Volume 9 Issue 2
PEER REVIEWED
How the “Four Pillars” of Modern Diagnostics are Improving Animal Health and Welfare A Meta-Analysis of the Relationship Between Lung Lesion Scores in Slaughter Pigs and their Daily Weight Gain Cannabis An Overview of Use in Veterinary Medicine Start with the End in Mind Formulation, Drug Delivery Technology, and Manufacturing Official Supporting Associations -
Sponsored companies -
www.international-animalhealth.com
AHEAD IN ANIMAL HEALTH
Your partner for contract research Royal GD is a partner within the animal health industry worldwide, performing in vivo, in vitro and field studies. We conduct safety and efficacy studies on veterinary biologicals and pharmaceuticals in compliance with the OECD principles of Good Laboratory Practice (GLP). Our portfolio includes, but is not limited to: • Safety and efficacy studies of veterinary biologicals and pharmaceuticals; • Studies to obtain vaccine or challenge-strain candidates; • Quality control tests on final products; • Development of models to demonstrate the efficacy or safety of veterinary biologicals and pharmaceuticals; • Surveys on the prevalence of (emerging) infectious diseases/agents. Get in touch and plan a meet up with our account managers and research project team: support@gdanimalhealth.com
www.gdanimalhealth.com
ROYAL GD IS AHEAD IN ANIMAL HEALTH WITH EXPERT AND INDEPENDENT CONTRACT RESEARCH
CONTENTS 04 FOREWORD INVESTMENT 06 Investment and Innovation in Animal Health: The Past, Present, and Future Investment and innovation in the animal health space has evolved drastically over the last decade driven primarily by the growth of protein demand and the humanisation of pets. The frenzy of investment activity has substantially increased with an estimated $4.5 billion invested in small to emerging start-ups since 2010 with over 400 + start-ups actively operating in the animal health ecosystem. Not to mention, the industry has seen the largest players spin-off from their human health parent company and garnered some record-breaking IPOs. Amanda Burkardt at Nutripeutics Consulting, talks about the changes in the investment and innovation within the animal health industry.
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
REGULATORY & MARKETPLACE 08 How the “Four Pillars” of Modern Diagnostics are Improving Animal Health and Welfare
BUSINESS DEVELOPMENT Jerome D’Souza info@senglobalcoms.com
Traditional diagnostic technologies – from ultrasounds and x-rays to testing kits and reagents – are a routine part of supporting good animal health through detecting disease and enabling treatment. However, recent innovations mean the field of diagnostics is moving beyond just point-in-time readings that confirm a veterinarian’s suspicion about an animal’s health. Carel du Marchie Sarvaas at HealthforAnimals, explains how the “four pillars” modern diagnostics are improving animal health and welfare.
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.
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 2 Summer 2022 Senglobal Ltd. www.international-animalhealth.com
12
Regulating Veterinary Drugs in India: A Case Study Based on the Drug and Cosmetic Act The Drug and Cosmetic Act (D&C Act) 1940 and rules 1945 mainly involve a systematic review or understanding of the statutory framework of laws and regulations applicable to drugs and cosmetics. The D&C Act came into effect on April 10, 1940, to regulate India's import, production, distribution, stocking, and sale of drugs and cosmetics. The primary purpose is to make the drugs and cosmetic products available in India are of standard quality, safety, and effectiveness for human use. It also provides penal provisions for violations of norms under various sections of the Act. In India, some cases on the pharmaceutical companies are pending in the Hon'ble trial courts and Higher Courts related to the contravention of the D&C Act. Balamuralidhara. V, Amaresh Tumbagi, Ashutosh Mishra and Deeksha K S at JSS College of Pharmacy discuss the consequence of violating the laws and regulations specified in the D&C Act by taking the example of a case filed against a pharmaceutical firm manufacturing veterinary products without a valid license.
18 Making the Vet Industry more Sustainable Top 5 Tips you can Initiate in your Practice Sustainability has become a buzzword in the twenties. COP26 and extreme weather events have pushed it even further up the agenda for governments, companies, and individuals. In its broadest sense it means much more than doing International Animal Health Journal 1
CONTENTS something for the planet and it may be argued that we have gone beyond sustainability to a more seismic requirement to regenerate. Sustainability is also about people and animals but also companies and professions. Anthony Chadwick at The Webinar Vet points out some tips to make the vet industry more sustainable. RESEARCH & DEVELOPMENT 20 Start with the End in Mind - Formulation, Drug Delivery Technology, and Manufacturing This is the second article in the "From Molecule to Market" series, where we address the different phases in the animal health product development journey. Darrell Morgan at Argenta, shares the insights on developing new Veterinary Medicinal Products. From selecting the drug delivery technology and developing the formulation to scale-up, validation and manufacture of your drug product. 24 A Meta-Analysis of the Relationship Between Lung Lesion Scores in Slaughter Pigs and their Daily Weight Gain A meta-analysis was performed on available published articles in which Ceva Lung Program (CLP) method of assessing enzootic pneumonia (EP) -like lesions was utilised and which also contained the record of average daily gain (ADG) data. Eight studies fulfilling the inclusion criteria were analysed using non-parametric tests. Roman Krejci at Ceva, Monika Kuncová and Jiří Kalina at Research Centre for Toxic Compound in the Environment, evaluate the original (previously published) data together with data from two other studies being comparable since utilising the same lung scoring method. Those data from multiple studies were analysed for the first time using a new statistical method quantifying the linear relation between lung score results and growth performance, not only the differences between treatment groups.
2 International Animal Health Journal
30 Cannabis: An Overview of Use in Veterinary Medicine Perhaps no other herb has recently received as much attention in the media — or in the courts — as Cannabis sativa. With more countries and local jurisdictions moving toward legalisation for recreational as well as medical purposes, use of cannabis in its many forms has expanded exponentially among the human population. As medical marijuana becomes more widely accepted and available, it’s no surprise that veterinary practitioners are increasingly asked to address questions about medical applications for nonhuman animals, while manufacturers are facing decisions regarding how to respond to customer demand. Jan Allegretti, the author of The Complete Holistic Dog Book: Home Health Care for Our Canine Companions overviews the use of cannabis in veterinary medicine. 34 Yeast Mannan Oligosaccharides: A Front-line Defense Mechanism for Pathogen control Bacterial adherence to host tissue is an important initial step in enabling gastrointestinal tract colonisation and infection. Adherence typically involves the interaction of complementary molecules on the surface of a bacteria with those of the host epithelium. Dr. Richard Murphy at Alltech, explains more about yeast mannan oligo-saccharides. COMPANION ANIMALS 36 Biometric Study Proves Pet Acoustics® CanineSpecific Music Mitigates Stress Levels in Dogs Canine behavioural stress is often triggered by their acute hearing to sounds in the environment. The benefits of music in the canine listening environment have been proven in previous studies with results showing calm and a more balanced behaviour. To further understand the calming effects, Janet Marlow at Pet Acoustics, Asaf Dagan at PetPace and Ron Pia at The Pet Calmer analyse the biometric data of mostly small dog breeds while listening to the species-specific designed music.
Volume 9 Issue 2
Animal health contract research Expert delivery of contract studies supporting product development and commercialisation. Efficacy studies
Facilities
• • • • •
• • • • • •
Broad portfolio of infectious disease models New model and protocol development VICH-GCP compliant studies Studies in all species of livestock Aquaculture studies
Target animal safety testing • • • •
GLP compliant studies All species of livestock Aquaculture studies All types of biological & pharmaceutical products
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
www.moredun-scientific.com
For further information please visit www.moredun-scientific.com or contact: Moredun Scientific, Pentlands Science Park, Bush Loan, Penicuik EH26 0PZ, Scotland, UK Tel: +44 (0)131 445 6206 Email: info@moredunscientific.com Follow us
FOREWORD Welcome to the latest edition of the Journal. It arrives towards (for some) the tailend of the Covid pandemic, conflict, rising inflation and monkey pox. Pressure on food supplies, particularly those which come from the Ukraine, are intense and are helping to fuel the inflation mentioned above. It reminds us that we normally take our food supply for granted but troubles now and troubles in the future such as climate change and dwindling water supplies, may threaten food availability in the future. Anyone who has seen photographs of Lake Mead and the area around the Hoover Dam will immediately notice the changes in water levels; changes which threaten farming in the immediate and in more distant areas. Animal diseases, at least in the Western world, rarely threaten famine. However, they can pose animal welfare problems and economic losses as well as financial ruin for individual producers. An article in this issue examines the effects of one such disease on pig production. Enzootic pneumonia in pigs is caused by the bacterium Mycoplasma hyopneumoniae. This organism does not usually cause severe disease but it does results in a reoccurring pneumonia with a dry cough, roughened hair coat, reduced growth rate and lower feed conversion efficiency. However, it can (and does) lead to secondary bacterial and viral infections such as those associated with Pasteurella multocida, swine influenza virus, porcine circovirus 2 and porcine reproductive and respiratory syndrome (PRRS). Clinical signs can then include a chronic dry cough, laboured breathing, elevated temperature and prostration. Economic losses, not to mention animal losses, can be severe.
Cannabis, which has a variety of other names including marijuana, is derived from the cannabis plant, Cannabis sativa and from other related plants of the same family. The main active constituent is tetrahydrocannabinol but there are up to almost 500 other active components including cannabidiol. Research avenues in human medicine, some better established than others, include dementia-related conditions, glaucoma, epilepsy, Tourette syndrome, glaucoma and multiple sclerosis. Some of these proposed uses have yet to show merit while other are promising. So, could cannabis have any uses in the animal field? Well, Jan Allegretti certainly believes so. She is a veterinary homeopath working in the USA and author of The Complete Holistic Dog Book: Home Care for Our Canine Companions and in this issue she reviews the potential uses of cannabis in the treatment of animals. I am sure you will find great pleasure in reading these two articles but please don’t ignore the others. They are equally informative and entertaining and well worth reading. Kevin Woodword, Managing Director, KNW Animal Health Consulting
In this issue, Roman Krejci, Monica Kuncová and Jiří Kalina report on the results of a meta-analysis of 8 studies relating pulmonary lesions in enzootic pneumonia affected pigs to quantify the relationships between lung lesion scores and pig growth performance. Although other studies have attempted to examine similar aspects previously, this meta-analysis, which also uses a new statistical approach to data analysis, is the most extensive to date. Many drugs start out life as therapeutic agents but later are adapted to recreational purposes, frequently resulting in problems associated with addiction and overdose. Examples include heroin (analgesic – as diamorphine), cocaine (local anaesthetic) barbiturates and benzodiazepines (tranquilisers) and nitric oxide (general anaesthetic). Readers will recognise that this is far from being a comprehensive list! Cannabis is slightly different. It has long been used as a recreational drug but it has spent a very long time looking for a medical use or uses.
EDITORIAL ADVISORY BOARD
Amanda Burkardt, MSc, MBA – CEO of Nutripeutics Consulting 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 2
INVESTMENT
Investment and Innovation in Animal Health: The Past, Present, and Future Investment and innovation in the animal health space has evolved drastically over the last decade driven primarily by the growth of protein demand and the humanisation of pets. The frenzy of investment activity has substantially increased with an estimated $4.5 billion invested in small to emerging startups since 2010 with over 400 + startups actively operating in the animal health ecosystem. Not to mention, the industry has seen the largest players spin-off from their human health parent company and garnered some recordbreaking IPOs. This, coupled with extreme M&A activity, has formed the industry into a highly consolidated space with innovation being driven by small and agile startup companies that quickly get consumed by the larger players. The animal health space has navigated the ebbs and flows of the economic rollercoaster shockingly well, emerging as a resilient and recession-resistant category; making investment in this space extremely attractive. A Decade in Review One of the most significant differences which has happened in the past 10 years has been the breakaway of large animal health corporates from their parent human health companies and the rapid mergers and acquisitions activity that follow suit. Probably the most notable shift, which moved the animal health industry into the spotlight, was in 2013 when Zoetis split from its human health parent company, Pfizer. At the time, this IPO was the largest seen on the stock exchange since the Facebook IPO, with an initial public offering of over $2 billion. This event garnered much needed validation for the industry and proved that animal health focused ventures can stand alone as robust, multi-billion-dollar corporations. Just taking a look back to 2012, we can see how quickly the players have evolved from the top 4 animal health companies being Pfizer, Merck, Merial, and Elanco to 2022 where the top 4 are now Zoetis, Elanco, Merck Animal Health, and Boehringer Ingelheim. Out of the current corporates at the top, only two are still tied to their parent human health company: Boehringer Ingelheim and Merck Animal Health. The chronologic flurry of activity in the animal health industry peaked in 2018 with Elanco’s bold move to acquire Bayer Animal Health, resulting in 2019 as being one of the biggest years for acquisitions in the industry with over $8.1 billion reported in public disclosures. An Overview of the Industry The global animal health market is comprised of every category that directly or indirectly touches animals. The majority of revenues come from livestock animals, companion animals, and aquaculture, however, there are other subsegments of the space that are quickly growing. The core animal health industry is projected to be worth over $40 billion with complementary categories such as nutrition, diagnostics, and digital technology adding another $35 billion1. Adjacent categories such as pet insurance, pet food, and agritech combine for an overall market size of $350 billion. In 2018, out of the top general 6,000 products, the top 25 generates over 75% of total sales. Over the last decade this market has outpaced the market S&P 500 index with over 44% growth with the market product categories being pharmaceutical, biological 6 International Animal Health Journal
and medicated feed additives. The surge of medicated feed additives and biologicals can be correlated with the shifting mindset of the animal health industry from a treatment perspective to preventive model of care for animals. Likewise, these product categories have seen multiple blockbuster drugs (over $100 million in annual sales) with next generation products such as Cytopoint from Zoetis for canine itch relief or Galliprant from Elanco for canine osteoarthritis. There are also complementary categories which are also emerging that are being wrapped up in the animal health ecosystem as sustainability and animal welfare are swiftly burgeoning to the forefront. Because of the demands placed on protein production, sub-categories such as insect protein are being utilised in all facets of the industry as a dietary supplement for companion and production animals. In fact, the largest ever raise from an animal health company happened in 2019 with a Series C raise of $372 million by French insect protein company Ÿnsect. In addition, the veterinarian is at the core of animal health as they are usually the target customer for many of the large animal health company’s products as well as being the medical epicenter, thus, solutions focused on the vet, such as practice management software, telehealth systems, and vet/pet owner interaction tools have gained significant investment recently. Investment Investing in the animal health industry has seen a fervor of interest from small to large investment entities. A decade ago, startup animal health companies would be hard pressed to find investment money from dedicated animal health investment firms. Almost always entrepreneurs would have to go to human health investment entities seeking money for their animal health product with limited success as in-house investment expertise on these products was limited. Now, there are several boutique investment firms ither spun off from their human health core or networks only focusing on only animal health such as Blue Rabbit Ventures, Anterra Capital, Veterinary Angels Network for Entrepreneurs, Borealis Ventures, and NovaQuest. In addition, most of the large animal health corporate have ventures arms which are recruiting innovators through partnerships, pitch competitions, or accelerators such as 9SquareVentures (Purina), Leap Venture Studio (Mars), PlugNPlay Animal Health (Topeka, KS) and Merck Animal Health Ventures. There has also been a swell of conferences, investment forums, networking events, and forums dedicated to investment and innovation in the animal health space with emphasis on subsegments such as microbiome, pet care, ag-tech, and aquaculture. Investment in the animal health space has correlated with the industry’s growth. In 2010, the average series B raise in animal health, would be seen from $20–$30 million. In just the past 12 months, three emerging companies have raised series B funding with ticket sizes exceeding $60 million: unprecedented for this space. Outside of smaller companies, the market has also seen increased funding in roll-ups, IPOs, and M&A activity with more and more investment banks, private equity, family offices, and external public companies funding large multi-milliondollar transactions such a Merrill Lynch, Barclays, and Bank of America. Innovation With an increase in market size, investment dollars, and Volume 9 Issue 2
INVESTMENT raised an oversubscribed series B of $60.5 million, making it the largest amount of pre-initial offering investment in a companion animal biotherapeutics startup ever. As was mentioned in the investment segment, a majority of investors did not have a background in animal health with funding coming from Google Ventures, Novo Holdings, and F-prime capital. Likewise, in December 2021, molecular pet diagnostics company, PetDx raised an impressive series B of $62 million and the most significant series B ever recorded in the pet care industry happened in August 2021 with Embark Veterinary, a pet DNA testing company, bagging a substantial $75 million.
changing social needs, a natural result is the quickly evolving and expanding solutions being developed for the market’s pain points. Traditionally, most innovations in the industry came from internal research and develop from the larger human health companies which would trickle down to their animal health departments. With the break away from these larger counterparts, more and more innovations and pipeline product expansions are being done through partnerships, joint research projects, licensing of technology, mergers, and acquisitions. Although all of the large animal health players have internal R&D departments and teams, majority of new products and services, that fall outside of the traditional pharmaceutical space, are obtained by licensing or acquisition. This has changed the landscape of the industry and has required the large corporates to hone their integration processes as well as step into unfamiliar adjacent categories of animal health such as next generation solutions and technology. In addition, more strategic partnerships and interdisciplinary development alliances have started to take shape, as the likes of Evergy, a large energy company, supporting the animal health accelerator Plug and Play or Amazon collaborating with VCA to enhance pet health care management systems. The innovation categories which have garnered the most traction in the past decade have been truly challenging old business models and industry’s standards, uncovering a more consumer aware and animal welfare oriented demand. Some the most prevalent innovation categories are: • • • • • •
Alternative protein (e.g. insect protein, cell cultured meat, aquaculture, plant based products) Next generation solutions (e.g. stem cell therapies, monoclonal antibodies, immunotherapy) Diagnostics (e.g. point of care diagnostics at the clinic, at home mail in tests for pet parents) Consumer facing products (e.g. education tools, pet insurance/preventative services, e-commerce) Veterinary technology (e.g. practice management software, telehealth tools, customer engagement platforms) Animal nutrition (e.g. pet treats and food, pre/pro/postbiotics, alternatives to antibiotics)
Although all of these categories are developing into spaces on their own, none have been as impressive nor as fast moving, at the pet care space. With the increase in pet ownership and the amount of time spent with pets at home drastically increasing over the course to the pandemic, the pet care space has enjoyed large investment sizes. In May 2022, biotherapeutics startup, Invetx, successfully www.international-animalhealth.com
It is clear with the flood of activity in investment and innovation in the animal health space that this is a market that will continue to grow and produce cutting-edge technologies to help animals and the humans that take care of them. The investment sizes and innovation activity not just endorse the validity and the appetite of the companion animal segment but also highlights investor interest in the wider animal health space. With all of the change and promise seen in the past decade, it will be exciting for those in this space to see what the next 10 years in the animal health industry will bring. REFERENCES 1.
https://www.grandviewresearch.com/industry-analysis/ animal-health-market
Amanda Burkardt Amanda Burkardt earned both her Bachelors of Science in Animal Science and her Masters in Animal Molecular Biology from Oklahoma State University. She has over seven years of laboratory experience domestically and internationally in various scientific fields. Amanda also has a Masters in Business Administration with an emphasis in Entrepreneurship and a Masters of Management Information Technology from the University of Oklahoma. Amanda not only worked with OSU to spinoff a startup company based on her Master's work, but she also collaborated with OU's Office of Technology Development assisting with due diligence, analysis and decision support for the evaluation of intellectual property created at OU. Through her experience, she has started consulting with other scientists, entrepreneurs, and innovators in evaluating technologies for start-up opportunities as well as the creation, protection and commercialization of intellectual property. Amanda is currently working with a large network of angel investors in the Midwest, scouting for innovations and disruptors in the life science, animal health, and agriculture industries. Through her immense and multi-national networks, she conducts investigations and discoveries, putting together large due diligence reports for investors to examine entrepreneurial value and product opportunity. With her company, Nutripeutics Consulting, she has consulted with the largest animal health companies and institutions in the industry and is frequently showcased in industrywide speaker series, judging panels, newsletters, articles, podcasts, and reports. She has grown her community and is currently working with clients domestically and internationally. She truly has a passion for innovations in science and technology, and desires to discover, develop, and fund products that will "Turn Research into Return".
