Partners

The development, validation, and implementation of non-animal tests for quality control of vaccines require a coordinated dialogue and collaboration between the different stakeholders.

The VAC2VAC consortium includes twenty organisations from eight different countries including all relevant stakeholders:

Sciensano, JRC, Intravacc and BPRC)

ISSAGESSciensano)

  • regulatory agencies (MEB)

  • human and veterinary vaccine industry (SPGSKBioZoetis

MSD,  BIAH FRBoehringer IngelheimPfizer)

 

VAC2VAC facilitates efficient partnership whereby all members provide scientific, technical and regulatory know-how, with the aim of ensuring the successful development of innovative non-animal methods and the implementation of the consistency approach for vaccine quality control.

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Description

The European Vaccine Initiative (EVI) is a non-profit Product Development Partnership supporting the development of vaccines for diseases of poverty by bridging conceptual and operational gaps in translational research. EVI supports the strengthening of the vaccine R&D infrastructure in Europe, harmonisation, knowledge sharing and aligning of major vaccine R&D stakeholders. Areas of EVI's expertise in vaccine development from preclinical to clinical proof-of-concept include process development, development of quality control assays, optimisation of GMP production, selection of the most appropriate delivery system, development of formulation with adjuvants and early stage clinical development. EVI has extensive experience of more than a decade in coordinating in large scale infrastructure and collaborative research projects funded by the EC and other funding agencies during the last decade.

Role of EVI in VAC2VAC project

EVI is the project coordinator of VAC2VAC and is in charge of administrative-financial management, dissemination and communication. Moreover, EVI will contribute to the development, dissemination and implementation of Standard Operating Procedures (SOPs) for key assays; contribute to development and reference preparations and common reagents, contribute to the harmonisation and standardisation of methods and assays. Additionally, EVI will also contribute to the preparation of a roadmap and engagement of regulatory bodies.

Partner representative/s

Hilde Depraetere has a PhD in Biochemistry from KULeuven, and more than 15 years experience in regulatory affairs (vaccines), preclinical and assay development and research management in several private and public organisations.  Her professional career commenced in 1995 at the University of Leuven.  Before joining EVI, Hilde worked as a Senior Regulatory Affairs Consultant for European Drug Regulatory Affairs Consulting (EUDRAC) GmbH, prior to which she was from 2006 - 2013 in the global regulatory department of GlaxoSmithKline Biologicals (GSK) in Belgium, Thrombogenics, in Belgium and RSR Ltd., a diagnostic company in Cardiff, Wales.

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Description

The Austrian Official Medicines Control Laboratory (AGES OMCL) is member of the European Network of Official Medicines control laboratories. The main task of an OMCL is quality control of medicinal products on the legal market.

The AGES OMCL is part of the business segment Austrian Medicines and Medical Devices Agency (AGES MEA) of the Austrian Agency for Health and Food Safety (AGES). Fully owned by the Republic of Austria, AGES MEA is responsible for a variety of tasks such as issuing marketing authorization for medicinal products (human and veterinary), assessing the efficacy and safety of medicinal products and medical devices, market surveillance and inspection of manufacturers.

Role of AGES in VAC2VAC project

The AGES OMCL is mainly involved in the development of immunological assays for the consistency testing of vaccines. The main goal for the AGES OMCL within this project is the reduction, refinement and replacement of in vivo testing. The development of alternative, substitute and complementary assays will ensure the safety and efficacy of vaccines in the absence of in vivo tests. Additionally, the AGES OMCL will help to design and participate in collaborative studies to improve the acceptance of alternative methods.

Partner representative/s

Dieter Pullirsch is the coordinator of the Expert Group 'Vaccines and Plasma Pool Testing' within the AGES OMCL and he is expert in the European Pharmacopoeia Group of Experts 15V - Veterinary Vaccines and Sera.

 

Heidemarie SchindlHeidemarie Schindl is Head of the Department 'Analytics of Biological Medicinal Products' and she is an expert in the European Pharmacopoeia Group of Experts 15 - Human Vaccines and Sera.

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Description

Bavarian Nordic is a fully integrated biotechnology company focused on the development, manufacturing and commercialization of live-saving vaccines. The company has a diverse and growing portfolio of vaccines, supported by proprietary development, public-private partnerships and industry collaborations.

At Bavarian Nordic, we aspire to save and improve lives by developing innovative vaccines that are designed to unlock the power of the immune system. We are a global leader in smallpox vaccines and our commercial product portfolio contains market-leading vaccines against rabies and tick-borne encephalitis as well as an Ebola vaccine, licensed to the Janssen Pharmaceutical Companies of Johnson & Johnson. We are also committed to the development of a next generation COVID-19 vaccine based on an in-licensed capsid virus-like particle technology.

Bavarian Nordic was founded in 1994 and has been listed on the Nasdaq Copenhagen Exchange since 1998. Headquartered in Denmark and with operations in Germany, Switzerland and USA, the company employs more than 750 people.

Role of BN in VAC2VAc project

Bavarian Nordic will be involved in the validation of immunochemical methods. Personnel involved in the project has experience in the development, implementation and validation of immunoassays under GMP. Bavarian Nordic will support the project with the quality control department and the regulatory affairs department, located in Germany and Denmark.

Partner representative/s

Dr. Darja Schmidt (F) has been trained as biologist in the field of molecular cell biology and immunology. She received her PhD in Molecular Cell Biology at the Max-Planck Institute of Biochemistry, focussing on molecular mechanisms of post-translational modifications. Since 2007 she holds various positions within Bavarian Nordic, overseeing the testing of GMP and GCLP samples in various studies.

 

 

Photo: Markus ZwickDr. Markus Zwick (M) studied molecular and cellular biology at the Friedrich-Alexander University Erlangen Nuremberg. He did his master and PhD in immunology, the latter at the Ludwig-Maximilian University Munich focusing on dendritic cells and their role in immune homeostasis. He has experience in the implementation and validation of immunoassays and Quality Control of vaccines.

