IAHJ V8 I2

Volume 8 Issue 2

PEER REVIEWED

A Clinical study Proving the Benefits of Feline-Specific Music Through Biometric Data A New Approach to Optimizing Nutrition for Dogs and Cats Innovative Project to Tackle Veterinary Waste Quality Assurance and Remote Site Audits in Veterinary Clinical Field

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CONTENTS 04 FOREWORD TALKING POINT 06 Alltech ONE Ideas Conference for a Planet of Plenty

IAHJ speaks with Dr Mark Lyons of Alltech about the The Alltech ONE Ideas Conference (ONE), recently held virtually. What did attendees experience with the online event?

MANAGING DIRECTOR Mark A. Barker EDITORIAL MANAGER Beatriz Romao beatriz@senglobalcoms.com

WATCH PAGES 08 Animal models for better animal health To make animals healthy and keep them healthy, research sometimes needs to be carried out on these animals – to test whether a vaccine is sufficiently effective in practice or to determine whether sick animals recover after being given a new medicine.

This kind of research for the benefit of animals is carried out using an animal model. The aim is always to improve the health of the farm animals that the tests are conducted on. Erik van Engelen at GD Animal analyses the importance of animal models for better animal health.

RESEARCH AND CIRCULATION Virginia Toteva virginia@senglobalcoms.com DESIGNER Jana Sukenikova www.fanahshapeless.com BUSINESS DEVELOPMENT Jerome D’Souza info@senglobalcoms.com ADMINISTRATOR Jessica Dean-Hill jessica@senglobalcoms.com

10 Gnubiotics gains allowance of patent of microbiome

markers for prediction, identification and treatment

of pet obesity from the European Patent Office Gnubiotics Sciences SA a Swiss biotech company pioneering novel microbiome targeted solutions for humans and companion animals recently announced the allowance from the European Patent Office (EPO) for its patent application 19812838.1 (EPO publication 3695018). Yemi Adesokan at Gnubiotics SA explains how this is a key patent filing covering the microbiomebased prediction, identification, and treatment of feline obesity.

FRONT COVER © istockphoto PUBLISHED BY Senglobal Ltd. J101 Tower Bridge Business Complex London, SE16 4DG Tel: +44 (0) 2045417569 Email: info@senglobalcoms.com www.international-animalhealth.com International Animal Health Journal – ISSN 2752-7697 is published quarterly by Senglobal Ltd.

The opinions and views expressed by the authors in this Journal are not necessarily those of the Editor, Publisher or the Supporting Organisations which appear on the front cover.

Please note that although care is taken in preparation of this publication, the Editor and the Publisher are not responsible for opinions, views and inaccuracies in the articles. Great care is taken with regards to artwork supplied, the Publisher cannot be held responsible for any loss or damage incurred. This publication is protected by copyright.

Volume 8 Issue 2 Summer 2021 Senglobal Ltd. www.international-animalhealth.com

IAHJ speaks with Dr. Mark Lyons, president and CEO of Alltech

REGULATORY & MARKETPLACE 12 Why Sustainability is Here to Stay and How to

Integrate it into your Veterinary Practice JP Morgan’s sustainability rating has been downgraded

by Standard Ethics, a sustainability rating agency, from adequate to non-compliant following its involvement in the failed European Super league. Standard Ethics judged both the orientation shown by the football clubs involved in the project and those of the US bank to be contrary to sustainability best practices, which are defined by the agency according to UN, OECD and European Union guidelines, and take into account the interest of the stakeholders. Anthony Chadwick at The Webinar Vet explains the importance of sustainability in the veterinary field.

RESEARCH & DEVELOPMENT

16 Quality Assurance and Remote Site Audits in Veterinary Clinical Field As clinical field studies serve as pivotal data to obtain a marketing authorisation for animal health products, quality requirements are abundant. Regular audits enhance the quality of studies and thus facilitate the International Animal Health Journal 1

CONTENTS review process by the regulatory authorities, by providing confidence in the data integrity of studies. In the past year, the ability to perform physical on-site audits was challenged due to travel restrictions and social distancing rules associated with the COVID-19 pandemic. Subsequently, remote site audits became a well-accepted and convenient alternative to conventional physical on-site audits. Claudia Laskowski and Klaus Hellmann at Klifovet will share some experience on what to consider when planning and conducting remote site audits for veterinary clinical field studies.

20 A clinical study proving the benefits of felinespecific music through biometric data Feline behavioural stress is triggered by their acute sensitivity to sounds in the environment. Cats can hear from 40Hz to 85,000 Hz, which is more than three times higher than human hearing, at 20Hz-20,000Hz. To modify behavioural stress in cats, Janet Marlow, Founder of Pet Acoustics and Dr. Asaf Dagan at PetPace LTD show the benefits of this, calming music has been repeatable and observable since its use for cats starting in 1997. To further understand the calming effects of this music, a study was initiated to analyse the biometrics of cats while listening to the music.

24 Canine Atopic Dermatitis: Skin Barrier Dysfunction and Topical Therapy Canine atopic dermatitis (CAD) is a common, yet challenging chronic, inflammatory skin condition and its complex, multifactorial aetiology means a polymodal therapeutic approach can hold the key to successful long-term management. Conventional treatment choices often involve steroids and/or immunomodulatory drugs, which are known to have deleterious side effects or may be contraindicated. In humans, extensive research has implicated the role of skin barrier dysfunction in the pathogenesis of the disease, hence topical therapy is the mainstay of treatment in human atopic dermatitis (AD) with approximately 75-80% of patients attaining safe and effective relief with topical methods alone. Pippa Coupe at Protexin reviews the evidence for skin barrier dysfunction in CAD and

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summarises the current evidence for the use of topical therapies in the management of the condition.

FOOD & FEED 30 A New Approach to Optimising Nutrition for Dogs and Cats In 2020, caregivers worldwide spent an estimated 96 billion USD (70 billion GBP) on food and treats for their companion animals. Every year brings innovations from industry manufacturers, some following market trends, others seeking to elevate the quality of nutrition for nonhuman family members. But are we providing our dogs and cats with the best nutrition available? Jan Allegretti, author of The Complete Holistic Dog Book: Home Health Care for Our Canine Companions, explores different ways to optimise the nutrition for dogs and cats.

MANUFACTURING 33 Innovative project to tackle veterinary waste Teat sealants, vaccines, antibiotics and drenches are just a handful of the products that result in an array of waste at the end of the veterinary process. The New Zealand animal pharmaceutical industry, rural recycling schemes and associations are tasked with finding a solution following a directive from the government to take responsibility for this waste. Jeff Howe at Agcarm shows how an innovative project for the recycling and responsible disposal of veterinary medicines is underway, involving pharmaceutical manufacturers, recyclers, and the farming community.

INNOVATIONS & TECHNOLOGIES 36 Bringing intelligence to the treatment point Digital monitoring of medical treatments is moving more and more into focus, while new technologies and systems allow collecting treatment information and data easily and securely. Jonas Riess at Henke-Sass, Wolf GmbH intends to provide information about valid reasons for a transition to digital monitoring of treatments and to give an overview of the technologies used.

Volume 8 Issue 2

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FOREWORD Just like the world around us, animal health has undergone transformative change in the 21st century. Animals are receiving better care, medicines are becoming more targeted, and diseases have even been eradicated.

Until recently, this revolution was not as prominent in the animal health world. However, this is quickly changing.

Satellite data predicting disease outbreaks. In late 2006, careful observation of satellite data by a team of researchers (including NASA and WHO) accurately predicted the outbreak of Rift Valley fever in East Africa.

There's no sign that this change will stop soon. Here are some trends that will drive animal agriculture and pet care in the coming years.

Areas with higher rainfall and denser green vegetation were identified as being at greater risk of mosquito-borne disease.

Paired with an analysis of data spanning 60 years, the team uncovered a correlation between the El Nino weather system and outbreaks of the disease. This allowed them to predict the 2006 outbreak, issuing warnings in September, before the first cases started to emerge two months later. This kind of analysis could buy governments and communities precious time in preparing for disease outbreaks and minimise the spread.

Better surveillance of Global Diseases, through portable technologies such as smartphone apps and ‘smart ear tags’ Greater emphasis on animal welfare for both pets and livestock to maintain their health and quality of life.

More treatments are available for all species, such as minor species like fish, to feed our growing appetite for animal proteins.

Change is inevitable across every sector, and veterinary care is no exception. But what does the future have in store for this industry? In all areas, we have moved quite dramatically away from fire engine medicine, which is “I have an ill animal, can you please help?”. We now recognize that preventative healthcare is a key component of overall wellbeing for all animals, large and small.

We have also moved from the idea of general practitioners who periodically refer on to specialists, to having specialists as a key component of the team. Vets are now specialised in equine, companion animal or food production. At the same time, the role and value of the pet as a family member has grown, and this will continue, particularly in the developing world.

We all recognize from a One Health perspective that pets are not only an important part of the family, but they are also an important part of the emotional wellbeing of that family. Pets are now being considered as therapeutics. It’s been shown that people with pets respond better after cardiovascular surgery, for example. People have a role to play in looking after the animals that look after them. The primary message is to take care of one another, especially from a preventative healthcare point of view.

‘Big data’ has been a hot buzzword in human healthcare for years. As computers and applications become more powerful, we’re able to analyse reams of data and discover new insights into disease. We’re monitoring, controlling, and treating diseases more effectively than ever before.

Wearable technologies are playing an increasing role in disease prevention by alerting farmers to the early warning signs of outbreaks. Tracking devices such as ear tags and biosensors can offer real-time data on an animal’s vital signs, as well as behaviour, movement and feeding and watering habits – all potential markers for disease.

Smartphone technology has enabled farmers, health workers and veterinarians in Uganda to report early signs of outbreaks and improve their collective response to threats.

In this issue of IAHJ, we bring you a portfolio of articles that defines our changing industry, and how to effectively harness these changes.

Erik van Engelen at GD Animal analyses the importance of animal models for better animal health.

Anthony Chadwick at The Webinar Vet explains Why Sustainability is Here to Stay and How to Integrate it into your Veterinary Practice.

Claudia Laskowski and Klaus Hellmann at Klifovet will share some experience on what to consider when planning and conducting remote site audits for veterinary clinical field studies, and Jan Allegretti, author of The Complete Holistic Dog Book: Home Health Care for Our Canine Companions, explores different ways to optimise the nutrition for dogs and cats.

I hope you all enjoy reading this edition, and my team and I look forward to bringing you more innovative articles in the autumn issue.

Kevin Woodword, Managing Director, KNW Animal Health Consulting

EDITORIAL ADVISORY BOARD Germán W. Graff - Principal, Graff Global Ltd Fereshteh Barei - Health Economist & Strategy Advisor, Founder of BioNowin Santé Avenue Association Carel du Marchie Sarvaas Executive Director Health For Animals Kimberly H. Chappell - Senior Research Scientist & Companion Animal Product Development Elanco Animal Health Dr. Sam Al-Murrani - Chief Executive Officer Babylon Bioconsulting & Managing Director at Bimini LLC Sven Buckingham - Buckingham QA Consultancy Ltd. Dan Peizer - Director Animal Health at Catalent Pharma Solutions Dawn Howard - Chief Executive of the National Office of Animal Health (NOAH) Jean Szkotnicki - President of the Canadian Animal Health Institute (CAHI) Dr. Kevin Woodward - Managing Director KNW Animal Health Consulting Norbert Mencke - VP Global Communications & Public Affairs Bayer Animal Health GmbH 4 International Animal Health Journal

Volume 8 Issue 2

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TALKING POINT

Alltech ONE Ideas Conference for a Planet of Plenty IAHJ speaks with Dr. Mark Lyons, president and CEO of Alltech

Q: The Alltech ONE Ideas Conference (ONE) was recently held virtually. What did attendees experience with the online event?

A: Every year during the ONE, we explore innovative solutions through the lens of technology, uncovering opportunities amid industry disruptions. So, pivoting the conference itself to a virtual experience reflects that spirit. As our flagship event, we wanted to create a unique experience for our customers and colleagues around the world, so even though we were not able to meet in-person, we could still connect, share ideas and be inspired.

We offered attendees a unique virtual experience on a new platform that was created by our team this past year.

This platform included keynote presentations streaming each day, live workshops, the Alltech Ideas Hub, which is our 3D exhibit hall, as well as networking opportunities that allowed attendees to interact with peers from around the world. We also feature presentations across 11 focus tracks that explore opportunities in dairy, beef, business, aqua, crop science, equine, health & wellness, academic, pet, pig, and poultry sectors. Altogether, more than 70 presentations from renowned experts are available through on-demand videos and on our ONE podcast for listening on the go. The content offers a convenient and customisable experience for attendees and will be available for them to watch — and rewatch — until April 2022.

We recognize that many people are experiencing virtual fatigue or have responsibilities away from their desk, so we have made ONE’s ideas and inspiration more accessible than ever. While we offered several live, interactive features for attendees to join at a designated time during the conference, all presentations will also be available on-demand so that registrants can watch when it’s convenient for them. Also, if sitting down to watch videos isn’t practical, registrants can listen to presentations on-the-go with downloadable audio versions, like a podcast.

Q: As the ONE conference took place over three days, tell us about the journey and the focus of each day?

A: On the opening day, we focused on the way we look at the world; exploring if we are really seeing the facts as they are, or if are we being controlled by instincts so innate to being human that sometimes we change the perceptions we have of reality into something different. We were thinking about the way we look at the world and looking for the good — making sure that we are thinking from different perspectives. Anna Rosling Rönnlund, co-author of “Factfullness,” joined us to explore the misconceptions that often shape our perceptions and methods for developing a more realistic worldview.

One of our other opening keynote speakers was Dewitt Jones, a professional photographer, filmmaker and former photojournalist for National Geographic. He has made a career of storytelling through images and has traveled the 6 International Animal Health Journal

world on a mission to find the extraordinary in the ordinary.

Through his compelling stories and captivating photography, he shared how changing your lens can change your life and help you to celebrate what’s right in the world.

On the second day, we took a virtual trip around the world to explore the challenges we all share, that often have varying outcomes and many possible solutions.

David McWilliams, a leading economist and professor, discussed the need to embrace long-term legacy thinking that will lead to healthier people, healthier societies and a healthier planet.

Dr. Ruth Oniang’o, board chair of the Sasakawa Africa Association, discussed how we can address food insecurity through inclusion, education and partnerships.

On day three, we began asking, “What are the ideas that we can take from ONE and apply to our future?” It starts with taking ownership of our actions as individuals.

Shirzad Chamine, CEO of Positive Intelligence, shared steps that attendees can take to move from self-sabotage to being mindful in mastering happiness and better performance.

From there, I shared our vision for a Planet of PlentyTM and the significance of collaboration to the next era of agriculture.

Q: There are many presentations and workshops as part of the Alltech ONE Ideas Conference across species and sectors. How do they all tie together?

A: Our program is uniquely designed to give attendees multiple opportunities to delve into their specialty, but to also explore universal themes that unite us all. From science, sustainability and storytelling to health and wellness, we have created a robust resource that resonates with people regardless of their industry or geographical location.

Ultimately, we are all part of the global food supply chain and have a vested interest in protecting the future of the planet we share.

So much of what is taking place during the Alltech ONE Ideas Conference really brings us that aspect of understanding an overall system and thinking across multiple scientific fields. We like to say what gets measured gets done.

This measurement is so critical as we start to think about the development of things like carbon credits, carbon exchanges, and economies that help us to make sure that we're linking up and reducing overall environmental impact.

There is so much that is being developed in terms of new management systems, including ways that we can use filtration to take out methane at source and potentially use this in other agricultural production systems. Manure management, pasture management and all sorts of areas around pasture nutrition help us to get back into that understanding of the microbiome and the importance of seeing all of these things as linked. Utilising the power of Volume 8 Issue 2

TALKING POINT

Dr. Mark Lyons, president and CEO of Alltech, launched the company's vision of Working Together for a Planet of Plenty™ at the Alltech ONE Ideas Conference in 2019.

enzymes is one of the areas I'm particularly excited about as it was the focus of my PhD. These biological catalysts can truly help us in so many ways, not just through improving digestion and feed utilisation – which is an area that we've worked in for years — but also in understanding how the microbiome works in both animal and soils and utilizing beneficial enzymes within these systems.

