IAHJ

Volume 9 Issue 1

PEER REVIEWED

Porcine Circovirus The Changing World of Cat Ownership What Does It Mean for Feline Parasite Prevention?

The ZAPI project True Partnership Leads to Success “From Molecule to Market” Series Part I: Finding the Money

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Project Management Pharmaceutical Sciences Innovative Drug Delivery Technologies Regulatory Services Pre-Clinical & Clinical Studies Data Management Manufacturing Klifovet is now part of the Argenta Group www.argentaglobal.com

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CONTENTS 04 FOREWORD TALKING POINT 06 One on One with Dr. Johnson Ouma, GALVmed's New R&D Director

MANAGING DIRECTOR Mark A. Barker EDITORIAL MANAGER Beatriz Romao beatriz@senglobalcoms.com RESEARCH AND CIRCULATION Virginia Toteva virginia@senglobalcoms.com DESIGNER Jana Sukenikova www.fanahshapeless.com BUSINESS DEVELOPMENT Jerome D’Souza info@senglobalcoms.com ADMINISTRATOR Jessica Chapman jessica@senglobalcoms.com FRONT COVER © istockphoto PUBLISHED BY Senglobal Ltd. Unit 5.02, E1 Studios, 7 Whitechapel Road, E1 1DU, United Kingdom 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.

In October 2021, GALVmed appointed Dr. Johnson Ouma as its new Executive Director in charge of Research & Development. Johnson, a seasoned researcher, will play a leading role in shaping and delivering GALVmed’s Research & Development strategy centred on sustainable technologies addressing animal health challenges facing small-scale livestock producers.

Dr. Johnson speaks with Beatriz Romao of IAHJ about GALVmed’s R&D strategy.

REGULATORY & MARKETPLACE 08 Veterinary Medicinal Product in United Kingdom: A Regulatory View Veterinary medicine is a field of medicine that addresses disease, disorder and injury prevention, control, diagnosis, and treatment. It also covers animal husbandry, breeding, nutrition research and product development. The Veterinary Medications Regulation in the United Kingdom lays down legislative criteria for veterinary medicines manufacturing, classifying, supplying, marketing and use. Dr. Balamuralidhara, Mr. Chandan BV and Mr. Akhilesh Akki at JSS College of Pharmacy provide an overview of the wide range of regulatory checks that control the licencing, provision, and monitoring of veterinary pharmaceutical goods.

16 Integrating a Workplace Wellbeing Initiative into Your Vet Practice and the Benefits it Brings Being a vet is one of the best occupations in the world.

However, numerous studies have shown that working in veterinary practice can be a stressful experience. Setting up a wellbeing initiative in practice is challenging work because it contains many facets and will fail unless it is embedded in the culture of the team. Anthony Chadwick at “thewebinarvet” explains why integrating a wellness initiative into a veterinary practice may help to lower individual stress and lead to a more collaborative team.

RESEARCH & DEVELOPMENT 18 From Molecule to Market Series (Part I): Finding the Money

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 9 Issue 1 Spring 2022 Senglobal Ltd. www.international-animalhealth.com

In this first article in the "From Molecule to Market" series, the focus is to address the separate phases in the animal health product development journey. Each step has its challenges and could potentially jeopardize all the work done to reach that point. The age-old problem is how to find the funding to support a project.

Whether you are a start-up with a great idea or a large multinational, there are always too many ideas or projects to support. Darrell Morgan and Clare Morgan at Argenta outlines some of the (more novel) options available to fund animal health developments.

22 The ZAPI Project – True Partnership Leads to Success The Innovative Medicine Initiative (IMI)-funded Zoonoses Anticipation and Preparedness Initiative (ZAPI) project was designed as a new consortium in 2014 and was International Animal Health Journal 1

CONTENTS launched in March 2015, almost 5 years before the Covid-19 outbreak impact started to affect our lives everywhere on the globe. This IMI project call was designed by the animal health industry and human pharma industry to deliver practical solutions to address the medical needs associated with the emergence of zoonotic infectious diseases. More than 70% of zoonotic diseases are originating from viral pathogens harboured by animals and new, highly scalable technologies, are necessary to address such global needs. JeanChristophe Audonnet at Boehringer Ingelheim discusses how achieving these huge needs, especially for human and veterinary vaccines, impose to radically revisit the classical manufacturing and regulatory pathways.

26 The Changing World of Cat Ownership – What Does it Mean for Feline Parasite Prevention?

The pandemic did not just cause a puppy boom – the numbers of new cat owners also soared. In fact, cats now outnumber dogs across European countries, surpassing dogs by a sizeable 30% in 2020. Historically, cats have received less attention than dogs in the veterinary setting. They are seen less frequently in clinics, there are fewer feline specific medications and cats are less often the focus of scientific research. But as cat ownership rises and cats become an even more integral part of families, feline preventative healthcare, including control of endo- and ectoparasites, has never been more important. Vetoquinol, one of the top ten global veterinary pharmaceutical company discusses why, tailoring communications to the changing demographic of cat owners and simplifying parasite prevention is vital, especially as pressure in veterinary clinics rises.

28 Porcine Circovirus Porcine Circovirus (PCV) type 2 (PCV2) is a nonenveloped virus with a single-stranded DNA genome that has been present and recognised in the pig population for a long time. From the late 1990s onwards, PCV2 has become one of the most economically important pathogens in swine production, therefore focus has been placed on effective control of the disease.

Systemic infection with PCV2 has many associated clinical manifestations which affect various organ systems. Christina Gale, Eduardo Velazquez, Roman Krejci at CEVA Animal Health, discuss how this will have a significant impact on animal health, welfare and productivity if not controlled effectively.

explains why analysis and risk measurement of the grains is necessary to identify how these weather conditions have affected the mycotoxin landscape and the represented threat.

FOOD & FEED 36 Can Cell-based Meat Play a Role in the Fight Against AMR? The development of cultivated meats, including seafood, holds the promise of providing an alternative to industrial animal farming. This editorial by Camilla Björkbom, Political Adviser at Eurogroup for Animals, (A European umbrella organisation for animal protection NGOs) explores the role of cultivated meats in the sustainable European food system envisioned in the European Commission’s Farm to Fork strategy. Can cellular agriculture be part of a new, environmentally friendly food system? What role can cell-based meat play in the fight against antimicrobial resistance?

LOGISTICS AND SUPPLY MANAGEMENT 40 The Design and Validation of Effective ThermoAssisted Drying and Decontamination Process for Biosecure Pig Transport All means of transportation (especially pig trucks) is likely to spread diseases. Especially in the winter, as the temperature turns low, disinfection effectiveness can be compromised, rendering biosecurity risks of disease introduction into farms. Thermo-Assisted Drying and Decontamination (TADD) had been pioneered and applied in the United States pig industry, as it was indicated that drying eliminated certain bacterial pathogens. Initially, TADD was applied at low temperatures for the purpose of bacterial pathogens mitigation; later, the drying unit went to higher temperatures at 72°C and higher, was used to effectively decontaminate the trucks for PRRSV and PEDV prevention. Dr. Xia Tian DVM at PIC shows how this technique has proven to be essential and highly effective for health assurance to protect the pig farms from disease invasion.

34 Higher Risk Mycotoxin Levels in Global Grains Compared to Harvest 2020 Grain represents a sizeable portion of the mycotoxin risk to livestock performance, reproduction, and health.

Grains are fed locally within countries and regions but are also transported globally to areas where grain production cannot meet the high demands for livestock feed. Harvest 2021 across the key grain-growing regions of the Northern Hemisphere suffered under turbulent weather conditions. Europe experienced a combination of drought in southern regions, while further north, flooding dominated. In the U.S., drought was a constant issue. These effects were compounded by late-season rains that delayed harvest in some regions. A similar picture surfaced across Canada, with large parts of the country being hampered by severe drought throughout the main growing season. Dr. Max Hawkins at Alltech 2 International Animal Health Journal

Volume 9 Issue 1

Animal health contract research Expert delivery of contract studies supporting product development and commercialisation.

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GLP accredited animal accommodation Conventional farm accommodation Category 3 containment Specific Pathogen Free Gnotobiotic units Aquaculture Testing Facilities (Seawater and Freshwater) • GLP accredited laboratory facilities

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FOREWORD As readers of this publication might expect, there are articles in this edition to please a wide audience. On this occasion, I have chosen to focus attention on a couple of articles included in this issue. Porcine Circovirus (PCV) type 2 (PCV2) is a nonenveloped virus with a single-stranded DNA genome that has been present and recognised in the pig population for a long time. From the late 1990s onwards, PCV2 has become one of the most economically important pathogens in swine production, therefore focus has been placed on effective control of the disease. Systemic infection with PCV2 has many associated clinical manifestations which affect various organ systems. Christina Gale, Eduardo Velazquez, Roman Krejci at CEVA Animal Health, discusses how this will have a significant impact on animal health, welfare and productivity if not controlled effectively.

International Animal Health Journal had the opportunity to speak with GALVmed. In October 2021, GALVmed appointed Dr. Johnson Ouma as its new Executive Director in charge of Research & Development. Johnson, a seasoned researcher will play a leading role in shaping and delivering GALVmed’s Research & Development strategy centred on sustainable technologies addressing animal health challenges facing small-scale livestock producers. Dr. Johnson speaks with Beatriz Romao of IAHJ about GALVmed’s R&D strategy.

to address such global needs. Jean-Christophe Audonnet at Boehringer Ingelheim discusses how achieving these huge needs, especially for human and veterinary vaccines, impose to radically revisit the classical manufacturing and regulatory pathways.

The pandemic did not just cause a puppy boom – the numbers of new cat owners also soared. In fact, cats now outnumber dogs across European countries, surpassing dogs by a sizeable 30% in 2020. Historically, cats have received less attention than dogs in the veterinary setting. They are seen less frequently in clinics, there are fewer feline specific medications and cats are less often the focus of scientific research. But as cat ownership rises and cats become an even more integral part of families, feline preventative healthcare, including control of endo- and ectoparasites, has never been more important.

Vetoquinol, one of the top ten global veterinary pharmaceutical companies discusses why, tailoring communications to the changing demographic of cat owners and simplifying parasite prevention is vital, especially as the pressure in veterinary clinics rises.

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

Veterinary medicine is a field of medicine that addresses disease, disorder and injury prevention, control, diagnosis, and treatment. It also covers animal husbandry, breeding, nutrition research and product development. The Veterinary Medications Regulation in the United Kingdom lays down legislative criteria for veterinary medicines manufacturing, classifying, supplying, marketing and use. Dr. Balamuralidhara, Mr. Chandan BV and Mr. Akhilesh Akki at JSS College of Pharmacy provide an overview of the wide range of regulatory checks that control the licencing, provision, and monitoring of veterinary pharmaceutical goods.

Kevin Woodword, Managing Director, KNW Animal Health Consulting

The Innovative Medicine Initiative (IMI)-funded Zoonoses Anticipation and Preparedness Initiative (ZAPI) project was designed as a new consortium in 2014 and was launched in March 2015, almost 5 years before the Covid-19 outbreak impact started to affect our lives everywhere on the globe. This IMI project call was designed by the animal health industry and the human pharma industry to deliver practical solutions to address the medical needs associated with the emergence of zoonotic infectious diseases. More than 70% of zoonotic diseases are originating from viral pathogens harboured by animals and new, highly scalable technologies, are necessary

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 9 Issue 1

ANIMAL HEALTH

GCPv STUDIES IN THE FIELD Clinical development for your animal health products - with knoell at your side Working through a pandemic, we all know that it makes a big difference where your personnel are located. International travel has been restricted suddenly and without warning many times over the past two years, leading to critical business issues. knoell has offices located all across mainland Europe, meaning our clinical development team are in an ideal position to attend study sites with minimal disruption – making the future of your clinical studies more secure.

Our clinical development team offers: ◗ Start-to-finish service ◗ Safety and efficacy field studies - pilot and pivotal ◗ 20+ years’ experience managing clinical studies across Europe and the US ◗ Project management ◗ Study monitoring ◗ Working in compliance with VICH GL9 GCP ◗ Study Protocol and Final Study Report writing ◗ EDC system data managers and data handlers ◗ Sponsor representation worldwide ◗ Pre-clinical study coordination and support ◗ Screening and selection of CROs ◗ Experienced with companion and food-producing species ◗ In-house Quality Assurance auditing ◗ In-house Regulatory Experts

knoell are attending Animal Health, Nutrition, and Technology Innovation Europe on 21st-23rd February 2022. COME AND MEET US!

TALKING POINT

One on One with Dr. Johnson Ouma, GALVmed's New R&D Director In October 2021, GALVmed appointed Dr. Johnson Ouma as its new Executive Director in charge of Research & Development. Johnson, a seasoned researcher will play a leading role in shaping and delivering GALVmed’s Research & Development strategy centred on sustainable technologies addressing animal health challenges facing small-scale livestock producers. He speaks to us about GALVmed’s R&D strategy.

How does GALVmed’s mission fit into the bigger picture of global agricultural/development?

GALVmed works with partners to develop and roll out animal health solutions that contribute to improved lives and livelihoods of millions of smallholder livestock producers and their dependents. Improved animal health translates into improved livestock productivity and hence improved economic status (income) and availability of sufficient, healthy, and nutritious animal-source foods. The expected end outcome is alleviation of poverty, hunger, and malnutrition, thus directly contributing to the attainment of global development goals SDG 1 (ending poverty) and SDG2 (zero hunger).

You are coming in at a critical time when GALVmed is shaping its new strategy. What does GALVmed plan to do differently?

In developing the new R&D strategy, GALVmed dived deep to understand the needs of smallholder livestock producers (SSPs) by conducting a series of technical reviews, meeting key experts and interviewing veterinarians in sub-Saharan Africa and South Asia. Overall, these efforts led to the identification of specific technical and supply chain gaps in disease control which could be addressed through animal health product development. To address the identified gaps as part of strategy implementation, GALVmed will shift from product-oriented R&D to platform-oriented R&D. It envisaged that the focus on cross-cutting technologies will lead to development of products that meet demonstrated SSP needs and fill gaps in Animal Health Company (AHC) product portfolios, thus incentivising AHCs to invest in sustainable and profitable animal health product development and commercialization.

Some would argue that small-scale livestock producers have often been overlooked by Big Pharma because they are seen as not profitable enough and are resource intensive as opposed to big/mechanised producers. As one who has interacted closely with small-scale production systems, what would you say to those who underestimate small-scale livestock producers?

Small-scale livestock producers (SSPs) in Low- and MiddleIncome Countries (LMICs) are estimated to generate up to 40% of agricultural GDP. This is not a market segment to be ignored or underestimated. Having grown up in a smallholder farming system and based on my experience interacting with SSPs over the years, I have come to appreciate that SSPs are businessmen/women in their own right. SSPs are increasingly being more market-oriented and willing to take 6 International Animal Health Journal

calculated risks to make their farms profitable. What SSPs need and are willing to pay for are quality farm inputs that work for them in their settings, and the evidence that such solutions work. This is the value proposition that GALVmed endeavours to deliver to SSPs through targeted product development and commercialisation and by supporting establishment of localised manufacturing capabilities.

As the new head of research and development for GALVmed, what is your plan for GALVmed’s R&D work?

My plan for R&D work is anchored on the execution of GALVmed’s 2030 strategy implementation plan with the view to develop animal health products that meet the identified disease control needs of smallholder livestock producers in sub-Saharan Africa and South Asia. This will be achieved by delivering on four strategic themes: 1) end-to-end product development, 2) use of current antigens with new technologies, 3) industry support for localised animal health product development technology platforms in LMICs and, 4) establishment and support of specialised manufacturing capabilities. Together with strategic initiatives in the commercial and the enabling environment domains, these four R&D themes will provide a systematic and comprehensive framework for impactful interventions across the animal health product development chain. To deliver on the strategic themes outlined above, we plan to enhance our collaboration with GALVmed’s existing animal health industry partners, and to identify and establish new partnerships where necessary.

Considering that human capital is the most critical resource of any organization, I plan to prioritise the strengthening of capacity of R&D team members to ensure alignment with product development needs.

What does GALVmed aim to achieve by delivering on the four strategic R&D themes you mentioned earlier/above?

Our overarching aim in the new R&D strategy is to continue to support the development of efficacious and high-quality animal health products that address the critical gaps identified in SSP-focused disease control portfolios. Under theme 1 above, we aim to identify gaps and additional product needs to enhance SSP disease control capabilities through combination products (e.g., large ruminant reproductive multivalent vaccine) or enhanced product attributes. In theme 2, we aim to have a series of platform technologies that can express appropriate antigens that can eventually replace older vaccine technologies that suffer from lack of safety and efficacy. Under theme 3, we aim to strengthen local R&D product development and clinical capacity and registration of animal health products needed by SSPs in Africa.

This will involve working closely with animal health industry partners in identifying and evaluating technical, production (manufacturability) and commercial feasibility of relevant disease control technologies. Such efforts are ongoing under the Transforming Animal Health Solutions and Services for Low-Middle Income Countries (TAHSSL) platform that brings together Clinglobal, GALVmed, and ILRI. But we intend to establish more platforms as the need arises. Lastly, under theme 4, GALVmed aims to improve the supply and supply security of quality and affordable animal health products that address SSP needs in specific geographies. To achieve this Volume 9 Issue 1

TALKING POINT

Small-scale livestock producers are SSPs are increasingly market-oriented and seek inputs that work for them – Photo credit: GALVmed

aim, we will partner with upstream antigen manufacturers such as Pirbright Institute’s Veterinary Vaccine Manufacturing Innovation Centre (UK), and facilitate downstream active principle provision and customised antigen formulation, packaging and labelling.

According to the GALVmed’s website your intention is to work on the development of 25 products and product related technologies (processes or platforms that will increase access to products). These will comprise an approximate 50:50 mix of new and enhanced existing products and technologies. Which 3 products and technologies are you looking forward to improving?

By 2023/24, we seek to develop up to six new high-impact vaccines that are suitable for widespread use by SSPs in subSaharan Africa and S. Asia. The focus will be on multivalent/ combination vaccines. GALVmed will also assess novel vaccine delivery approaches to enhance the current portfolio of vaccines relevant to SSPs needs.

In addition to the focus on current GALVmed priority diseases, does the R&D department plan to develop any new project/product pipelines that would help deliver more impactful disease control?

Effective and sustainable on-farm disease control requires integration of various interventions. GALVmed has traditionally focused on the development of vaccines, diagnostics and www.international-animalhealth.com

therapeutics that target its priority diseases, majority of which are viral and bacterial. In an effort to achieve more holistic and impactful disease control in the future, the R&D department plans to investigate the potential of investments in ecto-and endoparasites control.

Johnson Ouma Johnson Ouma is the Executive Director of Research & Development for GALVmed. He has over 25 years’ experience in agricultural and public health research and product development. Prior to GALVmed, he was Chief Scientist and Founding Director of Africa Technical Research Centre (ATRC), a multicultural R&D Centre which he led for 10 years. He stablished and managed product development teams and partnerships, leading to successful development and commercialization of a portfolio of products for agriculture and public health. Johnson previously served as senior scientist and Deputy Centre Director with national agricultural research institutions KETRI and KARI (now KALRO) in Kenya for 17 years. He holds a master’s degree in Veterinary Parasitology and Immunology, and a PhD in Entomology and Genetics.

