Prior Helen, Adedeji Adeyemi O, Allen Romalie, Angus Derek, Baker Daniel, Blunt Hollie, Coleman David, Dunmore Helen-Marie, Passini Elisa, Putnam Tara, Rosseels Marie-Luce, Spooner Neil, Stewart Jane, Strepka Carol, Stokes Alan, Verhaeghe Tom, Wilson Amanda, Sewell Fiona
National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), 215 Euston Road, London, NW1 2BE, United Kingdom.
Genentech Inc, 1 DNA Way, South San Francisco, CA, 94080, United States.
Toxicol Res (Camb). 2025 Mar 31;14(2):tfaf045. doi: 10.1093/toxres/tfaf045. eCollection 2025 Apr.
Adoption of a blood microsampling technique can reduce or avoid the use of satellite animals (rodents) for toxicokinetics or other purposes in discovery and toxicology studies and provides refinements applicable for both rodents and larger animals. Microsampling can increase the scientific value of data obtained from rodent studies during drug and (agro)chemical development, enabling multiple endpoints to be investigated and compared in an individual animal in the same way as non-rodents. A cross-sector survey was developed to understand the current use of microsampling in toxicology studies, with the aim of identifying the specific studies in which microsampling was employed and the barriers to wider uptake. A high proportion of the survey responses indicated that microsampling was used, however, the extent varied widely. Some organisations use the technique only in non-GLP studies. Microsampling was used most for pharmacokinetics or toxicokinetics, commonly within small molecule and agrochemical toxicity studies, but less frequently within large molecule, cell/gene therapies or industrial chemical studies. A wide variety of barriers to wider use of microsampling were provided, typically around reticence to change from using larger samples, or not wishing to validate another bioanalytical method given the resources and challenges associated with the validation of a new technology. Despite these barriers, some organisations have adopted microsampling routinely across many/all rodent toxicity studies and there are opportunities to further reduce and refine animal use across all sectors by wider adoption of microsampling.
采用血液微量采样技术可以减少或避免在发现和毒理学研究中使用卫星动物(啮齿动物)进行毒代动力学或其他目的的研究,并提供适用于啮齿动物和大型动物的优化方法。在药物和(农用)化学品开发过程中,微量采样可以提高从啮齿动物研究中获得的数据的科学价值,使单个动物能够像非啮齿动物一样以相同的方式研究和比较多个终点。开展了一项跨部门调查,以了解微量采样在毒理学研究中的当前使用情况,目的是确定采用微量采样的具体研究以及更广泛应用的障碍。调查回复的很大一部分表明使用了微量采样,然而,使用程度差异很大。一些组织仅在非GLP研究中使用该技术。微量采样最常用于药代动力学或毒代动力学,通常在小分子和农用化学品毒性研究中使用,但在大分子、细胞/基因疗法或工业化学品研究中使用较少。提供了广泛的阻碍微量采样更广泛使用的因素,通常围绕着不愿从使用大样本转变,或者鉴于与新技术验证相关的资源和挑战而不想验证另一种生物分析方法。尽管存在这些障碍,一些组织已在许多/所有啮齿动物毒性研究中常规采用微量采样,并且通过更广泛地采用微量采样,有机会在所有部门进一步减少和优化动物使用。