International Animal Health Journal 7
REGULATORY & MARKETPLACE
How the “Four Pillars” of Modern Diagnostics are Improving Animal Health and Welfare Traditional diagnostic technologies – from ultrasounds and x-rays to testing kits and reagents – are a routine part of supporting good animal health through detecting disease and enabling treatment. However, recent innovations mean the field of diagnostics is moving beyond just point-in-time readings that confirm a veterinarian’s suspicion about an animal’s health. Modern diagnostics encompass a much broader role that underpins the animal health ecosystem, bringing benefits from better animal welfare to greater efficiency and sustainability. Today, diagnostic tools are not only faster and more accurate when it comes to identifying ill-health, but they are also unlocking greater capacity for prevention, preempting diseases and other health changes before they adversely impact an animal. In addition, through advances in surveillance and monitoring, diagnostics can provide a more complete picture of animal health than ever before, allowing veterinarians and keepers to maintain animals in good health, comfort and wellness. Across the sector, developments in diagnostic technologies are creating new and emerging opportunities for animal health professionals by ultimately increasing veterinary intelligence. With more and better data, and new ways to interpret and aggregate it, veterinarians can make clinical decisions with a deep understanding of their patient’s condition, genetics, underlying health and more. All of this points to a revolution in how animals are raised, cared for and treated. From disease prevention to heightened, more holistic surveillance, seizing upon the “four pillars” of modern diagnostics technologies presents veterinarians and other professionals with an unprecedented opportunity to optimise both the wellness and wellbeing of the animals they treat. Surveillance To begin with, new technologies and systems that monitor animal health are providing veterinarians and health agencies with more insight, both at macro and micro levels. For example, technologies driven by diagnostics can track the prevalence and movement of specific diseases and parasites, which is vital at a macro level for maintaining infection control and bio-secure borders when it comes to the livestock trade. This information can also be shared with pet owners so they can take precautionary steps, including vaccination, other preventatives, and treatments to protect their pets from infection and the people around them. The Companion Animal Parasite Council, for example, produces a parasite forecast map1 to give county-level assessments of health risks to pets across the US, helping veterinarians and pet owners make informed choices based on clear science when developing parasite prevention strategies. This is essential since certain parasites are moving into new territories and the “traditional” risks for many regions may no longer be accurate. However, this is reliant upon pets 8 International Animal Health Journal
receiving regular, widespread testing to ensure an accurate picture of prevalence and movement. Such detailed surveillance of disease spread also plays a key role in One Health policies and approaches, particularly when it comes to vector-borne zoonotic diseases that pose a threat to both animals and people. Similarly, diagnostics can highlight where a disease is spreading to new areas, often now as a result of climate change and rising temperatures that allow parasites to thrive in different parts. This is crucial in ensuring that that the right control and treatment products are directed to affected areas. Meanwhile, diagnostics also offer an essential surveillance tool on farms, where regularly screening for a disease like influenza or porcine reproductive and respiratory syndrome (PRRS) can give an indication of a potential disease outbreak before it takes hold. Recent advances in digital diagnostics mean that blood, urine and tissue samples can now be analysed on-site, increasing the speed, accuracy and efficiency of identifying a health issue, which means veterinarians and farmers can treat a developing outbreak before it becomes symptomatic and starts spreading. However, effective surveillance relies upon effective sampling. Ensuring that farmers and veterinarians understand the need to test a representative sample of herds or flocks is crucial to unlocking the preventive value. Developments in automated monitoring, such as microphone sensors, heat and motion cameras, and pedometers, have also relieved the burden of observation on an ongoing basis, streamlining the process of managing herd health in a way that would be unviable without the help of technology. With an estimated one in every five2 farm animals typically lost to disease every year, this kind of surveillance can translate to savings on farms, gains for animal welfare and lower levels of emissions, not to mention more food reaching the supply chain. Prevention The rise of digital diagnostics, machine learning and the connectivity of the Internet of Things is fuelling a generation of powerful disease prevention tools that harnesses new capabilities to capture and analyse health indicators. For example, smart ear tag monitoring devices can digitally report back every 20 minutes on four aspects of cattle health: eating, movement, heat detection and fertility, allowing monitoring systems to flag the earliest sign of change that might indicate an illness before it manifests. Complementing this with rapid, point-of-care diagnostic testing means an illness can be detected, diagnosed, and treated before it has a chance to spark a wider outbreak or spill over to people. Meanwhile, “Big Data” can transform an animal’s existing health and diagnostic records into a tool of prevention, identifying the subtle onset of chronic illnesses before they take hold and harm an animal’s wellbeing. And when scaled up regionally, nationally, and even globally, animal health records become greater than the sum of their parts. Powered by tools like artificial intelligence, “patient-like-mine” platforms Volume 9 Issue 2
REGULATORY & MARKETPLACE
can cross-reference health characteristics and predict the likely health trajectory of an animal based on comparisons to other similar profiles. Veterinarians can then model potential treatments and consider how similar patents have responded. Genomic sequencing provides another tool in the prevention toolbox, allowing veterinarians to build a more comprehensive health profile for an individual animal to allow them to identify not only disease but genetic predispositions to disease and response to different treatments. Such technology enables the veterinarian and owner to develop a health plan directly tailored to the animal that aims to avoid certain conditions, detects them quickly if they occur and enables custom treatment protocols based on their genetic profile. This ultimately can lead to a longer, healthier life for the pet. Wellness Diagnostics are not only instruments of disease detection; they also provide a window into overall wellness, which is much more than the absence of infection. The vast amounts of data that veterinarians are now able to collect thanks to improved diagnostic technologies are helping to produce a www.international-animalhealth.com
more informative animal health “baseline”, which has multiple implications and advantages. When used regularly, diagnostics allow veterinarians to understand an animal’s typical health indicators, such as blood cell counts or urine gravity, which varies from animal to animal. This can then be complemented by monitoring tools that help track how it feeds, its behaviour, its activity, and other signs of wellbeing. Using this information, veterinarians can track health trends, recognise subtle indicators of change, and quickly diagnose serious problems such as kidney or liver disease, which, without the underlying baseline data, may remain hidden. For example, regular thyroid panels provide a clear picture of an animal’s typical hormone levels, a critical regulator of an animal’s metabolism. Minor shifts in this can lead to hypothyroidism, which causes weight gain, energy loss, and recurring infections, among other health issues. Understanding an animal’s baseline hormone level enables a veterinarian to International Animal Health Journal 9
REGULATORY & MARKETPLACE see when even minor shifts are occurring rather than relying on “typical” ranges for a breed, size, and age profile. Urinalyses are an important part of kidney assessment and can also help detect illnesses like diabetes. However, the physical and chemical properties of each pet’s urine will differ, which is why setting a baseline and tracking its profile offers a much deeper understanding of an individual pet. The indicators of kidney disease or urinary inflammation can often be subtle at first and a close understanding of a pet’s unique urine properties mean the first indicators can be better recognised, enabling early action that avoids unnecessary discomfort for a patient. Such baseline data can also be used alongside the big “patient-like-mine” tools, which refer veterinarians to previous treatments to guide their own case-by-case clinical decisions. With a clearer picture of what “good health” means for each individual animal, veterinarians can be better placed to respond when a change in health status occurs, and tailor care and treatment plans to be most effective. Such developments have contributed to the rising life expectancy of pets, with the average dog in the US living3 11.8 years in 2016, up from 10.5 years in 2002. Medicalisation Finally, modern diagnostics is the key to optimising medicalisation. Without the right information from an accurate diagnosis, it is impossible to effectively treat, create health plans, or understand hidden or underlying issues that an animal may have. Ultimately, diagnostics is data, data is knowledge, and knowledge is power – in this case, the power to act in a way that achieves better health outcomes for each animal. With preventative and predictive innovations in diagnostics, such as AI-powered tools, veterinarians are now able to parse this vast amount of data and identify diseases earlier, enhancing the probability that medicines will deliver a positive and timely impact in each case. Likewise, more accurate diagnostic data is also helping to inform more responsible and sustainable use of antibiotics, which helps to reduce the threat of antibiotic resistance and its risks for both people and animals. With more diagnostic data available, veterinarians can take more informed decisions about when, and if, antibiotics are required, and are able to apply other treatments and interventions before antibiotics may become necessary. For example, regular screening of herd and flock samples allows livestock veterinarians to identify a potential outbreak before it spreads among large numbers. This empowers veterinarians and farmers to firstly isolate the affected animals and limit the outbreak, and secondly, to determine whether a pre-emptive group treatment is needed to nip the disease in the bud. Moreover, it is now a requirement in the EU to have a clinical diagnosis before administering antibiotics, making reliable diagnostics crucial to the welfare of animals facing bacterial disease. Furthermore, the knowledge derived from diagnostics also enables precision therapies that are tailored to the individual animal’s medical condition. For instance, within the field of oncology, deeper understanding of a pet’s genetics can help a veterinarian select a treatment protocol specific to 10 International Animal Health Journal
that animal versus plans developed for the wider breed or even species. This can lead to higher probability of treatment success. Conclusion Across the board, technological innovations are creating a more active role for diagnostics, helping veterinarians to take a proactive, rather than reactive, approach towards animal wellness and wellbeing. Ultimately, the sustainability of caring for animals, whether livestock or pets, hinges on the capacity to deliver good animal health and wellbeing, and diagnostics play a fundamental role. From extending the life expectancy of pets through new tools that better monitor their baseline wellness to reducing the losses of food-producing animals to disease, the ability to monitor, identify and treat health changes comes back to diagnostic technologies. And not only do innovations that increase the efficiency, accuracy and functionality of diagnostics allow animals to remain in good health, they allow animals to thrive and reach their full potential, bringing benefits for people and planet. With more than half of households in major markets4 owning a pet, the ability to provide a longer, healthier life reinforces the human-animal bond and allows pet owners to enjoy more years of valuable companionship. Similarly, as demand rises around the world for meat, milk and eggs, livestock health is an increasingly important driver of productivity and sustainability, with positive impacts for food, nutrition and economic security. Just five animal diseases made up two-thirds of outbreaks5 between 2000 and 2016, impacting global food production and trade, making early and comprehensive diagnosis a tool of economic growth. In sum, these key developments in modern diagnostics technologies have transformed how animal health professionals plan for, and deliver, healthcare to animals. Early interventions to track, stop or treat a disease reduces the burden of ill-health – on animals, their guardians and society at large, with animal diseases directly impacting the income, employment, disease risk and food security of billions of people worldwide. The “four pillars” of modern diagnostics are upholding more than ever, that prevention is better than cure, supporting the foundation for healthier and happier animals. REFERENCES 1. 2. 3. 4. 5.
https://petdiseasealerts.org/forecast-map/#/ https://www.oie.int/fileadmin/Home/eng/Media_Center/ docs/pdf/Key_Documents/ANIMAL-HEALTH-EN-FINAL.pdf https://www.reuters.com/article/us-money-pets-longevity/ your-money-as-pets-live-longer-they-may-need-longterm-health-care-idUSKCN11J25D https://www.gfk.com/insights/mans-best-friend-globalpet-ownership-and-feeding-trends https://www.oie.int/fileadmin/Home/eng/Publications_%26_ Documentation/docs/pdf/TT/2016_A_84SG_9.pdf
Carel du Marchie Sarvaas Carel du Marchie Sarvaas, executive director of the global animal health association HealthforAnimals
Volume 9 Issue 2
Succeed Sooner. All the product development expertise you need, under one roof. 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 www.international-animalhealth.com
|
www.klifovet.com International Animal Health Journal 11
REGULATORY & MARKETPLACE
Regulating Veterinary Drugs in India: A Case Study Based on the Drug and Cosmetic Act Abstract The Drug and Cosmetic Act (D&C Act) 1940 and rules 1945 mainly involve a systematic review or understanding of the statutory framework of laws and regulations applicable to drugs and cosmetics. The D&C Act came into effect on April 10, 1940, to regulate India's import, production, distribution, stocking, and sale of drugs and cosmetics. The primary purpose is to make the drugs and cosmetic products available in India are of standard quality, safety, and effectiveness for human use. It also provides penal provisions for violations of norms under various sections of the Act. In India, some cases on the pharmaceutical companies are pending in the Hon'ble trial courts and Higher Courts related to the contravention of the D&C Act. This study discusses the consequence of violating the laws and regulations specified in the D&C Act by taking the example of a case filed against a pharmaceutical firm manufacturing veterinary products without a valid license. The study highlights the need to obey the rules to ensure that pharmaceutical or cosmetic or veterinary product of appropriate quality, safety, and efficacy is made available to the individuals in the country.
Indian veterinary drug regulation and the legal action by the Government with one relevant precedent. Regulation of Drug Products and the Indian Act4 The definition of a spurious drug is outlined under section 17-B of the D & C Act. It reveals the product shall be deemed to be spurious: (a) If it is manufactured under a name that belongs to another drug; or (b) If it is an imitation of, or is a substitute for, another drug or resembles another drug in a manner likely to deceive or bears upon it or upon its label or container the name of another drug unless it is plainly and conspicuously marked so as to reveal its true character and its lack of identity with such other drug; or (c) If the label or container bears the name of an individual or company purporting to be the manufacturer of the
Section 18 (a) (i)
It is an offence clause and indicates that no person shall by himself or by any other person on his behalf manufacture for sale or distribute or sell or stock any drug which is "not of standard quality" (NSQ) or is Misbranded, Adulterated or Spurious.
Section 18 (c)
It is an offence clause for preventing the illegal manufacture or sale of drugs. According to the D&C Act 1940, No person shall by himself or by any other person on his behalf manufacture for sale or distribute or sell or stock any drug except under, and in accordance with the conditions of, a licence issued for such purpose under the chapter of D & C Act. Any person who infringes it and sells drugs without a valid license as provided by section 18 of clause 'C' shall be punishable with imprisonment for three years, which may be extended to five years and fine not less than one lakh Rupees.
Section 17 B (e)
This clause describes the meaning of spurious drugs under the D&C Act. A Drug shall be considered spurious: If it purports to be the product of the manufacturer of whom it is not truly a product.
Keywords: Drug and Cosmetics act, India, Spurious drug, Veterinary Products, Regulation Introduction The 1940 Drugs and Cosmetics Act (D&C Act) is a preconstitutional Act. The legislature of all provinces passed a resolution in terms of section103 of the Government of India Act 1935 to regulate the import, manufacture, distribution and sale of drugs and cosmetics in the country. The objective of the Act is to make assurance of safety, effectiveness and quality of the drugs and cosmetics sold in India and comply with the standards set by the Government. The Drugs and Cosmetics Rules (D&C Rules) of 1945, which are related, contain p rovisions for classifying drugs under consideration.1 Veterinary drug products are not intended for human consumption. This type of product is used in animal disease prevention, deficiency diagnosis, and injury treatment. Veterinary medicine covers various conditions that can affect domesticated and wild animals, making it a very diverse field. It plays a crucial role in order to maintaining animal and human health. So, maintaining the safety, quality and efficacy of drugs is a primary concern and there are some legal concerns provided by the Act to maintain the same.1,2 In India, there are some cases on the pharmaceutical companies pending in both Hon'ble Trial court and Higher courts related to the contravention of the D&C Act. Not maintaining Good Manufacturing Practice (GMP) is a significant problem of arising substandard medicines. As per the D & C Act, the manufacturer should have a valid license to ensure the product's quality.3 In this light, we will discuss the Regulation of veterinary drugs activities related to drug products' quality, safety and efficacy by taking a case filed in the Hon'ble Special court for Economic offences Bangalore (India), where the accused was involved in the manufacture of the veterinary drug products without a valid license. The study will help the regulators, drug manufacturers and the public regarding the 12 International Animal Health Journal
Section 32
Cognisance of offences. No prosecution shall be instituted except by Inspector or any gazetted officer authorised by state or central Government or the person aggrieved or a recognised consumer association*. No Court inferior to that of the court of a session shall try an offence punishable under this chapter (Chapter IV of D & C Act)*. *effective from 10.08.2009
Section 33-M
Cognisance of offence: 1. No prosecution under this chapter shall be instituted except by an Inspector with the previous sanction of the authority specified under subsection (4) of section 33-G. 2.No court inferior to that of a Metropolitan Magistrate or of a Judicial Magistrate of the first class shall try an offence punishable under this chapter ( Chapter IVA of D & C Act).