International Animal Health Journal 7

REGULATORY & MARKETPLACE

Veterinary Medicinal Product in United Kingdom: A Regulatory View Abstract Veterinary medicine is a field of the medicine that addresses disease, disorder and injury prevention, control, diagnosis, and treatment. It also covers animal husbandry, breeding, nutrition research and product development. The Veterinary Medications Regulation in the United Kingdom lays down legislative criteria for veterinary medicines manufacturing, classifying, supplying, marketing and use. In addition, the Veterinary Medicines Directorate is the national competent body, as well as an Independent Regulator.

In the UK, there is an EU set of regulatory procedures covering veterinary medical products, including safety, licencing, and monitoring. The goal is to provide an overview of the wide range of regulatory checks that control the licencing, provision, and monitoring of veterinary pharmaceutical goods. These thorough inspections ensure that our animals' health and welfare are safeguarded by using safe, effective, and highquality veterinary medicines, as well as by people and the environment.

Keywords Veterinary Medicines, Veterinary Medicines Directorate (VMD), Department of Environment, Food and Rural Affairs (DEFRA), Directives, Market Authorisation, Regulations.

Introduction The United Kingdom of Great Britain and Northern Ireland, once in a while known as the United Kingdom (UK) or Britain, is a sovereign country situated off the north-western shoreline of Europe's centre region. The United Kingdom is comprised of the island of Great Britain, the north-eastern piece of the island of Ireland, and a sprinkling of more modest islands dissipated all through the British Isles.

Figure 1: Map of United Kingdom Cities23

The United Kingdom is a constitutional monarchy and a unitary parliamentary democracy. Over several hundred years, the United Kingdom has evolved through a series of annexations, unions, and separations of constituent countries.

The United Kingdom has the fifth biggest ostensible GDP and tenth-biggest buying power equality economy on the planet (PPP). It has a prosperous economy and is positioned thirteenth on the planet as far as human turn of events. The United Kingdom was the world's originally evolved country and the biggest and most impressive force during the nineteenth and mid-20th century.21,22 • • • • • •

Capital city – London Official language – English Area – 93,628 square miles (242,500 km2).

Population – 68,321,339 GDP – $3.12 trillion (nominal; 2021 est.), $3.17 trillion (PPP; 2020) Currency – Pound sterling (GBP, £)

Economy of United Kingdom The economy of the United Kingdom is an all-around created social market and market-arranged economy. It has the fifth-biggest ostensible GDP, 10th biggest buying power 8 International Animal Health Journal

Figure 2: United Kingdom on Globe24 Volume 9 Issue 1

REGULATORY & MARKETPLACE

Figure 3: Population Growth in United Kingdom25

equality (PPP), and twenty-first-biggest GDP per capita on the planet, representing 3.3 percent of worldwide GDP. The United Kingdom is comprised of England, Scotland, Wales, and Northern Ireland, and it is one of the world's most globalised economies. The United Kingdom was the fifthbiggest exporter and fifth-biggest merchant on the planet in 2019. It likewise had the third and fifth most noteworthy inward and outward unfamiliar direct speculations, separately. In 2020, exchange with the European Union's 27-part states represented 49% of commodities and 52 percent of imports in the United Kingdom.22 Climatic Conditions of United Kingdom • The climate in the United Kingdom is mild.

• The UK experiences chilly, rainy winters and warm, wet summers.

• It lacks the extremes of heat and cold, drought, and wind found in other regions. Weather is also incredibly unpredictably unpredictable.

The weather in the United Kingdom is not always consistent. The climate in London, which is located in the south-east of the United Kingdom, is warm and dry in the summer and cold and dry in the winter. Cumbria, in England's mountainous north-west, has colder winters and more rain.

Figure 5: Climatic Conditions in United Kingdome27

The United Kingdom's climate is separated into four main regions: South East

cold winters, warm and dry summers

South West

mild and very wet winters, warm and wet summers

North West

mild winter, cool summers and heavy rain all year

North East

cold winter, cool summers and steady rain all year

ICH Stability Zones – Zone I [Temperate Zone] Long Term Stability Testing Conditions – Climatic Zones

Temperature

Humidity

Minimum Duration

Zone 1

21ºC ± 2ºC

45% RH ± 5% RH

12 Months

Figure 4: Economy Comparison26 www.international-animalhealth.com

International Animal Health Journal 9

REGULATORY & MARKETPLACE Accelerated and Intermediate Stability Testing Conditions – Climatic Zones

Temperature

Humidity

Minimum Duration

Accelerated Ambient

40ºC ± 2ºC

75% RH ± 5% RH

6 Months

Accelerated Refrigerated

25ºC ± 2ºC

60% RH ± 5% RH

6 Months

Accelerated Frozen

5ºC ± 3ºC

No Humidity

6 Months

Intermediate

30ºC ± 2ºC

65% RH ± 5% RH

6 Months

Veterinary Medicine, the Branch of Science that Deals with Animals Veterinary medicine is the branch of medicine concerned with animal disease, disorder, and injury prevention, control, diagnosis, and treatment. Aside from that, it deals with animal husbandry, breeding, nutrition research, and product creation. Veterinary medicine covers a large range of animal species, both domesticated and wild, as well as a wide range of diseases that can affect them.

•

•

Veterinary science serves to human wellbeing both straightforwardly and by implication by observing and controlling zoonotic sickness (irresistible illness passed from nonhuman creatures to people). They likewise assist with food security by observing and treating animals, just as psychological well-being by guaranteeing that pets are solid and enduring.

Veterinary researchers every now and again team up with disease transmission experts and other wellbeing or regular researchers, contingent upon the kind of work they do. Ordinarily, veterinarians are ordered by law to really focus on the prosperity of creatures. To keep creatures protected and solid, veterinarians analyse, treat, and care for them.18

Figure 6: A domestic cat being operated on by a veterinarian19

The Veterinary Medications Regulation (VMR) establishes legal criteria for the manufacture, classification, supply, marketing, and use of veterinary medicines in the United Kingdom. Furthermore, veterinary medical products (VMPs) are subject to a number of EU regulatory regulations, including safety, licencing, and monitoring.1 The Veterinary Medicines Directorate is the UK's national competent authority and independent regulator (VMD).

The European Pharmaceuticals Agency (EMA) is in charge of scientific review and monitoring of medicines at the EU level.1 Before gaining a Marketing Authorisation (MA) or a licence for sale and supply in the UK, all authorised veterinary medications for animals must go through a rigorous regulatory clearance process.1 Each permitted veterinary medicinal product must fulfil the requisite standard of safety, efficacy, and quality, as determined by scientific research conducted by animal medicine businesses and subsequent examination by independent regulatory authorities. This guarantees that

Discussion: Factsheet Product

Veterinary Medicines

Country of Filing

U.K.

Regulating Agency

Veterinary Medicines Directorate

Department

Department of Environment, Food and Rural Affairs [DEFRA]

Regulatory Classification

Veterinary Medicinal Product

Definition of Veterinary Medicinal Product

Any drug or mixture of chemicals that can be employed in animals or given to them with the objective of restoring, correcting, or modifying physiological functioning by pharmacological, immunological, or metabolic action, or performing a medical diagnostic.

Form

Application forms (Annex A or on the VIVID's website): https://www.gov.uk/government/collections/ veterinary-medicine-licence-application-forms

Mode of submission

Submission through electronically (e-mail to): borderline@vmd.defra.gsi.gov.uk or in duplicate hard copy to the Enforcement team.

Directive 2001/82/EC

The Veterinary Medicinal Products Directive (as amended) establishes restrictions for the manufacture, authorization, marketing, distribution, and post- authorization surveillance of veterinary pharmaceuticals in all European Member States.

Licensing

£4,915,000 (paid for by the veterinary pharmaceutical industry)

Statutory Residues

£3,693,000 (paid for by the food industry)

Non-statutory residues

£1,054,000 (paid for by Defra)

Policy

£2,298,000 (paid for by Defra)

Validity

5 years Table 1: Factsheet on Veterinary Medicinal Products in U.K

10 International Animal Health Journal

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REGULATORY & MARKETPLACE animal medicines are both safe and effective, as well as meeting quality standards.1 In the United Kingdom, antibiotics are only available on prescription from a veterinary surgeon; as a result, all antibiotics are POM-V (prescription only drugs – through a veterinary surgeon).1 All veterinary medications obtained and used in foodproducing animals must be documented on the farm, according to the VMR. When farm animals are given veterinary medications, a mandatory residue surveillance programme is used to ensure the safety of the food they generate (meat, milk, eggs, etc.). This initiative ensures that the UK meets an EU regulatory need to test samples for veterinary medication residues.1

The Veterinary Medicines Regulations, 20133 Introductory Text

Part 1 Part 2 Part 3 Part 4 Part 5

Schedule 1

Marketing Authorisations

Schedule 2

The manufacture of veterinary medicinal products

Schedule 3

Classification and supply, wholesale dealers and sheep dip

Pharmacovigilance is a continual process of veterinary drug safety and efficacy monitoring that enables the safe use of effective medicines.1

Schedule 4

Administration of a veterinary medicinal product outside the terms of a marketing authorisation

Schedule 5

Medicated feeding stuffs and specified feed additives

Only licenced veterinary medications are allowed to be used in the United Kingdom. The VMD's enforcement division takes pre-emptive action in the case of a breach of the VMR, which may include criminal prosecution.1

Schedule 6

Exemptions for small pet animals

Schedule 7

Fees

The Veterinary Medicines (Regulation (EU) 2019/6) will modernise the current enactment in the European Union (EU) on veterinary medication authorisation and utilisation when it produces results on January 28, 2022. It contains further measures to work on veterinary drug accessibility and security, just as expanding EU antimicrobial obstruction endeavours.

The European Medicines Agency (EMA) is working intimately with the European Commission and other EU accomplices to plan for the Regulation's execution.

The Regulation's principal objectives are to: • promote the development of novel veterinary medications, notably those aimed at niche markets (minor use and minor species).

• streamline pharmacovigilance standards, for example, to improve the functioning of the internal market for veterinary medications by simplifying the regulatory environment and decreasing administrative cost for pharmaceutical businesses manufacturing veterinary medicines.

• improve EU antimicrobial resistance efforts by passing specific measures to ensure the responsible and appropriate use of antimicrobials in animals, such as reserving some antimicrobials for human sickness treatment.2 Regulation (EU) 2019/6 amends Regulation (EU) 726/2004 on veterinary medicine authorisation and supervision, which

Table 3: Contents of the Veterinary Medicines Regulations, 2013

presently supervises the centralised marketing authorisation system for both human and veterinary medications.

In December 2018, the European Parliament and the European Council enacted Regulation (EU) 2019/6. It will take effect on January 28, 2022.2 The Veterinary Medicines Directorate (VMD)4,5 A. Authorisation requirements B. Post authorisation requirements C. Manufacturing D. Selling/Marketing E. Using medicines F. Import/Export G. Other A. Authorisation Requirements6 I. Product Types: Pharmaceutical and biological products are divided into two categories.

Biological goods contain active compounds that are created or extracted from a biological source and require a combination of physiochemical and biological tests, as well as the production process and its control, to characterise and determine quality.

Benefits and EMA Responsibilities Benefits of the veterinary regulation2

Increased availability and access to safe and high-quality medicines for veterinarians, farmers and pet owners to treat and prevent animal diseases Reduced administrative burden and better incentives for pharmaceutical companies developing new and innovative veterinary medicines, benefiting in particular micro, small and medium-sized enterprises (SMEs) New and enhanced rules to keep antimicrobials (including antibiotics) effective based on a ‘One health’ approach for the benefit of animal and public health and every EU citizen Revising its procedures and regulatory and scientific guidance documents, in line with the Regulation and its implementing and delegated acts

EMA is also responsible for2

Leading the implementation of Information Technology (IT) systems required by the Regulation, including the Union Product Database, which will provide information on all authorised veterinary medicines and their availability in EU Member States Implementing the outcomes of the implementing and delegated acts Table 2: Benefits and EMA Responsibilities on Veterinary Medicinal Products www.international-animalhealth.com

International Animal Health Journal 11

REGULATORY & MARKETPLACE Biological veterinary drugs include the following items:

VI. UK Public Assessment Reports (UKPARs)

•

In most cases, a public assessment report (PuAR) will be published on the VMD's Product Information Database (PID), along with the SPC, label text, and a post-authorisation assessment (PAA). Since a product was initially approved, the PAA has kept track of all applications submitted for it.

• •

An immunological veterinary drug given to animals in order to create active or passive immunity, diagnose immunity in order to desensitise them to allergens, or cause an impact based on antigen-antibody interactions.

Veterinary medications made from plasma and blood Veterinary pharmaceuticals that come within Part A of Annex A to Regulation No. 2309/93

II. Authorisation Routes: There are five ways to get an MA in the UK, or parts of them: • • • • •

GB MA. – National NI MA. – National Centralised European procedure which will include NI Mutual Recognition European procedure with NI as concerned member state Decentralised European procedure with NI as concerned member state

These pathways govern the rules, methods, processes, and timeframes used in processing an application for a new MA. The authorisation is only valid in the territories for which it was granted, and it is subject to all applicable rules.

III. Legal Bases: There are numerous legal bases for requesting an MA, each reflecting the type and content of data needed to support an application.

IV. Distribution Categories: POM-V will be the distribution category for an extraordinary MA. For PMAs, if the product satisfies the following conditions, the distribution category can be modified from POM-V to POM-VPS: • •

Has been on the market for at least a year and is currently selling well exclusively makes preventative claims It has a low risk of adverse events (AE) and is suspected of being ineffective (SLE)

A MAPI product's distribution category will be the same as the parent product's distribution category.

V. Product Authorisation Number An approved item in the UK will have an authorisation number went before by the image Vm on item documentation and naming. This means that the item has been tried and approved for use as per the headings in the item writing.

The MAH organisation number is the initial five numbers, trailed by an item number all together. The principal number of the item number component will be the region recognisable proof number: • • •

4 – UK wide – Pre 2021 authorisations retaining a UK wide authorisation and these product numbers start with the number 4 3 – NI MA – For MAs authorised in NI only 5 – GB MA – For MAs valid in GB only

Focal authorisations gave by the European Commission (EC) are legitimate in all EU part states, including Northern Ireland, and will be appointed an EU MA number.

12 International Animal Health Journal

B. Post Authorisation Requirements7 Guidance: • Apply for special batch control of a pharmaceutical veterinary medicine • Submit an application for a batch release of an immunological veterinary medication.

• Veterinary Pharmacovigilance Responsibilities for Authorisation Holders C. Manufacturing8 Guidance: • Veterinary medicine manufacturing authorizations • Production and distribution of medicated feedstuffs D. Selling/Marketing9 Guidance: • Medicines for tiny pets are exempt from approval.

• Authorisation from a veterinary medicine wholesaler • Approval of facilities for the retail distribution of veterinary pharmaceuticals by appropriately authorised individuals (SQP) • Veterinary practitioners' registration and inspection E. Using Medicines10 Guidance: • The cascade: giving unapproved medications • Veterinary medicine • Horse medicine • Controlled drugs • Bee medicine availability in the UK F. Import/Export11 Guidance: • Importing a veterinary medicine into the United Kingdom • Exporting drugs and medicines: specific rules G. Others12 Guidance: • File an appeal against a VMD regulatory decision.

European Medicines Agency (EMA), Veterinary Medicines Regulatory Information13 This section contains information about veterinary medication regulation in the European Union (EU). It is especially relevant to the centralised procedure, in which the European Medicines Agency (EMA) plays a crucial role.

The navigation menu is divided into three categories, each of which corresponds to one of the essential stages in the lifespan of a pharmaceutical product: • • •

A. Research and development, including maximum residue limits (mrls); B. Marketing authorisation.

C. Post-authorisation.

Volume 9 Issue 1

REGULATORY & MARKETPLACE

A. Research and Development The European Medicines Agency (EMA) prompts and helps organisations that are exploring and creating veterinary prescriptions. This remembers logical and administrative data for how to plan and direct clinical preliminaries, consistence guidelines, setting up greatest build-up limits for prescriptions and biocides, advancement backing, and impetuses for organisations creating drugs for minor use/ minor species (MUMS)/restricted business sectors.14 B. Marketing Authorisation The European Medicines Agency (EMA) is liable for coordinating intelligent assessments of bound together promoting authorisation applications (MAA). The united displaying authorisation, once yielded by the European Commission, is authentic in all European Union (EU) Member States, Iceland, Norway, and Liechtenstein.15

C. Post-Authorisation The European Medicines Agency (EMA) prompts drug organizations whose therapeutic items have been endorsed in Europe on logical and administrative issues. This is alluded to as the item lifecycle's post-approval stage.

This information outlines marketing authorisation holders' responsibilities in areas such as pharmacovigilance, applying to vary a marketing authorization, submitting product data to the EMA, and reporting product defects or recalls.16 Summary and Conclusion The Veterinary Medicines Regulation in the United Kingdom builds up authoritative prerequisites for the assembling, arrangement, supply, showcasing, and utilisation of veterinary medications. The Veterinary Medicines Directorate (VMD) is the public capable position and free controller in the

Key Regulations17 Legal controls on veterinary medicines Future Veterinary Medicines Regulations The EU and UK Trade and Cooperation Agreement

• • • • • • •

The Veterinary Medicines Regulations (VIR) 2013, as revised, stay in power in the United Kingdom for the guideline of veterinary prescriptions.

The Northern Ireland Protocol (the Protocol) expresses that Northern Ireland will keep on being dependent upon EU law.

Continued acknowledgement of specific administrative capacities acted in the EU for clusters set available

by December 31, 2022 (depicted in Veterinary Medicines Directorate (VMD) Information Hub explainers) Many of the prerequisites starting in 2023 will be fused into the new Veterinary Medicines Regulations.

Proposed changes to the Regulations will be dependent upon formal, public discussion in 2021, during which time Veterinary Businesses will actually want to remark (date TBC).

The EU-UK Trade and Cooperation Agreement (TCA) builds up the terms for shared acknowledgment of GMP authentications gave by NCas for restorative items, including veterinary drugs In spite of the fact that clump (QC) testing isn't covered by the arrangement, the UK will singularly perceive bunch (QC) testing acted in the EU/EEA until December 31, 2022.

Table 4: Key Regulations on Veterinary Products in U.K.

www.international-animalhealth.com

International Animal Health Journal 13

REGULATORY & MARKETPLACE 9.

10.

11.

12.

13.

14.

15.

16.

17.

United Kingdom. Logical investigations directed by creature medication organisations, trailed by free administrative position assessment, guarantee that every veterinary restorative item endorsed fulfils the necessary guidelines of wellbeing, viability, and quality. This guarantees that creature drugs are ok for use, useful (compelling), and satisfy quality guidelines. These courses decide the guideline, systems, cycles, and timetables utilised in preparing an application for another MA. Once conceded, the authorisation may be substantial in the domains applied for and will be dependent upon material guideline. The dissemination class of a remarkable MA will be POM-V. An approved item in the UK will have an authorisation number went before by the symbol Vm on its item writing and marks. This shows that the item has been evaluated and endorsed for use as per the guidelines on the item writing.

