Micro-sampling in Toxicology studies

Micro-sampling in Toxicology Studies: Enhancing 3Rs While Maintaining Scientific Integrity

Lionel Hurst¹, Klaus Biemel¹, Corinne Guicheney²*

¹Pharmacelsus, Saarbrücken, Germany

²GBA Pharma, Plobsheim, France

Micro-sampling, defined as the collection of blood volumes ≤50 µL, is increasingly recognized as a valuable approach in toxicology studies. Conventional toxicokinetic (TK) designs often rely on satellite animals and large-volume sampling, contributing significantly to animal use and distress. Micro-sampling offers a practical solution aligned with the principles of Replacement, Refinement, and Reduction (3Rs), enabling exposure-response assessments in main study animals while reducing overall animal numbers and improving welfare.

This poster reviews the implementation of micro-sampling in rodent safety studies, highlighting technical, analytical, and regulatory considerations. Key challenges include ensuring bioanalytical sensitivity, managing limited sample volumes for ancillary analyses (e.g., ISR, metabolite characterization), and mitigating potential impacts on toxicological endpoints. Strategies such as sample dilution, use of highly sensitive instrumentation, and adoption of sparse sampling combined with population pharmacokinetic modelling have proven effective.

Operational success depends on robust training, validated procedures, and appropriate sampling devices (e.g., capillary tubes, Minivettes®). Regulatory guidance supports micro-sampling, provided bioanalytical methods are validated and species-specific factors are considered. Evidence indicates that micro-sampling can be performed without adverse toxicological consequences, even in repeated sampling scenarios.

In conclusion, micro-sampling represents a scientifically sound and ethically responsible approach for TK assessments in toxicology studies. Its adoption can significantly reduce animal use and distress without compromising data integrity, supporting industry commitments to the 3Rs.

Keywords: micro-sampling, toxicokinetics, 3Rs, rodent studies