Table 1. Different Offences are outlined in D&C Act for the manufacture and sale of certain drug products.1 Volume 9 Issue 2
REGULATORY & MARKETPLACE Drug Inspectors conduct the inspections of both pharmacies, manufacturing and sale premises
They verify whether the conditions of the license are being fulfilled or not
Inspectors take sample from the premises by describing the reason in Form No 17
The samples will be sealed, signed and sent to the government analyst by registered post
If the price is not accepted then the inspector shall render a receipt in prescribed Form 17A
They shall render a fair price for the sample and obtain acknowledgement
Based on the Government analyst report the lnspector will take further actions
In case of court proceedings, the report will be forwarded to the Honorable Judge for Final Judgment There are two types of actions
Administrative action Warning suspension of Licenses/Production permission Cancellation/Product permission Stop production orders
Prosecution Action Filing the Complaint in the Court of Law
Evidence from the prosecution will be produced before the court and accused have liberty to cross examine the evidence and defeat their case
After bearing the case following CRPC procedures honorable court makes the judgment Conviction or Acquittal Reason for acquittal or dropping? Figure 1. Inspection procedure as per the regulation of D&C Act and rules thereunder.1,8
drug, which individual or company is fictitious or does not exist; or (d) If it has been substituted wholly or in part by another drug or substance; or (e) If it purports to be the product of the manufacturer of whom it is not truly a product. As D&C Act and Rules provide the Regulation of drug products regarding the product's safety, efficacy, and quality, some offences are also outlined for the infringer as provided in Table 1. The infringement of the Regulation is found by the inspection procedure as provided in Figure 1.1,5 Also, as per the Act, the definition Drug Inspector, Government Analyst, Panchanama witness are provided, who are involved in the various activities, as below, and some of the forms related to the Regulation is provided in Table 2. Drugs Inspector is appointed under section 21) of the D & C Act by the Central or State Government for other than the Ayurvedic, Siddha, and Unani Drugs (ASU Drugs) and Drugs Inspector is appointed under Section 33 G of the D & C Act by the Central or State Government for Ayurvedic, Siddha, and Unani Drugs (ASU Drugs). That the Government Analyst is appointed under section 20 of D & C Act by the Central or a State Government to test or analyse the drugs and cosmetics other than the ASU products and for testing or analysing Ayurvedic, Siddha, and Unani medicines (ASU medicine) Government Analyst is appointed by the Central Government or a State Government under section 33F D & C Act. www.international-animalhealth.com
The person who acts as witnesses of the Panchanama (Mahazar) are known as "Panchas". It's important to remember that the Panchas must consist of two or more self-reliant and respectable individuals. Such a Panchanama (Mahazar) is critical when there are no direct eyewitnesses to the crime, and the case rests solely on circumstantial evidence. Indian Evidence Act, 1872, section 159 requires the Panch (witness) to refresh his memory before testifying in court.1,6 Case Presentation This is a case study of a prosecution instituted in the Hon'ble court of special Court of economic Offences Bangalore. The Complainant is the state of Karnataka at the instance of Drugs Inspector, Bangalore Circle-3, Drug control Department, Bangalore (India), filed against Accused No1(Proprietor) and Accused No-2 ( Person in charge ) of Caretech Pharmaceuticals, No.63/3, Devegowda Layout, P & T Road, Srigandakaval, Bangalore-91. The complaint alleges that the accused has committed offences under section 18 (a)(i) R/w. Section 17B(e), Section 18(a)(i) and section 18(c) Punishable under section 27(c) , Section 27(d) and Section 27(b)(ii)’ of the D&C Act and Rules.9 The Drugs Inspector, Blood bank and Intelligence wing, Bangalore (CW-2), received credible information that Accused No-1 is manufacturing veterinary drugs for sale at M/s. Caretech Pharmaceuticals is located at No. 63/3, Devegowda Layout, P&T Road, Srigandakaval, Bangalore-91 without the valid licence required under the D & C Act provisions. On 14.08.2007, the Drugs Inspector, BBWI (CW-2), and his colleagues and Panch witnesses raided the premises of M/s. Caretech Pharmaceuticals, Bangalore International Animal Health Journal 13
REGULATORY & MARKETPLACE Forms
Description
Form 17
It is a form prescribed under the Drugs and Cosmetics Act and Rules to be used by a drug Inspector for intimation to a person from whom a sample is taken. Whenever an inspector takes a sample of a drug or cosmetics for evaluation or examination, the details of products taken for testing shall be described in writing under Form 17 and informed to the person from whom it is taken.
Form 17A
It is the receipt for drug samples taken by the Inspector when a fair price of the sample is refused by a person from whom the sample is taken.
Form 25A
It is a Loan license issued for the manufacture for sale of drugs specified other than Schedule C & C1 and X. A Loan licence means a licence which a licensing authority may be issued to an applicant who proposes to avail of the manufacturing facilities owned by a licence in form -25.
Form 25
It is a licence issued for the manufacture for sale of drugs other than those specified in Schedule C & C1 and X.
Form 18
It is a request letter made by a Drug inspector to the Government analyst for analysis of the samples. It is sent as per the procedure. One copy of form-18 is sent with a sample and another copy separately for comparison by Govt Analyst.
Form 13
It is a test report of the sample issued by the Govt Analyst. The form-13 is issued in triplicate to the Drugs Inspector. In turn, the Drugs Inspector issues one copy to the person from whom the sample is drawn, Another to the person whose name is disclosed in reply to notice under section 18A of the D &C Act. The third one is used for prosecution,etc.
Form 16
It is a receipt issued to the person from whom the Drugs Inspector seized the stock of drugs and other incrementing articles. This is a receipt form for confiscated drugs, cosmetics, paperwork, documentation or any other factual thing. It is a receipt for the medication or cosmetic or articles /substance/documents stock seized under section 22(1) clause (c) or Clause (cc) by Drugs Inspector.
Table 2. Forms related to Regulation of drug products as per D&C Act.1,8
91 and found stocked veterinary drugs, namely Myciprol, pack size 100gms, Myciprol pack size 250 gms and Enro-10, 500ml, which are purported to be manufactured by M/s. Caretech Pharmaceuticals and labelled as manufactured by M/s. Caretech Pharmaceuticals, Peenya Industrial Area, Bangalore-58. On enquiry, the person in charge accused No-2, revealed that they do not have a drug manufacturing licence for the raided premises. They also found raw materials namely Ciprofloxacin and Enrofloxacin I.P., packing materials. Out of the stocked drug, the Drugs Inspector BBWI has drawn a legal sample of Enro-10, Myciprol, Ciprofloxacin, Enrofloxacin I.P., B.No. EN0678 and Ciprofloxacin, B. No. Nil by issuing Form 17 and Form 17A. The Drugs Inspector BBWI (CW2) seized the remaining stock of drugs, raw materials and packing material under Form 16 under Panchanama. The Drugs Inspector BBWI further enquired about the person in charge accused 2. During enquiry, accused 2 revealed that sales bills were prepared and issued in the name & address as M/s. Caretech Pharmaceuticals, Nandini Layout, Bangalore-96. They have obtained a loan license on M/s. Karnataka Antibiotics and Pharmaceuticals Limited, situated at No.14, 2nd Phase, Peenya Industrial Area, Bangalore-58 and documents pertaining to sales and loan licenses are in their premises situated at M/s. Caretech Pharmaceuticals, Nandini Layout, Bangalore-96. The Drugs Inspector BBWI has sent legal samples to the Government analyst for test and analysis under Form 18. 14 International Animal Health Journal
Further on enquiry with the person in charge of M/s. Karnataka Antibiotics and Pharmaceuticals Limited, situated at No.14, 2nd Phase, Peenya Industrial Area, Bangalore-58, revealed that M/s. Caretech Pharmaceuticals, Nandini Layout, Bangalore-96 have not given order to manufacture the product Enro10, B.No. 005 and drug Ciprofloxacin Water-soluble Feed Supplement MYCIPROL.They had not manufactured Enro10, B.No.005. The Drugs Inspector received the test report in Form 13 of the sample Ciprofloxcin -Myciprol pack size 100gms, Batch No 1048, D/M:08/2007,D/E 02/2009 declared as not of standard quality. The said drug does not confirm the label claim with respect to the identification test. The Drugs Inspector also received a test report of Ciprofloxacin Myciprol pack size 250gms, B.No 1048, D/M 08/2007. D/E 02/2009 declared as not of standard quality with respect to Assay for Ciprofloxacin, i.e.; it contains only 60.5% of the label claim. The Drugs Inspector sent a copy of Form 13 to the accused 1. On 14.08.2007, the Drugs Inspector, Bangalore Circle 4 (CW14), and other inspectors and panchas visited M/s. Caretech Pharmaceuticals, Nandini Layout, Bangalore-96. Accused-1 was present during the visit and on enquiry, revealed that drugs were manufactured without a valid license. Further, accused-1 produced a copy of the purchase invoice of the raw materials purchased from M/s. Mundra Enterprises, M/s. Harshad Enterprises and also produced sales invoices of certain finished products sold by them M/s. Venkateshwara Agency, M/s. Lotus Enterprises and M/s. Vangili Feeds. The Drugs Inspector, Bangalore Circle 4, seized the documents of raw material purchase invoice and sales invoices by issuing form 16 under panchanama. The Drugs Inspector, Bangalore Circle 4 verified the sale of drugs at M/s. Mundra Enterprises, M/s. Harshad Enterprises, M/s. Venkateshwara Agency, M/s. Lotus Enterprises and M/s. Vangili Feeds and found to be the accused sold the drugs to the said firms. The investigation reveals that drugs were seized from the premises of M/s. Caretech Pharmaceuticals, Bangalore 91 are spurious drugs as they are not the true products manufactured by M/s. Caretech Pharmaceuticals, Peenya, Bangalore 58. The drugs inspector, Bangalore Circle 3, after receiving the documents from the Drugs Inspector (CW2 & CW14 & CW3), verified the case's facts and submitted the report to the Drugs Controller And Controlling authority. The Drugs Inspector obtained the prosecution permission from the controlling authority and instituted the prosecution against the accused no 1 & 2 for the offence punishable U/s 27(c), 27(d) & 27(b) (ii) of the Drugs and Cosmetics Act. The Hon'ble Court took cognisance of the offence. The accused did not plead guilty and asked to conduct a trial. The prosecution has examined 1 to 20 witnesses and marked documents from P1 to P191 and material objects M.O. 1 to M.O 21.8,9 Contention of the accused 1.
2.
That the Complainant Drugs Inspector need to produce his appointment notification published in the official gazette. If not produced, it cannot be considered a public servant, leading to an acquittal of the case. The prosecutor's approval does not reveal all the elements. Expungement permission is invalid. Chapter IV-A requires prosecution permission. The accused submitted a ruling of the Hon'ble High Court of Karnataka in the case of M/s. Tejpal & Company (Karnataka) in Crl. A. No.1569/2004, where it is decided that "in the absence of a prior sanction, there cannot be any prosecution." In the cases like State of Madhya Pradesh vs Anil Soni reported in 2015(1) DC 154 & in case of Adhiyaman & others vs State reported in 2016(1) DC 477) had similar findings is given. In Dr. Om Prakash Singh vs State, reported in 2003 Drugs Cases 293 it is held that prior sanction is required. Volume 9 Issue 2
REGULATORY & MARKETPLACE 3.
4.
5.
6.
That merely on the basis of the confession statement, it cannot be said that the offence alleged against the accused is proved. The Accused submitted supporting ruling rendered by the Hon'ble High Court of Madras in the case of state V/s Anuradha Ramanth reported in LAWS (MAD,)-2002-3-113. The accused further contended that wrong labelling cannot be constituted as a spurious drug its only address mistake. The Gazette notification of the appointment of the Government analyst under section 20 of the D & C Act is not produced by the prosecution. Hence the test reports issued by the Government are not valid. The test reports do not reveal the test method's protocols applied and are incomplete and cannot be accepted. Therefore, the drugs can not be considered as not of standard quality. The independent witnesses have not supported the case. The seized materials does not establish that they are seized from the accused premises. Hence they are not dealing without valid licence. The accused no 1 is the proprietor of the firm,as per section 34 of D & C Act his responsibility in the offence of the company is not established. Similarly, Accused no 2 is an employee of the firm,he is also not aware of the firm's licence details. The accused is manufacturing veterinary medications in their facility, according to labour and commercial tax documents.9
Contention of the Prosecution 1. 2.
3.
4.
5.
The Complainant has submitted the gazette notification for having appointed him as a Drugs Inspector in 2003 & the contention of the accused is not valid. The controlling authority has permitted to institute of the prosecution against the accused in the jurisdictional court after carefully studying the investigating officer's report. The accuser's claim is false. This case does not belong to Ayurveda, Unani, and Siddha medications. This case is not under Chapter IVA of the D & C Act. This case is under chapter IV of the Drugs & Cosmetics Act. Nowhere else in Chapter IV the sanction is required to start a criminal case. According to rule 51 of the Drug and Cosmetics Rules, only permission is required for beginning proceedings under section 32 of the Drug and Cosmetic Act. That sanction is not required for filing the complaint under 18A,18B ,18(c) & 18(i)(a) punishable under 27. The prosecution has proved the offence of the accused with collaborative evidence along with a confession statement. The drug was not manufactured under a loan licence at Karnataka antibiotics and pharmaceutical ltd Bangalore-58. The manufacturer name indicated on the label of the container is not the true manufacturer of the product. Hence sampled and seized drugs fall under the definition of spurious drugs. The accused have manufactured drugs in the unlicensed premises and labelled them as manufactured in the licensed premises amounts to the manufacture of spurious drugs. The Analyst is appointed by the State Government. Only reason that the notification is not produced cannot be held that the analyst is not appointed as a Government analyst. The Analyst Report contains the method of testing adopted by him. Hence the reports are in compliance with rule 46 of Drugs and Cosmetics Rules 1945. The test reports are conclusive evidnce if they are not challenged by the accused. In this case, the reports are not challenged. Hence they are valid. The prosecution elaboratively argued that the drugs manufactured are not of standard quality and spurious drugs. The drugs are manufactured without valid licence and sale of drugs without a licence are also proved beyond doubt.
www.international-animalhealth.com
6.
The section 34 of the D & C Act does not apply to the properties ship firm. The Accused 1 is the sole proprietor of the firm. The Accused 2 is the in charge of the unlicensed manufacturing firm. Hence both are responsible for the offences.
Penalties First Offence: Section 27 of D & C Act covers the punishment clause: Whoever himself or by any person on his behalf manufacture for sale. a) A Not of standard quality or Adulterated or spurious drug when used cause grievous hurt within the meaning of section 320 of IPC shall be punishable with imprisonment for a term of B* ( ten years extended up to life and a fine of Rs 10 lakhs.) b) (i) Adulterated medications or (ii) dealing in drugs without a valid licence shall be punishable with imprisonment for the term which shall C* (not less be less than for three years extended up to five years and fine of Rs 1 lakh.) Provided that the court may, for any adequate and special reasons to be recorded in the judgement, impose a sentence of imprisonment for a term of D* (less than three years and of fine of less than one lakh rupees) c) Any drug deemed to be spurious u/s 17B but not referred under Clause (a) shall be punishable for imprisonment for the term which shall E* (not less than seven years but may extend to life and fine of Rs 3 Laks.) Provided that the court may, for any adequate and special reasons to be recorded in the judgment, impose a sentence of imprisonment for a term of F* (less than seven years but not less than three years and of fine of less than one lakh rupees). d) Any drug other than a drug referred in Clause (a),(b),(c), in violation of any of the provision of the D & C Act or any Rule shall be punishable with imprisonment for a term which shall not be less than one year which extended to two years and G* Fine not less than of Rs 20000/-. Provided that the court may, for any adequate and special reason to be recorded in the judgement impose a sentence of imprisonment for a term of less than one year. Note B* Substituted effective from 10.08.2009 for "Punishable with imprisonment for a term which shall not be less than five years but which may extend to a term of life and with fine which shall not be less than ten thousand rupees. C* Substituted with effect from 10.08.2009 for "not be less than one year but which may extend to three years and with fine which shall not be less than five thousand rupees. D* Substituted with effect from 10.08.2009 for "less than one year and of a fine of less than five thousand rupees". E* substituted with effect from 10.08.2009 for "not be less than three years but which may extend to five years and with fine which shall not be less than five thousand rupees." F* substituted with effect from 10.08.2009 for "less than three years but not less than one year". G* substituted with effect from 10.08.2009 for "and with fine".9 Subsequent Offences: The penalty for subsequent offfence are covered under section 30 of D & C Act. Whoever having been convicted of an offence: a) is again convicted for dealing in Adulterated medications or dealt in medicine without valid licence shall be International Animal Health Journal 15
REGULATORY & MARKETPLACE
punishable for imprisonment for seven years extended upto ten years and fine of Rs 1 lakh b) is again convicted for dealing in spurious drug is punshible for imprisonment punshible for ten years extended upto life and fine of Rs 3 lakhs c) is again convicted for offence punshible under section 27 (d) of D & C Act is punshible for imprisonment for two years, which may be extended to four years, and a fine of Rs 50000/-9 Decision of the Honourable Court 1. 2.
3.
4. 5. 6.
The Prosecution has proved the notification of the appointment of a Drugs Inspector. Hence Drugs Inspector has jurisdiction to inspect and investigate the case The Prosecution permission issued by the controlling authority contains all ingredients of offence and it reveals the controlling authority has appiled his mind, with due deliegince the permission is issued. The prosecution permission is valid. The Drugs Enro-10 500ml, Myciprol pack size 100gms, and 250gms are wrong labelled by original manufacturers M/s Caretech pharmaceuticals. They have mentioned the wrong manufacturing address.. Hence they are not spurious drugs. The Myciprol pack size 100gms, and 250gms are not of standard quality. They are supported by valid test reports. The Complainant has proved that accused -1 manufactured and stocked drugs for sale without possessing a valid licence under the D & C Act . The Complainant has not proved that the accused -2 has taken part in the offence of the firm. He is an employee of the firm. He is not legally bound to know whether the owner of the firm possess the licence or not.
16 International Animal Health Journal
The Hon'ble court ordered that accused-2 is acquitted and accused -1 is convicted for the offences punishable under sections 27(b)(ii), and 27D of Drugs and Cosmetics Act 1940. The Hon'ble Court ruled that the prosecution has not proved the charges punishable under section 27(c) and both the accused was acquitted. The Hon'ble Court convicted the accused-1 under CRPC section 248(2) for the offences punishable under D & C Act 1940 sections 27(b)(ii) and 27D. The accused-1 is sentenced to undergo imprisonment till raising of the court and to pay a fine of Rs. 5,000/- for the offences u/s 27(b)(ii), and the accused-1 is sentenced to undergo imprisonment till raising of the court and to pay a fine of Rs. 5,000/- for the offences u/s 27(d) of the D& C Act 1940. The accused No.1's sentence runs concurrently.8,9 Summary The Hon'ble court considered that Accused -2 is an employee of the firm. He is not legally bound to know whether the firm's owner possesses a valid licence or not. The Hon'ble court considered that wrong labelling would not fall under the definition of spurious drugs. Hence the accused are acquitted for the manufacture and sale of spurious drugs punishable U/s 27(c) of D &C ACT... Further, the court has considered the Govt. Analyst test report has conclusive evidence and convicted for manufacture and sale of not of standard quality drugs. The Hon'ble court also considered the manufacture of drugs in another site than the licensed premises is manufactured without a license. Hence accused No 2 is acquitted and accused -1 is convicted for the offence for the offences punishable under sections 27(b)(ii) and 27D of D & C Act 1940. Volume 9 Issue 2
REGULATORY & MARKETPLACE Conclusion There is no evidence that accused No. 2 (Person in Command) is in control of M/s. Caretech Pharmaceutical's manufacturing section. There is no proof to substantiate Accused No. 2's involvement in the firm's operations and also no indication that accused No. 2 was aware that M/s Caretech Pharmaceutical lacked a licence to manufacture the medications in the premises where they were manufactured. The accused No. 1 (Proprietor) is sentenced to undergo imprisonment till raising of the court and to pay a fine of Rs. 5,000/- for the offences u/s 27(b)(ii), and the accused-1 is sentenced to undergo imprisonment till raising of the court and to pay a fine of Rs. 5,000/- for the offences u/s 27(d) of the D& C Act 1940. The accused No.1's sentence runs concurrently. Samples must be returned to the Complainant once the appeal time has expired or to be disposed of legally. Significance Statement This study described the Laws and Regulations of veterinary drugs in India as per the Indian Drug and Cosmetic Act, focusing on the Regulation of drug products for quality drug products and the legal action by the Indian laws against the infringer. This study will help the regulators and drug manufacturers in ease understanding of the laws and Regulation of drugs and the strictness in action against the infringer like drug manufacturers. Thus, a new study on "Regulating veterinary drugs in India: A case study based on the Drug and Cosmetic Act" has been provided. REFERENCES 1.
