Albumin is a key component in life-saving vaccine and biopharmaceutical formulations, where it stabilises active ingredients and extends shelf-life. Recombinant albumin in particular has gained market share in recent years, partly to allay regulators’ concerns about viral contamination. However, not all recombinant albumins are the same, and the risks associated with batch-to-batch inconsistency and performance deficit deserve far greater scrutiny.
Product performance carries risks
In a sector with revenues of many millions, if not billions of dollars, the stakes are high, even when the risks are perceived as low. Lost batches leading to lower gross margins are just one consequence of a deficit in product performance for patent protected biopharmaceuticals and cell therapies containing human albumin ingredients. Adversely affected patients are another, far more serious potential consequence. This is especially true for products containing plasma-derived albumin, where the inherent risk of viral or prion pathogen contamination cannot be fully eliminated. Worse-case scenarios from a commercial perspective include regulatory suspension of market access, adverse publicity and loss of preference from key buyers.
Recombinant albumin is not a blunt instrument
Using recombinant albumin does mitigate these risks. At present, recombinant albumin is commercially available at scale from rice (Oryza sativa) or from yeasts such as Pichia pastoris and Saccharomyces cerevisiae (baker’s yeast). For many years, recombinant albumin from baker’s yeast was only available in its most pure and expensive forms, which are arguably over-engineered for some applications.
Albumin is a complex molecule, however. The factors that influence its performance and safety such as differences in potentially immunogenic post-translational modifications (PTMs), bound ligands, and process-related impurities, need to be expertly handled. So do costs. The highest quality recombinant albumin can be prohibitively expensive due to restricted supply. Lower-cost albumins are less expensive, but may have significant drawbacks in terms of safety and performance that aren’t always highlighted.
Drawbacks of rice and Pichia
While recombinant albumin from Pichia pastoris or rice is adequately functional in many cases, it has also been independently shown to contain potentially immunogenetic PTMs, which would be undesirable in injectable human therapeutics and cell therapies. Differences in the process-related impurities and bound ligands can impact performance, especially for cell therapies. Significant losses of correct albumin isoform occur during downstream processing when removing small amounts of albumin with undesirable PTMs, which are chemically very similar and difficult to separate.
QTL strains enable a range of purity levels
Fortunately, new strains of Saccharomyces cerevisiae for the manufacture of recombinant albumin are now being created at a range of purity levels, all controlled for undesirable PTMs. This has been made possible by the deployment of new QTL technology, resulting in albumin that is of the highest quality and suitable for the most challenging applications, including cell therapy development and manufacture.
This new generation of recombinant albumin provides a safer alternative to animal-derived albumin. Clinical testing demonstrates that albumin from Saccharomyces cerevisiae has an acceptable PTM profile. Baker’s yeast does not have any pathogenic lytic viruses or prions of concern. It has GRAS status (generally regarded as safe), with a long and safe track record in biopharmaceutical manufacturing, including insulins.
Improving access to recombinant albumin
Bespoke optimisation of production strains enabled by QTL technology promises to broaden access to premium quality albumin at lower prices, accelerating the transition away from animal-derived albumin.
That can only happen safely, however, if there is greater transparency about the PTM profiles and associated risks of different recombinant albumins on the market.
