Newsletter_56

56 WINTER 2019
NEWSLETTER
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Göttingen Minipigs in Embryofoetal Development
Toxicology page 3
Thinking out of the box to deliver improved animal
welfare and a better working environment page 6
Flashback on a magnificent year of celebrating
The First 50 Years with Göttingen Minipigs page 10
Congratulations to 10 Göttingen Minipigs Ambassadors! page 12
50 Years with Göttingen Minipigs celebrated in the USA page 13
New scientific publications on Göttingen Minipigs page 14
The 14th Minipig Research Forum 2020 page 15
See where you can meet us, Spring 2020 page 16
1969-2019
GÖTTINGEN MINIPIGS
50
We enable development
of safer and more effective
medicines

Dear
Reader
As Christmas and New Year approaches, it
is natural to look back at the year that has
passed – and what a memorable year it has
been, with the celebration of 50 years with
Göttingen Minipigs.
We have been celebrating the anniversary internally at Ellegaard
Göttingen Minipigs, and externally almost all over the globe.
Our internal celebration culminated at a teambuilding event
at Lykkesholm Castle focusing on our company values (animal
welfare, quality, respect and collaboration) combined with Hans
Christian Andersen’s fairy tales. This proved the dedicated team
spirit, which truly defines the foundation of our company.
The external celebration was manifested through 9 scientific
roadshows in 5 European locations and in Israel, Beijing,
Shanghai and the USA. Almost 1,000 attendees shared their
experiences and discussed advantages of using Göttingen Minipigs
for bio medical research. Additionally, 10 Göttingen Minipigs
Ambassadors were appointed, all devoted to promoting the use
of Göttingen Minipigs in various ways, ranging from housing,
care and welfare to scientific characterization, animal model
development and validation.
During 2019, we also presented a selection of webinars starring
well-known experts within their field of research – an initiative
that will continue in 2020, along with more white papers
and scientific peer-reviewed papers based on our numerous
scientific collaborations.
Our supporting services in our Research Barrier, such as the
development of both diet-induced and “ready-to-go” animals
plus the breeding of genetically modified disease models, will
also continue in 2020 with exciting new projects and partnerships
to be announced – not least as a follow-up to the recently
published paper on NASH inducing diets in Göttingen Minipigs.
Finally, I would like to thank all of you for your support in 2019
and good discussions at the many great networking and social
events. I will be looking forward to meeting many of you again in
2020 – maybe at the Minipig Research Forum (MRF) in Lisbon?
Follow us on !
www.linkedin.com/company/ellegaard-gottingen-minipigs
Follow us on LinkedIn to stay updated on scientific news,
events, webinars, publications and much more – all related
to the use of Göttingen Minipigs in biomedical research.
Happy Holidays and a Happy New Year,
Lars Friis Mikkelsen, CEO
Ellegaard Göttingen Minipigs A/S
CONTENTS
Göttingen Minipigs in Embryofoetal Development
Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . page 3
Thinking out of the box to deliver improved animal
welfare and a better working environment . . . . . . . page 6
Flashback on a magnificent year of celebrating
The First 50 Years with Göttingen Minipigs . . . . . . . page 10
Congratulations to 10 Göttingen Minipigs Ambassadors! . page 12
50 Years with Göttingen Minipigs celebrated in the USA . page 13
New scientific publications on Göttingen Minipigs . . . page 14
The 14th Minipig Research Forum 2020 . . . . . . . . page 15
See where you can meet us, Spring 2020 . . . . . . . . page 16
2