The initial 5 numbers are the MAH's organisation number followed by a successive item number. The main number in the item number component will be utilised to distinguish the domain. By and large, a public appraisal report (PuAR), just as the SPC, name text, and post-authorisation evaluation, will be accessible on the VMD's Product Information Database (PID) (PAA). The PAA contains a rundown of all applications finished on an item since its underlying endorsement. This segment contains data on the guideline of veterinary drugs in the European Union (EU). The European Medicines Agency (EMA) prompts and helps organisations that are exploring and creating veterinary medications. The European Medicines Agency (EMA) is accountable for leading logical appraisals of incorporated advertising authorisation applications (MAA). The European Medicines Agency (EMA) prompts drug organisations whose restorative items have been endorsed in Europe on logical and administrative issues.

REFERENCES 1.

2.

3.

4.

5.

6.

7.

8.

https://www.noah.co.uk/briefingdocument/controls-onveterinary-medicines/ https://www.ema.europa.eu/en/veterinary-regulatory/ overview/veterinary-medicines-regulation https://www.legislation.gov.uk/uksi/2013/2033/contents/ made https://www.gov.uk/government/organisations/veterinarymedicines-directorate https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#authorisationrequirements https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#post-authorisationrequirements https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#manufacturing

14 International Animal Health Journal

18.

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https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#selling/marketing https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#using-medicines https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#import/export https://www.gov.uk/government/collections/veterinarymedicines-guidance-notes-vmgns#other https://www.ema.europa.eu/en/veterinary-medicinesregulatory-information https://www.ema.europa.eu/en/veterinary-regulatory/ research-development https://www.ema.europa.eu/en/veterinary-regulatory/ marketing-authorisation https://www.ema.europa.eu/en/veterinary-regulatory/postauthorisation https://brexit.bakermckenzie.com/2021/06/30/veterinarymedicines-directorate-guidance-on-the-regulation-ofanimal-health-products-in-the-uk-post-brexit/ https://en.wikipedia.org/wiki/Veterinary_medicine https://en.wikipedia.org/wiki/Veterinarian https://studylib.net/doc/7349697/united-kingdomveterinary-medicines-directorate-woodham-lane https://en.wikipedia.org/wiki/United_Kingdom https://en.wikipedia.org/wiki/Economy_of_the_United_ Kingdom https://annamap.com/united-kingdom/united-kingdomcities-map.jpg https://en.wikipedia.org/wiki/File:United_Kingdom_ (orthographic_projection).png https://www.guildford-dragon.com/wp-content/ uploads/2021/05/107546557_population_line_chart_640nc.png https://www.bbc.com/news/business-57427997 https://www.bbc.co.uk/bitesize/guides/zpykxsg/revision/3

Dr. Balamuralidhara. V Associate Professor, Department of Pharmaceutics, JSS College of Pharmacy, Mysuru, JSS Academy of Higher Education and Research.

Mysuru-570015, Karnataka, India

Email: baligowda@jssuni.edu.in

Mr. Chandan BV Research Student, Pharmaceutical Regulatory Affairs, JSS College of Pharmacy, Mysuru, JSS Academy of Higher Education and Research.

Mysuru-570015, Karnataka, India

Email: bvchandanchandu@gmail.com

Akhilesh Akki Research Student, Pharmaceutical Regulatory Affairs, JSS College of Pharmacy, Mysuru, JSS Academy of Higher Education and Research.

Mysuru-570015, Karnataka, India

Email: akhileshakki209@gmail.com

Volume 9 Issue 1

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International Animal Health Journal 15

RESEARCH AND DEVELOPMENT

Integrating a Workplace Wellbeing Initiative into Your Vet Practice and the Benefits it Brings Being a vet is one of the best occupations in the world.

However, numerous studies have shown that working in veterinary practice can be a stressful experience.

Integrating a wellness initiative into a veterinary practice may help to lower individual stress and lead to a more collaborative team.

Setting up a wellbeing initiative in practice is hard work because it contains many facets and will fail unless it is embedded in the culture of the team.

As with any new business venture, the first question to ask is why it is needed?

• Is the culture and atmosphere positive at work?

• What are the values of the business?

• What is the vision and mission of the business?

If the answer to these questions is already known and the responses are positive, then this is, probably, a practice that is fun to work in; trust between employees and employers is high and individuals love what they do.

Stress will typically be lower in a practice like this; productivity will be higher and employee retention will be high.

If this is not the case, then work needs to be done to improve employee trust and motivation. Before any fancy well-being initiative is put in place, the team needs to be listened to by the owner and senior leadership.

• • •

What are the issues in the business?

Is there any bullying?

Do the team trust the senior leadership?

As part of a new initiative, everybody needs to feel they have been listened to. ‘Envisioning days’ for the team to look at the vision, mission and values of the business are vital.

Not only will this add clarity to the business and where it is going but will also make the team feel more appreciated.

This is also the time to name the values the business stands for. By naming the values, it will often become clear who in the team does not live up to or aspire to those values.

Those members of the team may find that they need to go elsewhere to be happy in their jobs. People who do not fit into the culture will often be disruptive and can easily create a toxic environment where everybody stops enjoying their work and dreads coming in. The team will become better at recognising behaviours that do not fit in with the business ethics and values and will feel more empowered to call them out once they have been written down. Values apply to leaders as much as employees!

Once the vision, mission and values are in place, it is a case of deciding what are the things that must be done to deliver on the vision and who will be responsible for them.

Choosing the right person to take on this job is a vital part of the senior manager’s duties in defining the role and bringing the best person in to do it, a role that the team member will enjoy and get excited by.

All of these things will reduce employee stress and help the employee enjoy or even love their job.

16 International Animal Health Journal

By this stage, the practice will, hopefully, have a positive practice culture with a clear vision and an obvious road map to get there. There will be a well-motivated team who love what they do and are in a good mental state because they are enjoying their job and they have civil or maybe friendly relationships with the other members of the team. There is nothing that will reduce an employee’s wellbeing more than a toxic environment.

With these sturdy foundations built, what are the next steps to continue to develop an excellent attitude towards wellbeing in the practice?

Leaders must first of all walk the talk and mirror the good behaviour to the rest of the team. To be truly effective in the workplace, it is important that shifts are not too long, and relevant breaks are taken. This allows the team to calm themselves before going back into the clinical environment but also allows for the person to eat, drink and go to the toilet without feeling they are letting the boss or team down. These are normal requirements in almost every job and should not be scrimped on in the veterinary field. Team members will be less stressed, more rested and will perform to a higher standard with their duties. Professor Matt Walker of Stanford University has noted that a loss of sleep below 7–8 hours can massively affect our ability to perform our work tasks. Being well-rested will lead to a team that produces higher quality work.

What makes up a good practice wellbeing initiative?

• Meetings • Rewards and recognitions • Access to resources • Fun Events • Accreditation schemes • CPD • Charity days Meetings and Team Training Regular meetings in teams and 1:1s with line managers can be very effective at increasing camaraderie amongst teams and also dealing with disagreements between team members before they become a larger problem. These meetings can often help teams and individuals become productive but also allow individuals in the team the ability to determine the best way that their team should function. This active listening by team leaders and thanks when such events lead to better work practices can raise individual and team morale.

Wellbeing and training plans can be reviewed on a monthly or quarterly basis alongside performance reviews.

If an employee can see that their work consistently meets or exceeds expectations, this will affect their wellbeing and feelings of worth. This ensures the team feels supported and motivated at work. Meetings can be fun too. Setting aside formal times for coffee breaks to allow team members to have some social time together is also very important.

Rewards and Recognitions Allowing team members to have a day off for their birthday is worth considering. Birthdays are important times to reflect and celebrate. By giving these days off if they occur during the working week, employees can see that their employer cares about them as people, not just as someone who helps them fulfil their business goals but also who wants the best Volume 9 Issue 1

RESEARCH AND DEVELOPMENT for the employee too. It is also important to celebrate work anniversaries, feast days like Christmas or Diwali, and to consider employee of the month or quarter awards. This again demonstrates the worth of the employee in the employer’s eyes. If all the employees can pick their teammate of the quarter, this gives more ownership to the team and again recognises the importance of their opinion. They can see what they think is important to the employer.

Access to Resources There are so many resources that can contribute to employees’ well-being. It is well recognised that exercise can be beneficial to everyone. Employers can pay for team members’ gym or swimming monthly membership or encourage a steps competition for a month. A veterinary practice can be an unhealthy place. However, by encouraging exercise and providing fresh fruit in the staff room, employers can demonstrate the importance of exercise and diet in good physical and mental health.

There are lots of great apps and webinars to help with mindfulness and meditation like Headspace and Sanctus.

The Webinar Vet has provided lots of useful resources on mindfulness and positive mindsets in conjunction with the Royal College of Veterinary Surgeon’s Mind Matters Initiative.

Vetlife also provides telephone services staffed by trained volunteers for those members of the profession to discuss a problem and hopefully minimise its impact. Numbers like this should be prominently displayed in the practice to allow easy access.

Fun Events Organising physical evenings out has been difficult over the last two years of the pandemic but the work’s night out should not be lost post-pandemic. However, neither should funding of large amounts of alcohol be countenanced either. The younger generation seems much less attracted to alcohol than the older generation. Fun events like paintballing or fun runs can engender greater teamwork skills. Social events allow team members to get to know each other better.

Accreditation Schemes Schemes such as Investors in People, Investors in the Environment and Great Places to Work can help to measure the success of the business in how well it engages its team.

In 2013 only 52% of people thought the Royal College was a great place to work. By following the advice of the scheme, this had risen to 91% two years later.

The RCVS chief executive at the time, Nick Stace, said the improvement demonstrated the great strides made by the college over the past three years and recognised the resolve of staff and council to improve its working practices, how members communicate with each other and overall wellbeing. He also said that it was testament to the importance of two-way communication – of giving staff the opportunity and freedom to come up with ideas and having a senior team willing to listen to and implement these where appropriate.

He felt that members of the RCVS council in particular had been very supportive of efforts to improve staff engagement and recognise a more motivated and happier workforce at the college and that that would be reflected in the quality of service offered to members of the profession. Passing accreditation schemes can also be a time for great pride within the organisation and helps to benchmark the business against its peers. In these times of the Great Resignation being seen as a great place to work as opposed to a good or mediocre business can massively help in staff retention and create stability in the business. www.international-animalhealth.com

Clinical and wellbeing CPD A poster at a pre-pandemic BSAVA Congress looked at the effect of good quality CPD on clinicians’ wellbeing and showed that it had a very positive effect. Many vets are perfectionists and lifelong learners. They want to become more confident, able clinicians. With the advent of online CPD, there is a wealth of knowledge that can be acquired at a much lower cost than physical training alone. Training can be done at a time suitable for the learner, fitting in with a heavy workload and the demands of homelife, without the need for travel. Whilst not decrying physical CPD, digitalising veterinary CPD has democratised learning and made it available to vets and nurses on low salaries in developing countries who become better professionals which in turn leads to improved animal welfare and greater work satisfaction.

Charity Contributions Giving each employee a couple of days to dedicate to charity shows the caring side of the business and allows the employee to spend some extra time doing something they are passionate about. These days have to be agreed upon and verified but are an important added benefit to working in a purpose-centred business. Events can also be organised to involve the team – working in a nature reserve or going to a care home or offering some help for free to a local animal charity. IVC Evidensia’s recent Positive Pawprint is a very interesting document showing the initiatives that one of the UK’s largest corporates is undertaking. A highlight is a budget that each clinical member of the team can use on stray animals or owned animals in precarious situations to support treatment. This treatment of animals who would otherwise not be treated can be a great morale boost for the practice. Some businesses decide on a charity for the year and raise money with raffles, sponsored events and cake sales. All of these activities can have beneficial effects on the organisers.

Integrating a wellbeing initiative into the practice can have massive benefits both for the productivity and profits of the business but also to help create a positive culture within the team as well. As a purpose-centred, service-orientated profession, the veterinary industry is used to giving of itself to the animals under its care. In a well organised business where this can be done sustainably, supporting the team at all times means that many good things can flow from this.

Anthony Chadwick Anthony Chadwick BVSc CertVD MRCVS qualified from Liverpool University in 1990 and received his certificate in Veterinary Dermatology in 1995 from the Royal College of Veterinary Surgeons. Anthony was involved in first opinion practice and dermatology referrals until 2016. In 2010 Anthony set up The Webinar Vet, the first online training platform for veterinarians and nurses, in an attempt to make veterinary education more accessible and affordable across the world. Since that time tens of thousands of veterinarians and nurses have accessed the platform from all over the world. The Webinar Vet’s first virtual conference took place in 2013.

During the pandemic, The Webinar Vet helped to take over 40 veterinary meetings and conferences online including WVAC2020 and WCVD9.

Web: www.thewebinarvet.com

International Animal Health Journal 17

RESEARCH AND DEVELOPMENT

From Molecule to Market Series Part I: Finding the Money Introduction This is the first article in our "From Molecule to Market" series, where we address the different phases in the animal health product development journey.

Each step has its challenges and could potentially jeopardize all the work done to reach that point. Due to the complexity and vastness of the topic, we'll dedicate an article series in order to take a deep dive into the intricacies of the drug development process and what it takes to get an animal health product to market.

In this article, we share our insights on funding your idea.

Finding the Money The age-old problem how to find the funding to support a project. Whether you are a start-up with a great idea or a large multinational, there are always too many ideas or projects to support. This paper will endeavor to outline some of the (possibly more novel) options available to fund animal health developments.

Regardless of the size of your organisation or business, to secure funding it is important to clearly articulate: 1.

Why the project is worth investing in.

2. What the potential financial reward on completion is.

3. How the risk profile and the chances of success look.

4. The road map for the project, including timeframe and budgets.

Types of Funding for your Idea There are a number of ways to fund your business or project: • Your own money.

• Government grants.

• Equity funding where an investor will take a stake in your business.

• Incubators.

• Borrowing money.

• Product financing.

• Partnering with a larger player, which is more applicable to smaller start-up organisations. it will depend greatly on the circumstances, which is appropriate, and often a combination of a few sources will ultimately be the outcome.

Government Grants These come in various forms and differ by country/state, it is worth investigating what is available and understand the nuances as it may inform some of the decisions you make, such as where development work is done.

Several governments offer R&D taxation incentives, where money spent on development and research can have tax benefits. Expert tax advice can be useful to ensure you are aware of what’s available.

In areas where the Government has a special interest, for example ruminants and their effect on climate change, they 18 International Animal Health Journal

may offer grants to support development of products that can support their efforts in a particular area.

Governments sometimes have grants available for new businesses, or a business that has the potential to benefit the country or state economically, such as employing people.

Typically, Government grants will pay a percentage of your investment, so you will still need to find other funds.

Equity Funding With equity funding you bring funds in by selling part of your company to investors, known as equity capital. This dilutes your overall shareholding, but often having a smaller share of something bigger is better than a large share of something small. Large multinationals will often raise funds through a capital raise to fund an acquisition or a major expansion. Smaller businesses bring in investors such as angel investors, venture capitalists or private equity. Angel investors are often successful entrepreneurs and bring in early money to an organisation. Given the risk profile of a start-up, they will be wanting a high return on the money invested. Venture capitalists invest in higher risk earlystage businesses and are also looking for higher returns.

Private equity tends to invest once a company has been operational for a number of years and has a successful track record. They invest as they see the potential to grow the business, possibly through additional investment and through acquiring a number of similar businesses to create a larger company. Private Equity usually has an investment window of 4 to 8 years depending upon the type of business, after which they sell to liquidate the return on the initial investment.

Volume 9 Issue 1

RESEARCH AND DEVELOPMENT Investors are buying into a business when they believe in the people and the project, and are seeing potential financial rewards in the medium term. The type of investor will depend on the stage the business is in. The higher the risk, the higher the return the investor wants.

The advantages of bringing on investors is that they bring additional knowledge and skills which can support the development of the product and may expedite the project.

Alternatively, diluting the shareholding and decision-making rights may not be attractive to some founders.

Incubators Specializing in Animal Health There are specialist incubators within the Animal Health sector looking for new, innovative solutions, usually early in the development process. These incubators assist with sourcing funding, management, and strategy development.

In return, they will take an equity position within the company. They can bring an established network that can act as advisors. The equity position that the incubator takes will dilute the founder’s shareholding. However, this dilution needs to be balanced with the benefits a specialist incubator can bring to expedite the development.

in the organisation. Large or small organisations needing funds to develop a product can look to this approach. The risk of the development is shared between the fund and the business. How the risk is shared between the parties will determine how the rewards are shared at the end of the development. The funds’ way to make a profit is through the sale of the developed/registered product. The cleaner and simpler this sale process is, the more attractive the proposition. The fund is unlikely to be interested in a drawnout payment schedule based on sales performance.

To expand on this financing method, let’s talk through a hypothetical example. A start-up has a potential vaccine and initial early-stage studies have indicated it may offer therapeutic benefit to prevent facial eczema in sheep. To fully develop this vaccine and achieve registration in the US, it will cost an estimated USD$20m and take 7 years. A fund specialising in pharmaceutical development may be interested in investing in this development with the intention of selling the registered vaccine on successful registration.

The return the fund requires from this sale will depend on the risk profile of the project. Before investing in the product, the fund will do significant due diligence, considering

Borrowing Money Money is usually borrowed from a bank or financial institution. The advantage is that there is no dilution to the ownership of the business. Though for a start-up, a financial institution may want additional security to protect themselves in a default situation. Typically, a financial institution will want to see a business plan, financial reporting and forecasted profits, and understand where the money is to be invested. The higher the risk the higher the interest rate.

• • •

Product Financing This is a more novel approach to funding the development of an animal health product. There are funds specialising in investing in pharmaceutical products and – more recently – specifically in animal health assets. They understand the risks and timelines associated with the product development journey of a new product.

•

The advantages of this type of funding are that it’s specific to the product and doesn’t dilute the shareholding

The fund needs to have confidence in the company that is doing the product development, clinical studies, and regulatory work. They will be looking for significant experience and a successful track record, including managing budgets and timelines. Prior to approaching a fund, having a detailed plan around the development and who is doing the work will support the discussion with the fund. If the work is being done in house, also provide examples and case studies of previous development projects and the credentials of the people working on the project. If being done by external parties, select well known, experienced partners that the fund will have confidence in to deliver the desired outcome.

• • • •

the market potential of the vaccine other treatments already on – or coming to – the market who is doing the development and if they have a successful track record the probability of technical success (pTS) the studies done to de-risk the project especially in the early stages required patent searches to confirm freedom to operate which companies would be interested in buying the vaccine to market on successful registration the cost effectiveness for the end user

A specialist pharmaceutical fund may take on some of the development risk. So, if the product development fails, the money may not need to be repaid. This risk/reward scenario means that the fund will want a signifcant share of the reward if the product is successful.

Partnering with a Large Animal Health Company Large companies are always looking for new and interesting therapeutic opportunities. Approaching one may present different options to extract value from your asset. There are several options: • the company may be interested in licensing and taking on the full development where the start-up would receive royalty payments if the product was successful • they may want to buy the asset outright • they could support with some funding to determine viability.

The partner, as with a product financing fund, will want to do due diligence and will ask similar questions to those above. www.international-animalhealth.com

International Animal Health Journal 19

RESEARCH AND DEVELOPMENT The discussion to date has been around funding a product through to registration. However, there are other ways for a business to extract value from an asset, without necessarily having to do the full development. It may be worth considering other options if a business has a number of opportunities liquidating one asset that may help fund some of the other opportunities. Liquidating an asset could be an outright sale based on some initial data, demonstrating strong indications. Alternatively, a license deal that has some upfront payment and then a royalty stream is another option. In these scenarios having good Intellectual Property protection is necessary.

