Designing Bespoke Stability Studies for Veterinary Drug Products
The Importance of Gut Health in Livestock: How Microbiota Can Solve Current Challenges in Livestock Farming
Horses as a Material Asset in Anti-venom Production: What is their Limit?
Mapping the Geographical Spread of PRRSv in the Netherlands
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REGULATORY & MARKETPLACE
06 Mapping the Geographical Spread of PRRSv in the Netherlands
Porcine Reproductive and Respiratory Syndrome virus (PRRSv) presents a major economic and welfare challenge to the global swine industry, as there is a lack of data on the direct and indirect contributing routes leading to transmissions on farms. Heinrich Kreutzmann of Royal GD explains, with the support of a conducted study, the need to focus on improved external biosecurity practices, specifically within the transportation and movement of animals, as means of preventing the introduction of new strains.
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Volume 11 Issue 3 Autumn 2024
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Veterinary Contract Research Organisations (CRO) phenomenon began during the second half of the last century, and Dr. Maggie Fisher of VRM and Dr. Peter Holdsworth of Animal Health Alliance inform us on just how integral CROs really have become in pharmaceutical, feed additive and diagnostic developments in the animal health industry.
As with pharmaceutical products used for humans, animal medical products are also subject to rigorous regulatory standards, with stability studies forming a crucial part of the testing process. Here, Beccy Bell of Broughton explains how vital it is that manufactures choose the right testing partners so to develop the best
bespoke, most accurate stability studies for veterinary medicines.
16 Optimising Silage: Management, Testing and Choosing the Right Inoculants
Silage quality poses a complex challenge, impacting the nutritional value, safety and effectiveness of feed. Gordon Marley of Alltech delves into the significance effective silage management can have in maximising feed efficiency and nutritional value, highlighting that if each stage is appropriately overseen, farmers are able to enhance their silage quality and overall farm productivity.
20 Developing a Complex, First-of-its-kind Antiparasitic Drug for Dogs
In the evolving field of veterinary medicine, the need for innovative treatments for parasitic infections in pets is more pressing than ever, and thus Alex Del Priore of Syngene gives insight into the best way to tackle this. He explains the complexities with approaching this as one individual company, discussing how multi-drug solutions derived from strategic partnerships is key to helping the next generation of treatments to move forward an evolve within the industry.
22 The Importance of Gut Health in Livestock: How Microbiota Can Solve Current Challenges in Livestock Farming
Gut health in livestock is something that can be largely overlooked, but holds great importance in animal health, productivity and sustainability levels. Julia Katrin Rohde of Corbiota explains the critical role of gut health in livestock and examines how novel feed compositions based on the approach of the effect of microbiota on intestinal health can make a significant difference.
MARKET REPORT
28 Horses as a Material Asset in Antivenom Production: What is their Limit?
Historically, horses have been presented as ‘soulless machines’ whose useful characteristics have been manipulated and exploited. In this discussion we see Ana Lucia Camphora present the considerations that justify a greater commitment to the fate and welfare of horses within the antivenom industry, offering a viewpoint that explore what is deemed morally acceptable to impose upon horses within the antivenom industry.
32 Artificial Intelligence for Authorisation Processes: From Collecting to Connecting Data
The demand for Artificial Intelligence (AI) is ever on the rise, seeing it being integrated into both personal and professional spheres. Regina Olhmann of Feed and Additives explores how adopting AI tools could be beneficial specifically to the approval process under the European Food Safety Authority (EFSA) and how applicants might leverage AI tools to streamline and expedite the preparation of dossiers.
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This autumn edition of the IAHJ highlights various challenges as well as a wealth of innovations and exciting opportunities within the field of animal health. This issue discusses a range of topics, including the emergence of CROs, the optimisation of silage, and the demand for groundbreaking treatments in parasitology.
In the veterinary sector, only a limited number of CROs have gained a global presence. Nevertheless, despite the challenges they face, these organisations have become a well-established component of the veterinary pharmaceutical, biological, and feed additive development landscape. It remains to be seen whether further consolidation and expansion will occur, like trends observed in human CROs.
Firstly, our Regulatory & Marketplace section features Heinrich Kreutzmann, Swine Veterinarian at Royal GD, who describes the scarcity of data on the relative roles of direct and indirect transmission routes for the Porcine Reproductive and Respiratory Syndrome virus (PRRSv) onto farms. He notes that the virus poses significant economic and welfare issues for the global swine industry. Heinrich’s research underscores the importance of factoring in the PRRS status of source herds within operational, regional, and national programmes for PRRS stabilisation and eradication.
Alex Del Priore of Syngene stresses the necessity for innovative treatments for parasitic infections in pets, as these
remain a significant threat to animal health. He urges the importance of integrating scientific expertise, innovation, and flexibility to address the challenges in drug development. As the veterinary health landscape evolves, the strategies for developing treatments must also adapt to ensure they are effective, accessible, and well-tolerated.
One of my favourite pieces, found under Research and Development, is by Beccy Bell, Operations Manager at Broughton. She emphasises the critical role of stability studies in the testing process and explains that, compared to human medicines, veterinary medicine product matrices are highly complex. She asserts that this necessitates the design of bespoke stability studies for veterinary drug products.
The Manufacturing section wraps up the journal with contributions from Ana Lucia Camphora at the Center for Contemporary Equine Studies. She explores the challenges of establishing limits on the use of seroproducing horses for antivenom production, discusses the limited understanding of horses' sensitivity to pain, and highlights how practices such as venom injections and bloodletting have led to a lack of specific criteria for identifying equine injuries.
I hope you enjoy this issue of IAHJ, and I look forward to meeting some of you at upcoming exhibitions.
Kelly Woods Editorial manager
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
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The Porcine Reproductive and Respiratory Syndrome virus (PRRSv) presents a major economic and welfare challenge to the global swine industry. In one retrospective study from the Netherlands, the economic losses during an outbreak varied between €59 and €379 per sow for an 18-week period, depending on the type of farm.1 Due to the prolonged nature and high prevalence within a farm, PRRSv has a significant impact on animal welfare.2 The risk of introducing a new PRRSv strain into a farm is not limited to PRRSv-negative farms; the impact of PRRSv introductions on both PRRSv-negative and PRRSv-positive farms can vary significantly, ranging from mild, asymptomatic cases to severe disease outbreaks, depending on the virulence of the strain and the crossreactivity of the existing immunity.3
Currently, there is a lack of data on the relative contribution of direct and indirect routes to the transmission of PRRSv onto farms. Whereas direct transmission is mostly attributed to trade and transport of infected pigs, indirect routes include people, semen, manure, domestic/feral animals, rodents, insects, aerosol, animal feed, water and fomites.4 In our analysis, it was aimed to compare the prevalence of Dutch PRRSv-positive farms in areas with high and low pig densities, respectively. Furthermore, the relative contribution of trade contacts to PRRSv introduction on farms was investigated, contrasting with other possible other risk factors for PRRS introduction such as proximity between farms and airborne transmission of the virus.
Materials and Methods
Between 2022 and 2023, a total of 49 farms were included: 38 farms, evenly distributed across four areas (two with high pig density and two with low pig density, as shown in Figure 1), along with 11 gilt- and piglet-producing farms that supplied animals to at least one of the participating farms. A biosecurity questionnaire was conducted on each of the farms. The collected data encompassed, for example, location, management of animal flow, and animal contacts between herds.
Blood samples from 30 piglets at the end of the nursery phase in pools of five, or, in case only fatteners were present, six oral fluid samples were analysed via PRRSv RT-qPCR and ORF5 sequencing from one sample with the highest viral load. Phylogenetic analysis of ORF5 aimed to identify close matches (≥98% nucleotide identity) and trace them back to potential direct or indirect contacts between farms. Chi-squared tests were applied to detect differences between areas using contingency tables.
Results
The farm-level prevalence of PRRS virus detection (RT-qPCR positive) in the two pig-sparse areas was 44% and 75%, while in pig-dense areas, it was 80% and 91% (Table. 1). The prevalence of field virus detection (<98% nucleotide identity in ORF5 with a licenced PRRSv MLV strain) ranged from 30% to 38% across all four areas, with no significant differences in the detection rates of field strains between the regions. 55% of the supplying farms were RT-qPCR-positive, and in 5/6 cases field virus could be detected (Table. 1). Farms with external animal supply
Figure 1. Illustration showing the density of pig farms across 2-digit postal code regions in the Netherlands in 2023 and the localisation of the four areas (blue circles; two pig-dense and two pig- sparse areas). Each UBN (=unique business/ farm number) is specific to a particular farm or business location.
showed higher PRRSv farm-level prevalence (84%) compared to those without (63%). Field virus was less frequently detected on farms without animal supply (5%) in contrast to those with animal supply (63%; X2=9.2, df=1, p=0.002, Table. 2). Analysis of ORF5 sequences identified four close matches, three linked to direct contact between suppliers and supplying farms (99.0 to 99.2% nucleotide identities). A match was detected in two farms located close to each other in a pig-sparse area. However, these farms also had the same supplier, who declined to participate in this project.
This pilot study revealed that farms with external animal supply exhibited a significantly higher farm-level prevalence of field virus positive samples. Whereas it is important to acknowledge the study's limitation due to the small number of suppliers included, the identification of three closely matched sequences from connected farms highlights the effectiveness of our approach. Furthermore, the findings are consistent with an U.S. study, which reported that the median number of case farms (farms with a specific PRRSv lineage) connected through animal movements was approximately 4.1 times higher than random expectations. In contrast, for farms linked by spatial proximity, this number was only 2.7 times higher than random expectations.5 This knowledge should be given particular consideration in regional and national PRRS stabilisation and eradication measures.