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Description

The Biomedical Primate Research Centre (BPRC) is an independent, not-for-profit research institute aiming to improve human health by understanding and fighting life-threatening diseases. The use of non-human primates to do so does not only come with the responsibility to maximize animal welfare and research quality but also to develop alternatives. BPRC has an active and expanding program to develop alternatives following the principles of reduction, refinement and replacement.

BPRC is certified for responsible environmental policy (ISO 14001/2004) and is internationally recognized for its animal welfare policy (AAALAC).

Role of BPRC in VAC2VAC project

BPRC participates by the development of physiochemical analytical methodology, by the development of immunochemical assays and we will utilize our library of bioassays that are based on mammalian cell lines to assess and standardize vaccine potency. This will all be done in the context of the development of alternative methods for animal tests that are currently in use in the approval process of traditional vaccines. The project fits seamless in the mission statement of BPRC in which the development of alternatives for animal research is one of the basics. With participation in VAC2VAC, BPRC establishes itself as a full partner in the development of alternatives for animal research.

Partner representative/s

Bart Faber (PhD, Department of Parasitology) is a biochemist that has been involved in protein subunit vaccine design, production and QA/QC for over 15 years. He will take part in the physiochemical and immunochemical assay development of protein vaccines.

Jeffrey BajramovicJeffrey Bajramovic (PhD, Alternatives Unit) is an immunologist and heads the Alternatives Unit.  He has helped to successfully develop innovative in vitro technologies, designer cell lines and bioassays to replace, reduce and refine the use of non-human primates in biomedical research. These assays will be utilized to make innate immune fingerprints of different vaccines, vaccine batches and vaccine components.

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Boehringer Ingelheim

Description

Improving the health and quality of life of patients is the goal of the research-driven pharmaceutical company Boehringer Ingelheim . The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients? lives. In animal health, Boehringer Ingelheim stands for advanced prevention.

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry?s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2017, Boehringer Ingelheim achieved net sales of nearly 18.1 billion euros. R&D expenditure, exceeding three billion euros, corresponded to 17.0 per cent of net sales.

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.

Boehringer Ingelheim is the second largest animal health business in the world. The company is committed to creating animal wellbeing through its large portfolio of advanced, preventive healthcare products and services. With net sales of ?3.9 billion and around 10,000 employees worldwide, it is present in more than 150 markets.

Role of Boehringer Ingelheim in VAC2VAC project

In line with other industry partners, Boehringer Ingelheim will provide technical support by product and process knowledge, including manufacturing operations as well as regulatory procedures. For the research, development and validation, this means generation and provision of samples dedicated to the specific needs. When an alternative method will be ready, the technical support will include the transfer of the method and the generation of in-house data. For validation and promotion to regulatory acceptance, we will share experience in regulatory documentation and contribute to define validation criteria, study design and facilitate the data-based discussion between stakeholders.

Partner representative/s

Dr. Elisabeth Kamphuis (International Regulatory Affairs Business Operations) has 10 years of experience at the Paul-Ehrlich-Institut, including 3Rs for rabies vaccine testing and corresponding European Pharmacopeia and OIE monograph revisions. At BI, she worked in Guadalajara, Mexico, and in Regulatory Affairs in Germany. Elisabeth leads VAC2VAC at BI.

 

Larry BondocDr. Larry Bondoc (Bioprocess Sciences) is involved in biologics development and manufacturing in the US for over 20 years, including biodefense (anthrax and botulinum) and commercial (chlamydia and H. pylori) vaccines. At BI, he works in St. Joseph, USA, on 3R alternatives and improvement to Quality Control testing. Larry co-leads work package 3 (Immunology).

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Boehringer Ingelheim Animal Health France (BIAH FR)

Description

Since January 1st, 2017, Merial is part of Boehringer Ingelheim .

Improving the health and quality of life of patients is the goal of the research-driven pharmaceutical company Boehringer Ingelheim. The focus in doing so is on diseases for which no satisfactory treatment option exists to date. The company therefore concentrates on developing innovative therapies that can extend patients? lives. In animal health, Boehringer Ingelheim stands for advanced prevention.

Family-owned since it was established in 1885, Boehringer Ingelheim is one of the pharmaceutical industry?s top 20 companies. Some 50,000 employees create value through innovation daily for the three business areas human pharmaceuticals, animal health and biopharmaceuticals. In 2017, Boehringer Ingelheim achieved net sales of nearly 18.1 billion euros. R&D expenditure, exceeding three billion euros, corresponded to 17.0 per cent of net sales.

As a family-owned company, Boehringer Ingelheim plans in generations and focuses on long-term success. The company therefore aims at organic growth from its own resources with simultaneous openness to partnerships and strategic alliances in research. In everything it does, Boehringer Ingelheim naturally adopts responsibility towards mankind and the environment.

Boehringer Ingelheim is the second largest animal health business in the world. The company is committed to creating animal wellbeing through its large portfolio of advanced, preventive healthcare products and services. With net sales of ?3.9 billion and around 10,000 employees worldwide, it is present in more than 150 markets.

Role of BIAH FR in the VAC2VAC project

BIAH FR, highly engaged in the 3Rs , brings to the VAC2VAC project experience and expertise in vaccines at different levels: testing on products and final batches, whole production process, innovative non-animal analytical tools, analytical development, validation and transfer and regulatory know-how. BIAH FR will also provide materials and reagents needed in the development of alternative, non-animal methods for consistency testing. This collaboration with the VAC2VAC consortium partners, including other vaccine industry partners, both human and veterinary, is an unique opportunity to implement science-based testing of our vaccines while reducing animal use.

Partner representative/s

Nathalie Moulian will facilitate and coordinate the interfaces (scientific, technical, reagents and materials) between the consortium partners and the BIAH FR experts.

Jacques Léchenet (Work Package 6)


Cécile Sigoillot-Claude (Work Package 1 & Work Package 2)

Hanane El Garch and Blandine de Saint-Vis (Work Package 3 & Work Package 4)

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Description

As the European Commission's science and knowledge service, the Joint Research Centre 's (JRC) mission is to support EU policies with independent evidence throughout the whole policy cycle. Its work has a direct impact on the lives of citizens by contributing with its research outcomes to a healthy and safe environment, secure energy supplies, sustainable mobility and consumer health and safety.