Göttingen Minipigs in Embryofoetal
Development Toxicology
Anette Blak Grossi 1 , Celine Pique 2 , Edward Marsden 2 , Sisse Ellemann-Laursen 1
1
Charles River, Copenhagen
2
Charles River, Lyon
Background data from our first embryofoetal development studies in Göttingen Minipigs were published in 1998 (Damm Jørgensen, K)
and since then several minipig embryofoetal development studies have been completed. In the following, the minipig characteristics will
be discussed together with our experience and some background data from studies performed at Charles River, Copenhagen (former
Citoxlab, Scantox) and Charles River, Lyon.
Species Considerations
In studies for effects on embryofoetal development, two mammalian
species have traditionally been required, one rodent
and one non-rodent species. Because of practicality and a large
amount of historical background data, the predominant rodent
and non-rodent species are the rat and rabbit, respectively. In
some cases, the use of these species is found unsuitable, because
of significant differences in the metabolism and kinetics of a test
item compared to humans, or test item or dose route related
harmful effects on the health of the mother e.g. destroying
effects on the intestinal flora for the rabbit. In such cases, the
microbiologically defined, genetically stable Göttingen Minipig
could be a possible non-rodent alternative. When working with
non-standard species for studies of this nature, a reliable study
design producing robust data is imperative, whilst taking into
consideration the requirements of the guidelines. The ICH S5
and OECD 414 guidelines make clear the study designs.
Placental transfer of compounds is dependent on fat-solubility,
molecular weight, ionizing of compound and presence of transport
systems. Most compounds, such as small molecules, administered
to the pregnant female will cross the placenta. However,
the minipig has a diffuse epitheliochorial placenta, and maternal
immunity is acquired postnatally by immunoglobulins secreted
in the maternal milk and taken up by FcRn mediated active
transport of IgGs over the polarized intestinal barrier.
Despite that FcRn is present in the minipig placenta on the maternal
side and in the fetal intestine, monoclonal antibody therapeutics
are not transferred to the fetuses in pigs as confirmed
in a recent study conducted at our site in Lyon. (Hey, A. et al).
For other therapeutics, such as small molecules, the minipig is a
relevant alternative, which is supported by studies with known
human teratogenic substances like thalidomide, hydroxyurea,
aminopterin, pyrimethamine, ethanol and tretinoin. (Damm
Jørgensen, K.).
Breeding Characteristics
The minipig has several benefits over other non-rodent species
e.g. sexual maturity is reached at approximately 5–6 months
of age, the average gestation length is 115 days, and the litter
size is typically 4–6 piglets in primiparous, and 5–9 piglets in
multi-parous, minipigs. By comparison, the cynomolgus monkey
attains puberty/sexual maturity much later (age 2.5–6 years);
gestation length is about 165 days and, in general, has a single
offspring only. There are also significant ethical issues involved
in using large numbers of non-human primates for reproductive
and juvenile toxicity studies. Whilst the dog (beagle) may also
appear a good alternative for several reasons such as body
weight (approximately 10 kg), gestation length (average of 63
days) and a litter size comparable with that of the minipig, animal
supply in the numbers required for regulatory embryofoetal
development studies is unrealistic due to the long and varying
dioestrus periods.
Practical Aspects of Study Conduct
Oestrus Synchronisation and Mating
A standard GLP embryofoetal study includes 4 groups of 18
primiparous minipigs. Oestrus in the minipig gilts is synchronized
in order to harmonize dosing and allow for staggered start
and manageable necropsy planning.
Regumate® (11mg Altrenogest/animal) added to the morning diet
for at least 18 days is used for oestrus synchronization. Females
are mated over 1-3 days, and maximum three successful matings
are allowed for each female. The day of the first successful
mating is defined as GD 0. The female is usually introduced to
the male two days after cessation of Regumate® treatment.
Oestrus length in minipigs is three days and hindering of successful
mating before the 6th day after cessation of Regumate®
results in tighter synchronization with more than 90% of the
documented GD0 synchronized to the same day after cessation
Background information (Göttingen Minipigs) for embryofoetal studies
• Sexual maturity: 5 months
• Polyoestrus
• Implantation: GD 11
• Closure of the hard palate: GD 35
• Diffuse epitheliochorial placentation
• Cycle length: 21-22 days
• Oestrus length: 3 days
• Gestation length: 114-116 days
Table 1:
Placental Transfer
and Susceptibility
to Teratogens
3

Figure 1 Figure 2
of Regumate® treatment (Figures 1 and 2). Such study setup can
be advantageous in situations where tightly controlled treatment
prior to mating is desired, i.e. when looking at effects on
the unfertilised egg or on other pre-mating parameters.
Study Design
Despite that toxicological and kinetic data from other toxicology
studies in the minipig are often available prior to the embryofoetal
development study, a preliminary study is usually performed
to determine any potential adverse effects on the pregnant sow
and fetuses and to set the dose levels for the main embryofoetal
development study. Blood sampling for toxicokinetics should be
included in the preliminary or main study.
Treatment is performed during organogenesis – gestation day
(GD) 11-35. Between gestation days 11-35, the pregnant minipigs
weigh between 18 and 23 kg and all commonly used dose
routes can be applied.
In preliminary and main embryofoetal studies, caesarean section
is usually performed on GD 60 and GD 110, respectively.
One of the inconveniences of using the minipig for embryofoetal
development studies is the gestation length. Charles River,
Lyon therefore evaluated if study duration and cost could be
optimized without impacting scientific validity by performing
all terminal procedures around mid-gestation (GD 60). At this
stage, minipig fetal size is not too dissimilar to the full-term
rabbit fetus and therefore better suited to fetal processing/
examination compared with at the end of gestation. This work
demonstrated, that time, resources and financial savings can
be made by performing a shortened study design for minipig
embryofoetal development studies with mid-term caesarean
sections and full fetal examinations without detrimental impact
on scientific validity. Morphological defects previously reported
with a known teratogen, pyrimethamine (Hayama, T. et al),
were detected in the fetuses examined at mid-term. In addition,
double staining of the bone and cartilage of the mid-term fetal
skeleton allowed a more refined examination than in specimens
only stained with Alizarin red (Pique, C. et al) (Figure 3).
Study design and standard endpoints are summarised in Table 2.
Figure 3:
Minipig fetus
at GD60 after
double staining
of skeleton.
Background Data
Another draw back from using the minipig in embryofoetal
development studies, which is also mentioned in the ICH guideline
S5R2, is malformation clusters and insufficient historical
background data. However, Charles River´s historical background
database, in conjunction with other studies in Göttingen
Minipigs, add substantial background data on the incidence of
spontaneous external and visceral congenital abnormalities
and provide context to findings in embryofoetal development
studies allowing for a correct evaluation of study-to-study
variability and low incidence findings (Ellemann-Laursen, S. et
al.). Table 3 lists some of the most common variations and malformation
observed in Göttingen Minipigs. Additional data on
variations and malformation are also available from the Charles
River webpage:
https://www.criver.com/products-services/safety-assessment/
toxicology-services/developmental-reproductive-toxicology/
historical-control-data?region=3696
4

