Exploring Microsampling: Live Panel Discussions
Bioanalysis Zone hosted a lively panel discussion with Charles River’s Head of Bioanalysis and Immunology, Tim Sangster, and four of his industry colleagues who gathered to speak about changes, challenges and the future.
Part 1: Changing landscape in the field: Increase in microsampling, where the increase is happening and regulatory approval.
The panel discussed the reasons for the increase in microsampling, which they feel is driven by a better understanding of techniques and better devices that are now available even from two years ago with DBS. It is a natural progression from dried blood spot (DBS), with more peer reviewed publications supporting microsampling and gaining confidence among regulators, drug developers and clients. Regulatory bodies now support use of microsampling in the nonclinical space.
The panel also highlighted the growth of microsampling in the nonclinical space, due to the 3Rs and the ability to create better study designs that use smaller volumes and optional biomarker parameters. They also pointed out the increase in microsampling for pediatric and geriatric clinical trials, where sample volume limitations or the need for increase monitoring is required.
Finally, regulators have supported small liquid samples and are encouraging the use of microsampling when appropriate in the nonclinical space. Where we see the limited or slower approval is with the solid samples in the clinical studies. Again, this is NOT due to the actual test itself but the limited number of people using it, case studies and peer reviewed approval around it.
Part 2: Challenges with microsampling
There is still a challenge in the preclinical studies using the standard toxicology design. Microsampling is a natural fit for bioanalysis, but in the main study there is an additional need for clinical pathology endpoints which have the highest blood volume requirement, and therefore, satellite TK animals are often required. Discovery studies benefit most because the goal here is pharmacokinetics, not toxicology. More rodent study designs can include serial blood samples.
Another barrier is moving from microsampling collection to the microsampling analysis. There is still a need to improve the clean up of in-life samples to increase assay sensitivity in the final aliquot. Automation is growing, and there are new devices and techniques to ensure that the cleanest sample goes into the equipment.
Last, clients have to approve the use of these techniques, and they are often the last to get on board. Content with traditional proven methods, they find it difficult to switch to newer technologies and smaller samples.
Part 3: Future of microsampling
Coming to a close, the panel turned the discussion to a growing portfolio of biologics. Within these programs, multiple samples are taken for TK, antibody response and biomarkers, which means taking large samples from a single animal. Microsampling has traditionally been LC-MS based, and questions remain about the stability of biologic compounds in the small samples. More studies are being conducted to build confidence in microsampling techniques with biologics, and it will just take time as it did with small molecules.
There could also be a future for microsampling in personalized medicine (patient-specific therapies) or rare diseases. These populations have limited patients, and it is harder to get the sample collected. New technologies, such as volumetric absorptive microsampling, (VAMS) are being used to facilitate these trials.
Finally, the group sees possible changes in the physical laboratory space to support microsampling. Current equipment is large and stationary; as technology advances and instruments become smaller, there might be developments in portable or remote systems.