentikats.eu/en/
Enantis Modification of protein properties, such as thermal stability, protease or solvent resistance,
for use in environmental and medical functionswww.enantis.com
Bor Biotechnology Build and operate eco-facilities for generation of electricity and heat from wood chips
www.borbiotechnology.cz/en/
i2L Research Facilities and service provider in plant chemical testing, and insect sales
www.i2lresearch.com/
Hungary Solvo A pioneer and leader in the commercialization of membrane transporter technologies, diag-
nostics, and drug discovery assays, selling over 100 products, which are targeted at
pharma and drug discovery companies.
www.solvobiotech.com
BioTalentum It focuses on medical and animal biotechnology, by having found itself a space in stem cell
research and serviceswww.biotalentum.hu
Gedeon Richter Nyrt. Drug research and development entails three strategic directions:
www.richter.hu –research and development on original small molecules,
–recombinant biotechnology,
–generic product development.
Egis Pharmaceuticals PLC Important fields of research are the central nervous system, oncology, the cardiovascular
system, rheumatology, and metabolic diseases.http://www.egis.hu
PannonPharma Ltd. PannonPharma Ltd. is a member of the Biotechnological Innovative Base operating in the
South Transdanubian region of Hungary. The most important operation is to increase
the capacity of testing new molecules in the aspect of safety and effectiveness.
www.pannonpharma.hu
Servier Hung
aria Ltd. Discovering new drugs to treat neurodegenerative and neuropsychiatric pathologies, cancer,
diabetes, neuropsychiatric pathologies is or Immune-inflammatory disease is a
major challenge.
http://www.servier.hu/
ThalesNano Zrt. ThalesNano’s products can improve chemistry by complying with many of the principles of
green chemistry.www.thalesnano.com
Geosan The biotechnological sub-division works on the industrial-size expending of the use of
microbiology, specifically for agricultural and environmental protection purposes.http://www.geosan.hu/en/
Evonik Agroferm Zrt. Amino acid production –production of threonine by recombinant E. Coli
www.evonik.com
Fermentia Ltd. Production of recombinant proteins
http://fermentia.hu/
3D Histech It develops high-performance hardware and software products for digital pathology.
www.3dhistech.hu
Omixon It develops molecular diagnostic tools for clinical and research laboratories.
www.omixon.com
Soft Flow It is a biotech being active in a number of areas including antibody development, bioana-
lytical services, reagents, and software development.www.softflow.hu
Seqomics Research focuses on the development of methods and kits for food safety, veterinary, agri-
cultural, and human diagnostic applications. There is special interest in the metagenomic
characterization of microbial communities in wastewater plants, biogas, and fermentation
reactors, in the discovery of novel molecular markers that may be used in diagnostics as
biomarkers, and in the molecular biology-assisted breeding.
http://www.seqomics.hu
(continued)
8 M. DETTENHOFER ET AL.

Table 3. Continued.
Company Specialization
Poland Celon Pharma Production and sale of generic pharmaceuticals
https://celonpharma.com
MABION Production of innovative pharmaceuticals; elaboration of an anticancer drug MabionCD20
https://www.mabion.eu/en/
SELVITA Drug discovery –research and development in oncology (elaboration of an anticancer
factor SEL24), product and diagnostic services in biomedicine and biotechnologyhttps://selvita.com
Polski Bank Kom
orek Macierzystych
(Polish Bank of Stem Cells)
Stem cells banking, cord blood collection and storage; the only stem-cell bank in Poland
accredited with the AABB Certificate
https://www.pbkm.pl/en
BIOTON Biopharmaceuticals, R&D, implementation and sale of novel biotechnological products, and
pharmaceuticals; focuses: genetic engineering (recombinant proteins, production of
human insulin analog Gensulin R), pharmacology (anthracycline antibiotics), pharmaco-
kinetics and pharmacodynamics of therapeutic substances
www.bioton.pl/bioton/
The Polpharma Group The largest Polish manufacturer and provider of high-quality pharmaceuticals; offers pre-
scription drugs and pharmaceuticals for in-patient care, specializing in pharmaceutical
preparations used in cardiology, gastroenterology, and neurology; dietary supplements,
medical devices, cosmetic products, phytopharmaceuticals, and other biotechnological
drugs (biosimilars)
https://www.polpharma.pl/en
Dr Irena Eris High quality, innovative, effective, and safe luxury cosmetics, individually tailored profes-
sional care (skin care institutes and SPA hotels)http://drirenaeris.com/en
TEVA Poland R&D in elaboration and manufacture of drugs and dietary supplements. Large portfolio of
medicinal products, comprising special-care and generic drugs, bioactive pharmaceutical
components and non-prescription preparations.
http://www.teva.pl
ADAMED Group R&D in innovative therapies; innovative research platforms to elaborate novel drugs;
improvement of the medicines currently available in the market and distribution on a
large scale; prescription products, non-prescription medicines, dermocosmetics
https://adamed.com.pl/en
DNA-Gdansk (department of BLIRT S.A.) Provider of solutions and tools for medical and molecular biology; manufacturer of quality
reagents and kits for molecular biology, biotechnology, genetics, and molecular diagnos-
tics; active in practical training programmes for customers
http://www.dnagdansk.com/en
A&A Biotechnology Production of recombinant proteins, enzymes; DNA, RNA purification, PCR & reverse
transcription; reagents for molecular biology, enzymes and protein analysis, cloning,
and transformation; manufacture and sale of laboratory equipment
http://www.aabiot.home.pl/MainEN/
A&A_Eng
BioContract R&D in drug development, diagnostic, and research methods; application of biotechnology
in health care; documentation, preparation, certification of products, quality control tests,
consulting, training, and teaching in biomedicine; manufacturer of genetically modified
melanoma vaccine AGI-101H (currently designated for clinical trials)
http://www.biocontract.com/en
Celther Poland R&D in the field of cell and targeted therapy; manufacture of state-of-the-art wound dress-
ing materials; service provider: R&D outsourcing, cell and molecular biology, genetic
engineering, cell line development, in vitro toxicity testing and chemical analyses
http://www.celther.com
Nanogroup Management of bio-med enterprises and projects Aimed at building up clusters of bio-tech
and bio-med companies related to prophylaxis, diagnostics, targeted therapies, trans-
plantology, and recovery of oncological patients; venture capital-based coordination of
Proof-of Concept phase projects
https://en.nanogroup.eu
Master Pharm Food technology: an outsourcing company focused on the development of novel dietary-
related projects and commercialization of supplementary food products; product docu-
mentation and certification
www.masterpharm.pl/en/home.html
Cambridge Chocolate Tech. Food technology: commercialization of health-beneficial chocolate products; e.g. Esthechoc,
chocolate improving biochemical skin parameters, helping to prevent skin agingwww.cambridgechocolate.com
BIOGAZ Zeneris The first Polish-technology based heat and power plant supplied by an agriculture- and
food-utilization biogas generating installationhttp://biogaz.com.pl
Bioxen (part of the Nutribiomed Cluster) Elaboration and implementation of modern washing preparations based on active enzymes,
surfactants and disinfection agents; evaluation of microbiological purity of surfaceshttp://www.nutribiomed.pl/en/
BAYER Crop Science Leader on the Polish crop protection market; product sale as well as consulting, elaboration,
promotion, and offer of complete plant protection programmeshttp://www.bayer.com.pl,https://agro.
bayer.com.pl
Herbapol Lublin Herbs, aromatic teas, and full-flavored syrups are produced from only the best and most
natural ingredientshttps://www.herbapol.com.pl/?lang¼en
Biotika, a. s. Slovensk
a L'up
ca Most important manufacturers working in the sphere of biotechnology and pharmaceutical
industry (penicillin V, oxytetracycline, chlortetracycline, dextran, L-lysine and others)
Slovakia http://www.biotika.sk/en
Imuna Pharm Holding,