2.
3.
Khan AN, Khar R.K.: 2015 January 1, Current Scenario of Spurious and Substandard Medicines in India: A Systematic Review. Indian J Pharm Sci; 77(1):2. Available from: http:// pmc/articles/PMC4355878/ Umesh S, Balamuralidhara V, Raghunandan H V, Swathi K.C., 2021 March 17: Legal aspects of spurious drugs in india. J Dis Glob Heal;14(1):23–36. Available from: https://ikppress.org/ index.php/JODAGH/article/view/6063 Barath B C, Balamuralidhara V, Venkatesh MP, 2019:
4. 5.
6.
7. 8. 9.
Veterinary Medicine: Drug Approval Process in Europe and USA; Available from: https://www.jpsr.pharmainfo.in/ Documents/Volumes/vol11issue07/jpsr11071940.pdf Chokshi M, 2015: Drug Quality and Safety Issues in India. New Delhi; Report No.: 310. Available from: http://icrier.org/pdf/ Working_Paper_310.pdf S. Umesh, V. Balamuralidhara, K. C. Swathi and H. V. Raghunandan, 2021:Spurious Drugs in India: Comparison with Europe and USA, Systematic Review. Journal of Disease and Global Health; 14(1): 37-52 Pai KG, Kumar TCS, Parida DP, Joseph A: 2018 June 1, A review on manufacturing operations of solid dosage forms: Design and implementation on GMP systems in the manufacturing facility. G. Balint, Antala B, Carty C, Mabieme J-MA, Amar IB, Kaplanova A, editors. J Glob Pharma Technol ;10(6):1– 10. Available from: https://manipal.pure.elsevier.com/en/ publications/a-review-on-manufacturing-operations-ofsolid-dosage-forms-design Spandana A, V Balamuralidhara, Devaraju K, 2019: Overview of Veterinary Medicines Regulatory Environment in the Russian Federation. Int Anim Heal J;6(2):16–22. Malik V, 2016: Law Relating to Drugs and Cosmetics. Eastern Book Company. Available from: www.twitter.com/ebcindia Amaresh Tumbagi, V. Balamuralidhara, S. Narmada, Ashutosh Mishra: 2022, Not of Standard Quality Drugs In India: A Case Study; Journal of case reports in medical science:7(3), 11-16.
Amaresh Tumbagi Research Scholar in Pharmaceutical Regulatory Affairs, JSS College of Pharmacy, Mysuru, JSS Academy of Higher Education and Research. Mysuru-57001, Karnataka, India Email: amareshtumbagi@yahoo.co.in
Balamuralidhara. V Associate Professor – Department of Pharmaceutics, JSS College of Pharmacy, Mysuru, JSS Academy of Higher Education and Research. Mysuru-57001, Karnataka, India Email: baligowda@jssuni.edu.in
Ashutosh Mishra Research Student in Pharmaceutical Regulatory Affairs, JSS College of Pharmacy, JSS Academy of Higher Education and Research. Mysuru570015, Karnataka, India Email: lipuashu42@gmail.com
Deeksha K S Research Scholar in Pharmaceutical Regulatory Affairs, JSS College of Pharmacy, JSS Academy of Higher Education and Research. Mysuru570015, Karnataka, India Email: ldeekshaksjss@gmail.com
www.international-animalhealth.com
International Animal Health Journal 17
REGULATORY & MARKETPLACE
Making the Vet Industry more Sustainable Top 5 Tips you can Initiate in your Practice Sustainability has become a buzzword in the twenties. COP26 and extreme weather events have pushed it even further up the agenda for governments, companies and individuals. In its broadest sense it means much more than doing something for the planet and it may be argued that we have gone beyond sustainability to a more seismic requirement to regenerate. Sustainability is also about people and animals but also companies and professions. Some would argue that the veterinary industry itself is not sustainable at the moment due to factors like the shortage of vets due to Brexit; the effect of the pandemic on professionals’ mental health; the explosion in pet numbers due to lockdown and the attendant pressure on already poorly staffed practices. This is an incredibly complex issue that needs to be approached in a holistic manner. However, the purpose of this article is to look at how the veterinary industry can become more eco-friendly in the choices that many businesses make corporately and individually. It will also point out some of the amazing initiatives already taking place. As mentioned previously, the topic of how to be more environmentally aware is becoming more popular and is linked also with mental health. Multiple studies have shown that spending time in a nature-enriched environment is good for mental well-being. At the recent Webinar Vet Virtual Congress Dr. Catriona Mellor introduced the concept of solastalgia. Solastalgia is defined as an existential dread for the future of the planet and often afflicts the young. It leaves people thinking that it is not worth making any effort to save the planet. However, if we begin to take actions to improve our environment this will help us to become more optimistic about the future of our planet. Small actions multiplied many times over by businesses and individuals can have a massive impact. All of this will improve mental well-being as well as the well-being of the planet. Craig Bennett, the CEO of the Wildlife Trusts, explained the importance of the veterinary industry in being leaders to other industries and members of the public in a recent podcast (VetChat). What vets do in their practices matter! They are highly trusted members of their local communities. People in the community look at what happens at the vets. If the vet has solar panels on the roof; a wildflower garden as you enter the practice and educates people about wildlife, then those people in the community may follow suit. Therefore, there can be a massive additional effect if the industry becomes more involved in this area. Climate change At the recent Webinar Vet virtual Congress, an afternoon was set aside to discuss environmental issues at The Sustainability Summit. Over 300 people attended the live event demonstrating that the industry is already embracing the concept of sustainability and regeneration of the environment. 3 main areas need to be examined as an industry 1. 2. 3.
Climate change Resource use Biodiversity
18 International Animal Health Journal
At COP26, Alok Sharma, the president of the Congress, summed up by saying that he and the official delegates can now say with credibility that we have kept 1.5 degrees alive but its pulse is weak and it will only survive if we keep our promises and translate commitments into rapid actions. The UK held the presidency at last year’s event in Glasgow which happens annually. The Paris Agreement set an upper limit of 1.5 degrees centigrade above pre-industrial levels to prevent severe climate change leading to sea level rises, droughts and wildfires which will lead to further positive feedback accelerating the deteriorating situation. Temperature increases are correlated with the amount of greenhouse gases released into the atmosphere. Carbon dioxide is the main greenhouse gas but there are other much more potent substances like anaesthetics and refrigerants as well. Carbon dioxide is released by burning fossil fuel; cutting or burning tracts of forests; extracting peat for garden use or ploughing fields. Resource use Running a business uses resources. These are often reused or need to be disposed of. One of the mantras of the environmental movement is reduce, reuse, recycle and this is an important mantra to remember in practice. Can less material be used to bandage your dog’s leg without reducing the effectiveness of the bandage? Do drapes, gowns and hats need to be used only once or can material be chosen that can be used several times after appropriate sterilization? How much can plastic usage be reduced by a practice and are there suitable services for increasing plastic recycling? These are all questions that a modern veterinary practice must begin to ask. Biodiversity COP26’s prime aim was to reduce carbon usage but COP15 is happening in China this year and will be focusing on biodiversity. Our environmental crisis is made up of several elements: climate change due to increasing carbon in the atmosphere; seas polluted by plastics and a loss of species across the world due to loss of habitat: use of chemicals or hunting. These three topics must be dealt with together. Planting non-native pine trees will help eventually with carbon capture but will likely be sterile places for native birds and insects. As a young boy I used to wake up to the sound of house sparrows chirping in the elm trees on my road in inner-city Liverpool. The trees were later removed due to disease and the sparrows gradually disappeared. 50 years later there are 50 million fewer sparrows in the UK. Sparrows require a mixed diet including insects. Potent insecticides used in gardens and farms have reduced populations of insects some of which may be deemed pests, but often beneficial insects are killed by these indiscriminate molecules. The EU has banned 74 pesticides because of health or environmental concerns; however, these substances can sometimes be found in food imported into the UK from other countries. Where the substances have not been banned. Indeed, some of these substances are manufactured in the UK and the EU before being exported abroad. It is essential that countries work together to ensure that biodiversity is increased. Dangerous chemicals should be banned globally; birds that migrate between different countries need protection at both of their home bases and over the areas in which they travel. International agreements are very important, and the UN leads the way in bringing countries to the table and debating them at COP conferences. At COP26, 197 countries signed an accord Volume 9 Issue 2
REGULATORY & MARKETPLACE committing to a phasing-down rather than a phasing-out of fossil fuels. Whilst this was not the best solution, gaining consensus from 197 countries was a huge feat of diplomacy. COP15 is taking place on May 20–22 in Abidjan in the Ivory Coast looking at how to stop desertification. The UN estimates that over 40% of land is degraded worldwide. An area of forest the size of Italy was cut down in 2016 and about 20% of the world’s greenhouse gas emissions come from the clearing of tropical forests. Later on in 2022, COP15 will continue in Kunming, China. One of the key parts of the deal being negotiated known as the post–2020 biodiversity framework is a goal to make 30% of land and seas into protected areas by 2030. To put this into context the UK is the most nature-depleted nation in the G7. Over the past decade, the UK has failed to meet most of its international targets to prevent declines in the state of nature. This is often because targets are not joined up across government departments to address biodiversity loss. Much of the UK’s protected land like national parks was set up for people’s enjoyment, not for the benefit of nature and are often deserts of grass with little biodiversity. There are 3 constituents involved in improving our natural world governments businesses and individuals. Whilst governments have done some good work, for example, encouraging uptake of electric cars through tax breaks, they often move slowly and don’t keep to their promises. The role of individuals and large and small businesses to help make our planet a better place to live cannot be overstated. Anders Holch Povlsen has used personal wealth to purchase 221,000 acres for the purpose of rewilding this makes him the largest landowner in Scotland. Recently, it was reported that Vets4pets partnered with the Woodland Trust to protect 20,000 hectares of woodland. How can a practice owner make their practice more sustainable? Here are 5 tips: One The crisis in the Ukraine has encouraged European countries to be less dependent on Russian oil and gas but prices for fuel have skyrocketed. Whilst this will undoubtedly cause hardship over the next few years, it should be a catalyst to reduce our dependence on fossil fuels for heating our houses, clinics and for our cars. Every practice needs to become more energy conscious. It is worth fitting a smart meter in the business and purchase the most energy-efficient equipment like computers, ultrasounds etc. Low energy lighting with motion sensors fitted will massively reduce energy use and save money. Insulating buildings more effectively and considering the most energy efficient boiler or fitting an air-source heat pump, whilst expensive, will reduce energy usage further. Installing solar panels will produce local energy which can be stored in batteries or exported back into the grid. They can also charge electric vehicles for practice visits. Range between charges and availability of public chargers can be a problem but is improving year-on-year. Using a sustainable energy supplier like Good Energy or Ecotricity which can provide carbon neutral electricity is a very quick win on any practice’s journey to carbon-neutral status. Changing suppliers may be difficult during this time of crisis and will be impossible if the practice is in a contract. Two Carbon dioxide is not the only greenhouse gas. The substances used to anaesthetise animals like nitrous oxide, isoflurane and sevoflurane are potent greenhouse gases too. Jones and West at Davies Vet Specialists has done fabulous work on reminding the profession of their potency and suggesting ways that these gases can be reduced by safely reducing flow rates during www.international-animalhealth.com
surgery and curtailing the most potent substance nitrous oxide in clinical use. Similarly, the gases used in fridges and freezers and air conditioners such as HFC-134a has a global warming potential 3,400 times that of carbon dioxide. They are being phased out; however, older units may contain them so careful recycling is important. Three The concept of reducing, reuse, recycle is well embedded in environmentally aware people. The concept of consuming less has been well covered in Jen Gale’s book Sustainable. Jen did not buy anything new apart from food for a full year and relied on reusing already owned articles. The problem with recycling is that it sometimes is sent abroad and dumped and contaminated matter cannot be recycled. Care is needed. However, with all environmental audits a thorough approach to recycling is very important. Of course, in the clinical setting much can be done to reduce consumption through careful rotation of stock; not ordering too much and recycling hard to recycle waste like PPE in zero waste boxes as a pilot study of vetPartners proved and also in the longer run committing to a zero to landfill policy as IVCEvidensia have done have by 2025. Four Plant some wildflowers in your outside areas. Not only will they improve the mental health of the team but a recent study in the Journal of Insect Conservation reported that a 2 meter by 2-meter plot of wildflowers resulted in 111 percent more bumblebees, 87 percent more solitary bees and 85% more solitary wasps than in unmodified gardens. The veterinary team can also encourage farmers to farm in a more environmentally friendly way through the new Defra agricultural stewardship schemes. Five Join an accreditation scheme and commit to a timespan for getting the accreditation. The body will hold you accountable and will ensure that you are running a sustainable business. More and more people are understanding the importance of sustainability in all businesses and businesses will be perceived in a bad light by suppliers, customers and staff if they are not beginning on the journey of sustainability. The beginning is always the most difficult but small steps made consistently by many practices will make a big difference. REFERENCES 1. 2.
https://www.thewebinarvet.com/pages/vetchat-podcasts/ Jones, R.S. and West, E. Environmental sustainability in veterinary anesthesia and analgesia.
Anthony Chadwick Anthony Chadwick, BVSc, CertVD, MRCVS qualified from Liverpool University in 1990 he 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. 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.
International Animal Health Journal 19
RESEARCH AND DEVELOPMENT
Start with the End in Mind – Formulation, Drug Delivery Technology, and Manufacturing Introduction This is the second article in the "From Molecule to Market" series, where we address the different phases in the animal health product development journey. In this article, we share our insights on developing new Veterinary Medicinal Products. From selecting the drug delivery technology and developing the formulation to scale-up, validation and manufacture of your drug product. Start with the End in Mind – Defining the Target Product Profile In drug development, it is important to create a Target Product Profile (TPP). A TPP sets out the indication, route of administration, dosage form, dose, and includes ideas on the target market and commercial opportunity. A key challenge in developing a robust TPP is defining how the pharmaceutical compound gets delivered to its target site in the animal to achieve the desired therapeutic effect. Working in partnership with pharmaceutical scientists and evaluating all of the known data on the Active Pharmaceutical Ingredient (API) is at the core of this. Once the basic information is collected, decisions need to be made on the route of administration. E.g., if the class of the molecule indicates that it is poorly soluble and poorly permeable i.e., Bio Classification System (BCS) Class IV (see Figure 1), it is likely to be poorly orally bioavailable and poorly absorbed over intestinal mucosa. Such an API often presents significant challenges to the product developer and requires a range of drug delivery strategies to achieve therapeutic levels in vivo. The pharmaceutical industry has multiple drug delivery technologies to select from and many companies have proprietary technologies available that can help you overcome these challenges. Many of these technologies are available for license or some may require purchase of a specific ingredient such as a BioAvailability enhancer from an excipient supplier.
Figure 1 Biopharmaceutical Classification System 20 International Animal Health Journal
Whilst the choice of drug delivery technology is largely driven by the physicochemical characteristics of the molecule such as its BCS Class, it is also heavily influenced by commercial considerations: • • • • •
What are the existing commercial opportunities? What will the market look like in 5-7 years (most likely the timeframe it will take to develop your product)? What will the Cost of Goods be for your product? What distribution channels will be required e.g., Rx-Vet only, OTC or online only? What will be the expected retail price and margins?
Product Development With a detailed TPP and Drug Delivery Technology identified, developing the formulations is the next step in the journey. This part of the process is led by Pharmaceutical Sciences, which includes four interlinked disciplines: 1. 2. 3. 4.
Formulation development Analytical development Packaging development Process development
Formulation Development With your preferred route of administration mapped out you can begin to develop your formulations. First step is to determine Excipient compatibility with your API and in parallel start the development of a “Fit-forPurpose” assay method for your API in your formulation. This is a series of accelerated stability studies looking at binary or sometimes tertiary mixtures of your API and the chosen excipients. The aim being to see if there are any physical changes (appearance/colour) along with a loss of potency. These studies usually result in the preparation of a heatmap such as the one shown in Figure 2.
Figure 2 Example of an Excipient Compatibility Heatmap Volume 9 Issue 2
RESEARCH AND DEVELOPMENT
Figure 3. The partnership of Pharmaceutical Sciences, Regulatory Affairs and Clinical Sciences in product development
Once the team have some ideas of what may be compatible with your API, it’s time to put some trial formulations together. The aim of the formulation scientist is to develop robust formulations, that meet the requirements of the TPP, can be consistently processed at an acceptable cost of goods, and deliver the correct quantity of drug to the therapeutic target in the animal to be treated. In addition, the pharmaceutical scientist in Animal Health must also take into account species specific issues, the subtle effects of breed and if the product is taken orally, to develop a highly palatable formulation. Once the formulator has some trial formulations, they will need to manufacture small scale batches for stability testing, for initial process development, packaging compatibility and some initial analytical development activities. Analytical Development Analytical Development often begins by adapting methods that may be available from the literature or from Pharmacopeial methods for APIs or from existing products that can be adapted for your own product. With New Chemical Entities, the method developer has to work from first principles using a detailed knowledge of the molecule. These initial methods are further refined, optimised and ultimately validated. The analytical scientist supports the formulators efforts providing methods for potency and degradants, that allows the formulator to check excipient compatibility and to perform early potency checks on formulations. The analyst also helps build an understanding of how the product will behave when faced with standard degradative conditions of acid, base, oxidation, reduction, heat and light. These studies present significant challenges to the chemist who must find ways of teasing out complex pathways of degradation of both actives, excipients and degradants of degradants! Once these pathways have been elucidated and the degradants identified and quantified, the chemist must then validate the stability indicating nature of the methods. This provides a range of tools that will prove to regulators that the product is robust, stable and has an acceptable shelf-life. Process Development, Scale-Up and Packaging Development Often the Process and Packaging engineer work handin-hand, with the Process Engineer developing bench-top www.international-animalhealth.com
scale manufacturing processes, taking the gram scale formulations developed by the formulators, through a series of increasing scale-ups to at least 1/10th or higher of the proposed commercial scale, whilst the Packaging Engineer’s role is to work with the formulation team to develop a container-closure system that protects the product from the environment, provides an easy to access pack for the end user, but also one that is cost effective and complies with Child Resistance/Senior Friendly regulations. All Pharmaceutical Sciences disciplines partner from an early stage with Clinical Services and Regulatory Affairs to ensure that the product development and regulatory strategies are clear, and the clinical studies required for successful progression to registration and approval are designed, budgeted, and planned. The partnership is visualised in Figure 3. Final Product Development Stages The final stages of pharmaceutical product development are the most costly. They typically require manufacturing of clinical and VICH (Veterinary International Conference on Harmonization) batches at more than 10% of the proposed commercial batch size. These batches are used to generate the pivotal clinical safety and efficacy data, and the pivotal shelf- life supporting data that will be submitted to regulatory agencies such as the FDA Centre for Veterinary Medicine (CVM), the Veterinary Medicines Inspectorate (VMD) in the UK or the European Medicines Agency (EMA). At the end of this phase the Chemistry Manufacturing and Controls (CMC) package will be created, which includes development pharmaceutics, validated analytical method information, the proposed shelf-life, and the manufacturing process. This package – combined with the clinical data generated on the product – forms the Technical Sections of the Common Technical Document (CTD), which is needed to seek approval for your product. We will elaborate more on that in the upcoming articles. Technology Transfer (TT) It is desirable that the pivotal clinical and VICH stability batches are made at the commercial manufacturing site, on equipment that is representative of the commercial process. The aim of TT is to transfer the knowledge gained during development of the product to the manufacturing and quality teams that will produce, test and release the product for International Animal Health Journal 21
RESEARCH AND DEVELOPMENT
Figure 4
years to come. Argenta has implemented a “Pull-Model” across its global footprint as shown in Figure 4 below. In this model the manufacturing sites actively pull the product from R&D, partnering early in the development process to fully understand the product, enabling later stages of development to smoothly transition into manufacturing. Manufacturing The manufacturing site must be ready to accept the transfer of the product from R&D (the so-called “donor site”) into operations (the “receiving site”) to timelines dictated by the business and its launch timetables. The operations team will lead the process validation activities and manages further changes to the validated process through a rigorous change control process.