The European Commission's involvement in activities targeted to the validation of alternative approaches to animal testing started in 1991, with the launch of ECVAM (the European Centre for the Validation of Alternative Methods), hosted by the Joint Research Centre. As from 2011, ECVAM's tasks are assigned to the European Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM). EURL ECVAM coordinates the validation of alternative methods at the EU level, acts as a focal point for the exchange of information on alternatives, manages database services and ensures that the scientifically validated methods undergo a rapid procedure to gain regulatory acceptance.

Role of JRC in VAC2VAC project

The JRC represented by EURL ECVAM will participate in the project as leader of Work Package 5 being responsible for the tasks related to validation. The JRC will contribute to work package 6 with its experience gained in international dissemination, harmonisation and regulatory acceptance.

Partner representative/s

Dr Marlies Halder is a Senior Scientist at the European Commission's Joint Research Centre, Directorate F - Health, Consumers and Reference Materials, Chemical Safety and Alternative Methods Unit / European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) in Ispra, Italy. She is responsible for EURL ECVAM's activities on replacement, reduction and refinement related to the quality control of biologicals and environmental toxicity testing of chemicals.

Over the past 10 years, EURL ECVAM promoted the use of the consistency approach for the quality control of vaccines by sponsoring and co-organising three workshops and supporting activities at EPAA level.

"It is encouraging to witness the launch of the VAC2VAC project and eventually put the theory into practice."

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Description

GlaxoSmithKline Biologicals (GSK) is one of the world's leading vaccine companies, involved in vaccine research, development and production. We have 15 vaccines in development and our broad portfolio of 39 vaccines prevent illnesses such as hepatitis A, hepatitis B, diphtheria, tetanus, whooping cough, measles, mumps, rubella, polio, typhoid, influenza and bacterial meningitis. Globally, we have more than 16,000 people working to deliver nearly 2 (1.9) million vaccines every day to people in around 90% (172) of the world's countries. In 2015 we distributed around 690 million doses of vaccine, over 70% of them to less developed, low and middle income countries.

The role of GSK in the VAC2VAC project

GlaxoSmithKline Biologicals (GSK) is one of the industry partners of VAC2VAC contributing as member of the scientific management team and bringing the biggest in-kind contribution made available for the project. GSK is supporting, through its internal expertise, the development, optimisation and evaluation of physicochemical and immunochemical methods, cell-based and other assays for routine batch quality, safety and efficacy testing of vaccines according to the Consistency Approach. In addition, GSK will work towards a consensus with regulatory agencies on acceptance of the new methods developed that would significantly reduce the future use of animals for batch testing in routine vaccine production.

Partner representative/s

GSK's internal Quality and R&D experts on physicochemical and immunochemical methods, cell-based and other assays for routine batch quality, safety and efficacy testing of vaccines; its experts on Regulatory Affairs and Product Life Cycle Management will work to help to ensure that VAC2VAC reaches its goal.

Denis Lambrigts, Head of Vaccines Global Animal Welfare, Ethics and Startegy, 3R programme Lead.

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Description

The Association Internationale de Standardisation Biologique pour L'Europe (IABS-EU) was created in April 2014. Its objective is to support the mission and projects of the International Alliance for Biological Standarization, to enhance its image and to develop its outreach within the European Union. IABS-EU contributes to scientific and medical advancement of biologicals by facilitating communication among those who develop, produce and regulate biological products for human and animal health. More specifically, it focuses on issues concerning the regulation and satndardization of biological products that are intended for market use.

Role of IABS-EU in VAC2VAC project

IABS-EU is leader of Work Package 6. Its role is to define a roadmap for regulatory acceptance of the consistency approach with the goal to provide a basis for guidance on regulatory implementation of new tests developed for the consistency approach; and to facilitate discussion between different stakeholders on specific questions and issues that the introduction of the consistency approach might raise. In collaboration with all partners of the VAC2VAC project, IABS-EU will evaluate progress and gaps in its regular meetings, build consensus to fill gaps and communicate progress with regulatory agencies and relevant EMA committees/working groups for future implementation, reach out to regulatory authorities when project results are considered sufficiently concrete and robust by the group or specific guidance is required, reach out with work package members to EDQM, USDA, FDA, WHO SAGE, WHO, WCBS, OIE, ICH/VICH, JEG3rs, etc. when project results are considered to allow such discussions in order to maximise impact, organise meetings and congresses for presentation and discussion of resluts and publication in biologicals, other editions if needed as well as through social media.

Partner representative/s

Dr. Joris Vandeputte has 19 years experience in the vaccine industry as global business director and international regulatory affairs director (Merial). He now coordinates regulatory affairs in ZAPI, the IMI project on prepardness for zoonoses. Doctor in Veterinary Medicine, a virologist, he was researcher, developer and disease control specialist on flue (both human and animal) rabies, TB, Brucellosis, Hydatosis etc. Regulatory expertise: responsibility for product registration at Rhone-Merieux, later Merial, as Director of Regulatory Affairs and Product Registration for Merial International. Main achievements: pandemic and zoonoses preparedness, vaccine development and market access.

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Description

Originating from the Institute for Translational Vaccinology (Intravacc), Intravacc  B.V., a private company with limited liability (B.V.), was established on 1 January 2021. Intravacc B.V. is one of the world's leading organisations in translational vaccinology and continues to move forward with its vision and mission to reduce global disease burden through innovative technology.

Role of Intravacc in VAC2VAC project

Intravacc will be involved in developing physico-chemical and immunochemical models (Work Package 1 and Work Package 2) for conformational fingerprinting of protein antigens to ensure preservation of B-cell epitopes as well as immunochemical methods to monitor antigen degradation.

In addition, Intravacc will be leader of Work Package 3 and will as such coordinate the activities of the partners involved in this WP.  Within WP3, Intravacc will be involved in the development of a tetanus- or diphtheria toxoid-specific T cell hybridoma activation assay and a cell-based test to assess the toxicity of C. perfringens C non-inactivated antigen.  