Sari
ssk
e Michal'any Oldest and largest pharmaceutical company today present in infusion solutions, culture
media, tablets, blood derivate, dietetics, hemodialytic solutions, bacteriological and bio-
chemical preparations
http://imuna.sk/en/
Saneca Pharma, Hlohovec 3rd biggest and fastest growing European generic pharma company
https://www.saneca.com/
Hameln rds Toxicological/clinical studies and extensive laboratory services that covers the entire value
chain from drug development right through to drug sales and distributionhttp://www.hameln-rds.sk/
BioScience Slovakia, s.r.o. Diagnostics of infectious diseases targeting immunocompromised patients, including organ
transplant recipients and patients on dialysishttp://bioscience.sk/en/homepage/
Danubeclone, s.r.o. Monoclonal antibodies production, as well as on the neuroimmunology research
DB Biotech, s.r.o., Ko
sice Designs and products of high-quality rabbit clonal antibodies developed by a novel “in vitro
cloning technology”http://www.dbbiotech.com/home.html
(continued)
CRITICAL REVIEWS IN BIOTECHNOLOGY 9

1990 [13]. Hungarian BT has experienced strong growth
in the last decades, especially between 2004 and 2008.
Impressive growth in the establishment of new firms
was witnessed, as well as a steady increase in the num-
bers of employees working in Hungarian BT, averaging
12% annual growth between 2004 and 2013 (Figure 1).
These statistics and additional data support the notion
that Hungary assumed a leading position among new
EU member states by 2009 (Figure 2). In 2010, the
sector’s growth had lost its dynamism, and since then
there have been few traces of the old boom [14].
Among the four subsectors of the Hungarian BT
industry, namely the bioinformatics (gold), the agricul-
tural (green), and food (yellow) sectors. The industrial/
environmental (white) and the red (medical) BT sectors
are the most developed.
Country priority in BT
The most important subsectors and techniques are in
the fields of molecular, cell and tissue biology, material
processing, bio-IT, and the nanotechnology sectors.
Biotech firms carrying out research and development
activities in Hungary are internationally recognized, and
they provide opportunities for cooperation and invest-
ment in the following fields: research and development
of pharmaceutical products, cancer research, nano-
technology, and human medicine. Together with BT
services, bar coding, next-generation sequencing, bio-
informatics, and human diagnosis being important [15].
Smart specialization strategy (RIS3) related to BT
Within the national research priorities of the V4
Countries, there are both sectoral and horizontal prior-
ities which emphasize the role of Hungarian BT, namely
a healthy society and well-being; sustainable environ-
ment, natural resource management, advanced envir-
onmental technologies, and agricultural innovation.
Hungary’s focus within the priority of “Energy and
Environment”as it relates to green energy includes the
field of environmental BT. The country’s priority of
“Healthy society and well-being”is focused on under-
standing diseases, early diagnosis, advanced medical
Table 3. Continued.
Company Specialization
Glaston, s.r.o. Stem cells research
http://glaston.webnode.sk/o-nas/
Vestigen, s.r.o. Technology for point of care diagnostics for portable use
http://www.vestigen.com/
Imunoglukan, s.r.o.
http://www.imunoglukan.com/en/
R&D and distribution of drugs and food supplements on the natural basis
HighChem, s.r.o. Experimental spectra and organism-specific biochemical data that are indispensable in the
modern pharmaceutical, metabolomics, forensic, and environmental applicationshttp://www.highchem.com
Axon Neuroscience R&D drug against Alzheimer disease –on the basis of Tau protein
http://www.axon-neuroscience.eu/
Evonik Fermas L-threonine producer
http://www.fermas.sk/
Azoter Small plant-fermentation enterprise in Petrova Ves for the production of enzymes utilized
in the food industryhttp://www.azoter.sk/english.
phtml?id5¼22668
Envien Group Production of biofuels, used in mixtures with conventional diesel and gasoline
https://www.enviengroup.eu/en/
Tate & Lyle (Amylum Slovakia) Global provider of distinctive, high-quality ingredients and solutions to the food, beverage,
and other industrieshttps://www.tateandlyle.com/home
Axxence Slovakia, s.r.o./Monoprix s.r.o. Production technologies and the manufacturing of selected natural aroma chemicals,
flavoring substances and concentrates for foods based on herbs and plants specieshttps://www.axxence.de/en/axxence-slo-
vakia.html
Koppert, Nov
eZ

amky Production of bumblebees for plant controlled pollination
https://www.koppert.com/
Color of fields within the table indicates the type of BT in which the company is engaged (red –䊏–medical or veterinary BT; white –w–industrial BT;
green –䊏–agricultural BT; yellow –䊏–food BT; gold –䊏–bioinformatic).
Figure 1. Increasing number of Hungarian BT company
employees (CAGR: company average annual growth) [13].
(Permission granted for use given by the Hungarian
Biotechnology Association).
10 M. DETTENHOFER ET AL.

and instrumental therapies, clinical methods, pharma-
ceutical research and development, the innovative
health industry, and medical tourism solutions.
Regarding the priority of “Agro- and bioeconomy,”
Hungary selected food production through agricultural
innovation as its RIS3 [16,17] priority.
Education in BT
In Hungary, several universities provide MSc and/or
PhD programs in the BT field, among them: Szent
Istv
an University, University of Pannonia, University of
P
ecs, Pazmany Peter Catholic University, University of
Szeged, Budapest University of Technology, University
of Debrecen, E€
otv€
os Lor
and University, and
Semmelweis University (for more detail please see
Table 1).
Research institutions in BT
According to the National Biotechnology Platform, 70%
of active BT research and education institutions oper-
ated in Budapest and its agglomeration. There are red
biotech and bioinformatics company clusters in certain
university towns (Debrecen and East Hungary; Szeged
and South East Hungary; and Pecs and South West
Hungary) [18]. Accredited innovation clusters include
Pharmapolis Debrecen Innovative Pharmaceutical
Cluster, Goodwill Biotechnology Cluster, and
Biotechnology Innovation Base Cluster [19]. The main
non-university academic organizations and their
research areas are listed in Table 2.
The majority of biotech firms are represented by the
Hungarian Biotechnology Association (HBA). The mis-
sion of HBA is to strengthen the position of BT as a stra-
tegic industry in Hungary by bringing together the
academic, business and public sectors. HBA has
established several committees: Healthcare Biotech and
Diagnostics, Agri-Food, White Biotechnology,
Bioinformatics, Science Policy and Education, Science
and Bioethics, EU, Investment and Trade Development,
Communication and Information Resource, and a Legal
Committee. HBA is a member of several important
international biotechnology organizations, such as BIO
(Biotechnology Industry Organization), EuropaBio (The
European Association for Bioindustries), and EFB
(European Federation of Biotechnology). HBA also par-
ticipates at major international exhibitions, such as BIO
International Convention, BIO-Europe, BioForum, and
BioMed, among others.
Bay Zolt
an Nonprofit Ltd. (Division for Biotechnology
in Szeged, BAY-BIO) activities target transforming
research into high-value products within the BT indus-
try. The Aquincum Incubator, is a unique, structured
meeting platform between startups, business angels
and competitive business entities. It works to build a
community of innovative startups in IT, mobile commu-
nication technologies, BT, and med-tech by providing
advice for business development, market analysis on
product and service uptake, and facilitating down-
stream business opportunities [20].
Besides the above-mentioned, the following institu-
tions are also active in Hungarian BT, namely
Semmelweis University, University of Szeged, University
of Pecs –Medical School, Research Centre for Natural
Sciences, Hungarian Academy of Sciences, Institute of
Experimental Medicine –Hungarian Academy of
Sciences, and Szent Istvan University.
Important research projects
Several Hungarian projects have been funded directly
from EC (e.g. FP7, Horizon 2020) or through shared
management at the national level, through various
Figure 2. Quantitative and Qualitative Factors in the 14 new Member States and Candidate Countries [21]. The assessment for
the qualitative factor includes the level of government support, the availability of a qualified workforce, the advancement of
technology transfer systems, the awareness of IP protection, the existence of technology parks and clusters, the level of public
and private financial support and the presence of a pharmaceutical industry. The calculation of the quantitative factor is based
on the number of biotechnology companies present, their category of activity (therapeutics, services, and other biotechnology
sectors), and the number of products under development. (Permission granted for use given by EuropaBio).
CRITICAL REVIEWS IN BIOTECHNOLOGY 11

