Artificial Blood & Blood Substitutes: HBOC Class Effect

A mindset shaped by its time. The blood-replacement approach reflected the clinical priorities, scientific knowledge and technological tools available during early development. As that knowledge evolved, advances in vascular biology, oxygen sensing, microcirculation and protein engineering provided a stronger foundation for reconsidering the question. Some of these discoveries are recognized by Nobel Prizes. For BHOC, the question is no longer whether one product can reproduce blood, but which oxygen-delivery function needs support and under which physiological conditions. These discoveries inform that question; they do not validate a particular product.

The marketing trap. “Artificial blood” was a powerful shortcut: simple, memorable and easy to communicate. In our view, that clarity came at a cost. It encouraged expectations of replacing the whole blood system rather than supporting a defined biological function. As regulatory evaluation developed alongside these technologies, the broad label also risked obscuring the product-specific questions: which formulation, which indication, which physiological endpoint and which evidence?

The class-effect problem. We challenge the assumption that results from different early HBOC products can be treated as a single, permanent verdict on every hemoglobin-based oxygen carrier. Our criticism concerns that generalization, not the need to examine the findings for each tested product. In our view, broad replacement expectations and class-wide interpretations damaged confidence in an entire field and helped turn limitations of particular products and trial settings into presumed limits of the whole approach.

Biopure illustrates why the distinction matters. Among the major historical HBOC programs covered in our archive, Biopure followed a distinct regulatory and real-world path. Oxyglobin obtained veterinary authorizations in the United States and Europe, while Hemopure reached human-use authorization in South Africa. Their product-specific approvals and use are documented in our historical and regulatory record. They should not be collapsed into the same history as candidates that never reached those milestones.

Reassessment is already under way. In recent years, further analyses and comparative reviews have provided a basis for revisiting earlier conclusions about HBOCs and how they are applied across different products. We believe this reassessment should distinguish molecular design, formulation, clinical context and physiological endpoints, rather than treat all hemoglobin-based oxygen carriers as a single, uniform class. Revisiting broad class-wide conclusions does not mean dismissing product-specific safety findings.