For more than 40 years, Charles River’s exceptional team of scientists, including toxicologists, pathologists, veterinary surgeons, regulatory specialists, and support personnel, has designed and performed safety programs ranging from acute through chronic toxicity and carcinogenicity studies. We offer a broad range of animal models and numerous routes of administration. In addition, Charles River leads the industry in the fields of developmental and reproductive toxicology, photobiology, inhalation toxicology, intravenous infusion, immunotoxicology, bone research, and other specialty toxicological assessments.
Charles River is firmly committed to the 3Rs (Replacement, Reduction, and Refinement) to help limit the number of animals used in research. The use of microsampling in preclinical drug development helps reduce small animal usage in toxicology studies while refining data by measuring full toxicokinetic profiles from each animal. There are several approaches, but the most common at present are the use of Dried Blood Spots (DBS) and Capillary Microsampling (CMS).
DBS is very useful as it reduces the sample volume required and also eliminates the need for frozen storage or shipment, which is more applicable to clinical toxicokinetics than in preclinical studies. Since the spot size is dependent on the hematocrit level in the sample, there are still some questions regarding the precision of data generated from the DBS method. This can be overcome by using an accurate volume for spotting and then analyzing the whole spot. However, there are also concerns over the recovery of analytes from the spot. Nonetheless, the advantages of DBS in clinical applications far outweigh the current issues and a lot of focus is targeted on moving to Dried Plasma Spots.
CMS is a technique that allows for the accurate collection of a microsample. Generally 30µL of blood is collected and then an accurate 8µL aliquot of plasma is collected and sent for analysis. This may allow for the reduction of satellite groups in preclinical toxicology studies, although is generally of little benefit in the majority of clinical programs.
Overall, the advantages of microsampling in terms of reduction and refinement far outweigh its limitations in applicable bioanalytical techniques. The use of more sensitive analytical techniques is helping to address these limitations. We are currently validating this method for use in small molecules and once completed will be progressing this work into large molecules. A presentation about our CMS capabilities is now available online through our information portal, The Source℠.
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