Merck's perspective on the implementation of dried blood spot technology in clinical drug development - Why, when and how

摘要

This paper communicates Merck's thoughts on why, when and how to use dried blood spot (DBS) technology in a clinical setting, and provides a strategic approach, emphasizing the necessary steps, for successful clinical implementation of this microsampling technique. PK consideration based on relevant in vitro data, that is, blood-to-plasma ratio, hematocrit, plasma unbound fraction and/or blood cell partition, is suggested to be part of the decision tree on when to choose DBS as a surrogate matrix for PK analysis. A quick feasibility assessment addressing analytical challenges, including sensitivity, hematocrit impact and storage stability, needs to be evaluated before initiating DBS studies. Special attention should be paid to the clinical sample collection procedures to ensure data quality. Bridging studies are required to establish the correlation between plasma and DBS data to ensure that pooling of data from the various clinical studies can be used in population PK or PK/PD assessment. Seeking regulatory feedback and guidance on a case-by-case basis is recommended.