About Argenta Founded in 2006 in New Zealand, Argenta holds a unique position as the only combined global contract research organisation (CRO) and contract development and manufacturing organisation (CDMO) dedicated to animal health. Argenta’s talented and committed employees are dedicated to deliver excellence in animal health to customers around the world. With research and GMP manufacturing operations in the United States, New Zealand, the United Kingdom and Germany, Argenta operates from ‘Molecule to Market’ in partnership with customers of all sizes from all corners of the world, to seamlessly support their research & development, clinical research, regulatory, scale up and manufacturing needs along their veterinary product development journey.

Recently, Argenta has taken a pro-active approach in accelerating new product development opportunities. There are instances where this journey is fully funded by the client or, in other scenarios, Argenta can help source funding to support the development. The sweet spot is molecules that have a strong initial data package indicating a greater than 40% probability that the product will successfully achieve registration.

How it Works When Argenta is approached by a company looking for a partner to develop their product, Argenta does an initial due

diligence after signing an NDA (Non-Disclosure Agreement).

This is a screening exercise to ensure that Argenta can add value. If this is the case, a much more detailed review is undertaken.

Part of this is a commercial discussion on how the parties can work together and if external funding is required. After this, a number of work streams start, including developing a detailed Product Development Plan along with estimated costs and commercial arrangements. Once the product development starts, there will be regular governance meetings to keep the parties updated on progress and to make key decisions as the project passes through the various gates towards the goal of successful registration.

For more information, visit www.argentaglobal.com.

Stay tuned for new articles in the “From Molecule to Market” series: • • • •

Part I: Finding the Money (this article).

Part II: Start with the end in mind – Formulation, drug delivery technology, and manufacturing.

Part III: Is it Safe & Effective? Clinical Studies, Data Management and Quality Assurance.

Part IV: Getting your product approved – Regulatory considerations for the EU and US.

Darrell Morgan A Biologist from Wales in the UK, Darrell started his career in immunodiagnostics for Amersham International before moving to “big pharma” in human health, where his career included developing sterile ophthalmic products, Metered Dose Inhalers, Zavesca® a NCE for rare developmental diseases in children and sterile large molecules for inflammatory conditions (Cimzia®). Darrell went on to gain post-graduate qualifications in management, people and change as well as Industrial Pharmaceutical Sciences before joining a Belgian biopharmaceutical company (UCB) in 2004. Darrell relocated to New Zealand in 2012 to join Argenta where he led Pharmaceutical Sciences.

During his tenure leading Pharmaceutical Sciences, Darrell led the development of multiple animal health products including Galliprant, and two other products for Aratana, plus a range of products for the Asia Pac region. More recently he has led the start-up of Argenta’s new Product Development organization, leading all technical aspects of Product Development. Darrell lives rurally with his family near Auckland, and has a small flock of sheep, ducks, and two rescued rabbits!

Clare Morgan A career spanning 30 years in commercial roles, predominately in consumer goods. Clare has a wealth of commercial global experience, recently returning home to New Zealand, after living in Singapore responsible for launching a range of nutritional based beverages throughout South East Asia. Clare has been working with Argenta for over 18 months, supporting Argenta's new Product Development organisation, leading the commercial aspects of Product Development.

20 International Animal Health Journal

Volume 9 Issue 1

INSIGHT / KNOWLEDGE / FORESIGHT

SUPER PUBLICATIONS FOR SUPER PHARMACEUTICALS IPI

Peer Reviewed, IPI looks into the best practice in outsourcing management for the Pharmaceutical and BioPharmaceutical industry.

www.international-pharma.com

JCS

Peer Reviewed, JCS provides you with the best practice guidelines for conducting global Clinical Trials. JCS is the specialist journal providing you with relevant articles which will help you to navigate emerging markets.

PHARMA’S DNA

www.journalforclinicalstudies.com

Listen to industry experts on the latest in drug discovery, development, research, industry regulations and much more at Pharma,s DNA, the podcast channel by Senglobal Ltd., available on Sound Cloud, Spotify, iTunes and YouTube.

IAHJ

IBI

www.international-animalhealth.com

www.international-biopharma.com

Peer Reviewed, IAHJ looks into the entire outsourcing management of the Veterinary Drug, Veterinary Devices & Animal Food Development Industry. www.international-animalhealth.com

Peer reviewed, IBI provides the biopharmaceutical industry with practical advice on managing bioprocessing and technology, upstream and downstream processing, manufacturing, regulations, formulation, scale-up/technology transfer, drug delivery, analytical testing and more.

International Animal Health Journal 21

RESEARCH AND DEVELOPMENT

The ZAPI Project – True Partnership Leads to Success Introduction The Innovative Medicine Initiative (IMI)-funded Zoonoses Anticipation and Preparedness Initiative (ZAPI) project was designed as a new consortium in 2014 and was launched in March 2015, almost 5 years before the Covid-19 outbreak impact started to affect our lives everywhere on the globe.

This IMI project call was designed by animal health industry and human pharma industry in order to deliver practical solutions to address the medical needs associated with the emergence of zoonotic infectious diseases. The intent was at the time to develop new manufacturing technologies in order to deliver very rapidly both vaccines and neutralizing antibodies.

Based on the recent SARS-CoV-1 and MERS-CoV outbreaks, it was estimated that the needs for specific pharmaceutical products to control such an outbreak would require the manufacturing of a few hundreds of millions of vaccine doses, and only a few thousands of therapeutic antibody treatments for hospitalized patients. Obviously, the emergence of SARS-CoV-2 was a “black swan event” (The Black Swan Theory Nassim Nicholas Taleb) (The Black Swan: Second Edition – Random House Books) showed that the occurrence of a new emerging disease, even if considered as being rare, can have global medical and economic consequences very rapidly. More than 70% of zoonotic diseases are originating from viral pathogens harboured by animals and it is clear that new, highly scalable technologies, are necessary to address such global needs.

And achieving these huge needs, especially for human and veterinary vaccines, impose to radically revisit the classical manufacturing and regulatory pathways.

One cannot predict where exactly and to which target species an emerging / re-emerging virus will trigger the next pandemic or pan-epizootic event.

All outbreaks in humans and veterinary species in the past 20 years (SARS-CoV, Ebola, MERS-CoV, influenza H1N1, West Nile Virus, Bluetongue Virus (BTV-8 and BTV-1 serotypes), Schmallenberg Virus (SBV) have occurred unexpectedly and as full surprises regarding time and location.

But we can have good guesses on the most likely suspects: Viruses transmitted by contact or air • Paramyxoviruses • Orthomyxoviruses • Coronaviruses

Insect-borne viruses

• Bunyaviruses Rift Valley Fever Virus • Orbiviruses BTV, AHSV • Flaviviruses WNV As the ongoing SARS-CoV-2 pandemic showcases with the continuing occurrence of variants, emerging infections still catch us by surprise, with no vaccine candidate or only 22 International Animal Health Journal

very early-stage candidates available. Delays in vaccine availability will mean that the vaccine typically arrives too late to affect the course of the first pandemic waves. Hence, a key principle of preparedness is to do as much work as possible before an emergency happens, so that the response can be decisive and efficient. For pathogens we have not yet encountered, there is a need for platform technologies that can rapidly produce prototype vaccines and, if successful, produce sufficient amounts of vaccine against a new pathogen. To enhance quick responses, continued innovation in designing and studying vaccine efficacy trials that address the challenges of emergencies is needed.

Being “prepared” for any size of outbreak is the only way to face future “black swan events” and to rapidly protect as many human or domestic animal lives as possible.

The ZAPI project was set up as an industrial manufacturing demonstrator for achieving surge capacity, both for vaccines and antibodies. The effort was based on a set of a priori “rules” creating “constraints for driving innovation” (see infra). The main objectives were the following: • • • •

Vaccine candidates based on soluble subunits Antibody lead candidates to be classical monoclonal antibodies or “nanobodies” (single chain antibodies from camelids) Systems to achieve surge capacity (100 Millions vaccine doses) within 3–4 months after identification of candidates Full in vitro Quality Control for batch release, according to the 3R EU guidelines

To achieve a surge manufacturing capacity able to deliver billions of doses in a few months, it is necessary to have an easy deployment and production at multiple sites. To facilitate this, it is essential to have an easy manufacturing system, with a limited number of steps in both upstream and downstream processes, to have a minimum number of in vitro QC assays, and robustness and consistency of the selected platforms. The principles for such a future manufacturing system have been nicely described by Pardee K. et al. in 2016.2 The ZAPI Project Objectives, Structure, and Built-In Constraints Emerging infectious human and animal diseases (zoonoses) can spread very fast in wide geographical areas (several recent examples: BTV, SBV, Zika, avian influenza, African Swine Fever…), we have more and more the necessity to act for providing very fast medical countermeasures, which include fast-track delivery of vaccines. The practical challenge is to provide millions of doses within a few months), driving a need to rethink our classical approaches from the scientific, industrial and regulatory perspectives.

The ZAPI consortium gathered multiple scientists from pharma industry, academic and SMEs, and was especially strong with veterinarians having long experience with transboundary emerging disease vaccines and with pragmatic approaches. The ZAPI call for project was designed with multiple built-in constraints in order to stimulate the innovation: the new vaccine manufacturing technologies Volume 9 Issue 1

RESEARCH AND DEVELOPMENT could not use live vaccines, live vectored vaccines, or mammalian cell lines. On top of this, and in line with EU recommendations, a full in vitro QC system was required (no animal used for manufacturing and QC batch release).

Three zoonotic (or “quasi-zoonotic”) viral targets were selected in order to develop a fast-track vaccine manufacturing methodology with the potential to be used if needed on most of the emerging viruses responsible for highly virulent diseases in the future: Rift Valley Fever Virus (RVFV), Middle-East Respiratory Syndrome Coronavirus (MERSCo-V) and Schmallenberg Virus (SBV) (new orthobunyavirus infecting ruminants in Europe and belonging to a viral family containing true zoonotic viruses).

The rationale for this selection was that for all these 3 viruses, the possibility to achieve protective vaccines had been already demonstrated with classical technologies (modified live, inactivated, viral vectored vaccine), and that challenge models in target species were available.

These models were thus used to explore whether new vaccine designs and manufacturing technologies could deliver vaccines as potent as the classical ones.

The initial concept of the ZAPI vaccine was to develop subunit-based vaccines on the hypothesis that these subunits would be fused to protein carriers in order to increase their immunogenicity, but there was no precise idea of how this would be achieved. Fortunately, the ZAPI consortium was exposed at the start of the project to very interesting publications on protein nanoparticles that could be used as vaccine carriers and also on the very innovative bacterial superglue technology.3 It was decided to combine the use of these 2 technologies in order to develop an efficient “plug-and-play” assembly, and to establish a simple modular vaccine system.

The ZAPI Modular Vaccine Concept The design of the ZAPI modular vaccines evolved from the idea of presenting subunits genetically fused to protein carriers (including VLP carriers) to the more simple plugand-display when the breakthrough bacterial superglue technology innovation was published4 and was applied to the presentation of immunogens on VLPs.5 All publications on vaccine and multiple other applications of the bacterial superglue technology are available at the Oxford University Spyinfo database.6 At the same time several papers have described the possibility to use protein nanoparticle structures expressed by thermophile micro-organisms: lumazinesynthase from Aquifex aeolicus,7 E2 core from Geobacillus stearothermophilus8 and also semi-synthetic nanoparticles designed from an enzyme core protein (KDPG aldolase) expressed by Thermotoga maritima.9 A new concept rationale was then developed on the basis that conjugation of an immunogen subunit to a partner carrier with the bacterial superglue SpyTag/ SpyCatcher technology was simpler and more efficient than a genetic fusion (prone to unpredictable changes in the properties of the fusion protein). This new strategy also opened the way to design a modular vaccine platform based on a scaffold carrier decorated with the protective subunit selected from the outbreak (emerging) virus of interest. Instead of using a standard protein carrier for the coupling/conjugation. It was also decided to explore the particle-display presentation and compare three of the published protein nanoparticles: lumazine-synthase www.international-animalhealth.com

(LS), E2, and the semi-synthetic KDPG aldolase (ALD) (also known as I3-01 protein). Interestingly, these 3 nanostructures have the same overall dodecahedron symmetry and are generated by a natural self-assembly of 60 monomers.

Although they present some differences in their size and other features, they all have a “virus-like particle” structure which is typically well-recognised by the immune system.

The SpyTag or SpyCatcher peptides were fused to the specific monomer (either at the N-terminus or the C-terminus) of each protein nanoparticle and expressed in E. coli to produce enough research-grade materials on which the specific viral subunits could be subsequently coupled.

These 60-mer nanoparticles fused with one of the bacterial superglue moiety were designated as Multimeric Protein Scaffold Particle or “MPSP” and they constituted the “platform component” of the ZAPI modular vaccine methodology.

Implementation and Results Generated with the 3 Viral Disease Models This approach was declined for all 3 viral models in the ZAPI project, and led to the demonstration that the different immunogen subunits coupled to a MPSP could induce a satisfactory level of protection in target species (for the RVFV and SBV challenge models) and for adapted animal models for the MERS-CoV challenge model.

• • •

RVFV Gn_DVII subunit10 SBV GcN+C subunit11 MERS-CoV RBD subunit12

Further, the ZAPI project did demonstrate that if the same immunogen subunit (RVFV Gn_DVII) was coupled to 3 different MPSPs, there was no difference in the immunogenicity and protection levels in the sheep target species (WichgersSchreur P et al.),10 demonstrating that the MPSP platform was “neutral” for the vaccine quality, and the MPSP could be selected mainly on the large scale manufacturing yields.

Other data, generated in the course of the exploration of the characteristics of the ZAPI modular vaccine project, indicated a very high flexibility for the use of the MPSP complex (= immunogen coupled to the MPSP) vaccine platform. This flexibility can be implemented at different levels according to the needs.

This ZAPI vaccine platform concept is in practice quite versatile at different levels: •

Nature of the MPSP platform itself (“interchangeability” between LS, E2, ALD (I3-01); concept now extended by other teams to fully synthetic (computer-designed) scaffold particle;13 with a spinoff company Icosavax.14 Ferritin (24-mer).15 Bacteriophages (Q beta and others) can be used for the particle-display16 as well as more classical VLPs such as HBVc (Hepatitis B virus core) or CuMV (Cucumber Mosaic Virus)17

•

Flexibility for the superglue coupling: choice of either SpyTag or SpyCatcher (“MPSP-ST” ot “MPSP-SC”) (or other superglue 2-moiety systems in the future).

•

Flexibility for the coupling ratio: the coupling of the subunit on the MPSP can be performed within a quite broad domain to “decorate” the particle. One can theoretically go from one subunit (1 immunogen subunit for 60 monomers) up to a “saturation level” (full decoration) of 60 subunits (1 subunit for each monomer). This is opening quite intriguing avenues for dissecting how the immune International Animal Health Journal 23

RESEARCH AND DEVELOPMENT system recognizes a minimum antigen dose and develop specific responses profiles.

•

Flexibility for the orientation of the immunogen subunit on the surface of the MPSP.

•

Flexibility for coupling small (short peptides, SARS-CoV-2 RBD) or large subunits (SARS-CoV-2 Spike, Influenza virus HA).

Conclusion The ZAPI project successes for the design and development of a fast-track vaccine platform to be implemented in response to large outbreaks in a context of health emergency were built on a true partnership, with a lot happening transversally between the public and private partners. There are several reasons why this project has worked well. First, all partners involved in the consortium were working on mutually beneficial goals. Targets like high yields or low-cost manufacturing are not usually a priority among academia scientists, because it demands compromises, and the sharing of the industrial constraints was a learning curve for everyone. Then, the excellence of the team members, the open-mindedness and the mutual trust, which are soft skills that need to be sustained over the long run if we need to go faster. Also, the fact that the work started in peace time, and allowed to establish a solid partnership before the storm came. And finally, the quality of the coordination. This partnership should not stop because the project ended but it should find opportunities to continue working together in the future.

5.

The ZAPI project consortium has delivered a lot of key practical data which can now be directly used for manufacturing vaccines in animal health and human health, in a true One Health perspective. This IMI project showcased a remarkable return on investment from the EU public funding, and it would be very important to keep building on the ZAPI project learnings and momentum.

6.

The Covid-19 pandemic is only a first warning and this crisis allowed the very successful and striking introduction of the mRNA vaccine technology that could be developed very rapidly at a very large scale (but this technology benefitted from a dozen of years in development). No one knows today whether the mRNA vaccine can work efficiently against all viruses, and it is critical to develop other platform backups.

The ZAPI MPSP complex modular vaccine is an example of a massive manufacturing technology that should be pursued through partnerships between industry and scientists in order to reach a higher level of preparedness for protecting the EU citizens and domestic animal populations against future highly transmissible infectious diseases. The ZAPI Project Consortium would like to thank the EU Commission and the IMI program for having provided the resources which allowed to start from a concept and achieve remarkable results in terms of process, yields and vaccine efficacy. We are now looking forward to seeing this momentum being implemented to reality in the HERA and IHI programs, and establish, through new private-public partnerships, simple and practical solutions to efficiently protect the human and animal populations, not only in EU but everywhere in the world.

10.

REFERENCES 1.

2.

3.

4.

http://www.randomhousebooks.com/books/176226/ Cell. 2016 Sep 22;167(1):248-259.e12. doi: 10.1016/j. cell.2016.09.013.).

Zakeri et aL; + other reference Zakeri B. et al. Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):E690-7. doi: 10.1073/pnas.1115485109. Epub 2012

24 International Animal Health Journal

7.

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17.

Feb 24.PMID: 22366317 Brune K.D. et al. Sci Rep. 2016 Jan 19;6:19234. doi: 10.1038/ srep19234 SpyInfo (ox.ac.uk) https://www2.bioch.ox.ac.uk/howarth/ info.htm Song Y et al. Sci Rep. 2015 Oct 23;5:15656. doi: 10.1038/ srep15656.

D’Apice L. et al. Vaccine. 2007 Mar 1;25(11):1993-2000. doi: 10.1016/j.vaccine.2006.11.047. Epub 2006 Dec 5 (Hsia et al. Nature. 2016 Jul 7;535(7610):136-9. doi: 10.1038/ nature18010. Epub 2016 Jun 15.PMID: 27309817) Wichgers-Schreur P. et al. Vaccines (Basel). 2021 Mar 23;9(3):301.doi: 10.3390/vaccines9030301.

Aebischer A. et al. Vaccines (Basel). 2021 Jun 15;9(6):651. doi: 10.3390/vaccines9060651 Emerg Microbes Infect. 2020 Dec;9(1):1080-1091. doi: 10.1080/22221751.2020.1760735 references from King N, Baker D. et al.

Icosavax – Developing Best-in-Class Vaccines https:// icosavax.com Kanekiyo M. et al. Nature. 2013 Jul 4;499(7456):102-6.doi: 10.1038/nature12202. Epub 2013 May 2 references from Bachmann M. et al.

Biswas S et al.; Bachmann M. et al.

Jean-Christophe Audonnet Jean-Christophe AUDONNET is a DVM (Alfort Veterinary School; France), a Ph.D. in Molecular Bacteriology Molecular, and Molecular Virology degree (Institut Pasteur Paris, France). He has more than 30 years of experience in recombinant and viral vectored vaccines.