Operational Programmes. The statistics show that 70
Hungarian stakeholders participated in FP7 projects in
the areas of public health, medicine and life sciences.
For example, the SME, BioTalentum Ltd., has been
involved in more than 30 research projects funded by
the EC investigating stem cell-based regenerative medi-
cine. BioTalentum is heavily involved in Horizon 2020,
coordinating the iNanoBIT project, which hopes to
develop the engraftment, survival, and function of cell
transplants for the replacement of beta- and islet cells
in the pancreas. The company is also participating in a
number of other projects, including EU-ToxRisk, CaSR
Biomedicine, SciChallenge, and GROWTH [20]. A further
example, is the DDOP-1.1.3–11-2011 tender of PEIK,
which was financed through the South Transdanubia
Operational Programme. In addition, the Health
Industry Innovation Centre of the P
ecs Company served
as the coordinator of the program of the same name
and was established by the government, the University
and enterprises within the framework of “P
ecs the Pole
of Life Quality”(BIB Cluster). Over the past few years,
several projects were additionally funded through the
Norway Grants.
Enterprises and companies in BT and links to R&I
Most firms in the sector are small- and medium-sized
enterprises that were spin-offs from one of the major
universities, which currently form clusters in the
Budapest, Szeged, Debrecen, and P
ecs areas. Almost
half of all Hungarian BT companies, in terms of the
number of companies, employment, and revenue, oper-
ate in the red BT sector (see Table 3 for more detail).
Funding support schemes for BT
In the early 2000s, the lack of international venture cap-
ital for life science applications resulted in the majority
of small companies being dependent on state grants.
From 2005 to 2010, the Hungarian government made
BT a priority sector in the national development plan.
During the first year of this plan, a national startup and
pre-startup funding program was established with 11
new BT firms being created. Incentives such as research
subsidies, tax credits and other tax benefits were grad-
ually increased by the state to encourage investment in
R&D. The Europa Bio-Venture Valuation study in 2009,
however, identified the lack of coordination between
various programs and the means of accessing funding
as a major obstacle for companies intending to benefit
from such initiatives [21,22]. In 2006, the Hungarian
Biotechnology Association set up a “Biomanager
Training Program”supported by the National Office for
Research and Technology (NKTH), with the aim of pro-
viding professional guidance for students in areas like
business management, intellectual property, and tech-
nology, although this program was discontinued due to
funding cuts.
After the first decade of the 21st century, the situ-
ation has changed significantly. In 2010–2011, the
national government cut funding for BT, whereas the
EC introduced the Joint European Resources for Micro
to Medium Enterprises (JEREMIE), a program initiated
through a venture capital fund for Hungarian SMEs.
This effort, however, provided limited opportunities for
BT firms.
Regulatory environment
Several government programs –the National
Biotechnology Strategy (2005–2010), the Biotechnology
National Technology Platform strategic research plan
(2010), and the Hungary 2025 vision –focus on the role
of the BT sector. With regards to agricultural BT, The
Cartagena Protocol was ratified by the Hungarian
Parliament, coming into effect on 12 April 2004 and
was published as Act CIX/2004. In 2006, the parliament
formulated Hungary’s GMO-free strategy and the
Fundamental Law of Hungary, which has been in force
since 1 January 2012 and pertains to the pursuit of
GMO-free agriculture. The principal piece of legislation
is Act No. XXVII from 1998, which provides guidelines
for Biotechnology Activities [23]. The patentability of
biotechnological inventions is covered by Act XXXIII/
1995 on patent protection of inventions.
Brief critical evaluation of the current situation of
BT in Hungary and comments on future prospects
The BT sector is small by US and Western European
standards and the increasing gap needs to be bridged
between the regional, Vienna and Hungarian sectors.
The major goal, however, remains the same as a decade
ago, namely development of a sustainable BT sector
with a critical mass of highly skilled labor. The ability to
attract and retain scientific and management talent,
combined with resources for both frontier research and
science for society, as well as development capacity
through a spectrum of funding vehicles is
highly desirable.
12 M. DETTENHOFER ET AL.

Poland
Development of BT in Poland
In Poland, BT is still an emerging sector of the country’s
economy [24]. However, as highlighted in a recent
review [25], BT is regarded as a key factor of techno-
logical progress relating to the bioeconomy since it
promotes the use of biological methods in industrial
applications, facilitates the integration of science, and
the business and the social environment. Thus, it sub-
stantially contributes to sustainable development.
Although the Polish economy is still dominated by agri-
culture and food production, other areas such as aqua-
culture, climate and environment protection, energy
generation, chemical, pharmaceutical, wood, and cellu-
lose industries have also been expanding due mainly to
rapidly developing green (agricultural), white (indus-
trial), and red (medical) BT.
The bio-based industry consisted of almost three mil-
lion employees, in 2014, and contributed 10% of the
Polish gross production volume (e82 Bn.) of the total
e821 Bn. [26]. Detailed statistical data regarding the
size, share, and productivity of particular sectors, as
well as trends observed in the Polish bio-economy, are
detailed in previous reviews [25,26]. The most import-
ant areas are agriculture (41% share, with 80% of the
total bio-based workforce employed), production and
processing of food and feed (53% share), as well as for-
estry (6%).
Poland is the eighth largest food exporter in the EU
and is known for good-quality agricultural products,
with e21.9 Bn. in agro-food products exported in 2014
[25,27]. Similar with the other EU states, agro-BT in
Poland meets a growing environmental and social
demand to increase its productivity and improve food
and biomaterials quality including the introduction of
novel, highly efficient crops, mostly obtained through
innovative plant culture techniques. The key challenges
being addressed include insufficient water resources,
climatic changeability, limited cultivable land area for
expansion, and the growing risk of pest and pathogen
attack. However, tough legislative regulations have the
effect of lowered competitiveness for Poland with
other, non-European countries, which are considerably
less legally restrictive.
Bioenergy production in Poland in 2014 contributed
to 11% of the total energy generated [25], and was
based mainly on renewable-source raw materials: solid
biomass (mainly wood and straw, 87% share of total
bioenergy), bio-ethanol, bio-diesel (both amounted to
10% of bioenergy), and biogas (3%) [26]. Utilization of
renewable resources fully agrees with the concept of a
circular bioeconomy [25] and is strongly promoted by
the EC Circular Economy Package [28] as a basis for sus-
tainability, development, and environmental protection.
The principles of economic circularity are reflected in
country-wide efforts to modernize waste management
systems, minimize exploitation of water resources,
implement optimized bioprocesses (e.g. biogas gener-
ation), and develop novel technologies for bio-based
products (e.g. biodegradable polymers) [25,29].
Poland has achieved high levels of performance in
the advanced segment of recombinant DNA-based bio-
pharmaceuticals. The pharmaceutical industry employs
20,400 workers (2013) [27], and is represented by more
than 100 companies, including large international cor-
porations, and has witnessed a steady growth of 40%
within the period of 2006–2013, reaching a e6 billion
market and is predicted to grow to e7 Bn. by 2018 [25].
The data regarding biopharmaceuticals [29] show 10%
growth within 2014–2016, currently amounting to
e830 Mn. This market is expected to expand further
because of demographic changes, such as society
aging, epidemiological global trends, and elaboration
of novel products, especially biosimilar pharmaceuticals.
The other sectors of medical BT, in general, are at the
research level and it may take many years to reach their
final application stage [29], however, there are exam-
ples of successful commercialization. Genetic diagnos-
tics (e.g. familial testing, cancer risk evaluation) is now
offered by a number of small companies, often linked
to research or forensic medicine units. Gene therapy
studies have led the Wielkopolska Centre of Oncology
to development an anti-cancer vaccine which is now
undergoing clinical trials. In addition, in vitro fertiliza-
tion is offered by both private clinics and public hospi-
tals, and stem-cell related treatments are now being
commercialized widely by private biomedical compa-
nies and clinical institutions.
Environmental BT applications rely on studies on the
biodiversity and metabolic potential of microorganisms.
Microbial strains have been used for biological pest
control [30], to promote plant growth and improve ani-
mal welfare. The BT market has become dominated by
foreign companies, which have enough potential to
cope with complex formal requirements and financial
barriers while obtaining commercial permits for micro-
bial-based products [29,30]. Specialized microbial com-
munities, consisting of environmental isolates, have
also been used in large-scale ex situ and in situ bio-
remediation projects for the cleanup of polluted sites
(mainly soil reclamation) and in modern biological
wastewater treatment systems. It has to be identified,
however, that for many biotechnological applications
CRITICAL REVIEWS IN BIOTECHNOLOGY 13