In the study group, no statistically significant difference in field virus prevalence at the farm level was observed between pig-dense and pig-sparse areas. Due to the sample size and
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Negative indicates that all samples were below the detection limit of the PRRSv RT-qPCR
2 PRRSv ORF5 sequencing was not possible due to a low viral load
3 Vaccine strain was defined as ≥98% nucleotide identity in ORF5 with a licenced PRRSv MLV strain
4 Field strain was defined as <98% nucleotide identity in ORF5 with a licenced PRRSv MLV strain
Negative indicates that all samples were below the detection limit of the PRRSv RT-qPCR
2 PRRSv ORF5 sequencing was not possible due to a low viral load
3 Vaccine strain was defined as ≥98% nucleotide identity in ORF5 with a licenced PRRSv MLV strain
4 Field strain was defined as <98% nucleotide identity in ORF5 with a licenced PRRSv MLV strain
Table 2. Detection of PRRSv by RT-qPCR at participating farms and typing by ORF5 sequencing, stratified by farms with and without external animal supply. Supplier herds were omitted.
limited sequencing results per farm, definitive conclusions cannot be drawn, and there is potential for false negatives inherent to the cross-sectional study design. Additionally, the analysis was limited to the ORF5 gene, covering only approximately 4% of the genome. It is recognised that relying solely on ORF5 analysis can lead to misclassification, such as mistaking field strains for vaccine strains.6 Nevertheless, it is well documented in the literature that external biosecurity plays a crucial role, particularly in the introduction of new strains.4 For instance, factors related to animal movements, specifically each additional farm contact through outward animal shipments, incur a 3.0% increased likelihood of a specific strain occurrence on the farm.7 This suggests potential deficiencies in external biosecurity practices on these farms during loading and transportation of pigs.
In conclusion, this study highlights the importance of considering the PRRS status of supplying herds in operational, regional, and national PRRS stabilisation and eradication programmes, as farms with external animal supply showed a higher farm-level prevalence of field virus detection. Notably, no significantly higher prevalence of field virus was detected in pig-dense regions, emphasising the need to focus on improving external biosecurity practices, particularly during animal movements, to prevent the introduction of new strains.
Acknowledgments
Preliminary results were presented as a poster presentation at the 15th European Symposium of Porcine Health Management (ESPHM), Leipzig, Germany, 4th–7th June 2024 (VVD-PP-46).
The farmers and herd-attending veterinarians are acknowledged for their participation to the study. The project was funded by internal resources of GD.
REFERENCES
1. Nieuwenhuis N, Duinhof TF, van Nes A. Economic analysis of outbreaks of porcine reproductive and respiratory syndrome virus in nine sow herds. Vet Rec. 2012;170(9):225.
2. Nielsen SS, Houe H, Denwood M, Nielsen LR, Forkman B, Otten ND, et al. Application of methods to assess animal welfare and suffering caused by infectious diseases in cattle and swine
populations. Animals (Basel). 2021;11(11).
3. Clilverd H, Li Y, Martin-Valls G, Aguirre L, Martin M, Cortey M, et al. Selection of viral variants with enhanced transmission and reduced neutralization susceptibility alongside lateral introductions may explain the persistence of porcine reproductive and respiratory syndrome virus in vaccinated breeding herds. Virus Evol. 2024;10(1):veae041.
4. Filippitzi ME, Brinch Kruse A, Postma M, Sarrazin S, Maes D, Alban L, et al. Review of transmission routes of 24 infectious diseases preventable by biosecurity measures and comparison of the implementation of these measures in pig herds in six European countries. Transbound Emerg Dis. 2018;65(2):381-98.
5. VanderWaal K, Paploski IAD, Makau DN, Corzo CA. Contrasting animal movement and spatial connectivity networks in shaping transmission pathways of a genetically diverse virus. Prev Vet Med. 2020;178:104977.
6. Dortmans J, Buter GJ, Dijkman R, Houben M, Duinhof TF. Molecular characterization of type 1 porcine reproductive and respiratory syndrome viruses (PRRSV) isolated in the Netherlands from 2014 to 2016. PLoS One. 2019;14(6):e0218481.
7. Makau DN, Paploski IAD, Corzo CA, VanderWaal K. Dynamic network connectivity influences the spread of a sub-lineage of porcine reproductive and respiratory syndrome virus. Transbound Emerg Dis. 2022;69(2):524-37.
Heinrich Kreutzmann (Dr. med. vet., Dipl. ECPHM) is a Swine Veterinarian at Royal GD. In this role, he is focused on monitoring swine diseases and actively participates in the national PRRS plan. Kreutzmann completed his doctoral thesis on PRRSv at the Vetmeduni Vienna. PRRSv is also one of his primary research focuses at Royal GD.
Co-authors
K. Eenink1, H. Kreutzmann1, C.J. Vermeulen1 , K. Koenders-van Gog2, V. Manders2, M.A.M. Houben1
1Royal GD, Deventer, the Netherlands
2LintjeshofVeterinary Practice, Nederweert, the Netherlands
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The Veterinary Contract Research Organisations (CRO) phenomenon began during the second half of the last century. In this article we will take a look at their development into becoming an integral component of pharmaceutical, feed additive and diagnostics development. A CRO is defined by the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH) in GL9 (VICH, 2000) as “an individual or organisation contracted by the sponsor or investigator to perform one or more of the obligations of the sponsor or investigator”. Although this guideline is restricted to Good Clinical Practice, nonetheless, the definition is useful throughout industry.
Veterinary CROs, independent of universities and pharmaceutical companies, originated to service a commercial need arising with veterinary pharmaceutical companies where R&D facilities within those companies were either over committed or did not exist in house. Outsourcing of R&D components of product development offered veterinary pharmaceutical companies flexibility in both resource allocation and risk management. It also provided a means of reducing the substantial overhead cost of an in-house physical facility with accompanying specialised staff.
Whilst veterinary CROs were generally originally small businesses, they originated in several different ways (Figure 1). Vetspin is an example of a CRO that originated as a spin out from a university, in this case the University of Bologna, Italy, some 20 years ago. Ridgeway Research Ltd (RRL) began as an overflow facility for Pfizer when its United Kingdom (UK) base was located in Sandwich, Kent, where since 1954 it had developed both human and veterinary pharmaceuticals. NorthWest Biopharm (NWB) represents a start-up CRO established in the Republic of Ireland by personnel with industry and regulatory experience in 2012. Each of these CROs has a physical site which enables studies to be conducted under controlled conditions.
Other CROs, notably Klifovet which was established in 1997 in Germany, did not have its own physical site to conduct animal studies and instead focused on coordinating clinical studies across a number of other sites.
Since their inception, CROs have grown against a backdrop of pharmaceutical and feed additive companies choosing to outsource components of their R&D projects. Meanwhile, the outsourcing companies have not remained static, national companies have been acquired by multinationals and, in turn, multinationals have taken over other multinationals. Standalone animal health companies have been spun out from their original parent human/animal health companies. Hence CROs have had the challenge of developing relationships with a changing customer base.
The CRO development timeline is overlaid by radical changes in the animal populations that are the eventual targets for animal medicines and feed additives. For example, in the UK, the dog and cat populations have approximately doubled since the 1980s (PFMA, 2024), whilst the UK cattle population, including both milking and beef animals, has reduced by approximately two thirds (Table 1). Over the same time, whilst red meat consumption has decreased, chicken consumption has increased, with UK broiler production more than doubling to 1113.3 million birds by 2023 from 439.3 million birds in 1982. In contrast, the layer population has stayed relatively constant (UK government, 2024).
Despite the changes in the surrounding landscape, CROs have not only survived but grown and expanded in the 21st century, providing a range of services supporting all stages of development from small scale pilot studies through to environmental assessment, potentially making it unnecessary for a company to have in house R&D facilities.
The development timeline of NWB, RRL and Vetspin is given in Figure 2, showing their growth in the years since their establishment. Within the industry as a whole, CRO growth and development has to some extent followed the pattern established by CROs in the human pharmaceutical sector,
Spin out from university
Overflow for pharmaceutical company
Farmers’ Research Institute
Human pharmaceutical CRO
Vertical development
Geographical expansion
Horizontal development
Achieved by: Organic growth and/ or Acquisition Startup
NWB
RRL
Vetspin
1987: RRL established
GLP accredited 2008: new ownership
2004: established
2006: GLP accreditation
where there has been considerable growth both organically and through acquisition. Key examples being Labcorp and Charles River, both of whom have established an international presence, and coincidentally both also have an animal health presence.
Within the veterinary sector there are relatively few CROs that have achieved a global presence. Two notable examples which have come about through organic growth and acquisition are Argenta and Clinglobal. Argenta, was established in New Zealand in 2006 and has since developed into a global company with a major presence in the USA and Europe. Unique among veterinary CROs, Argenta also offers contract manufacturing and so is able to supply a service from proof of concept through to manufacture of a product. Clinglobal has developed out of Africa to offer a range of preclinical and clinical services including data handling and an -omics division.
The development of CRO services on offer for the veterinary pharmaceutical industry over time now covers:
1. Conducting a study as directed by the client;
2. Input to the design of the study that the client directs the CRO to undertake;
3. All of 2. plus the CRO input to the study regulatory interpretation;
4. All of 3. plus development of dossier for application for registration;
5. All of 2. 3. or 4. plus addressing comments received by
2010: farm purchased and NWBP established
2011: farmland improved
2012: companion animal facility completed
Growth in range of studies offered and Level 2 biosecurity facility developed
2014: offices and laboratory external to the university
2015: first animal facility approved
2021: slatted cattle shed extended
2022: second building phase begun
2023: new 600m2 facility completed for housing farm animals
2020: GM registered
2021: authorisation of the second animal facility
the client from the registration authority on the product application based on the study conducted by the CRO;
6. All of 2, 3, 4 or 5. plus input to marketing the product (publications/scientific papers; conference presentation; marketing material) based on science relating to study conducted by the CRO;
7. Vertical integration of CRO services as demonstrated by the company Argenta becoming a contract research, development and product manufacturing organisation.
There are also CROs that have focused on a particular specialised area of expertise such as sample analysis, a service offered by a number of CROs including Vetspin, or environmental assessment, a service offered by Cemas . Other specialisations include regulatory advice and dossier submission, as well as food and feed services.
A number of initiatives, whilst not directly aimed at CROs, have facilitated the ability of customers or sponsors to outsource work, hence the development of CROs. Non-industry specific developments such as in information technology will not be considered here, despite having played a considerable role in growth of CROs.
It may be argued that the introduction of harmonised guidance on the conduct and quality standard of preclinical and clinical studies has facilitated the ability of sponsors to outsource development studies. First developed was Good
Laboratory Practice (GLP) which applies to the veterinary sector but also extends across various industries where chemicals are evaluated. It was established during the 1970s in response to fraudulent safety studies being submitted for regulatory approval (OECD, 2016). Its principles were subsequently consolidated into a harmonised guideline by OECD in 1982, and these have been integrated into national and international law. They provide a system whereby the CRO is responsible for the appropriate conduct of the study, with the study controlled by one accountable person, the study director.