Study design in minipig embryofoetal toxicity studies
Preliminary study
Main study
Group size 4-6 (6 is recommended) 18
Treatment GD11-GD35 (organogenesis) GD11-GD 35 (organogenesis)
Dose administration Oral gavage, capsule dosing, subcutaneous injection,
intravenous (VAP) injection
Oral gavage, capsule dosing, subcutaneous injection,
intravenous (VAP) injection
Pregnancy check Ultra-sound scanning between GD25 and GD30 Ultra-sound scanning between GD25 and GD30
Caesarean sectioning GD60 GD60 or GD110
Examination of uterus
and ovaries
Weight uterus & placenta, appearance placenta, no.
of live and dead fetuses, early and late resorptions
and implantations.
Weight uterus and placenta, appearance placenta,
no. of live and dead fetuses, early and late resorptions
and implantations.
Fetal examination External examination: sex, body weight, nose-rumpand
jaw length. (For enhanced preliminary studies:
visceral and skeletal examination with alcian blue
and alizarin red s staining)
External examination: sex, body weight, nose-rumpand
jaw length.
Visceral examination (fresh body dissection and
fixed head in Harrison’s fluid).
Skeletal examination (alcian blue and alizarin red s
staining on GD60 or alizarin red s staining only on
GD110)
Table 2
Site Malformation/variation
Litter
incidence
(%)
Fetal
incidence
(%)
Cranium Flattened head 1.1 0.4
Misshapen head 4.3 0.8
Domed head 4.3 1.2
Face Cleft jaw (upper) 1.1 0.2
Limb Limb hyperflexion 4.3 0.8
Foot Polydactyly 10.8 2.3
Tail Angulated tail 3.2 0.8
Trunk Umbilical hernia 1.1 0.2
Absent anus 1.1 0.2
Scoliosis 2.2 0.4
Heart Misshapen heart 1.1 0.2
Atrium septum defect 2.2 0.4
Ventricular septum defect 6.5 1.2
Truncus
Bicaroticus
Long truncus bicaroticus 1.1 0.2
Absent truncus bicaroticus 18.3 5.4
Pulmonary
trunk
Dilated pulmonary trunk 1.1 0.2
Diaphragm Diaphragmatic hernia 1.1 0.2
Gallbladder
Absent gallbladder 2.2 0.4
Gallbladder
Small gallbladder 4.3 0.8
Kidney Cyst on kidney 1.1 0.2
Testis Small testis 1.1 0.2
Cryptorchidism 20.4 5.8
Table 3:
Polydactyly, ventricular septum defect, absent truncus bicaroticus, absent
or small gallbladder and cryptorchidism (incidences highlighted in red) are
common findings in minipig embryofoetal development studies.
Conclusion
The first embryofoetal development studies in Göttingen
Minipigs were performed more than 20 years ago and since
then a significant amount of experience and background data
have been gathered at Charles River. Minipigs are susceptible
to known teratogens and characteristics such as availability,
polyoestrus and large litter size make the microbiologically
defined, genetically stable Göttingen Minipigs an attractive species
for embryofoetal development studies. The authors believe
that time, resources and financial savings could be made by
performing mid-term caesarean sections with full fetal examinations
according to regulatory requirements without detrimental
impact on scientific validity.
References
1) Damm Jørgensen, K. Minipig in Reproduction Toxicology.
Scand. J. Lab. Anim. Sci. Suppl. 1. 1998. Vol 25
2) Hey, A. et al. “Simulect” as a model compound for assessing
placental transfer of monoclonal antibodies in Minipigs.
Reprod. Toxicol. 2019 Nov. 4 (In Press)
3) Pique, C. et al. A shortened study design for embryo-fetal development
studies in the minipig. Reprod. Toxicol. 80 (2018):
35-43
4) Ellemann-Laursen, S. et al. The incidence of congenital
malformations and variations in Göttingen Minipigs. Reprod.
Toxicol. 64 (2016): 162–168
5) Hayama, T et al. Use of the Goettingen miniature pig for
studying pyrimethamine teratogenesis. Crit Rev Toxicol. 14
(1985): 403-421
5