(e.g. environmental projects, production of biochemi-
cals, renewable materials, bioproducts) there is no sys-
tematic market analysis available and a straightforward
statistical evaluation in the wide economic context has
not been developed [26].
Country priorities in BT
Polish economic policy is expected to conform to the
aims of the “Europe 2020”strategy [31], as well as the
national program for bioeconomy development [25,26].
Prioritized innovative BT projects will deal with the
application of renewable materials to develop environ-
mentally friendly, energy-efficient industries, optimize
resource utilization and waste management, novel
food/feed production and processing, generation of
biopharmaceuticals, and finally, promotion of new con-
sumption patterns. Among the most important RD&I
priorities are [26] (1) energy and high-value-added
chemicals obtained from biomass, (2) biomaterials and
biodegradable polymer composites based on bio-nano-
cellulose, (3) new biomass-based biocatalysts and bio-
catalyst mimetics for production of fuel and industrially
important organic compounds or platform molecules,
(4) functional foods, (5) integrated fermentation and
bioconversion processes with product separation, purifi-
cation, and batching, and (6) biorefineries based on
waste and renewable resources.
Smart specialization strategy (RIS3) as related
to BT
BT has been selected as a key sector of the National
Smart Specializations (NSS) [25,32] determined within
the concerted European RIS3 strategy [33]. In Poland,
on identifying the RD&I fields [34], 18 NSS were defined,
at least 13 are in-line with BT-related tasks, and
grouped into the following areas [34,35]: (1) healthy
society, (2) agro-food, forestry-timber and environmen-
tal bioeconomy, (3) sustainable energy, (4) natural
resources and waste management, and (5) innovative
technologies and industrial processes.
Education in BT
Poland’s higher education offerings in BT are well
developed. According to educational web portals [36],
there are 42 faculties offering BT programs at 40 public
universities including medical and technological facul-
ties. The recent rankings from 2017 list 32 universities
with Master’s degrees in BT studies (selected most rec-
ognized are in Table 1).
Most of the universities offer three levels of BT stud-
ies. First-level programs (BSc or engineering-(degree)
typically covering general BT and in a few cases, indus-
trial or food BT. Second-level (MSc) studies provide a
wider choice of programs (e.g. applied, plant and envir-
onmental, molecular, analytical biotechnologies) with
many specializations. Third-level studies (Doctoral,
offered by 31 universities) are much more individual-
ized and depend on particular faculty profiles. The stu-
dents are given good opportunities for international
exchange, through programs like Erasmus Plus,
Visegrad-countries agreement, and individual cooper-
ation agreements between universities. The estimated
number of Polish BT students is 13,000 per year, of
which over 1000 graduates gaining employment or
embarking on the further study with companies, labora-
tories, and universities worldwide and are generally
considered to be well-educated and professionally
trained specialists.
Research in BT: institutions and patents
In Poland, R&D activity in BT is carried out by over 110
scientific institutions and 6 biotechnological clusters
[37]. Among the scientific units, 58% are nonprofit
operations belonging to either governmental or private
sectors, and 42% are linked to the higher education sys-
tem [27]. The internal expenditure on BT R&D in scien-
tific institutions amounted to e126 Mn. in 2015, and
continued the growing trend observed in preceding
years (9.5% increase compared to 2014). Over 75% of
all the funding was provided by the state budget, 20%
came from abroad with only 2.2% coming
from industry.
Similarly, to other countries, most of the Polish
inventors’patent applications, including in BT, originate
from universities and research institutes [29] (selected
recognized institutions are in Table 2). The structure
and number of Polish and international-range European
patents in 2015 are shown in Figure 3. The data suggest
a low patenting rate compared with other EU countries
and seemingly does not reflect Poland’s potential for
biotechnological innovation [29].
Enterprises and companies in BT
There were 160 enterprises active in the Polish BT field
in 2015, with a 27% increase compared with 2014 [27].
In 2014, 35 companies categorized as R&D in BT dealt
with health care, whereas for BT-related production, the
main areas were: environment (32 companies), health
care (17 companies), and industrial processing (16
14 M. DETTENHOFER ET AL.

companies) [27]. A map of the largest BT enterprises in
Poland is presented in Figure 4. BT sector employment
in 2014 totaled 10,326. More than 7500 employees
worked in scientific institutions and 2765 in the private
sector. The internal expenditure by BT enterprises was
e81 Mn., with 38% provided by foreign financing and
3% coming from the state budget.
A 2016 business survey report [32] revealed positive
trends and moderate optimism following a survey of 86
Polish BT companies. Among the conclusions were (1)
positive or moderate evaluation of the business environ-
ment, well-qualified employees, satisfactory cooperation
with academia, plans for expansion; and (2) disadvanta-
geous aspects –little experience in commercialization,
limited access to investment money (decreased com-
petitiveness), complex legislation system.
The BT sector is present on the Warsaw Stock
Exchange (WSE). At the end of 2017, there were 25
joint-stock companies (of the total 481) with a capital-
ization of e1.57 Bn., and a share in a total WSE capital-
ization of 0.46%. Interestingly, most of the companies
(23) belong to the biomedical category and they
represent 99.1% of the total biotech/life science sector
capitalization [38] (selected recognized Polish compa-
nies are also listed in Table 3).
Important funding schemes to support BT
In Poland, the total internal 2015 expenditure on BT
R&D activities amounted to e203.4 Mn. [29]. Various
alternative funding schemes are available to Polish uni-
versities, research institutes, BT clusters, enterprises,
and business consortia together with academia [35,39].
There are two main R&D funding agencies, supported
by the National Science Centre (NSC), focusing on fun-
damental research, and the National Centre for
Research and Development (NCRD), dedicated to
applied research. Both are related to the Ministry of
Science and Higher Education. NCRD, and closely inter-
acts with PAED, Polish Agency of Entrepreneurship
Development, and is involved in coordination with EU
structural funds distribution. The total NSC annual
budget is e239 Mn., whereas NCRD will support e6.22
Bn. during the 2014–2020 period.
31%
17%
15%
7%
4%
2%
7%
13%
4%
Biotechnology (14)
Organic fine chemistry (8)
Pharmaceucals (7)
Macromolecular chemistry, polymers (3)
Food chemistry (2)
Basic materials chemistry (1)
Surface technology, coang (3)
Chemical engineering (6)
Environmental technology (2)
Micro-structural and nano-technology (0)
Figure 3. The structure and number of patents granted in 2015 by European Patent Office to Polish inventors in technological
fields including biotechnology (total: 46). Note: 150 was the total number of patents granted in all of the fields [49].
Figure 4. Map of the Polish biotechnological sector. Source: with permission for use given by the Polish Investment and Trade
Agency [37].
CRITICAL REVIEWS IN BIOTECHNOLOGY 15

