Cell and gene therapy is set to change the face of medicine just as monoclonal antibodies did before it, with many treatments for key indications at the research stage or progressing steadily through clinical development. But without the means of growing cells that generate the desired product, this new generation of biological therapeutics risks getting bogged down in delays and spiralling costs.
Cell and gene therapy (C>) depends on high quality cell culture media, many of which contain albumin. Albumin enables a precisely controlled environment to be maintained for cells to grow and generate the required therapeutic product. Historically, however, patents and protected manufacturing know-how have restricted recombinant albumin supply. This has created a potential bottleneck – and higher prices.
While alternatives to albumin exist for some biologic products, they are less viable for C>. That’s why an abundant and reliable supply of premium recombinant albumin – which possesses critical properties for the protection of cells – underpins the future expansion of C>.
Alternatives carry risks
Traditionally, albumin – which is the most abundant protein in blood plasma – was extracted from mammalian or human blood serum. However, regulators are less likely to approve products using serum-derived albumins due to the risks from inconsistent quality and infective viral or prion contaminants. This has discouraged the use of serum-derived albumin in biological therapy manufacture – except for existing products with historic albumin processes.
Investors putting their money into complex innovations that require a scalable and reliable means of manufacture, naturally want to minimise their risks. A sub-optimal cell culture media that is under the regulatory spotlight is unlikely to be their preferred choice when developing a process for a new C>.
Using recombinant albumin is expensive
However, using recombinant albumin is currently expensive. The batches required for clinical testing carry costs that restrict the number of novel therapeutic projects pipelines can sustain. Scaled commercial manufacture is costly too, driving up the prices of vital therapies that already stretch health budgets. Margins tend to suffer as a consequence.
Baker’s yeast offers a sustainable solution
Fortunately, a number of recent patent expiries have enabled researchers to develop premium quality albumin from baker’s yeast, an animal-free source. Quantitative Trait Loci (QTL) technology uses a proprietary breeding method combined with genomic-based screening to overcome the know-how barriers surrounding recombinant protein manufacture. It also enables albumin production at a commercial scale.
Recombinant albumins secreted from baker’s yeast (Saccharomyces cerevisiae) were independently shown to have fewer post-translational modifications than plasma-derived albumin or recombinant human albumin from rice or Pichia pastoris (Frahm et al. 2014). They also tend to be of the highest quality and provide superior performance. For C>, and also for certain types of biologics, recombinant albumin produced in this way makes the best cell culture media possible.
Spreading the benefits of albumin
Commercial scale manufacturing using baker’s yeast enables the numerous benefits of recombinant albumin to be spread more equitably. Albumin’s antioxidant properties can help to neutralise free radicals and reduce oxidative stress. Recombinant Human Albumin (rHA), in particular, provides important stabilisation properties to prevent damage or denaturation to cells or proteins.
Albumins bind to and sequester various toxins or harmful metabolic byproducts, reducing their availability to interact with and potentially damage cells and biologics. They help maintain the acid-base balance in the culture media, acting as a buffer to changes in pH. As a carrier protein, they are also able to bind and transport various hydrophobic molecules, helping to deliver essential nutrients to cells in culture.
Importantly, premium recombinant albumin can now be adapted during formulation to meet the needs of specific applications, such as C>. Furthermore, the production strains developed using QTL technology enable the key genomic features specific to albumin production to be patent protected. This enables the manufacturing strains to be licensed.
The ability to access high quality recombinant albumin at a commercial scale will be of strategic value to any business with ambitions in the emerging C> market. Acquiring the relevant manufacturing know-how and capability is a logical step towards securing the supply of this critical C> product.
Strains devised by QTL technology can be used to improve albumin manufacture and extend patent protection, enabling the technology’s transformative capabilities to be deployed by first-movers across a range of therapeutic categories – especially new markets.
By spurring innovation and lowering costs over the longer term, rHA manufacturing resulting from QTL technology deployment is taking what software engineers call an open source approach, which is designed to ultimately benefit the many, not the few.