Good Clinical Practice for veterinary medicines was introduced in 2000 (VICH, 2000) and aims to provide public assurance about the conduct of clinical studies including animal welfare and protection of the public. It consists of a set of principles for the roles and responsibilities within a clinical study. Unlike GLP, the sponsor retains responsibility for the study and has a monitoring role to assure the study integrity. Whilst VICH is not a global organisation, it represents a harmonised approach between the EU, USA and Japan with consideration given by Australia and New Zealand.
Good manufacturing practice (GMP) began as a set of principles for ensuring the quality and safety of human medicines after a series of tragedies in the USA and Europe, and was subsequently extended to cover veterinary medicines. Whilst not applicable to most veterinary CROs, any contract manufacturing organisation will work to GMP principles.
A series of guidelines have been developed by various organisations, such as the World Association for the Advancement of Veterinary Parasitology and VICH, that aim to provide guidance on technical elements relating to the planning and conduct of a wide range of preclinical and clinical studies. These guidances permit the development of specific protocols for one or more studies that can be agreed between the sponsor and the CRO.
The strategic position a CRO takes in relation to whether it focuses its business offerings, locally, regionally or globally can be influenced by the commercial and/or regulatory environment it works within. Regulatory requirements in regions may dictate that certain types of work/studies to support a regulatory submission are undertaken exclusively within that jurisdiction. Such requirements may lead to duplication of studies to meet regulatory requirements globally, despite efforts at harmonisation, and may limit the applicability of studies conducted in other parts of the world.
Despite the challenges faced by CROs, they now form a well-established part of the veterinary pharmaceutical, biological and feed additive development landscape. Time will tell whether there is further consolidation and expansion as has been seen within human CROs.
1. Gov.uk www.gov.uk/government/statistics accessed 20th October 2024
2. OECD 2016. OECD Series on principles of Good Laboratory Practice and Compliance Monitoring no. 18
3. UKpetfoodreports.co.uk. PFMA, 2021.
4. VICH website (www.vichsec.org) accessed 20 October 2024
5. VICH, 2000. Good Clinical Practice VICH GL9
Thanks go to Vetspin for permission to use their images of Office, analytical and animal facilities at Vetspin.
Dr. Maggie Fisher BVetMed CBiol MSB MRQA DipEVPC MRCVS graduated in 1986 from the Royal Veterinary College and is director of VRM Ltd, a project management company (www.vrm. uk.com). Dr. Fisher has been active in the establishment and advancement of a number of animal health associations including WAAVP and ESCCAP. She is a Diplomate of the European Veterinary Parasitology College.
Email: maggie@shernacre.co.uk
Dr. Peter Holdsworth AO BSc (Hon) PhD
FRSB FAICD was the founding Chief Executive Officer of Animal Health Alliance (Australia) Ltd – the peak industry body in Australia representing R, D&E companies, registrants, manufacturers and marketers of veterinary medicines, veterinary chemicals and biologics in Australia. Dr Holdsworth is a past president of WAAVP and a former president of the Australian Society for Parasitology.
Email: peter.paragon60@gmail.com
The National Office of Animal Health, which represents over 97 per cent of the UK’s animal medicine market, states that approximately £745 million is made each year in sales of authorised veterinary medicines. As with pharmaceutical products used for humans, animal medical products are also subject to rigorous regulatory standards, with stability studies forming a crucial part of the testing process. Here, Beccy Bell, Operations Manager at analytical testing specialist Broughton explains how manufacturers can develop bespoke stability studies for veterinary medicines.
Stability testing can help determine a product’s shelf life and recommended storage conditions. These studies provide evidence of how the quality of a drug substance or medicinal product varies over time under the influence of different environmental factors, such as temperature, humidity, and light.
Stability studies are also used to establish a re-test period for a drug substance that is then applicable to future batches of that substance manufactured under similar circumstances. Usually, manufacturers will determine this by testing a minimum of three batches of the drug substance and evaluating the stability information generated (including, as appropriate, results of the physical, chemical, biological, and microbiological tests).
The degree of variability of individual batches impacts the confidence that a future production batch will remain within specification throughout the assigned re-test period.
The data may show so little degradation and variability that it is apparent from looking at the data that the requested re-test period will be granted. Under these circumstances, it is normally unnecessary to go through a formal statistical analysis. If so, justifying the omission should be sufficient.
Several design factors must be considered before initiating a stability study. Sometimes, stability study designs may be straightforward with a single formulation and strength, but this is rarely the case.
Firstly, for formal registration stability studies required to support the regulatory submission for a veterinary product, these studies must be performed on no fewer than three representative batches of the manufactured product. This will allow manufacturers to assess the potential batch-tobatch variability in the product's shelf life. Those tests include biological and physiochemical stability studies carried out at regular intervals, for the finished product until three months beyond the claimed end of shelf life.
In addition, stability studies for veterinary drug products may consist of multiple strengths, packaging types, storage orientations, and container closure systems, resulting in numerous stock-keeping units (SKUs). For studies of multiple strengths and packaging types, the requirement of the study may be reduced if bracketing is applied.
When designing a stability study consideration should be given to the impact of the product's packaging. Generally, the impact will depend on the study, and packaging assessments may not be required for all stability studies. Manufacturers may also want to consider the impact of the surface area contact ratio of the substance to the container. For veterinary drug products, shelf-life stability studies should be performed in the primary container closure system proposed for marketing. However, suppose the secondary packaging has protective properties, and the labelling states that the product is to be stored in the primary and secondary packaging. In this event, manufacturers must also assess the secondary packaging as part of the stability study.
As part of the study design, you may also want to consider an in-use stability study. In-use stability tests assess product quality after any packaging has been opened, simulating the expected use of the product.
Finally, when designing a stability study, the sample quantities set down at the start of the study are critical. Insufficient quantities can have a huge impact on cost and timelines, as stability studies may need to be repeated. It is crucial to have adequate sample quantities to cover all testing specified in the stability study protocol and account for potential repeat testing, investigation of atypical results, and subsequent confirmation of data. Additionally, we recommend a sample quantity overage is applied for flexibility, to allow for additional ad-hoc testing that may be required at unspecified stability time points.
A significant difference between veterinary drug products and those specified for human consumption is the dosage forms and the product matrices as those required for many veterinary medicines are highly complex. This is particularly true of products with active ingredients administered via animal feed. Often, feeds and premixes are based on natural products such as grains, which can be variable by their nature. This can present challenges in developing sufficiently specific test methods. Grains sourced from different locations may have taken on different levels of components from various soil compositions. Therefore, new interferences can appear during product analysis.
Additionally, premixes often contain high levels of vitamins and minerals, potentially interfering with the separation and detection of analytes of interest. During method development, scientists must use sample extraction and clean-up techniques such as Solid Phase Extraction (SPE) to maximise the specificity of the method, which can help address these issues. Additionally, many medicines for companion animals (such as cats and dogs) may require complex flavourings to ensure the product is enticing enough to consume. Complex flavourings can introduce significant challenges when developing methods employing chromatographic separation.
The variety of dosage forms required for veterinary products is vast. Some products are delivered as pastes, which can make accurate and precise measurement difficult given their highly dense and sticky nature. The right choice of solvent becomes essential to disperse the paste, and dissolve the active
ingredient and any impurities to allow accurate quantitation. Granular and feed products may be prone to settling and segregation during transport and handling, so developing robust procedures for homogenisation and sampling are also critical to establishing a reliable testing method.
Manufacturers must consider all possible dosage forms in which the drug may be delivered during method development. There may be a requirement to analyse the active as a raw material even where the final delivery may be in the form of feed in an intermediate premix product.
An additional challenge relates to sourcing reference materials. Although this is rare, when a product is not medically relevant to humans, suitable reference materials can be challenging to source. Appropriate reference materials are critical to ensuring accurate quantitation of the analytes of interest in the product.
How stability data is evaluated depends on the type of study and its objective. Therefore, data evaluation should be considered on a case-by-case basis and defined upfront in the stability study protocol. Similarly, the point in time when the data is assessed is also important. Short-term stability tests, such as excipient compatibility, may be assessed at the end of the study when all the data can be reviewed as a single data package. However, for longer-term stability studies where stability time points are months apart, it is critical to evaluate the data at each time point to determine any changes in the product and assess the potential risk of that change on the subsequent time points.
When manufacturers perform stability studies early in product development, such as when assessing excipient compatibility, there is usually no specification for comparison against stability study data. These tests are usually performed as exclusionary studies to rule out certain excipients based on the degradation profile. As such, the data evaluation can be relatively simple and limited to comparing assay value and degradation profile across excipients.
Stability data generated at the long-term storage conditions can help when proposing a retest period or shelf life longer than the period of stability data generated through extrapolation. In other words, 12 months of real-time data may substantiate 24 months of real-time storage on the pre-requisite that no change is observed in the data sets at accelerated and longterm stability storage. Additionally, stability data generated at accelerated storage conditions may be used to substantiate
the long-term stability of the product not yet generated through extrapolation, i.e., six months of accelerated data may substantiate 12 months of real-time storage. Manufacturers can use this approach if no change has been observed under accelerated conditions. They can also perform statistical data analyses to contribute to shelf-life justifications where notable changes have been observed.
To perform more detailed testing of veterinary animal health products, businesses have started using more advanced analytical equipment, and it is becoming common to commission independent testing, rather than conduct it inhouse. Often, manufacturers will turn to third-party partners for both technical and regulatory support, to streamline the process of bringing animal health veterinary products to market and obtain data that demonstrates safety.
Stability testing is vital for characterising and understanding drug substances and products. Working with an experienced analytical testing partner, like Broughton, from the project’s outset can help manufacturers design stability studies tailored to their veterinary health product and the intended application. For more information, visit Broughton’s analytical and testing services page.
1. https://www.gov.uk/guidance/veterinary-medicines-regulationsannex-ii-requirements/section-iiib
Operations Manager Beccy oversees all laboratory activities and works with her team to deliver excellent customer satisfaction whilst continuously striving to improve current processes and laboratory efficiencies. Beccy studied a BSc (Hons) in Chemistry with Pharmaceutical and Forensic Science from the University of Bradford and joined Broughton in 2009 as a Scientist. During her career, Beccy has gained experience testing a wide variety of products for both the human and veterinary pharmaceutical markets, gaining product knowledge and troubleshooting experience. Beccy works closely with customers to understand their testing requirements and individual business needs to help these be achieved.