Thinking out of the box
to deliver improved animal welfare
and a better working environment
Stable design considerations in Novo Nordisk
and AstraZeneca pig research
Lotte Martoft, DVM, PhD, Senior Director, Animal Sciences & Technologies, Clinical Pharmacology and Safety Sciences, R&D, AstraZeneca,
Gothenburg, Sweden and Stine Øvlisen, DVM, PhD, Senior Director, Head of Animal Unit Ganløse & Bioethics, Novo Nordisk
Building a new pig facility for pharmaceutical research is not
without challenges. Details to consider are many and catalogues
from experts with examples are hard to come by. Most material
on stable designs concerns conventional farms. This is in many
aspects relevant, but pen systems specifically designed to accommodate
the needs of pharmaceutical research differ from
industrial farming pen systems.
In a recent talk at the Minipigs Research Forum we were asked
to share our learnings from building and revamping our pig
research facilities. Here, we try to capture the most important
aspects.
Introduction
Besides the building and specific frameworks such as the manure
disposal system and the temperature and air control, it is crucial
that areas relevant for pharmaceutical research are considered
carefully when building a new research facility for pigs. In our
experience a focus on the environment in the stable including
welfare of the animals and the safety and well-being of the staff
will facilitate the research. The key areas to consider are: 1)
regulatory demands, 2) natural pig behaviour, 3) functionality
necessary for specific types of research and 4) safety of the
employees (Figure 1). If these areas are covered in the design, it
will lead to less stressed animals and a better working environment
for the employees; ultimately leading to better data.
In our experience incorporating advanced flexibility into the
pen system design, including smart aids for the research staff, is
what makes it possible to meet all the needs of research when
building a modern well-functioning facility.
Considerations in the early part of the design phase
The diverse nature of the key areas calls for diverse expertise,
specialist knowledge and importantly, experience of the staff.
It is highly recommended to invite technical staff, research
scientists, veterinarians and caretakers to participate in early
brainstorming sessions and to employ their review and ad -
vise during all project phases. The employees working in the
facilities have the best insights and knowledge of what should
be a part of the considerations. Another good way to ensure that
all imaginable constraints are considered and incorporated into
the building project is to tap into the pool of experience found
among peers.
AstraZeneca and Novo Nordisk has collaborated across company
borders for the benefit of the research, the employees working
in the facilities and most certainly for the benefit of the pigs.
The key learnings from the early project phase for both parties
has been:
• Draw on experience and visit your network
• Consider and draw workflows in the facility for safety and
functionality
• Involve caretakers
• Make a model for corrections prior to building a complex
flexible pen system (Figure 2)
Figure 1:
Key factors to
consider at an
early point in the
design process
Regulatory demands
In the early design face, it is important to consider national and
international regulations on laboratory animals and national/
local environmental regulations. Factors such as accessibility
to the facility, air filtering, light and noise levels, temperature,
ventilation, housing demands, animal care and waste handling
are described, and needs to be considered. In Europe space
considerations for housing of pigs/minipigs are described in the
"DIRECTIVE 2010/63/EU" but also national requirements and
local environment requirements must be considered.
In the EU directive the minimum space requirements are
described as is the need for social housing, training and
socialization. The Directive allows for pigs to be confined
in smaller enclosures than outlined for short periods of time
when justified on veterinary or experimental grounds. When
6

Figure 2: A mock-up (left) is a help in designing complex, flexible pen systems (right)
designing a facility, it is crucial that foreseen as well as
un-foreseen needs for single housing versus group housing
are considered. Likewise, the requirements for enrichment,
training and socialization must be considered to ensure that
there is room for these activities and the related equipment/
materials.
Critical to pig housing
In a research setting there is a risk for a constraint of the natural
behaviour of the pigs. But if the design of the pen structures
is well thought through and made flexible it can accommodate
both pig behavioural needs and research needs. The flexible
solution should enable the social and curious nature of the pigs.
This includes adequate space for enrichment in the pens and
functionality of the surrounding areas for daily exercise and
training. Group housing should be the standard but the need
for single housing during studies is frequent and during these
solitary periods, no matter how short, the social needs of the
animals should be accomodated. For individually housed pigs
the flexible stable design should allow the pigs to have visual,
olfactory, and auditory contact with other pigs to prevent social
deprivation (Figure 3).
Pigs are not “pigs” – they are clean animals. They will naturally
rest and sleep in dry nesting areas and defecate furthest away
from where they are fed. If this natural behaviour is thought
into the design, it can facilitate clean and dry space for the pigs
and for ongoing research activities in the pen including clean
environments for possible post-surgical convalescence. Placing
the water access in one end of the pen and hay/bedding in the
other creates a wet-dry environment that stimulates the pigs to
retain this natural separation of the living area.
In their natural environment pigs use their strong snouts for
rooting in the soil. Taking this behaviour into the research
stable pigs will use their snouts to manipulate all loose objects.
This requires a very solid construction of the pen walls, of all
flexible walls and doors and of additional fittings such as water
systems.
Pigs are intelligent, adaptive and highly inquisitive and providing
diverse enrichment is the optimal way to help the pigs
express their natural behaviour including their need to exercise
and root during their awake hours. Access to exercise areas can
vary from custom made outdoor areas to the work areas just
outside the pens or even inside the pens if the space permits.
Exercise can easily become a part of the daily training routines
Figure 3:
Means for visual,
olfactory, snout to
snout and auditory
contact during
periods of single
housing
7

Figure 4: Corridors can be used as exercise areas, and if outdoor access is possible, it will be appreciated by the pigs!
and corridors are easily used for this (Figure 4). Particularly
if this is thought into the design and gates have been placed
strategically throughout the facility to create extra enclosures
in the corridors. The areas outside the pens can also be used for
the training and socialization. Think out of the box!
A variety of items can be used as environmental enrichment, including
food items, durable balls, chains, a broom head attached
to the pen wall or a big cardboard box (Figure 5). The key is the
diversity of the enrichment since curiosity of pigs are satisfied
best by novelty. A frequent rotation of the enrichment items
and limited time with specific items each day will help maintain
the novelty.
Flexible housing of pigs
- Spacing enabling natural pig behaviour
Flexibility, including connectivity between pens and research
infrastructure, is vital for the overall success of the design. The
flexible design of pen walls and doors should permit space for
Figure 5: Environmental enrichment examples: pig fodder popsicle, a tunnel toy, a cardboard box, and a “dry bath”. The latter supports the natural rooting behaviour
– especially if food items such as raisins are hided in the wood chips
8

