(T0930-09-50) Evaluation of the Tasso-M20 Microsampling in Support of Clinical PK Studies

Purpose: Over the past few years, there have been technological advancements in volumetric blood microsampling with more reliable and convenient techniques for at-home sample collections. A novel automated sampling approach using the Tasso-M20 collection device, which is less painful and simpler to operate than fingerstick self-sampling, has been evaluated for home sampling for the first time in one of our clinical programs. To evaluate the feasibility of adopting Tasso-M20 for broader clinical use, we characterized the Tasso-M20 tip, described the bioanalytical method development and validation approaches by leveraging our experience using Volumetric Absorptive Microsamping (VAMS), and recommended a standard approach for the assay development using Tasso-M20, ensuring sample and data quality.

Methods: A total of nine model compounds in clinical development programs were selected based on various physico-chemical properties. A decision tree was developed to evaluate the recovery and stability at room temperature and stressed conditions at 40℃/75% Relative Humidity (RH). For the seven compounds which already had a VAMS bioanalytical method, the decision tree was followed to assess the feasibility of direct method transfer or the need for modification. For the compounds showing a difference in stability between VAMS and M20, the root cause of the instability on Tasso-M20 sorbent was investigated. In addition, the M20 blood absorbing volume was measured with wet and dry M20 sorbent weighing. The potential clinical sampling deviations and storage variations were investigated, and associated impact on sample quality in bioanalysis was assessed (e.g., overflow, drying process). To understand the blood anticoagulant impact on the matrix calibrators compared to capillary blood clinical samples that are devoid of anticoagulant, Tasso-M20 samples collected from volunteers in EDTA, sodium heparin or capillary blood were dried and weighed. Furthermore, quality control samples prepared in EDTA and sodium heparin for the model compounds were tested for accuracy and stability. To improve the efficiency of Tasso-M20 sample handling in the lab, tools were designed, and 3-D printed to dry, store, and handle the Tasso-M20 samples. An automated workflow using Hamilton is under development for standard and quality control sample preparation and clinical sample extraction.

Results: A high-level standard approach for feasibility assessment was proposed for Tasso-M20 sample preparation covering least to most complex with extraction methods and specific solvents. Overall, among the nine compounds evaluated, all achieved acceptable precision (≤15%), accuracy (≤15%), sensitivity, recovery ( >85%), matrix factor and minimum 1 week stability at RT and 40℃/75%RH. However, four compounds failed at extended 1 month stability at 40℃/75%RH. Among the seven compounds with VAMS method available, five of the VAMS methods were directly transferable to the Tasso-M20 method, while two methods required significant extraction modification to pass the acceptance criteria. The use of EDTA or sodium heparin as anticoagulant for preparation of calibrators seems not to impact the recovery and stability for majority of the compounds evaluated. However, for a method (compound A) using enzymatic sample preparation process, EDTA impact on stability was observed after overnight drying due to a potential analyte degradation. By switching to sodium heparin and effective drying of the blood M20 cartridge, the analyte stability was established for at least 77 days at 40℃/75%RH. The M20 sorbent showed consistent CV (≤5%) in blood volume by weight. Precautions on the sampling and drying process were discussed to ensure data accuracy.

Conclusion: The evaluation has demonstrated the feasibility of using Tasso-M20 to support regulated bioanalysis for clinical samples. If a VAMS method is available, it may be transferrable to Tasso-M20 with minimum modifications to the extraction procedure. However, in some cases, major modification to the extraction procedure may be needed. The proposed standard extraction approach will guide future M20 method development. The lessons learned in the model compound evaluation will be valuable for other M20 clinical studies or other studies that can use M20 as an alternative sampling procedure. In addition, an automated procedure of preparing standard and QC samples can be set up in a bioanalytical lab to improve assay throughput and reproducibility while reducing ergonomic related injuries.

Acknowledgements: We would like to acknowledge Tasso for the initial discussions on the Tasso-M20 device evaluation.


Table 1: Evaluation summary of Tasso-M20 in model compounds


Figure 1: Evaluate Tasso-M20 Recovery and Stability – Decision Tree


Figure 2: Characterize Tasso-M20 volume in venous and capillary blood by weighing