Alternative fermentation can help us to breakdown waste and create new efficiencies, and we can consider environmental toxins that already exist that can be broken down through enzyme systems.

Much as these scientific systems are interrelated, so are we. Economist David McWilliams presented during ONE and told us that the pandemic has shown us that no one is alone.

No one can isolate themselves. The world is smaller and more interrelated than we ever realised. We are better when we work together, and certainly we can see that we have achieved a huge amount and can keep improving.

Q: What are the major takeaways that you want to share from ONE? A: It's incredible what can be achieved when no one cares who gets the credit. If we work together, I believe our industry will create climate-neutral food. We will continue to be one of those core industries that can sequester carbon, and we will be a big part of the answer to climate change. This is what has led us from our ACE principle into such an optimistic and positive view of the world with our Planet of Plenty initiative.

Planet of Plenty has become more than a mission. It is our purpose. It is our “why.” It's our opportunity to work together to create a planet of abundance. Let's learn from our keynote speakers and celebrate what's right in the world every day. This will immunise us from negativity, granting us www.international-animalhealth.com

new energy and new resilience to push forward, creating a positive contagion as we share this energy with those around us, putting ourselves in the place of most potential, making sure that we can maximise our impact, and free ourselves to realise that there is more than one right answer to the challenges posed to us.

We are in this together, and COVID has reminded us of that fact. We need each other, and we have always needed each other. We could always achieve so much more when we work together. No industry can have a more positive impact on the future of the planet than agriculture. It's the industry that I'm most excited about, and it's a great honor to be working in it. We can nourish the world, while cooling its climate. We can leave not just a footprint, but a legacy.

What an extraordinary opportunity to create a Planet of Plenty.

Dr. Mark Lyons Dr. Mark Lyons grew up in the Alltech business, having traveled with his father and Alltech’s founder, Dr. Pearse Lyons, from a young age to visit customers. With experience working in all regions and nearly all departments – from palletizing bags in production to researching in the lab – he has a deep and uniquely personal knowledge of the company. He received his bachelor’s degree in political science and environmental science in 1999 from the University of Chicago. He received his master’s degree in brewing and distilling in 2001, followed by a Ph.D. in the area of solid state fermentation, at Heriot-Watt University in Edinburgh. Dr. Lyons is fluent in Spanish, Portuguese, French and German, and he has a working knowledge of Mandarin.

International Animal Health Journal 7

WATCH PAGES

Animal Models for Better Animal Health Balancing Between Goal and Used Resources

In order to make animals healthy and keep them healthy, research sometimes needs to be carried out on these animals – to test whether a vaccine is sufficiently effective in practice or to determine whether sick animals recover after being given a new medicine. This kind of research for the benefit of animals is carried out using an animal model. The aim is always to improve the health of the farm animals that the tests are conducted on.

Royal GD has been working with animal models for many years and strives to continuously improve these, because an animal model has to meet many requirements and regulations. Erik Engelen, who is involved in developing animal models at GD, explains: “That makes sense, of course. You only carry out research on animals when there are no valid alternatives or when this is required by law. There are a lot of legal procedures that need to be followed and the animal model has to make a significant contribution to animal health.”

In the Interest of Animals This last point is definitely the case. For example, GD may conduct the statutory research required to guarantee that

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a vaccine or veterinary medicine actually complies with all the necessary quality requirements. The use of good and effective vaccines in the sector prevents animal diseases, and only veterinary medicines that meet strict standards can protect animals against pathogens or help them recover. So we work together to improve animal health, in the interests of animals, their owners and society at large. Information obtained through this kind of research can sometimes also be used to promote animal health in other ways, such as, to make a distinction between viruses that are harmful and less harmful, or to look at which diagnostic tool is the best to make an early correct diagnosis.

Specific Models GD has an excellent international reputation when it comes to applied research, being the link between science and practical applications. “We have a lot of experience within the poultry sector in particular,” says Erik. “But of course there are other species that suffer from particular health problems too.

For example, respiratory problems in calves or post-weaning diarrhoea in piglets come to mind. During the weaning period, a pig’s gastrointestinal tract undergoes huge changes. It has to go from processing easy-to-digest sow’s milk to difficultto-digest solid food. This can cause diarrhoea and health problems. If we can check the effectiveness of veterinary

Volume 8 Issue 2

WATCH PAGES

medicines against these kinds of specific problems in an animal model and improve animal health, that’s obviously brilliant.”

The Three Rs You might wonder whether testing medicines on animals is responsible. In some cases there are other options, according to Erik. “For example, cells, tissues, or lower animals whose level of consciousness is (as yet) less developed, such as larvae and eggs. These kinds of alternatives are used wherever possible but, in the final stages of the development of a medicine, for example, we often do need to look at whether it does in fact also work in the target species. The three Rs always need to be taken into account when using animal models: replacement, refinement and reduction. If possible, we replace animals with other media, we refine the animal models as much as possible and we reduce the number of animals to a minimum. This last point is possible because the conditions are so strictly controlled.”

Final Goal Refinement can be achieved through innovation. “Our laboratories, facilities and equipment are becoming more advanced all the time. At the moment we’re working on biosensors. These deliver knowledge while allowing us to handle the animals less. That’s another great new development within the use of animal models.”

In the end, it all comes down to improving animal health.

That’s the final goal, and that goal has to be in balance with the resources used. If this is the case, you can achieve great www.international-animalhealth.com

results in the field of animal health with an animal model,” concludes Erik van Engelen.

Knowledge and Expertise GD has a lot of knowledge and expertise in the field of animal models, including specific expertise in the areas of animal health, data analysis and the laboratory. GD has a huge range of laboratory tests at its disposal, and is ISO-certified and able to carry out GLP work.

Erik van Engelen After finishing his master degree in biology with focus on the immune system, Erik also succeeded in his studies for becoming a veterinarian.

After some years working as a bovine practitioner, he became a lecturer at the veterinary faculty, teaching physiology. His PhD thesis focused on the calving process of cows, which can be described as an inflammatory process. About ten years ago, Erik started working at the Animal Health Service as an immunologist; however, after some years he changed to bacteriology for which he received the Dutch specialisation. Erik is involved in several studies on detection and characterisation of veterinary important pathogens. This also includes the production and improvement of autologous vaccines, a really promising topic at this moment.

International Animal Health Journal 9

WATCH PAGES

Gnubiotics gains allowance of patent of microbiome markers of pet obesity from the European Patent Office Gnubiotics Sciences SA (Gnubiotics), a Swiss biotech company pioneering novel microbiome targeted solutions for humans and companion animals, recently announced the allowance from the European Patent Office (EPO) for its patent application 19812838.1 (EPO publication 3695018). This is a key patent filing covering the microbiome-based prediction, identification, and treatment of feline obesity.

Gnubiotics has a growing pipeline of microbiome targeted candidates designed for both animals and humans. Beyond its pipeline, the company has also developed REVELAbiome™, a proprietary ultra-high resolution sequencing approach that enables detection and quantitation of bacterial taxonomy up to the strain level.

Bacteria that reside in human and animal guts are called collectively the gut microbiome. These bacteria play a vital role in the digestion of essential nutrients as well as defence against undesirable gut microbes. Imbalances in the microbiome can be correlated to a range of diseases, including obesity.

According to the Association for Pet Obesity Prevention, an estimated 56% of dogs and 60% of cats were overweight or obese in 2018. Excess weight in pets may lead to conditions such as high blood pressure, difficulty breathing, arthritis and joint health issues, as well as a weakened immune system.

“This allowed patent will be the first covering a microbiome-based paradigm to predict, diagnose and treat feline obesity; a major cause of diabetes and chronic kidney disease (CKD) in felines. We believe that early detection and predictive microbiome-based modalities could provide more effective methods for management of chronic diseases in our pets.” commented Dr. Yemi Adesokan, Chief Scientific Officer and Co-Founder of Gnubiotics.

Scientists have long studied the links between the gut microbiome and body weight. However, the specific bacterial species and strains correlated to weight had remained unclear, until this filing.

“Our quest to find these species and strains brought us deep into the microbiome of these felines to gain access into what truly differentiates obese and lean phenotypes.

We are excited that, through this innovation, we can better serve our pets and monitor their weight before it becomes too late. This is a fundamental step in understanding the microbiome in general and a natural progression towards our human applications where we continue to use the same approach to understand and stratify patients.” added Adesokan.

REVELAbiome™, Gnubiotics product based on these novel markers in designed to unlock the immense potential of the microbiome as a predictor of a range of conditions and paves the way for early, new and personalized care options for pets. This allowed patent by the EPO, enables a new standard in animal care.

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Yemi Adesokan Yemi Adesokan is Chief Scientific Officer and Co-Founder at Gnubiotics SA, a Lausanne, Switzerland biotech company pioneering the development of Human Milk Oligosacchrides (HMOs) for infants and adults as well as Animal Milk Oligosaccharides (AMOs) for companion animals. Yemi has been recognized for his innovative and pioneering work with awards such as the Boston Business Journal 40 under 40 award and the MIT Technology Review’s annual list of 35 top global innovators under the age of 35 TR35. Yemi has a PhD in Chemistry from the University of California, Irvine and completed a post-doctoral fellowship in Genetics with George Church at Harvard Medical School.

Volume 8 Issue 2

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International Animal Health Journal 11

RESEARCH AND DEVELOPMENT

Why Sustainability is Here to Stay and How to Integrate it into your Veterinary Practice JP Morgan’s sustainability rating has been downgraded

by Standard Ethics, a sustainability rating agency, from adequate to non-compliant following its involvement in the failed European Super league. Standard Ethics judged both the orientation shown by the football clubs involved in the project and those of the US bank to be contrary to sustainability best practices, which are defined by the agency according to UN, OECD and European Union guidelines, and take into account the interest of the stakeholders. 1 (Guardian, Jasper Jolly 21 April) What has this got to do with sustainability in veterinary practice? It shows that when sustainability rating agencies exist and banks and football teams are bothered about what a sustainability agency thinks, then we know that sustainability is here to stay.

It’s been a long time coming but big businesses and investors are paying a lot more attention to environmental, social and governance data. This became even more obvious when the Business Roundtable lobbying group recently reversed its position, held since 1977, that businesses existed merely to create profit for their shareholders to one where other stakeholders such as the environment, clients, employees and suppliers were also important. It is good to see that corporate greed is being attenuated as more purposecentred people come into investment banks and big business and challenge the status quo. Hopefully this is a genuine attempt to protect the planet and not just greenwashing and represents a sincere desire towards a sustainability and regeneration agenda and a move to a fairer world. Increasing evidence is also coming to light that those businesses that begin the journey to becoming purpose-centred are more likely to be more productive, retain their team better and be more profitable than businesses who only care about profit.2 Many experts now consider that global warming is the biggest existential threat to humankind. This means that more and more money and expertise is being placed into sustainability budgets to try to solve this intractable problem.

It was so important to see that the new president of America made very firm commitments when coming into office and has gone further than expected at the recent G20 summit to reduce greenhouse gases in the USA over the next decade which will be critical to hold temperatures to 2% above preindustrial levels. There are still climate change deniers, but most people accept that the burning of fossil fuels, the use of potent greenhouse gases in air conditioning and fridge units and the cutting down of mature rainforests are contributing to increased environmental temperatures, rising sea levels, erosion of coastlines and increased prevalence of forest fires.

President Biden re-joined the Paris Agreement for climate change when he commenced his presidency after his predecessor withdrew in 2020. The Paris Agreement came into force on November 4th, 2016 and is a landmark event because, for the first time, a binding agreement brings 196 parties into a common cause to combat climate change and adapt to its effects. The Paris Agreement set an ambitious long-term goal to limit global average temperatures to 1.5 degrees centigrade 12 International Animal Health Journal

above pre-industrial levels. This is dependent on the amount of carbon dioxide and other greenhouse gases that are emitted into the environment. At current rate of use, the excess carbon that will be emitted into the atmosphere over the next decade will take us above the 1.5 degrees centigrade target. There is, therefore, a real urgency to cut emissions. This decade is critical to the legacy and the future that is passed onto the next generation which Greta Thunberg represents so eloquently. Whilst governments can make a difference, it is so important that businesses and individuals work hard and creatively to come up with ways to save carbon, reduce plastic use and live more lightly on the planet.

Sustainability focuses on meeting the needs of the present generation without compromising future generations.

The concept of sustainability is composed of three pillars: economic, environmental and social. This is more informally known as profits, people and planet. Deep green activists may talk about saving the planet but not caring for people living in developing countries who actually live much lighter on the planet than the rich west. True sustainability looks for solutions that recognise that all three pillars are important.

However, in the past, profit was put above everything and the environment was not considered in the profit and loss data or the balance sheet.

Companies and individuals must now work towards measuring their own greenhouse gas emissions as well as recycling, eating food that has been sustainably produced and with good welfare standards and decreased use of pesticides and fertilisers. Interestingly, what gets measured can then be managed to improve those key performance indices. Only Sweden measures and reports on its greenhouse gases on a quarterly basis. This close attention to this key metric allows them to work hard on bringing in new strategies to keep the emission number going down. Reporting on these figures annually is a bit like getting accounts annually but not keeping management accounts during the year. It is only at the end of the year that the company finds out if it has done well or not. All rich countries measure their per capita GDP growth on a quarterly basis. It is essential that they begin to measure their greenhouse gas emissions quarterly as well to see how well strategies are working to decrease emissions.

The pandemic has, undoubtedly, increased the strength of the sustainability lobby. Many people have spent more time at home and outside listening to birdsong and falling in love with the natural world. There is much to lose! This means that vets and clients will be thinking more seriously about the environment and sustainability. The pandemic has been a time of great sacrifice and sadness but hopefully, in the future, it will be seen as a time when a reset occurred and people were able to consider what was really important and became more careful how they travel, what they eat, and how they can live more lightly on the planet.

How is it Possible to Integrate these Ideas on Sustainability into Veterinary Practice?

The most important attitude to have when trying to bring sustainability strategies into the veterinary practice is to be passionate about it. Veterinary practices are made up of Volume 8 Issue 2

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caring, passionate teams. Most people working in practice care about animals and the natural world. That energy is important to harness to get a whole team approach.

In a recent webinar by Zoe Halfacree from VetSustain a survey was launched about the presence of green teams in a practice. Only 14% of attendees had a green team in their practice but 65% were thinking of creating one. The idea of developing sustainability as part of a practice’s ethos is still a recent one. If sustainability is just a theoretical idea by the leader of the practice or a passionate employee it is very likely to fail. Team involvement is essential.

Investors in the Environment is a charity encouraging businesses to be more eco-friendly. There are a number of veterinary businesses already accredited including Davies Vet Specialists, The British Veterinary Association and The Webinar Vet. The Investors in the Environment accreditation system is a good framework to start the journey to becoming more sustainable and covers areas such as energy usage, paper usage and waste management. When thinking about sustainability it is sensible to consider the whole veterinary system of the practice and this is where lobbying is also possible.

When considering suppliers, the practice can ask probing questions about the factories where products are manufactured. Do these factories use renewable energy? Is packaging excessive? Are by-products of production disposed of safely? These questions can be asked before the decision is made to supply the product in the practice. www.international-animalhealth.com

Once the products are at the wholesalers, are the employees treated fairly at the company? Has the wholesaler invested in green vehicles to transport the product to the practice? Does the wholesaler take back cardboard from packaging to recycle at their warehouse? How are out-ofdate drugs and consumables destroyed when sent back to the wholesaler?

These questions do take time and may not be possible for every practice, but they encourage suppliers to do their best because they know their clients are watching them closely.

There is also a lot that can be done within the practice. In fact, it is imperative that we do this since Healthcare Without Harm, an environmental charity, has calculated that if global healthcare were classed as a country, it would be the fifth largest carbon emitter in the world. The veterinary profession certainly must play its part to mitigate against this.

There is a massive amount that can be done with veterinary premises and their grounds. If there is room, consider planting trees and a wildflower meadow to capture carbon and encourage insect pollinators. If space allows, a ground source heat pump can be sited and solar panels can be fitted on suitable roof space. A local practice in Bryn has built a new practice using the German Passivhaus system. This creates a very energy-efficient space.3 The Greener Veterinary Practice Sustainability checklist was launched in March 2021 by Vet Sustain, BVA, SPVS and BVNA. Its objectives are to encourage: International Animal Health Journal 13

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2.