Silage quality poses a complex challenge, impacting the nutritional value, safety and effectiveness of feed. Base nutrition is determined by forage type and harvest timing, with further feed value influenced by managing air and microbiology during fermentation, storage and feed out. In fact, effective silage storage is just as vital as ensiling. Damage to the plastic cover – whether standard, vacuum or oxygen barrier – can allow air to enter, changing the silage’s microbiology and fermentation characteristics. This can lead to the production of moulds, mycotoxins and undesirable acids, resulting in greater losses and reduced palatability.
Mycotoxin Influence on Silage Quality Mycotoxins are detrimental to silage quality because they can contaminate feed, leading to reduced nutritional value, compromised animal health and decreased feed intake.
The Alltech Harvest Analysis, a decade-long global initiative, is a comprehensive step in understanding the complexities of new crop quality and mycotoxin prevalence worldwide. The programme captures trends and enables robust data comparisons across years and regions. This analysis plays a pivotal role in empowering feed and livestock producers with the knowledge they need to make informed decisions.
The Effect of Weather Conditions on Global Harvest Environmental conditions significantly influence mycotoxin contamination in crops. The most important factors for mould growth, development and mycotoxin contamination are temperature and humidity during crop development.
Recently, Europe has experienced varied weather conditions impacting the harvest. Regions marked in green and dark green indicate areas with heavy rainfall, which may delay harvest. Conversely, areas in orange and red are experiencing hot and dry weather, which favours aflatoxin production in corn.
France and Romania may be affected, as they produce a lot of corn and have experienced high precipitation. This environment is conducive to Fusarium species, which produce mycotoxins such as deoxynivalenol (DON), T-2 and HT-2 toxins, zearalenone (ZEN), fumonisins (FUM), and emerging mycotoxins.
Contrarily, many regions such as southern Hungary are experiencing very hot and dry weather, which is ideal for Aspergillus flavus, a producer of aflatoxins. Similarly, Spain is very hot and dry, and as in previous years, a high incidence and significant levels of aflatoxins are expected.
This year in the U.S., recent observations in the Midwest show promising corn crop conditions with regional variations. From
Indianapolis to northern Illinois, the corn is progressing well, with most fields tasseled and ample rainfall. Northern Illinois into Iowa also looks good but with less tasseling and more maturity variation. Iowa and Minnesota show delayed maturity due to earlier wet weather.
Stay tuned for further updates on crop conditions and mycotoxin risks as the Harvest Analysis Programme continues.
Given the potential risks posed by mycotoxins and other fermentation issues, regular testing of silage is essential to ensure feed quality and safety. Regular silage testing is essential for dairy farmers aiming to maximise milk production from forage. Especially as winter approaches, analysing silage helps determine the exact supplementary feed needed, ensuring optimal nutrition and cost efficiency.
Key components to test include:
• Dry Matter Digestibility (DMD): Measures the percentage of digestible organic matter, indicating usable energy. Higher DMD can reduce the need for additional concentrate feeds.
• Dry Matter (DM): Indicates the actual nutritional content. High DM promotes intake, but excessively dry silage can lead to mould and heating issues.
• Crude Protein: Reflects the quality of the grass at harvest. Higher protein content reduces the need for supplementary protein, lowering feed costs.
• Metabolisable Energy (ME): Represents the energy available from silage. Higher ME supports better milk production.
• pH: Indicates silage acidity and fermentation quality. Proper pH levels ensure silage stability and feed intake.
By also testing these components, farmers can fine-tune their feeding strategies, improving herd health and farm profitability. Silage testing provides crucial insights to enhance forage quality and maximise returns.
Based on the analysis above, Alltech’s experts can provide tailored advice on enhancing silage management, from harvesting and storage techniques to inoculant selection.
Even the best-managed silage can sometimes become spoiled or contaminated. An effective silage inoculant provides extra protection by enhancing the fermentation process, improving nutrient retention, and ensuring feed quality over time.
Silage inoculants come in three main types:
• Homofermentative inoculants maximise dry matter and nutrient retention.
• Heterofermentative inoculants or those combined with salts are ideal for early opening or slow feed out, as they reduce heating despite lower dry matter retention.
• Combination inoculants balance efficient fermentation, early opening and long-term stability.
With Alltech’s leading-edge Egalis® range of silage inoculants, fermentation is controlled by high-specification homolactic bacteria and broad-spectrum inhibitory salts. Egalis technologies include:
• Egalis® Ferment: Ideal for all forages, this solution harnesses the combined power of Lactiplantibacillus plantarum and Pediococcus pentosaceus to rapidly achieve a stable final pH, regardless of dry matter or buffering capacity.
• Egalis® Rapid: Designed for maize/corn and sorghum silage, Egalis Rapid employs Pediococcus pentosaceus and Lacticaseibacillus rhamnosus to drive lactic fermentation while maintaining dry matter and palatability.
• Egalis® Stability: Suitable for all forages, especially highdry-matter silage at higher risk of heating, this technology uses Lactiplantibacillus plantarum, Pediococcus pentosaceus and potassium sorbate to inhibit yeast and mould growth, bolstering silage stability during feeding.
Based in Hungary, Hunland Group is a global leader in livestock farming, managing 38,000 cattle, including fattening cattle, calves, dairy cows and breeding heifers. Committed to innovation and sustainability, Hunland Group leverages advanced farming techniques and partnerships with industry leaders like Alltech to enhance feed quality and efficiency.
Since implementing Egalis Ferment, Hunland has seen remarkable improvements in feed production efficiency and cost management. Simply by adding this one Alltech solution to preserve nutritional content and prevent losses, Hunland is creating significant cost savings.
“By achieving such high nutritional content in the product, we were able to reduce the cost of the feedstuff per unit, which is essential for me,” says Zoltán Guti, production director at Hunland. “We place a huge focus on this, aiming to store and preserve the feedstuff with high nutritional content with minimal losses. This helps to reduce the need for additional feed supplements in the total mixed ration (TMR), thereby reducing our costs and the cost per kilogram of feed for milk production.”
Effective silage management is the cornerstone of maximising feed efficiency and nutritional value. By meticulously overseeing each stage, farmers can significantly enhance their silage quality and overall farm productivity.
Alltech recognises the need to holistically support producers, ensuring that animals receive the best nutrition every day. The company’s programmes and technologies, such as mycotoxin testing, in-vitro ration analysis, nutritional technologies and expert technical support, combine to meet the growing demands of modern livestock production.
For more information on Egalis and other Alltech solutions and services, visit https://www.alltech.com/egalis, or contact your local Alltech representative for farm-specific advice.
Gordon Marley oversees all silagerelated technologies and services at Alltech. Managing the EGALIS projects across Europe, he previously served as the Global Sil-All Manager, showcasing his wealth of knowledge and expertise in the field in over 45 countries through practical support and training as well as developing condition specific formulations. Gordon holds professional qualifications in Biology and Microbiology as well as being a cow signal trainer and a master black belt in six sigma. With over 30 years professional experience in the silage field Gordon has positively influenced dairy and beef producers, improving feed conversion efficiencies and farm profitability along the way.
In the evolving field of veterinary medicine, the need for innovative treatments for parasitic infections in pets is more pressing than ever. Parasites such as ticks, roundworms, hookworms, and pinworms are persistent threats to animal health, demanding solutions that are both effective and easy to administer such as oral palatable chewable tablets.
The development of these treatments is a complex, multifaceted challenge that requires not just scientific expertise but also sophisticated manufacturing capabilities. This is where Contract Research and Development Manufacturing Organisations (CRDMOs) play a crucial role, offering a unique blend of research, development, and manufacturing services that can significantly accelerate the delivery of new therapies to the market.
The role of CRDMOs in the pharmaceutical industry, particularly in animal health, is becoming increasingly important as the demand for specialised treatments grows. These organisations offer a strategic advantage by providing end-to-end services, from initial research and development through to large-scale manufacturing. This model allows veterinary pharmaceutical companies to leverage the specialised expertise of CRDMOs, accessing cutting-edge technology and innovative solutions without the need for significant in-house investment.
In the context of anti-parasitic drug development, the challenges are particularly acute. Developing a drug that can effectively target multiple parasites often involves combining several active pharmaceutical ingredients (APIs) into a single formulation. This process requires not only a deep understanding of the pharmacological interactions between these ingredients but also sophisticated techniques to ensure stability, efficacy, and palatability – especially in veterinary medicine, where patient compliance can be difficult to achieve. Moreover, the regulatory landscape for veterinary drugs is becoming increasingly stringent, with higher standards for safety, efficacy, and environmental impact. CRDMOs are well-equipped to navigate this complexity, offering tailored solutions that meet both regulatory requirements and market demands. By partnering with a CRDMO, veterinary pharmaceutical companies can accelerate their development timelines, reduce costs, and mitigate risks, all while maintaining the highest standards of quality.
One company that exemplifies the potential of CRDMOs in this space is Syngene, a leading CRDMO that recently developed an innovative and complex multi-antiparasitic drug formulation for a prominent animal healthcare company.
Syngene partnered with a leading animal health company to deliver a ‘first-in-class’ complex formulation that could treat a range of parasitic infections in dogs, including ticks, roundworms, hookworms and pinworms. The complexity of this task lay in the need to combine multiple APIs into a single tablet, each with its own chemical properties and stability concerns. In addition, the formulation had to be palatable to
ensure that dogs would willingly consume the medication, a critical factor in the treatment’s overall effectiveness.
The technical challenges were significant. One of the APIs was highly prone to degradation under acidic conditions, posing a risk to the drug’s long-term stability. Syngene’s approach involved conducting extensive drug-to-drug and drug-to-excipient compatibility studies, which were crucial in ensuring that the APIs could coexist without compromising the drug’s efficacy. These studies included preparing prototypes and subjecting them to stressed stability tests to quickly identify and mitigate potential issues.
Beyond the scientific challenges, the need for a palatable formulation required Syngene to explore various flavour profiles that would appeal to dogs without destabilising the drug. The bitter taste of one component was masked by appropriate polymer selection. This aspect of the project highlights an important trend in veterinary medicine: the shift towards patient (or pet) centricity. By considering the behavioural aspects of animal patients, CRDMOs like Syngene are helping to redefine what successful drug development looks like in the veterinary field.
