Quality by design in advanced anticancer therapeutics: bridging design space, manufacturing, and clinical performance

Anticancer therapies increasingly rely on complex formulations and potent compounds with narrow therapeutic windows, making consistent product quality and performance essential. Quality by Design (QbD), supported by ICH Q8-Q10 guidelines, offers a systematic framework integrating formulation design, process understanding, and product quality throughout development, particularly for modern oncology therapeutics. A literature search in PubMed and Google Scholar identified studies published 2016 onwards, prioritizing high-quality (Q1-Q2) journals, yielding 83 references.

This review discusses how QbD principles guide anticancer drug development, highlighting Quality Target Product Profiles, Critical Quality Attributes, and design space in controlling variability affecting bioavailability, therapeutic index, and clinical outcomes. It examines how Process Analytical Technology, mechanistic modeling, and digital twins support robust manufacturing and scale-up of complex oncology formulations. Selected examples, including imatinib- and paclitaxel-based therapies, illustrate how QbD-informed strategies influence formulation optimization, process robustness, and lifecycle management.

The next phase of oncology drug development will likely depend on integrating QbD with predictive modeling, real-time release testing, and continuous manufacturing to manage targeted therapy complexity. QbD should evolve from a compliance framework into a translational tool linking formulation attributes with in vivo performance, enabling more reliable development and lifecycle management of precision oncology therapeutics.