Conclusion This paper has provided an overview of some of the key areas to consider when pursuing the development, registration, technology transfer and manufacture of a veterinary medicinal product. Starting with the end in mind means having a robust Target Product Profile with a sound regulatory and project progression strategy. These will provide solid foundations for the development of the product and provide the operations teams with a product that has been well characterised so that it can be consistently manufactured to the highest quality standards. Partnering with experts at each step of the journey – and ensuring seamless transitions between the phases – increases the chance of a successful commercialisation.
Darrell Morgan 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 startup 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!
22 International Animal Health Journal
Volume 9 Issue 2
Listen to our podcast
Available on
Apple Podcasts,
Google Podcasts, and Spotify
MEET THE MASTERS OF MEDICAL WRITING
Dr. Lisa Chamberlain James, Senior Partner Master Skills — Laser focus, unwavering tenacity, infectious charm
We’re taking aim at inefficient medical writing. Rescuing clients from inefficiencies takes precise writing and a proven process. Our writers are experts at engaging reviewers through crystallized messages, all while guiding and managing complex teams. With so much at stake, doesn’t it make sense to hire the very best?
Visit us at TrilogyWriting.com writers@TrilogyWriting.com www.TrilogyWriting.com/TriloTalk www.international-animalhealth.com
International Animal Health Journal 23
RESEARCH AND DEVELOPMENT
A Meta-Analysis of the Relationship Between Lung Lesion Scores in Slaughter Pigs and their Daily Weight Gain
Abstract A meta-analysis was performed on available published articles in which Ceva Lung Program (CLP) method of assessing enzootic pneumonia (EP)-like lesions was utilised and which contained also the record of average daily gain (ADG) data. Eight studies fulfilling the inclusion criteria were analysed using non-parametric tests. All of them were field trials comparing the efficacy of Mycoplasma hyopneumoniae vaccines. The results of the analysis showed that in terms of EP scores in different treatment groups the median difference between pairs of values was 0.365 units (P<0.001). For ADG the median difference was 39.0 g/day (P<0.001). Each point in the EP reduction thus corresponds to 106.8 g of ADG increase. All estimations were significant with P<0.001, demonstrating the dependency of the ADG on EP values both for individual subsets calculated separately as well as for all data put together. The relationship between EP-like lesion scores and the growth performance was confirmed, indicating the relevance of lung check providing a predictive value for the growth of pigs. Enzootic pneumonia, lung scoring, growth performance, meta-analysis Mycoplasma hyopneumoniae (M. hyopneumoniae) is the primary pathogen of enzootic pneumonia (EP), a chronic respiratory disease in pigs, and one of the primary agents involved in the porcine respiratory disease complex (PRDC) (Maes et al. 2017). EP is characterised by a chronic, nonproductive cough, decreased growth rate and feed conversion ratio (Sibila et al. 2009), typically with no or low mortality. PRDC develops as a consequence of coinfections of both bacterial and viral pathogens, especially porcine reproductive and respiratory syndrome virus (PRRSV), swine influenza virus (SIV) and porcine circovirus type 2 (PCV2) (Sibila et al. 2009). PRDC can result in an increased mortality and severe performance losses. The major threat for the farm economy is represented by the decrease in the daily weight gain and eventual increased medication cost. Infection with M. hyopneumoniae often appears to have a subclinical course, where only the growth performance is reduced. It is difficult to assess the economic effect of mycoplasmal pneumonia due to the multifactorial origin of PRDC. It has been reported that enzootic pneumonia can result in a 17% decrease in daily weight gain and a 14% decrease in feed efficiency in affected herds (Straw 1989). When healthy pigs free from M. hyo were mixed into M. hyo positive herds and were thus exposed to the natural infection, their performance was lower. The ADG of pigs with a noncomplicated mycoplasmal pneumonia compared with those which remained free from M. hyopneumoniae was decreased by more than 60 g per day after adjusting for herd, pen, weight and sex (Rautiainen et al. 2000). The presence of the infection is usually confirmed by M. hyopneumoniae specific seroconversion or by the detection of germs by PCR in the laryngeal swabs (Sibila et al. 2009; Pieters et al. 2017). Lung tissue infected with 24 International Animal Health Journal
M. hyopneumoniae develops consolidation and catarrhal broncho-pneumonia with purple to grey regions of meaty aspect. The consolidation can be observed from 3–12 weeks post infection. The lesions are mainly localised in the apical and cardiac lobes, as well as in the anterior part of the diaphragmatic lobes and in the accessory lobe. Lesions resolve after 12 to 14 weeks with formation of interlobular fissures (Maes et al. 2008). Considering the chronic type of such lesions, bronchopneumonia with the cranioventral consolidation of lungs is very indicative for EP also in slaughter pigs. Several methods of identifying and scoring those lung lesions were developed and are implemented to monitor the presence and severity of EP in swine herds (Madec and Kobisch 1982; Straw et al. 1986). The aim of this study was to evaluate the original (previously published) data together with data from two other studies being comparable since utilising the same lung scoring method. Those data from multiple studies were analysed for the first time using a new statistical method quantifying the linear relation between lung score results and growth performance, not only the differences between particular treatment groups. The relationship between quantified lung lesions and weight gain will demonstrate whether lung inspection of slaughter pigs can indicate potential losses in weight gain of commercial pigs to the farmer. This may be an important information for justifying the efforts in scoring lung lesions, not only for their diagnostic value but also as an indication of the economic impact of EP in swine herds. Materials and Methods We have analysed data describing the impact of vaccines against M. hyopneumoniae on respiratory health especially the presence of EP-like lesions in slaughter pigs. For sake of comparability, only articles using the Ceva Lung Program (CLP) scoring methodology (Krejci et al. 2013; Cvjetković et al. 2018) were considered. The bulk of data originate from our previously published work, however papers of other authors using the same methodology were added to cover all available articles on that topic published at conferences and scientific journals. CLP consists of the modified (Madec et al. 1982) method for scoring enzootic pneumonia-like lesions. Cranio-ventral consolidation of lungs is scored from 1–4 for each pulmonary lobe with a maximum possible score of 28 per lung. In this system, enzootic pneumonia index (EP index) is calculated as the sum of all scores per batch of pigs examined divided by the number of lungs scored (Merialdi et al. 2012). From the studies using CLP, we focused on the ones in which performance data were also investigated and presented. Finally, we selected published results of comparative trials in which groups of pigs were treated differently and both lung scoring data and growth performance were known, allowing us to compare the differences in achieved average daily weight gain (ADG) in growing-fattening period, corresponding to the differences in their respiratory health. Inclusion criteria for the publications: • •
Results of comparative field trials (not experimental challenge trials) The use of CLP for scoring lung lesions in slaughter pigs in those trials Volume 9 Issue 2
RESEARCH AND DEVELOPMENT •
Growth performance data available for both treatment groups
Eight publications met these criteria, varying in the sample size and degree of data aggregation. The dataset of each study consisted of two subsets of individuals, namely Group 1 (treatment groups vaccinated with Hyogen®, Ceva, Libourne, France) and Group 2 (treatment groups vaccinated with different vaccines in different studies or unvaccinated ones). Each of these sets was characterised by pairs of the Enzootic Pneumonia index (denoted EP) and the corresponding (dependent) average daily weight gain (denoted ADG). Numbers of individual pigs or groups of pigs in each study and character of the data (primary/aggregated) are listed in Table 1:
values of ADG were selected/repeated. In case the original number of individuals was higher than n (ie. large enough studies with primary data available), random selection of n values of EP and ADG were selected; in case that less than n values were available (ie. small studies with primary data or studies with aggregated data only) random repetition of samples was conducted to generate n new values of EP and ADG. If the original data were recorded in paired design (mutually corresponding values of EP and ADG in publications Cvjetković et al. 2018; Espigares et al. 2018; Guadagnini et al. 2018b and Krejci et al. 2017b), these pairs of data were preserved in the selection. The process of random selection/ repetition introduces a random error which is reduced by repeating the whole process N times. Also, such selection/ repetition may decrease the total variance of the dataset. This implies a deployment of robust non-parametric methods
Group 1
Publication
Group 2
EP
ADG
EP
ADG
n=32
n=3
n=32
n=3
aggregated
aggregated
aggregated
aggregated
Cvjetković et al. 2018
n=280 primary
n=280 primary
n=271 primary
n=271 primary
Espigares et al. 2018
n=14 aggregated
n=14 aggregated
n=13 aggregated
n=13 aggregated
Guadagnini et al. 2018a
n=2 aggregated
n=4 aggregated
n=2 aggregated
n=3 aggregated
Guadagnini et al. 2018b
n=9 aggregated
n=9 aggregated
n=3 aggregated
n=3 aggregated
Krejci et al. 2013
n=38 primary
n=1 aggregated
n=103 primary
n=1 aggregated
Krejci et al. 2017a
n=6 aggregated
n=6 aggregated
n=6 aggregated
n=1 aggregated
Krejci et al. 2017b
n=108 primary
n=108 primary
n=103 primary
n=103 primary
Costa et al. 2019
EP = enzootic pneumonia index, ADG = average daily gain Table 1: Numbers of individuals and character of data in eligible publications
In Table 1 “primary” data consist of one value of EP or ADG for each individual whereas aggregated data characterise a whole group of individuals (cluster) by one value, as a result of selected aggregation function (mean, median). In case of aggregated data there was no information on variance within the cluster. Data Treatment Considering all eight publications as having the same relevance, a simulation was performed to align numbers of individuals in all eight studies to the same number n. This simulation prevents larger studies from overweighting the smaller ones. In total n values of EP and corresponding n www.international-animalhealth.com
for consequent statistical analysis which does not improve significance by repeating the same value multiple times. The non-parametric Mann-Whitney-Wilcoxon (Mann and Whitney 1947) U test was used for testing both the differences between the set of EP and ADG in the Group 1 and Group 2 subsets with 95% level of confidence. The Theil-Sen linear estimator (Theil et al. 1950; Sen et al. 1968) was used to quantify the (linear) relation between the EP and ADG in Group 1 and Group 2 with the same level of 95% confidence. In order to obtain robust results with a 95% confidence interval for the trend, the values of n and N were set to n = 100 International Animal Health Journal 25
RESEARCH AND DEVELOPMENT values and N = 200 repetitions. This provided a set of 200 results from which the P-value of Mann-Whitney-Wilcoxon test was taken as 95th percentile from the 200 P-values and the trend estimates were characterised as median trend with 95% confidence interval. Results Results of the statistical treatment of the dataset are divided into three groups according to the three hypotheses tested; 1. difference in EP values between the Group 1 and Group 2 subsets, 2. difference in ADG values between the Group 1 and Group 2 subsets, 3. linear relationship between EP and ADG. Hypothesis # 1: EP Group 1 vs. Group 2 The total number of N = 200 generated datasets were used for comparison of EP values in Group 1 and Group 2 subsets of individuals. The median value of EP in the Group 1 subset was 0.560 units and the median value in the Group 2 subset was 1.260 units. Median difference between pairs of values was 0.365 units (higher for Group 1). The difference was statistically significant with the 95th percentile of the P-value less than 0.001. This demonstrates the positive effect of Hyogen® vaccination on the EP index. Hypothesis # 2: ADG Group 1 vs. Group 2 The same method of comparison of the whole set of N = 200 samples was applied for ADG in Group 1 and Group 2 subsets. The median value in Group 1 subset was 794.0g/day and in the Group 2 subset 707.0g/day. Median difference was 39.0g/day in favour of the Group 1 subset. The difference between both subsets was again statistically significant with 95th percentile of the P-value less than 0.001. The positive effect of Hyogen® vaccination on daily gain of weight was also demonstrable. Hypothesis # 3: Linear relation between the EP index and ADG For each of the N = 200 datasets a median daily loss of weight for one unit of EP was computed. All estimations of the Theil-Sen linear regression were significant with p<0.001. The median trend in Group 1 was equal to 869.4g/day–86.0g/ day/EP unit × EP unit. In Group 2 the dependency had a form of 827.2g/day–30.0g/day/EP unit × EP unit. The 95% slope confidence interval were 77.2g/day/EP–99.7g/day/EP unit in the Group 1 subset and 23.9g/day/EP–37.1g/day/EP in the Group 2 subset. In case both subsets were treated together, the overall median dependency was 859.6g/day –42.7g/ day/EP × EP unit. Results of the Theil-Sen estimator based linear dependency are depicted in Figure 1:
Figure 1: Median linear dependency between EP and ADG based on the set of N = 200 simulations. 26 International Animal Health Journal
The blue points represent pairs of values of EP and ADG for the Group 1 subset of individuals, and the red points represent the Group 2 subset of individuals. The straight lines of corresponding colours show median Theil-Sen regressions in both subsets and the black line shows the overall dependency of all data put together. Discussion In our study we analysed data achieved in field trials in which the scoring of cranioventral consolidation of lungs was used as a major indicator of M. hyopneumoniae vaccine efficiency. Enzootic pneumonia is characterised by chronic lesions in lung parenchyma which can be easily recognised also in slaughter pigs. M. hyopneumoniae-like gross lung lesions consist of purple to grey areas of pulmonary consolidation, mainly located bilaterally in the apical, cardiac, accessory and the cranial parts of the diaphragmatic lobes (Maes et al. 2008) often described as cranioventral pulmonary consolidation (CVPC) (Garcia-Morante et al. 2016). Quantitative assessment of cranioventral consolidation lesions is recommended as a parameter to measure vaccine efficacy by European Pharmacopoeia (Ph. Eur. 2448). At the slaughterhouse, evaluation of lung lesions is commonly used to estimate the prevalence and severity of respiratory diseases and their impact on carcass market price, risk factor assessment and vaccine efficacy (Sibila et al. 2009; Merialdi et al. 2012). Even fast scoring on the slaughter line provides relevant information about the presence and extension of those lesions. High correlation was found between the fast and slow-detailed inspection of lungs and it was concluded that Enzootic pneumonia has distinct visual lesions that are easily identified and therefore estimating the extent of the lesion can be done quickly (Hurnik et al. 1993). Several scoring methods for EP-like lesions were described (Madec and Kobisch 1982; Straw et al. 1986; Christensen et al. 1999; Holt et al. 2011). In the studies included in this analysis, the CLP was utilised for scoring lungs and processing the data. CLP scoring system is based on modified Madec methodology and utilises a specific software to register, store and calculate the results (Cvjetković et al. 2018). The CLP was implemented as a routine tool to assess EP-like lesions in multiple field trials in which vaccine efficacy was measured (Lisgara et al. 2018; Palares et al. 2018) and large-scale country or continental surveys (Espigares et al. 2017; Krejci et al. 2018). We have analysed all reported studies which included both CLP results and growth performance data. The fact that EP affects the growth rate was described extensively (Straw et al. 1989; Maes et al. 1996). The link between lung lesion scores and corresponding impact on growth performance was described. Market hogs had a mean decrease in final weight of 1.8 kg for each 10% of lung lesion involvement (Morris et al. 1995). In addition, it has been measured that for every 10% of the lung with pneumonia, the mean daily gain is reduced by 37 grams (Thacker 2002) with the estimation of the cost per pig for mycoplasmal pneumonia equal to $4.08. The correlation between the lung scores and corresponding impact on the growth performance was estimated previously (Straw et al. 1989). However, methodologies were different and sometimes the results were not conclusive (Paisley et al. 1993). We were interested to determine whether the improvements in lung lesion scores recorded in several described comparative studies correlated with the decrease in weight gains and, if so, how much. In our analysis a strong negative correlation was found between the decreased EP indexes and higher average weight gains. The efficacy of different vaccination strategies has been compared in field trials and experimental challenge models with different commercial vaccines. Vaccination of pigs against M. hyopneumoniae proved to be efficient in reducing lung lesions observed in the abattoir (Sibila Volume 9 Issue 2
RESEARCH AND DEVELOPMENT et al. 2007). Moreover, the economic benefit of vaccination against M. hyopneumoniae due to higher growth rate was demonstrated and reviewed (Maes et al. 2003; Dinslage et al. 2008; Maes et al. 2008). Although the positive effect of Hyogen® vaccination on the prevalence and extension of lung lesions (EP index), as well as on the daily weight gain of commercial pigs, is indisputable when using the whole dataset, the analysis of the relationship between the two variables requires a more comprehensive interpretation. If only the available primary data from the Cvjetković et al. 2018 and Krejci et al. 2017b studies were used, without the other publications with aggregated values and without the selection/repetition of values, the dependency is still statistically significant. However, due to the Cvjetković et al. 2018 study, which significantly outweighs the Krejci et al. 2017b study in primary numbers, the dependence is relatively low (approx. 5.4g/day/EP in both Group 1 and Group 2 subsets). Although a comparison of these primary values demonstrates differences in the EP index, the difference in ADG does not show a statistically significant result (p = 0.213). This is also mainly due to the very small difference between the median of the Group 1 and Group 2 subsets in the Cvjetković et al. 2018 study, which is the largest study in terms of the number of individuals. In case of the alignment of the individuals’ numbers of all eight studies (ie. the use of simulated datasets with n = 100 for each study) and repeating the analysis N = 200 times, the dependences between EP and ADG are also statistically significant with significantly higher effect on increment per unit of EP index. In case of the Group 1 subset, it is 86g/day/ EP unit, whereas in the case of the Group 2 sample it is only 30g/day/EP unit. An additional value of 43g/day/EP unit can be obtained if all values (n = 1,600) are processed together, regardless of inclusion in the Group 2 or Group 1 sample. In conclusion, all three established hypotheses can be confirmed. As for quantitative results, we recommend to follow the simulation study results, which represents the distribution of values in different farms better than unaligned analysis of primary/aggregated data. Conclusion The results of this meta-analysis bring a confirmation that scoring of lungs in slaughter pigs for typical EP-like lesions provides the quantitative informational value not only concerning the presence and intensity of enzootic pneumonia in the swine herd. It also indicates the losses in weight gain of the pig populations investigated. Following the evolution of the EP index, it can serve as a monitoring tool predicting the improvements or degradation of growth performance. In 8 published field trials using the same scoring methodology and measuring the weight gain, Hyogen® vaccination resulted in a reduction of the EP index by 0.365 units and an increase in ADG by 39.0g. The present results thus demonstrated that the change of each EP-index point corresponds to 106.8g of ADG. REFERENCES 1.
