Recombinant human serum albumin-A paradigm shift: From laboratory development to industrial-scale production, and...

The transition from plasma-derived to recombinant human serum albumin (rHSA) represents a pivotal advancement in ensuring a safe and sustainable supply of this essential therapeutic protein. This review delineates the industrialization pathway of rHSA, highlighting yeast (Komagataella phaffii) and transgenic rice as the two dominant production platforms. Our analysis demonstrates that this paradigm arises not merely from considerations of yield, but from an optimal integration of scalability, cost-effectiveness, regulatory feasibility, and compatibility with next-generation purification strategies. Integrated multimodal purification technologies are critical for achieving the ultra-high purity required for high-dose therapeutic applications. We further synthesize clinical evidence confirming the biosimilarity and safety of rHSA produced from both platforms across key indications, thereby validating the entire technological pipeline from gene to final product. Looking ahead, we posit that the value of rHSA extends beyond substitution; its engineerability positions it as a versatile platform for innovative drug delivery and an essential animal-free component in advanced therapies. Realizing its full potential depends on overcoming the economic challenges of production scale-up, ensuring product consistency, and leveraging synthetic biology and intelligent manufacturing to pioneer a new generation of multifunctional biotherapeutics.