In Work Package 4, Intravacc will focus on the investigation of the effects of canine Leptospira vaccines on APC using a systems immunology approach with the aim to identify biomarkers suitable for the determination of vaccine quality.  Once biomarkers are known, Intravacc will assist in developing specific assay in the context of WP3.

Partner representative/s

Dr. Bernard Metz received his master's degree in chemistry from the University of Groningen in 1998 and obtained his PhD on Structural Characterisation of Diphtheria toxoid at the University of Utrecht in 2005. He has an extensive track record in vaccine characterisation and assay development. He identified formaldehyde-induced modifications by mass spectrometry, discovering novel covalent modifications in proteins but also developed immunochemical and physicochemical assays that were predictive for potency. Besides this, his research interests are in the area of molecular biology and systems vaccinology.

 

Dr. Arjen Sloots obtained his PhD at the University of Frankfurt in 2004. His field of expertise is vaccine development, immunomodulation by bacterial pathogens and innate immunity. At Intravacc, he is responsible for Intravacc's 3R research activities and actively involved in the development of cell-based in vitro models for consistency testing of vaccines. Within the VAC2VAC project, he is the work package leader of Work Package 3 and a member of the Steering Committee.

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Description

The Istituto Superiore di Sanitá (ISS) is the leading technical and scientific body of the Italian National Health Service. ISS is the Italian Official Medicine Control Laboratory (OMCL) responsible for testing biological and chemical medicines within the network coordinated by the European Directorate for the Quality of Medicines and Health Care, Strasbourg, Fr (EDQM). The fields in which ISS is active range from medical/veterinary/food safety to technology, therapeutic, epidemiology and environmental issues.

The main tasks in all fields are research, control, certification, inspection, clinical trials and training. ISS is involved in the collaboration and consultation with other institutions responsible for the public health, including the Italian Agency for Drugs (AIFA), the Ministry of Health, regional health authorities, local health agencies and hospitals. ISS provides scientific advice and assessments in the framework of international organisations such as EDQMWHOECDEEFSAEMA.

Role of ISS in VAC2VAC project

ISS researchers will contribute their expertise to several tasks:

  1. They will be involved in the development and optimisation of an in vitro assay to determine the antigen content of avian infectious bronchitis vaccine (IBV) (which is widely used in poultry industry), which aims at replacing the current in vivo test. For this purpose, specific monoclonal antibodies will be obtained and characterised.

  2. ISS will contribute to the development and optimisation of cellular assays to analyse human tick-borne encephalitis virus vaccine (TBEV). In particular, traditional monocyte-derived DC (moDCs) or primary monocytes will be used to assess vaccine-induced activation and maturation of primary APC. In addition, monocyte activation tests will be performed to determine endotoxin content in vaccine preparation.   

  3. Furthermore, as OMCL and as experts are present in the European Pharmacopeia and Biotechnology Working Party, ISS will contribute to the development of a road map for the regulatory acceptance of the consistency approach.

Partner representative/s

Dr. Laura Campitelli has worked on human and animal influenza research and surveillance and participated in EU projects aimed at developing pandemic vaccines from field isolates to evaluate vaccine efficacy. More recently, the Campitelli research unit has focused on activities concerning batch release of viral vaccines, including the standardisation of release methods, as well as development of alternative potency assays for viral vaccines.

Dr. Eliana Coccia's research unit focuses on the mechanisms of cytokine expression regulation in human dendritic cells (DCs) upon pathogen encounter and the impact of these cytokines on anti-microbial immune response. More recently, Dr. Coccia is testing the strength of an in vitro model, represented by human DCs, for in vitro analysis of the immunogenicity of different vaccine candidates (Mycobacteriun tuberculosis and Staphylococcus aureus).

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Description

The Medicines Evaluation Board (MEB) assesses and monitors the efficacy, risks and quality of human and veterinary medicines, and the safety of novel foods for human consumption. The MEB is an independent administrative body residing under the Government of the Netherlands. The MEB independently decides about the authorisation and monitoring of human medicinal products.

Role of MEB in VAC2VAC project

MEB will contribute to the application and optimization of cellular assays based on analysis of vaccine-induced activation of antigen presenting cell (APC) and reporter cell lines and development of cell- or cell line-based assays for assessment of novel biomarkers identified. In these projects the MEB will work on assays for DTaP vaccine in collaboration with the RIVM.

Furthermore the MEB will contribute by proposing rational arguments for regulatory acceptance based on analysis and comparison of information obtained from the animal testing and the information from proposed set of alternative tests. Also a meta analysis will be performed of the information that the current testing (including in vivo test) yields and that the proposed testing will yield. The meta analysis is expected to reveal the different gaps in relevant information that the current (in vivo) and proposed testing strategies will have. This is expected to contribute to the argumentation for accepting the replacing testing strategy

Partner representative/s

Marcel H.N. Hoefnagel Ph.D. Senior Assessor Biopharmaceutical: Marcel Hoefnagel is a biochemist/biotechnologist who has been working as assessor of chemical-pharmaceutical assessment biologicals (with a focus on vaccines, allergens and cell-based therapies) since 2002. He is involved as an expert in several) working groups of the European Medicines Agency (EMA).

 

He has led several research projects including:

development of a in vitro assay for immunogenicity of biologicals;
5-year PhD student project at University of Utrecht (UU Group of W. van Eden) on immunological activity testing of vaccines and cell-based therapies.
He has (co-) authored 39 peer-reviewed papers, including a paper on in vitro testing of vaccines. 

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Description

Today's Merck is a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships.

MSD Animal Health, known as Merck Animal Health in the United States and Canada, is the global animal health business unit of MSD. Through its commitment to the Science of Healthier Animals, MSD Animal Health offers veterinarians, farmers, pet owners and governments one of the widest range of veterinary pharmaceuticals, vaccines and health management solutions and services. MSD Animal Health is dedicated to preserving and improving the health, well-being and performance of animals. It invests extensively in dynamic and comprehensive R&D resources and a modern, global supply chain. MSD Animal Health is present in more than 50 countries, while its products are available in some 150 markets. For more information, visit www.msd-animal-health.com or connect on LinkedIn.