3.

4.

Responsible resource use Being sustainable in your operation Using medicines responsibly Sustaining the team

Considering surgical practice can have a big impact on the carbon footprint of the practice. Cloth scrub caps regularly washed can reduce environmental contamination in the operating theatre compared with one-use caps and can also be personalised to help with identification and communications with masks on. Scrubbing up the traditional way can use up to 15 litres of water. In the UK there is plentiful water most of the time but there is also an energy cost to produce this clean water and warm the water up. Alcohol hand preparation is a viable alternative. Stainless steel sterilisation tins are costly to purchase but will last a lifetime and will help to reduce the number of plastic sterilisation pouches. It is also important to consider the use of reusable drapes and surgical gowns over single-use ones.

A recent paper by Vozzola et al. at AORN 2020 suggested that using reusable gowns reduced natural resource consumption by 64% and greenhouse gas emissions by 66% compared with disposable gowns.4 If there are significant amounts of fluids at the operation site then disposable gowns and drapes may be a better alternative because the polypropylene material is more impermeable.

Separating waste correctly is important since as little as 5% of medical plastic is recycled,5 and much of the clinical waste produced by practice is plastic. There is enormous scope for the industry to improve on this. There is a huge problem with plastic pollution. Plastic production is energy-intensive and burning of plastic in incinerators may lead to health problems in people and animals near the incinerators.

Some easy methods to reduce plastic use include reusable sharps bins, changing to Becton Dickinson’s Emerald syringe range that uses 30% less plastic than the average syringe, and purchasing a distilled water maker to replace plastic bottles.

Recycled plastic for protective collars and rubbish bags is another sensible option.

Perhaps among the most serious greenhouse gases used in practice, however, are the gaseous anaesthetics. Nitrous oxide can remain in the atmosphere for over 100 years and is 36 times more potent as a greenhouse gas than carbon dioxide. There are now very good analgesics that can take its place. Isoflurane is also a potent greenhouse gas.6 Low flow anaesthesia using capnography can help to limit this effect.

In the field of large animal practice, we must continue to research how to limit the amount of methane and other greenhouse gases that are emitted by our livestock. Part of the solution seems to be in eating less meat and moving towards more organic, extensive strategies that reduce antimicrobial and anti-parasiticide usage. Recent research has suggested that the addition of small amounts of seaweed can reduce methane production in cattle by over 80%.7 Finally, it is worth every practice developing a travel strategy. Is it possible that people can walk, cycle or use public transport to go to work? Also, there is now lots of online training which can help reduce travel to conferences.

The next ten years are a crucial time in society’s attempts to sustain and regenerate the planet. Everybody must do their part. Veterinary surgeons should be at the vanguard of this movement to utilise their expertise in clinical and agricultural practices.

14 International Animal Health Journal

REFERENCES 1.

https://www.theguardian.com/business/2021/apr/23/jpmorgan-misjudged-football-fans-over-european-superleague 2. Serafeim, G. Social-impact efforts that create real value. Harvard Business Review. 98, 38-48 (2020).

3. https://www.brynvets.co.uk/2020/01/13/how-to-build-apassivhaus-vet-surgery/ 4. Vozzola, E., Overcash, M. and Griffing, E. An Environmental Analysis of Reusable and Disposable Surgical Gowns. AORN. 111, 315-325 (2020).

5. Rizan, C., Mortimer, F., Stancliffe, R. and Bhutta, M.F. Plastics in healthcare: time for a re-evaluation. Journal of the Royal Society of Medicine. 113, 49-53. (2020).

6. Jones, R.S. and West, E. Environmental sustainability in veterinary anaesthesia. Veterinary Anaesthesia and Analgesia. 46, 409420 (2019).

7. Roque, B. M., Venegas, M., Kinley, R.D., de Nys, R., Duarte. T.L., Yang, X. and Kebreab. E. Red seaweed (Asparagopsis taxiformis) supplementation reduces enteric methane by over 80 percent in beef steers. PLoS ONE 16 2021 e0247820. doi.org/10.1371/journal. pone.0247820

Anthony Chadwick Anthony Chadwick, a serial entrepreneur, is the founder and CVO of The Webinar Vet, the largest online veterinary education provider in the world. He is one of the most recognised and respected thought leaders in the UK veterinary sector. Anthony founded The Webinar Vet in 2010, when the word webinar was not in the veterinary dictionary. A vet by trade, whilst at an internet conference he spotted a gap in the market to make veterinary education and training more accessible and affordable, via the medium of webinars. Trailblazers in the industry, the company grew very quickly and now has over 70,000 veterinary professionals accessing the training in over 120 countries. Students currently spend a combined annual total of approximately 200,000 hours a year training on the site.

Volume 8 Issue 2

Naturally more profitable.

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To find out how Orego-Stim can help your business, visit www.anpario.com/orego-stim or email orego-stim@anpario.com www.international-animalhealth.com

International Animal Health Journal 15

RESEARCH AND DEVELOPMENT

Quality Assurance and Remote Site Audits in Veterinary Clinical Field Studies As clinical field studies serve as pivotal data to obtain a marketing authorisation for animal health products, quality requirements are abundant. Regular audits enhance the quality of studies and thus facilitate the review process by the regulatory authorities, by providing confidence in the data integrity of studies. However in the past year, the ability to perform physical on-site audits was challenged due to travel restrictions and social distancing rules associated with the COVID-19 pandemic.

Subsequently, remote site audits became a wellaccepted and convenient alternative to conventional physical on-site audits. This article will share some experience on what to consider when planning and conducting remote site audits for veterinary clinical field studies.

Introduction As clinical field studies serve as pivotal data to obtain a marketing authorisation for animal health products, clinical studies should meet the required standards and strive for high quality. To understand how high quality may be ensured, it is fundamental to understand what is meant by the term quality.

The ISO Standard1 defines quality as the degree to which a set of inherent characteristics of an object (here – a clinical study) fulfils predefined requirements. To put it more simply, the quality will be good if the characteristics fulfil the requirements, while quality will be poor if requirements are not met.

But who is actually responsible for the quality in a veterinary clinical study? The VICH guideline 9 on GCP2states that the sponsor is and ultimately remains responsible for the quality of a study. Nonetheless, he may delegate his quality assurance duties and functions to another responsible, including independent quality assurance units of a contract research organisation (CRO). To ensure a consistent and high level of quality at all phases of a clinical study, any company – be it the sponsor or CRO – should set up an efficient quality management system to direct, control and coordinate quality, including the aspects of the classical quality circle: quality planning, quality control, quality assurance and finally quality improvement measures. In addition, all participants in a clinical study are encouraged to adopt and adhere to relevant quality assurance practices, which should be a fundamental component of sound scientific practice.

In Figure 1, some of the measures which may directly or indirectly influence the quality of a study are detailed. While this list is clearly non-exhaustive, it should sensitise the reader to the fact that quality may be influenced at various stages and by all parties involved in a clinical study. In particular, regular quality control (QC) and quality assurance (QA) measures at different stages of a clinical field study will assure the quality and should finally lead to enhanced quality.

These two terms describe the fundamental procedures by which quality is checked and ensured during a clinical study (please see Box for details).

Audits are typically conducted at specific phases of a clinical study, e.g. before finalisation of the study protocol or study report. In addition, site audits of facilities such as farms, 16 International Animal Health Journal

veterinary practices/clinics, and diagnostic laboratories may be performed during the in-life phase of a clinical study.

In multicentre studies, however, not all sites are usually subject to an audit. Hence, the auditor needs to select the site to be audited using a risk-based approach. Common factors influencing this choice are the experience of the study personnel, the history of deviations of a site, the enrolment rate and thus the criticality for the entire study, the complexity of a study and critical phases of a study. Under certain circumstances, an audit may also be triggered by certain events, such as a high number of reported serious adverse events or deviations, or also if fraud or serious scientific misconduct is suspected. Fortunately, however, triggered audits are rare.

In the past year, the ability to perform physical on-site audits was challenged due to travel restrictions and social distancing rules associated with the COVID-19 pandemic.

Despite not being able to travel, it remained a prerequisite to ensure the safety of animals, their owners and the entire study personnel, while maintaining GCP compliance and integrity of the study data at the same time. Therefore, COVID-19 forced us to reassess and modify common quality assurance practices and extraordinary measures had to be implemented to face the continuously changing epidemiologic situation.

Regulatory agencies reacted fast and published multiple guidance documents both for human and veterinary clinical trials to help manage this challenging situation3,4,5. The majority of these papers, however, are aimed at providing Definitions according to VICH GL9 (GCP) Quality control: “The operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the studyrelated activities have been fulfilled”2. Quality control is a continuous process that checks the quality of each individual operative process and activity by trained and experienced members of the operative team, for example monitors actively participating in the study.

Quality assurance: “A planned and systematic process established to ensure that a study is performed and the data are collected, documented (recorded) and reported in compliance with GCP and the applicable regulatory requirements”2. As opposed to quality control, quality assurance measures are periodic sampling processes conducted by an independent person (not part of the operative team), usually an auditor of the independent quality assurance unit of the CRO or sponsor. These periodic sampling processes are also referred to as audit.

Audit: “A systematic and independent examination of study-related activities and documentation to determine whether the study is properly conducted and whether the data are recorded, analysed and reported accurately according to the study protocol, SOPs, GCP and applicable regulatory requirements”2.

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Figure 1. Factors influencing the quality of a clinical field study. Study outline: Should provide sufficient detail on scope and objectives of the study. Study participants: The selection should be based on qualification, availability and experience in clinical studies / target disease. Contractual arrangements: Limited financial resources for monitoring or QA measures may decrease the chances of discovering non-compliances. Kickoff meeting: Discussion of the individual expectations, roles and responsibilities and definition of the critical phases of a study in order to minimise the study-specific risks. Study protocol: Design should be well-structured, comprehensive and easy to understand in order to avoid amendments and deviations. Training: Each individual involved should be qualified by education, training, and expertise to perform their respective tasks. Monitoring: The experience of a monitor, frequency of monitoring as well as the evaluation of study-specific critical processes should be defined in a monitoring plan to ensure a coordinated and risk-based approach to monitoring. Motivation: Optimal communication between all study participants creates the basis for a good cooperation. The monitor should support and motivate the investigator, who in turn should motivate his team and the animal owners. The investigators´ ability to successfully recruit and follow up on patients will have a considerable impact on the quality of a study. Data integrity: Raw data, whether handwritten or electronic, should be attributable, original, accurate, contemporaneous and legible.

information on how to plan, conduct and report a remote site audit. Subsequently, the sponsor, auditor and auditees should reach an agreement on what the process is going to look like in detail, i.e. the scope of the audit, discussions about confidentiality and how information is going to be shared, ways of communication and how the timings of the audit are going to work. Furthermore, it is important to define the roles and responsibilities of each party involved regarding provision of the technology platforms, access to file shares, provision of documentation, responsibility for the organisation of meetings, etc. Selection of the platform(s) used for communication as well as sharing of documentation should be based on the individual requirements of the audit. A simple solution is desired – with the least technical requirements – yet a solution which is reliable, allowing the audit objectives to be met. Moreover, the option should be secure, compliant with the general data protection regulation (GDPR), and should compromise neither confidential nor blinded information. Once everything has been discussed and decided (best in writing) it is important to perform a dry run of the technology, so that all parties involved in the audit have the required tools and a comfortable working environment, and are familiar with handling the technology as far as is possible. Once everything is decided, the audit agenda needs to be prepared, which typically takes a bit more time to prepare than for on-site audits. Importantly, the agenda should contain information on the scope, on the audit deliverables and on how the auditor plans to check the individual deliverables remotely. In addition, the agenda should reference critical areas that will be more challenging if it is to be done remotely and that might need revisiting onsite once the restrictions have been lifted.

A large proportion of a remote audit will be covered by the so-called desktop audit, where the majority of the documentation and data that would usually be reviewed on site is now reviewed upfront. On one hand, this will reduce

guidance on the management, conduct and monitoring of clinical studies. Nonetheless, some suggestions and guidance on how auditing should be performed in these unprecedented times is included. The consensus seems to be that on-site audits should be avoided wherever possible and should only be conducted if permitted under national, local and organisational social distancing restrictions. For critical studies, on-site audits may be performed but should be prioritised, reduced or postponed wherever possible using a risk-based approach.

Remote Site Audits Subsequently, remote or virtual site audits became a wellaccepted and convenient alternative to conventional physical on-site audits. In fact, whether an auditor conducts an onsite audit or a remote audit, the intent will essentially be the same: the protocol, SOPs, study documentation and activities need to be independently reviewed and examined and the adequacy of the processes and compliance at all phases of a study needs to be evaluated. In Figure 2, a possible timeline of a remote site audit procedure is depicted, which is similar to a routine on-site audit. However, there are a few important points that need to be taken into account.

Before starting, standard QA policies and procedures may need to be revised and adapted to provide sufficient www.international-animalhealth.com

Figure 2. Timeline of a remote site audit. A) Audit agenda: The auditor agrees on an agenda (scope, deliverables and timing) with the auditees and with the sponsor. B) Desktop audit: The auditor reviews data and study documentation provided by a secure web share upfront to the actual audit. C) Opening meeting: All parties involved in the audit attend a virtual opening meeting using videoconference call. D) Virtual tour: A virtual tour of the premises / facility including observation of study procedures is conducted via videoconference call. E) Interviews: The auditor conducts individual interviews with the study participants (monitor, investigator, examining veterinarian and dispenser) via video conference call. F) Closing meeting: The auditor communicates results and discusses timelines for reporting as well as corrective and preventive actions (CAPA) via videoconference. G) The auditor issues an audit report including possible observations and recommendations. CAPAs have to be implemented by the auditees, as applicable.

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the time that the auditor needs to spend at the site, but will possibly lead to more work for the site upfront. For studies, using electronic data capture (EDC) the auditor may access the data by receiving a read-only login to review the live data and audit trail. For paper-based studies on the other hand, copies, photographs or scans of raw data need to be prepared and sent to the auditor via courier or uploaded to a secure web share. Also, copies of training records, owner consents and diaries, practice records and records to drug accountability may need to be prepared. This will pose a challenge especially for smaller sites, where the personnel and technical infrastructure resources may be limited. Hence, it is advisable to work collaboratively and to find adequate solutions from a cost-benefit point of view. For example, emphasis should be put on the audit deliverables that are critical for the study. Also, best options should be considered to collect some of the required documentation, whether any technical equipment needs to be provided (scanner, web camera) or whether personnel need to be trained on the use of new platforms used during the audit, etc. If certain documentation may not be provided upfront, it may be shown to the auditor via screen-sharing on the day of the audit. Finally, it is important to keep in mind that all copies of the documentation shared with the auditor should be disposed of or archived safely after termination of the audit.

Virtual tours of the premises are probably the point that auditors and auditees are most apprehensive about and 18 International Animal Health Journal

where most challenges may lie. However, using simple technology such as livestreams via smartphone or a web camera, virtual tours do work very well. Importantly, the wi-fi signal and technology should be tested beforehand.

Ideally, the auditor should decide upfront on critical areas and rooms where processes need to be observed. In case of unavailability of wi-fi signal, which can be the case in either geographically unfavourable locations or if thick walls trim off the signal, it is feasible to make use of pre-recorded videos or photographs; however, data protection will need to be considered and may limit certain aspects. Ideally, the auditor will pro-actively guide the auditee with the smartphone through the facility and ask open questions at the same time. Importantly, while planning the virtual tour, the auditor needs to be optimistic about what may be covered, but he also needs to be clear about what is realistic and achievable and what may need to be followed up at a later time point once the COVID-19 restrictions have been lifted.

After the virtual tour (and observation of study procedures), individual interviews with all relevant study participants should be part of such audit, to assess the awareness of study protocol and procedures, knowledge of GCP, and compliance to regulatory and animal welfare requirements. In addition, all applicable documentation should be looked at that was not available during the desktop audit or virtual tour. For studies blinded by personnel, the examining veterinarian and dispenser should be interviewed separately, ideally by using Volume 8 Issue 2

RESEARCH AND DEVELOPMENT different video conference calls and roaming the camera to make sure that blinding is kept. It is important to be aware while planning the interviews that remote audits can be more intense than on-site audits. The audit can be made more pleasant by scheduling short meetings with each participant and by introducing regular breaks. In addition, all parties should be encouraged to use their video to make the audit experience more authentic, as it can be good to see each other; to be able to communicate non-verbally and as it helps to bear trust.