2.
Christensen, G.; Sørensen, V.; Mousing, J.; Straw, B. E. (Ed.); D’Allaire, S. (Ed.); Mengeling, W. L. (Ed.); & Taylor, D. J. (Ed.) Diseases of the respiratory system. Diseases of Swine. 1999, 8 ed., pp. 913-940. Costa, W.; Calveyra, J.; Lunardi L.; Souza, M.; Barbosa, T.; Santana, D.; Krejci, R. A field trial comparing the efficacy of two vaccines against PCV2 and Mycoplasma hyopneumoniae in terms of viremia, lung lesions and growth performance.
www.international-animalhealth.com
Proc ESPHM, 2019, IMM-PP-16 Cvjetković, V.; Sipos, S.; Szabó, I. Clinical efficacy of two vaccination strategies against Mycoplasma hyopneumoniae in a pig herd suffering from respiratory disease. Porc Health Manag 2018, 4, 19. 4. Dinslage, T.; Buwden, J.; and Karriker, L. An application of evidence based medicine: The impact of Mycoplasma hyopneumoniae vaccine on average daily gain in swine. Proc. AASV Congress San Diego, 2008, p 49-54 5. Espigares, D.; Del Carmen, P.; Carmona, M.: Survey of pulmonary lesions and pleuritis in slaughtered pigs in Spain. Proc. ESPHM, 2017, BBD-010, 185 6. Espigares, D.; Del Carmen, P.; Lasierra, M.; Cárceles, S.; Carmona, M. Comparison of the impact of three oneshot vaccines against mycoplasma hyopneumoniae on productive parameters in a field trial. Proc. ESPHM, 2018, BBD-017, 193. 7. European Pharmacopoeia Monograph 07/2009:2448 8. Garcia-Morante, B.; Segalés, J.; Fraile, L.; Pérez de Rozas, A.; Maiti, H.; Coll, T.; Sibila, M.: Assessment of Mycoplasma hyopneumoniae-induced Pneumonia using Different Lung Lesion Scoring Systems: a Comparative Review. J Comp Pathol. 2016 Feb-Apr;154(2-3):125-34 9. Guadagnini, G.; Salvini, F.; Ottolini, F.; Paoletti, F.; Rosina, S.; Casappa, P.; Cominotti, F.; Krejci, R.; Lisgara, M.; Mazerolles, P.: Comparison of the growth performance of heavy pigs vaccinated with Hyogen® or another single shot vaccine against M. hyopneumoniae in Italy, Proc. ESPHM, 2018, HHM022, 281 10. Guadagnini, G.; Salvini, F.; Ottolini, F.; Paoletti, F.; Rosina, S.; Casappa, P.; Cominotti, F.; Krejci, R.; Lisgara, M.; Mazerolles, P. Evaluation of the efficacy of a single shot vaccine, Hyogen®, in comparison with a two-shot vaccine, on protection against swine enzootic pneumonia in the Parma ham pigs in Italy, Proc. ESPHM, 2018 HHM-023, 282 11. Holt, HR.; Alarcon, P.; Velasova, M.; Pfeiffer, DU.; Wieland, B. BPEX Pig Health Scheme: a useful monitoring system for respiratory disease control in pig farms? BMC Vet Res. 2011, Dec 30;7:82 12. Hurnik, D.; Hanna, PE.; Dohoo, IR. Evaluation of rapid gross visual appraisal of swine lungs at slaughter as a diagnostic screen for enzootic pneumonia. Can J Vet Res. 1993, Jan;57(1):37-41 13. Krejci, R.; Merialdi, G.; Luppi, A.; Saldivar, D.; Lopez, A. Efficacy of Coglapix® and Hyogen® vaccines in prevention of pleuropneumonia and enzootic pneumonia, Proc. 6th APVS, 2013 OR39 14. Krejci, R.; Bijasa, R.; Lopez, A.; Lung lesion survey in the Philippines. Proc. 6th APVS, 2013, OR6. 15. Krejci R, Gobbi S, Mazerolles P. 2017a: Efficient prevention of enzootic pneumonia with Hyogen® in high health status farm, Proc ESPHM, HME-047, 304 16. Krejci R, Brilland S, Piel Y, Gobbi S, Mazerolles R, 2017b: Clinical and economical improvements due to better control of enzootic pneumonia with Hyogen®, Proc ESPHM, HME-049, 306 17. Krejci R, Mazerolles P 2018: Lung lesions in slaughter pigs in 2017. PIG PROGRESS 34 18. Krejci R., Mazerolles P, Mortier M. 2018: Lung scoring survey in European countries in 2017, Proc. ESPHM, HHM-029, 288 19. Lisgara M, Poulaki K, Kalogeropoulos L, Krejci R. 2018: A field trial comparing the efficacy of two vaccines against Mycoplasma hyopneumoniae in terms of lung lesions and growth performance, Proc. ESPHM, BBD-032, 208 20. Madec F, Kobisch M. 1982: Bilan lésionnel des poumons de porcs charcutiers à l‘abattoir. Journees. Rech porcine en France.;14:405–12. 21. Maes D, Verdonck M, Deluyker H, de Kruif A., 1996: Enzootic pneumonia in pigs. Vet Q. Sep;18(3):104-9 22. Maes D, Verbeke W, Vicca Jo, Verdonck M, Kruif A, 2003: Benefit to cost of vaccination against mycoplasma hyopneumoniae in pig herds under Belgian market conditions from 1996 to 2000, Livestock Production Science, 83, 85-93 23. Maes D, Segales J, Meyns T, Sibila M, Pieters M, Haesebrouck F. 2008: Control of Mycoplasma hyopneumoniae infections 3.
International Animal Health Journal 27
RESEARCH AND DEVELOPMENT
in pigs. Vet Microbiol. Jan 25;126(4):297-309. 24. Maes D, Sibila M, Kuhnert P, Segalés J, Haesebrouck F, Pieters M. 2018: Update on Mycoplasma hyopneumoniae infections in pigs: Knowledge gaps for improved disease control. Transbound Emerg Dis.; 65(Suppl. 1): 110–124. 25. Mann, H. B., Whitney D. R.: On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other. Ann. Math. Statist. 18 (1) 50 - 60, March, 1947. DOI: 10.1214/ aoms/1177730491 26. Merialdi G, Dottori M, Bonilauri P, Luppi A, Gozio S, Pozzi P, Spaggiari B, Martelli P. 2012: Survey of pleuritis and pulmonary lesions in pigs at abattoir with a focus on the extent of the condition and herd risk factors. Vet J. Jul;193(1):234-9 27. Morris CR, Gardner IA, Hietala SK, Carpenter TE.,1995: Enzootic pneumonia: comparison of cough and lung lesions as predictors of weight gain in swine. Can J Vet Res. Jul;59(3):197-204. 28. Paisley LG, Vraa-Andersen L, Dybkjaer L, Møller K, Christensen G, Mousing J, Agger JF. 1993: An epidemiologic and economic study of respiratory diseases in two conventional Danish swine herds. I: Prevalence of respiratory lesions at slaughter and their effects on growth. Acta Vet Scand.;34(4):319-29 29. Pallarés F.J., Espigares D., Cano L.D., Del Carmen P., Ramis G. 2018: Vaccination against Mycoplasma Hyopneumoniae with Hyogen®: Prevalence and severity of lung lesions, Proc. ESPHM, BBD-055, 231 30. Pieters M, Daniels J, Rovira A. 2017: Comparison of sample types and diagnostic methods for in vivo detection of Mycoplasma hyopneumoniae during early stages of infection. Vet Microbiol. May; 203:103-109. 31. Rautiainen E, Virtala AM, Wallgren P, Saloniemi H. 2000: Varying effects of infections with Mycoplasma hyopneumoniae on the weight gain recorded in three different multisource fattening pig herds. J Vet Med B Infect Dis Vet Public Health. Aug;47(6):461-9. 32. Sen, P. K.: Estimates of the Regression Coefficient Based on Kendall's Tau. Journal of the American Statistical Association 63 (1968). 1379–1389. DOI: 10.1080/01621459.1968.10480934 33. Sibila M, Nofrarías M, López-Soria S, Segalés J, Valero O, Espinal A, Calsamiglia M. 2007: Chronological study of Mycoplasma hyopneumoniae infection, seroconversion and associated lung lesions in vaccinated and non-vaccinated pigs. Vet Microbiol. May 16;122(1-2):97-107 34. Sibila M, Pieters M, Molitor T, Maes D, Haesebrouck F, Segalés J. 2009: Current perspectives on the diagnosis and epidemiology of Mycoplasma hyopneumoniae infection. Vet J. Sep;181(3):221-31 35. Straw BE, Tuovinen VK, Bigras-Poulin M. 1989: Estimation of the cost of pneumonia in swine herds. J Am Vet Med Assoc. Dec 15;195(12):1702-6. 36. Thacker EL, Thacker BJ, Clark LK, 2002: Mycoplasmal Pneumonia of Swine, Pork Industry Handbook, 1-3. 28 International Animal Health Journal
37. Theil, H.: A rank-invariant method of linear and polynomial regression analysis. Proceedings of the Royal Netherlands Academy of Sciences 53 (1950) Part I: 386-392, Part II: 521525, Part III: 1397-1412. DOI: 10.1007/978-94-011-2546-8_20
Roman Krejci Roman Krejci DVM, is a veterinarian, graduated at the University of Veterinary Medicine in Brno, Czech Rep. He 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.
Jiří Kalina Jiří Kalina Mgr, is a data analyst, leading the data analytical team at RECETOX, Masaryk University in Brno, Czech Republic. He’s an reputable expert in statistics, data analysis, mathematical modelling, environment, persistent pollutants, air sampling, mass spectroscopy. He’s also teaching at the university. Jiri is an author or co-author of numerous articles published in international scientific journals.
Monika Kuncová Monika Kuncová is a student in the newly accredited study program Environment and Health, where she learns to comprehensively connect scientific knowledge with statistical data processing. This study program is under the auspices of RECETOX – Research Centre for Toxic Compounds in the Environment, Brno, Czech Republic. In addition to study and research, Monika is also involved in projects for the popularization of science.
Volume 9 Issue 2
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 29
RESEARCH AND DEVELOPMENT
Cannabis: An Overview of Use in Veterinary Medicine Perhaps no other herb has recently received as much attention in the media – or in the courts – as Cannabis sativa. With more and more countries and local jurisdictions moving toward legalisation for recreational as well as medical purposes, use of cannabis in its many forms has expanded exponentially among the human population. As medical marijuana becomes more widely accepted and available, it’s no surprise that veterinary practitioners are increasingly asked to address questions about medical applications for nonhuman animals, while manufacturers are facing decisions regarding how to respond to customer demand. The professional veterinary community is just beginning to formulate guidelines for clinical use, and confusion remains regarding how to apply historical knowledge about other herbs and natural supplements to its use. Availability of cannabis products in a range of forms adds to the confusion. Anecdotal reports of toxicosis, in the context of decades of legal restrictions and prohibitions by some veterinary governing bodies, have raised concerns to an unnecessary degree. Cannabis has demonstrated its medicinal benefits across thousands of years of use, however using it to optimum efficacy is in fact complicated, and can best be achieved through study and experience. Still, its safety, efficacy, and broad range of clinical uses – from treatment of pain and inflammation to neuroprotection, slowing or reversing tumour growth and metastasis, and much more – make it an important addition to the practitioner’s and caregiver’s therapeutic resources and to pharmacies’ and manufacturers’ product offerings. A discussion here of a few applicable principles will serve to clarify issues and options, provide a starting point for further study, and generate inspiration to give this medicine the attention it deserves. Broad Application and Exceptional Safety Profile Not only does cannabis offer an effective option in the treatment strategy for many forms of disease, it’s also one
Photo by Kimzy Nanney on Unsplash 30 International Animal Health Journal
Photo by Jeff W on Unsplash
of the safest. A key reason for both attributes lies in its synergy with animal biology. The phytocannabinoids that are key therapeutic components of the plant mirror endogenous cannabinoids and cannabinoid receptors that are present in virtually every animal species that has been assessed (with the apparent exception of insects), within what has been named the endocannabinoid system (ECS). These receptors have been found in the brain and throughout the central nervous system, in organs and connective tissue throughout the body, and even in cells of the immune system. The ECS is responsible for maintaining homeostasis in immune, neurological, and digestive systems; inflammatory response; apoptosis and carcinogenesis; energy and metabolism; sleep; emotions; and more. When an animal’s health is disrupted by disease, trauma, or other stress, exogenous cannabinoids, like those found in the cannabis plant, can interact with the endocannabinoid system to help restore balance. Into the Weeds: Cannabinoids At least four hundred active compounds that affect the body and mind have been identified in the cannabis plant. Those include more than sixty cannabinoids, hundreds of terpenes, more than twenty flavonoids, as well as lipids and omega fatty acids. All of these compounds work synergistically in what is known as “the entourage effect,” to balance and modulate the action of each component. Together they provide greater benefit than any one or two or a few components given separately. That’s why medicine made from whole plants is generally preferable to any single isolated component. Tetrahydrocannabinol, or THC, and cannabidiol, or CBD, are the two most prominent cannabinoids in Cannabis sativa, and are best known for their medicinal properties. For our purposes here, and for most therapeutic purposes, knowing the amounts and proportions of CBD and THC in the medicine is most relevant for assessing safety and efficacy and choosing the appropriate form and formula to meet a patient’s needs. THC is the most abundant cannabinoid in plants grown for recreational use, and is the one responsible for the psychoactive “high” associated with marijuana. CBD is also present in large amounts, particularly in strains of the plant grown for medicinal purposes; while it is often used to reduce anxiety and promote sleep, it is not considered Volume 9 Issue 2
RESEARCH AND DEVELOPMENT psychoactive because it does not produce the intoxicating effect of THC. It does in fact modulate the psychoactivity of THC, and can even help reverse it if needed. The relative amounts of CBD and THC in the medicine you choose is a determining factor in its therapeutic benefits, since each has a distinct effect on the body and mental state of the patient. Concerns about the safety of using cannabis in veterinary practice are widespread – and largely unfounded. We’ve all read reports of dogs who have suffered THC toxicosis. But it’s important to note that those cases are generally attributable to ingestion of a large amount of a food made with recreational cannabis – think of a pan of marijuana brownies or slab of butter laced with a THC extract. Dogs have far more endocannabinoid receptors in their brains than humans do, so they’re more susceptible to the intoxicating effects of THC. Even so, such cases are rarely fatal, and can easily be avoided. Obviously, edible marijuana products made for humans should be kept well out of reach of canine family members. In therapeutic usage, with products that are standardized, tested, and analysed for the amount of THC and other cannabinoids, the risk of an overdose is all but eliminated. Also, using products that contain as much or more CBD as THC reduces the risk even further, since CBD counteracts the psychoactive effects of THC. Extensive Therapeutic Value An exploration of the vast range of applications for cannabis illustrates why it’s such a valuable ally in veterinary practice. Neurological Disorders: CBD and other compounds in cannabis have been shown to have neuroprotective properties. They can reduce the frequency and severity of
seizures, slow the progression of neurodegenerative disease like degenerative myelopathy and dementia, and support recovery from traumatic brain and spinal cord injury. Emotional/behavioural issues: CBD is an anxiolytic, effective in treating anxiety disorders, including separation anxiety, as well as situational fears such as fear of fireworks and thunderstorms or stress related to a visit with the veterinarian. It has also been useful in treating compulsive disorders and calming fear-based aggression. THC can also be calming, but in some individuals it can increase anxiety, so formulas higher in CBD than THC are recommended. In all cases it’s necessary to monitor the individual patient’s response. Inflammation: CBD is effective in reducing both chronic and acute inflammation. It has been used successfully to ease discomfort from osteoarthritis, traumatic injury, and overexertion. Pain: THC is particularly useful for pain management, including nerve pain and pain in cancer patients. Cancer: Cannabis is known to slow or reverse tumour growth by promoting apoptosis and inhibiting blood supply; it has also been shown to prevent metastasis. Other indications include: • • • • •
motion sickness, anorexia, inflammatory bowel disease, skin eruptions and infections, immune support.
Photo by Elsa Olofsson on Unsplash www.international-animalhealth.com
International Animal Health Journal 31
RESEARCH AND DEVELOPMENT benefits of medicine made from marijuana with it’s full array of active compounds. Still, in jurisdictions where marijuana and products made from it are illegal, CBD from the hemp plant is well worth considering. Whole Plant Medicine vs. Isolated Compounds In recent years, many products have emerged that offer CBD, THC, or other key cannabinoids extracted as isolated components. While there is some merit to identifying a specific “active ingredient” to target a particular symptom or illness, this approach eliminates the synergistic and modulating benefits of the entourage effect cited above, and is likely to reduce the efficacy of the medicine; it may also increase the risk of side effects or toxicity. Medicines based on whole-plant formulas are likely to yield better outcomes overall.