Role of MSD in the VAC2VAC project

MSD is one of the industry partners participating in the VAC2VAC initiative.

MSD will support VAC2VAC by contributing technical, scientific and regulatory expertise to the research, development, validation and implementation of non-animal methods for Quality Control testing, as well as by providing materials and reagents needed in the development of alternative non-animals methods for consistency testing.

Participation in the VAC2VAC initiative underlines the company's commitment to the philosophy of using the best scientific methodologies and animal alternatives, and to promote the principles and practice of the 3 Rs - Replacement, Reduction, Refinement.

Partner representative/s

Imke Kross is a trained Veterinarian, who received her PhD in Molecular Biology in Berlin in 1993. She has been working in the areas of vaccine development, Quality Control of Vaccines and Biological Assay development and improvement for 20 years in Intervet International, Intervet Schering-Plough AH and MSD AH. She has been involved in the 3Rs for approximately 10 years, in particular in the development of alternative methods to replace animal testing for Quality Control testing.

 

Chris FarrellChris Farrell is a Biochemist who received his PhD in Pharmacology and Molecular Sciences from the Johns Hopkins School of Medicine, in Baltimore, MD, USA in 2005. After a brief postdoctoral Fellowship at Princeton University, NJ, USA, he began his career at Merck in West Point, PA, USA. Chris has been working in the Vaccine Bioprocess R&D group, specializing in biophysical characterization of vaccines to support clinical and Pre-clinical development. Chris is industry co-chair for WP1. 

M. Hartmann will contribute technical expertise to Work Package 1, J. Divelbess, H. Glansbeek and C. Vester will contribute to Work Package 2, P. Vermeij and Urs Bruderer to Work Package 3 and 4. M. Kaashoek will contribute Regulatory expertise to Work Package 6.

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Description

The National Insitute for Biological Standards and Control (NIBSC) is a centre of the UK Medicines and Healthcare Products Regulatory Agency (MHRA) which is an executive agency of the UK Department of Health. NIBSC is the UK Official Medicines Control Laboratory and a WHO International Laboratory for Biological Standardisation. Operating at the interface between scientific research, product development, regulation and policy, NIBSC's mission is to safeguard and improve public health through assuring the quality of biological medicines and provision of biological reference materials.

Role of NIBSC within the VAC2VAC project

NIBSC will be involved in the development and characterisation of in vitro methods and will lead on development of immunochemical methods. NIBSC will also provide expert advice for validation of methods and regulatory acceptance of non-animal methods.

Partner representative/s

The group at NIBSC involved in the VAC2VAC project is responsible for the control testing of diphtheria and tetanus vaccines and antitoxins and the development of biological standards for these products. Research interests include development and validation of in vitro immunochemical and cell based assays for the characterisation of vaccines, toxins and antitoxins.

NIBSC representatives for VAC2VAC are Dr. Paul Stickings, Dr. Thea Sesardic, and Laura Coombes.

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Description

The Paul-Ehrlich-Institut (PEI) is the German Federal Institute for Vaccines and Biomedicines and reports to the German Federal Ministry of Health (Bundesministerium f?r Gesundheit). It is a senior federal authority in the field of medicinal products providing services in public health.

The PEI assesses and monitors vaccines and biomedicines to ensure that all biomedicines available on the German and European markets have a favourable benefit-risk-ratio. These activities include the assessment of documents submitted, as well as experimental tests, such as batch release testing, and on-site inspections of manufacturing facilities. The PEI assess and monitors the benefit-risk balance before, during and after the marketing authorisation of biomedicines for human use and immunological medicines for veterinary use.

The PEI's own experimental research in the field of life sciences is an indispensable basis for the fulfilment of its duties.

Role of PEI in VAC2VAC project

In the VAC2VAC project, the research focus of PEI's involved groups is on Diphtheria-, Pertussis-, Tetanus- and Leptospira vaccines.

In a proteomic approach, a combination of liquid chromatography and mass spectrometry will be applied to tetanus toxoid and to an array of antigens from seed material to the final vaccine product of Leptospira vaccines.

In a cell-based assay, peripheral blood mononuclear cells will be used to quantify and characterize vaccine-induced activation of human B cells in response to a new vaccine batch. This response will be measured for example as proliferation or immunoglobulin production by means of flow cytometry, ELISpot or BrdU incorporation. The goal is to evaluate the feasibility and applicability of this approach for batch release consistency testing, especially assessing batch potency.

PEI will also contribute to elaborate guidance documents on validation and implementation strategies of the newly developed methods. Regulatory experts will be involved at all stages of discussion of data.

Partner representative/s

Dr. Elisabeth Balks is leader of Work Package 1. With 18 years of experience in OMCL batch control, she is responsible for the evaluation of alternative testing methods in "Product testing of Immunological Veterinary Medicinal Products". She has an active role in numerous collaborative studies and 3R research projects.

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Description

Pfizer is a international pharmaceutical company with the purpose of bringing breakthrough therapies to patients that significantly improve their lives. Pfizers belief is that all people deserve to live healthy lives and therefore employees worldwide are ?working on breakthroughs that change patients? live?. This drives the desire to provide access to medicines that are safe, effective, and affordable. Pfizer researches, develops and markets drugs and vaccines to treat or prevent some of the most threatening diseases of our time. Pfizer Manufacturing Austria GmbH is part of the Pfizer group based in Orth at the Danube in Lower Austria, close to Vienna. The site produces the drug substance for Pfizers worldwide demand of two vaccines against. One vaccine against early summer meningococcal encephalitis ? TBE and one vaccine against meningitis caused by serogroup C meningococcus ? MenC. Approximately ten million vaccine doses are produced every year. Pfizer Manufacturing Austria also provides Quality Control and Analytical Development on site.

Role of pfizer in VAC2VAC project

As industry partner Pfizer Manufacturing Austria participates in the VAC2VAC initiative by contributing comprehensive scientific expertise in the field of human vaccines in development of an in vitro potency assay.

