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Wegweiser Tierversuchsfreie WissenschaftInterview - Helena Kandarova

Für unsere Publikation Wegweiser Tierversuchsfreie Wissenschaft haben wir mit Dr. Helena Kandarova, ERT, über Hautreizungstests an menschliche Hautmodellen gesprochen. Das Interview wurde in englischer Sprache geführt.

Helena Kandarova steht im Labor
Dr. Helena Kandarova, ERT

Dr. Helena Kandarova, ERT ist Senior Scientist am Institut für Pharmakologie and Toxikologie des Zentrums für Experimentelle Medizin und Lehrbeauftragte am Institut für Biochemie and Mikrobiologie der Fakultät für Chemie- und Lebensmitteltechnik (FCHPT) Bratislava, Slowakei. Sie war unter anderem wissenschaftliche Mitarbeiterin am Bundesinstitut für Risikobewertung, Nationale Koordinatorin für die Slowakei im Rahmen des Chemikalienprüfrichtlinienprogrammes der OECD und Geschäftsführerin und Leiterin der europäischen Niederlassung der Biotechnologie-Firma MatTek In Vitro Life Science Laboratories. Aktuell ist sie u.a. Präsidentin der Europäischen Gesellschaft für in vitro-Toxikologie (European Society for in vitro Toxicology, ESTIV). 

What motivated you to work in the field of animal-free methods?  

Dr. Helena Kandarova, ERT: My career in toxicology, particularly focused on alternative methods, began with a passion for science that reduces harm to animals. It was during my Bachelor’s thesis that I discovered the existence of in vitro and in silico tools, which had the potential to reduce and replace animal testing — especially in the safety assessments of cosmetic products, but also in other areas such as chemical, pharmaceutical, and medical device testing.  

Over the years, I’ve been heavily involved in projects aimed at refining, reducing, and replacing animal testing through alternative methods (now known as New Approach Methodologies or NAMs), driven by a strong ethical and scientific standpoint. My work on 3D reconstructed human skin and cornea-like tissue models, and their validation for regulatory toxicology purposes, aligns with the goal of promoting humane science, which has been a significant motivation throughout my career. 

Could you explain your research on animal-free models to our readers? 

Dr. Helena Kandarova, ERT: My research primarily focuses on developing in vitro (animal-free) models, which use 3D reconstructed human tissue to assess the potentially harmful effects of chemicals, cosmetics, and medical devices. These models provide an ethical and scientifically robust alternative to animal testing and meet the high standards required for regulatory testing. Several of the tests I’ve worked on, in collaboration with various international teams and projects, have already been accepted for use in topical toxicity testing worldwide. Currently we are expanding our research into the areas of lung and intestinal toxcity.

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Could you give examples of successful test methods from your research that have helped replace animal testing? 

Dr. Helena Kandarova, ERT: I’ve contributed to several internationally recognized methods that have been adopted into OECD guidelines, such as the skin corrosion test (OECD TG 431, the Skinethic method and the extension of the EpiDerm method for sub-classification) and the skin irritation assay using reconstructed human epidermis (OECD TG 439). The development of these 3D tissue models based assays for skin irritation and corrosion testing was closely linked to my PhD thesis conducted at ZEBET at the BfR in Berlin. I was really lucky, that I could learn from the best scientits and experts on the validation within the validation project funded by ECVAM.  After completing my PhD studies, I joined MatTek in 2007, where I worked on a follow-up skin irritation validation project of the EpiDerm test, a model that has since become widely used in regulatory toxicology. Along with my former colleagues from MatTek and in collaboration with Cosmetics Europe, we developed and validated the eye irritation method using the cornea-like tissue model, EpiOcular. This method has since been implemented into regulations as OECD TG 492. 

Around the same time, my research interest expanded also into the field of medical devices. In 2012, we started a project with Medtronic and RIVM on the development and validation of an in vitro skin irritation test for medical devices testing. In collaboration with 23 partners, we successfully completed the validation of this test method in 2018, leading to its inclusion into the regulatory frameworks as ISO 10993:23 in 2021. 

After my departure from MatTek, I continued working on 3D tissue models at the Slovak Academy of Sciences. In collaboration with IIVS and colleagues from the US NIH, we developed a comprehensive database that supported the adoption of EpiDerm model based method for the assessment of phototoxicity, which was later formalized as OECD TG 498.  

It’s important to note that none of these achievements would have been possible without the support of many partners and appropriate funding. The success reached was a result of collaborative efforts from numerous companies and individuals, all of whom played an important role in the process.  

Which project do you look back on with particular enthusiasm and pride? 

Dr. Helena Kandarova, ERT: It is definitely the validation of the EpiDerm skin irritation test, which is now part of global regulatory guidelines as OECD TG 439. This project was a key milestone in my career, as it provided me with essential knowledge on how to manage validation projects and optimize test assays to fine-tune the sensitivity and specificity of a particular test method to match the “gold standard,” which was initially the rabbit test. 

During this project, I transitioned from working in a German governmental institute to joining the US industry, which gave me a broader perspective on the importance of validating alternative methods not only from a scientific viewpoint, but also from a business perspective. 

