Demand for animal-free recombinant albumin across a widening range of biopharmaceutical applications has driven up prices, limiting access to this key ingredient for the development and production of affordable vaccines and innovative monoclonal antibodies. New technologies, however, are set to boost production, spreading the benefits of high-quality albumin beyond therapeutics to other uses such as skincare.
Albumin’s potential is stifled by supply issues
Albumin is the most abundant protein in the blood and is widely used as a constituent of diagnostics, medical devices and regenerative medicine. It plays multiple roles in cell culture media, supplying essential nutrients, stabilising key growth factors, and protecting cells and final protein products from oxidative damage.
Monoclonal antibody manufacture is increasingly adopting chemically defined media, which uses recombinant albumin, where the constituents and their concentration are fully characterised and quality controlled. Regulators prefer this approach to others that use animal-derived albumin or foetal serum because it mitigates safety and tolerance risks, especially the transmission of viral and prion pathogens.
However, patent protections and closely guarded know-how among a small number of incumbent suppliers of recombinant albumin have created shortages at the requisite grade, cost and commercial scale of manufacture. Formulations also tend to differ in levels of quality, consistency, and purity, causing regulatory and manufacturing issues.
The outcome is higher prices of cell culture media for the development and manufacture of key biological medicines – and lower levels of innovation.
Higher volumes meant lower quality
Lower quality albumin tends to come at more affordable prices but presents manufacturing and regulatory issues that limit its usefulness, especially when it is animal-derived from mammalian blood serum and therefore not halal compliant.
At the other end of the quality spectrum are extremely pure recombinant albumin and/or specialist formulations such as those used in cell or gene therapies. These are typically from baker’s yeast, Saccharomyces cerevisiae, which defines the United States Pharmacopeia (USP) monograph reference standard recombinant albumin. This high-purity specialist albumin is in short supply and also expensive, restricting its use to high-value products such as childhood vaccines and therapeutics, where they form part of the final protein or for cell-based products introduced directly into patients.
To meet unmet demand, alternative sources of recombinant albumin have entered the market from Pichia pastoris or rice, although independent studies have shown quality and consistency issues, raising concerns about potential immunogenicity and performance risks.
New technology enables customised strains
Fortunately, new baker’s yeast strains have been created to manufacture high-quality, pure, affordable recombinant albumin at scale. Crucially it enables the production of different grades and types of albumin, unlocking its potential in both new and existing applications without over-engineering.
This has been achieved using Quantum Trait Loci (QTL) technology that harnesses the power of natural evolution in iterative breeding combined with functional genomics to optimise unique regions of the genome for improved performance. The resulting recombinant albumin is suitable for inclusion in chemically defined cell culture media, avoiding the impurity and infection risks of alternative sources while providing consistent high-quality material. It is, therefore, well-suited for new biologics currently being developed from mammalian cell culture, as well as some of those already on the market.
Conclusion
The availability of affordable forms of albumin of the requisite grade, tailored to specific applications and markets, promises to accelerate research in exciting areas of innovation, such as monoclonal antibodies and cell and gene therapy. Customised new strains of baker’s yeast could finally unleash the full potential of albumin, one of nature’s most ubiquitous proteins.