Figure 6:
A flexible pen for multiple
housing, single housing,
clean space and access
for dosing from
outside the box.
group housing with means for natural socialization with fellow
pigs and at the same time give the possibility for periodic
conversion into a single housing system (Figure 6). The flexible
pen system should also give an option to create a short-term
small research enclosure where employees can reach the pig
from outside of the pen and the pig can remain calm during
dosing and blood sampling, or where the pig can undergo
anaesthesia induction/awakening in a calm local and known
space. Also, in direct conjunction to the small short-term research
enclosure ample space and infrastructure for research
equipment and aids for good and safe work processes should
be considered.
Safe work processes and space and aids for ensuring this is critical
to consider when working with large animals. To support the
lifting of anaesthetized pigs a hoist system should be included
in the construction of the facility. The system needs to be easy
to use and compliant to lifting of animals between home pens
and research areas. It does not need to be specifically designed
for pigs. A system developed for human use can easily be converted
with a hammock refitting to suit pigs of different seizes
(Figure 7).
A well-designed facility creates a better work environment with
reduced noise levels, no or reduced need for physical restraint
and fewer heavy lifts. Making room for exercise and complex
training makes it more fun for both animals and employees.
A flexible design becomes more agile facilitating changes in
research strategies and refined procedures.
Summary
Share design considerations and build flexible pen systems.
It will pave the way for better science, increased safety and
welfare.
The elements to incorporate and factors to consider when designing
a research facility are numerous and ingenuity is a plus.
The optimal way forward is to have welfare, research and safety
aspects incorporated early in the design phase and optimized
by users including mock-ups. Learnings made by peers, and
visits to other facilities helps reduce mistakes and increases the
creativity needed when planning functionality and design of
your facility.
A well-designed research facility has a flexible interior and
levers better science, animal welfare and working environment.
Figure 7: Hoist system made for human healthcare system used for staff safety to lift anaesthetized pig onto examination table.
9

1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
1969-2019
GÖTTINGEN MINIPIGS
50
Flashback on a magnificent year
of celebrating The First 50 Years
with Göttingen Minipigs
By Lars Friis Mikkelsen, CEO, Ellegaard Göttingen Minipigs
It is with great pleasure, pride and indeed
humbleness that I would like to share with you
a flashback on some of the events which have
characterized 2019 as the year of celebration
of The First 50 Years with Göttingen Minipigs.
In 1969, renowned researchers at the Georg-August University in
Göttingen, Germany, succeeded in establishing the first barrier-
bred population of Göttingen Minipigs aimed at developing a
small non-rodent animal model for biomedical research. In 1992,
Lars Ellegaard, the founder of Ellegaard Göttingen Minipigs, entered
into an exclusive license agreement with the University to
breed, develop and sell Göttingen Minipigs world-wide. Twenty
years later, Lars Ellegaard received the Gold Medal of Honor,
Aureus Gottingensis, from the University for his great efforts
and achievements expanding the use of Göttingen Minipigs
for biomedical research! Of course, one of our first celebration
events therefore took place ‘at home’, at our facility in Dalmose,
Denmark, together with our Guests of Honor: Lars and Bodil
Ellegaard.
Global availability of Göttingen Minipigs
means global celebration
Today, Göttingen Minipigs are being used for biomedical
research almost all over the world, available also from our
partners, Marshall BioResources in the US, Oriental Yeast Co.
in Japan and WoojungBio in South Korea. With our recent
expansion efforts into both China and India, those two major
R&D markets will also soon benefit from having access to our
high-quality and genetically well-defined Göttingen Minipigs.
This global approach anchored the planning of our series of
scientific symposia which we have conducted at nine different
locations all over the world. It has been a great recognition, that
so many people have participated in the very successful and
well attended global roadshows, which have included various
scientific topics presented by knowledgeable speakers sharing
their experiences and data using Göttingen Minipigs. In the
update from Marshall BioResources on page 13, you can get a
more detailed idea of the topics of the symposium held in the
USA. In addition to the focus on science, the roadshows were an
excellent opportunity for users of Göttingen Minipigs to network
with fellow researchers, which many benefited from.
9 roadshows 58 speakers
78 presentations ≈ 1.000 participants
10

