Regulatory bodies, specifically the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), are steadily moving away from traditional animal testing in favor of more ethical, efficient, and predictive alternatives. In recent years, both agencies have endorsed advanced in vitro models, computational methods, and human-relevant testing systems to enhance drug, healthcare and cosmetic safety assessments.
A major milestone in this shift came with the FDA Modernization Act 2.0, signed into law in 2022, which eliminated the federal requirement for animal testing in drug development. This groundbreaking change enables companies to adopt cutting-edge technologies such as organ-on-a-chip systems, human-derived cell cultures, and ex vivo skin models like Ten Bio’s TenSkin™ to generate safety and efficacy data. Similarly, the EMA has embraced New Approach Methodologies (NAMs), reinforcing a broader global movement toward more humane, scientifically advanced, and clinically relevant testing platforms across the pharmaceutical, healthcare cosmetic, and chemical industries.
The challenge of change
Despite strong regulatory momentum, the effected industries face substantial hurdles in adapting to these reforms, leading to slow progress in NAM adoption. The entrenched reliance on animal models is deeply embedded in regulatory pathways, company infrastructure and their processes, and long-standing validation frameworks. Many preclinical research protocols, toxicology assessments, and approval standards are still built around animal data, making the transition to human-relevant alternatives both complex and resource-intensive.
A major barrier is the lack of standardized validation processes for NAMs. Without clear regulatory guidelines, companies hesitate to invest in unproven models. Additionally, decades of infrastructure and process development, expertise, and supply chains built around animal testing make the shift toward ex vivo, computational, or organ-on-a-chip technologies a financial, operational and even cultural challenge.
A path forward for skin research: explant models as a ready solution
As the industry moves beyond animal testing, an immediate and practical solution is available—explant models, particularly in dermatology. Surplus clinical waste tissue from elective cosmetic surgical procedures can provide a readily available and highly human-relevant alternative for preclinical skin testing.
Ex vivo or explant human skin models like Ten Bio’s TenSkin™ can provide a superior, predictive, and reproducible platform for evaluating drug penetration, inflammatory responses, and tissue-level effects under physiologically relevant conditions. By maintaining native human skin architecture, including epidermal, dermal, and extracellular matrix components, which animal skin often lacks, explant models provide realistic skin barrier function avoiding species-specific differences that make drug absorption and metabolism in animal models poorly translatable to humans.
Explant models maintain native human skin architecture, including epidermal, dermal, and extracellular matrix components, which animal skin often lacks. These models provide realistic skin barrier function and avoid species-specific differences that make drug absorption and metabolism in animal models less applicable to humans.
The predictive power of explant models
Explant human skin models offer several advantages over traditional animal models, particularly in dermatological research, drug development, and medical device testing. Explant human skin models are particularly advantageous for studying inflammatory and immune-mediated skin conditions such as psoriasis and atopic dermatitis due to their preservation of native human immune components, such as Langerhans cells, macrophages, and T cells. This retention allows for more accurate modeling of human-specific immune responses. In contrast, animal models often exhibit species-specific differences in cytokine signaling pathways, leading to discrepancies in treatment responses. Indeed, mice and humans even differ in their epidermal layer immune composition, where mice feature a unique dendritic epidermal T cells (DETC) population.
Another key advantage of explant models is their ability to generate more predictive drug penetration and absorption data. Human skin has a distinct barrier function that differs significantly from common laboratory animals such as mice, rats, or pigs. As a result, transdermal drug delivery studies, topical formulation testing, and microneedle applications are more accurately evaluated using explant skin.
Regulatory leadership in standardization
To fully unlock the potential of explant models, regulatory bodies need to establish clear evaluation criteria for their use in preclinical testing. Key considerations include:
- Robustness – Ensuring the explant model can consistently deliver reliable and reproducible results.
- Longevity – Determining the viability and usability of the model over extended testing periods.
- Disease Relevance – Developing and validating explant-based disease models to accurately reflect human conditions.
TenSkin™ and similar explant models offer a compelling alternative to traditional animal testing. By setting regulatory standards around their validation and use, agencies can facilitate their adoption across dermatology and related fields, ensuring they become the new gold standard in preclinical evaluation.
The business case for change
Ultimately, widespread industry adoption of NAMs will be driven by economic incentives. Explant-based NAMs do not just replace animal models, they offer improved data quality, better predictability, and enhanced regulatory confidence, leading to:
- More informative preclinical data, refining translational and clinical trial design.
- Faster time to market, accelerating drug and product approval processes.
- Optimized pricing strategies, particularly in key markets like the U.S.
- Increased revenue and profitability, as companies capitalize on more efficient and cost-effective testing methodologies.
There is a significant opportunity to accelerate the adoption of New Approach Methodologies (NAMs) in emerging skin testing areas where standardized guidelines are lacking, such as microneedle patch applications. Microneedles are increasingly used for drug delivery, medical aesthetics, cosmetics, and vaccines, yet regulatory frameworks for assessing their penetration, distribution, and efficacy remain underdeveloped. Traditional models, including animal testing, fail to replicate human skin physiology, leading to inconsistencies in data translation. Ex vivo human skin models like TenSkin™ provide a more predictive and reproducible platform, enabling accurate evaluation of microneedle penetration, drug diffusion, and tissue response under physiologically relevant conditions. As the field progresses, adopting NAMs in microneedle research will accelerate product development, improve clinical translation, and reduce reliance on animal testing, paving the way for broader implementation across skin testing applications.
Applying a microneedle patch onto TenSkin™ to study transdermal drug delivery
Final thoughts
The potential to combine explant human skin models with other New Approach Methodologies (NAMs) presents a significant opportunity to advance preclinical skin research. By integrating explant models with computational modeling, organ-on-a-chip systems, and advanced imaging techniques, researchers can create a more comprehensive and predictive testing framework. For example, combining ex vivo human skin with microfluidic organ-on-a-chip platforms can provide real-time insights into drug absorption, metabolism, and immune responses in a way that each approach alone cannot achieve. Additionally, integrating high-throughput computational modeling and AI-driven analytics can enhance predictive toxicology by identifying long-term safety risks and optimizing formulation strategies. These hybrid approaches not only reduce reliance on animal models but also improve translational success, ensuring that preclinical skin studies more accurately reflect human physiology, disease mechanisms, and treatment responses.
Ten Bio team, March 2025