Coordinator of the IMI ZAPI 5-year project (20 partners) since March 2015.

Web: www.zapi-imi.eu

Volume 9 Issue 1

www.international-animalhealth.com

International Animal Health Journal 25

RESEARCH AND DEVELOPMENT

The Changing World of Cat Ownership – What Does it Mean for Feline Parasite Prevention?

Historically, cats have received less attention than dogs in the veterinary setting: they are seen less frequently in clinics, there are fewer feline specific medications and cats are less often the focus of scientific research.

But as cat ownership rises and cats become an even more integral part of families, feline preventative healthcare, including control of endo- and ectoparasites, has never been more important. Tailoring communications to the changing demographic of cat owners and simplifying parasite prevention is vital, especially as pressure in veterinary clinics rises.

A New Generation of Cat Owners The pandemic did not just cause a puppy boom – the numbers of new cat owners also soared.i In fact, cats now outnumber dogs across European countries, surpassing dogs by a sizeable 30% in 2020.1 So why are we not seeing more cats than dogs in veterinary clinics? Cats are masters at hiding pain and have traditionally lived more independently from their owners. There is also a perception that cats are more self-sufficient than dogs, along with the perceived barriers around handling, transporting and medicating cats.

But cat ownership is changing: many new cat owners are younger and more in tune with their cat’s healthcare needs, taking a proactive and educated approach. In fact, more than half now see their cat as their family member and place more importance on protecting the bond with their cat.2 There is more emphasis on training cats to accept handling and veterinary interventions, as well as making practices ‘cat friendly’ such as through the worldwide Cat Friendly Clinic Scheme from the International Society of Feline Medicine (ISFM).

Dr. Samantha Taylor, European Veterinary Specialist in Small Animal Internal Medicine and RCVS Recognised Specialist in Feline Medicine in the UK explains: “This new generation of cat owners is often more digitally adept, easier to reach via digital communications and is potentially more likely to engage with remote consultations. Increasingly they want cat-specific information and options. So now is the perfect time for veterinary practices to refresh the way they engage with cat owners about preventative health.”

Reprioritising the Lifestyle Assessment As well as an increase in the number of cats as pets and a shift in the type of owner, the way that owners interact with cats is also changing. Increasingly owners and cats are living in closer proximity, with more people working from home and many cat owners sharing a bed or bedroom with their pet(s).3 Although this increasingly close relationship between pet and owner can have health, emotional and social benefits, cats can expose their owners to a number of zoonotic diseases. This can occur via disease vectors such as ticks and fleas or exposure to parasites with zoonotic potential such as the roundworm, Toxocara cati or the tapeworm Dipylidium caninum.4 26 International Animal Health Journal

It is thought around 65% of cats have contact with children and the elderly, who are at particular risk of zoonotic diseases.5 Interestingly, research suggests that Toxocara cati causes severe human disease more frequently than Toxocara canis.

Inadequate feline parasite prevention represents a potentially significant and likely underestimated health risk.6 Cats’ lifestyles are also changing. Despite the cultural shifts which have seen cats evolve into companions rather than rural pest controllers, cats have retained their natural behaviour as highly territorial hunters.

Hunting behaviour and outdoor access are risk factors for feline lungworm, which is attracting increased attention.

Aelurostrongylus abstrusus has been regarded as the most significant respiratory parasite of domestic cats in Europe for some time but epidemiological data now indicates that Troglostrongylus brevior is now the second most diagnosed lungworm in domestic cats in Europe.7 Dr. Taylor said: “Conducting a lifestyle assessment to inform parasite prevention regime might not be top of the mind in a short consultation amidst other priorities. But it’s useful to remember that situations and lifestyles might have changed for a lot of our clients and many new owners might not have owned a cat before. In fact, research indicates that the majority of cats actually fall into the highest risk group for endoparasitic infection.”8 Simplicity – The Key to Compliance?

For such a fundamental aspect of pet care, parasite prevention can be extremely complex – for both vets and owners. There are so many treatment combinations available with varying clinical and lifestyle factors to consider. Ultimately, parasite prevention should be as straightforward as possible for all involved, including the cat.

Recent research shows that: • All owners struggle to deworm their cats at least four times a year as recommended8 • 44% have negative feelings about giving parasite protection to cats2 • One in eight skip treatment altogether2 • 48% want advice from their vet about parasite prevention2 • 70% prioritise protection from tapeworms, fleas, ticks, and mites2 Dr. Taylor pointed out: "Many cats will have had a break with their parasite prevention during the pandemic, and with a new influx of cat owners it’s an important time to boost preventative health practices. The lives of both vets and owners are increasingly busy and both need a simple and effective protocol, especially avoiding complex combinations of medications with different timings.”

She continued: “With a three-monthly treatment for example, even the busiest owner can simply think about treating four times a year, at the beginning of each of the four seasons.”

Coming Soon - A New Three-Monthly, Cat-Specific Solution Vetoquinol is delighted to be able to meet cat owners’ needs Volume 9 Issue 1

RESEARCH AND DEVELOPMENT

with Felpreva®, a new endectocide and the first spot-on antiparasitic for cats to treat both internal and external parasites, including tapeworms, for up to three months.

Felpreva® has now been granted marketing authorisation by the European Commission, for cats with, or at risk from, mixed parasitic infestations/infections. It is anticipated that Felpreva® will be made available to veterinarians in early 2022.

Felpreva® combines three active ingredients: emodepside and praziquantel (known antiparasitic compounds, also found in the Profender® range) and tigolaner (a novel active substance).

Norbert Mencke, DVM, PhD, Vetoquinol International Medical Veterinary Parasitology added: “Unlike many veterinary treatments, Felpreva® has been designed solely with cats in mind. With its cat-friendly spot-on and threemonthly application, Felpreva® will be a real game changer for veterinarians by reducing prescribing complexity and increasing confidence in owner compliance.

Call For Cat Owner Engagement So, do changes in cat ownership call for a different way for veterinarians to communicate with this new demographic?

Dr. Taylor believes it does: “There are now so many ways to connect with customers in a more targeted way, be it digital or face-to face. And with more feline-focused treatments becoming available, it’s the perfect time for vets to re-start the conversation about parasite prevention with cat owners.”

For more information on Felpreva® visit: https://ec.europa.eu/health/documents/communityregister/html/v277.htm REFERENCES 1.

Statista Numbers of Cats in Europe. July 2021 https://www.

www.international-animalhealth.com

2.

3.

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8.

statista.com/statistics/516041/cat-population-europeeurope/ Accessed 05.10. 2021.

Vetoquinol Data on File (SAPIO).

Smith BP, et al. A Multispecies Approach to Co-Sleeping Integrating Human-Animal Co-Sleeping Practices into Our Understanding of Human Sleep. Hum Nat DOI 10.1007/s12110017-9290-2.

Stull JW, et al. Reducing the risk of pet-associated zoonitic infections. CMAJ. July 14, 2015: 187(10).

Overgaauw PA, van Knapen F. Veterinary and public health aspects of Toxocara spp. Vet Parasitol. 2013;193:398–403.

Fakhri Y, et al. Toxocara eggs in public places worldwide - A systematic review and meta-analysis. Environ Pollut. 2018 Nov;242(Pt B):1467-1475.

Brianti E, et al. Troglostrongylus breviour Parasite of the Month, 37, issue 6 p 569-570 June 1, 2021.

McNamara, J., Drake, J., Wiseman, S. and Wright, I., 2018. Survey of European pet owners quantifying endoparasitic infection risk and implications for deworming recommendations.

Parasites & vectors, 11(1), pp.1-12.

Vetoquinol Vetoquinol is one of the top ten global veterinary pharmaceutical company in the world but remains, first and foremost, an independent, family-owned business.

The company is deeply committed to serving veterinarians and the animals whose health they safeguard. This is demonstrated by Vetoquinol’s commitment to listen, understand and meet their customers’ requirements, worldwide. Developed specifically with the needs of veterinarians and cat owners in mind, the launch of Felpreva® demonstrates Vetoquinol’s expertise, passion, and commitment to innovation in feline parasite prevention and treatment, an essential category of veterinary medicine.

International Animal Health Journal 27

RESEARCH AND DEVELOPMENT

Porcine Circovirus

Introduction Porcine Circovirus (PCV) Type 2 (PCV2) is a non-enveloped virus with a single-stranded DNA genome (Allan and Ellis, 2000) which has been present and recognised in the pig population for a long time (Jacobsen et al., 2009). From the late 1990s onwards, PCV2 has become one of the most economically important pathogens in swine production (Opriessnig et al., 2007), therefore focus has been placed on effective control of the disease. Systemic infection with PCV2 has many associated clinical manifestations which affect various organ systems (Opriessnig and Langhor, 2013), hence the large impact on animal health, welfare and productivity if not controlled effectively.

Disease associated PCV2 was initially referred to as postweaning multisystemic wasting syndrome (PMWS), characterised by wasting (Figure 1), paleness of the skin, respiratory distress and in some cases diarrhoea and jaundice (Segalés et al., 2005). As the pathogen was further studied and understood, more multiple clinical manifestations became apparent, such as reproductive disorders and enteric disease, the disease is now termed porcine circovirus disease in Europe (PCVD). The terms PCVD covers multiple disease complexes including PCV2 subclinical infection (PCV2-SI), systemic disease (PCV2-SD), porcine dermatitis and nephritis syndrome (PDNS), or PCV2 reproductive disease (PCV2RD) (Segalés, 2012). PCV2 is also one of the major primary agents involved in porcine respiratory disease complex (PRDC). Effective control is required to reduce and eliminate the impact of the disease on farm, which can be achieved by a combination of methods including disinfection, good management and vaccination. The purpose of this review is to summarise current knowledge in the area of PCV2, including diagnostic methods and vaccination practices.

The Pathogen PCV2 is part of the Circoviridae family and falls under the Circovirus genus, meaning it has a circular structured DNA genome. Viruses in the Circovirdiae family are nonenveloped and contain a single-stranded DNA genome

Figure 1: Wasting syndrome due to PCV2 infection 28 International Animal Health Journal

(Saikumar and Das, 2019), which is approximately 1.7kB in size in the case of PCV (Meng, 2013). PCV2 particles are morphologically small at around 15–20um (Saikumar and Das, 2019). The genome contains 11 open reading frames (ORF); ORF1–ORF11, 6 of which code for different proteins.

Each of these has a different function, with ORF1 coding for the replicase protein (Rep gene) and ORF2 coding for the capsid protein (Cap gene) (Meng, 2013). The presence of the ORF1, ORF2 and ORF3 proteins has been suggested to be linked with the pathogenesis and virulence of PCV2 (Hua et al., 2013, Liu et al., 2006).

Based on sequence identity in ORF2, PCV2 can be further subdivided into 8 currently described different genotypes PCV2a–PCV2g (Link et al., 2021). New strains of PCV have continued to be identified (Trible and Rowland, 2012) which demonstrates that the pathogen may not be that genetically stable. In 2005 and 2006, PCV2b spread throughout North America resulting in high mortality and morbidity (Opriessnig et al., 2013). However, cross protection has been demonstrated when pigs are vaccinated with commercially available PCV2a vaccines (Fort et al., 2008). In 2012 there was a discovery of PCV2d in America (Opriessnig et al., 2020) and it has since become the predominant genotype of PCV2 over PCV2b (Xiao et al., 2015) worldwide.

Transmission Transmission of PCV2 occurs primarily via direct contact of susceptible animals with secretions from infected animals (Rose et al., 2012). Viral shedding most commonly occurs through respiratory and oral secretions but can also occur via urine and faeces (Meng, 2013). Transmission has been shown to occur vertically from the sow to piglets, potentially resulting in abortions or persistently infected piglets at birth (West et al., 1999). Brunborg et al. (2007) supports this in a study of 36 gilts, reporting PCV2 to be a contributor to the increased levels of still births and mummified piglets in the herd studied. PCV2 has also been demonstrated to be present in semen (Larochelle et al., 2000), therefore poses a risk of transmission, most likely to occur when practising natural mating.

Pathogenesis The pathogenesis of porcine circovirus disease (PCVD) is not fully understood, including the interaction of the pathogen with the immune system (Darwich and Mateu, 2012), but there are thought to be numerous routes via which PCV2 causes damage (Meng, 2013). Lymphoid depletion and lymphopenia are common in pigs which are infected with PCV2 (Opriessnig and Halbur, 2012). Macrophages have been shown to have presence of PCV2 antigen or nucleic acids in their cytoplasm (Sorden, 2000), as well as dendritic cells replacing macrophages in lymphoid tissue (Opriessnig and Halbur, 2012). Dendritic cells are thought to play a role in the pathogenesis of PCV2 due to their ability to migrate throughout the host and the maintenance of infectivity of the virus within these cells (Vincent et al., 2003). Mechanisms leading to lymphoid depletion include apoptosis, direct virusinduced lysis and necrosis within lymphnodes.

The interactions between PCV2 and other pathogens and host responses in concurrent infections cases play Volume 9 Issue 1

RESEARCH AND DEVELOPMENT a significant role in the pathogenesis. PCV2 has been reported to suppress the production of IFN-α (which plays a prominent role in controlling virus infections) and TNF-α by natural interferon producing cells (NIPCs). PCV2 infection also impairs the phagocytic and microbicidal ability of macrophages. These findings indicate that interactions of PCV2 with NIPCs and macrophages render host more susceptible to concurrent or secondary infection (Shi, 2021).

hindlimbs, the perineal area and the ventrocaudal abdomen, leaving subsequential scarring (Figure 3).

The kidneys are enlarged, pale and the lymph nodes are enlarged and oedematous (Segalés et al., 1998).

The outcome of PCV2 infection is dependent on multiple factors including the virus, the host, coinfections and immune modulation (Opriessnig et al., 2007). Studies have noted that even small differences in the genome structure of the PCV2 virus can result in significant differences in the virulence of the pathogen (Fenaux et al., 2004, Opriessnig et al., 2006a).

Host factors include breed, which has been shown to have an impact on susceptibility to PCV2 infection (Opriessnig et al., 2006b). In addition, an in vitro study using immune cells taken from different crossbred animals reported differences in susceptibility of macrophages to infection by PCV2 (Meerts et al., 2005) therefore suggesting differences in the generation adaptive immune response against the pathogen. Clinical manifestation of PCVD can be exacerbated by interaction with other swine pathogens such as Mycoplasma Hyopneumoniae (M.hyo) and Swine Influenza virus (SIV).

This has been demonstrated by increased viral load with PCV2, increased lesions associated with PCV2 and increased incidence of PCVD (Opriessnig et al., 2007).

Figure 2: Interstitial pneumonia lung lesions in a PCV2 infected pig

The pre-immunocompetence infections (pre-natal or early post-natal) and the ability of PCV2 to alter T cell maturation in the thymus, including host’s central tolerance (PCV2 will be then recognised as belonging to the host), can influence the outcome of PCVD and explains the varying pathogenicity of different PCV2 genotypes (Sidler, 2020).

Clinical and Gross Macroscopical Lesions Many clinical syndromes are covered under the term PCVD. However, the most common presentation of PCV2 is in the subclinical form. In this case, a decreased daily weight gain may be noted without evident signs of clinical disease (Segalés et al., 2012). Case definitions of different PCVDs can be found extensively in the literature and for the review these terms will be used (Opriessnig et al., 2007).

•

PCV2 systemic disease (PCV2-SD): Poor body condition, poor performance, wasting, paleness, dyspnoea and occasionally jaundice (Rosell et al., 1999). Diarrhoea has also been reported (Harding et al., 1998). Most common lesions include non-collapsed lungs and enlargement of lymph nodes (Segales and Domingo, 2002).

•

PCV2 lung disease (PCV2-LD): Characterised mainly by respiratory distress and dyspnoea (Kim et al., 2003).

Macroscopically the main findings are lack of pulmonary collapse, interstitial pneumonia (Figure 2) and lung oedema (Gjurovski et al., 2014).

•

PCV2 enteric disease (PCV2-ED): Evidence of diarrhoeic animals, catarrhal enteritis and colitis (Kim et al., 2004, Baro et al., 2015).

•

PCV2 reproductive disease (PCV2-RD): Presence of myocardial lesions in piglets (Brunborg et al., 2007).

When PCV2 has been administered intrauterinely, it has caused reproductive failure in naïve sows with the presence of mummified piglets (Madson et al., 2009).

•

Porcine dermatitis and nephropathy syndrome (PDNS): Common to find erythematous plaques located in the

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Figure 3: Erythematous plaques in hindlimbs and perineal area in a clinical PDNS case

Microscopic lesions •

•

•

•

•

PCV2-SD: The most frequent microscopic lesions observed in this syndrome are lymphocyte depletion with granulomatous inflammation of lymphoid tissue, interstitial pneumonia and nephritis, lymphohistiocytic hepatitis and granulomatous enteritis among others (Segales et al., 2012) PCV2-LD: Interstitial pneumonia with bronchiolitis was initially reported (Ellis et al., 1998) and bronchointerstitial pneumonia has been observed in pigs experimentally infected with PCV2 (Magar et al., 2000) PCV2-ED: Presence of granulomatous enteritis and lymphoid depletion in the Peyer’s patches in the small and large intestines (Kim et al., 2004). Also moderate to severe lymphoplasmacytic infiltration can be observed within the intestinal mucosa (Baro et al., 2015).

PCV2-RD: Microscopic changes associated with this syndrome include myocardial degeneration, fibrosis, and nonsuppurative to necrotising myocarditis (West et al., 1999, O’Connor et al., 2001).

PDNS: Fibrinous glomerulitis and necrotising vasculitis in the glomeruli and arterioles of the renal pelvis (Segalés et al., 1998, Drolet et al., 1999) are the most common microscopic lesions.

International Animal Health Journal 29

RESEARCH AND DEVELOPMENT Diagnostic Methods Observation for the clinical signs described in this paper is the first step in diagnosis of PCVD. However, it is important to note, these signs and lesions are not pathognomic for PCV2 and they are also apparent with other commonly found pathogens on farm. Therefore, other diagnostic tools are necessary for confirmation of the disease. The use of in situ hybridisation (ISH) (Figure 4) and immunohistochemistry (IHC) are very practical to demonstrate the presence of PCV2 nucleic acid and PCV2 antigen, respectively (Rosell et al., 1999). Also, the use of quantitative PCR has been explored as a very useful tool and there are several publications that show different thresholds of the quantification of PCV2 loads for the majority of the PCV2 associated syndromes in naïve herds (Segalés et al., 2012). These thresholds vary depending on the study, laboratory and technique performed. As the virus is ubiquitous, the use of serology or qualitative PCR is not of great help as it would not differentiate between clinically and non-clinically affected herds. Moreover, there is limited information about PCV2 detection rates and loads in different materials from farms using PCV2 vaccines, which would be needed to establish diagnostic benchmarks (Wozniak, 2019).

data extrapolated from the Netherlands was extrapolated to generate an estimated cost of the disease of €562–900 million per year in Europe (Tucker, 2006). Further to these estimates, Alarcon et al. (2013) carried out a unique study utilising data generated from both pigs affected with PMWS and those affected sub-clinically to estimate the economic impact of PCV2. The results of the study are presented in Table 1.