Poland also has access to financial programs
launched by the EC. The general funding scheme to
support RD&I project is based on balanced financing by
both the national budget and EU structural funds, as
well as on synergy between NSS, Operational Programs
Smart Growth (OPSG) and other existing programs
(Regional OP, COSME, PRRI, OP Digital Poland, Horizon
2020, PAED & NCRD projects) [34].
Both PAED and NCRD have initiated a wide variety of
financial support schemes from strategic, sector-related,
international, and regional. They are dedicated to pro-
moting novel BTs and to encouraging linking businesses
and academia to result in enhanced innovation and
improved competitiveness. The calls for grant competi-
tions address specified areas or actions [35]. Different
paths vary broadly depending on the terms of the
amount of financial support and/or the rate of refund,
the beneficiary target institution (enterprise, scientific
unit, or a consortium), or the expected outcomes.
To bridge a gap between basic research and applica-
tion projects, new transitional-like grant types have
been proposed, which enables early verification of ideas
(Proof-of-Principle, PoP), or combining basic and
applied research (Proof-of-Concept, PoC). Accordingly,
the NSC has initiated competitions for TANGO PoC
grants, and NCRD launched pre-seed phase PoC grants
(PoC-Bridge Alfa). Polish entities are also free to obtain
support from grants approved by other dedicated
funds (e.g. Norway grants, NATO) or due to direct inter-
national scientific cooperation links [35,39].
Regulatory environment
In Poland, there is no single and strategic document
dedicated to legislation on the use of biotechnological
methods [25]. Both the academic and market sectors
complain about the complexity and/or stringency of
regulations together with costly certification procedures
[29]. This situation hampers the industrial-scale imple-
mentation of innovative bioprocesses, microorganisms
and plants, and the introduction of novel bioproducts,
especially biopharmaceuticals. This, in turn, favors for-
eign companies, still able to cover high expenses. A
complicated funding support system is also inherent in
the grant approval schemes, which discourages submis-
sion of project applications and makes cooperation
between universities and business entities very difficult!
As genetic engineering techniques are ubiquitous in
modern BT [29], the latest Polish regulations introducing
restrictive amendments to GMO legislation practically bans
any GMO commercial use on Polish territory [25]andis
expected to slow down progress in the advanced bio-
sciences. The problem has been growing due to low
acceptance of GMO by the conservative part of Polish soci-
ety and interference by legislative authorities, motivated
politically rather than scientifically [40]. In the recently pub-
lished opt-in concept, competent experts are urging the
EC to develop improved legislation to overcome these
obstacles [41]. The Polish Ministry of Agriculture and Rural
Development is, however, now considering a 5-year post-
ponement of the ban of GMO Soya use.
Brief critical evaluation of the current situation of
BT and future prospects
BT in Poland receives considerable feedback from aca-
demia, business, human resources, and a well-perform-
ing, fast-growing economy (GDP expected to grow
above 4% p.a. in 2018). To release the potential for
development, the following steps should be under-
taken: (1) introduction of appropriate legislation
amendments to support innovation, (2) efforts to
educate society to enhance understanding of modern
BT-related issues, (3) further development and optimiza-
tion of both national and EU-based financial support
schemes to encourage academic entrepreneurship and
business innovation, and (4) stimulation of cooperation
between universities and industrial institutions [40].
Poland’s most significant contributions to innovative
BT includes bacterial nanobiocellulose, medical linen
dressings made from genetically modified plants,
Gensulin
V
R
(the recombinant human insulin by Bioton,
Inc.), in vitro plant production, transgenic plant breeding,
systems for DNA sequencing, and a globally competitive
agro-food and fermentation industry. However, with
regard to market success, many of these, such as large-
scale installations for green energy production or plants
for biomass conversion into higher-added value products
are yet to be implemented industrially. Similarly, for med-
ical BTs, long-term certification procedures will require
decades to reach full commercialization.
Slovakia
Development of BT in Slovakia
Slovakia is classified as a moderate innovator based on
its RD&I output according to the EC [42] and is at a
similar level to its CEE Visegrad neighbors. Slovakia ori-
ginally was agriculturally oriented until the second half
of the 20th century when industrialization influenced
BT progress. During the 1980s, within former
Czechoslovakia –the Development Programme of
Priorities was elaborated and BT was one of four top
priorities. By 1996, a new initiative at the state level
with the name, “Programme on Development and
16 M. DETTENHOFER ET AL.

Elaboration of Biotechnology in Agriculture”was pre-
pared as part of the “National Programme on the
Biotechnology Development.”Unfortunately, this was
never fully implemented. Life sciences projects were
generally supported with Framework 6 and 7, if
accepted by both the Ministry of Education SR (includ-
ing APVV grant agency) and the Slovak Academy of
Sciences (for details, see [43]).
Slovakia, in the past, mostly emphasized industrial
BT. However, in recent years, increasing focus has been
placed on agricultural, pharma- and medicinal BT fields
[44]. Development of BT research capacities, based on
domestic companies still lags behind expectations,
necessitating a strengthening of the link between BT
and the bioeconomy [45].
Smart specialization strategy related to BT
in Slovakia
The Smart Specialization Strategy promotes an innova-
tive approach of the EC’s efficient and targeted use of
public investment in RD&I to enable countries and
regions to capitalize on their strengths and create new
competitive advantages. These strategies serve as
national and regional Smart Specialization Strategies
compasses for ESI Funds’investments. The EC supports
the public authorities responsible for the allocation of
investment resources with analysis and guidance.
Slovakia has elaborated a basic concept document of
its RIS3 strategy in 2011–2014 [44], in which
“Biomedicine and Biotechnology”is among the key
research and innovation sectors (see Figure 5).
However, when developing the implementation pro-
gram [46], BT is not, however, specifically identified
among specialization domains with implementation
programs. BT could contribute to the general domains
such as Industry for the 21st century, healthy food and
environment, population health, and medical technol-
ogy, among others. Broadly generalized definitions of
domains are unfortunate, perhaps leaving too much
scope for the interpretation of priorities, which may be
difficult to coordinate. Other questions will arise regard-
ing the implementation of strategic and transparent
mechanisms of funding the EU structural funds.
Figure 5. Smart Specialization –the concept strategy in Slovakia [50].
CRITICAL REVIEWS IN BIOTECHNOLOGY 17

Education in BT
Several Slovak universities offer full programs (BSc/MSc/
PhD) in BT (selected most established are in Table 1). In
addition, many universities offer courses in biochemis-
try and molecular biology, but these programs are not
specifically targeted to BT as disciplines translating
basic and theoretical studies. Nevertheless, several of
these programs are contributing significantly to
BT education.
Research in BT
Besides the R&D in universities already listed in Table 1,
there is a range of other universities (University of
Constantine Philosopher in Nitra, Technical University in
Ko
sice, Pavol Jozef