Once the audit has been completed, writing the audit report for a remote audit is not much different from an onsite audit. The audit report will need to list and document the evidence collected to corroborate the auditor´s findings.

In addition, however, the auditor needs to detail how he collected the evidence remotely, if there were any areas that could not be fully audited, limitations in the audit method, if he deems a follow-up audit necessary or not, etc. In other words, there might be a little bit more justification and rationalisation necessary on how the audit was conducted. Finally, once the auditor received the answered report including the corrective and preventive actions, the auditor needs to follow up on the audit findings. Depending on whether all deliverables were verified, the next audit may take place remotely or a followup on-site audit may be necessary as soon as the COVID-19 restrictions have been lifted.

Benefits and Challenges of Remote Site Audits Clearly, remote auditing is associated with various benefits.

Remote site audits allow for social distancing, which is a prerequisite during the current pandemic. Furthermore, global access to audit participants and access to audit information/documentation is facilitated. More flexibility in terms of timing and attendance is another advantage.

For example, it will be easier for sponsor and monitor to participate in audit sessions, even if they are currently located in geographically separate locations. Remote audits are also beneficial, as they may increase the efficiency from a cost, time and resource point of view. The costs associated with travelling and accommodation as well as the environmental impact are reduced. Also, the auditor will spend less time travelling, which, in theory, should result in an increased efficiency as more audits may be conducted in the same period. In addition, the participation time of study participants at the site is also reduced, as the remote audit is primarily focused on a tour of the facility and the individual interviews, since the review of documentation by the auditor has already taken place upfront. But in our experience, it usually turns out to be at least as time-consuming as an on-site audit, considering the required input of all those involved upfront.

On the other hand, remote auditing is associated with diverse challenges. A considerable amount of time is dedicated to discussions with the participants, sponsor, monitor and investigational sites defining requirements for document exchange and access during the remote audit as well as the platforms used for the virtual tour and interviews. Lack of electronic systems, lack of technical infrastructure such as broadband, reliable wi-fi and computer hardware, scanners, copy machine, etc. or lack of resources and personnel who are familiar and confident with hosting electronic meetings might pose a challenge as well. In addition, remote audits require a certain degree of flexibility by the personnel involved. In other words, willingness by the auditees to host the audit and willingness of the auditor to support the auditees. Another common challenging perception is that for remote audits, accessibility to facilities is restricted and thus it might be more difficult www.international-animalhealth.com

to gather objective evidence. Finally, finding a suitable work environment for the time of the audit – essential for both the auditor as well as the auditee – might pose a challenge if working from home.

In conclusion, during the last year we actually have had no choice but to overcome all the challenges and think innovatively in order to qualify suppliers and to perform site audits. But even as we will eventually move out of the current epidemiologic situation with complex test strategies and increasing numbers of COVID-19 vaccinations, the chances are high that remote auditing will become part of the auditing routines in the future as well, based on a benefitrisk approach.

REFERENCES 1.

2.

3.

4.

5.

ISO 9000:2015. Quality management systems - Fundamentals and vocabulary.

VICH-Topic GL9 (GCP). CVMP/VICH/595/98-FINAL, London, 4 July 2000.

Guidance on the Management of Clinical Trials During the COVID-19 (Coronavirus) pandemic (latest Revision, 04 February 2021).

Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency, Guidance for Industry, Investigators, and Institutional Review Boards (latest Revision, 27 January 2021).

Questions and Answers Paper on Regulatory Expectations for Veterinary Medicinal Products (VMPs) during COVID-19 pandemic (latest Revision, 01 July 2020).

Claudia Laskowski Dr. Claudia Laskowski is a qualified auditor in the clinical development of pharmaceuticals and medicinal products (GQMA). Since 2016, Claudia has been heading the independent quality assurance department at Klifovet, dealing with all aspects within the ISO 9001 certified quality management system, covering the GxP aspects for animal health products. Before diving into quality assurance, she worked in scientific research in neurobiology. Her research work focused on understanding the intracellular regulation of nerve growth following traumatic spinal cord injury.

Email: claudia.laskowski@klifovet.com

Klaus Hellmann Dr. Klaus Hellmann is a veterinarian with nearly with 30 years´ experience in the animal health industry. Prior to founding Klifovet in 1997 as a CRO and extending it to a CDMO, he worked in veterinary practice, science and the animal health industry. He is a Board-certified veterinary pharmacologist, Diplomat of the European College of Veterinary Pharmacology and Toxicology, and a trained Quality Manager and Auditor (European Organisation of Quality). As CEO of Klifovet, he acts as consultant on international animal health product development.

Email: klaus.hellmann@klifovet.com

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A Clinical Study Proving The Benefits of Feline-Specific Music Through Biometric Data Abstract

Feline behavioural stress is triggered by their acute sensitivity to sounds in the environment. Cats can hear from 40Hz to 85,000 Hz, which is more than three times higher than human hearing, at 20Hz-20,000Hz. To modify behavioural stress in cats, Janet Marlow, Founder of Pet Acoustics innovated science-based music designed for feline acute hearing. The benefits of this calming music has been repeatable and observable since its use for cats starting in 1997. To further understand the calming effects of this music, a study was initiated to analyse the biometrics of cats while listening to the music. The three-month clinical study monitored nine adult cats measuring their pulse rates, HRV, and activity levels determining the effects of the music. Each cat's vital signs and behaviour patterns were continuously collected in real time wearing a PetPace smart collar. By having a deeper understanding of how feline-specific music diminishes stress in cats on a biometric level can further define its use for feline welfare.

Purpose of Study The clinical study began on 10/7/2020 with the purpose of documenting the biometric effects of feline-specific calming music. Two cat breeders volunteered their multiple cat homes in Southern Australia for the study. The nine adult cats monitored were different breeds, which included Abyssinian, American Shorthair Black Silver Classic Tabby, Domestic mixed, Russian Blue and Selkirk Rex Shorthair. Their ages ranged from two years to twelve years.

Each cat’s vital signs of their pulse, HRV and activity were recorded using a PetPace smart collar for cats.

Pulse, or heart rate, is the measurement of the number of times a pet’s heart beats per minute. Heart rate is one of the most important vital signs caregivers can measure for your pet.

When the heart rate is measured peripherally by palpating or sensing the pulse in a limb, it is called pulse. The job of the heart is to pump blood throughout the body, supplying oxygen to the cells. Your pet’s heart rate is controlled by a sophisticated mechanism that takes into account the oxygen demand from the cells and makes sure the heart is able to provide it. For example, when a dog runs, its muscles work hard and consume a lot of oxygen. Therefore, the heart must work faster to supply the demand. Fear is another condition that is associated with increased heart rate in pets. When a pet (or a human) is afraid, the body gets ready for a fightor-flight situation and prepares for the anticipated increase in demand for oxygen.

Heart rate variability (HRV) is a statistical analysis of the small variations in time intervals between heartbeats. The variations are innate and normal physiological phenomena.

Studies have shown that changes in HRV are associated with a wide range of diseases as well as pain, stress, and obesity.

HRV is recognised as a marker for autonomic nervous system activity. The autonomic (parasympathetic and sympathetic) nervous systems as well as hormonal factors provide the main input to the heart’s pacemaker, and the beat-to-beat interval 20 International Animal Health Journal

variability is a reflection of the balance between these two.

High HRV indicates a good fitness level and a healthy heart and nervous system. Low HRV is associated with stress, pain, heart disease and other pathologies.

Activity score is a calculated value that provides a quantitative representation of a pet's activity during the selected time range. It is based on summarising all the separate activity readings and producing a total value for the pet's overall activity. What is known is that monitoring and analysing activity patterns and levels can provide valuable medical insights. For example, a decline in activity levels may indicate the development of a disease-causing pain or weakness.

Activity is also affected by stress levels, but this effect is more complex. Some cats respond to stress by being restless and vocal, while others respond by freezing and hiding. The study evaluated each cat’s activity levels.

The purpose of this study is to support the hypothesis that Pet Acoustics feline calming music induces a physiological and behavioural calmer state in cats. By measuring the pulse, HRV and activity scores, we can show the physiological and behavioural responses to the music. The nine adult cats were male and female, neutered and not neutered, different breeds and different ages.

Materials and Methods There were two catalysts used for the study: the PetPace smart collar and the Pet Acoustics feline calming music. Each of the nine adult cats wore the PetPace collar over a four-day period. Biometric data was collected by an array of sensors in the collar for twelve to twenty-four hours without the music playing. After this time period, the Pet Acoustics feline calming music was turned on for twelve to twenty-four hours in the area of the collared cat. The music was broadcast from a Volume 8 Issue 2

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Pet Bruce Chelsea Derrick George Leon Nikon Stella Yoda Total

Median Pulse None

158 146 135 131.5 143 136 148 149 143.3

Music

148 138 136.5 129 137 138 154 154 141.8

Median HRV difference

10 8 -1.5 2.5 6 -2 -6 -5 1.5

None

8.97 9.57 9.69 9.72 9.64 9.67 9.38 9.43 9.51

portable Pet Acoustics Pet Tunes speaker which is pre-loaded with the music on a micro SD card. The feline-specific music played continuously until it was turned off. During the listening session, the pulse rate, HRV and activity data was collected.

The data occurred in real time and could be seen on a cloudbased analysis engine program.

The music is specific to the comfort hearing of cats which is within 60 to 80dB. Additionally, the music is modified by frequency content to stay within the frequency levels that do not trigger hypervigilant response. This proprietary process was innovated by Janet Marlow in 1997.

After the first cat’s testing was completed, the collar was removed and placed on the next cat. The same method was done with each of the other eight cats collecting the biometric data every fifteen minutes during the four-day period. Each cat was tested with half of the session with no music playing and then with the music playing.

When the music wasn’t playing, each cat heard and responded to the natural sounds of home life. During the threemonth period, however, there were sounds of workmen and construction in the home and several intense thunderstorms.

One cat travelled in a car in a crate. Within the two homes of the nine cats tested, there were multiple cats and a dog.

Results The pulse rate and the activity were lower as well as the HRV being higher when the cats were exposed to the calming music.

Pulse The pulse rate was lower, and the distribution of results was narrower. The overall median pulse rate was 3.3% lower during times when the cats were exposed to the music (148) compared to times when the cats were not exposed to the music (153). Four of nine cats had a lower median pulse rate during music time. Moreover, the distribution of pulse readings during the music time was lower (range 101-216, delta 115) compared to the non-music times (range 89-232, delta 143).

Each point on the graph indicates a specific pulse measurement made by the collar. By moving the cursor

Music

9.20 9.69 9.76 9.79 9.71 9.76 9.52 9.48 9.61

Median Activity difference

-0.23 -0.13 -0.07 -0.07 -0.07 -0.09 -0.14 -0.05 -0.11

None

43.6 47.4 48.4 44.2 50.0 36.1 40.3 40.5 43.8

Music

40.3 30.0 44.8 39.1 42.0 29.4 31.7 35.4 36.6

difference

3.3 17.4 3.6 5.1 8.0 6.8 8.6 5.2 7.2

over the point, one can see the actual reading and the time it was made. The line is a simple moving average of the pulse readings.

If the pulse rate is too high (tachycardia) or too slow (bradycardia) for the dog or cat’s activity level, an alert will be generated to have your pet examined by a veterinarian.

HRV HRV is higher with music and the distribution of results is narrower. In this study, the overall median HRV was 4.6% higher during times when the cats were exposed to the music (9.48) compared to times when the cats were not exposed to the music (9.06). All cats had a higher median HRV during music time. The distribution of HRV readings during music time was lower (range 8.1-10.36, delta 2.26) compared to the no-music times (range 6.7-10.47, delta 3.77).

Each point on the graph is a statistical analysis of the small variations in time intervals between heartbeats. The variations are innate and normal physiological phenomena. Studies have shown that changes in HRV are associated with a wide range of diseases as well as pain, stress and obesity. High HRV indicates good fitness level and healthy heart and nervous system. Low HRV is associated with stress, pain, heart disease and other pathologies. There is no published reference range for HRV-VVTI. Based on preliminary analysis, we estimate that the following ranges apply for dogs: >11.5 – normal 11.0-11.5 – suspicious <11.0 – likely to indicate a health problem The normal range for cats is not yet completely established.

Values >9.5 are likely a deviation (decrease) from the typical values indicating a possible health problem or stress.

Activity Activity score is a calculated value that provides a quantitative representation of a pet's activity during the selected time range. It is based on summarising all the separate activity readings and producing a total value for the pet's overall activity. The overall median activity score was 8.2% lower during times when the cats were exposed to the music (46.9)

Data of Each Cat Tested Name Bruce Derrick Bennet Stella Yoda Chelsea

Breed Domestic Abyssinian Domestic Domestic Domestic

Leon Harry George Nikon

Abyssinian American Shorthair Selkirk Rex Russian Blue

www.international-animalhealth.com

Age 12y 3m 2y11m 12y 7m 12y4m 11y1m 2y 11m 5y1m 3y 5m 10y 3 m

Weight Collar on 15 10/7/20 10 10/13/20 10 10/23/20 9 11/02/20 12 11/11/20 9 12 7.9 11

11/23/21 1/14/21 1/23/21 1/31/21

Without music 10/7-10/8/20 10/12-10/13/20 10/27-10/28/20 11/4/-11/6/20 11/10-11/11/20

With Music 10/9-10/10/20 10/14-10/17/20 10/29-10/31/20 11/6-11/8/20 11/12-11/14/21

Environment Indoor/Cattery Indoor/Cattery Indoor/Cattery Indoor/Cattery Indoor/Cattery

11/23-11/27/20 1/15-1/16/21 1/23-1/24/21 1/31-2/1/21

11/28-11/29/20 1/18-1/19/21 1/24-1/25/21 2/1-2/2/21

Outdoor/Storms Indoor/Car/StudPen Indoor/Cattery Indoor /Cattery

Neutered/Spayed Yes No Yes Yes Yes

Sex M M F F F

No Yes Yes Yes

M M M M

International Animal Health Journal 21

RESEARCH AND DEVELOPMENT Pulse Rate Chart

HRV Chart

compared to times when the cats were not exposed to the music (51.1). All nine cats had a lower activity score during music time compared to no-music times.

This chart divides the pet’s activity intensity into four levels – resting, low, medium and high activity. Low activity helps identify pain from orthopedic problems, like joint disease, or general health issues causing fatigue and lethargy. High activity may be associated with restlessness, agitation, alertness and discomfort. Monitoring activity is useful when pets are recovering from trauma, surgery or disease, to ensure that they get the rest they need and gradually resume normal activity patterns.

Conclusion The Pet Acoustics music that was tested in this study caused physiological and behavioural changes indicating a calmer state for cats. The activity levels of all the cats tested was lower. The overall pulse rate was lower and the distribution of 22 International Animal Health Journal

the results was narrower. The HRV for all cats was higher with the music and the distribution of the results was narrower.

All these findings supported the hypothesis of a calming effect as a result of the cats listening to the music. The most significant finding was the HRV, which showed a considerable elevation from baseline, even more than what we see with the pulse. HRV was lower when the sympathetic tone (fightor-flight mode) was higher, and vice versa. Therefore, a calm animal should have a higher HRV. Benefits for Feline Welfare The results of the Pet Acoustics study proved that felinespecific music modifies behaviours in cats. The stress scores were significantly lower in cats listening to the music as compared with no music. There were no significant differences when comparing the sex, age or breed of the cats, whether they were neutered or not and whether they were outdoor or indoor cats, all responded positively to the music.

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RESEARCH AND DEVELOPMENT Activity Chart

Janet Marlow

For veterinarians, when listening to the Pet Acoustics feline calming music there is a reduction in stress, which allows the team to conduct better physical examinations and take more accurate vitals. Broadcasting this music in the waiting rooms of veterinary clinics helps to ease the anxiety of waiting cats.