I am particularly proud that after this successful validation, I was entrusted with establishing MatTek’s production facility in Europe (Slovakia), where we  started commercial production of 3D tissue models for the entire EU market and part of Asia in 2012. Besides production, we also established a training programme on in vitro assays and worked on the development of new 3D models-based tests directly in Slovakia. This part of my life-path was an exceptionally fruitful combination of sucesfull business and science, supported by a passionate team of scientists in my hometown of Bratislava.  

How do you view the current financial support for research on animal-free methods? 

Dr. Helena Kandarova, ERT: Funding for the development of non-animal testing methods has increased over the years, but it still falls short of the needs and rarely supports full validation efforts. This is partly due to regulatory inertia and a lack of political prioritization. I advocate for more substantial investment, not only for ethical reasons, but because these methods can provide faster, cheaper, and may provide more relevant results concerning human health across various fields. 

However, I am not particularly in favor of large multimillion-euro projects, as they can be difficult to manage. For faster progress in validation, I believe society would benefit from smaller, more flexible funding schemes, which could be divided into several phases based on reported progress. This approach would also allow for more adaptable and responsive project administration, ensuring that resources are effectively allocated based on real-time advancements. 

What challenges do you see in the broad acceptance and implementation of non-animal test methods in toxicology testing?   

Dr. Helena Kandarova, ERT: The main challenges, in my opinion, include the slow regulatory acceptance of novel testing methods, a lack of harmonization, and sometimes the lack of mutual acceptance of data across industrial sectors and countries. The slow pace of international validation and insufficient infrastructure in some regions further contribute to the problem. Moreover, industries and regulators may resist change due to the costs associated with transitioning from animal-based tests to alternative methods. However, ongoing advancements in technologies like 3D tissue models, microphysiometry, human-on-a-chip systems, and AI-driven predictive testing are helping to overcome these barriers and will gradually increase the possibilities for the adoption of non-animal testing methods. 

In your opinion, how important is the role of legislation for the further development of animal-free methods in general? Where do you see the greatest need for political action? 

Dr. Helena Kandarova, ERT: Legislation plays a critical role. Without it, alternative methods won’t gain the regulatory traction needed for widespread adoption. We need to advocate for stronger EU and international regulations that promote alternative methods, particularly in industries such as chemicals, pesticides, pharmaceuticals, and medical devices. Greater political action is essential to expedite the regulatory acceptance of these methods and to increase funding for developing innovative solutions. 

I would also like to see stricter requirements and pressure from the European Commission toward member states to fund 3Rs activities directly at the national level. This could include mandating a percentage of the annual budget to be allocated specifically for the development, validation, and implementation of New Approach Methodologies (NAMs) within each member state. Almost every EU member state has at least one 3R centre and one EU-NETVAL laboratory, however there are dramatic differences in the funding and suport of these important efforts.  

Is there a particular country that you would see as a role model for the establishment and research of animal-free methods? 

Dr. Helena Kandarova, ERT: Countries like the Netherlands and the UK are often cited as pioneers in promoting animal-free testing. Germany also has many excellent initiatives, and I personally learned the “art of validation” at ZEBET at the BfR in Berlin, which was a role model for the establishment of ECVAM nearly 30 years ago. Most Western European countries have robust regulatory frameworks and have invested in the necessary infrastructure to support alternative testing methods. Their proactive approach to integrating these methods into legislation sets a good example for other countries, including Slovakia. 

To what extent can cooperation between scientists, authorities, and industry contribute to promoting safe and ethical toxicology assessments? 

Dr. Helena Kandarova, ERT: Collaboration is vital. Scientists provide innovation, authorities ensure regulatory oversight, and industries bring practical applications. The success of projects like ECVAM and Medical devices validation projects on skin irritation or the Cosmetics Europe project on eye irritation demonstrate how interdisciplinary cooperation can lead to the creation of methods that are not only ethical but also scientifically advanced. 

What is your next goal? What projects are you planning next? 

Dr. Helena Kandarova, ERT: My friends and colleagues know that I usually plan my life in five-year cycles, and we are now nearing the end of one that started in 2020. I have several goals for the upcoming five years, many of which focus on the continued development of methods for assessing the safety of medical devices, provided funding is available. We recently published a new protocol for ocular irritation testing in ATLA, and an article on intra-oral irritation testing has been accepted for publication in Toxicology in Vitro. 

Over the past three years, we have begun exploring new areas of research, particularly in lung and intestinal toxicity testing in combination with microfluidic systems. Recently, I received the PSCI award for a project related to pulmonary toxicity testing of novel drugs in COVID-19 treatment. My young team at CEM and I are passionate about exploring cutting-edge technologies, such as microfluidic systems and organ-on-a-chip platforms, to further enhance in vitro testing and driving the acceptance of these methods into regulatory frameworks.  

We are also involved in the EU-funded ONTOX project -  one of the most innovative scientific undertakings in advancing the field of repeated systemic toxicity testing in combination with AI-driven probabilistic risk assessment. We hope the results from this project will be a significant breakthrough in the future of safety assessments for chemicals and drugs. 

Last but not least, as president of ESTIV, now in the second term of my appointment, I aim to further professionalise the society as we are growing rapidly. Our goal is to establish ESTIV as the primary platform for advancing in vitro, in silico AOP-oriented research, fostering collaboration among scientists, and driving innovation in the field of toxicology. We hope that ESTIV will remain attractive platform for early career researchers as well as established experts in toxicology.  

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