Economic Impact There are few studies that describe the economic impact PCV2 can have on an infected farm. In Europe between 1996 and 2004, the mortality and morbidity rates on farm ranged from 4–20% and 50–60% respectively (Madec et al., 2000, Segales and Domingo, 2002). Armstrong and Bishop (2004) reported that the estimated cost of PMWS in the UK was £30 million per year, although this only considered the reduction of the number of pigs to slaughter. At a similar time point,

The estimation of the cost due to subclinical disease is essential to understand the true impact of this pathogen.

As it was already mentioned before, the current most common form of PCV2 is the subclinical infection and the pigs infected may have higher susceptibility to other pathogens (Opriessnig et al., 2007) which it could even increase further the cost associated to the deterioration of health and performance.

Figure 4: PCV2 nucleic acid in In-situ hybridisation 30 International Animal Health Journal

Clinical picture

Economic impact (£)

PMWS resulting in mortality

84.10

Animal recovered from PMWS

24.50

Subclinical PMWS resulting in mortality

82.30

Subclinical PMWS reaching slaughter

8.10

Table 1 – Economic impact estimates of various PCV2 infections (Adapted from: Alarcon et al. 2013)

Vaccination Vaccines are one of the most important tools available for the prevention and control of PCV2, both clinical and subclinical disease. The first commercial PCV2 vaccine became available in 2006 (Opriessnig et al., 2007) and vaccination has since been used as a reliable control and prevention method for the related disease. Vaccination has been shown to reduce clinical signs associated with PCVD and cross-protection of PCV2a vaccines against the most widespread genotypes (PCV2a, PCV2b, and PCV2d) has been demonstrated (Franzo and Segales, 2020). This is particularly important with the increase in prevalence of the PCV2d genotype, where several publications have shown good protection with the commercial PCV2 vaccines (Jeong et al., 2015, Opriessnig et al., 2014, Park et al., 2019, Opriessnig et al., 2017).

The vaccination of piglets before or at weaning has proved to reduce the viral shedding and provide protection as demonstrated by a significant improvement in clinical parameters (Heißenberger et al., 2013). On sub-clinically infected farms, piglet vaccination can improve the ADWG and the number of days to slaughter, as well as reducing the number of pigs treated and consequently the health remark recorded at the slaughterhouse (Mortensen et al., 2015). Vaccination of the breeding herd against PCV2 benefits both the sow or gilt which is actively protected, but also the foetuses and newborn piglets. This is due to a reduction of PCV2 viremia during pregnancy and a significant amount of antibodies passed to the piglets through colostrum (Madson and Opriessnig, 2011). Furthermore, vaccination of the sows has been shown to improve reproductive parameters such as increasing the number of live-born piglets and reducing the number of stillborn foetuses in studies from Denmark (Bech and Kunstmann, 2008, Kunstmann and Lau, 2008), France (Delisle et al., 2008), and Germany (Joisel et al., 2008). Vaccination may also have an effect in reducing the prevalence of Ear Necrosis Syndrome (Pejsak et al., 2011). It is Volume 9 Issue 1

RESEARCH AND DEVELOPMENT assumed that vaccination limits the viremia and shedding of PCV2, but it is unclear what virus levels, e.g., in serum, are acceptable or alarming (suggestive of vaccination failure) (Wozniak, 2019).

Vaccination protocols can be implemented to involve treatment of both the breeding animal and piglets. It is important to evaluate the potential risk of too high maternally derived antibody (MDA) levels and their interference with the protection generated from the vaccine. However, a recent study has shown that standard MDA levels from nonvaccinated sows do not have a significant effect on vaccineinduced protection. In addition to this, the study interestingly demonstrated that in piglets with a low MDA level developed a humoral response developed faster when given a whole virus vaccine compared to a subunit vaccine (Kiss et al., 2021) There are a range of types of commercial vaccines available in the marketplace, including monovalent intradermal and intramuscular products as well as ready-to-use (RTU) combination products. Recently there is the possibility of using two separate Mycoplasma hyopneumoniae and PCV2 commercial vaccines as a ready-to-mix (RTM) product (Figure 5). It has shown to offer the equivalent virological, immunological and pathological results as used separate (Sibila et al., 2020) and reduce the lung lesion score and percentage of extensive Enzootic Pneumonia-compatible lesions compared with a commercial ready-to-use bivalent vaccine (Boulbria et al., 2021).

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Figure 5: Vaccination with commercial ready-to-mix Mycoplasma hyopneumoniae and PCV2 vaccines

Conclusion PCV2 remains a worldwide ubiquitous pathogen causing substantial losses to swine industry. Its genetic instability has led to the differentiation into 8 different genotypes with the PCV2d genotype most commonly found on infected farms.

Genetic heterogeneity together with a wide range of clinical expressions of the disease make diagnosis, monitoring and preventive strategies complex. Fortunately, new diagnostic approaches are being implemented and a high level of cross protection exists, helping to ensure good efficacy of commercially available PCV2 vaccines. The interaction between PCV2 and the host immune system, as well as with other pathogens, increases the importance of good control of concurrent secondary infections, as well as ensuring a good quality pig in general, to combat PCVD and related diseases efficiently. www.international-animalhealth.com

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62. Wozniak, A., Miłek, D., Matyba, P. and Stadejek, T., 2019. Real-time PCR detection patterns of porcine circovirus type 2 (PCV2) in Polish farms with different statuses of vaccination against PCV2. Viruses, 11, p.1135.

63. Xiao, C.T., Halbur, P.G. and Opriessnig, T., 2015. Global molecular genetic analysis of porcine circovirus type 2 (PCV2) sequences confirms the presence of four main PCV2 genotypes and reveals a rapid increase of PCV2d. Journal of General Virology, 96(7), pp.1830-1841.

Christina Gale Christina Gale BSc studied Bioveterinary science at Harper Adams University and graduated with first class honours in 2018. She has worked for Ceva Animal Health since 2016, including completing her industry placement as part of her BSc and continuing post-graduation. Christina is currently in her final year of studies for her MSc in Livestock Health and Production at the Royal Veterinary College whilst also working as a Product Manager for Ceva in the UK and Ireland, which involves marketing and technical support for the full swine range.

Eduardo Velazquez Eduardo Velazquez MRCVS graduated from the University of Las Palmas de Gran Canaria, where he then worked in small animal practice. He moved to the UK in 2009 and worked for the Food Standards Agency in several roles including an official veterinarian and auditor. After this he worked as a swine practitioner in an intensive clinical role.

He joined Ceva in 2017 as the Swine Veterinary Service Manager. Eduardo provides technical support for both commercial and autogenous vaccines, mostly related to respiratory and enteric health.

Roman Krejci

Porcine health management, 6(1), pp.1-11.

56. Sidler, X., Sydler, T., Mateos, J.M., Klausmann, S. and Brugnera, E., 2020. Porcine Circovirus Type 2 Pathogenicity Alters Host’s Central Tolerance for Propagation. Pathogens, 9(10), p.839.

57. Sorden, S.D., 2000. Update on porcine circovirus and postweaning multisystemic wasting syndrome (PMWS).

Journal of Swine Health and Production, 8(3), pp.133-136.

58. Trible, B.R. and Rowland, R.R., 2012. Genetic variation of porcine circovirus type 2 (PCV2) and its relevance to vaccination, pathogenesis and diagnosis. Virus research, 164(1-2), pp.68-77.

59. Tucker, A.W. and Donadeu, M., 2006. Porcine multi-systemic wasting syndrome (PMWS): a review. The Pig Journal, 14, pp.23-24.

60. Vincent, I.E., Carrasco, C.P., Herrmann, B., Meehan, B.M., Allan, www.international-animalhealth.com

Roman Krejci DVM Roman is originally from the Czech Republic but has spent the last 11 years spent in Libourne, France. He studied and received his degree from the University of Veterinary Medicine in Brno, Czech Rep in 1988 and then started his professional carrier at the Research Institute of Parasitology, studying I. suis infections in piglets.

He then joined Ceva Animal health and has specialised in swine health and reproduction management in the last 20 years, including responsibility for the technical and marketing support of Ceva swine products worldwide.

Roman’s role is currently Swine Corporate Veterinary Service Manager for both PCV2 and Mycoplasma hyopneumoniae vaccines.

International Animal Health Journal 33

RESEARCH AND DEVELOPMENT

Higher Risk Mycotoxin Levels in Global Grains Compared to Harvest 2020 Grain represents a significant portion of the mycotoxin risk to livestock performance, reproduction and health.

Grains are fed locally within countries and regions but are also transported globally to areas where grain production cannot meet the high demands for livestock feed. Harvest 2021 across the key grain-growing regions of the Northern Hemisphere suffered under turbulent weather conditions.

Europe experienced a combination of drought in southern regions, while further north, flooding dominated. In the U.S., drought was a constant issue throughout June, July and August, and it was felt from the upper midwest to as far as parts east of the Mississippi River, covering large amounts of corn-growing country. These effects were compounded by late-season rains that delayed harvest in some regions. A similar picture surfaced across Canada, with large parts of the country being hampered by severe drought throughout the main growing season. Analysis and risk measurement of the grains is necessary to identify how these weather conditions have affected the mycotoxin landscape and the represented threat.

Alltech’s Annual Harvest Analyses Programs Each year, Alltech carries out comprehensive mycotoxin testing programs across Europe, the U.S. and Canada that help uncover the mycotoxin threat in newly harvested crops.

A total of 2,134 grain samples from the harvest seasons of 2021 were analysed for mycotoxin presence and risk. The samples were tested at the Alltech 37+® mycotoxin analytical services laboratories via LC-MS/MS or locally with the Alltech RAPIREAD® system, utilizing Neogen lateral flow technology.

Alltech also collaborated for the first time with SGS, a world leader in mycotoxin testing services. Working together with SGS in Europe to collect and examine corn samples has allowed us to expand the number of samples that we analyze and deliver a larger geographical representation of the crop quality throughout the continent. All results are reported in parts per billion (ppb) and can be used to assist in grain storage management, assignment to species or phases of production, and formulation and are a vital part of a mycotoxin management program. The 2,134 samples were made up of 1,596 samples of corn and 538 samples of wheat and barley.

Mycotoxin Risk in 2021 Harvested Corn The corn samples came from North America (638), Europe (714) and Latin America (244). In general, across all regions, the mycotoxin risk was higher than that which was identified in 2020 harvested grains. The numbers of mycotoxins per sample of corn averaged near 6.03 mycotoxins per sample, with 87.5% containing 2 or more mycotoxins. The major mycotoxins present were Fusarium-produced and included fusaric acid, type B-trichothecenes, fumonisin, zearalenone and emerging mycotoxins. This group of mycotoxins can impact feed intake, digestion, reproduction, embryo and fetal health, gut health, liver function and immune response.

Drought periods in North America did not appear to increase the occurrence of aflatoxin B1. However, in eastern and southern Europe, the occurrence and level of aflatoxin B1 were higher, averaging 4.4 ppb with a maximum identified at 62.2 ppb. Many corn samples from this region exceeded the 34 International Animal Health Journal

regulatory levels for aflatoxin, with raw materials containing 20ppb or above of aflatoxin deemed unsafe for use in animal feed, according to EU regulatory limits. This data is especially relevant for the dairy industry due to the risk of aflatoxin transfer from the cow through the milk supply. A multi-faceted approach, engaging all steps along the supply chain, is necessary to tackle this challenge.

Fig 1. An example of the multiple mycotoxin challenge in European corn

Mycotoxin Risk in 2021 Harvested Wheat and Barley Wheat and barley samples comprised 330 samples from Europe and 208 samples from Canada. These samples averaged 2.3 mycotoxins per sample, with 58.5% containing two or more mycotoxins. Type B-trichothecenes and emerging mycotoxins made up the greatest risk. As with corn samples, these Fusarium mycotoxins can contribute to risk on feed intake digestion, ADG, FE, gut health, liver function and immune response.

Increased presence and levels of Fusarium mycotoxins are associated with increased moisture and moderate to warmer temperatures. These environmental risks tend to be present more on a regional basis. These conditions were present in eastern North America and parts of central and eastern Europe. However, the risk of Fusariums can be localised, depending on events such as plant disease, wind, hail and agronomic practices. This creates the need for grains to be analysed for mycotoxin risk.

Low Risk Does Not Mean No Risk Although small grain samples (wheat, barley) show a universal lower mycotoxin risk across Europe and Canada, only presenting around half of the mycotoxin levels contained in corn, producers should recognise that ‘low risk’ does not mean ‘no risk’. Research shows that prolonged exposure to mycotoxins can harm livestock, even at low levels. Producers still need to develop a plan to combat the issue.

Mycotoxins in Grain by Products As these grains are manufactured into by-products, the mycotoxin content will be magnified due to the same mycotoxin presence in the original grain being concentrated into a lesser mass. Similarly, as grains and their by-products transported across the globe, mycotoxin risk will also be potentially exacerbated.

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RESEARCH AND DEVELOPMENT

The Environmental Impact of Mycotoxins A mycotoxin challenge also leads to more than just risks to animal health and production profits. By combining mycotoxin contamination data with the impacts on animal health and performance, we are learning more about how mycotoxins also contribute to the overall carbon footprint of an agricultural operation – the greater the scale of the challenge, the greater the impact. These concerns and effects further indicate the need to identify, interpret and mitigate this risk. Working with Alltech E-CO2 and their carbon footprint models, figure 2 demonstrates what mycotoxin contamination can mean for the environmental sustainability of a broiler operation.

For the production of 1,000 tonnes liveweight (LW) across a 37 day finishing period

Fig 2. The impact of mycotoxin contamination on the environmental footprint of a broiler operation.

Managing the Mycotoxin Challenge Mycotoxin management requires a holistic approach, and www.international-animalhealth.com

the only accurate way to understand the true risk in the feeds that animals are consuming is to use a routine mycotoxin testing program when purchasing feed ingredients and establishing nutrition plans.

Dr. Max Hawkins Dr. Max Hawkins began his work with Alltech in October 2011. His current focus is working with the Alltech Mycotoxin Management team by providing technical support directly to customers and sales staff to improve livestock health and performance. He provides the livestock industry with up-to-date information on mycotoxin risk on a worldwide basis. In addition, Hawkins provides support to the Alltech Feed Division and beef and swine groups. Hawkins received his bachelor’s degree from Western Illinois University and obtained his master’s and doctoral degrees at the University of Tennessee. While completing his degrees at the University of Tennessee, he conducted research on feeder cattle evaluation and osteochondrosis in swine.

He also coached the Livestock Judging Team and taught various livestock production classes. Hawkins taught animal science at Morehead State University and led a land development project in conjunction with mining companies in Eastern Kentucky. He later joined the staff at California Polytechnic State University, coaching the Livestock Judging Team and teaching animal nutrition and production classes. In addition, he became the director of genetic outreach for the National Purebred Swine Registry, directing the field staff and working with producers on genetic and performance programs.

Hawkins has worked as a technical consultant with Continental Grains Wayne Feed Division, providing nutritional support and formulation to swine producers throughout the central United States. He later joined Hubbard Feeds in the same capacity. He also worked with Micron Bio-Systems, providing sales and technical support for mycotoxin management, forage inoculant and probiotics. Hawkins was raised in Illinois on a grain and livestock farm. When not working, he enjoys spending time with his wife, children and grandchildren.

International Animal Health Journal 35

FOOD & FEED

Can Cell-based Meat Play a Role in the Fight Against AMR? The development of cultivated meats, including seafood, holds the promise of providing an alternative to industrial animal farming. This editorial explores the role of cultivated meats in the sustainable European food system envisioned in the European Commission’s Farm to Fork strategy. Can cellular agriculture be part of a new, environmentally-friendly food system? What role can cell-based meat play in the fight against antimicrobial resistance?

The EU’s Farm to Fork strategy, which was launched in 2020 and aims to create a fair, healthy and environmentallyfriendly food system, recognises the interconnectedness between animal welfare, human health and the environment.

The strategy sets out to both reduce sales of antimicrobials by 50% within the current decade, and to improve animal welfare.1 This dual goal is a prominent example of the interlinkages between animal welfare and human health as the overuse of antimicrobials in livestock production is a main contributor to antimicrobial resistance.2,3 Poor animal welfare, crowded conditions and deprivation from performing speciesspecific behaviours are contributors to stress in animals.

Stressed animals are more susceptible to disease, whereby improved animal welfare is a measure that can decrease the use of antimicrobials.4 The link between animal welfare and antimicrobials is true also for aquaculture, where fish are kept in barren high-density systems.5 The current over-consumption of animal protein has negative impacts not only on animal and human health but also on the planet as animal agriculture and the demand for animal protein are driving forces behind climate change. The EAT-Lancet Planetary Health Diet identifies the levels of animal products that can be consumed to stay within the planetary boundaries.6 The estimations prescribe a predominantly plant-based diet with small amounts of animal proteins.7 While EAT-Lancet calls for a 50% reduction of animal products globally by 2050, high-consuming Western industrialised countries, including Europe, need to reduce more to achieve the overall reduction needed on the global scale.8 In Europe that would mean a reduction from the current consumption of red meat and poultry from 1,320 g per person/week to no more than 300 g per person/week. This means that a reduction by 77% of the current levels of red meat and poultry consumption would be needed to align European diets with the EAT-Lancet Planetary Health Diet.9 At the same time, the global population is expected to reach almost 10 billion by 2050 and, as many people want to continue eating meat, this would lead to an increase in meat demand.10,11,12 In this context, cultivated meat innovators state that their products will be able to support the shift to a sustainable food system. Cultivated meat, grown from animal cells, can contribute to closing the gap between the amount of animal protein that can be sustainably produced and the actual global demand.13 In cellular agriculture the cell cultivation is a technique that uses tissue engineering to produce different types of 36 International Animal Health Journal

meat, including fish.14 A small amount of cells are extracted through a biopsy without harming the animal and the cells are then placed in a nutrient culture medium. The growth and development into muscle, fat or other tissue takes place in bioreactors that resemble brewery fermentation processes.15,16 The final product has the same properties as animal meat.17,18 The novelty is that the production process for the first time decouples meat production from the need to raise and slaughter large numbers of animals.19 Cultivated meat can be a more sustainable source of protein than all conventionally produced meat, with significant reductions in land and water use. Freeing up land currently used to grow animal feed can bring wildlife and biodiversity back.20 When produced with renewable energy, the environmental impact can be reduced by 93% compared to beef, by 53% compared to pork and by 29% compared to poultry.21,22 Future projections predict that, if by 2040 cultivated meat represents 35% of global meat production and plantbased meat alternatives constitute 25%, conventional meat production could be reduced by 60%. Not only would the closed systems of bioreactors used in cellular agriculture contribute to a decrease in antibiotic use in overall meat production, but the significantly reduced number of animals needed would allow for animals to be kept in high welfare systems with less need for medicines.23 Singapore is the first country to have tasted cultivated meat as cultivated chicken nuggets received regulatory approval to be sold commercially for the first time in 2020.24 In Europe, several start-up companies are currently developing a range of cultivated meat and seafood products. The products fall under the EU Novel Foods Regulation (EU) 2015/2283 that applies to all food that has not been used for human consumption to a significant degree within the EU prior to 1997. Before being available to EU consumers, the cell-based products will need pre-market authorisation that ensures that they are safe for human consumption.25 Apart from the regulatory approval, economic and technical issues remain to be solved before the scaling up of cultivated meat production. Fetal bovine serum (FBS), derived from blood drawn from the fetus of slaughtered cows, is commonly used in biomedical research as a nutrient media for cell-growth. Apart from FBS being expensive, it is not a viable option for cell-based meat production due to Volume 9 Issue 1

FOOD & FEED the animal welfare and ethical aspects of extracting blood from unborn calves. A key for the cultivated meat sector is to develop cost-efficient animal-free media that will allow to decrease the costs of cultivated meat.26,27,28,29,30 A recent publication shows the scientific progress made by Mosa Meat, revealing how the company has managed to replace FBS with an animal-free medium and without genetically modified cells.34 One of the environmental benefits that have been identified with the arrival of cellular agriculture is that it allows for the possibility to switch agricultural production from animal-feed crops to crops grown for human consumption, and to combine conventional farming with cellular agriculture. However, concerns have been raised that cultivated meat risks leading to loss of income for smallscale farmers.35 The fear is that cultivated meat might replace the organically certified and higher animal welfare meat from small farms rather than the industrially produced meat. However, with production costs for cultivated meat decreasing, the sector will likely target the latter market and replace the industry of cheap, mass-produced meat that has been allowed to grow at the expense of animal welfare, human and animal health and the environment.33 A further concern is that cultivated meat might be used by large meat-processing corporations to increase their power over the food system through patents and monopoly of the technology. The fear is that the cultivated meat sector would follow the same trajectory as the conventional meat one, which is already subject to corporate concentration. However, a more diverse approach seems likely for cultivated meat.