Furthermore Pfizer provides technical and regulatory expertise by offering wide-ranging experience in method development, qualification and transfer, process-related investigations, small scale process development as well as regulatory submissions.

Pfizer's expertise in developing an in vitro potency lot-release assay based on ELISA method to replace animal testing will significantly support the initiative's goal of developing non-animal alternatives.

By constantly working on 3R's (replace, reduce and refine) animal testing,  Pfizer's participation in VAC2VAC emphasizes the company's commitment to deliver first-in-class science by knowledge investment and cross-border cooperation to advance science-based testing.

Partner representative/s

Annett Hessel, PhD

Annett obtained her MS in Biology in 2006 (Faculty of Biosciences, Pharmacy and Psychology/University Leipzig/Germany). She joined the Molecular Vaccines/Virology R&D group at Baxter and graduated with a PhD in Medical Science in 2011 (Medical University Vienna/Baxter). Annett?s work at the Baxter Orth Molecular Vaccines group focused on recombinant Poxviruses, Influenza viruses and Flaviviruses. After Pfizer acquired the vaccines business from Baxter in 2014 she joined the Vaccines Analytical Development (MSAT) group and worked on recombinant Flaviviruses, FSME small scale model development and on various other bioassays (qPCR and ELISA). Since June 2017, Annett heads the Vaccines Analytical Development group.

 

Bernd Rinne, MS

Bernd obtained his MSc in Bio Sciences at the Institute for Molecular Infection Biology, at the University W?rzburg in Germany (1996). Since 1996 he worked in several QC and QA functions at the pharmaceutical industry. For Baxter he was responsible for the oversight of the analytical testing of plasma, at Novartis he worked as QP and at MSD he acted as Quality lead of a manufacturing site. At Pfizer Bernd is heading site Quality groups for several years now, since 2017 he is the Quality Lead for vaccines manufactured at Orth, Austria.

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Description

The Rijksinstituut voor Volksgezondheid en Milieu (RIVM) performs several tasks to promote both public health and a healthy and safe living environment. The principal task of RIVM is to collect knowledge worldwide and conduct research. The results are used to support the Dutch government in formulating its policy. RIVM has a public function and works on issues with political and societal relevance on behalf of government bodies. The institute is responsible for providing impartial and reliable information to members of the public and professionals who work in the fields of health care, infectious diseases, medicines, the environment, nutrition and safety.

In its current 5-year plan (2015-2020), RIVM has designated 'Alternatives to Animal Testing' and 'Effectivity of the Immune Response' as two of its fields of expertise. RIVM is responsible for vaccine safety and efficacy testing (Official Medicines Control Laboratories , OMCL) and test regulation guidelines (WHO, European Directorate for the Quality of Medicines (EDQM)). Moreover, RIVM is responsible for the Dutch National Vaccination Program.

Role of RIVM in the VAC2VAC project

The role of RIVM in VAC2VAC can be seen from different perspectives. Firstly, the Dutch government has designated RIVM as national contact point for the 3Rs (Replacement, reduction, refinement of animal testing) in regulatory testing. The VAC2VAC project is an important opportunity for RIVM to take this role in the field of vaccine batch release testing. Secondly, the Dutch OMCL is part of RIVM, and RIVM employees are members of the European Pharmacopoeia group 15, the Official Control Authority Batch Release (OCABR) drafting group, and relevant WHO and EDQM groups. This situation makes RIVM well suited to participate in the VAC2VAC work related to drafting criteria for method development, (pre-) validation studies, (pre-) validation methods and for providing guidance on implementation strategies. Thirdly, RIVM is responsible for the Dutch National Vaccination Program and has therefore a long tradition in research on vaccine-induced immune responses, supported by bioinformatics. This makes RIVM well equipped to perform cell-based assays and provide bioinformatics support.

Partner representative/s

Rob Vandebriel is a board-certified immunologist. He has been working on vaccine-induced immune responses and the effects of chemicals and drugs on the immune system in national and EU projects.

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Description

Sanofi Pasteur (SP), the vaccines business unit of Sanofi, is the largest company in the world devoted entirely to human vaccines. The company produces a portfolio of high quality vaccines that match its areas of expertise and meet public health demand. We distribute more than 1 billion doses of vaccine per year, making it possible to vaccinate more than 500 million people across the globe. Our vaccines protect against 20 infectious diseases: cholera, diphtheria, dengue, haemophilus influenzae type b infections, hepatitis A, hepatitis B, influenza, Japanese encephalitis, measles, meningococcal infections, mumps, pertussis, pneumococcal infections, poliomyelitis, rabies, rubella, tetanus, tuberculosis, typhoid fever and yellow fever. Sanofi Pasteur currently operates fifteen production and/or R&D sites located in France, USA, Canada, Argentina, China, India, Mexico and Thailand. As a key element of Corporate Social Responsibility, Sanofi commits to meet or exceed regulations and standards for the use of animals and to develop alternative approaches. Sanofi fully adheres to the 3Rs principles.

Role of Sanofi Pasteur in the VAC2VAC project

SP will provide overall project input as a member of the scientific management team. For Work Packages 1, 2, 3, and 4, SP will provide input in the selection and development of the methods by advising based on our internal scientific expertise in the field and by providing relevant samples to develop the methods and assess their capability to replace existing methods. In addition, SP will co-lead Work Package 2 and Work Package 4, ensuring the coordination of these two Work Packages. In Work Package 5, SP will contribute to the establishment of common criteria to assess methods development and to the evaluation of the transferability of developed methods by participating to the pre-collaborative studies that will be organized

Moreover, SP will co-lead Work Package 6 by sharing our internal experience on interacting with health authorities and regulators for introducing new methods for the testing of our products as well as for introducing new methods in Regulations.

Sanofi Pasteur is committed to the success of this project which is a unique chance to bring all stakeholders together and overcome global regulatory road blocks in acceptance of novel science-based testing methodologies without the use of animals.