Webinars: A way of expanding knowledge
on the use of Göttingen Minipigs
As another jubilee activity, we decided to launch a series
of webinars on relevant and exciting topics within the use of
Göttingen Minipigs. A total of three webinars were conducted,
each of which were attended by an impressive number of
people, and it goes without saying, that this particular method
of knowledge sharing will continue, and we look forward to
inviting you to more webinars in the new year: follow us on
LinkedIn to stay updated!
A dream tour for all employees
Of course, we also wanted to celebrate The First 50 Years with
Göttingen Minipigs with our employees, who were invited to a
day of celebration at a beautiful castle only a one-hour drive
from Dalmose. In advance, we had asked all participants to work
together in groups to prepare a short theatrical performance
for their colleagues onsite illustrating our four company values:
Animal Welfare, Quality, Respect and Collaboration matched
with different fairy tales by the famous Danish author, Hans
Christian Andersen. Everybody was blown away by the creativeness
of those performances and was awarded with an enjo yable
and truly great party in the evening!
THANK YOU VERY MUCH!
Finally, on behalf of all of us at Ellegaard Göttingen Minipigs, I
would like to shout out a big and warm thank you to everyone
who have taken part in our year of celebrating The First 50
Years with Göttingen Minipigs! We are truly grateful for all
contributions which have made our jubilee year such a great
success, and we will strive to continue to expand knowledge
about the use of Göttingen Minipigs as a highly relevant large
animal species for biomedical research.
Filipe Nunes,
Associate Principal Specialist Veterinary
at AstraZeneca:
“I was honoured to participate in the 50th Anniversary
celebration in Copenhagen. It was a great day focusing
on leading science on Göttingen Minipigs and an incredible
opportunity to get into contact with other in vivo scientists
across both pharma industry and academia and share our
experiences. Events like these foster the sense
of community among us scientists and allow
successful collaborations to
be established.”
Joanna Harding,
Project Toxicologist at AstraZeneca:
“In May this year, I was lucky enough to be
invited to speak at the London celebration of 50
years of Göttingen Minipigs. The celebration was held at
the beautiful ‘Royal Society’ Building and the presentations
included a range of topics from researchers across the UK.
Ample time was given for networking which lead to many
interesting introductions and discussions. This was a
perfect way to celebrate 50 years of these amazing
animals and their role in research and drug
development.”
Copenhagen, Denmark
London, United Kingdom
Antwerp, Belgium
Kibbutz Lahav, Israel
11

Congratulations to 10
Göttingen Minipigs Ambassadors!
During our year of jubilee celebrating The First 50 Years with
Göttingen Minipigs, we have had the honor and pleasure of
appointing a total of 10 Göttingen Minipigs Ambassadors!
A common characteristic for all Ambassadors is that they
have received the recognition for their high-level international
knowledge-dissemination and promotion of the use
of Göttingen Minipigs in biomedical research.
Additionally, we want to thank the Göttingen Minipigs
Ambassadors once again for their huge and persistent efforts
also in connection with, but certainly not limited to:
• Characterization, validation and development of
Göttingen Minipigs disease models
• Development of an extensive genetic quantification
and breeding program
• Dedication to improve the health and welfare of Göttingen
Minipigs as well as to ensure ‘good practice’ use of
Göttingen Minipigs in biomedical research
Andy Makin was announced Ambassador of Göttingen Minipigs
28 February 2019 in Copenhagen, Denmark
Susanne Mohr was announced
Ambassador of Göttingen
Minipigs 15 October 2019
in Basel, Switzerland
Henner Simianer – Professor of Animal Breeding and Genetics
University of Göttingen, Germany
Andy Makin – CEO
Andrew Makin Preclinical Consulting, Denmark
Hanne Gamst Andersen – Laboratory Animal Veterinarian
Novo Nordisk, Denmark (retired)
Steven van Cruchten – Associate Professor
University of Antwerp, Belgium
Laurence Bishop – Senior Business Development Lead
Sequani Limited, UK
Berit Østergaard Christoffersen – Principal Scientist
Novo Nordisk, Denmark
Laurence Bishop
was announced Ambassador
of Göttingen Minipigs
9 May 2019 in London, UK
Jo Harding - Project Toxicologist
AstraZeneca, UK
Edward Marsden – Associate Director
Charles River Laboratories, France
Susanne Mohr – Senior Toxicology Project Leader
F. Hoffmann-La Roche, Switzerland
Ofer Doron – Managing Director
Institute of Animal Research (Lahav CRO), Israel
Henner Simianer
was announced
Ambassador of
Göttingen Minipigs
19 February 2019 in
Göttingen, Germany
12

50 Years with Göttingen Minipigs
celebrated in the USA
Marshall BioResources was very pleased to collaborate with
Ellegaard Göttingen Minipigs to host the 9th scientific symposium,
this time in the United States. The session was the final
event following a series of symposia held across the world over
the course of 2019, celebrating 50 years with Göttingen Minipigs.
Efficacy is the leading reason why new drugs fail to get to market,
and the symposium began with a presentation highlighting that
minipigs can help bridge the efficacy gap in specific therapeutic
areas given the physiological similarities between minipigs and
humans. This was followed by a section highlighting the ethical
importance of selecting the right models for the right research,
and why the minipig may be advantageous in many ways.
Peter Vestbjerg of Ellegaard Göttingen Minipigs reviewed the
history and development of Göttingen Minipigs from the beginning
and the collaborations that have helped drive the development
of the model. Nicole Navratil from Marshall BioResources
discussed the expansion of Göttingen Minipigs into the United
States, the growth of the Marshall BioResources production facilities,
and services available to researchers in North America.
Michelle Salerno of Marshall BioResources ended the morning
sessions with an overview of minipig behavior and behavioral
management. She also discussed the training and enrichment
program at Marshall BioResources, and opportunities to enhance
minipig welfare.
To demonstrate the translational value of Göttingen Minipigs,
Lars Friis Mikkelsen, CEO of Ellegaard Göttingen Minipigs, kicked
off the afternoon sessions with a discussion about the scientific
value of Göttingen Minipigs as models for human disease and
several advancements in this area. This was followed by a
presentation about an exciting translational minipig model of
human urinary tract infection. Michael Pellizzon of Research
Diets, Inc. offered a comprehensive review of diet induced
minipig models of metabolic disease and the impact of diet on
the research design.
The final sessions transitioned into a focus on the future, and
Troy Arends of Exemplar provided an overview of their plans
to provide transgenic models of disease developed in Göttingen
Minipigs. He stated their ultimate goal is to “change the world by
providing better treatments and therapies.”
In the last session, Patricia Turner of Charles River provided
an overview of their global approach to minipig welfare. She
reminded us not to focus just on our favorite species and focus
on ways we can cultivate a high quality of life for all laboratory
animals, including minipigs.
The day concluded with a networking reception where attendees
could further ask questions and share ideas about the value
of minipig models, and ways to enrich and enhance minipig
welfare.
Patricia Turner of Charles River
on global approach to minipig
welfare.
Michelle Salerno of Marshall
BioResources on minipig behavior
and behavioral management.
Lars Friis Mikkelsen of Ellegaard
Göttingen Minipigs on Göttingen
Minipigs as models for human disease.
13