Saf
arik University in Ko
sice). In add-
ition, several non-university organizations are engaged
in research in different areas of BT, especially the insti-
tutes of the Slovak Academy of Sciences (SAS) and the
Ministry of Agriculture research institutes associated
with the National Agricultural and Food Centre (NAFC)
(see Table 2). Some of them have been established dur-
ing the recent period (2007–2016; see Table 2, marked
in light blue color) thanks to the implemented EU OP
R&D structural funds projects. They are specifically ori-
ented to biomedicine and red biotechnology.
Obviously, this list is limited due to the limited size of
this paper.
A complete list of established research centers and
implemented projects in all sectors of R&D can be
found in the document “Implementation plan -
Research and Innovation Strategy for Smart
Specialization of the Slovak Republic”[46].
Paradoxically, more than 100 projects were funded to
establish centers of excellence, and an additional 30
projects established scientific parks through the imple-
mentation of Structural Funds in the Slovak Republic,
which across all branches of R&D (total expenditure
estimated to e478.8 Mn.). The long-term sustainability
of these facilities presents a number of challenges.
Enterprises and companies performing R&I in BT
BT companies are only a minor part of the Slovak econ-
omy. Most companies operate within red BT relevant to
medical and veterinary products and services. Although
major foreign BT companies have some presence in the
Slovak Republic, much of their activities do not include
R&D, but rather focus on regional sales and marketing
(Biotika, Evonik/Fermas, Imuna Pharm Holding, Saneca
Pharmaceuticals). Several companies of Slovak origin,
dedicated to red BT, target the area of diagnostics for
animal and/or human health (see Table 3). Several firms
are based on DNA or protein-based techniques
(BioScience Slovakia, Vestigen). A relatively more
mature set of companies include those focused on ani-
mal vaccines, with Danubeclone and DB Biotech having
a large portfolio of products. Four companies, namely
Hameln rds, HighChem, Glaston and Axon
Neuroscience are focused on red BT research. Three
companies are oriented to the production of food addi-
tives and supplements. Of the industrial biotechnology
companies, Envien group is a cluster of companies
(Enviral, Meroco, Polnoservis) producing first generation
biofuels and are investing in the preparation of the pro-
duction of advanced biofuels from agro-wastes. The
Envien group cluster also has activities in several other
CEE countries (Czech Republic –Vrdy, Hungary –
Kom
arom, Feh
ert
o, Croatia –Vukovar).
Funding support schemes for biotechnology
The funding system within the Slovak Republic consists
of several different organizations. Competitive financing
for R&D includes funds from the Slovak Research and
Development Agency of the Ministry of Education,
Science, Research and Sport of the Slovak Republic,
state programs, and Structural Funds of EC. Institutional
R&D financing comes from the Research Grant Agency
for universities and institutes of the Slovak Academy of
Sciences. The specific funds for R&D financing come
from international grant agencies such as Horizon 2020.
The most substantial source of the R&D funding
comes from OP R&D structural EC funds. These funds
have reached approx. e438 Mn., of which e129.9 Mn.
were to biomedicine and biotechnology. The activities
within the projects involved 1263 researchers and 50
managing staff members. [46].
In order to reach an R&D expenditure target of 1.2%
GDP in Slovakia by 2020, it is necessary to increase the
share of private funds receiving RD&I support. Business
investment in R&D should increase from 0.31% of GDP
in 2012 to 0.8% in 2020. This will, however, require a
series of measures and support from the government,
as well as the development of a more entrepreneur-
ial attitude.
Regulatory environment
In 2002, legislation was approved regarding the regula-
tion of GMO, which is compatible with EU directives.
The competent authority for the contained use of GMO,
became the Ministry of Environment, SR. In intellectual
18 M. DETTENHOFER ET AL.

property rights protection, Slovakia is aligned with EU
directives and is a member of the IPO organization.
Brief critical evaluation of the current situation of
BT and future prospects
Slovakia has built during the recent period a fairly good
research capacity in various branches of BT, which was
aided by substantial EU structural funds. These sources
also helped to build much-needed infrastructure, but
adequate support for human resources and running
costs is partially lacking. The long-term sustainability of
these centers is therefore questionable. The gap
between high-quality research, technology transfer, and
commercialization must be tackled in the near future!
This will require concerted actions by government,
institutions, entrepreneurs, and investors to create ena-
bling mechanisms to bridge this divide allowing for
these centers’sustainability.
The contribution of BT to the Smart Specialization
Strategy in Slovakia has been stressed during the last
five years as it takes part in the crucial role of the
European Bio-economy. It is somewhat surprising that
in the last definition, current “smart specialization
domains”[46] are only loosely connected to
“Biotechnology and the Bio-economy.”Too much
emphasis is placed with domains linked to the car
industry, perhaps influenced by the current sectoral
industrial structure of Slovakia, which is the similar situ-
ation in other V4 countries. The high innovative poten-
tial of the BT industry faces priority risks under these
policy suggestions and thus would lose the chance to
contribute efficiently to the development of the CEE
region. Opportunity to increase the cooperation in RD&I
could be based on the establishment of high-tech net-
works which would include companies and clusters
that would span the whole CEE region.
Regarding education in BT, despite the existence of
several specialization programs, there is still a need to
further develop the educational structure offering
through inter-university cooperation, better coordin-
ation, as well as the involvement of Slovak universities
in Pan-European educational programs. At the same
time, entrepreneurship education remains in
great demand.
Conclusions
The CEE countries have significantly contributed to the
foundations of early biological discoveries such as
Gregor Mendel’s work in establishing the Principles of
Inheritance in the 1860s, have made further significant
scientific contributions, and have been at the forefront
of innovative industry establishment in the region. The
CEE countries, Moreover, the CEE countries have a trad-
ition of using yeast for fermentation processes in bread,
beer, and wine, which continues to be uninterrupted
through the centuries until today.
The birth of modern BT led to the almost immediate
realization of the commercial potential of genetic
engineering. During this early period of BT, work in this
domain was mainly restricted to the academic settings
within the CEE countries, and had a slower start, as for-
profit companies were only realizable in the period
after 1989. Some countries, such as Hungary progressed
more rapidly, as the gradual introduction of “market-
oriented economy”proceeded prior to the fall of the
centrally planned economy [13]. This may explain the
relative abundance of profitable private sector BT firms.
Over the last EU framework funding periods, much cap-
ital has been allocated to the CEE countries to assist
building R&I infrastructures, resulting in some of the
most advanced science facilities from an instrumenta-
tion perspective [47]. With subsequent introduction of
the RIS3 formulation, a sharpening of the focus of R&D
efforts to align with innovative enterprises has been
required. A key to improving the utilization of structural
funds has been in the access and absorption of funds
from Horizon 2020 through synergistic activities (Figure
6). Although to differing degrees, all four member-
states are participants in Horizon 2020, their overall
involvement still needs optimization to compete with
the advanced original EU member states. At the same
time, the preparatory phase of EU Framework
Programme would require a deeper involvement of
institutions from CEE countries.
In general, the overall gap between the functioning
of the academic and research environments, with that
of the profitable private sector BT companies is a
0
100
200
300
400
500
600
700
800
900
1000
0
20
40
60
80
100
120
CZ H PL SR
The number of parcipants
EU contribuon [€ mil.]
EU contribuon [€ mil.]
The number of parcipants
Figure 6. The comparison of the financial contribution of R&D
from Horizon 2020 and the number of participants for coun-
tries of V4 [50].
CRITICAL REVIEWS IN BIOTECHNOLOGY 19