Partner representative/s

Dr. Laurent Mallet (Associate Vice President, Head of Analytical R&D, Europe) is co-leader for Work Package 6. Laurent Mallet is highly involved in Regulatory Science as he is member of the European Pharmacopoeia group 15 'Sera and vaccines' since 2008.

Dr. Sue Nelson (Director, Analytical Expert 3Rs, Global Analytical Process & Technology) is co-leader for Work Package 2.  She has been involved in 3Rs as Director in the Analytical Process & Technology group and now as analytical expert, in charge of ensuring implementation of the 3Rs strategy in Industrial Operations.

Dr. Sylvie Uhlrich (Senior Director, Strategic alignment & expertise, Research & Development) is member of Scientific Management Team and co-leader for Work Package 4. She has been involved in developing 3Rs approaches in analytical R&D and now as analytical expert in charge of strategic alignment for new vaccines.

Eric Abachin, Manager Microbiology Research Unit, Analytical R&D, Europe will contribute to Work package 4.

Nolwenn Nougarede, Director Characterization Immunology & Microbiology platform head, Analytical R&D, Europe will contribute to Work package 3.

Romain Pizzato, Manager Immunology Research Unit, Analytical R&D, Europe will contribute to Work package 2.

Patrice Riou, Director, Virology and Immunology platform head, Analytical R&D, Europe will contribute to Work package 5.

Laurent Thion, Senior Scientist, Analytical R&D, Europe will contribute to Work packages 1, 3 & 4.

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Description

Sciensano  provides support for public health policy through scientific research, expert opinions and divisional tasks. Through innovative research, analyses, monitoring activities and expert advice, it formulates recommendations and solutions in respect of priorities for a proactive health policy at the Belgian, European and international levels. Sciensano assesses the status of health and health indicators on the basis of scientific methods that it approves and/or improves within a certified quality framework. Sciensano develops advanced solutions for the diagnosis, prevention and treatment of current and emerging diseases, as well as the identification and prevention of health risks, including those resulting from the animals and the environment in a one-health approach. The specific target groups of Sciensano are (1) policy makers at national and international levels (providing them with science-based expert advice), (2) research and governmental institutions (through collaborations and knowledge exchanges), (3) healthcare professionals (to monitor the population's health status and to provide them with expert advice) and (4) the general population (by conveying messages to improve the general health status). The institute hosts about 470 staff members, of which half are scientists.

Role of Sciensano in the VAC2VAC project

Sciensano brings into the VAC2VAC project the expertise of two services: the Biological Standardisation lab and the Medicines lab. These Official Medicines Control Laboratories (OMCL) are in charge of the quality control respectively of vaccines and blood-derived products and of medicines. Their roles perfectly match the evaluation of the consistency approach proposed by this 3R project. Indeed they are in first line for the regulatory changes that VAC2VAC will bring to the vaccine quality control (QC). These laboratories will develop and validate innovative techniques for this QC. For example, the toxin production by different bacteria strains will be characterised by mass spectrometry. This better control of toxin production will pave the way for a diminution of in vivo testing. Similarly the development of the antigen characterisation in non-desorbed vaccines by Luminex should allow to get rid of such in vivo QC. Sciensano will also participate to the validation of selected new methods. Finally, it will help the regulatory acceptance of these changes.

Partner representative/s

Alexandre Dobly (PhD) worked on rodent biology, virus epidemiology and prionology. He has a good expertise of ELISA and protein analysis. He now coordinates research in the OMCL in Sciensano that controls human vaccines from various manufacturers. Some of these quality controls imply in vivo testing.

Celine Vanhee (PhD) is active in the field of molecular biology and biochemistry. She engineered and purified different proteins. She also studied protein-protein interactions with a whole range of biochemical techniques, including mass spectrometry. In Sciensano she is responsible for the identification and characterisation of illegal polypeptide biopharmaceuticals.

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Description

The University Medical Center Groningen (UMCG) is one of the largest hospitals in the Netherland. More than 12,000 employees provide patient care and perform cutting-edge scientific research. For its research and educational function, the hospital has close ties with the University of Groningen. The Department of Medical Microbiology within the UMCG comprises the areas of microbiological diagnositics, infection prevention and microbiological research. One of the research fields of the department is vaccinology, the branch of medicine concerned with the science of vaccines. The Vaccinology research group focuses on design of new and improved vaccines for diverse viral infections on a rational basis. The work of the group comprises evaluation of new vaccines and adjuvants, exploration of new administration routes, and the development of in vitro systems suitable for testing new vaccine candidates and for revealing working mechanisms of vaccines and adjuvants.

Role of UMCG in the VAC2VAC project

UMCG will contribute its expertise to the VAC2VAC project in in vitro vaccine evaluation. In particular, UMCG will develop cell-based systems which are suitable for the evaluation of vaccine properties like safety and immunogenicty. To this end, cell lines and primary human blood cells will be exposed to the vaccines to be evaluated and the responses of the cells with respect to gene expression, activation, and production of cytokines will be measured. A major task will be to integrate the different responses such that the response profile as a whole will allow conclusions about the quality of a particular vaccine or vaccine batch.

Partner representative/s

Anke Huckriede received a PhD in cell biology from the University of Bielefeld, Germany. In 1990 she joined the Faculty of Medical Sciences of the University of Groningen, as a postdoc. After having worked on mitochondrial diseases she switched to the field of vaccine development working on tumor vaccines and vaccines for viral diseases. In 2011 she was appointed Professor of Vaccinology at the Department of Microbiology, UMCG. Currently, her interest is in rational vaccine design. Anke Huckriede is involved in several EU consortia devoted to vaccine development and exploration as co-leader or as work package leader.

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Description

The research group Innovative Testing in Life Sciences and Chemistry started its work in 2008. The group works in close co-operation with the Bachelor programs of the Institute for Life Sciences and Chemistry (part of  HU University of Applied Sciences Utrecht ) and is located in the same building.

Working together with universities, research institutes, biotechnology and other
Life Sciences and Chemistry companies, as well as large corporations, the group has been involved in many regional, national and international research projects (www.innovativetesting.nl/projects ).