Photo by Avery Meeker on Unsplash
Choosing the Optimal Source, Form, and Delivery Method Countless strains of the Cannabis sativa plant have been developed for medicinal purposes, and the medicine itself may consist of whole plant material, tinctures, extracts, or infusions; any and all of those can be used to create foods or products for topical application. Tinctures and extracts can be ingested or administered via mucosal membranes. There’s a lot to consider, and selecting the right source, form, and delivery method is key to a safe and successful outcome. Marijuana vs. Hemp The amounts of THC and CBD vary between different strains of cannabis, and growers of the plant have developed strains to meet differing purposes and needs. Those with much higher levels of THC have been produced to meet demand for recreational marijuana, where the euphoria THC is known for is desirable. Plants grown for medicinal purposes are generally more balanced, with levels of CBD comparable to or higher than THC; these strains can be used to treat illness little or no risk of intoxication. The hemp plant, which is the same species as marijuana, has long been cultivated for industrial purposes, and has extremely low levels of cannabinoids, particularly THC; in the United States hemp is defined as a Cannabis sativa plant that contains 0.3 percent or less THC, and that designation has to a great extent been adopted globally. Because of the miniscule amount of THC, hemp is not considered psychoactive, and for that reason it is legal in many locales to grow and produce medicine from the hemp plant. But even industrial hemp has approximately 3% to 4% CBD, which producers extract for medicinal purposes. In response to demand, growers are now developing strains of hemp with much higher levels of CBD. As long as THC levels remain low, the plant is considered nonpsychoactive, and it is legal to grow hemp and sell medicine made from it in many countries where marijuana is illegal. That’s a good thing, because it greatly expands the availability of high-CBD medicinal products. However, many illnesses respond better to treatment with THC than CBD. Even those for which a higher-CBD medicine is recommended, we know that CBD is more effective in the presence of THC. Due to the entourage effect, it’s beneficial to use a CBD product that also has some THC, as well as the many terpenes and flavonoids that are present in the marijuana plant but much less so in hemp. For that reason, hemp-derived CBD formulas simply cannot provide the comprehensive and synergistic 32 International Animal Health Journal
Plant Matter vs Tinctures Human patients commonly use cannabis as an unprocessed whole plant, either smoking it or incorporating it into brownies, cookies, or other edible form. For nonhuman patients, particularly those smaller in body size, this is risky, primarily due to the difficulty in calibrating precise dosage. Fortunately, oil-based tinctures are now widely available, and allow for the precise dosing necessary to ensure safety as well as enabling practitioners and caregivers to find the optimum dose for a given patient. In areas where cannabis is legal and regulated, most tinctures have been analysed and tested for their levels of CBD and THC, and that information is provided on the label. These tinctures are typically offered in a base of olive, coconut, or salmon oil, which are palatable for most species. CBD:THC Ratio The ratio of CBD to THC is an important factor in choosing the right medicine, since these two primary cannabinoids have different effects and therapeutic benefits. It’s also a safety factor, since large amounts of THC can cause negative psychoactive effects in some species, particularly canines, when not balanced with a similar or greater amount of CBD. A quality medicinal cannabis tincture will have the CBD:THC ratio clearly indicated on the product label. Below are some commonly available ratios and their applications: •
• •
High CBD (4:1 to 20:1 CBD:THC): Seizures, degenerative and other neurologic disorders, gastro-intestinal issues, pain, inflammation, anxiety/fearfulness, sleep disruption, behavioural problems Even Ratio (1:1 CBD:THC): Cancer, neurologic disorders, brain or spinal trauma, pain, gastrointestinal problems High THC (1:4 to 1:20 CBD:THC; should be used only under the supervision of a veterinary practitioner who is experienced in the use of cannabinoids): Cancer, anorexia, severe pain
Dosing and Administration Because of the intimate relationship between CBD, THC, and the endocannabinoid system, dosing protocols are different from those for other herbs. One of the hallmarks of effective cannabis therapy is the principle that “less is more”—that is, the patient may respond better to a very small dose than to a larger one. And since every animal’s endocannabinoid system is unique, the ideal dose for one individual may be different from that for another of similar species and size. In the initial phase of treatment, microdosing, trituration, and careful monitoring of patient response are key to a successful outcome. Volume 9 Issue 2
RESEARCH AND DEVELOPMENT •
• •
•
For most companion animals, a good minimum starting dose is 0.1 mg of total cannabinoids (CBD + THC) per kilogram of body weight. For larger species, 1 mg per 100 kilograms may be appropriate. If there is no improvement within 2 to 3 days, increase the dose by ¼ to ½ the amount of the starting dose. Continue increasing the dose until a response is observed; be aware that while a dose that is too high is unlikely to be harmful, if the animal receives more medicine than he needs, you may see less benefit, not more. If that happens, stop giving the medicine for two or three days, then resume treatment at the dose at which you saw the best response.
When cannabis is ingested, as much as 30% to 60% of cannabinoids are metabolised by the liver. That’s why, for most species, applying the oil-based tincture to the oral mucosa is the preferred mode of administration. With a mucosal application, benefits may be observed within ten to twenty minutes, with the most pronounced effects lasting three to four hours. With ingestion, benefits are observed after one to two hours and generally last six to seven hours or longer. With both methods, cannabis has an underlying cumulative effect that will be sustained much longer, providing lasting therapeutic benefits. An Opportunity for Wellness The excellent safety profile and extensive range of indications for medicinal cannabis therapy reveal it as an exciting addition to our treatment protocols for all species. With governments and professional oversight organisations easing restrictions on its use, we have an opportunity to bring a new and powerful ally in healing to our clients, customers, and patients. As our community of veterinary professionals gains experience and expertise in the application of this
Photo by Karina Vorozheeva on Unsplash
complicated but very forgiving medicine, we can look forward to a greater understanding of the synergy between the plant and animal kingdoms and the health and wellness it engenders. REFERENCES 1.
2.
3. 4.
5.
American Veterinary Medical Association. Cannabis in Veterinary Medicine. Aug 14, 2020. https://www.avma.org/ sites/default/files/2021-03/APH-CannabisResourcesReport-20201207.pdf, accessed May 9, 2022. Atakan Z. Cannabis, a complex plant: different compounds and different effects on individuals. Ther. Adv. Psychopharmacol. Dec 2012; 2(6):241-54. https://pubmed. ncbi.nlm.nih.gov/23983983/, accessed May 9, 2022. Hazzah, T., André, C.M., Richter, G., & McGrath, S. Cannabis in Veterinary Medicine: A Critical Review. AHVMA Journal. Vol. 61, Winter 2020, 17-41. Silver, R.J. Veterinary Cannabis: Regulatory, Pharmacology, Safety, Applications (Pain & Cancer), ISVMA.org, https://www.isvma.org/wp-content/uploads/2019/10/ SilverVeterinaryCannabis.pdf, accessed May 9, 2022. Silver R. J. The Endocannabinoid System of Animals. Animals: an open access journal from MDPI. 9(9), Sept 16, 2019, 686. https://doi.org/10.3390/ani9090686, accessed May 9, 2022.
Jan Allegretti Jan Allegretti, D.Vet.Hom., is the author of The Complete Holistic Dog Book: Home Health Care for Our Canine Companions. She has more than thirty years’ experience as a teacher and consultant in holistic health care for nonhuman animals, offering workshops and consultations to caregivers, rescue organizations, veterinarians, and other animal health professionals. Web: www.JanAllegretti.com Photo by Elisa Kennemer on Unsplash www.international-animalhealth.com
International Animal Health Journal 33
RESEARCH AND DEVELOPMENT
Yeast Mannan Oligosaccharides: A Front-line Defense Mechanism for Pathogen Control Bacterial adherence to host tissue is an important initial step in enabling gastrointestinal tract colonisation and infection. Adherence typically involves the interaction of complementary molecules on the surface of a bacteria with those of the host epithelium. Historically, the first adherence specificity recognised in intestinal bacteria involved binding via mannose-selective receptors. Almost all isolates of E. coli, as well as other members of the Enterobacteriaceae, such as Enterobacter, Klebsiella, Shigella and Salmonella, attach to mannose receptors by means of type 1 fimbriae. Attachment of type 1 fimbriae to D-mannose receptors can be blocked by means of mannose-containing receptor analogs. From a nutritional standpoint, many feed supplements focus on pathogen adhesion and GI tract exclusion, with the most commonly used being yeast cell wall mannan oligosaccharides (MOS). These are complex mannose-containing preparations linked to a protein group. The use of MOS to protect and enhance gastrointestinal health stemmed from research that focused on the ability of mannose, the pure single unit of the complex sugar in MOS, to control and prevent the risk of Salmonella colonisation in the intestinal tract. Subsequently, distinct forms of mannosetype sugars were found to interact differently with type 1 fimbriae, and it was noted that the α-1,3 and α-1,6 branched mannans present in the cell wall of Saccharomyces cerevisiae were particularly effective. Based on the in vitro findings, applied research trials determined that the inhibition and reduction of Salmonella colonisation resulted in improved in vivo performance. Within the cell wall of Saccharomyces cerevisiae, there are two main locations where MOS is found; attached to cell wall proteins as part of –O and –N glycosyl groups or as components of larger α-D-mannose polysaccharides. These larger mannose-containing polysaccharides consist of α-(1,2)- and α-(1,3)-D-mannose branches, which are attached to extended α-(1,6)-D-mannose chains. Yeast MOS are widely used in animal nutrition, given their well-documented ability to bind and limit the colonization of gut pathogens, thereby acting as a front-line defense mechanism for pathogen control (Figure 1). They have proven to be an effective solution for antibioticfree diets, as well as providing support for immunity and digestion, leading to notable improvements in performance and wellbeing. As first-generation variants, most commercially available MOS products are derived from the cell wall of the yeast, Saccharomyces cerevisiae. Subsequent research fractionated the yeast cell wall and isolated a mannose-rich fraction (MRF), which, as a ‘second generation’ product, can best be described as an enhanced MOS-type product with capabilities beyond simple bacterial adherence and agglutination. 34 International Animal Health Journal
One of the more interesting capabilities of MRF is its ability to increase microbiome diversity and, in doing so, enhance the colonisation resistance of the GI tract. By enabling greater GI tract resilience, foodborne pathogens, such as Campylobacter, for instance, can be controlled more effectively. A comparison of first- and second-generation MOS and MRF products is highlighted in table 1. MOS Developed through nutrigenomic studies Branched mannan structure
MRF
x
✓
✓ (low)
✓(high)
Enhances diversity of microbiome
x
✓
Agglutinates E. coli and Salmonella
✓
✓✓
Broad-spectrum Salmonella control
✓
✓✓
Reduces Campylobacter
x
✓
Increases weight gain
?
✓
Improves FCR
✓
✓✓
Decreases mortality
?
✓
Modulates immune response
✓
✓
✓
✓✓
x
✓
Protects the gastrointestinal tract • Enhances protective mucin barrier • Improves gut structure Improves villus height to crypt depth ratio Increases goblet cell size Protects against leaky gut (improves barrier function)
x
✓
Enhances digestive enzyme production
✓
✓✓
Enhances energy production
✓
✓✓
Reduces foot pad lesions
x
✓
Table 1: Comparison of MOS and MRF capabilities
Salmonellosis, as a disease, requires an efficient control system, including dietary measures, and is critical to producing safe food for human consumers. The variable nature of Salmonella serotype prevalence is well documented, and in the highly regulated environment of food production, information on the occurrence of individual Salmonella spp. is readily available. One such source for serotype occurrence in US domestic chicken samples, for instance, is the USDA’s food safety and inspection service (FSIS). Figure 2, in the form of a heat map, presents accumulated data with respect to Salmonella isolated from domestic chicken samples, with green representing low prevalence and red indicating high prevalence. These heat maps highlight some interesting features associated with Salmonella occurrence in the preceding number of years. Firstly, one can appreciate the highly variable nature of serotype recovery in chicken samples from 2016–2021. Of more interest, however, are the quite striking temporal changes in Salmonella serotype prevalence. While Salmonella Kentucky was the predominant serotype isolated in 2016, by 2021, Salmonella Infantis had become the dominant serovar. In the intervening period, Salmonella Enteritidis was isolated less frequently. From a pathogen control viewpoint, this presents a challenge for poultry producers in that any Salmonella control mechanism needs to be ‘broad-spectrum’ to account for not only the variable nature but also the temporal changes in Salmonella abundance. Volume 9 Issue 2
RESEARCH AND DEVELOPMENT
Figure 1: Yeast mannan oligosaccharides adsorb pathogenic bacteria
Figure 2: Salmonella prevalence over time (FSIS 2016–2021)
Adherence and agglutination studies have demonstrated the ability of MRF to adhere to a wide range, or broad spectrum, of Salmonella isolates. In controlled studies with chickens, a reduction in the prevalence and concentration of different strains of Salmonella spp., as well as E. coli and Campylobacter, have also been reported with the use of MRF. As such, MRF represents an exceptional control mechanism for pathogens with food safety implications. Given the increasing restrictions on the use of antibiotic gut microflora modifiers in animals, yeast mannans represent
a technology that has become a critical part of the arsenal for veterinarians and animal producers. MOS, due to cost of production, extraction technology and potential infinite supply, has been used widely in animal diets over the last 20 years, but is now being superseded by the next generation, MRF.
Dr. Richard Murphy Dr. Richard Murphy, research director at Alltech’s European Bioscience Centre in Dunboyne, Ireland, received a bachelor’s degree in biochemistry in 1994 and a doctorate from the Department of Biochemistry at National University of Ireland, Galway in 1999. Murphy maintains strong links with numerous academic institutions and is an adjunct professor on the faculty of science and health studies at Dublin City University. He also sits on the board of management of the National Institute for Cellular Biology at Dublin City University, where he is the external chairman. His research activities are diverse, including areas such as trace element and mineral bioavailability, gastrointestinal health, pathogen control, antimicrobial resistance, coordination chemistry and cellular redox reactions. Email: rmurphy@alltech.com
www.international-animalhealth.com
International Animal Health Journal 35
COMPANION ANIMALS
Biometric Study Proves Pet Acoustics® CanineSpecific Music Mitigates Stress Levels in Dogs Abstract Canine behavioural stress is often triggered by their acute hearing to sounds in the environment. Dogs can hear from 67Hz to 45,000 Hz which is more than two times higher than human hearing which is 20Hz-20,000Hz. To modify behavioural stress in dogs, Janet Marlow, Founder of Pet Acoustics innovated a science-based music process specifically for canine, feline and equine acute hearing. The benefits of this music in the canine listening environment has been proven in previous studies with results showing calm and a more balanced behaviour. To further understand the calming effects, this new study was initiated to analyse the biometric data of mostly small dog breeds in particular while listening to the speciesspecific designed music. Why a focus on small dog breeds? Behaviourally, small dog breeds show more fearful and anxious behaviours for various reasons: their comparative size creates a threatened and defensive posturing; owners tend to be overprotective, limiting social confidence; their sonic and vibrational environment triggers an intense physical response. For example, a dog may exhibit compulsive grooming by repeatedly licking or chewing at their skin and fur to help relieve their anxious feelings. Therefore, determining the calming effects of caninespecific music on a biometric level for small dog breeds can provide a tool that promotes calm behavior for a longer, healthier life. The four month biometric study monitored twenty varying small and larger dog breeds of different ages by measuring their pulse rate, HRV rate, and activity level determining the effects of the music to mitigate anxiety. Each dog's vital signs and behavior patterns were collected by wearing the Petpace smart collar. Purpose of Study The study began in January, 2022, with the purpose of documenting each dog’s biological responses when the canine music was playing and comparatively, when the music was not playing. The music was disbursed by the pre-loaded, Pet Acoustics Pet Tunes Bluetooth® speaker and placed near the dog. The canines for the test were provided by Ron Pia, canine behaviourist in Australia, who facilitated the study. The dogs were volunteered by their owners to participate in the study, with a stay over in a home where the testing took place. Each dog’s daily schedule included rest, walks and play activity. Twenty dogs were monitored, one by one, of different ages and breeds which included: West Highland Terrier, Beagle, Long Haired Chihuahua, Cavalier King Charles Spaniel, French Bulldog, Lagotto Romagnolo, Pomeranian, English Springer Spaniel, Border Collie, Labradoodle, Poodle and a German Shepherd. The ages ranged from six months to twelve years. Each dog’s vital signs were documented in real time by wearing the Petpace smart collar. The Petpace collar measured each dog’s pulse rate, HRV rate and activity levels with the music playing and without the music playing. Pulse, or heart rate, is the measurement of the number of times a pet’s heart beats per minute. Heart rate is one of the 36 International Animal Health Journal
most important vital signs caregivers can measure for a pet. When the heart rate is measured peripherally by palpating or sensing the pulse in a limb it is called pulse. The job of the heart is to pump blood throughout the body, supplying oxygen to the cells. A pet’s heart rate is controlled by a sophisticated mechanism that takes into account the oxygen demand from the cells and makes sure the heart is able to provide it. For example, when a dog runs, its muscles work hard and consume a lot of oxygen. Therefore, the heart must work faster to supply the demand. Fear is another condition that is associated with increased heart rate in pets. When a pet (or a human) is afraid, the body gets ready for a fight or flight situation, and prepares for the anticipated increase in demand for oxygen. Heart Rate Variability (HRV) is a statistical analysis of the small variations in time intervals between heartbeats. The variations are innate and normal physiological phenomena. Studies have shown that changes in HRV are associated with a wide range of diseases as well as pain, stress, and obesity. HRV is recognised as a marker for autonomic nervous system activity. The autonomic (parasympathetic and sympathetic) nervous systems as well as hormonal factors provide the main input to the heart’s pacemaker, and the beat-to-beat interval variability is a reflection of the balance between these two. High HRV indicates a good fitness level and a healthy heart and nervous system. Low HRV is associated with stress, pain, heart disease and other pathologies. Activity Score is a calculated value that provides a quantitative representation of a pet's activity during the selected time range. It is based on summarising all the separate activity readings and producing a total value for the pet's overall activity. What is known is that monitoring and analysing activity patterns and levels can provide valuable medical insights. For example, a decline in activity levels may indicate the development of a disease causing pain Volume 9 Issue 2
COMPANION ANIMALS Median Pulse Pet_Name
Pet_ID
Before
After
Median HRV Difference
Before
After
Median Activity Difference
Before
After
Difference
Bailey
18252
73
58
-15
10.75
11.57
0.82
33.18
33.18
0
Bernie
17724
61.5
51
-10.5
11.52
11.85
0.33
32.19
28.01
-4.18
Biscuit
17672
52.5
52
-0.5
11.84
11.79
-0.05
31.13
28.69
-2.44
Buddy
18315
61
71
10
11.75
11.68
-0.07
30.57
25.66
-4.91 -1.65
Byron
17619
49
48
-1
11.92
11.965
0.045
35.74
34.09
Casey
17490
59
57.5
-1.5
11.7
11.755
0.055
29.97
29.97
0
Coco
17629
53
49
-4
11.755
12.1
0.345
37.87
30.57
-7.3 -1.43
Fifi
18036
63
67.5
4.5
11.355
11.42
0.065
28.69
27.26
Gracie
18162
56.5
53
-3.5
11.65
11.795
0.145
31.13
31.13
0
Jasper
18227
77.5
68.5
-9
10.83
11.185
0.355
34.94
37.87
2.93 -1.13
Maisie
17584
53.5
59.5
6
11.49
11.2
-0.29
40.25
39.12
Margot
18151
55
58
3
11.49
11.49
0
32.67
35.35
2.68
Max
17516
63
62.5
-0.5
11.505
11.37
-0.135
28.01
31.68
3.67 -0.55
Millie
18321
71.5
58
-13.5
11.13
11.4
0.27
31.68
31.13
Mojo
17982
60
70.5
10.5
11.415
11.17
-0.245
25.66
31.68
6.02
Molly
18112
61.5
50
-11.5
11.74
12.08
0.34
32.7
34.53
1.83
Murphy
17441
64
57
-7
11.415
11.8
0.385
35.35
37.87
2.52
Ollie
17636
66
50.5
-15.5
11.315
11.905
0.59
45.86
27.26
-18.6
Tyra
18273
64
56.5
-7.5
11.63
11.79
0.16
23.83
25.66
1.83
Wilbur
18218
67
61
-6
11.375
11.315
-0.06
38.2
36.12
-2.08
61.58
57.95
-3.63
11.48
11.63
0.15
32.98
31.84
-1.14
Average Percent change
-5.9
or weakness. Activity is also affected by stress levels but this effect is more complex. Some dogs respond to stress by excessive barking, pacing or shaking, while others respond by hiding or loss of appetite. The study evaluated each dog’s activity levels. The purpose of this study is to support the hypothesis that canine-specific music induces a physiological and behavioral calmer state in small dog breeds as well as larger dog breeds, helping them modify stress-triggered behavior for better health and balance. The twenty dogs in this study
1.3
-3.5
were male and female, neutered and not neutered, different sized breeds and different ages. Materials Petpace Smart Collar There were two catalysts used for the study; the Pet Acoustics canine-specific music and the Petpace smart collar. Each of the twenty dogs wore the PetPace collar for approximately six hours within a twenty-four hour period during various activities. Biometric data was collected by an array of sensors in the collar device. The music was played for three hours. After this time, the
Data of Each Dog Tested www.international-animalhealth.com
International Animal Health Journal 37
COMPANION ANIMALS
Pulse Rate Chart
HRV Chart
music was turned off for three hours in the area of the collared dog for comparison. During the six hour session with the collar, the data was collected in real time and could be seen on a cloud-based analysis engine program provided by Petpace. Pet Acoustics® Canine-Specific Music The canine-specific music used in the study is a sciencebased process with measurable and repeatable results to calm behavioral stress in dogs. Different from music for human hearing, the instruments, frequency and decibel levels are digitally modified in original compositions to accommodate the 38 International Animal Health Journal
comfort range of canine acute hearing. Species-specific music is a copyrighted, proprietary process innovated in 1997 by Janet Marlow, sound behaviourist and composer for Pet Acoustics®. Methods After the first dog’s testing was completed, the collar was removed and placed on the next dog visiting the testing site. The same method was done with each of the other dogs collecting the biometric data every two minutes during the sessions. Each dog was tested with half the session without the music playing and then with the music playing. Volume 9 Issue 2
COMPANION ANIMALS
Activity Chart
When the music wasn’t playing, each dog heard and responded to the natural sounds of home life as well as several daily walks and playtime. During the four month period however, there were sounds of passing intense thunderstorms with lightning. Within the testing home of the twenty dogs, there were multiple dogs in the same environment.