Applications and Benefits • • • • • • • •

Calms behaviours in cat shelters Relieves muscle tension during grooming sessions Masks agitating sounds of thunderstorm and firework events Calms behaviour for breeding and birthing Reduces stress introducing a newly adopted cat Ideal for stress management for postsurgery healing Diminishes crate travel anxiety Lessens nocturnal activity

REFERENCES 1.

2.

www.petacoustics.com https://petpace.com/

www.international-animalhealth.com

Janet Marlow, M.A., Sound Behaviourist, is internationally known as a researcher, composer and author. In 1997, Janet Marlow innovated a science-based method of altering the frequency and decibel levels in designed music that elicits calm behaviour in dogs, cats, horses and birds. By acknowledging acute hearing ranges in each species, music can be altered accordingly, thereby Janet Marlow’s innovation of species-specific music. Results have been clinically proven with repeatable and measurable results over twenty years. Her work on species-specific music has been published in the Journal of Equine Veterinary Science and the International Animal Health Journal. In 2009, she founded Pet Acoustics Inc., an award-winning global brand with multiple species-specific products that have helped thousands of animals worldwide to diminish stress in their living environment for better animal welfare. Janet Marlow was named Woman of Influence in the Pet Industry

by Pet Age Magazine. She has authored books on animal hearing, most recently, What Dogs Hear: Understanding Canine Hearing and Behavior. Janet Marlow's research continues for agricultural swine environments with music published by Dr. Beatriz Zapata, Santiago, Chile entitled “Evaluation of the Behavioral and Productive Effect of Music with Frequency-Modified in Piglets in a Commercial Production System.”

Email: janetmarlow@petacoustics.com

Dr. Asaf Dagan Dr. Asaf Dagan DVM, DABVP, CVA, LLB serves as Chief Veterinary Scientist of PetPace LTD. Dr Dagan is a Diplomate of the American Board of Veterinary Practitioners (ABVP), specialising in canine and feline medicine.

International Animal Health Journal 23

RESEARCH AND DEVELOPMENT

Canine Atopic Dermatitis: Skin Barrier Dysfunction and Topical Therapy Canine atopic dermatitis (CAD) is a common, yet challenging chronic, inflammatory skin condition and its complex, multifactorial aetiology means a polymodal therapeutic approach can hold the key to successful longterm management. Conventional treatment choices often involve steroids and/or immunomodulatory drugs, which are known to have deleterious side-effects or may be contraindicated. In humans, extensive research has implicated the role of skin barrier dysfunction in the pathogenesis of the disease, hence topical therapy is the mainstay of treatment in human atopic dermatitis (AD) with approximately 75-80% of patients attaining safe and effective relief with topical methods alone.1 Given pathogenetic similarities between dogs and humans, the use of topical therapies in CAD management is garnering greater attention within the veterinary community. This article reviews the evidence for skin barrier dysfunction in CAD and summarises the current evidence for the use of topical therapies in the management of the condition.

The Epidermal Skin Barrier The epidermis is the dynamic, self-restoring outermost layer of skin; acting as a protective, waterproof barrier to limit transepidermal water loss (TEWL) and percutaneous penetration of exogenous substances. The predominant epidermal cell type is the keratinocyte, originating in the germinal stratum basale then migrating through several more strata before reaching their terminal position in the stratum corneum (SC).

During this journey keratinocytes evolve into tough, flattened corneocytes via the accumulation of keratin filaments, tightlybound together by the protein filaggrin.2 This process, known as keratinisation (or cornification), produces corneocytes which are perfectly adapted to perform their role as a primary barrier to the external world. Meanwhile, filaggrins undergo enzymatic degradation to produce natural moisturising factor (NMF), contributing to epidermal hydration and skin barrier function.2 Keratinocyte cytoplasmic inclusions, called lamellar bodies (LB), exocytose specific lipids and proteins into the inter-corneocyte space to form the extracellular (EC) lipid matrix.3 Contributing largely to the EC matrix is a family of bioactive lipids known as sphingolipids, with ceramides being the predominant type comprising approximately 50% of the total EC lipid content.4 Fatty acids and cholesterols make up the remainder, and the resulting ratio is important for the maintenance of epidermal permeability barrier function.3,4 Epidermal abnormalities The role of epidermal abnormalities in skin barrier dysfunction has led to the outside-to-inside pathogenetic hypothesis of CAD (Figure 1): Alterations in epidermal proteins such as filaggrin, NMF and antimicrobial peptides (AMPs), along with abnormalities in the EC lipid composition and ultrastructure,5,6 can allow increased transcutaneous penetration of allergens which incites and propagates the inflammatory cycle subsequently resulting in further barrier dysfunction, microbial colonisation and additional sensitisations (i.e. outsideinside-outside).7,8,9 Humans and dogs share a remarkably comparable ceramide profile,10 and due to striking similarities in the pathogenesis, immunological and histological changes, 24 International Animal Health Journal

and clinical distribution of AD, canine models are commonly used for research into human disease.5 Given the limitations commonly encountered in veterinary research, valuable and applicable inter-species comparisons are often made.

Figure 1. The outside-to-inside pathogenesis of canine atopic dermatitis.

Primary skin barrier abnormalities allow exogenous allergens (Ag) to penetrate the stratum corneum (SC) to interact with Langerhan cells (L) and stimulate the adaptive immune response (T-cell, B-cell).

SG=Stratum Granulosum, SB=Stratum Basale, DC=Dendritic Cell, NMF-Natural Moisturising Factor, AMP- Antimicrobial Peptide.

Filaggrin Filaggrin is an epidermal keratin-binding protein essential for effective formation of a functional cornified envelope, and following terminal enzymatic degradation creates hygroscopic NMF’s,11 important for maintaining skin hydration and barrier function.2 Filaggrin reductions have been identified in atopic dogs through immunohistochemical staining,12 although the relevance of this in relation to the severity of clinical signs remains unclear.13 Filaggrin gene mutations (FLG) are well documented in atopic humans and are associated with abnormal epidermal differentiation and proliferation, and increased TEWL.14,15 Approximately 20-30% of humans with AD are carriers of FLG mutations,14 with a similar prevalence in atopic dogs of 22% reported by Chervet et al.

However, abnormalities in filaggrin protein expression were seen in 83% of dogs,15 mirroring findings in atopic humans where filaggrin deficiency was observed irrespective of FLG mutation.16 Not only does this implicate filaggrin deficiency as a key factor in disease development, but indicates that factors other than genotype are instrumental in the filaggrin deficiency seen in AD.14 Inflammation appears to be one of these factors, as multiple in vitro studies have demonstrated downregulation of filaggrin expression following cytokine stimulation.17-19 In vivo, filaggrin and filaggrin-2 reductions have been identified in healthy and sensitised dogs respectively, following allergen challenge.12,20 The relationship between CAD and FLG mutation remains unclear,2 and conflicting results have been reported regarding filaggrin expression in atopic dogs, with upregulation,20,21 no significant change,22 or only breed-specific reductions observed.23 Therefore, a complex interplay of primary genetic mutations, epigenetic changes Volume 8 Issue 2

RESEARCH AND DEVELOPMENT and environmental factors likely affect filaggrin expression and disease development.

Antimicrobial Barrier Cutaneous AMPs have multifaceted roles in skin barrier homeostasis through regulation of the skin microbiome and by forming a crucial part of the innate immune system.24 Decreased microbial diversity and increased relative abundance of certain commensal microbes have been identified in humans with AD.25 Similarly in atopic dogs, superficial pyoderma lesions and skin exposed to allergen challenge demonstrated increases in Staphylococcus spp, particularly S.pseudintermedius, indicating an alteration to the cutaneous microbiota.26,27 One possible mechanism for this alteration is the dysregulated expression and function of AMPs that have been identified in atopic dogs,28 with specific decreases in anti-staphylococcal AMPs in the lesional skin of human AD patients also having been identified.29 Impaired antimicrobial barrier function may explain the increased susceptibility of atopic patients to cutaneous microbial infections, and the isolation of bacteria containing ceramidedegrading enzymes from human AD patients could provide one mechanism whereby the antimicrobial and permeability barriers appear to show interdependence, with a failure in one initiating or exacerbating a failure in the other.30,31 However, a better understanding of the genetic variability and expression of AMPs in normal and disease states in veterinary species is required as much for the current research is in humans.

Extracellular lipids 1. Lipid metabolism and transport The cause of ceramide deficiencies seen in AD is subject to discussion, with many hypotheses pertaining to defects in epidermal lipid metabolism and impaired ceramide homeostasis.32,33 In healthy individuals hydrolysis of sphingomyelin (SM) by the enzyme sphingomyelinase is important for the normal production of ceramides.33 However, enhanced activity of SM deacylase has been identified in lesional and non-lesional skin of human AD patients and through increased competition for their common substrate (SM), ceramide production is reduced and an epidermal deficiency results.32 Furthermore, atopic dogs have shown an epidermal accumulation of a ceramide precursor, glucocerebroside, due to decreased activity of β-glucocerebrosidase, an enzyme important for ceramide production and normal barrier function.34 Lipid-secreting LB’s found within maturing keratinocytes are integral to the formation of the waterproof epidermal barrier through extrusion of their contents into the EC space.36 Although the formation, density and content of LB’s appears normal,35 atopic humans, mice and dogs have all demonstrated an increased number of retained LBs within developing corneocytes of the SC suggesting that some aspect of the exocytosis process is disrupted, resulting in abnormal and decreased lipid secretion.6,35,36 2. Lipid organisation A healthy EC lipid matrix is a densely-packed and highlyordered three-dimensional structure of lipid lamellae.37 Changes in the lamellar organisation has been identified in atopic humans and appears to be strongly associated with an abnormal ceramide composition, increased TEWL and even disease severity.37,38 Whilst evidence in atopic dogs is less abundant, comparable changes in lipid composition and organisation have been observed.10,39–41 Electron microscopy has revealed that at baseline, atopic dogs had focally severe abnormalities in lamellar organisation, with intercellular spaces containing atypical, heterogenous or absent lipid material in disorganised lamellae,41,51 which was further impaired following allergen challenge.6 www.international-animalhealth.com

3.Lipid quantity and composition The major epidermal lipids exist in approximately equimolar amounts and their presence in physiological levels, particularly regarding ceramides, is intrinsically linked to the maintenance of normal skin barrier function.8,42–44 Lipid abnormalities in humans with AD have been well documented, with multiple studies attributing skin barrier dysfunction to altered ceramide profiles, changes in ceramide chain length, and deficiencies in protein-bound ceramides.32,42,45 The normal canine ceramide profile closely resembles that found in humans,10 and similar ceramide reductions in both lesional and non-lesional skin of atopic dogs have been seen.39,43,46 An association with increased TEWL has been observed suggesting such lipid abnormalities result in significant disruption to skin barrier function.44–46 Stahl et al demonstrated that inflammation can further exacerbate ceramide deficiencies in sensitised dogs even in sites distant to the allergic insult. Interestingly, normalisation of ceramide levels was seen once the insult was removed, implying that skin barrier integrity is at least partially impacted by inflammation.47 From a clinical perspective, this is consistent with the self-perpetuating and escalating nature of AD, supporting the importance of therapies which not only control inflammation, but also aid skin barrier repair.

Hence, topical therapies tend to favour a sphingolipid or ceramide-dominant formulation with the aim to correct such deficiencies.48–55 The Evolution of Topical Therapy Following this paradigm shift in our understanding of the pathogenesis of AD towards skin barrier dysfunction, employing an ‘outside-in’ approach could be as revolutionary in CAD as it has been in human AD; topical therapy is considered a first-line treatment for atopic paediatric patients,56 and emollients are a mainstay of treatment in atopic adults.57 Topical therapies are regularly employed in the management of dermatological conditions, however their action has traditionally been to soothe and moisturise the skin, remove debris and grease, or treat antimicrobial infections.58 Sphingolipid-based therapies are one of the most recent advances in the topical management of AD, and therefore form the focus of the following sections which review topical sphingolipids and their potential to reinforce the epidermal barrier and ameliorate clinical signs associated with AD. Effects on visual scores and clinical signs The updated 2015 International Committee on Allergic Diseases of Animals (ICADA) guidelines on the treatment of CAD recognises the place of lipid-based topical formulations due to their success in humans, although acknowledge that further high-quality research is required for CAD. 59 Since 2015, further studies have demonstrated promising results; Marsella et al studied a group of house dust mite (HDM) sensitised atopic beagles experiencing bi-weekly allergen exposure and concurrent treatment with a topical sphingolipid and hyaluronic acid formulation as a monotherapy for 8 weeks. There was a significant reduction in Canine Atopic Dermatitis Extent and Severity Index (CADESI) score after 1 week (Figure 2A) and Pruritis Visual Analogue Score (PVAS) after 8 weeks (Figure 2B) in treated animals compared to the control group,50 confirming findings from earlier research using topical ceramide formulations.49–51 Other studies have failed to report significant differences in similar clinical parameters,60,61 however it is difficult to directly compare these studies due to inconsistencies in the lipid formulation, study design and extraneous variables.

In humans, the success of ceramide-based products in AD management has been widely reported, with evidence supporting improvements in clinical signs, sleep habits, pruritis, quality of life, severity of lesions and TEWL.53–55,62 International Animal Health Journal 25

RESEARCH AND DEVELOPMENT

Figure 2a: CADESI scores in treatment vs control group (Image from Marsella et al. 202048 under license CC-BY 4.0)

research has shown that the type of sphingolipid within a formulation affects its ability to alter epidermal lipid properties, with sphingomyelin(SM) rich lipid extracts appearing to exert greater beneficial effects. SM-rich lipid extracts applied to an in vitro canine skin model significantly increased total ceramide levels, with the most SM-rich extract (SPE-1) significantly increasing 44/99 ceramide metabolites,(Figure 4) whilst electron microscopy revealed increased intercellular lipids and LB’s compared to pre-treatment levels.69 Interestingly, no significant increases were seen in ceramide metabolites with the ceramide-rich extract, suggesting SM can support enhanced endogenous de novo ceramide production. Bearing in mind the positive results demonstrated in vivo,48 SM-rich products could be a potentially exciting advancement in skin barrier repair for CAD, with the role of hyaluronic acid warranting further investigation.

Figure 2b: PVAS scores in treatment vs control group (Image from Marsella et al. 202048 under license CC-BY 4.0)

Drug-sparing effects in humans The drug-sparing effect of topical therapies in humans with AD has been thoroughly established,63,64 although the evidence base is smaller for more recently evolved topical sphingolipid therapies. However, comparative studies have demonstrated the efficacy of ceramide-dominant formulations when evaluated against pharmaceutical agents, with one product achieving an equivalent efficacy to fluticasone (a mid-potency topical steroid) as a sole therapy in reducing disease severity and pruritis in children with moderate to severe AD.54 Another showed equal efficacy to pimecrolimus, a calcineurin inhibitor commonly used to manage human AD.65 Such drugs have been associated with negative effects on skin barrier function through the reduction of numerous ceramide classes, LB secretion, antimicrobial function, and increased TEWL.66,67 Although their potent immunomodulatory action addresses increased inflammatory cycling, prolonged use can contribute to barrier dysfunction.66,67 Concurrent application of a ceramide-containing lipid mixture can mitigate these adverse effects by repairing barrier permeability and the interdependent anti-microbial barrier.31,66 Although this has not yet been studied in dogs, these findings indicate a potential role for topical sphingolipids in facilitating an immunomodulatory drug-sparing effect, in addition to negating the adverse effects of these topical drug classes on both the permeability and antimicrobial skin barrier.