challenge. The introduction of innovation-oriented BT
training programs will help to bridge this divide, as
many research centers have state-of-the-art facilities.
However, these research programs could be greatly
aided by an exchange of personnel and ideas from
both introducing industrial scientists into the academic
setting and also having students exposed to intellec-
tually challenging problems originating from mar-
ket demand.
The full developmental cycle of BT from research dis-
covery to commercialization remains fragmented for
much of the CEE. However, entrepreneurial business
experience in V4 countries is gaining momentum from
within the information technology sector, which has
shorter cycles to profitability. A comparison of public
R&D expenditure, venture capital, private sector invest-
ment within different European countries, and its rela-
tive levels comparing 2016 with 2010, is shown in
Figure 7. It reveals that financing for RD&I from private
companies may have fluctuated slightly over this
period, but that the extent of venture capital expend-
iture has retrenched in most EU countries other than
Estonia and Finland. The overall gross income from
operating activities, as well as the numbers of persons
employed within the bio-economy of the V4 member
states for the year 2015, is displayed in Figure 8.
The BT sector in CEE, if considered collectively in the
region, could overcome some of its challenges which
are due to scale, but are also working in concert, could
build a critical mass. The combination of cross-national
institutional training both in BT industrial process and
business development would enhance the situation.
Moreover, if a long-term commitment from the national
authorities placed the development of the RIS3 prior-
ities on track for committed target goals of establishing
self-sustaining SMEs, it would certainly boost the BT
sector across the region [46]. Due to the traditionally
strong orientation of CEE countries on agro-sector and
the abundance of biomass, it is also expected that the
green (agro) BT combined with the industrial BT will
boost the biobased industry sector in these countries.
This, –by combining high-end technological solutions
with mass production –might trigger interesting “chain
Figure 7. Comparison of selected European countries by the interactive tool of the European Innovation Scoreboard within
selected indicators such as Public R&D Venture capital and Firm investments (change in performance 2016 to 2010 –performance
relative to EU average in the year 2010 (in %) [2].
0 5000 10000 15000 20000 25000 30000
CZ
H
PL
SK
CZ H PL SK
Gross Income (in k €) 8766 8044 27252 4462
Gross Income (in k €)
0 500 1000 1500 2000 2500 3000
CZ
H
PL
SK
CZ H PL SK
No. of persons (1000s) 376 391 2636 174
No. of persons (in 1000s)
Figure 8. The gross income within the bioeconomy sector (in
thousands of Euro; in k e) from operating activities after
adjusting for operating subsidies and indirect taxes for the V4
member states (CZ, Czech Republic; H, Hungary; PL, Poland;
SK, Slovakia) in 2015. A number of persons (displayed in
1000s) employed by the indicated country in 2015 for the
whole bioeconomy sector [51].
20 M. DETTENHOFER ET AL.

reactions”from both economic and societal points of
view. Considering the current trends in personalized
medicine, an emphasis on genomics has not been
explicitly stated under the RIS3 policy for the V4 coun-
tries. Efforts are, nevertheless, starting within Poland
[48] to develop cohorts of human genomes for analysis,
which will serve as a benchmark for biomedical
research. In addition, both the Czech Republic and
Hungary are initiating pilot projects.
Note
Due to space constraints, it would not have been
possible to perform an exhaustive listing of all biotech-
nology activities and institutions within the above-
named countries. We apologize if not all activities
were included.
Acknowledgments
This paper was prepared as a follow-up of the JRC-
EC–ICGEB–CEI European Workshop “Smart Specialization
Strategy in the field of Biotechnologies in Europe: A
Challenge for Central and Eastern Europe Countries”which
was organized in Bratislava, Slovakia in September 2017 by
University of Ss. Cyril and Methodius in Trnava, Slovakia.
Therefore, the support of international organizations, namely
JRC-EC, ICGEB, and CEI to the workshop is acknowledged.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by Agent
ura na Podporu V
yskumu
aV

yvoja. This work was also supported by the Slovak
Research and Development Agency grants APVV-14–0294,
APVV-14-0393, APVV-15-0111, APVV-16-0088, and APVV-
17-0239.
ORCID
Markus Dettenhofer http://orcid.org/0000-0003-1972-7026
References
[1] Smart Specialisation Platform [Internet]. Seville (Spain):
European Commission, Joint Research Centre. [cited
2018 Jan 25]. Available from: http://s3platform.jrc.ec.
europa.eu/contact
[2] European Commission. European innovation score
board 2017. 2017 [cited 2017 Dec 27]. Available from:
https://ec.europa.eu/growth/industry/innovation/facts-
figures/scoreboards
[3] European Commission. R&D expenditure in the EU
remained stable in 2016 at just over 2% of GDP.
Eurostat –New Releases. 2017 [cited 2018 Jan 1].
Available from: http://ec.europa.eu/eurostat/web/sci-
ence-technology-innovation/publications
[4] Government of the Czech Republic. National research,
development and innovation policy of the Czech
Republic 2016-2020. Praha (CZ): Government of the
Czech Republic (CZ); 2016.
[5] SOTIO [Internet]. Praha (CZ): Sotio, a. s.; [cited 2018
Mar 2]. Available from: http://www.sotio.com/
[6] Kadlecov
aV,B

rezina V, Drbal K, et al.
BioTechnologick
aRo

cenka [The Biotechnology
Report]. Ceske Budejovice (CZ): The South Bohemian
Agency for Support to Innovative Enterprising (CZ);
2012.
[7] Government of the Czech Republic. National research
and innovation strategy for smart specialization of the
Czech Republic (National RIS3 strategy). 2016 [cited
2018 Jan 3]. Available from: http://s3platform.jrc.ec.
europa.eu/documents/20182/223684/CZ_RIS3_201607_
ENG_Final.pdf/8a0ae331-d729-4550-b837-82000a4236cd
[8] Council for Research, Development and Innovation of
the Czech Republic. National priorities of oriented
research, experimental development and innovations.
2012 [cited 2018 Jan 3]. Available from: https://rio.jrc.
ec.europa.eu/en/file/7548/download?token¼1yhTww5T
[9] Bud R. History of “biotechnology”. London: Nature;
1989.
[10] Bud R. Janus-faced biotechnology: an historical per-
spective. Trends Biotechnol. 1989;7:230–233.
[11] Judge LR. Biotechnology: highlights of the science
and law shaping the industry. Santa Clara High
Technol Law J. 2004;20:79–93.
[12] F
ari MG, Kralov
anszky UP. The founding father of
biotechnology: K
aroly (Karl) Ereky. Int J Hortic Sci
Technol. 2006;12:9–12.
[13] Feh
er A. A magyar biotechnol
ogiai szektor bemu-
tat
asa, K€
ulgazdas
agi

Ertekezlet. 2015 [cited 2017
Nov 12]. Available from: http://businesshungary.gov.
hu/download/7/6a/01000/Hungarian%20Biotech%20-
Sector.pdf
[14] T
ark
anyi Z. A biotechnol
ogiai ipar v
allalkoz
oit k
epzik
Debrecenben [The entrepreneurs of the biotechnol-
ogy industry are trained in Debrecen]. Innot
eka
[Internet]. 2014 [cited 2017 Nov 14]. Available from:
http://www.innoteka.hu/cikk/a_biotechnologiai_ipar_
vallalkozoit_kepzik_debrecenben.969.html
[15] ALX Greece. Health care and medical sector. 2016
[cited 2017 Nov 17]. Available from: http://www.alx.
com.gr/en/sectors-of-interest/healthcare-and-biotech
nology
[16] Radosevic S, Walendowski J. The prospective com-
parative analysis of the national Smart Specialization
Strategies in Central Europe. Paper presented at
Networking Workshop on the Smart Specialisation
Cooperation in Central Europe Initiative; 2016
December 8–9; Zagreb, Serbia.
[17] National Innovation Office. National smart specialisa-
tion strategy. 2014 [cited 2017 Nov 14]. Available
from: http://www.nih.gov.hu/strategy/national-smart/
national-smart-specialisation
CRITICAL REVIEWS IN BIOTECHNOLOGY 21