Syngene also demonstrated its strength in process development and scale-up, ensuring that the final formulation-maintained content uniformity across all tablets, even with one API present in a very low dose. This level of precision is critical in veterinary medicine, where dosage accuracy can directly impact the effectiveness of the treatment. The successful scale-up of the manufacturing process, from development to clinical supply production, was completed in just six months – a testament to Syngene’s efficiency and expertise.
As veterinary medicine evolves, the complexity of developing multi-functional, stable and palatable drug formulations is a challenge that not all organisations are equipped to handle. While many CRDMOs can provide standard services, what distinguishes the truly innovative players in this space is their ability to address unique scientific and technical hurdles. In this case, Syngene's deep expertise in managing complex drug formulations – particularly its ability to stabilise multiple APIs and ensure both content uniformity and palatability – demonstrates how sophisticated CRDMOs can play a pivotal role in advancing veterinary care. Rather than simply filling capacity gaps, Syngene brings a
solutions-oriented approach that integrates cutting-edge R&D with scalable manufacturing, ensuring that even the most challenging formulations meet the highest standards of safety and efficacy. This level of innovation and precision is essential in today’s veterinary pharmaceutical landscape, where the stakes for timely and effective treatments are higher than ever.
The collaboration between Syngene and its client on this multi-antiparasitic drug formulation highlights how CRDMOs can drive meaningful advancements in veterinary medicine. This project underscores the importance of bringing together scientific expertise, innovation, and agility to overcome complex challenges in drug development. As veterinary health needs evolve, so too must the approach to developing treatments that are not only effective but also accessible and well-tolerated. Syngene's success in creating a complex, multi-drug solution serves as a reminder that strategic partnerships are essential to pushing the boundaries of what’s possible in animal healthcare, enabling the industry to deliver next-generation treatments that improve the lives of pets and the people who care for them.
Alex is the Senior Vice President, Manufacturing Services at Syngene International and has three decades of experience in developing, commercialising and life-cycle management of products in various life science industries. Holding positions in both the US and Europe at Syngene International, his experience includes senior roles with global P&L responsibility. As a member of the Executive Committee, Alex plays a techno-commercial role, providing technical expertise to the API plant at Mangalore while building a sustainable client base for the business in collaboration with the commercial and business development teams. In addition, Alex is also responsible for biologics operation at Syngene International.
Gut health in livestock is a cornerstone of animal husbandry, influencing not only the health and productivity of the animals but also the sustainability of farming practices globally. A well-functioning gut ensures efficient digestion and nutrient absorption, supports a robust immune system, and enhances the animal's ability to resist diseases. Recent advancements in microbiome research and innovative feed compositions, such as those incorporating specialised microbiomes, offer promising solutions to enhance gut health and reduce reliance on antibiotics. This article explores the critical role of gut health in livestock and examines how novel feed compositions based on the approach of the effect of microbiota on intestinal health can make a significant difference.
The Role of Gut Health in Livestock
Gut health is a fundamental aspect of livestock management that significantly influences the overall health, productivity, and welfare of animals. The gastrointestinal tract, often referred to as the gut, plays a crucial role in various physiological processes, making its health paramount for the efficient functioning of livestock.
The primary function of the gut is to digest food and absorb nutrients. A healthy gut ensures that feed is broken down efficiently, allowing for maximum nutrient absorption. This is essential for the growth and development of livestock. When the gut is functioning optimally, animals can convert feed into energy and body mass more effectively, leading to better growth rates and improved feed efficiency. This not only enhances the productivity of the animals but also reduces feed costs for farmers. All standard feed is developed based on the optimised utilisation in the gut.
In addition, the gut is a major component of the immune system. It houses a large number of immune cells and beneficial microorganisms that help protect the body from pathogens. A balanced gut microbiota supports the development and function of the immune system, making animals more resilient to infections and diseases. By maintaining a healthy gut, livestock can better withstand environmental stressors and pathogen exposure, reducing the need for medical interventions such as antibiotics.
When the gastrointestinal tract is able to maintain a healthy gut microbiome it acts as a barrier against harmful pathogens. Beneficial bacteria in the gut compete with pathogenic microorganisms for nutrients and attachment sites, preventing the colonisation of harmful bacteria. This natural defense mechanism reduces the incidence of gastrointestinal diseases and other infections. Consequently, animals with a healthy gut are less likely to suffer from illnesses, leading to lower mortality rates and improved overall health.
Gut health can also influence the behaviour and welfare of livestock. Animals with a healthy gut are generally more comfortable and less stressed. Digestive discomfort or diseases can lead to behavioural changes such as reduced feed intake, lethargy, and increased aggression. By ensuring
gut health, farmers can promote better welfare and more stable behaviour in their livestock, which is crucial for ethical and sustainable farming practices. A Healthy gut function contributes to more efficient feed utilisation, which can have positive environmental implications. When animals digest feed more efficiently, they produce less waste, reducing the environmental footprint of livestock farming. This is particularly important in the context of sustainable agriculture, where minimising waste and optimising resource use in line with lowering the carbon footprint are key goals.
In summary, gut health is a critical factor in the overall health and productivity of livestock. It affects nutrient absorption, immune function, disease resistance, behaviour, and environmental impact. Maintaining a healthy gut through proper nutrition, management practices, and innovative feed compositions can lead to healthier, more productive animals and more sustainable farming operations. As research in this field continues to advance, the importance of gut health in livestock will only become more evident, highlighting the need for ongoing attention and innovation in this area.
Maintaining gut health in livestock can be challenging due to several factors. First of all, sudden changes in diet can disrupt the gut microbiota, leading to digestive issues and reduced feed efficiency. But also, stress can negatively impact gut health too. Transportation, weaning and environmental changes can cause heavy stress to the animals with consequences that are difficult to calculate when it comes to the microbiota.
The most negative influence on deterioration of gut health is the antibiotic use. Livestock are often exposed to various pathogens that can compromise gut health and overall productivity, but once those have to be treated with antibiotics these can further disrupt the gut microbiota, leading to imbalances and increased susceptibility to infections, starting the downward spiral for a healthy gut.
Maintaining gut health in livestock is a complex and multifaceted challenge that requires careful management and attention to various factors. The gastrointestinal tract of livestock is not only crucial for nutrient absorption and digestion but also plays a significant role in immune function and overall health. One of the most significant challenges in maintaining gut health is managing dietary changes. Livestock often experience changes in their diet due to seasonal variations, availability of feed, and changes in production stages (e.g., weaning, finishing). Sudden changes in diet can disrupt the gut microbiota, leading to digestive issues such as diarrhoea, reduced feed efficiency, and overall poor health. Gradual transitions and careful formulation of diets are essential to minimise these disruptions and maintain a stable gut environment.
But also, stress is a major factor that can negatively impact gut health in livestock. Stressful conditions such as transportation, handling, weaning, and environmental changes can lead to a condition known as “stress-induced dysbiosis,” where the balance of gut microbiota is disturbed. This can result in decreased immune function, increased
Less interactions of drug molecules and formulations with the inner glass surface
• Optimized lyophilization process (less fogging)
• Reduced risk of glass delamination
Water for injection | Aqueous NaCl solution Lower pH shift
• Reduced risk of glass delamination
susceptibility to infections, and poor growth performance. Implementing stress-reducing practices, such as gentle handling, providing comfortable housing, and minimising abrupt changes, can help mitigate these effects.
Finally, livestock are frequently exposed to various pathogens that can compromise gut health. Pathogens such as Salmonella, E. coli, and Clostridium can cause severe gastrointestinal diseases, leading to high morbidity and mortality rates. Maintaining biosecurity measures, such as proper sanitation, vaccination programmes, and controlled exposure to new animals, is crucial in preventing the introduction and spread of these pathogens.
Having said that, the use of antibiotics in livestock production has been a common practice to prevent and treat such infections. However, overuse and misuse of antibiotics can disrupt the gut microbiota, leading to imbalances and increased susceptibility to infections. Moreover, the development of antibiotic-resistant bacteria is a growing concern. Reducing reliance on antibiotics through alternative strategies, such as improved management practices, vaccination, and the use of natural feed additives, is essential for maintaining gut health and addressing antibiotic resistance.
Environmental conditions, including temperature, humidity, and housing, can too significantly impact gut health. Extreme temperatures can stress animals and affect their feed intake and digestion. Poor housing conditions, such as overcrowding and inadequate ventilation, can increase the risk of disease transmission and stress leading again to a higher usage of medication starting the downward spiral for a healthy gut. The quality of feed and the presence of contaminants can also pose challenges to gut health. Poor-quality feed, contaminated with mycotoxins, pesticides, or other harmful substances, can damage the gut lining and disrupt the microbiota. Ensuring the use of high-quality feed ingredients, regular testing for contaminants, and proper storage practices can help mitigate these risks and support gut health.
Maintaining gut health in livestock is a dynamic and ongoing challenge that requires a holistic approach.
Addressing dietary changes, managing stress, preventing pathogen exposure, reducing antibiotic use, optimising environmental conditions, and ensuring feed quality are all critical components of a comprehensive gut health management strategy. By focusing on these areas, farmers and producers can enhance the health, productivity, and welfare of their livestock, leading to more sustainable and efficient farming practices. By continuing research and innovation in this field it will inevitably further improve our understanding and thus, our ability to maintain gut health in livestock.
Innovative Solutions:
Microbiota and Specific Pathogen Free Feed Composition
Recent advancements in microbiome research have led to the development of specialised feed compositions designed to enhance gut health. These innovative feeds incorporate beneficial microbiomes that can significantly improve the health and productivity of livestock as they are formulated with specific strains of beneficial bacteria and other microorganisms that promote a healthy gut environment. By introducing these beneficial microbes, the feed helps maintain a balanced gut microbiota, enhancing nutrient absorption and immune function.5
In addition to this is that of Pre- and Probiotics. Prebiotics are non-digestible food ingredients that stimulate the growth of beneficial bacteria in the gut. Probiotics are live beneficial bacteria that can be added to the feed. Both prebiotics and probiotics play a crucial role in maintaining gut health and preventing the colonisation of harmful pathogens. Fermented feeds, on the other hand, are produced through the fermentation of feed ingredients, which enhances their
Distribution in % of Pododermatitis between the two stables (Control vs earthworm)
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nutritional value and introduces beneficial microbes. These feeds can improve gut health by promoting a balanced microbiota and enhancing nutrient absorption. Other Innovative feed compositions, include specific pathogenfree (SPF) components like worms and vermicompost. These components are free from harmful pathogens and help inoculate the gut with beneficial microbiota, reducing the need for antibiotics.