Effects on extracellular lipids The topical application of sphingolipids has been associated with a multifactorial effect on EC lipids: Increased lipid biosynthesis from keratinocytes, intercellular ceramide concentrations, LB extrusion and an improvement in ultrastructural organisation of lipid lamellae (Figure 3) following the application of ceramidebased formulations has been reported.51,52,68 More recently, 26 International Animal Health Journal

Figure 3. A, C: Atopic dogs demonstrate reduced inter-corneocyte spaces filled with highly disorganised lipid lamellae. B, D: Following treatment, increased inter-corneocyte spaces filled with more organized lipid lamellae and an almost normal lipid bilayer. (E) Magnified field from Fig. 3B (Image from Jung et al51 under license CC BY-NC 3.0)

Anti-inflammatory properties of sphingolipids Sphingolipids have many biological functions in cell signalling and intracellular messaging,4 and when applied exogenously may have anti-inflammatory effects: A significant inhibition in the secretion of the pro-inflammatory cytokine PGE2 was demonstrated following application of SM in various concentrations to stimulated canine keratinocytes in vitro (Figure 5).70 PGE2 has been detected in biologically-active levels in human AD skin,71 whilst both lesional and non-lesional skin in atopic dogs have shown increased expression of the enzyme prostaglandin E synthase 1, important for PGE2 synthesis.72 Taken together these findings indicate reduction of PGE2 as a therapeutic goal in AD. Further in vitro studies have demonstrated similar anti-inflammatory effects through the inhibition of nitric oxide (NO) production, cyclooxygenase-2 (COX-2) and tumour necrosis factor- α (TNF-α) expression following treatment with a ceramide mixture,73 even following application of a bacterial lipopolysaccharide.74 Given the evidence for the down-regulation of ceramide levels47,75 and filaggrin expression,16-18 along with ultrastructural alterations6 following inflammatory stimuli, these results may hold major significance in the management of canine inflammatory skin disorders.

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RESEARCH AND DEVELOPMENT

SM Concentration (%) Figure 5. (Image adapted from Cerrato et al70)

Summary Advancing the management of CAD has increasing importance due to the growing popularity of predisposed breeds and rising clinical prevalence. Only relatively recently has the concept of skin barrier dysfunction been recognised, with the outside-to-inside pathogenesis gaining greater traction within the wider veterinary community as a major therapeutic target. In vivo studies have demonstrated the potential for topical sphingolipid-based formulations to improve clinical signs and visual appearance of atopic lesions by reducing PVAS and CADESI scores. In vitro findings support these clinical observations by demonstrating the potential of sphingolipids to restore skin barrier permeability by increasing EC ceramide concentrations, LB extrusion and improving the ultrastructural organisation of lipid lamellae. The potential anti-inflammatory effects of topical sphingolipids indicate a further mechanism in mitigating the role of immunological and inflammatory mediators in the perpetuation of CAD, whether pre-existing or secondary to a fundamentally disrupted skin barrier. Whilst cautious extrapolation of data between species is prudent, it is difficult to ignore the striking similarities in pathogenesis, clinical distribution and immunological patterns seen in humans and dogs, and applicable comparisons between species can be valuable particularly given limitations within veterinary research. As such, topical sphingolipid formulations may be considered a safe, adjunctive therapy in the long-term, multimodal management of CAD. REFERENCES 1.

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Figure 4. Heat map showing lipid profile of different skin lipid metabolites obtained when comparing treatment groups (sphingolipid extracts: SPE-1, SPE-2 and SPE-3) with the control group. Red denotes increased level.

Green denotes decreased level. (Image from Cerrato et al69 under license CC BY-NC-ND 4.0) www.international-animalhealth.com

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Borodzicz S, Rudnicka L, Mirowska-Guzel D, CudnochJedrzejewska A. The role of epidermal sphingolipids in dermatologic diseases. Lipids Health Dis 2016;15:13.

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10. Popa I, Remoue N, Hoang LT, et al. Atopic dermatitis in dogs is associated with a high heterogeneity in the distribution of protein-bound lipids within the stratum corneum. Arch Dermatol Res 2011; 303(6):433-40.

11. Kezic S, Kemperman P, Koster E et al. Loss-of-function mutations in the filaggrin gene lead to reduced level of natural moisturizing factor in the stratum corneum. J Invest Dermatol 2008; 128(8):2117-9.

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13. Marsella R. Does filaggrin expression correlate with severity of clinical signs in dogs with atopic dermatitis? Vet Dermatol 2013; 24:266-e59 14. Thyssen J, Kezic S. Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol 2014; 134(4):792-9.

15. Chervet L, Galichet A, McLean W et al. Missing C-terminal filaggrin expression, NF kappaB activation and hyperproliferation identify the dog as a putative model to study epidermal dysfunction in atopic dermatitis. Exp Dermatol 2010;19(8) 16. Pellerin L, Henry J, Hsu CY et al. Defects of filaggrin-like proteins in both lesional and non-lesional atopic skin. J Allergy Clin Immunol 2013;131(4):1094-102.

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18. Segarra S, Bernard F-X, Flores J, Naiken T. Effects of sphingolipids, glycosaminoglycans, and their combination on in vitro filaggrin expression using reconstructed human epidermis. In: Abstracts of the 30th Annual Congress of the ECVD-ESVD, Dubrovnik, Croatia. Vet Dermatol 2018;29(5):372.

19. Pin D, Pendaries V, Keita Alassane S, et al. Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal Cornification Proteins, Filaggrin, and Corneodesmosin. J Histochem Cytochem 2019; 67(2):85-97.

20. Santoro D, Marsella R, Ahrens K, Graves TK, Bunick D. Altered mRNA and protein expression of filaggrin in the skin of a canine animal model for atopic dermatitis. Vet Dermatol 2013; 24(3):329-36.

21. Theerawatanasirikul S, Sailasuta A, Thanawongnuwech R, Suriyaphol G. Alterations of keratins, involucrin and filaggrin gene expression in canine atopic dermatitis. Res Vet Sci 2012; 93(3):1287–1292.

22. Schamber P, Schwab-Richards R, Bauersachs S, Mueller RS. Gene expression in the skin of dogs sensitized to the house dust mite Dermatophagoides farinae. G3 (Bethesda) 2014; 4(10):1787–1795 23. Roque JB, O'Leary CA, Kyaw-Tanner M, Duffy DL, Shipstone M. Real-time PCR quantification of the canine filaggrin orthologue in the skin of atopic and non-atopic dogs: a pilot study. BMC Res Notes 2011 ;21(4) :554.

24. Leonard BC, Affolter VK, Bevins CL. Antimicrobial peptides: agents of border protection for companion animals. Vet Dermatol 2012; 23(3):177-e36.

25. Bjerre RD, Bandier J, Skov L, Engstrand L, Johansen JD. The role of the skin microbiome in atopic dermatitis: a systematic review. Br J Dermatol 2017;177(5):1272-1278.

26. Older CE, Rodrigues Hoffmann A, Hoover K, Banovic F. Characterization of Cutaneous Bacterial Microbiota from Superficial Pyoderma Forms in Atopic Dogs. Pathogens 2020; 6;9(8):638.

27. Pierezan F, Olivry T, Paps JS, et al. The skin microbiome in allergen-induced canine atopic dermatitis. Vet Dermatol 2016; 27(5):332-e82.

28. van Damme CM, Willemse T, van Dijk A, Haagsman HP, Veldhuizen EJ. Altered cutaneous expression of betadefensins in dogs with atopic dermatitis. Mol Immunol 2009; 28 International Animal Health Journal

46(13):2449-55.

29. Hata TR, Gallo RL. Antimicrobial peptides, skin infections, and atopic dermatitis. Semin Cutan Med Surg 2008; 27(2):144-150.

30. Ohnishi Y, Okino N, Ito M, Imayama S. Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol 1999;6(1):101-104.

31. Park KY, Kim DH, Jeong MS, Li K, Seo SJ. Changes of antimicrobial peptides and trans-epidermal water loss after topical application of tacrolimus and ceramide-dominant emollient in patients with atopic dermatitis. J Korean Med Sci 2010;25(5):766-771.

32. Imokawa G. Cutting Edge of the Pathogenesis of Atopic Dermatitis: Sphingomyelin Deacylase, the Enzyme Involved in Its Ceramide Deficiency, Plays a Pivotal Role. Int J Mol Sci 2021;22(4):1613.

33. Borodzicz S, Rudnicka L, Mirowska-Guzel D, CudnochJedrzejewska A. The role of epidermal sphingolipids in dermatologic diseases. Lipids Health Dis 2016;15:13.

34. Popa I, Portoukalian J, Haftek M. Specificity in the alteration of lesional and non-lesional skin lipids in atopic dogs. World J Dermatol 2015; 4(1): 1-7 35. Scharschmidt TC, Man MQ, Hatano Y, et al. Filaggrin deficiency confers a paracellular barrier abnormality that reduces inflammatory thresholds to irritants and haptens. J Allergy Clin Immunol 2009; 124(3):496-506.

36. Fartasch M, Bassukas ID, Diepgen TL. Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics. Br J Dermatol 1992;127(3):221-7.

37. van Smeden J, Bouwstra JA. Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients. Curr Probl Dermatol 2016; 49:8-26.

38. Janssens M, van Smeden J, Gooris GS, et al. Increase in shortchain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J Lipid Res 2012; 53(12):2755-2766.

39. Popa I, Pin D, Remoué N, et al. Analysis of epidermal lipids in normal and atopic dogs, before and after administration of an oral omega-6/omega-3 fatty acid feed supplement. A pilot study. Vet Res Commun 2011;35(8):501-9.

40. Chermprapai S, Broere F, Gooris G, Schlotter YM, Rutten VPMG, Bouwstra JA. Altered lipid properties of the stratum corneum in Canine Atopic Dermatitis. Biochim Biophys Acta Biomembr 2018; 1860(2):526-533 41. Inman AO, Olivry T, Dunston SM, Monteiro-Riviere NA, Gatto H. Electron microscopic observations of stratum corneum intercellular lipids in normal and atopic dogs. Vet Pathol 2001; 38(6):720-3.

42. Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol 2002;119(1):166-73.

43. Reiter LV, Torres SM, Wertz PW. Characterization and quantification of ceramides in the non-lesional skin of canine patients with atopic dermatitis compared with controls. Vet Dermatol 2009;20(4):260-6.

44. Meguro S, Arai Y, Masukawa Y, Uie K, Tokimitsu I. Relationship between covalently bound ceramides and transepidermal water loss (TEWL). Arch Dermatol Res 2000; 292(9):463-8.

45. Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 1998;78(1):27-30.

46. Shimada K, Yoon JS, Yoshihara T, Iwasaki T, Nishifuji K. Increased transepidermal water loss and decreased ceramide content in lesional and non-lesional skin of dogs with atopic dermatitis. Vet Dermatol 2009; 20(5-6):541-6.

47. Stahl J, Paps J, Bäumer W, Olivry T. Dermatophagoides farinae house dust mite allergen challenges reduce stratum corneum ceramides in an experimental dog model of acute atopic dermatitis. Vet Dermatol 2012; 23(6):497-e97.

48. Marsella R, Segarra S, Ahrens K, et al. Topical treatment with sphingolipids and glycosaminoglycans for canine atopic dermatitis. BMC Vet Res 2020; 16:92 49. Marsella R, Genovese D, Gilmer L, Ahrens K, Gatto H, Navarro C. Investigations on the effects of a topical ceramidesVolume 8 Issue 2

RESEARCH AND DEVELOPMENT

containing emulsion (Allerderm spot on) on clinical signs and skin barrier function in dogs with atopic dermatitis: a double-blinded randomized controlled study. Int J Appl Res Vet Med 2013;11(2):110–6.

50. Fujimura M, Nakatsuji Y, Fujiwara S, Rème C, Gatto H. Spot-on skin lipid complex as an adjunct therapy in dogs with atopic dermatitis: an open pilot study. Vet Med Int 2011; 281846.

51. Jung JY, Nam EH, Park SH, Han SH, Hwang CY. Clinical use of a ceramide-based moisturizer for treating dogs with atopic dermatitis. J Vet Sci 2013;14(2):199-205.

52. Piekutowska A, Pin D, Rème CA, Gatto H, Haftek M. Effects of a topically applied preparation of epidermal lipids on the stratum corneum barrier of atopic dogs. J Comp Pathol 2008; 138(4):197-203.

53. Kircik LH, Del Rosso JQ, Aversa D. Evaluating Clinical Use of a Ceramide-dominant, Physiologic Lipid-based Topical Emulsion for Atopic Dermatitis. J Clin Aesthet Dermatol 2011;4(3):34-40.

54. Sugarman JL, Parish LC. Efficacy of a lipid-based barrier repair formulation in moderate-to-severe pediatric atopic dermatitis. J Drugs Dermatol 2009;8(12):1106-11.

55. Chamlin SL, Kao J, Frieden IJ, et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J Am Acad Dermatol 2002; 47(2):198-208.

56. Glines KR, Stiff KM, Freeze M, Cline A, Strowd LC, Feldman SR. An update on the topical and oral therapy options for treating pediatric atopic dermatitis. Expert Opin Pharmacother 2019; 20(5):621-629.

57. Silverberg JI. Atopic Dermatitis: An Evidence-Based Treatment Update. Am J Clin Dermatol 2015; 15:149–164.

58. Nuttall T. Topical therapy in canine atopic dermatitis: new products. Companion Anim 2020; 25:76-82 59. Olivry T, DeBoer DJ, Favrot C, Jackson HA, Mueller RS, Nuttall T, Prélaud P; International Committee on Allergic Diseases of Animals. Treatment of canine atopic dermatitis: 2015 updated guidelines from the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res 2015; 16(11)210.

60. Marsella R, Cornegliani L, Ozmen I, Bohannon M, Ahrens K, Santoro D. Randomized, double-blinded, placebo-controlled pilot study on the effects of topical blackcurrant emulsion enriched in essential fatty acids, ceramides and 18-beta glycyrrhetinic acid on clinical signs and skin barrier function in dogs with atopic dermatitis. Vet Dermatol 2017;28(6):577-e140.

61. Hobi S, Klinger C, Classen J, Mueller RS. The effects of a topical lipid complex therapy on dogs with atopic dermatitis: a double blind, randomized, placebo-controlled study. Vet Dermatol 2017;28(4):369-e84.

62. Draelos ZD. A clinical evaluation of the comparable efficacy www.international-animalhealth.com

of hyaluronic acid-based foam and ceramide-containing emulsion cream in the treatment of mild-to-moderate atopic dermatitis. J Cosmet Dermatol 2011; 10(3):185-8.

63. van Zuuren EJ, Fedorowicz Z, Christensen R, Lavrijsen A, Arents BWM. Emollients and moisturisers for eczema. Cochrane Database Syst Rev 2017; 2(2):CD012119.

64. Harcharik S, Emer J. Steroid-sparing properties of emollients in dermatology. Skin Therapy Lett 2014;19(1):5-10.

65. Frankel A, Sohn A, Patel RV, Lebwohl M. Bilateral comparison study of pimecrolimus cream 1% and a ceramide-hyaluronic acid emollient foam in the treatment of patients with atopic dermatitis. J Drugs Dermatol 2011; 10(6):666-72.

66. Kao JS, Fluhr JW, Man MQ, et al. Short-term glucocorticoid treatment compromises both permeability barrier homeostasis and stratum corneum integrity: inhibition of epidermal lipid synthesis accounts for functional abnormalities. J Invest Dermatol 2003;120(3):456-64.

67. Kim M, Jung M, Hong SP, et al. Topical calcineurin inhibitors compromise stratum corneum integrity, epidermal permeability and antimicrobial barrier function. Exp Dermatol 2010; 19(6):501-10.

68. Popa I, Remoue N, Osta B, et al. The lipid alterations in the stratum corneum of dogs with atopic dermatitis are alleviated by topical application of a sphingolipid-containing emulsion. Clin Exp Dermatol 2012;37(6):665-71.

69. Cerrato S, Ramió-Lluch L, Brazís P, Fondevila D, Segarra S, Puigdemont A. Effects of sphingolipid extracts on the morphological structure and lipid profile in an in vitro model of canine skin. Vet J 2016;212:58-64.

70. Cerrato S, Ramió-Lluch L, Brazís P, Segarra S, Puigdemont A. Effects of sphingomyelin and hyaluronic acid on prostaglandin E2 secretion in canine keratinocytes. Poster. Abstracts from the 8th world congress of veterinary dermatology, Bordeaux, France. Vet Dermatol 2016;27(1):6–121.

71. Fogh K, Herlin T, Kragballe K. Eicosanoids in skin of patients with atopic dermatitis: prostaglandin E2 and leukotriene B4 are present in biologically active concentrations. J Allergy Clin Immunol 1989;83:450–455.

72. Schlotter YM, Riemers FM, Rutten VP, Knol EF, Willemse T. Enzymes involved in the conversion of arachidonic acid to eicosanoids in the skin of atopic dogs. Exp Dermatol 2010; 19(8):e317-9.