Members of the research team are experts in the fields of biology and medical laboratory research. The group consists of post-docs, technicians, lecturers, graduate students and undergraduate students. Our laboratory is well equipped to run large scale projects and answer complex research questions. Its main focus is on the practical application of research, but the group is also involved in fundamental research.

The group concentrates its efforts on developing, optimizing and validating methods for testing the safety and effects of (natural) substances. By relying on in vitro methods, the group offers alternatives to experiments involving live animals. That is one of the ways in which it contributes to the 3Rs (the refinement, reduction and replacement of animal testing).

The team has facilities and technology to work on both biological and chemical research questions. Technologies available fall in one or more of three research themes: interactions of food and health, bacterial resistance to anti-biotics, safety and efficacy of (natural) compounds and mixtures.

Role of hu in the VAC2VAC project

In this project our research group contributes to the setup of a kinomics based safety assay for live attenuated pertussis toxin vaccines. The initial steps are to culture human and animal-derived barrier cells, expose these to different types and concentrations of pertussis toxin and perform kinome analysis. Kinome analysis is the collection of kinases that is actively expressed after a biological stimulus. Kinases are important regulators of cellular mechanisms and are known to play an important role in cellular signalling. On the basis of this important role of the kinome in cellular physiology, one can hypothesize that toxins like pertussis toxin can cause measurable changes in the kinome. This work will be the basis for an innovative method to assess safety of pertussis toxin vaccines in an animal-free manner.

Furthermore, our group will play a role in the validation of methods and the dissemination of knowledge obtained in the project. In the latter half of the project we will organize specific educational activities.

Partner representative/s

The Innovative Testing research team is headed by Dr. Cyrille Krul , director Predictive Health Technologies at TNO and associate professor at the University of Applied Sciences (Hogeschool Utrecht). She is a specialist in the refinement, reduction and replacement of animal testing. As the head of the research team her goal is to inspire (young) professionals to achieve results that contribute to a sustainable future. As a business line manager at TNO she leads an innovation program in the field of biomedical research and brings the results to market. She is driven by the passion to find innovative solutions for complex challenges.

 

Dr. Saertje Verkoeijen studied biology (fundamental biomedical sciences) at Utrecht University. She went on to do her PhD research at Leiden University. She joined the Research Centre for Innovative Testing in Life Sciences and Chemistry in September 2007. Saertje is an expert in the field of molecular biology, cancer cell biology and signal transduction. Techniques she masters include cell culture, cell viability assays, Western blotting and ELISA.

 

Associate professor Dr. Marc A.T. Teunis obtained his Master's degree at the Faculty of Biology in Utrecht where he specialised in animal physiology and neurosciences. Teunis completed his Ph.D. in 2003 which was performed at Wilhelmina's Children's Hospital in Utrecht, where he worked on brain-immune inteactions and tumor angiogenesis. He is currently leading several applied research projects on development and validation of innovative alternative methods that contribute to reduction and replacement of animal testing.

Renate Nawrocki joined the University of Applied Sciences in 2001. She has experience as a research technician at the National Institute for Public Health and the Environment (RIVM).

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Description

The Faculty of Veterinary Medicine at Utrecht University (UU) is the only place in the Netherlands where veterinarians are trained. This means that our Faculty is the centre of expertise and point of reference for veterinary issues for the entire country, and increasingly for the world abroad as well. Our activities include providing primary health and welfare care for a variety of types of animals, monitoring food safety and the prevention of zoonoses (diseases transferable from animals to humans). The Faculty is considered one of the leading veterinary medicine faculties in Europe and is ranked in the top ten world-wide.

Role of UU in the VAC2VAC project

The tasks of UU will be the development of cellular assays that monitor antigen presenting cell (APC) maturation and its T cell (phenotypic) skewing capacities in veterinary animal systems. In addition, the APC maturation (and other phenotypic changes) will be analysed in cells collected from veterinary animal species such as chicken, cow or pig.

Partner representative/s

Prof. W. van Eden, MD, PhD is a full professor of Veterinary Immunology and head of the division of Immunology of the UU Veterinary Faculty. He is an expert in the immunological safety testing of vaccines and has a track record in models of experimental autoimmunity and immunological tolerance.

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Description

Zoetis (zo-EH-tis) is the leading animal health company, dedicated to supporting its customers and their businesses. Building on more than 60 years of experience in animal health, Zoetis discovers, develops, manufactures and markets veterinary vaccines and medicines, complemented by diagnostic products and genetic tests and supported by a range of services. Zoetis serves veterinarians, livestock producers and people who raise and care for farm and companion animals with sales of its products in more than 100 countries. In 2015, the company generated annual revenue of $4.8 billion with approximately 9,000 employees.

Role of Zoetis in the VAC2VAC project

Zoetis will provide scientific and technical input to the scientific work packages (Work Packages 1, 2, 3, and 4) as well as industry knowledge and expertise to Work Package 5 on validation. Industry regulatory knowledge and experience as well as global regulatory network access will be a key part of our contribution to Work Package 6, and we will provide overall project input through our role in Work Package 7.

Zoetis will also provide samples of vaccines/antigens for the assay development work that is the core part of Work Packages 1-4 and take part in relevant validation studies in Work Package 5. Zoetis brings a long history of industry experience to help ensure project success, assays and approaches that can be used in manufacturing and are acceptable to regulators to be developed.

This project is a unique chance to bring all stakeholders together to make real progress in this area and Zoetis is committed to its success.

Partner representative/s

Dr. Catrina Stirling is industry co-lead for the overall project representing the animal health sector and is part of the Steering Committee and Scientific Management Team as well as the veterinary industry co-lead for Work Package 6 (Regulatory).

Dr. Rudiger Raue is the veterinary industry co-lead for Work Package 5 (Validation), and Dr. Anne Thomas is the co-lead for Work Package 2 (Immunological techniques).

Dr. Nancee Oien and Dr. Duncan Mwangi will contribute technical expertise to Work Package 3,  Dr. Gonzalo Rincon to Work Package 4 and Dr. John Hoogerheide to Work Package 1.