New scientific publications on Göttingen Minipigs
Ellegaard Göttingen Minipigs gives high priority to collaborative projects that aim to better characterize and validate Göttingen
Minipigs as a translational animal model and which facilitate and refine the use of Göttingen Minipigs in research projects and
safety testing. Please contact us if you have an idea for such a collaborative project. Below is a list of a few recent articles on
Göttingen Minipigs.
• Hey A, Hill M, Calonder C, et al. "Simulect" as a model compound for assessing placental transfer of monoclonal antibodies
in minipigs. Reprod Toxicol. 2019;Nov 4. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31698003
• Viuff BM, Straarup EM, Nowak J, et al. Lipid Embolism in Obese Göttingen Minipigs. Toxicol Pathol. 2019;Oct 23. [Epub ahead
of print] https://www.ncbi.nlm.nih.gov/pubmed/31645215
• Soegaard S, Aarup V, Serup J, et al. High-frequency (20 MHz) high-intensity focused ultrasound system for dermal
intervention: A 12-week local tolerance study in minipigs. Skin Res Technol. 2019;Sep 20. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/31541524
• Paradis FH, Downey AM, Beaudry F, et al. Interspecies Comparison of Control Data from Embryo-Fetal Development Studies
in Sprague-Dawley Rats, New Zealand White Rabbits, and Göttingen Minipigs. Int J Toxicol. 2019;Aug 30. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/31470750
• Negro Silva LF, Li C, de Seadi Pereira PJB, et al. Biochemical and Electroretinographic Characterization of the Minipig Eye in
the Context of Drug Safety Investigations. Int J Toxicol. 2019;38:415-422 https://www.ncbi.nlm.nih.gov/pubmed/31470746
• Bergadano A, Amen EM, Jacobsen B, et al. A minimally-invasive serial cerebrospinal fluid sampling model in conscious
Göttingen minipigs. J Biol Methods. 2019;6(1):e107 https://www.ncbi.nlm.nih.gov/pubmed/31453257
• Eddleston M, Clutton RE, Taylor M, et al. Efficacy of an organophosphorus hydrolase enzyme (OpdA) in human serum
and minipig models of organophosphorus insecticide poisoning. Clin Toxicol (Phila). 2019;Aug 27. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/31452424
• Thompson A, Dunn M, Jefferson RD, et al. Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt
edetate in a porcine model of acute cyanide salt poisoning. Clin Toxicol (Phila). 2019;Aug 7. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/31389254
• Gad SC, Sullivan DW Jr, Mujer CV, Spainhour CB, Crapo JD. Nonclinical Safety and Toxicokinetics of MnTE-2-PyP
(BMX-010), a Topical Agent in Phase 2 Trials for Psoriasis and Atopic Dermatitis. Int J Toxicol. 2019;38:291-302
https://www.ncbi.nlm.nih.gov/pubmed/31333066
• Leonhäuser D, Kranz J, Leidolf R, et al. Expression of components of the urothelial cholinergic system in bladder and
cultivated primary urothelial cells of the pig. BMC Urol. 2019;Jul 9;19(1):62. doi: 10.1186/s12894-019-0495-z.
https://www.ncbi.nlm.nih.gov/pubmed/31288793
• Jones K, Harding J, Makin A, Singh P, Jacobsen B, Mikkelsen LF. Perspectives From the 12th Annual Minipig Research Forum:
Early Inclusion of the Minipig in Safety Assessment Species Selection Should be the Standard Approach. Toxicol Pathol.
2019;47:891-895 https://www.ncbi.nlm.nih.gov/pubmed/31280706
• Sievert KD, Daum L, Maurer S, et al. Urethroplasty performed with an autologous urothelium-vegetated collagen
fleece to treat urethral stricture in the minipig model. World J Urol. 2019;Sep 9. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/31502031
• Rasmussen BS, Sørensen CL, Kurbegovic S, et al. Cell-Enriched Fat Grafting Improves Graft Retention in a Porcine
Model: A Dose-Response Study of Adipose-Derived Stem Cells versus Stromal Vascular Fraction. Plast Reconstr Surg.
2019;144(3):397e-408e https://www.ncbi.nlm.nih.gov/pubmed/31461016
• Soukup P, Maloca P, Altmann B, Festag M, Atzpodien EA, Pot S. Interspecies Variation of Outer Retina and Choriocapillaris
Imaged With Optical Coherence Tomography. Invest Ophthalmol Vis Sci. 2019;60:3332-3342
https://www.ncbi.nlm.nih.gov/pubmed/31370061
• Rupniak NMJ, Katofiasc MA, Marson L, Ricca DJ, Thor KB, Burgard EC. Prokinetic effects of the neurokinin NK2 receptor
agonist [Lys5,MeLeu9,Nle10]-NKA(4-10) on bladder and colorectal activity in minipigs. Neuropeptides. 2019;77:101956
https://www.ncbi.nlm.nih.gov/pubmed/31324387
14