[18] Golya G. Agricultural biotechnology annual –Hungary.
Budapest (HU): Ministry of Agriculture and Rural
Development; 2016. (GAIN Report Number: HU16002).
[19] National Research, Development and Innovation
Office. Hazai klaszterek/Akkredit
alt klaszterek
[Domestic clusters/Accredited clusters]. 2016 [cited
2017 Nov 14]. Available from: http://nkfih.gov.hu/inno-
vacio/klaszterek/hazai-klasztere
[20] Dale A. Feed your appetite for biotech with the top 5
companies in Hungary. Labiotech [Internet]. 2017
[cited 2017 Dec 12]. Available from: https://labiotech.
eu/hungary-top-biotech-solvo/
[21] EuropaBio and Venture Valuation. Biotechnology
report –Biotech in the new EU member states: an
emerging sector. 2009 [cited 2017 Nov 18]. Available
from: http://www.gate2biotech.com/documents/down-
load/4.pdf.
[22] Biopharmaceutiques. Hungary, a leader among young
European biotech players. 2016 [cited 2017 Nov 24].
Available from: http://www.biopharmaceutiques.com/
en/article/125_2124.html
[23] Ministry of Agriculture, Hungary. Together for a GMO-
free agriculture. [cited 2017 Nov 14]. Available from:
http://gmo.kormany.hu/en
[24] Wo
zniak E. The biotechnology sector in science and
research in Wielkopolska Province: the current state
and prospects for the future. Bio Technologia. 2016;1:
41–49.
[25] Wo
zniak E, Twardowski T. The Bioeconomy in Poland
within the context of the European Union.
N Biotechnol. 2018;40:96–102.
[26] Wicki L, Wicka A. Bioeconomy sector in Poland and its
importance in the economy. Econ Sci Rural Dev. 2016;
41:219–228.
[27] Statistics Poland [Internet]. Warsaw (PL): Statistical
Information Centre; [cited 2017 Dec 18]. Available
from: http://stat.gov.pl/
[28] European Commission. Circular Economy Strategy.
2015 [cited 2017 Dec 17]. Available from: http://
ec.europa.eu/environment/circular-economy/index_en.
htm
[29] Twardowski T. Bioeconomy, biotechnology and new
genetic engineering techniques. Modern biotechnol-
ogy-based bioeconomy in circular economy. Opinion
of the Committee of Biotechnology of Polish
Academy of Sciences. Nauka. 2017;4:183–196.
[30] Institute of Plant Protection, National Research
Institute. Specification of plant protection products for
use in ecological agriculture. [cited 2018 Jan 12].
Available from: https://www.ior.poznan.pl
[31] Europe 2020. A strategy for smart, sustainable and
inclusive growth. 2010 [cited 2018 Jan 12]. Available
from: eur-lex.europa.eu/legal-content
[32] Biotechnology in Poland. Business trade point of view.
Business report elaborated in cooperation with NCRD
and Life Science Business Consulting Co. Ltd. #2016
Deloitte Poland.
[33] Miller M, Mroczkowski T, Healy A. Poland’s innovation
strategy: how smart is ‘smart specialisation’? IJTIS.
2014;3:225–248.
[34] Kamie
nski Z. Poland: Towards a RIS3 strategy. Paper
presented at: National Peer Review Workshop; 2014
July 3–4; Dublin, Ireland.
[35] NCRD [Internet]. Warsaw (Pl): National Centre for
Research and Development; [update 2018 Jan 19;
cited 2018 Jan 22]. Available from: http://www.ncbr.
gov.pl
[36] Perspektywy [Internet]. Warszawa (Pl): Perspektywy
Education Foundation; [cited 2018 Jan 12]. Available
from: http://www.perspektywy.pl/
[37] PAIH [Internet]. Warsaw (PL): Polish Investment and
Trade Agency; [cited 2018 Jan 12]. Available from:
http://www.paih.gov.pl/sektory/biotechnologia
[38] Trigon [Internet]. Krakow (PL): Sobieszcuk I. Trigon
Dom Maklerski S.A.; [cited 2018 Jan12]. Available from:
www.trigon.pl
[39] NCN [Internet]. Krakow (PL): National Science Centre;
[cited 2018 Jan 12]. Available from: https://ncn.gov.pl/
finansowanie-nauki/konkursy/typy
[40] Twardowski T. Comments to position paper presented
by Biotechnology Committee of the Polish Academy
of Sciences concerning recent amendments to GMO
legislation in Poland. Nauka. 2015;1:185–188.
[41] Eriksson D, de Andrade E, Bohanec B, et al. Why the
European Union needs a national GMO opt-in mech-
anism? Nat Biotechnol. 2018;36:18–19.
[42] European Innovation Scoreboard [Internet].
Brusseles: European Commission; 2017. [updated 2017
Dec 15; cited 2017 Dec 27]. Available from: http://
ec.europa.eu/growth/industry/innovation/facts-figures/
scoreboards_sk
[43] Stuchl

ık S, Turna J. Current status of biotechnology in
Slovakia. Curr Opin Biotechnol. 2013;24:S14–S18.
[44] Government Council of the Slovak Republic for
Science, Technology and Innovation. Strat
egia
v
yskumu a v
yvoja v Slovenskej republike do roku
2020 v oblasti: Biomedic

ına a Biotechnol
ogia [The
strategy of research and development in the Slovak
Republic by 2020 in the field: Biomedicine and
Biotechnology]. 2013 [cited 2018 Jan 5]. Available
from: https://www.vedatechnika.sk/SK/VedaATechnika
VSR/Rada%20vldy/Rokovanie%20vlady%20SR%2024.
%209.%202013/PO%20Biomed%20Biotech/Prioritna
%20oblast%20Biomedicina%20a%20Biotechnologia-
%20-%20MZ.pdf
[45] Miertus S. The report of the JRC-EC –CEI –ICGEB
European Workshop “Smart Specialization Strategy in
the Field of Biotechnologies in Europe: A Challenge
for CEE Countries”. University of SS. Cyril and
Methodius in Trnava, 2017 [cited 2017 Oct 30].
Available from: https://www.ris3-eu-biotech-workshop-
2017.eu/final-report/
[46] Deputy Prime Ministers Office for Investments and
Informatization of the Slovak Republic, Ministry of
Education, Science, Research and Sport of the Slovak
Republic, Ministry of Economy of the Slovak Republic,
Government Office of the Slovak Republic.
Implementation plan. Research and Innovation
Strategy for Smart Specialisation of the Slovak
Republic. 2017 [cited 2018 Jan 5]. Available from:
https://www.opvai.sk/media/98686/implementation-
plan_eng_final_ec.pdf
22 M. DETTENHOFER ET AL.

[47] KPMG. EU Funds in Central and Eastern Europe:
Progress Report 2007–2015. 2016. [cited 2018 Mar5].
Available from: https://assets.kpmg.com/content/dam/
kpmg/pdf/2016/06/EU-Funds-in-Central-and-Eastern-
Europe.pdf
[48] European Centre for Bioinformatics and Genomics
[Internet]. Pozna
n (PL): Institute of Computing
Science, Poznan University of Technology; [cited 2018
Jul 25]. Available from: http://ecbig.pl/
[49] European Patent Office [Internet]. Munich: European
Patent Office; 2017 [cited 2017 Nov 16]. Available
from: http://www.epo.org/about-us/annual-reports-sta-
tistics/statistics
[50] Pastorek J. RIS3 in Slovakia. Current state and rele-
vance to biotechnology. Paper presented at: JRC-EC –
CEI –ICGEB European Workshop “Smart Specialization
Strategy in the Field of Biotechnologies in Europe: A
Challenge for CEE Countries; 2017 September 4–6;
Bratislava, Slovakia.
[51] Bioeconomy Knowledge Centre [Internet]. European
Commission, Joint Research Centre; [cited 2018 Jul
25]. Available from: https://biobs.jrc.ec.europa.eu