Bioanalysis – but not as we knew it: an AstraZeneca perspective of the last 10 years evolution to meet a diversifying portfolio

Here we will share an insight to the Translational Biomarker and Bioanalysis group (TBB) analytical strategies used to support AstraZeneca’s new treatment approaches including antisense oligonucleotides (ASOs) and modified messenger RNA (mRNA) therapeutics that modulate protein production in vivo, novel protein therapeutics and novel approaches to small-molecule drug delivery. [...]to fully understand the safety and PK/PD relationship for a modified mRNA drug project, numerous bioanalytical end points may be required, including analysis of the mRNA, the produced protein, the LNP and markers of immune activation in response to 1-3 (including anti-drug antibodies and inflammatory cytokine profiles). [...]a key component of any study setup is ensuring that optimal sample collection occurs, for example, whole blood is collected directly into Paxgene protectorate for mRNA analysis or plasma is acidified prior to freezing in order to stabilize the LNP component; these steps are essential to have confidence in the data generated and the decisions made upon that data. [...]these approaches have increased the complexity for bioanalysts, since end points are required for circulating ‘total’ drug to understand the longevity of pharmacological effect as well as a released circulating drug concentration, which drives the potential toxicological and therapeutic thresholds. Since the amount of therapeutic agent contained within a nanomedicine can be very large relative to the circulating released drug the handling of the samples is critical to not generate artificially high levels of released drug through ex vivo degradation of the nanomedicine.