An industry perspective on the FDA modernization act 2.0/3.0: Potential next steps for sponsors to reduce animal use in drug development DOI
Sarah A. Carratt,

Christina L Zuch de Zafra,

Elias M. Oziolor

et al.

Toxicological Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Abstract Pharmaceutical developers are encouraged to adopt the best practices of being purposefully thoughtful about use animals, seeking alternatives wherever possible. They should engage with health authorities increase their familiarity methods, study designs, data outputs, and context for new approach methodologies (NAMs). Although current state technology does not yet provide adequate models fully replace in vivo studies, many sufficiently good an augmented that will enhance our understanding vitro correlations advance long-term goal reducing animal through innovative NAMs. The future nonclinical safety packages is utilization such enabling technologies toward appropriate human risk characterization. Establishing confidence NAMs a critical first step. For example, sponsors may include both “traditional” NAM-based regulatory submissions establish authorities. In addition, regulators create “safe harbor” hybrid facilitate iterative learning, refinement, implementation assessment strategies. Sponsors urged contribute evolution consortia participation, peer-reviewed publications, documenting reduction studies/programs, accelerating eventual elimination pharmaceutical development, as envisioned FDA Modernization Act 3.0.

Language: Английский

Complex in vitro models positioned for impact to drug testing in pharma: a review DOI Creative Commons
Michael S. Kang, Eugene C. Chen, Helen Cifuentes

et al.

Biofabrication, Journal Year: 2024, Volume and Issue: 16(4), P. 042006 - 042006

Published: Aug. 27, 2024

Abstract Recent years have seen the creation and popularization of various complex in vitro models (CIVMs), such as organoids organs-on-chip, a technology with potential to reduce animal usage pharma while also enhancing our ability create safe efficacious drugs for patients. Public awareness CIVMs has increased, part, due recent passage FDA Modernization Act 2.0. This visibility is expected spur deeper investment adoption models. Thus, end-users model developers alike require framework both understand readiness current enter drug development process, assess upcoming same. review presents selection based on comparative -omics data (which we term model-omics), metrics qualification specific test assays that may support context-of-use (COU) assays. We surveyed existing healthy tissue ten development-critical organs body, provide evaluations suggestions improving model-omics COU each. In whole, this comes from perspective, seeks an evaluation where are poised maximum impact roadmap realizing potential.

Language: Английский

Citations

4
Computational histology reveals that concomitant application of insect repellent with sunscreen impairs UV protection in an ex vivo human skin model DOI Creative Commons

Sophie Charrasse,

Titouan Poquillon,

Charlotte Saint-Omer

et al.

Parasites & Vectors, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 4, 2025

Histological alterations such as nuclear abnormalities are sensitive biomarkers associated with diseases, tissue injury and environmental insults. While visual inspection human interpretation of histology images useful for initial characterization, low-throughput procedures suffer from inherent limitations in terms reliability, objectivity reproducibility. Artificial intelligence digital morphometry offer unprecedented opportunities to quickly accurately assess morphotypes relation damage including skin injury. In this work, we designed NoxiScore, a pipeline providing an integrated, deep learning-based software solution fully automated quantitative analysis nucleus-related features histological sections biopsies. We used evaluate the efficacy safety three dermato-cosmetic products massively sold at time study Montpellier area (South France): sunscreen containing UV filters, mosquito repellent (with synthetic active ingredient IR3535) product combining natural insect plus sunscreen. Hematoxylin eosin or hematoxylin-eosin saffron staining was performed structure before morphometric parameter computation. report identification specific feature based on variation texture information that can be after oxidative stress exposure. Our data show application commercial sun cream provided efficient protection against effects our ex vivo model, whereas single exerted no protective toxic effect. Notably, found concurrent significantly decreased UVB effect Last, histometric biopsies multiple donors indicates sunscreen-insect combo displayed variable levels irradiation. To knowledge, is first potential toxicity real-life using samples, which most closely imitate cutaneous physiology. The NoxiScore wet-plus-dry methodology has provide about pharmaco-toxicological profile topically applied formulations may also diagnostic purposes evaluation exposome pesticide exposure, air pollution water contaminants.

Language: Английский

Citations

0
Validation of a new 3D epidermis model for the SENS-IS assay to evaluate skin sensitization potency of chemicals DOI

Françoise Cottrez,

Elodie Boitel,

Essia Sahli

et al.

Toxicology in Vitro, Journal Year: 2025, Volume and Issue: 106, P. 106039 - 106039

Published: March 5, 2025

Language: Английский

Citations

0
3D-Printed Tool for Creating Standardized Burn Wounds in Ex Vivo Skin Tissues DOI Creative Commons

Mojtaba Javid,

Fahimeh Tabatabaei

Annals of 3D Printed Medicine, Journal Year: 2024, Volume and Issue: 15, P. 100162 - 100162

Published: Aug. 1, 2024

: The development of biomaterials and medical devices for burn wound treatment necessitates thorough investigation through in vitro/ex vivo models before transitioning to animal studies. Establishing a standardized high-throughput model ex skin presents considerable challenge. Our objective was address this challenge by developing practical cost-effective 3D-printed tool capable uniformly inducing burns 12 samples simultaneously. Utilizing Autodesk Inventor software, we designed 3D comprising plate-base component (PBC) rod-base (RBC). design exported as Standard Triangulation Language (STL) file, processed "Slicer" software generate G-code file tailored printing. Rod-Base underwent iterative modifications optimize weight, airflow, material consumption, resulting final featuring unique star shape enhanced airflow. Simultaneously, the Plate-Base evolved enable easy secure plate placement, demonstrating compatibility with 12-well plates. average production time 14.5 hours, cost approximately $20 (USD), covering printing steel rods. In conclusion, study provides valuable insights into required equipment empowering researchers efficiently produce their accurate controlled reproducible creation viable tissues.

Language: Английский

Citations

1
An industry perspective on the FDA modernization act 2.0/3.0: Potential next steps for sponsors to reduce animal use in drug development DOI
Sarah A. Carratt,

Christina L Zuch de Zafra,

Elias M. Oziolor

et al.

Toxicological Sciences, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

Abstract Pharmaceutical developers are encouraged to adopt the best practices of being purposefully thoughtful about use animals, seeking alternatives wherever possible. They should engage with health authorities increase their familiarity methods, study designs, data outputs, and context for new approach methodologies (NAMs). Although current state technology does not yet provide adequate models fully replace in vivo studies, many sufficiently good an augmented that will enhance our understanding vitro correlations advance long-term goal reducing animal through innovative NAMs. The future nonclinical safety packages is utilization such enabling technologies toward appropriate human risk characterization. Establishing confidence NAMs a critical first step. For example, sponsors may include both “traditional” NAM-based regulatory submissions establish authorities. In addition, regulators create “safe harbor” hybrid facilitate iterative learning, refinement, implementation assessment strategies. Sponsors urged contribute evolution consortia participation, peer-reviewed publications, documenting reduction studies/programs, accelerating eventual elimination pharmaceutical development, as envisioned FDA Modernization Act 3.0.

Language: Английский

Citations

1