Leading treatments of cancer and many blockbuster medications depend on monoclonal antibodies (mAbs), but they are expensive to develop and manufacture. Recent innovations promise to accelerate efficiency gains in the creation of cell line production, promising far-reaching benefits in the field of biological therapeutics.
Cell culture media costs
Chinese Hamster Ovary (CHO) cells commonly used to secrete monoclonal antibodies are developed, grown and sustained in cell culture media. Production efficiency and the quality of the end product all depend on cell culture media ingredients being of the highest standard.
Historically, albumin, growth factors and certain nutrients important for cell culture media came from foetal bovine serum, which is animal-derived and not ideally suited for safe, reliable biopharmaceutical manufacturing. Other supplies exist to make equivalent animal-free chemically defined media, but they are also expensive and have the potential to affect product quality.
The high cost of cell culture media has several downstream impacts. It limits research experiments, deterring innovation and medical breakthroughs. It raises the costs of batches for clinical testing. It also impacts commercial scale manufacture, driving up the prices charged for healthcare.
Existing ingredients have limitations
Albumin is an important ingredient in cell culture media, but because animal-derived albumin has inconsistent quality and risks pathogenic viral or prion contamination, the best alternative source is recombinant albumin derived from Saccharomyces cerevisiae (baker’s yeast). Unfortunately, patent protection and know-how have restricted access to high quality recombinant albumin, which has made it prohibitively expensive for commercial manufacture.
Chemically defined media is the other popular option for new antibody products, partly because it is fully characterised in terms of constituent ingredients and concentrations – which is useful for regulatory purposes and process optimisation. But the technical barriers to affordable, high-quality, pure and scalable recombinant albumin and other key cell culture media ingredients, such as growth factors, are still a real problem in the field of biological therapeutics.
A new approach
Fortunately, the advent of Quantitative Trait Loci (QTL) technology now enables new strains of S. cerevisiae to be created for the manufacture of recombinant albumin that is of the highest quality and consistency.
The albumin produced is regulatory friendly, suitable for inclusion in chemically defined media – which are preferred for monoclonal antibody development and manufacture – and able to meet large-scale supplies of affordable recombinant albumin. S. cerevisiae is also the source of monograph standard recombinant albumin in the United States Pharmacopeia-National Formulary (USP-NF). An independent analysis comparing recombinant albumins from different sources to albumin from human plasma shows the highest quality and consistency for recombinant albumin derived from baker’s yeast (Frahm et al. 2014).
Benefits for biological therapeutics
An affordable form of high quality recombinant albumin, and the ability of QTL technology to create similar high quality ingredients for cell culture media, such as transferrin and growth factors, will catalyse widespread benefits across the biological therapeutics market.
It promises to reduce the cost of research and development for monoclonal antibodies and other biologics derived from mammalian cell culture. This should ultimately lower the cost of goods for many existing and future therapies. This benefits the manufacturers of monoclonal antibodies and also the health services and insurers who pay for them, making life-saving treatments more accessible to those in need.
Unleashing the potential of monoclonal antibodies, as a class of biological therapeutics, have become a key workhorse of the global formulary of medicine, but their potential has yet to be fully realised. QTL technology’s ability to circumvent the know-how barriers of existing suppliers is creating an abundant source of affordable high quality recombinant albumin using the accepted manufacturing source of S. cerevisiae. This promises to lighten the financial burden on developers of new treatments and reduce costs for monoclonal antibody therapies that are already approved and on the market.