73. Song M, Kim S, Yun H.S. et al. Anti-inflammatory effect of the ceramide mixture extracted from genetically modified Saccharomyces cerevisiae. Biotechnol Bioproc 2017;22:653–658.

74. Hsu YW, Chi KH, Huang WC, Lin WW. Ceramide inhibits lipopolysaccharide-mediated nitric oxide synthase and cyclooxygenase-2 induction in macrophages: effects on protein kinases and transcription factors. J Immunol 2001; 1;166(9):5388-97 75. Sawada E, Yoshida N, Sugiura A, Imokawa G. Th1 cytokines accentuate but Th2 cytokines attenuate ceramide production in the stratum corneum of human epidermal equivalents: an implication for the disrupted barrier mechanism in atopic dermatitis. J Dermatol Sci 2012; 68(1):25-35.

Pippa Coupe Pippa Coupe BVSc MRCVS qualified from the University of Bristol in 2015.

After several years working in general practice as a Small Animal Veterinary Surgeon, she joined ADM Protexin as a Veterinary Product Manager. Pippa is passionate about the adjunctive role that nutraceuticals can play in disease management and in particular, the importance of topical therapy in the multi-modal management of canine atopic dermatitis.

Email: pippa.coupe@protexin.com

International Animal Health Journal 29

FOOD & FEED

A New Approach to Optimising Nutrition for Dogs and Cats In 2020, caregivers worldwide spent an estimated 96 billion USD (70 billion GBP) on food and treats for their companion animals.1 Every year brings innovations from industry manufacturers, some following market trends, others seeking to elevate the quality of nutrition for nonhuman family members. But are we really providing our dogs and cats the best nutrition available? Is there a better way to provide meals that will meet each animal’s needs and support optimum health? There is – and it’s far easier and more accessible than you might expect.

When I was growing up, my mother liked to feed my sister and me a breakfast cereal called “Total”, so named because it offered “total” nutrition – 100% of the recommended daily allowance of vitamins and minerals as determined by the USDA. The theory – and Mom’s strategy – was that it was the best way to ensure we were well fed, and that all our dietary needs were met.

We can debate the validity of the theory, but my mother’s intentions were the best, and she didn’t succumb entirely to the marketing. Her strategy for feeding her daughters well also included a lunch and dinner made from scratch. She was an excellent cook, and had a broad repertoire of favourite dishes.

My sister and I were the beneficiaries.

Fast forward a few decades, and we’ve all learned that the best diet for a healthy human is based on a wide variety of whole foods – fresh ingredients, minimally processed. We track the ever-changing food pyramid, with its recommendations for how many servings of fruits and vegetables we should eat each day, and make a point of eating all the colours of the rainbow. We tolerate leftovers as a matter of convenience or thrift, but are generally happiest and feel well fed when our plates are filled with different foods and flavours from one day to the next.

And yet, we rarely apply the same principles to strategies for feeding non-human family members. Instead, we’re deeply entrenched in the practice of feeding dogs and cats highly processed food that comes from a can or bag – in particular, the same food day after day, week after week, for months and years on end. We advise caregivers to choose a quality food from a reputable brand, one that’s made to meet AAFCO standards for the nutritional requirements of dogs or cats. We then caution caregivers not to make abrupt changes in the diet, and often warn against feeding “table scraps”, to avoid triggering digestive upsets or weight gain.

Again, the intentions here are good. A great deal of research is behind those AAFCO standards, and they provide a valuable way to help guardians avoid foods that are lacking in key nutrients. But is the practice of choosing a single, highquality commercial food, and using it as the primary source of nutrition for months or years at a time, really the best we can do for our companions? What if my mother had chosen to feed my sister and me Total breakfast cereal every day – not just for breakfast, but for dinner, too – for our entire childhood?

It’s an absurd notion, to be sure. But isn’t that essentially the way we feed companion animals as a matter of course?

30 International Animal Health Journal

Is there a better option?

Clearly there is, or should be. But to identify solutions, we need first to understand the problem. If a dog or cat food is designed to meet all the known nutritional requirements for the species, why isn’t that enough?

Our Knowledge Base is Evolving There are a few reasons why a static diet falls short, but the first goes to the very heart of our reliance on “nutritional standards”. We know that animal nutrition is an evolving science. We’ve learned a lot about the needs of canines and felines over the past century, but research is ongoing, and new information emerges every year. That’s good – but it also suggests there’s still a lot we don’t know, and that raises serious questions about the foods we produce today based on standards that will presumably change as our knowledge base grows.

Perhaps a more challenging issue is that nutritional needs vary from one breed to the next, and from one individual to the next, even within a given breed. We can even agree that the needs of a single individual vary over time – as he or she ages, to be sure, but also as activity levels change from day to day, or in times of physical or emotional stress. How is it possible to create a single food that will meet the needs of every individual, or of a single individual when her needs are a moving target?

Quite simply, there is no single formula that will precisely meet the nutritional needs of every dog or cat, or of a single dog or cat whose needs are changing every day.

Deficiencies and Imbalances are Magnified Over Time The second problem with current feeding practices is the lack of variety. When the nutrient profile never changes, any deviation from an individual’s unique nutritional needs will cause deficiencies to be magnified over time. An animal will tolerate a diet that does not deliver optimum macro- or micronutrients for a day, or for a week, or perhaps a month. But over a prolonged period, those same deviations may lead to organ stress, obesity, skin disease, gastrointestinal problems, hyperactivity, and more.

A Repetitive Diet Leads to Food Sensitivities Additionally, eating any one food every single day for weeks, months, and years is a perfect setup for the development of food sensitivities, as is eating the same combination of ingredients in a single commercial food over an extended period of time. Too many animals suffer from chronic skin eruptions, ear infections, gastrointestinal disorders, and other disruptions unnecessarily due to a repetitive diet.

The Benefits of Fresh Foods Can’t be Replicated Perhaps the most fundamental deficit in commercial foods is that they are, of necessity, highly processed, and likely sit on a shelf for weeks or months. We’re very clear in our recommendations to humans that the best nutrition comes from fresh, whole, minimally processed foods. And yet a fresh-food diet has only marginally begun to enter the conversation in strategies for feeding dogs and cats. We know that valuable nutrients are lost in the manufacturing process, and developers aim to mitigate deficiencies with the addition Volume 8 Issue 2

FOOD & FEED of supplements. But it would be a fallacy to believe we’re able to replicate the vast array of micronutrients, enzymes, probiotics – and the vitality – inherent in fresh foods.

The Optimum Diet for Dogs and Cats It’s a complex problem, to be sure. But the solution is simple – and it’s right in front of our eyes. The key to optimal nutrition for every dog and cat is to feed each one the way we feed ourselves: Like us, non-human family members thrive when they eat minimally processed foods, as fresh as possible, made with different ingredients every day or every few days.

The notion of feeding home-prepared meals to companion animals is not new – it’s been gaining ground among caregivers and recommended by more veterinarians in recent years. But it generally comes with an emphasis on following a prescribed recipe – again formulated to meet AAFCO standards – and with cautions about the risks of deviating from the formula. To be sure, simply switching to fresh food has real benefits. However, following a single recipe for an extended time carries many of the same drawbacks as feeding the same commercial food. There is no single recipe that meets the needs of every dog or cat, and any deviation from the individual animal’s actual nutritional needs will be amplified over time. And with the lack of variety, the risk of developing food sensitivities is substantial.

Feeding a varied diet made with an ever-changing selection of healthy, wholesome ingredients solves those problems. It allows companion animals to receive everything they need the same way we do – by drawing nutrients from a broad array of foods over a period of days or weeks.

Think of it this way: How many of your meals, on their own, supply every nutrient you need in amounts listed in the RDA? I’m sure you don’t know because you don’t monitor your nutritional intake at that level. But you eat a variety of healthy foods from one day to the next, one week to the next, and know that over time you’ll get everything you need.

and weeks – again, variety is key. Additional instruction should include types and amounts of supplements, assistance in including an array of different ingredients in each category, and encouragement to use organic ingredients as much as possible. And, of course, guidance must include instruction to avoid potentially harmful foods, such as onions, chocolate, grapes, raisins, and macadamia nuts.

Everyone in the Family Benefits The benefits of feeding the Fresh and Flexible meal plan are many, and extend to caregivers as well as their companions.

They include the following: •

•

• •

The plan provides all the benefits of a fresh, varied, whole-food diet. Since the animal is eating a different combination of highly nutritious foods every day or every few days, he or she has the best opportunity to encounter the nutrients he needs in a short amount of time.

Ingredients and proportions can be adjusted to: • meet the unique needs of each individual, even when there are multiple dogs and/or cats in the household.

• meet the changing needs of an individual over time.

For example, as an animal ages, protein requirements often increase, and this can be accommodated by increasing the proportion of the higher-protein food in the bowl.

• manage health issues, such as obesity or hyperactivity. For example, a dog on a weightreduction diet can still enjoy a generous serving of food when vegetables replace higher-calorie ingredients.

When the animal eats different foods from day to day, there is far less likelihood of developing food sensitivities or nutritional deficiencies.

This plan is far easier for caregivers to implement than most home-prepared diets. There is no need to follow a recipe, and no need to shop a separate grocery list or prepare a separate meal. Most – and in some cases all – ingredients can be drawn from human family members’ meals, often with little or no modification.

Caregivers report that their relationship with their dog or cat is enhanced as they become more involved in selecting and preparing meals, and see the animal’s appreciation and enjoyment of the meals along with improved health and vitality.

Similarly, our dogs and cats do not need to have every single one of their meals meet AAFCO standards. If they eat a variety of high-quality foods, something different every day, their bodies can draw the proper nutrients to meet their own unique needs over the course of a few days or weeks.

•

The Fresh and Flexible Meal Plan™ This doesn’t mean we usher caregivers out the door to fend for themselves, with an order to just feed different foods all the time.

Some level of guidance is warranted – and wanted. That’s easy enough to deliver. I’ve created a simple guide, the Fresh and Flexible meal plan, that provides basic guidelines, so caregivers know what to put in the bowl. Parameters are intentionally broad, to allow for the variety of ingredients that is so critical.

Adjustments can and should be made to suit particular dietary needs, limitations, or preferences, but the essentials look like this:

Results are Clear, and Often Dramatic I’ve been teaching and recommending the Fresh and Flexible plan – and feeding it to my own animal companions – for nearly twenty years. I’ve found it to be the most powerful tool to begin the healing process for a range of illnesses, restore mobility in seniors, and rejuvenate those recovering from abuse or neglect. Many symptoms are reversed, lab results improve, and vitality is enhanced simply by implementing this change in the diet.

• • • • • • •

Higher-protein foods: 30% to 60% of the meal (may be higher for cats) Higher-carbohydrate foods: 30% to 60% Vegetables and fruits: 10% to 30% Fats Nutrition boosters (nutrient-dense or other beneficial foods such as spirulina, nutritional yeast, wheat germ, probiotics) Multi-vitamin supplement Calcium supplement (for meat-based diets)

Within these parameters, caregivers are urged to rotate through as many foods as possible over the course of days www.international-animalhealth.com

What Does This Mean for Commercial Pet Food Manufacturers?

While it’s my experience that a fresh-food diet provides the best outcomes, there are times when it’s helpful for caregivers to have a quality canned or packaged food available for occasional use as a matter of convenience. And the reality is that many have no desire or are unable to feed homeprepared meals to their dogs or cats. To meet the needs of these families, principles of the Fresh and Flexible meal plan can be applied to develop a new approach to commercial foods.

The first step is to create products based on wholefood or minimally-processed ingredients. More and more International Animal Health Journal 31

FOOD & FEED

manufacturers are moving in this direction, and dogs and cats will benefit greatly as that trend continues.

But the strategies outlined here offer an opportunity for a truly innovative approach to commercial pet foods. As we’ve seen, variety is key to optimum nutrition. It would be exciting to see commercial foods produced and packaged in a way that facilitates feeding a varied diet, with different ingredients in the bowl from one day to the next. This could be achieved by creating four or five or six distinct formulas – not just a different primary ingredient, such as switching from lamb to chicken while other ingredients remain the same, but with all ingredients unique to each formula. A package of food would then include smaller packets, each containing a different formula. The caregiver could then easily rotate among the various packets to provide a different formula at each meal.

While the food sources would be more limited than a true Fresh and Flexible plan, the dog or cat would benefit from a substantially more varied diet than what is currently available in a commercial food. It would be reasonable to expect that the array of micronutrients would increase, and food sensitivities would be substantially decreased.

The Path Forward We are fortunate to bear witness to a time when companion animals are valued more than ever as integral members of families and society. As our understanding of their cognitive and emotional capacities grows, we are increasingly aware of 32 International Animal Health Journal

the many ways they are more like us than we once believed. It makes sense, as well, that the time is right for us to recognise that their dietary needs are not radically different from our own, and can best be met with an approach similar to that which we apply to our own nutritional health. A whole-food diet with plenty of variety will benefit our much-loved dogs and cats, just as it does us.

REFERENCES 1.

https://www.mordorintelligence.com/industry-reports/ global-pet-food-market-industry, visited on 10 April 2021.

Jan Allegretti Jan Allegretti, D.Vet.Hom., is the author of The Complete Holistic Dog Book: Home Health Care for Our Canine Companions. She has more than thirty years’ experience as a teacher and consultant in holistic healthcare for nonhuman animals, offering workshops and consultations to caregivers, rescue organisations, veterinarians, and other animal health professionals.

Web: www.JanAllegretti.com

Volume 8 Issue 2

MANUFACTURING

Innovative Project to Tackle Veterinary Waste

An innovative project for the recycling and responsible disposal of veterinary medicines is underway, involving pharmaceutical manufacturers, recyclers, and the farming community.

Teat sealants, vaccines, antibiotics and drenches are just a handful of the products that result in an array of waste at the end of the veterinary process. The New Zealand animal pharmaceutical industry, rural recycling schemes and associations are tasked with finding a solution following a directive from the government to take responsibility for this waste. The extent and nature of veterinary medicines, as well as the materials used and what they contain, will lead to some head-scratching on how to manage such a diverse array of products in a sustainable way – with a priority towards recycling them and turning them, where possible, into useful new products.

In July 2019, the New Zealand government announced an ambitious goal to determine certain products as ‘priority products’ under the Waste Minimisation Act, including veterinary medicines. As part of the New Zealand Government’s wider plan to reduce the amount of rubbish ending up in landfills or polluting the environment, it declared six priority products for regulated product stewardship under the Act. These product categories involve plastic packaging, tyres, electrical and electronic products (e-waste) and refrigerants, along with agrichemicals and their containers.

Veterinary medicines are included in the ‘agrichemical’ product category. As there is no product stewardship scheme in place for these medicines, the industry is tasked with co-designing a scheme.

This is the first time that the New Zealand government has taken such a hard line on product packaging. The directive puts the onus on importers and manufacturers to take responsibility for their products by ensuring that they can be recycled or, at least, safely disposed of. The Act’s associated guidelines direct them to pay for this through a levy for the recovery costs through a not-for-profit product stewardship scheme – whereby a recycling organisation will be tasked with finding the most sustainable solution. Full net costs for stewardship will be proportional to the producer’s market share and ease of reuse or recyclability of their product.

Responsibility is also spread throughout the supply chain – through the distribution, sale and use, to the end-of-life disposal of the products, so all who have a hand in any of these processes wear some of the responsibility. There is no point determining that the manufacturer or importer bears this solely, as someone at the end of the supply chain will need to take action to enable the recycling of the product.

The guidelines also stipulate the free and convenient collection of the priority product for household and business consumers at end of life, including rural populations.

With New Zealand being geographically spread out with some isolated communities, the bar is raised extremely high. Add to this the expectation that legacy and orphaned www.international-animalhealth.com

products be substantially funded by the scheme, and it will be no mean feat.

Trials to investigate which products can be recycled are already underway, but there are some challenges. There is no similar known scheme in place for these products and there is still much research to be done.

Each product will need to be assessed to determine its hazardous properties and ascertain which have no or limited effects on the environment, so that they can safely be rinsed, handled and transported. Those that can’t be safely managed will need specialist treatment, transportation and handling. Products such as vaccines and antibiotics will bring challenges, especially as they are often applied with needles.

The options for recycling these may be limited, as the risk of exposure from some of the residue of the medicine is just too great for the safety of people and the environment.

