A variety of animal and recombinant sources exist for albumin, which is a key component of vaccine and therapeutic protein formulations. Choosing the right albumin is not a simple price comparison exercise, however. Lower cost plasma-derived human serum albumin (HSA) and recombinant albumins carry hidden risks, while the premium recombinant albumins that are ideal for biologics manufacture and formulation can be prohibitively expensive due to scarce supply.
Serum albumin brings hidden risks
Using albumin from blood donors and recombinant sources for biopharmaceutical manufacture or cell and gene therapies carry a number of risks, such as unnatural post-translational modifications. Animal-derived albumins also face supply issues, such as batch-to-batch inconsistency that can impact performance. Ethical considerations are another concern. Because plasma-derived albumin is at inherent risk of viral and prion contamination, proving its absence in one batch does not mitigate subsequent batches. It is also impossible to prove the absence of unknown emerging pathogens in each batch. The ever-changing sources of animal and human serum albumin are another complicating factor.
Regulators have therefore set a high bar. They need to be satisfied that these risks are being sufficiently mitigated. This creates a substantial overhead in terms of additional processing, testing, quarantining, documentation and administration systems, as well as extra hours for skilled staff.
A high price for recombinant albumin
Recombinant albumin derived from Saccharomyces cerevisiae (baker’s yeast) has always been the high quality alternative to serum albumin that also delivers consistency. It avoids the contamination and immunogenicity issues of cheaper sources of albumin, such as plasma-derived HSA, or recombinant albumins from Pichia pastoris or rice. It is also the United States Pharmacopeia (USP) monograph reference standard recombinant albumin. However, the technology was patent protected for many years, which kept prices high, and limited its use to very high-value therapeutics such as vaccines or cell and gene therapies.
QTL innovation promises to widen access
Fortunately, recent innovations in QTL technology have allowed new strains of Saccharomyces cerevisiae to be developed for high-quality recombinant albumin manufacture from optimised bioprocesses.
This promises to catalyse wider access to high-quality albumin at lower prices.
When the overheads and risks associated with using plasma-derived albumin are taken into account, large-scale recombinant albumin production from optimised baker’s yeast has the potential to be both safer and more cost competitive than the alternatives. As the regulatory environment continues to encourage the adoption of recombinant albumins for manufacturing instead of serum albumin, the advantages of QTL technology look set to increase.