The technology of cellular agriculture can be part of rural farming where small herds of animals are allowed to graze and root while at the same time serving as cell-stocks for local meat production. In addition, instead of focusing on selective breeding for high productivity, there would be room to keep more robust and healthy traditional breeds.34 The concept of “the pig in the backyard” visualises this farming approach: it refers to the possibility of a highly localised meat production where consumers can visit the cell farms and meet the local cell-donor animals, a combination of high welfare animal farming and cultivated meat production.

Moreover, it has the potential to reverse the general public’s alienation from animals and food production. Interestingly, van der Weele and Driessen note that people’s initial perception of cultivated meat as “unnatural” or “artificial” led to a discussion about the unnatural conditions under which animals in industrial meat production are raised.35 Heideman et al. found increased willingness to eat cultivated meat when people were made aware of the animal welfare benefits, as well as of the environmental ones.36 While localised cultivated meat production can work from a technological perspective, production costs and competition

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from conventional meat could be a challenge. Not only must cultivated meat become economically viable but the cost of conventional meat must also significantly increase.37 Heideman et al. consider two main scenarios under which animals in the remaining conventional meat production could be held by the year 2040. In the first scenario farm animal welfare decreases due to the pressure for low-cost conventional meat to compete with cell-based meat. In this scenario there is an increase in the overuse of antibiotics due to deteriorating animal welfare.

There is also the related risk that cultivated meat could only add on to the overconsumption of animal protein. Thereby it would not lead to any positive effects on animal welfare, public health and the environment.38 In the second scenario, farm animal welfare increases due to a demand for high-quality conventional meat that meets high animal welfare standards. In this scenario, conventional meat from these high welfare systems is sold as a premium niche product and cultivated meat dominates in the lowprice segment. Conventional meat would become a more expensive luxury product for which consumers are willing to pay premium prices. This would allow for animal welfare improvements in conventional meat production, such as outdoor systems, more room per animal, possibilities for social contact, exploration, nesting and playing, and other behaviours that can lead to positive mental experiences. In this second scenario, developments to further strengthen the animal welfare legislation become possible.42 Considering the social and ethical effects of cultivated meat, Heideman et al. hypothesize that cellular agriculture can increase people’s awareness of animal sentience and welfare.

The arrival of cultivated meat will show that meat production is possible without the need of confining, transporting and killing animals. Subsequently it may lead to stronger public demands for stricter animal welfare legislation. The public will show less tolerance for the keeping of animals in high-density indoor systems.43 Advancements in scientific knowledge about the emotional needs and cognitive abilities of animals are already affecting our view of animal welfare legislation.44 From a previous focus on the Five Freedoms, a framework that seeks to mitigate suffering, the Five Domains model is attracting increasing attention as a scientifically based model of animal welfare assessment that also promotes the importance of positive mental experiences for the welfare of an animal. Positive mental experiences may include opportunities for the animal to explore the environment, to scratch or root for food as well as social interaction with other animals, and other experiences that give the animal pleasure and a sense of control.45 The advancement of the Five Domains model would fit well with the hypothesis by Heidemann et al. that cultivated meat can lead to the public starting to demand higher levels of animal welfare.46

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FOOD & FEED between human health and animal welfare. The arrival of cultivated meat can create new possibilities for improving animal welfare and decrease the overuse of antibiotics in animal agriculture. Cellular agriculture should be seen as one piece in the puzzle of the food system transformation.

I am grateful to Alex Holst, Policy Manager at The Good Food Institute Europe, for providing helpful comments.

REFERENCES For cell-based meat to be able to play this positive and transformative role in a healthy and sustainable food system that connects improved animal welfare to human health, several policy reforms are needed. A recent report by FAO, UNDP and UNEP concludes that current financial support to animal production, including in the EU, is an obstacle to the shift to healthy, sustainable food systems.47 The externalities of conventional meat production in terms of animal welfare, human health and environment are significant. Incentives for less damaging food production are needed as well as a rebalancing of current agricultural subsidies.

Firstly, Stephens et al. suggest a system of true cost accounting as a means to reflect the societal costs of different types of food production. Exposing the true costs would make the differences between cell-based meat and conventionally produced meat visible with regards to the use of land, contribution to pollution, as well as impact on animal welfare and antibiotic use in animal agriculture.48 Secondly, although cultivated meat is increasingly attracting public research funding, the investments have mainly come from the private sector.49 Governmental investments in research that is published with free access is important to make cellular technology available to small-scale farmers and local food producers.50 Apart from the benefits for animal welfare, a reduction in the number of animals raised for food is not only needed for staying within the planetary boundaries, it is also an effective way of reducing antimicrobial resistance.51 The transition to a sustainable food system, sprung from the recognition that human health and well-being are deeply interconnected with animal welfare and the environment, will require substantial changes in how we treat animals. The EU’s Farm to Fork strategy is based on this interlinked understanding in its strive to improve animal welfare and thereby also fight antimicrobial resistance.

The Farm to Fork strategy also notes that we need to shift to more plant-based food and reduce the consumption of red meat to achieve a healthy and environmentally-friendly food system.52 The question remains if we really need cultivated animal products as the plant-based meat alternatives are both improving and becoming more and more available.

However, while plant-based alternatives appeal to many people, Bryant and Sanctorum argue that we need multiple approaches as cultivated meat tends to appeal to those who desire meat from animals and are not satisfied with the plant-based alternatives.53

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

European Commission. 2020. Farm to fork strategy. For a fair, healthy and environmentally-friendly food system, p. 10.

Van Boeckel, Thomas P. et al. 2017. Reducing antimicrobial use in food animals. Consider user fees and regulatory caps on veterinary use. Science, 357(6358):1350. https://doi.org/10.1126/ science.aao1495 Djisalov, Mila et al. 2021. Cultivating Multidisciplinarity: Manufacturing and Sensing Challenges in Cultured Meat Production. Biology, 10(204): 2. https://doi.org/10.3390/ biology1003020 EMA and EFSA. 2017. Joint Scientific Opinion on measures to reduce the need to use antimicrobial agents in animal husbandry in the European Union, and the resulting impacts on food safety (RONAFA). EFSA Journal, 15(1): 4666, 106-108. https://doi.org/10.2903/j.efsa.2017.4666 Reis, Germano Glufke et al. 2021. Can radical innovation mitigate environmental and animal welfare misconduct in global value chains? The case of cell-based tuna. Technological Forecasting & Social Change, 169 (2021) 120845: 3. https://doi. org/10.1016/j.techfore.2021.120845 Willett, Walter et al. 2019. Food in the Anthropocene: the EAT–Lancet Commission on healthy diets from sustainable food systems. The Lancet, 393(10170): 447-492. https://doi. org/10.1016/S0140-6736(18)31788-4 Springmann, Marco et al. 2018. Options for keeping the food system within environmental limits. Nature, 562: 519-525.. https://doi.org/10.1038/s41586-018-0594-0 Falk, Johan et al. 2019. Exponential roadmap 1.5. Future Earth.

Based on the European Commission. 2020. EU agricultural outlook for markets, income and environment, 2020-2030. European Commission, DG Agriculture and Rural Development, Brussels.

Tomiyama, A. Janet et al. 2020. Bridging the gap between the science of cultured meat and public perceptions. Trends in Food Science & Technology, 104: 144. https://doi.org/10.1016/j. tifs.2020.07.019 O’Neill, Edward et al. 2020. Considerations for the development of cost-effective cell culture media for cultivated meat production. Comprehensive review of food science and food safety, 20:686–709: 686. https://doi.org/10.1111/1541-4337.12678 Treich, Nicolas. 2021. Cultured Meat: Promises and Challenges.

Environmental and Resource Economics, 79: 37. https://doi. org/10.1007/s10640-021-00551-3 Recht, Lee and Didier Toubia. 2021. An inclusive transition to a sustainable and resilient meat sector. White paper. Aleph farms, p. 13. https://www.aleph-farms.com/white-paper Accessed 12 December 2021.

In order to mitigate climate change and fight antimicrobial resistance, we will need a range of approaches, and a fundamental systemic change to address the interlinkage

38 International Animal Health Journal

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15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

Stephens, Neil et al. 2018. Bringing cultured meat to market: Technical, socio-political, and regulatory T challenges in cellular agriculture. Trends in Food Science & Technology 78 (2018): 156 https://doi.org/10.1016/j.tifs.2018.04.010 Reis, Germano Glufke et al. 2020. Livestock value chain in transition: Cultivated (cell-based) meat and the need for breakthrough capabilities. Technology in Society, 62 (2020) 101286: 4. https://doi.org/10.1016/j.techsoc.2020.101286 Van der Weele, Cor and Johannes Tramper. 2014. Cultured meat: every village its own factory? Trends in Biotechnology, 32(6): 296. https://doi.org/10.1016/j.tibtech.2014.04.009 Theng Ng, Ee et al. 2021. Cultured meat - a patentometric analysis. Critical Reviews in Food Science and Nutrition, p. 1. https://doi.org/10.1080/10408398.2021.1980760 Broad, Garret M. 2020. Making Meat, Better: The Metaphors of Plant- Based and Cell-Based Meat Innovation. Environmental Communication, 14(7): 925. https://doi.org/10.1080/17524032.

2020.1725085 Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 2-3. https://doi. org/10.3389/fpsyg.2020.01824 Ibid p. 6.

Sinke, Pelle and Ingrid Odegard. 2021. LCA of cultivated meat.

Future projections for different scenarios. CE Delft.

Recht, Lee and Didier Toubia. 2021. An inclusive transition to a sustainable and resilient meat sector. White paper. Aleph farms, p. 3. https://www.aleph-farms.com/white-paper Accessed 12 December 2021.

Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 2-4. https://doi. org/10.3389/fpsyg.2020.01824 Treich, Nicolas. 2021. Cultured Meat: Promises and Challenges.

Environmental and Resource Economics, 79:33. https://doi. org/10.1007/s10640-021-00551-3 Djisalov, Mila et al. 2021. Cultivating Multidisciplinarity: Manufacturing and Sensing Challenges in Cultured Meat Production. Biology, 10(204): 5. https://doi.org/10.3390/ biology1003020 O’Neill, Edward et al. 2020. Considerations for the development of cost-effective cell culture media for cultivated meat production. Comprehensive review of food science and food safety, 20:687.. https://doi.org/10.1111/1541-4337.12678 Djisalov, Mila et al. 2021. Cultivating Multidisciplinarity: Manufacturing and Sensing Challenges in Cultured Meat Production. Biology 2021, 10(204): 4. https://doi.org/10.3390/ biology1003020 Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 8. https://doi. org/10.3389/fpsyg.2020.01824 Tomiyama, A. Janet et al. 2020. Bridging the gap between the science of cultured meat and public perceptions. Trends in Food Science & Technology, 104: 149. https://doi.org/10.1016/j. tifs.2020.07.019 Kolkmann, A.M. et al. 2019. Serum-free media for the growth of primary bovine myoblasts. Cytotechnology, 72: 118. https:// doi.org/10.1007/s10616-019-00361-y Messmer, Tobias et al. 2022. A serum-free media formulation for cultured meat production supports bovine satellite cell differentiation in the absence of serum starvation. Nature Food. https://doi.org/10.1038/s43016-021-00419-1 Reis, Germano Glufke et al. 2021. Can radical innovation mitigate environmental and animal welfare misconduct in global value chains? The case of cell-based tuna.

Technological Forecasting & Social Change, 169(120845): 8. https://doi.org/10.1016/j.techfore.2021.120845 Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 8. https://doi.

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org/10.3389/fpsyg.2020.01824 34. Stephens, Neil et al. 2018. Bringing cultured meat to market: Technical, socio-political, and regulatory T challenges in cellular agriculture. Trends in Food Science & Technology 78 (2018) 158–161. https://doi.org/10.1016/j.tifs.2018.04.010 35. van der Weele, Cor and Clemens Driessen. 2019. How Normal Meat Becomes Stranger as Cultured Meat Becomes More Normal; Ambivalence and Ambiguity Below the Surface of Behavior. Frontiers in Sustainable Food Systems, 3(69): 2. https://doi.org/10.3389/fsufs.2019.0006 36. Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 11. https://doi. org/10.3389/fpsyg.2020.01824 37. van der Weele, Cor and Johannes Tramper. 2014. Cultured meat: every village its own factory? Trends in Biotechnology, 32(6): 296. https://doi.org/10.1016/j.tibtech.2014.04.009 38. Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 10. https://doi. org/10.3389/fpsyg.2020.01824 39. Ibid p. 10.

40. Ibid p. 3.

41. Treich, Nicolas. 2021. Cultured Meat: Promises and Challenges.

Environmental and Resource Economics, 79: 35-36. https://doi. org/10.1007/s10640-021-00551-3 42. Mellor, David.J. et al. 2020. The 2020 Five Domains model: including human–animal interactions in assessments of animal welfare. Animals, 10(10): 1870. https://doi.org/10.3390/ ani10101870 43. See Heidemann, Marina Sucha et al. 2020. Uncoupling meat from animal slaughter and its impacts on human-animal relationships. Frontiers in psychology, 11(1824): 10. https://doi. org/10.3389/fpsyg.2020.01824 44. FAO, UNDP and UNEP. 2021. A multi-billion-dollar opportunity.

Repurposing agricultural support to transform food systems.

Rome, FAO. https://doi.org/10.4060/cb6562en 45. Stephens, Neil et al. 2018. Bringing cultured meat to market: Technical, socio-political, and regulatory T challenges in cellular agriculture. Trends in Food Science & Technology 78 (2018) 158. https://doi.org/10.1016/j.tifs.2018.04.010 46. Reis, Germano Glufke et al. 2020. Livestock value chain in transition: Cultivated (cell-based) meat and the need for breakthrough capabilities. Technology in Society, 62(101286): 2. https://doi.org/10.1016/j.techsoc.2020.101286 47. Broad, Garret M. 2020. Making Meat, Better: The Metaphors of Plant- Based and Cell-Based Meat Innovation. Environmental Communication, 14(7): 930. https://doi.org/10.1080/17524032.

2020.1725085 48. Van Boeckel, Thomas P. et al. 2017. Reducing antimicrobial use in food animals. Consider user fees and regulatory caps on veterinary use. Science, 357(6358):1351. https://doi.org/10.1126/ science.aao1495 49. European Commission. 2020. Farm to fork strategy. For a fair, healthy and environmentally-friendly food system, p. 14.

50. Bryant, Christopher and Hermes Sanctorum. 2021. Alternative proteins, evolving attitudes: Comparing consumer attitudes to plant-based and cultured meat in Belgium in two consecutive years. Appetite, 161 (105161): 9. https://doi.org/10.1016/j. appet.2021.105161

Camilla Björkbom Camilla Björkbom is Political Adviser at Eurogroup for Animals, a European umbrella organisation for animal protection NGOs.

International Animal Health Journal 39

LOGISTICS AND SUPPLY MANAGEMENT

The Design and Validation of Effective Thermo-Assisted

Drying and Decontamination Process for Biosecure Pig Transport

All means of transportation (especially pig trucks) is likely to spread diseases. Especially in the winter, as the temperature turns low, disinfection effectiveness can be greatly compromised, rendering biosecurity risks of disease introduction into farms. Thermo-Assisted Drying and Decontamination (TADD) had been pioneered and applied in the United States pig industry, as it was indicated that drying eliminated certain bacterial pathogens. Initially TADD was applied at low temperatures for the purpose of bacterial pathogens mitigation; later, the drying unit went to higher temperatures at 72°C and higher, was used to effectively decontaminate the trucks for PRRSV and PEDV prevention. It was proven to be essential and highly effective for health assurance to protect the pig farms from disease invasion.

Fig 1B. The washing room to baking room

However, the proper design and monitoring for effectiveness of a TADD facility is not always clear to pig veterinarians and operators. There are many important details that can be overlooked, and as a result, mistakes made, allowing viable infectious microorganisms to escape the inactivation process.

The purpose of this paper is to illustrate PIC’s experience in China about designing and implementing TADD, especially in the backdrop of the application of this approach to inactivate the African Swine Fever virus (ASFV).

1. The Layout of a Truck Washing Facility with Clear Boundary of Clean-Dirty Areas When designing a washing facility, there is a need to demarcate the clean area from the dirty area with clean dirty lines (CDLs), and the number of washing rooms and baking rooms was decided based on the number of trucks to be washed for the needs of transfer and pig haul. The CDLs concept is to ensure biosecurity, and the capacity of the site is determined by the maximum numbers of pigs to be transported. A truck comes in the washing site with presumed contamination, needing to go through a single direction flow process of pre-flushing, foaming, complete flushing, disinfecting, draining and sitting time to remove water before baking, then being driven by a driver who is mandated to change into clean clothes and boots to drive the truck into the baking room (TADD). After being baked, the driver must take a shower, and change into clean clothes and boots to drive the baked truck into the parking area defined as a clean zone. In PIC’s facility, the parking place was roofed,

Fig 1C. The baking room and the parking room

and bird proofed to avoid further contamination and potential contamination by aerosols. Here, the key purpose of each step was defined: Pre-flushing: to remove all crude materials in the interior and exterior of the power unit and the trailer part.

Foaming: to assist for effective washing.

Power washing: to remove all organic materials present in the interior of the trailer, and exterior of the truck.

Draining/drying of water: after power washing, to allow time for the water to drip and drain, to be ready for the next step disinfection.

Disinfection: allow disinfectant to cover all surfaces and to effect for a minimum of 30 minutes. In our practice, 2% Virkon S was used, but many disinfectants had been validated by scientists to be effective against ASFV.5 Baking: to use the heating to effect further decontamination. we require water to be removed before baking, and effect decontamination at 56°Csurface temperature for a minimum of 70 minutes.1,4 To ensure effectiveness, we need to safeguard the process so truck, people, and materials follow the one-way direction flow and avoid crossing (Fig 1A, 1B and 1C).

It was especially required that the driver to take a shower and change into clean clothes after the truck is washed, and to be driven into baking room (Fig 1B).