Results When looking at the aggregated data for all the dogs that participated in the study, we can see that the median pulse rate was lower, the median HRV was higher, and the median activity score was slightly lower when the dogs were exposed to the calming music compared to these values when no music was being played.
Aggregate Data Chart www.international-animalhealth.com
International Animal Health Journal 39
COMPANION ANIMALS Pulse Pulse rate decreased in response to music. The average of median pulse rates was 5.9% lower during times when the dogs were exposed to the music (57.95) compared to times when the dogs were not exposed to the music (61.58). HRV Music caused the HRV to increase (high HRV indicates lower stress level). In this study, the overall average of median HRVs was 1.3% higher during times when the dogs were exposed to the music (11.63) compared to times when the dogs were not exposed to the music (11.48). Activity The activity score value showed varying results. The median activity score was lower for 10 dogs out of the 20 that participated in the study, and higher for the other 10 dogs. The total average of median Activity Scores was 3.5% lower during times when the dogs were exposed to the music (31.84) compared to times when the dogs were not exposed to the music (32.98). Conclusions The Pet Acoustics music that was tested in this study caused physiological and behavioural changes indicating a calmer state for dogs. The pulse rate was lower and HRV was higher in response to music, both being physiological changes associated with a calmer state (lower relative sympathetic tone, or a weaker “fight or flight” state). All these findings supported the hypothesis of a calming effect as a result of the dogs listening to the music shown by the biometric data. The most significant finding was the HRV, which showed a considerable elevation from baseline, even more than what we see with the pulse. HRV was lower
40 International Animal Health Journal
Volume 9 Issue 2
COMPANION ANIMALS Applications and Benefits For veterinarians – When playing Pet Acoustics® caninecalming music, there is a reduction in stress which allows the team to conduct better physical examinations and take more accurate vitals. Broadcasting this music in the waiting rooms of veterinary clinics can also help to ease the anxiety of waiting dogs. More applications Modify stress for separation anxiety Modify stress in animal shelters Calmer response to thunderstorms and firework events Less stressful breeding and birthing Use for post-surgery healing Use for travel anxiety REFERENCES 1. 2. 3.
www.petacoustics.com www.petpace.com www.thepetcalmer.com
Janet Marlow Janet Marlow, M.A., Sound Behaviorist and Founder of Pet Acoustics, is internationally known as a composer, researcher and author. In 1997, Janet Marlow innovated a proprietary process of modified frequency and decibel music as the invention of species-specific music. In 2017, Janet Marlow was named Women of Influence in the Pet Industry by Pet Age Magazine. Her work on the benefits of species-specific music for dogs, cats, horses and birds has been featured on CNN as well as studies published in the Journal of Equine Veterinary Science and the International Animal Health Journal. Email: janetmarlow@petacoustics.com
Dr. Asaf Dagan
when the sympathetic tone (fight or flight mode) was higher, and vice versa. Therefore, a calm animal should have a higher HRV. Benefits for Canine Welfare The results of the study proved that canine-specific music modifies stress behaviours in small dogs. The stress scores were significantly lower in dogs listening to the music as compared with no music. There were no significant differences when comparing the sex, age or breed of the dogs, whether they were neutered or not and whether they were outdoors or indoors, all responded positively to the music. Therefore, small dog breeds inclination for more intense stress responses to their environment can be successfully mitigated by the use of canine-specific music regardless of the owners consistency of training or environment. Additionally, this study showed larger sized dogs have the same ratio of biometric calming response to the music. www.international-animalhealth.com
Dr. Asaf Dagan DVM, DABVP, CVA, LLB Dr. Asaf Dagan serves as Chief Veterinary Scientist of PetPace LTD. Dr. Dagan is a Diplomate of the American Board of Veterinary Practitioners (ABVP), specializing in Canine and Feline medicine.
Ron Pia Ron Pia has worked with dog behavior for over 5 decades. A specialist in canine lifestyle management, dog and cat behavioral modification, pet anxiety and stress reduction, and creator of home environment fundamentals for healthy, sustainable living with animals. In 2016, Ron Pia established The Pet Calmer, an affiliate of Pet Acoustics Inc., to introduce Pet Tunes species-specific music concept to veterinarians, animal behaviorists and pet owners in Australia and New Zealand. Over recent years, thePetCalmer has become an integrated collaborator to Pet Acoustics Inc. research studies using specific sound environments for the management of both canine and feline stress.
International Animal Health Journal 41
COMPANION ANIMALS
APPLICATION NOTE
Felpreva®: New Unique Combination
Spot-on to Help Simplify Feline Parasite Control
Currently, cat owner compliance for parasiticide use is a challenge for veterinarians with data suggesting that on average, cats are only dewormed 2.2 times per year.1 While multiple factors need to be considered when it comes to compliance, the negative impact that administering parasiticides has on the bond between owner and their cat cannot be underestimated. Many veterinarians, keen to improve owner compliance, are recognising the importance of prescribing parasite treatments that are both easy to give and long-lasting and which minimise stressful owner/cat interactions. Importance of the Human-companion Animal Bond The attitudes of cat owners are changing, with more than half now seeing their pet as a family member.i Owners simply enjoy the companionship and unconditional affection their cat brings and are reluctant to have negative and potentially relationship-damaging interactions with their pet. Often, giving parasite treatments can do just that. In a recent survey of European cat owners:2 • •
44% have negative feelings about giving parasite protection to cats Over half felt their cat reacted negatively to parasiticide treatments and one in eight stopped treatment altogether
The fact that many parasiticides require frequent application to provide adequate protection, and often multiple products are needed for complete cover, particularly for tapeworms, exacerbates this compliance challenge. “Having to apply parasite prevention every month can really affect the bond between cat and owner. Owners often tell me that their cat disappears for a day or so after having been treated. This is obviously really distressing and also puts the owner off keeping up with parasite prevention.”
and lungworms), and ectoparasites (fleas, ticks and mites) in a single dose. It is licensed for treatment of cats with, or at risk from, mixed parasitic infestations/infections. The lower frequency of application – only four times per year – results in fewer potentially negative interactions between cats and their owners compared to typical monthly treatments, while the broad-spectrum cover negates the need for additional products. The low volume solution also makes it more tolerable to many cats and may reduce stress of application. This is thanks to Felpreva®’s unique formulation, combining three active ingredients: emodepside and praziquantel (known antiparasitic compounds, also found in the Profender® range) and tigolaner (a novel active ingredient). Tigolaner – New Chemical Class for Long-lasting Action Against Fleas and Ticks Tigolaner is at the forefront of innovation in feline parasitology, as the first active ingredient of the bispyrazole chemical class. It treats and protects against fleas and ticks for up to 13 weeks, and is also effective against head and ear mites.3 Its unique mode of action inhibits the parasite’s gamma-aminobutyric acid (GABA) receptors, disrupting nervous system function, resulting in death. Alongside its long duration of action, tigolaner has excellent efficacy against fleas*, being more potent than other commonly used isoxazolines and fipronil.4 These properties make it an ideal choice for long-lasting parasite control in cats. Felpreva® is now available for veterinarians to prescribe in Austria, France, Germany, Italy and United Kingdom. For more information please contact your local Vetoquinol Representative. * Adult Ctenocephalides felis
Dr. Rosy Nye PGCert SAM BVetMed MRCVS, first opinion veterinarian. A lapse in parasite protection can lead to its own challenges to the owner/cat bond too. Many owners are understandably distressed by seeing evidence of parasites, not to mention concern of zoonotic risk of some parasitic species. Making prescription recommendations which are sympathetic to the special relationship between owner and cat by considering factors such as duration of action, spectrum of cover and administration route can help to aid compliance, helping protect both animal and human health. Felpreva® – Now Available for Long-lasting, Broad-spectrum Parasite Protection for Cats Felpreva® is a breakthrough in companion animal parasitology. Designed specifically for cats, it is the first threemonthly spot-on parasiticide that that covers tapeworms, in addition to other endoparasites (roundworms, hookworm 42 International Animal Health Journal
Volume 9 Issue 2
APPLICATION NOTE
COMPANION ANIMALS REFERENCE 1.
2. 3.
4.
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) Study of 1416 cat owners in UK, Germany, France and Italy. Conducted by Sapio Research in August 2021. European Commission Union Register of Veterinary Medicinal Products – Felpreva. 2021. Available from: https:// ec.europa.eu/health/documents/community-register/ html/v277.htm [Accessed 16 November 2021]. Data part of the Marketing authorization dossier
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.
A breakthrough IN PARASITE PROTECTION FOR CATS NEW ACTIVE: Tigolaner
3 MONTHS’ flea & tick protection PLUS treatment against roundworm, tapeworm & ear mites, ALL in a SINGLE spot-on Felpreva® contains tigolaner, emodepside and praziquantel (POM-V). See the datasheet at www.noahcompendium.co.uk. The SPC and further information is available from Vetoquinol UK. Advice should be sought from the medicine prescriber. Use medicines responsibly – see www.noah.co.uk.
International Animal Health Journal 43
www.international-animalhealth.com
For more details, please contact:
+44 (0) 1280 814500
uk_office@vetoquinol.com
www.vetoquinol.co.uk
14 & 15 September 2022 | Geneva, Switzerland
The new event at the heart of European pharma dedicated to innovative packaging, drug delivery systems, CDMO/CMO and filling & assembling processes
New event designed to drive innovation for pharma and biopharma businesses ‘Connect in Pharma’ is the new event that will bring together key players in the pharma and biopharma production industry. The event will take place on 14 & 15 September 2022 at major exhibition space Palexpo Congress Centre, in the heart of the pharma and biopharma industry and conveniently located next to the Geneva airport. Leading global events company Easyfairs say they are launching this new event after spotting a gap in the market.
www.international-animalhealth.com
FACTFILE When: 14 & 15 September 2022 WHERE: Palexpo, Geneva, Switerland EXHIBITORS: 100+ COST: Free to attend KEY SECTORS: Drug Delivery - Filling & Assembling - Innovative Packaging - CDMO FIND OUT MORE AND SECURE YOUR PLACE quote code 5017
International Animal Health Journal 44
Bringing Together Innovators The event is designed to inspire collaboration and innovation between suppliers, specifiers and other influencers in four key areas of pharmaceutical production downstream from the molecule: packaging, medical devices, contract manufacturing (CMO/CDMO) and processing. Visitors to Connect in Pharma can expect to discover a range of innovations that are changing the way drugs are brought to market. With new developments in the field, including personalised treatments and nanotechnology among others, even greater changes are expected in the near future.
Isabelle Levy-Dessart, WW Marketing Communication Associate Director at BD, said: “We believe that Connect in Pharma will be an exciting new force driving business and innovation in the pharma market, and we can’t wait to meet the whole market in Geneva.”
Founding partners
SINGLE BEST WAY TO DELIVER
Heike Lang, Head of Marketing & Communications at Sanner GmbH, said: “Connect in Pharma has the potential to become the top event for pharmaceutical packaging and for CDMOs in Europe. As one of the key players for primary packaging and medical devices, we want to be part of this development from the very start.”
Collaboration and Partnerships The event is partnering with leading associations such as Biopole SA, Polepharma, Lyonbiopole, BioAlps, Swiss Biotech, Bionow in the UK and more. Over 70 industry-leading suppliers and associations in the pharma and biopharma sector have already signed up to exhibit at the event, including Becton Dickinson SAS, Catalent, Uhlmann, Staubli Robotics, ARaymondlife, Essentra, Gerresheimer, IMA Automation, Körber AG, MARCHESINI GROUP SPA, Nextpharm, and Unither Pharmaceuticals, among others. A full list can be found at www.connectinpharma.com/ exhibitor/.
Stephanie Pellet, Marketing Manager at ARaymondlife, said the company was looking to showcase new injectable drugs and meet other companies. “We decided to join this new event because the pharmaceutical industry in Switzerland is a highly developed sector, from large corporations to small startups and research centres. This European-wide event is perfect in terms of the format and the time of year.” www.international-animalhealth.com
connectinpharma.com
International Animal Health Journal 45
Your gateway to the global life science community
OCT. 2426, LEIPZIG, GERMANY NOV. 24 DIGITAL PARTNERING
2022
BIO-Europe is back in person! The 28th BIO-Europe will be held in Leipzig, Germany from October 24–26, 2002, to fulfil its pivotal role of bringing together the global biopharma community to accelerate dealmaking.
Produced by:
Over the years, BIO-Europe has become Europe’s flagship partnering event bringing together over 4,000 executives from biotech, pharma and finance companies from around the world. Your access to the entire life science ecosystem all under one roof. Be part of the 20,000+ one-to-one meetings that will take place at the event that will ultimately shape the future of our industry—one partnership at a time.
Take advantage of the best registration rates available now! In collaboration with:
www.international-animalhealth.com
LEARN MORE: BIOEUROPE.COM
International Animal Health Journal 46
Get your
ticket now!
INSPIRING SUSTAINABLE CONNECTIONS #back2live: 22 – 26 August 2022 Frankfurt, Germany
www.achema.de
www.international-animalhealth.com
World Forum and Leading Show for the Process Industries ACHEMA is the global hotspot for industry experts, decision-makers and solution providers. Experience unseen technology, collaborate crossindustry and connect yourself worldwide to make an impact. Are you ready? Join now!
International Animal Health Journal 47
AD INDEX
Page 47
ACHEMA 2022
Page 5
Alltech
Page 11
Argenta Limited
Page 46
BIO – EUROPE 2022
Page 44–45
Connect in Pharma (Easy Fairs)
OBC
Knoell Animal Health
Page 3
Moredun Scientific
IFC Royal GD Page 29
Senglobal Ltd
IBC Stäubli International AG. Page 23
Trilogy Writing & Consulting GmbH
Page 42–43
Vetoquinol UK Ltd
I hope this journal guides you progressively, through the maze of activities and changes taking place in the animal health industry.
IAHJ is also now active on social media. Follow us on:
Subscribe today at
www.international-animalhealth.com or email info@senglobalcoms.com
48 International Animal Health Journal
www.twitter.com/AHMJournal
www.facebook.com/Animal-Health-Media
www.plus.google.com/+Animalhealthmediajournal www.animalhealthmedia.tumblr.com/
Volume 9 Issue 2
ROBOTICS
Discovering new pharma automation solutions Robots for Life Sterile or standard environments, high-end or routine tasks, Stäubli robots deliver clean, consistent performance ensuring the highest levels of product hygiene, safety, flexibility and productivity. Benefit from our know-how and discover the new automation possibilities of intelligent and safe robot technology. Stäubli – Experts in Man and Machine www.staubli.com
Stäubli Faverges SCA, Tél. +33 (0)4 50 65 62 87, robot.sales@staubli.com 49 International Animal Health Journal
Volume 9 Issue 2
THINK GLOBALLY, ACT LOCALLY
GLOBAL ANIMAL HEALTH PRODUCT DEVELOPMENT AND REGISTRATION SERVICES Global regulatory and scientific support for your animal health products is now at your fingertips: our regional teams in North America, Europe and Asia will develop solutions tailored to your needs. Take advantage of our services - total outsourcing or individual solutions.
Products ◗ ◗ ◗ ◗ ◗
Pharmaceuticals Biologicals Nutritional Products Pet Healthcare Products Novel Therapies
Services ◗ ◗ ◗ ◗ ◗ ◗ ◗
Regulatory Affairs Clinical Studies CMC Safety Project Management Training, Pharmacovigilance, QA Start-to-Finish Product Development
Are you missing any product area or service? Contact: info@knoell.com
www.knoell.com
knoell are attending the Kisaco Animal Health, Nutrition & Technology Innovation USA event in Boston MA, on 21-23 June 2022. COME AND MEET US!
50 International Animal Health Journal
Volume 9 Issue 2