The 14 th
Minipig Research Forum
Join us in:
Lisbon, Portugal
13-15 May 2020
Online registration opens
in December 2019!
Join the 14 th Minipig Research Forum - a unique opportunity for minipig users to meet, discuss and share knowledge and experiences
within all areas of minipig use related to biomedical research. Take part in this 3-day conference packed with scientific lectures, poster
presentations and the opportunity of networking with minipig users from all over the world.
SCIENTIFIC SESSIONS
• Immune System
• Pain: Models and Management
• Nutrition and Metabolism
• Pharmacological Models
• Juvenile and Reproductive Toxicology
BREAKOUT SESSIONS
• Dosing and Sampling (continuing education)
• Training and Monitoring Welfare (continuing education)
• The Ethical Landscape (open forum discussion)
The full scientific program incl. speakers will be available during
February/March 2020.
POSTER SUBMISSION
Every year the best MRF poster is elected and awarded.
Posters with technical content (e.g. tips and tricks) or scientific
content (including data) are accepted. Poster intructions incl. deadline
for submission are available on www.minipigresearchforum.org
The MRF is one of my favorite
conferences: Not too big, great
people and networking
Good mixture of science,
practical topics, animal
welfare and networking/
discussions
My first MRF: loved it totally
and found everything to be
very well organized
PRACTICALITIES
Starts at
Ends at
13 May 2020 (Wednesday)
14:00 hrs CEST
15 May 2020 (Friday)
12:00 hrs CEST
Registration fee Early Bird: €350 (register before 1 April 2020)
Late registration: €400
The registration fee covers welcome lecture, five scientific sessions,
one open session of choice, catering (lunch, coffee and snacks),
get-together Wednesday evening incl. dinner, drinks and network,
event Thursday evening followed by buffet dinner at venue hotel,
and conference material.
Venue
Accommodation
Hotel Iberostar Selection Lisboa
Rua Castilho 64, Lisbon
The venue is located in the heart of the city
and only 15 minutes from the airport.
Rooms can be booked at a special MRF conference
rate of €175/night incl. breakfast. Download
the booking form from our website and email it
to the hotel ASAP.
Alternative accommodation may also be found
in the area.
IMPORTANT NOTICE: Book your accommodation early!
Lisbon is a very popular destination during May. Therefore the
hotel will gradually release the MRF room allotment starting 1st
February 2020, to accommodate the demand.
The MRF is a non-profit organization with more than 500 members worldwide working with minipigs in industry, academia and
regulatory bodies. Participation in the annual MRF conference requires membership (free of charge). Read more and apply for
membership at www.minipigresearchforum.org
15

Meeting Calendar 2020
Name Date Location
SOT and ToxExpo 15-19 March Anaheim, California, USA
AST Congress 23-26 March Edinburgh, Scotland
Minipig Research Forum 13-15 May Lisbon, Portugal
Symposium AFSTAL 27-29 May Marseille, France
AFLAS 22-26 June Chiang-Mai, Thailand
World Congress WC11 23-27 August Maastricht, Holland
EUROTOX 6-9 September Copenhagen, Denmark
SPS Annual Meeting 13-16 September Montréal, Canada
GV-SOLAS 16-18 September Würzburg, Germany
Janssen Juvenile Toxicity Symposium TBA Beerse, Belgium
CALAS TBA TBA
© 2019 Ellegaard Göttingen Minipigs A/S. All rights reserved.
Europe and Asia
Ellegaard Göttingen Minipigs A/S
Sorø Landevej 302,
DK-4261 Dalmose,
Denmark
Tel.: +45 5818 5818
ellegaard@minipigs.dk
North America
Marshall BioResources
North Rose, NY 14516, USA
Tel.: +1 315 587 2295
Fax: +1 315 587 2109
infous@marshallbio.com
Japan & Taiwan
Oriental Yeast Co. Ltd.
3-6-10, Azusawa, Itabashi-ku
Tokyo, 174-8505, Japan
Tel.: +81 3 3968 1192
Fax: +81 3 3968 4863
fbi@oyc.co.jp
Korea
WOOJUNGBIO
B-3F, 145 Gwanggyo-ro,
Yeongtong-gu, Suwon, Korea
Tel.: +82 31 888 9369
Fax: +82 31 888 9368
sjbaek@woojungbio.kr
minipigs.dk
JANNERUP GRAFISK