Fig 1A, the entry to washing room 40 International Animal Health Journal

The practitioners should always be mindful that this risk mitigation approach is a multiple layer process, each layer plays its role for the goal of pathogen elimination.

Adopting only one layer of practice might risk in pathogen introduction.

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LOGISTICS AND SUPPLY MANAGEMENT 2. Determine the Target Temperature and Lasting Time in the Baking Room It was first and foremost to develop a science-based and practically feasible heating procedure before a TADD facility was set up. The guiding principle is to determine the heating temperature and time according to the characteristics of a specific pathogen and the time needed to inactivate, to ensure that during the temporal monitoring of different points in the vehicle, the target temperature can be achieved consistently.

The below table (table 1) showed the survival time of the ASFV and Porcine Reproductive and Respiratory Syndrome (PRRS) virus under various conditions as reported in the literature. The target heating temperature and duration widely adopted in the swine industry were 65–72°C for 45–60

minutes.1 PIC China had conducted some trials and developed the procedure based on published research data that at 56°C, it takes 70 minutes to inactivate ASF virus.1,2,4 Virus ASF

PRRS

Condition 50°C 56°C 60°C 56°C Heated at 71°C Dried at 20°C after washing

Survival time 3h 70 min 20 min 6-20 min 10 min 8h

Source USDA, 1997 Mebus et al., 1997 Benfield DA, 1992 Scott Dee, 2005

Table 1: Survival time of ASF and PRRS viruses under various conditions

2.1 Illustration of Three Most Commonly Used Pig Transport Trucks in China IIn China, there are three types of pig transport trucks being commonly used in the industry. The high-open-crate truck (Fig 2A) is usually used for the transfer of pigs (from the loading facility in a pig farm to the external transfer site) and the transportation of cull sows and slaughter pigs, etc.

Nowadays, the use of this type of truck to haul breeder pigs is on the decline. The enclosed non-air-conditioned truck (Fig 2B) is mainly used for the transportation of piglets, finishing pigs and breeding pigs. The enclosed air-conditioned truck with air filtration (Fig 2C) is used for the transportation of high-value breeder pigs. Knowing the structure and purpose of the different types of vehicles helps us identify and implement the critical control points for effective washing, disinfection and heating.

2.2 PIC China’s Drying Room Design As biosecurity was increasingly recognised, across the industry, car washing rooms and heating rooms were being upgraded with enhanced equipment. The author hereby summarised the vehicle/truck heating and drying.

ASFV was introduced into and spread around China since 2018, over time, PIC China has gradually improved the procedure from drying vehicles at 20°C overnight to heating them up at 56°C for 70 minutes.

Currently, PIC China has two models of the heating room, as illustrated below: •

Fig 2. high-open crate truck (A), enclosed non-air-conditioned truck (B) and enclosed air-conditioned truck with air filtration (C) www.international-animalhealth.com

Model 1: thermal exchange with air circulation, with air outlets on the side walls, a turbo-blower and a fan at the rear end (Fig 3A). Despite the additional turbo-blower and rear fan, there are noticeable temperature differences to the left and right sides of the truck during heating. It poses safety risks to tires close to the air outlet sides.

Fig 3 A. Model 1: air outlets on side walls, a turbo-blower and a rear end fan International Animal Health Journal 41

LOGISTICS AND SUPPLY MANAGEMENT can hardly reach greater than 55°C. Over time at increased heating costs with enhanced equipment, these locations may finally reach the thermal target. Besides, it is a question to note if the tires can withstand that high heat for prolonged heating.

Third, be attentive to the temperature of the inside surface of the trailer and the tail plate/cover, because these are the main areas contacting with pigs and the loading facility in a pig farm. When not being completely decontaminated, viruses can possibly be carried and spread into the farm via contamination in the loading process and can also pose a major biosecurity threat to downstream customers.

Fig 3 B. Model 1: A rear end air outlet and a rear end fan (no air outlets on the side walls)

•

Model 2: thermal exchange with air circulation, with a rear end air outlet and a rear end fan (Fig 3B). It directly heats up the truck trailer and so takes less time and energy to reach the target temperature compared with Model 1.

2.3 Heating Process Validation During the biosecurity audit for truck/car washing for biosecure transport, the team often found that some farm operators were mistaking the ambient temperatures (room temperatures) as actual surface temperatures at different points of the truck.

The half-life of viruses varies at different temperatures.

Temperature and holding time (i.e. the temperature and time pathogenic microorganisms are exposed to this temperature) are two major factors that affect the survival of a virus. Therefore, it is important to know the temperature of space in the heating room and the interior surface of the trailer.

Take the enclosed non-air-conditioning truck (Fig 2B) as an example. Under the conditions of the first heating room model (Fig 3A), the heating equipment is set to run at 65°C for 160 minutes (local temperature at about 20°C) in the 300-minute run experiment (fully monitored with the temperature recorder/sensors). The temperatures of the front left, the front right, the rear left, and the rear right corners in the first layer of trailer (Fig 5) are compared with the readings of the thermos-sensors of the heating equipment outside the truck (i.e. ambient temperature). In this case, the hot air outlet is on in the rear left side wall of the heating room.

(Note: truck terminology: in countries such as the USA and UK, the truck is comprised of a power unit and a trailer, each can be separated; in China, the power unit (the driver cabin) and the trailer part are connected, usually not separable).

For truck decontamination, we need be especially cognizant of these aspects: First, the viruses mainly contaminate the surfaces of the vehicle rather than the space of the heating room. Second, be mindful that viruses harboured on the vehicle surfaces probably ca not be completely and thoroughly inactivated by the single heating process. The decontamination is a multiple layer process of cleaning, disinfection, and TADD. Each step plays a role to mitigate. We found that the temperatures vary at different heights in the heating room. The closer to the ground, the lower the temperature usually is (Fig 4).

Even when the temperature inside the trailer exceeds 70°C, the temperature of undercarriage and other lower areas

Fig 5. The front left and the front right corners (A); the rear left and the rear right corners (B) in the first layer of the trailer.

Fig 4. Monitoring of temperature at different points of a truck in the heating process 42 International Animal Health Journal

The data showed that the ambient temperature was inconsistent with the inside surface temperature of the trailer. When the ambient temperature of the heating room reached the target temperature, the temperature of some spots inside the trailer and in the cabin stayed below the Volume 9 Issue 1

LOGISTICS AND SUPPLY MANAGEMENT target because hot air can not reach such areas (Fig 6 & 7).

Therefore, if the heating procedure was set based on the ambient temperature, the temperature and holding time of certain spaces inside the trailer may not reach the target.

to target, especially when a rear end fan was not in place, because it was difficult to blow adequate hot air into inside the trailer (Fig 8). It was quite often that when the ambient temperature outside the truck exceeds 70°C, the innermost corner in the first layer of the trailer of the air-conditioning truck not yet reached the temperature of 56°C. To mitigate, all heating rooms were installed with a rear end fan (Fig 9).

Fig. 6 Temperature profile of various spots in the trailer and the environment

Fig. 7 Time taken for the different spots inside the trailer and for the heating room to reach 56°C, and holding time for them to stay over 56°C.

Fig 8. Enclosed air-conditioning trailer with air filtration

2.4 Lowest-Temperature Point Inside the Trailer It is necessary to identify the lowest-temperature point inside the trailer. Some spots inside the trailer may not receive adequate heated air thus not sufficiently decontaminated, and the viable viruses might escape the heating, especially in high moisture situations.

Generally, the lowest-temperature points inside the trailer is linked with the vehicle design, the model of the heating room and the equipment used. Multiple measurements suggested that the lowest-temperature points inside the trailer were usually one of the four corners in the bottom layer of the inside trailer (i.e. the front left, the rear left, the front right, and the rear right corners, as shown in Fig 5). It is necessary to make multiple measurements with temperature recorders placed at these corners and different parts in the cabin to determine proper operating temperature for a specific type of trailer. You should set up the heating procedure (the target temperature and time) to ensure the spots identified to be the slowest to heat up to the target and sustain the time needed. For that reason, you might need to adjust the outlet direction of the hot air blower and the configuration of the turbo-blower.

The continuous monitoring of the heating temperature also showed that the more enclosed the vehicle, i.e. the enclosed air-conditioning truck with air filtration (Fig 2C), the longer it took for the temperature in the trailer to get www.international-animalhealth.com

Fig 9. A rear end fan International Animal Health Journal 43

LOGISTICS AND SUPPLY MANAGEMENT 2.5 The Effects of Sitting and Draining Water and the Rear End Fan on Heating It was a crucial but often an overlooked step to drain water and dry after washing and disinfection, to remove all water on the surfaces (Fig 10). In the heating room for some farms, quite often water was seen inside the trailer after heating (Fig 11). This can have an impact on the effectiveness of decontamination.

Fig 12. Temperature curve of group 1

Fig 10. The truck is draining water before heating

Fig 13. Temperature curve of group 2

Fig 11. Water remain in the vehicle trailer after heating

Use the enclosed non-air-conditioning truck (Fig 2B) as an example. Under the conditions of the first heating room model (Fig 3A), the experiment was split into three groups: • • •

Group 1, Drained and heated with a rear end fan, Group 2, Drained and without a rear end fan, Group 3, Not drained and with a rear end fan.

The heating equipment was set up to run at 65°C for 160 minutes (local temperature at about 20°C) in the 300-minute experiment (fully monitored with the temperature recorder).

Group 1 2 3

Front right corner

Front left corner

48 mins, held for 159 mins 51 mins, held for 222 mins Fail to reach 56°C, due to water in the compartment after heating

Rear right corner

36 mins, held for 174 mins 42 mins, held for 225 mins

57 mins, held for 138 mins 63 mins, held for 114 mins

111 min, held for 180 mins

72 mins, held for 112 mins

Table 2: Time taken for each heating group to reach 56°C and the holding time (after reaching the target temperature) 44 International Animal Health Journal

Fig 14. Temperature curve of a truck of group 3

The data was shown in Fig 12, 13 & 14, and the time taken to reach 56°C and the holding time above 56°C during the heating are shown in Table 2. In Group 3, when water remained inside the trailer and the undrained group was heated, and some spots failed to meet the temperature requirements. As such, draining and removing water before baking was critical for the heating effectiveness.

Compared the results of Group 1 & 3 with that of Group 2, we saw that the rear end fan can remarkably shorten the time to reach the target temperature by ensuring an even air flow.

Interestingly, the front left and the front right corners in the first layer stay above 56°C longer in group 2, without a rear end fan than the groups 1 and 3 with one. But in group 2, the temperature maintenance time of the rear right corner was the shortest. Once the dryer stopped working in 160 minutes after start-up, in group 2, the heat in the front left and front right corners in the trailer dissipated more slowly, but the temperature of the rear right corner dropped quickly due to rapid heat dissipation, resulting in a reduced temperature maintenance time. The shorter the time for each temperature point inside the trailer to reach the target and the similarity Volume 9 Issue 1

LOGISTICS AND SUPPLY MANAGEMENT of time for different spaces to sustain temperature as set, the lower the heating costs.

We emphasized that the driver cabin doors should stay open and the side windows of the trailer be lowered down during heating, to enhance hot air circulation and water evaporation to raise up the temperature (Fig 15).

Fig 15. Keep the doors and windows open during heating

2.6 Setting the Height of the Tail Plate/Cover During Heating Almost all large trucks for the transport of breeding pigs commercially available now have an escalate tail plate/ cover. There was no uniform standard for the tail plate height during heating. In a trial when the tail plate/cover was placed at different heights (Fig 16 & 17), the results showed that it was difficult to reach the target temperature when the rear plate/cover was adjusted at the lowest possible (below the floor of the bottom layer of the trailer) (Fig 18).

Fig 17. The tail plate is at the same height as the bottom layer

Fig 18. Temperature curves of the tail plate at different heights during heating

•

Fig 16. The tail plate is at its lowest point

2.7 Setup and Regular Adjustment of Vehicle Heating Equipment There are two operation modes of the heating equipment in the heating room: •

Mode 1. to set the temperature and the total operating time of the equipment, that is, the heating equipment starts timing when powered on. If we set it for 60 minutes, the equipment will start timing on start-up, and stop operating in 60 minutes.

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Mode 2. to set the temperature and the holding time, that is, the heating equipment starts timing when the temperature sensor reaches the set-up target temperature. For example, if we set it to hold for 60 minutes at 70°C, the heating equipment will start timing when the temperature sensor reaches 70°C and stop operating in 60 minutes.

The set heating temperature should allow the lowesttemperature point inside the trailer to reach and consistently stay above the target temperature.

Efficiency-wise, the higher the target temperature, the shorter the holding time, which was undoubtedly preferred for large-scale pig farms. However, we need to consider the time for heat penetration, that is, the time for the vehicle to be evenly heated and for the lowest-temperature point to reach the target temperature.

International Animal Health Journal 45

LOGISTICS AND SUPPLY MANAGEMENT Setting up for the heating equipment mode 1: Vehicle type

Set temperature of heating equipment T (°C)

Time required for the lowest point of the inside trailer to reach the target temperature after start-up X (minute)

High-open rack truck

T1

X1

Enclosed nonairconditioning

T2

X2

Enclosed airconditioning with air filtration

T3

X3

As the baking room is one room fits all vehicles, technically we do not recommend changing it often by the room operator. As such, other key considerations when setting up temperature of equipment.

Holding time for each target temperature Y (minute)

Y

Safety cushion time (minute)

Total run time (minute)

15

X1 (high) +Y+ 15

15

X2 +Y+ 15

15

X3+Y+ 15

You need to know the X and Ys for each type of trucks, and technically, it is needed to use the highest set up temperature for the three types of vehicles (choose from T1, T2 and T3) and choose the longest running time (X+Y).

Setting up for equipment mode 2:

Vehicle type

Set temperature of heating equipment N (°C)

The time interval between the start-up and when the lowest point of the compartment reaches the target temperature X1 (minute); the time interval between the start-up and when the heating equipment starts timing X2 (minute)

High-sided

T1

(X1-X2)1

Enclosed non-airconditioned

T2

(X1-X2)2

Enclosed air-conditioned with air filtration

T3

(X1-X2)3

Apply the same setting up principles as mode 1.

Holding time required for each target temperature Y (minute)

Y

Guard time (minute)

Holding time (minute)

15

(X1-X2)1 + Y+ 15

15

(X1-X2)2 + Y+ 15

15

(X1-X2)3 + Y+ 15

(note: superscripts denotes type of truck)

The heating process is affected by many factors including the ambient temperature (the temperature inside the TADD chamber), equipment stability, truck sitting after washing and water drainage, etc. Therefore, be it the mode 1 or 2, the values​​ of X and X1–X2 are changing all the time. The purpose of safety cushion time is to ensure sufficient temperature sustaining time when the heating temperature is compromised for certain reasons. It is suggested to adjust the equipment setup twice a month, and once a week at change of seasons. We use past data as reference to set up the machine with proper X and X1–X2.

3. Other Critical Control Points Over the Heating Room Operation 3.1 Continuous Monitoring of the Heating Temperature Continuous temperature monitoring allowed us to keep an eye on the heated vehicles. Even automated heating equipment cannot guarantee that all heating processes measure up to the standards. When a vehicle was being heated, there may be occasional “hiccups”. During the longterm temperature monitoring, we found that there was one incident that the heating temperature was below the target (Fig 19). After investigation, it turned out that the heating was interrupted because equipment run out of fuel.

To avoid such “hiccups”, it is necessary to check whether there is sufficient fuel and fill in the inspection records before each heating. Use a wireless temperature recorder to monitor the heating temperature in real time if available.

46 International Animal Health Journal

Fig 19. Recording showing an incident when the temperature is not meeting standard

3.2 Heating Cost Calculation For the heating room, it took about 29.7L of diesel for each heating. Counting the electricity bill, the overall cost was about 250 yuan (40 dollars) per vehicle per heating. At present, when pig prices were sluggish, it had become the focus of the whole swine industry to reduce costs and increase efficiency. One may realize cost reduction from the following good practices: • Drain the vehicle and remove surface water before TADD to shorten the time to reach the target temperature.

• Reasonably adjust the heating time when requirements are met.

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LOGISTICS AND SUPPLY MANAGEMENT and avoid potential cross contamination. All staff involving in truck washing should have a mindset of clean-dirty lines. For baking purpose, the heating effectiveness can be affected by a range of factors, including vehicle design, washing and water removal, disinfection and sufficient contact time, the installation of a rear end fan, the height of the tail plate, the temperature differences between the sensor reading and the actual temperature inside surface of the trailer, the timing set up modes of the heating equipment, available fuel, and water residue in the trailer.

It is critical to be aware of the nature and design of trucks, know the potential pitfalls, thus set up equipment correctly so they fit for different type vehicles, and continuously monitor the temperature to ensure the targets being med rightly.

Another critical point for managers to be mindful is that nowadays clients ask for one source breeder supply, and demand breeders to be delivered less frequently. In coupling with the need for truck downtime, our experience and recommendation are that, a washing facility is better designed with a maximum washing/baking capacity for 7 trucks per day to accommodate the peak need.

A TADD facility can only function effectively when it does what you expect it to do, and you need to monitor and use data to prove and sustain your confidence for health assurance.

Acknowledgements The authors would like to thank Mr. Xiaokang Liu, Mr. Guoqing Jiang and Mr. Jiwei Pu for their valuable support.

REFERENCE 1.

2.

3.

4.

5.

1W. Plowright and J. Parker. The Stability of African Swine Fever Virus with Particular Reference to Heat and pH Inactivation.

Animal Virus Research Institute, Pirbright, Surrey, England.

I.D. Kalmar, A.B. Cay, M. Tignon. Sensitivity of African swine fever virus (ASFV) to heat, alkalinity and peroxide treatment in presence or absence of porcine plasma. Veterinary Microbiology 219 (2018) 144-149.

Melina Fischer et. Al.. Stability of African swine fever virus on heat-treated field crops. Transboundary and Emerging Diseases. 2020. https://doi.org/10.1111/tbed.13650.

C. Turner and S.M. Williams, 1997. Laboratory-scale inactivation of African swine fever virus and swine vesicular disease virus in pig slurry. Journal of Applied Microbiology 1999, 87, 148–157.

Andrew D. Wales and Robert H. Davies. Disinfection to control African swine fever virus: a UK perspective. Journal of Medical Microbiology 2021;70: 001410 DOI 10.1099/jmm.0.001410.

Dr. Xia Tian

• • •

Use a large air flow blower for heated air circulation to balance the temperature all over the inside trailer.

Check whether there is sufficient fuel to ensure the high performance of each heating.

Use more intelligent heating equipment for the automatic adjustment of the vehicle-specific heating procedure.

4. Conclusions A truck washing facility and bio-secure truck washing and decontamination are essential for pig businesses to sustain and thrive. When building a truck washing facility, there is a need to have the right infrastructure to ensure the single directional flow always from dirty to clean, and to minimize www.international-animalhealth.com

Dr. Xia Tian DVM, MS obtained his Master of Veterinary Medicine degree from Huazhong Agricultural University.

He has 11 years of pig production experience, currently works for PIC as the Health Assurance Manager, being responsible for managing the health for PIC farms and PIC multipliers. Prior to that, he worked for Hypor in different roles as the nucleus farm manager, production director and veterinary manager.

Authors Miles Yao, DVM, MS, Jian Long, DVM, MS; Rodney B. Baker, DVM, MS; Dan Tucker, DVM, PhD.

International Animal Health Journal 47

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