This innovative project will see the animal health industry increase the recycling of animal health products and packaging. The rural recycling programme, Agrecovery, is taking the lead in driving the project in conjunction with New Zealand animal health manufacturers. When considering the vast array of veterinary medicines available in an agricultural nation like New Zealand, the project's scope is extensive.

Agrecovery has managed and operated successful voluntary product stewardship schemes for agrichemicals and their containers in New Zealand since 2006. In this time, more than 3000 tonnes of product packaging has been recovered and recycled into new materials, and more than 150 tonnes of unwanted agrichemicals have been collected and safely disposed of. The organisation delivers two product stewardship schemes: 1. The Agrichemical Container Collection Scheme, which receives and recycles agrichemical containers.

2. The Agrichemical Chemical Recovery Scheme, which receives and dispose of unwanted residual agrichemicals.

The rural recycling programme has a long-standing commitment to expanding its focus to include other farm waste and strives to improve the efficiency and delivery of its services.

As the organisation takes on the challenge of veterinary medicines, it has three attributes in its favour. It is already a not-for-profit organisation. Agrichemical manufacturers pay a levy to Agrecovery for the recycling of plastic containers as well as any leftover product. This is what funds the programme.

It is also familiar with managing hazardous materials, having procedures in place to manage the health and safety of its contractors and staff when dealing with the chemicals.

Thirdly, its operational model already includes the recycling of drench containers for veterinary medicine manufacturers.

In total, the drench containers it recycles each year holds a total of 1,766,674 litres of animal product. This is already set to increase, as new product manufacturers have recently signed up to support the scheme. The organisation’s history, expertise, structure and sustainability measures make it the International Animal Health Journal 33

MANUFACTURING best-suited organisation for undertaking the recycling of veterinary medicines.

Consistency of product packaging is also a consideration for recyclers. Part of the solution will involve the recycler identifying packaging specifications for manufacturers to ensure the recycling of products without compromising their efficacy and shelf-life. Having a centralised service to collate and specify requirements for this, in collusion with manufacturers, will ensure consistency and allow more product to be recycled.

Considering these factors, the development of the product stewardship scheme will take several years. Now in its first year, the project, being run by Agrecovery, is working through the recycling issues and forming a stakeholder advisory group to formulate a cross-industry approach to them. The veterinary industry is being asked to share commerciallysensitive information about its products and their share in the marketplace. This information needs to be protected, so processes are being established to manage this as part of the scheme development. Alongside understanding the amount and types of product packaging, the scheme is working through understanding the users of it and its channels to market. It is also assessing what is currently being done with the packaging at the end of its life – including mapping existing services, activities, and behaviours. Integral to all of this is identifying existing barriers to effective product stewardship and finding opportunities to remove them. The project is focused on ensuring a strong foundation for a resilient and robust scheme that is fair and minimally disruptive to the industry and product users.

Overview of the Guidelines In July, 2020 the Ministry for the Environment gazetted a finalised ‘General Guidelines for Product Stewardship Schemes for Priority Products Notice’ which laid out its expectations and requirements for product stewardship schemes.

Circular Resource Use • • •

Continuous improvement in minimising waste and harm and maximising benefit from the priority product at end of life.

Increasing end-of-life management of the priority product higher up the waste hierarchy to support transition to a circular economy in New Zealand.

Investment in initiatives to improve circular resource use, reusability, recyclability, and new markets for the priority product.

Internalised End-of-life Costs •

• •

Full net costs for stewardship of priority products at end of life met by product or producer fees proportional to the producer’s market share and ease of reuse or recyclability of their product.

Free and convenient collection of the priority product for household and business consumers at end of life, including rural populations.

Collection and management of legacy and orphaned priority products fully or substantially funded by the scheme.

After this scoping is done, a process of prioritising products to recycle will be completed. It makes sense that the products that are easiest to recycle and have the greatest volumes will be the first in line. Determining fair and reasonable criteria for prioritising products to focus on and selecting products for development will follow, including small-scale pilot trials and sharing of trial data as appropriate. Alongside this, identifying potential collection, recycling and/or options for safe disposal need to be investigated.

Public Accountability

The next stage of the project will be driven by what is uncovered during the first stage of the project. One thing that is certain is that it will include meeting the requirements of the government’s guidelines and delving into the logistics of initiating a new scheme for the veterinary pharmaceutical industry.

•

Summary of the Regulations The relevant priority product for veterinary medicines is ‘All agrichemicals and their containers up to and including 1000 litres in size or equivalent packaging for dry goods that are used for: • any horticulture, agricultural and livestock production, including veterinary medicines; • industrial, utility, infrastructure and recreational pest and weed control; • forestry; • household pest and weed control operations; or • similar activities conducted or contracted by local and central government authorities.

This includes, but is not limited to, all substances that require registration under the Agricultural Compounds and Veterinary Medicines Act 1997, whether current or expired, and their containers (packaging), which are considered hazardous until they have been triple-rinsed.’

34 International Animal Health Journal

• •

Clear information to household and business consumers on how the scheme works, how it is funded, and how to find the nearest collection point.

Transparent chain of custody for collected and processed materials, to both onshore and to offshore processors, and published mass balances showing rates of reuse / recycling or environmentally sound disposal of the priority products.

Publicly available annual reports that include measurement of outcomes and achievement of targets, fees collected and disbursed, and net cash reserves held as contingency.

Collaboration Optimal use of existing and new collection and processing infrastructure and networks, and co-design and integration between product groups.

Governance The scheme will be managed by a legally registered not-for-profit entity. Annual independent audits will be conducted on scheme performance and included in scheme’s annual reports to the Ministry for the Environment.

The annual reports must contain the following: • • •

financial performance and scheme costeffectiveness; environmental performance; and agreements with scheme service providers.

Governance arrangements will be established for the initial setup and ongoing development and operation of the scheme that are appropriate to the size and scale of the scheme.

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MANUFACTURING

All governance activities will adhere to the Commerce Commission guidelines on collaborative activities between competitors, including but not limited to considering the option of applying for collaborative activity clearance from the Commission for the scheme.

The scheme will be the only accredited scheme for that product, or • have agreements in place with other scheme managers to enable cooperation and cost-effective materials handling and to prevent confusion for household and business consumers; and • demonstrate how net community and environmental benefit (including cost-effectiveness and nonmonetary impacts) will result from multiple schemes for that priority product.

Directors or governance boards will: • be appointed through an open and transparent process; • represent the interests of producers and consumers of the priority product and the wider community as informed by stakeholder advisory groups; and • follow governance best practice guidelines, for example the Institute of Directors of New Zealand Code of Practice for Directors, including for the identification and management of conflicts of interest.

changes in the market, natural events, and technology.

The gazetted guidelines provide timelines for securing accreditation or reaccreditation for priority products: •

•

•

within one year from the date of priority product declaration for product categories with existing accredited voluntary schemes that wholly or substantially cover that priority product; within one year from the date of priority product declaration or co-design recommendations to the Government, whichever is later, for product categories not substantially covered by voluntary accredited schemes for which a co-design process has commenced; or within three years from the date of priority product declaration for all other priority product categories.

This indicates that accreditation must be sought within one year of completing the co-design process, which is not specifically time-limited.

Scheme Operations •

• • •

•

Services (e.g. collection, sorting, material recovery and disposal) will be procured using transparent, nondiscriminatory and competitive processes open to all competent entities whether existing, new entrant or social enterprise.

Clear, regular and open reporting and communication will be given to scheme participants and stakeholders.

Processes exist to manage commercially confidential or sensitive information appropriately.

All people involved in the scheme will have completed suitable training to complete their roles, including in best practice in prevention and reduction of harm to people and the environment.

Ability to obtain new or existing permits held, for all necessary activities in New Zealand in relation to processing and potential export of priority products or their constituent components.

Targets All schemes will set and report annually to the Ministry for the Environment on targets that include: • significant, timely and continuous improvement in scheme performance; • performance against best practice collection and recycling or treatment rates for the same product type in high-performing jurisdictions; • a clear time-bound and measurable path to attain best practice; • implementation phase-in to reflect availability of markets and infrastructure; • new product and market development to accommodate collected materials; and • measures for public awareness of scheme participant satisfaction and a record of response by the scheme to concerns raised.

Targets will be reviewed and adjusted no less than every three years from the date of accreditation, accounting for

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Jeff Howe Jeff Howe commenced with Agcarm in December 2020 as Technical Manager – Animal Health, after twenty years developing international business at Victoria University of Wellington. Before that, he worked for the Foundation for Research, Science and Technology – where he developed research strategies for animal industries and intellectual property policy, and for the then-Ministry of Agriculture and Forestry Policy Group where he worked on the development of the Agricultural Compounds and Veterinary Medicines (ACVM) and Hazardous Substances and New Organisms (HSNO) Acts.

Email: jeff.howe@agcarm.co.nz

International Animal Health Journal 35

INNOVATIONS & TECHNOLOGIES Bringing intelligence to the treatment point

Digital monitoring of medical treatments is moving more and more into focus, while new technologies and systems allow collecting treatment information and data in an easy and secure manner. The following article intends to provide information about valid reasons for a transition to digital monitoring of treatments and to give an overview over the technologies used.

The Farm Changes A large number of technology companies are working on the digital change on the farm these days, with various sensing and monitoring technologies belonging to everyday farm life already. There are modern, intelligent venting systems allowing optimal ventilation. Smart feeding systems are ensuring that each individual animal is provided with the perfect type and quantity of food. Machine fleets are becoming digital, and tractors are communicating with their owners and other machines. Even the health status of animals can be monitored through multiple kinds of sensors. Against this backdrop, it is surprising that medical treatments are still manually recorded with pen and paper in most farms.

Trends require Digital Monitoring and Tracking of Medical Treatments This is even more surprising when considering the fact that various stakeholders seek for treatment information due to different reasons.

36 International Animal Health Journal

To begin with, the final link in the chain of meat production: end customers desire more and more maximum transparency with regard to the meat they want to consume – triggered, among other things, by reports on food scandals, multiresistant germs due to routine use of antibiotics on livestock, and economic and ecological consequences of meat production. Consumers not only wish to know where their meat is coming from but also if the animal has been treated with antibiotics or any other medical product and if so, when and how long. Against this background, rules for antibiotic treatments become stricter in most countries. At the same time, legislative requirements with regard to documentation of medical treatments are increasing.

For the pig farmer it is important to monitor the medical treatments of the animals in a better, more efficient and reliable way. All with the goal to prevent health issues, increase welfare and herd health. Another important key factor for the farmers is the reduction of time and effort for documentation tasks. Although requirements with regard to documentation have increased, medical treatments and vaccinations are often still manually recorded in the traditional way: with pen and paper. This approach is not only prone to errors and manipulation, but it is also a very time consuming task without direct economic benefit for the farmer.

In addition, the economic system pig farmers are operating in has changed, is changing and will continue to change. There is an ongoing trend worldwide from

Volume 8 Issue 2

INNOVATIONS & TECHNOLOGIES smaller independent farms towards large swine production companies and grower–integrator relations. Like the grower, also the integrator faces different economic risks and pressures associated with disease or consumer demands.

In order to limit the risks, the integrator usually establishes requirements in production contracts in which concrete standards – also with regard to medical treatments – are defined. Monitoring the compliance with the agreed standards is resulting in a huge management effort both for grower and integrator making digital monitoring and tracking necessary or at least very helpful.

Need to Track and Trace Medical Treatment Although driven by different individual goals – whether in relation to growing desire for transparency by end customers, a more efficient health management or for economic reasons - all stakeholders in today’s pig production industry are triggering a clear need to measure, track, trace, report and analyse medical treatments in an easy, safe and efficient manner.

There is a need to track: • • • • • •

When? was the treatment performed?

Which animal? has been injected?

What or which product? has been given?

Which dose? has been administered?

Where? was the treatment carried out?

Who? did the injection?

Medical Treatment Monitoring Technologies To identify individual medical treatments, existing systems use different sensing technologies such as contact sensors or fluid sensors. In most of today’s systems, the user is able to define and set medicine and dose shortly before the treatment process allowing the user to choose from an available product inventory enabling a fast and easy setting on the go. Time saving is not the only advantage of using a digital product inventory – it can also operate as a stock monitoring giving real-time information about the current stock of medicines. To make dose setting easier, some systems have built-in weight based dosing calculators, computing the right dose for each individual animal. During the treatment process, the applicator is registering and recording each dose automatically through its built it sensors in real-time.

Meanwhile, very sophisticated systems are even monitoring the vaccination quality through intelligent sensor technology – informing the user in real time if there is a need to adjust or to improve the handling of the device and/or animal.

Some medical treatment monitoring systems are also allowing to identify individual treated animals utilising RFID as the standard technology in today’s pig farms. RFID ear tags are used to record individual feeding and drinking behaviour or movement patterns of the pigs for example. Additional benefit of this technology derives from the fact, that RFID tags are placed in the ear of the animal. Since most of the treatments are given in the shoulder area (injections) or mouth area (oral drenching), the treatment side usually is right next to the RFID ear tag, which makes identification of the animal fast and easy without additional effort or additional working steps during the treatment. More complex systems are even providing the possibility to use RFID tags not only to identify the individual animal but also to mark different locations such as buildings, areas, zones or barns. This expands the scope of RFID tags from being animal tags to also being location tags which in turn further extends the www.international-animalhealth.com

information value and the frame of possibilities for data evaluation of such a system.

RFID scanner and intelligent applicator can be either designed as two separate hardware components which can be connected to each other or as one integrated device.

All modern systems are using Lithium Ion battery power providing energy for at least one work day in the farm.

Besides the hardware components, a modern treatment monitoring solution also consists of additional applications and programs. A corresponding mobile application plays a crucial role as bridge between the hardware components and the data storing system. At the same time it operates as a mini cockpit for managing and receiving real time information about applied medicine, dose, animal and real time alerts on the fly. Some solutions also provide the possibility to take notes during the treatment process, which is especially valuable in case the user notices something unusual while treating the individual animal. Such a mobile application is usually able to connect itself to the hardware components via Bluetooth - taking into account that WiFi coverage might not be guaranteed in every nook and corner of the farm.

International Animal Health Journal 37

INNOVATIONS & TECHNOLOGIES

it necessary to use standard technologies and established know-how and expertise across many different systems and applications. An overarching system spanning over a large range of applicators and syringes - which in the best case cover the whole range of applied doses, bottle and tubing attachments as well as several accessories to give injectable, oral or topical treatments - would provide the flexibility needed to track all medical treatments on the farm.

Ideally, the gathered data can be exchanged through standardised and consistent interfaces, providing the user with the possibility to merge and evaluate data in a meaningful manner.

When returned to the office, the gathered medical treatment data can be synchronized easily with a central management system through WiFi connection. A modern central management system is enabling the management of farms, users, devices, products and animals, as well as providing a secure location to store all data gathered using the system. In several dashboard views the treatment data is presented graphically and comprehensibly and can be analysed or filtered in any way wished. In some systems even different types of reports can be generated providing the user with an overview of available medicine stock or withdrawal times for specific animals for example.

Outlook into the Future To really benefit from the gathered data, it is important to get the “big picture” and bring together animal treatment data and other farm data in an effective and useful way.

This will not only require an even more advanced fusion of applicators and software in future but would also make 38 International Animal Health Journal

Summary Digital treatment monitoring systems have the potential to not only satisfy the informational thirst of stakeholders but also to meet the increasing legislative and documentation requirements in easy, safe and secure manner. Used meaningfully, a system with all its different options for data evaluation is able to increase welfare and heard health effectively. As a practical benefit, digital monitoring and tracking of treatments helps to reduce the volume of paperwork and to avoid manipulation or mistakes in documentation.

Jonas Riess Jonas is an Industrial Engineering graduate from University of Stuttgart.

He has been Product and Sales Manager for Veterinary Products at Henke-Sass, Wolf GmbH for the last 5 years. Within his role, he is also responsible for the injection tracking technology V-ETiC which provides automatic recognition of animals, treatments, animal health product inventory and usage. www.v-etic.com. Henke-Sass, Wolf GmbH is a leading player in veterinary products such as injectors, applicators and needles.

Volume 8 Issue 2

INSIGHT / KNOWLEDGE / FORESIGHT

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International Animal Health Journal 39

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International Animal Health Journal 41

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