In 2022 a patent was published describing a highly innovative feed composition designed to improve the health and productivity of livestock by providing a pathogen-free diet based on a fully natural solution. The feed composition includes live worms (dendrobena veneta) that are free from harmful pathogens such as Salmonella, Campylobacter, and Histomonas meleagridis. The inclusion of SPF worms in the feed provides a natural source of beneficial microbiota. These worms help inoculate the gut with positive microbiota, enhancing the overall microbial balance. Therefore, these worms serve as a natural source of beneficial microbiota.4 In addition, as fed alive and not as dried product, the feed enhances the mobility of animals and reduces stress factors by triggering instincts which leads to higher wellbeing factors and less aggressions. The feed also contains vermicompost, which is free from the same pathogens.
Vermicompost is rich in nutrients and helps improve the gut health of the animals. By including pathogen-free worms, the feed composition helps inoculate the gut of the animals with beneficial microbiota, enhancing their overall microbial balance and immune function.4 This feed composition has proven to reduce the need for antibiotics by improving the animals' natural resistance to infections through a healthier gut environment and, therefore, also addresses the issue of antibiotic resistance not only in livestock but also in humans. In addition, Livestock fed with this innovative feed composition show improved growth rates and overall productivity due to better nutrient absorption and a healthier gut. The feed composition can be used for various livestock, including poultry, swine, and cattle, to improve their health, growth rates, and overall productivity.4 This innovative approach addresses the critical issue of antibiotic resistance by promoting natural gut health and reducing the reliance on antibiotics in livestock farming.
Several studies have demonstrated the effectiveness of those specific pathogen-free feed compositions in improving gut health and productivity in livestock:
Research has shown that broiler chickens fed with SPF feed compositions exhibit lower mortality rates and better
Mortality (%) in birds receiving experimental diets across two runs (N=480)
growth performance compared to those on conventional diets. They are more active, show lower diseases rates and feather picking could be reduced. Also, the feed conversion rate significantly improved. In addition, the moisture in litter could be reduced, which even refers beyond animal health and welfare but towards reduction of carbon footprint of farms.
Studies on pigs have indicated that SPF feed compositions can enhance gut health, leading to improved weight gain and feed efficiency. Also, Ear-and Tail biting could be significantly reduced.
In cattle, the use of pathogen-free feed has been associated with reduced incidence of gastrointestinal diseases and better overall health. Although no animal protein (such as live worms and worm products) is allowed
to be fed, liquidised vermicompost contains the same microbiomes, leading to similar results as in Swine or Broiler chicken.
The development of innovative feed compositions like the one described in the above-mentioned patent represents a significant advancement in livestock nutrition. Future research and development should focus on exploring the use of SPF feed compositions in different livestock species and production systems to maximise their benefits conducting long-term studies to assess the sustained impact of these feed compositions on gut health, productivity, and antibiotic resistance.
In addition, evaluating the cost-effectiveness of implementing SPF feed compositions on a large scale to ensure their feasibility for farmers will be a key direction as well as ensuring that these innovative feed compositions meet regulatory standards and are approved for use in various regions.
Conclusion
Gut health is a crucial factor in the overall health and productivity of livestock. Innovative solutions like the specific pathogen-free feed composition described above offer promising benefits by enhancing gut health, reducing pathogen exposure, and minimising the need for antibiotics. As the livestock industry continues to evolve, such advancements will play a vital role in promoting sustainable and efficient animal production.
By focusing on gut health and embracing novel feed compositions, we can improve the welfare of livestock, enhance productivity, and address critical issues like antibiotic resistance and carbon footprint. Continued research and
development in this field will pave the way for a healthier and more sustainable future for livestock farming.
1. Ruminant microbiome data are skewed and unFAIR, undermining their usefulness for sustainable production improvement – Ortiz-Chura et al. Animal Microbiome (2024) 6:61
2. Multi-omics analyses reveal rumen microbes and secondary metabolites that are unique to livestock species – Victor O Emondi et al. – February 2024 Volume 9 Issue 2
3. Editorial: Microbiome genomics for livestock production – Bruno G. N. Andrade et al. – Frontiers in Genetics 09 September 2022
4. SPECIFIC PATHOGEN FREE FEED COMPOSITION – WO 2022/117691 Published 2022.
5. Microalgal-based feed: promising alternative feedstocks for livestock and poultry production – Imen Saadaoui et al. (2021) 12:76 - journal of animal science and biotechnology
Julia Katrin Rohde is CEO and cofounder of Corbiota GmbH, a spinoff of BASF. Prior to that, she held international strategy and commercial roles in start-ups and corporations. She worked in M&A for many years and co-founded the management consultancy advisoryteam, where she holds the role of a strategic leadership advisor in transformation projects. She holds degrees as biomedical engineer (Dipl. Ing.), economist (BA), psychologist (BSc) and economist (BA).
Historically, horses have been manipulated as ‘soulless machines’ whose useful characteristics may be expanded. In 1833, the Journal of the Franklin Institute described the expression ‘horse power’ as technically applicable “to any apparatus by means of which a horse is made to exert his power in propelling machinery.”1 In the late 19th century, a new use emerged and equine bodies were subjected to scientific appropriation as a material asset for modern immunology. Since then, equine blood has functioned as an essential raw material in the antivenom industry. Even so, or for this very reason, just as horses have been trapped in a nest of vampires, their dramatic and unequivocal contribution as blood suppliers has been left to oblivion. Equine use in the serotherapy industry remains the horse’s most disregarded role, a systematic exploitation of animal bodies and suffering that has been carefully erased from history. Today, the absence of specific criteria to detect equine injuries resulting from continuous injections of venoms and subsequent bloodletting continues to be a major problem in the antivenom industry. What are the limits of a horse's body? The answer to this question contributes to discussion on the connections between ethics, human-equine interactions and experimental techniques by examining antivenom production in Brazil, as well as related international challenges. With no intentions of exhausting the topic, this paper presents considerations that justify a greater commitment to the fate of horses serving the antivenom industry.
For 130 years, the conditions that serum-producing horses face has been a systematically neglected topic. These animals have been subjected to repetitive use in scientific experimentation, without adequate guidelines for managing the multiple impacts that the hyperimmunisation process has on their bodies. Although some improvements have been made, the current method of using horses to produce plasma follows the traditional model for producing anti-diphtheria serum, initiated in Europe in 1894.2
It consists of successive injections of toxins with adjuvants followed by bleeding to obtain hyperimmunised plasma for the production of antivenins, anti-rabies, antibotulism, and antitetanus serums. It was not until 2016 that the World Health Organisation Guidelines for the Production, Control and Regulation of Snake Venom Immunoglobulins recommended that the antivenom industry adopt ethical practices regarding the animals it uses.3 According to WHO Guidelines, monitoring of animals used to produce antivenom must include postmortem examination, necropsy and histopathology, allowing a careful analysis of causes of death which must, in turn, be made available for external review.
This commitment to transparency regarding the condition of seroproducing horses has not been assumed by the antivenom industry. Until now, animal welfare directives for horses used in the industrial production of hyperimmunised plasma have not established specific guidelines regarding production procedures. When they do exist, such guidelines are defined by the industry itself, comprising an obvious
conflict of interests.4 Official standards regarding the limit of blood that can be extracted, frequency of collection, and criteria to be observed to define when an individual should be removed from the program have not yet been established.5
The broad impact of this lack of official standards are quite significant. In 2021, according to the Research and Market report, the global antivenom market was valued at USD 1.08 billion in 2023 and is anticipated to project impressive growth in the forecast period, and is expected to reach USD 1,585.01 billion, in 2026. In such a workplace, millions of horses and other equids have been used as a source of raw material for serum as well as in experimental activities. This data does not cover other types of equine serum, such as anti-rabies, anti-diphtheria, anti-botulism, and anti-tetanus varieties. Neglecting to monitor the condition of horses used to produce antivenom is a silent ingredient of endemic crises involving snakebite. Since 2017, the World Health Organisation has added the latter to its list of neglected tropical diseases, mainly affecting rural populations in Africa, Asia and Latin America. The highly complex and inefficient production system of the worldwide antivenom industry remains a current challenge mostly within the poor countries of these regions.3
In Brazil, the equine serum industry faces a series of problems that have not been resolved over the last 130 years. In 2016, the Ministry of Health issued a not explaining that the distribution situation of anti-rabies and anti-venom serums had been faulty “due to constant rescheduling of deliveries caused by workers’ strikes, theft of animals, and problems in the supply of raw materials”.
It is worth highlighting that Brazilian hyperimmune serum was first subjected to specific regulation in 2017, through Resolution 187. The resolution, approved by the National Health Surveillance Agency, aims to guarantee the quality, safety and effectiveness of antivenoms and other equine serums. Since its implementation, the production of antivenoms has been suspended by three of the four public producers of horse serum. Currently, only the Butantã Institute continues to supply the public health system, significantly compromising the national supply of antivenoms and other sera. According to the aforementioned Resolution, registering a new hyperimmune serum requires a technical report with specifications on the side effects, adverse reactions, restrictions or precautions to be considered, as well as precautions and warnings, and product development history including pre-clinical and clinical trials, among others. Specific information must also be included on all stages of manufacturing, including the equine immunisation plan and the site where the source material or toxin injections, bleeding procedures, and rest period will take place.
In 2023, for the first time, complaints of animal welfare regulations violations were accepted by a court. Then, the Supreme Court of Delhi, India, upheld a legal complaint filed by the People for the Ethical Treatment of Animals (PETA) to protest the atrocious and illicit conditions to which horses used in the commercial production of antivenoms were subjected. The court's decision ordered responsible regulatory authorities
to conduct rigorous and continuous inspections to assess the welfare of these horses, as well as the immediate enforcement of punitive measures for violations of India's existing national welfare laws and regulations. It also mandated that the results of such inspections be transparent, ensuring public visibility.
Significantly, the court set a precedent by opining that “we can also not be oblivious to the dawn of cutting-edge, non-animal-centric techniques for antibody generation. Such advancements suggest a trajectory that these [serum] manufacturers might, and arguably should, consider in truth.” Further emphasising that “the responsibility is on the (federal government's) regulatory authorities to not just delve cursorily into these contemporary methodologies but to diligently adopt them, thereby diminishing reliance on equines.”
