A large-scale concordance study of toxicity findings across preclinical species and humans for small molecules and biologics
By Xin Lui and Fan Fan
Translating preclinical safety findings into reliable insights for human risk assessment remains a fundamental challenge in drug development. The authors created a comprehensive cross-species database comparing drug side effects across over 7,500 drugs. Their approach identifies related safety signals using advanced statistics, considering species, drug type, and exposure levels. 850 direct matches and nearly 3,000 additional related endpoints were found. Results are provided open access via an interactive web application and should help scientists design better preclinical studies, reduce animal use, and develop safer medicines.
Establishment of human-relevant in vitro models using animal-free serum replacement and recombinant antibodies
By Zahra Miri et al.
The use of animal-derived reagents in biomedical research poses challenges due to variability between batches and species. In this paper, the authors investigated the use of serum replacement in cell culture and recombinant antibodies with an animal-free blocker in immunocytochemical staining of cells. In both experiments, the authors found encouraging results, but identified the need for protocol optimisation for some cell type used. Findings overall indicate that animal-derived materials can reliably be replaced.
Revisiting ICH S7A after 25 years: outcomes of a multi-stakeholder workshop and strategic pillars for modernizing safety pharmacology
By Jean-Pierre Valentin et al.
The ICH S7A guideline on safety pharmacology studies, finalized in 2000, is now 25 years old. Between scientific advances, evolving drug development paradigms and technological innovations with the emergence of NAMs, a workshop was held in Brussels in February 2026 to modernise the guideline. these discussions support the development of a modernized, risk-based framework for safety pharmacology that maintains robust protection of human subjects while enabling innovation, global regulatory harmonization, and implementation of the 3Rs principles.
The FDA roadmap to reducing animal testing in preclinical safety studies: where will it lead us?
By M. Fossler and C. Garner
With drug agencies’ increasing concerns about the number of animals used in drug research, especially in toxicology studies, a roadmap was published by the FDA in 2025 to reduce animal testing in preclinical safety studies. The authors argue here that for the most part, preclinical toxicology studies do a good job of predicting human safety, that there is currently no alternative to identify potential adverse effects, and therefore replacing whole animal general toxicity studies in drug development is unlikely. They answer several key questions needed to assess the success of alternative approaches.
MHRA – Common nonclinical issues identified during clinical trial applications
By the Medicines & Healthcare products Regulatory Agency
The Medicines & Healthcare products Regulatory Agency (MHRA) lists the most common non-clinical Grounds for Non-Acceptance (GNAs), relating to a lack of information about pivotal safety studies submitted. Those GNAs can be, non-exhaustively: a lack of justification for the starting dose in humans from a safety perspective, no description of the analytical methods used in the pharmacokinetic and toxicology studies or a lack of data availability for review, such as pharmacology, pharmacokinetics, and toxicology aspects.
Ames concordance with the in vivo transgenic rodent (TGR) gene mutation assay for NDSRIs and relative in vivo TGR potency with nitrosamines with robust dose-response carcinogenicity data
By Robert A. Jolly et al.
Nitrosamines (NAs) are a diverse class of mutagenic impurities that display a broad range of carcinogenic potential, from high carcinogenic potency to being weak or even non-carcinogenic. This study focuses on hazard identification of nitrosamine drug substance-related impurities (NDSRIs) via a comparative analysis of Ames tests and Transgenic Rodents (TGR) results for 33 NDSRIs and revealed an accuracy of 79 % between the overall mutagenic calls in the two assays. Results demonstrated a strong correlation between carcinogenic potency (TD50) and TGR mutagenic potency (BMDL50).
Breathing lung-on-chip: a versatile tool for assessing respiratory toxicity across multiple therapeutic modalities
By Linnea Johansson et al.
This study aimed to assess the predictive capability of a Lung-on-Chip model in determining respiratory toxicity of several inhaled substances of varying modalities. Comparison of their results to in vivo toxicology studies demonstrated that the Lung-on-Chip model predicted drug-induced inflammatory responses, capturing a spectrum of lung pathologies from mild toxicity to severe inflammatory damage, and illustrates the potential of the technology to identify inhaled compound toxicity across various modalities.
Virtual Control Groups (VCG) to replace Concurrent Control Groups (CCG) in rat non-GLP Dose-Range Finding (DRF) studies
By the European Medicines Agency
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) considers that Virtual Control Groups (VCGs) can be used to substitute for Concurrent Control Groups (CCGs) ) in non-clinical non-GLP rat dose range finding (DRF) studies to inform on dose selection for subsequent pivotal rat GLP-compliant repeated dose studies, when applied in accordance to the SOP.
The Adenovirus Vaccine Problems, Explained
By Derek Lowe
In this article, Derek Lowe dives into the mechanisms causing vaccine-induced immune thrombocytopenia and thrombosis (VITT) in some rare case of patients vaccinated with the AstraZeneca or Janssen/J&J adenovirus-vectored vaccines during the COVID-19 pandemic. A new paper published in 2026 explains that some rare patient reacted to the adenovirus and generated antibodies to adenoviral core protein VII – and these antibodies cross-react with platelet factor 4 (PF4).