The evidence that supported this first legal decision in defense of horses used as a source of raw material for the antivenom industry can be found in the current antivenom production system that reproduces the method implemented 130 years ago. Successive regimes for injecting toxins and adjuvants, followed by the extraction of large volumes of blood, have severe and often fatal consequences for equines. Localised ulcers and abscesses on the spots where venom is injected, as well as thrombophlebitis from repeated venous punctures in the external jugular vein are the most obvious. Less visible, are the known systemic pathologies resulting from repeated injections of toxins, including chronic anemia, inflammation of the lymph nodes and inevitably, irreversable deterioration of the liver (amyloidosis) and kidney (amlyodosis), commonly
leading to organ rupture and agonising peracute death.4 ,6,7 Abdelkader et al identified advanced liver amyloidosis in the majority of the horses regularly immunised with live cultures of the endotoxin-releasing bacteria Escherichia coli or Pasteurella multocida, over periods varying from 2 weeks to 10 years.8
For John Locke, one of the early theorists of contemporary liberalism, humans acquire property rights over animals through their labour, reducing them to mere tools or assets. It is only recently that scholars have started to focus on the ethical claims of animal workers as part of interspecies justice.9 Horses and other species of the Equidae family, such as donkeys and mules, are the largest, and most exploited, group of non-human workers in capitalist and colonial development.
These species present a very specific feature of hiding or masking signals of and emotional reactions to pain. Hence, due to the absence of vocalisation or other perceptible reactions, consolidated beliefs assume that these species do not feel pain. This in fact is fallacious. Horses, as well as all ungulates, developed an evolutionary adaptation built as a defensive reaction against predators that is based on their physiological processes of pain reception. Any harmful response to an injury or pain may signal a potential victim. Therefore, emotional reactions to pain or other signs are not easy to pick up on.10 To undo this conflation of what is felt and how it is manifested, several studies have been conducted on horses to develop methods to identify and evaluate their
subtle signs and emotional responses to pain, as well as aspects of their physiological processes of pain reception.11,12 Until recently, most experimental animal injury studies have been conducted on primates and other mammals, such as cats, and dogs, but most often applying models based on work with rodents. This has hindered the comparison of certain behavioural, as well as cellular, biochemical and molecular mechanisms which were only based on experimental animal models.13
The history of modern serotherapy presents a longstanding tradition of intense instrumentalisation, exploitation, and degradation of horses in which equines figure not only as sources of hyperimmunised plasma but as objects of experimental activities. Unlike other forms of horse use, the system for exploiting the equine organism for the production of ativenes and other types of serum is based on invasive techniques for modifying and exploiting equine physiology. Under these conditions, clear evidence of the painful effects of such interventions emerges. Scientific literature is replete with findings that identify the countless damages that have been inflicted on these horses. It is noteworthy that, until now, horses, and mules as well, have been described as docile and easy to manage “objects” of antivenom production.
The Question Remains: Why is it so Difficult to Set Limits on the Use of Seroproducing Horses?
There is sufficient evidence that leads us to conclude that there is an urgent need to establish regulatory guidelines for the continued use of serum-producing horses as well as other equids. The greatest pressure falls on these horses in terms of ensuring (never reached) self-sufficient and efficient antivenom production at the national level, guaranteeing product quality in terms of producing a satisfactory level of antibodies. Concomitantly, equids are submitted to experiments that are carried out to test new serums, such as anti-covid and antizica serums, among others that have received wide media coverage. In this case, as experimental animals, horses are used repeatedly, normalising abusive practices as standards in the use of animals for scientific purposes, as established in Brazil and abroad.
The antivenom industry has a history of chronic neglect of good practices in animal welfare in which the entire range of specific interventions involving protocols of horse hyperimmunisation is neglected. To justify the lack of transparency regarding hyperimmunisation procedures, their protocol is often considered as ‘production confidentiality’, even though the standards that are currently in effect have, in essence, not moved beyond those developed in the last decade of the 19th century, when serotherapy was born inside stables.
In the end, horses have fascinated us not only because of their physical potential, in a technological sense, but due to the moral character of the aims and activities in which they are embedded. From a moral point of view, since the social context of their use is beneficial to us, it is deemed morally fit.14 How long such an argument will be enough to validate the uncountable injuries inflicted on horses by the antivenom industry, in the present?
1. Tarr, J. A. and Mcshane, C. (2008) The Horse as an Urban Technology, Journal of Urban Technology, 15:1, 5-17, DOI: 10.1080/10630730802097765.
2. Pucca, M.B., Cerni, F.A., Janke, R., Bermúdez-Méndez, E., Ledsgaard, L., Barbosa, J.E. and Laustsen, A.H. (2019) History of Envenoming Therapy and Current Perspectives. Front.
Immunol. 10:1598. doi: 10.3389/fimmu.2019.01598.
3. World Health Organization (2016). WHO Guidelines for the Production, Control and Regulation of Snake Antivenom Immunoglobulins. WHO Press, Switzerland.
4. Paludo, E. y Bones, V.C. (2023) Puntos críticos y posibilidades de mejora en el uso de équidos en la medicina moderna. Revista Latinoamericana de Estudios Críticos Animales, 9(2). https://revistaleca.org/index.php/leca/article/view/377.
5. Vilanova, X. M., De Briyne, N., Beaver, B., Turner, P. V. (2019). “Horse Welfare during Equine Chorionic Gonadotropin (eCG) Production”. Animals, 9, 1053.
6. Vilanova, X. M., Beaver, B., Uldahl, M., Turner, P. V. (2021). “Recommendations for ensur-ing good welfare of horses used for industrial blood, serum, or urine production”. Animals, 11, 1466.
7. Miranda, A.L.S.d.; Antunes, B.C.; Minozzo, J.C.; Lima, S.d.A.; Botelho, A.F.M.; Campos, M.T.G.; Chávez-Olórtegui, C.; SotoBlanco, B. (2023). The Health Status of Horses Used for at Least Six Complete Cycles of Loxoscelic Antivenom Production. Toxins 2023, 15, 589.
8. Abdelkader SV, Gudding R, Nordstoga K. Clinical chemical constituents in relation to liver amyloidosis in serumproducing horses. J Comp Pathol. 1991 Aug;105(2):203-11. doi: 10.1016/s0021-9975(08)80076-x. PMID: 1685737.
9. Blattner, Charlotte E., Kendra Coulter, and Will Kymlicka (2019) Introduction: Animal Labour and the Quest for Interspecies Justice. In Animal Labour: A New Frontier of Interspecies Justice? Blattner, Charlotte E., Kendra Coulter, and Will Kymlicka (ed.) Oxford, online edn, Oxford Academic, 23 Jan. 2020), https://doi. org/10.1093/oso/9780198846192.001.0001, accessed 19 July 2024.
10. Nekrasova, A. (2012) Endogenous mechanisms of modification of pain sensitivity in horses. In Equestrian sport: the secrets of the ‘art’. Nevzorova, L. (ed.) Nevzorov Haute Ecole: Charleston, USA, 131:140.
11. Andersen, Pia Haubro, Karina Bech Gleerup, Jennifer Wathan, B. Coles, Hedvig Kjellström, Sofia Broomé, Y. J. Lee, Maheen Rashid, Claudia Sonder, E. Rosenberg and Dennis Forster. “Can a Machine Learn to See Horse Pain? An Interdisciplinary Approach Towards Automated Decoding of Facial Expressions of Pain in the Horse.” (2018).
12. Kim, Su Min and Gil-Jae Cho. “Analysis of Various Facial Expressions of Horses as a Welfare Indicator Using Deep Learning.” Veterinary Sciences 10 (2023): n. pag.
13. Mert, Tufan (2007). Roles of axonal voltage-dependent ion channels in damaged peripheral nerves. European Journal of Pharmacology, Volume 568, Issues 1–3, 30 July 2007, Pages 25-30.
14. Maguire, R. and Ropa, A. (2021) Introduction: The Horse as a Liminal Being. in: Rena Maguire and Anastasija Ropa (ed.) The liminal horse: equitation and boundaries. Trivent Medieval, Book Series - Rewriting Equestrian History.
Ana Lucia Camphora is a Brazilian Psychologist and holds a Master Degree in Psycho-sociology of Communities and Social Ecology, and PhD in Social Sciences. Is the author of the book, 'Animals and society in Brazil from the 16th to the 19th century' (Brazil, 2017), which presents a pioneering overview of how colonial relations were constructed as interspecies relations. It’s English edition was launched in 2921 by The White Horse Press, UK. She is associated director of the Center for Contemporary Equine Studies (CA, USA), and since 2021 has developed studies on the use of equines as a source of raw material in pharmaceutical industry.
Everyone seems to be talking about integrating Artificial Intelligence (AI) into both personal and professional spheres. Smart tools are being developed to handle all kinds of tasks, especially where there’s access to substantial data. When processes become time-consuming and costly, the demand for AI solutions grows even stronger. In this article, we’ll explore how AI tools should be developed so that they could be beneficial specifically to the approval process under the European Food Safety Authority (EFSA) and how applicants might leverage AI tools to streamline and expedite the preparation of dossiers.
Experts widely recognise that obtaining authorisation for feed additives, novel foods, traditional foods, and similar socalled regulated products is not only time-consuming but also costly. The reasons are clear: consumers and manufacturers alike demand food for both people and animals that is safe and risk-free. Additionally, laws require that products are produced in ways that pose no risk to manufacturers or the environment (including animals), with strict monitoring in place. To assess these factors, numerous studies must be conducted and then reviewed through multiple, lengthy stages – resulting in a significant workload for regulatory authorities and applicants.
For the applicant of a new regulated product (e.g. a feed additive), there has been further complications since 2021 in addition to the already very time-consuming preparation of a dossier. The reason for that, was that the Transparency Regulation (EU) 2019/1381 came into force on March 27th 2021.1 The aim of this new regulation was to give consumers, authorities, policymakers, scientists, non-governmental organisations, and industry the opportunity to access and review publicly available scientific data on 'Open EFSA’.2 However, applicants for new regulated products have the right to keep certain parts of their dossier confidential. To exercise this right, each confidential section must be individually identified, with a justification for confidentiality provided for each request before submission. After submission, new discussions frequently emerge with the confidentiality assessment team regarding nearly every 'blacked-out' section. Ultimately, the final non-confidential version of the dossier is made publicly available, accessible to everyone –including competitors.
To reduce the significant workload, both applicants and the regulatory authority EFSA, would greatly benefit from smart solutions that streamline dossier preparation and review –while ensuring that all safety and confidential questions are thoroughly addressed.
But for utilising any kinds of machine learning data needs to be provided. Looking at the huge amount of data sources (research studies, literature, consumer feedback) that is being presented to EFSA by every submitted dossier, it should be possible to use AI solutions, like EFSA stated in its theme (concept) paper about the usage of AI in context of evaluating the risk assessment: ‘AI will reduce workload, gather and analyse more evidence, and improve the quality
of risk assessments’.3 As a possible impact for EFSA and its partners the following can be quoted: “Data is at the core of AI Applications: as such, any kind of labour where resources are spent to take in and process information to support decision making or recommendations can be replaced by AI”. 3 Gathering and analysing information to support decisionmaking is at the heart of EFSA’s work, as well as that of other regulatory agencies. Therefore, the impact of AI on EFSA’s activities will be substantial. But implementation of AI support into the authorisation work of EFSA needs to be well prepared.
With the integration of AI tools into the approval process, planned for 2027, questions arise about how the new system might accelerate approval times and benefit applicants. Alternatively, could other AI tools designed specifically for applicants further enhance the process' efficiency?
In 2022, EFSA released a concept paper outlining a vision of how AI could support the authority across a range of fields.3 That same year, an external scientific report was published, providing a roadmap for implementing AI in evidence management specifically for risk assessments.4 The external consultants evaluated the current state of AI technology and identified potential challenges and obstacles that authorities encounter when applying AI-based solutions. They also summarised that potential applications and benefits of AI include expanding and enhancing access to the body of evidence, as well as increasing confidence in risk assessments. The envisioned AI model is to be human-centered and designed to work in close collaboration with human expertise. EFSA aims to realise these objectives by 2027. To make this vision a reality, multiple steps will be needed to enhance data management. This involves considering not only current data but also anticipating and integrating future data flows. Establishing a tailored data infrastructure, tools to support Big Data and AI development, and a data governance framework that addresses AI – while considering people, processes, and policies – are essential steps toward building a more resilient structure aligned with EFSA’s organisational goals.4
The desired AI technology, which is to take over various steps of evidence-based management in the future, has not yet been established. The already existing AI-based tools or methods that would be potential candidates to be established at EFSA (including those that are commercially available) “require customisation, as they need to be trained on comprehensive subject-specific ontology”.4 This adaptation will increase the efficacy of both unsupervised and supervised AI tools. To find the perfect fit the open innovation approach was suggested to be useful. 6 The open innovation approach involves the strategic exchange of knowledge – bringing in external insights and sharing central ideas – to speed up internal innovation, while also considering opportunities to broaden market applications for new developments. EFSA should, therefore, be open to numerous collaborations and cooperations that promote the development and use of AI tools (Figure 1). Not only existing stakeholders are eligible for collaboration, but also those from academia, industry, other competent authorities, etc. since a few of them have already developed strategies
or services that can be useful for EFSAs internal processes. Some of those stakeholders might even have expertise in the evidence management using AI tools.
Looking back at the roadmap 4 the external consultant suggested the following deliverables for the year 2024:
• Adoption for a Data Infrastructure for Big Data and AI
• Implementation of a Development and Operation Management
• Adoption of a Trustworthy AI framework – Risk Management Framework
Ongoing training and upskilling of the current staff will be essential, especially in the coming years. By the end of 2027, the consultants who developed the roadmap envision EFSA as having established the foundational capabilities needed to integrate AI into the organisation. This includes not only establishing the technical tools to responsibly manage, control, and utilise AI, but also fostering the required skills and cultural shift. Additionally, EFSA is expected to have implemented AI solutions across several applications, leading to a more efficient, effective, and automated evidence management process. The outcome is eagerly awaited, as the hope of a time-saving authorisation procedure is of great interest to both the authority and the applicant. As other international authorities also have to work with a large amount of data for assessments and there are always overlaps in the data with e.g. EFSA authorisations, the introduction of an AI solution could be advantageous not only at the level of one authority.
The basis for shared data utilisation would be 5:
• Accessibility of the data at any time
• Definition of a common storage location
• Specification of unique identifiers
• Introduction of a common terminology
Collaborations with Member States and Different Authorities
EFSA continually seeks new data sources to enhance and support scientific excellence. Exploring the potential uses of data from industry, academia, social media, and other sources requires careful evaluation of how these could be utilised and validated for specific applications. For each use, understanding data quality requirements is essential, and discussions on new data sources should include an assessment of these standards. For now, priority is being given to the consideration of incorporating data from various international agencies for risk assessment.
As noted, EFSA is considering involving various Member States and international agencies in developing AI tools to support evidence management. Member States are already mandated under different legislative requirements to report and share data with numerous national institutions, the European Commission, and a range of EU and international bodies, including the European Medicines Agency (EMA), European Centre for Disease Prevention and Control (ECDC), European Chemicals Agency (ECHA), European Environment Agency (EEA), World Health Organisation (WHO), Food and Agriculture Organisation of the United Nations (FAO), and the World Organisation for Animal Health (OIE). Since many of these organisations, or their subdivisions, have overlapping or similar roles, Member States often face duplicative reporting requirements, which increases workload and complicates data management.5
Transitioning from traditional data reporting and collection to real-time data access would allow for the immediate use of diverse data sources across various formats and locations – such as official controls, monitoring programmes, scientific research, and industrial and academic contributions – as they become available. Streamlining these requirements could reduce redundant reporting, simplify data formatting
and collection processes, and improve interoperability, thus enhancing the efficiency of data analysis and fostering innovation. A well-designed AI tool could be of significant value in effectively utilising these insights.
Perspective
Implementing AI tools is a time-intensive process, yet it holds significant promises. AI offers the potential to build tailored, reliable, and current bodies of evidence, examining these in a comprehensive, system-oriented way. Given the rapid pace of evidence generation, EFSA views AI as essential for managing vast and diverse datasets, helping address complex challenges like non-linear response interactions. Understanding the relationships among multiple interacting factors is a key objective to ensure that AI-based systems remain consistent and accurate. Involving several stakeholders and different authorities into this process might result into an even more efficient risk assessment and might lead to reduced studies and enquiries required for authorisation of a new regulated product.
Similar to the planning of the introduction of AI systems under EFSA, there is currently no corresponding intelligent tool that could support the creation of a dossier. However, software assistants are increasingly available that can identify and extract data from documents. It is conceivable that reliable AI tools will soon be available that can find data that, for example, will make it unnecessary creating own studies. Until now, finding relevant studies has always been a challenge, even for agencies that require data sharing (ECHA - European Chemical Agency). With a reliable AI tool which work close to human expertise companies that specialise in data trading, such as 4ReValue, could find relevant studies in an even more time-saving and efficient way. This would benefit customers of these companies, as finding an appropriate study not only saves applicants money but also reduces time and uncertainty about achieving the desired results. Access to such an AI solution would significantly lighten the workload involved in preparing a dossier.
As mentioned before the introduction of the transparency regulation has further complicated the creation of a dossier. But it is precisely in this context that companies are working on solutions, as can be read in the article “Confidentiality in European feed additive authorisation procedures: How AI can facilitate dossier handling and how temporal copyright transfer can help protect your data”.7 The main focus is that an AI driven software supports the automatic redaction and creates automatically the justification report.
At the moment, there is no major AI support for the preparation of dossiers, but perhaps the introduction of a large data network by EFSA and the development of AI tools specifically for certain areas of dossier preparation could soon lead to a significant reduction in the current workload.
AI applications will be the key to big data handling, meaning that any task focused on gathering and processing information for decision-making or recommendations could potentially be handled by AI services. Since EFSA and other agencies are primarily engaged in information processing to guide decisions, the potential impact of AI on EFSA’s operations is significant. As for now no AI tools are available, whether for EFSA nor the applicant. But solutions are on the rise. It will be worth to follow the next developments closely.
Looking ahead, attention should focus on the already existing activities of the European Open Science Cloud (EOSC), which strongly promotes the adoption of FAIR principles (findability, accessibility, interoperability, and reusability). Proposed by the European Commission, EOSC aims to provide 1.7 million European researchers and 70 million professionals across science, technology, humanities, and social sciences with a virtual environment offering open and seamless services for storage, management, analysis, and reuse of research data – bridging borders and disciplines by federating existing scientific data infrastructures currently scattered across EU Member States.5
1. Regulation (EU) 2019/1381 of the European Parliament and of the Council of 20 June 2019 on the transparency and sustainability of the EU risk assessment in the food chain and amending Regulations (EC) No 178/2002, (EC) No 1829/2003, (EC) No 1831/2003, (EC) No 2065/2003, (EC) No 1935/2004, (EC) No 1331/2008, (EC) No 1107/2009, (EU) 2015/2283 and Directive 2001/18/EC (Text with EEA relevance).
2. https://open.efsa.europa.eu/
3. European Food Safety Authority (EFSA), et al., 2022. Artificial Intelligence in risk assessment. EFSA supporting publication 2022:e200501. 8 pp. doi:10.2903/sp.efsa.2022.e200501
4. PwC EU Services & Intellera Consulting, 2022. Roadmap for action on Artificial Intelligence for evidence management in risk assessment. EFSA supporting publication 2022: EN-7339. 120 pp. doi:10.2903/sp.efsa.2022.EN-7339
5. EFSA (European Food Safety Authority), et al., 2020. Report of the Advisory Forum Task Force on Data Collection and Data Modelling. EFSA supporting publication 2020:EN-1901. 63 pp. doi:10.2903/sp.efsa.2020.EN-1901
6. Eelko K.R.E.,Huizingh; Open innovation: State of the art and future perspectives; Technovation; 2011
7. Schreiner, R. Confidentiality in European feed additive authorization procedures: How AI can facilitate dossier handling and how temporal copyright transfer can help protect your data, FeedMagazine, December 2024
The veterinarian Dr. Regina Ohlmann was working as a senior scientist in the consultancy company ‘Feed and Additives’, which exclusively serves the feed industry when she became interested in integrating AI into regular workflows. The founding of the data trading portal 4ReValue GmbH in May 2023 further fuelled this interest, as intelligent data processing from approval processes could significantly accelerate work and further reduce animal testing.
Email: ohlmann@4Revalue.com
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