Recombinant Human Albumin
Albumin is a 66-kDa plasma protein with a variety of physiological and stabilizing functions in vivo.13,14 In cell culture, albumin (usually in the form of BSA or HSA) is known to serve several important functions, including acting
as a carrier protein and protecting cells from mechanical stress, and it is also thought to be a major serum survival factor,
functioning as an inhibitor of apoptosis.15
Several recombinant human albumin (rHA) products are now commercially available and are offered as alternatives to HSA for
a range of biopharmaceutical applications. rHA expressed from S. cerevisiae has been shown to exhibit similar safety, tolerability, and pharmacokinetic/pharmacodynamic profiles to native human albumin,10 and it has shown equivalent capacity to protect immunological, biological, and biochemical cell function.15
rHA from other yeast hosts, such as Aspergillus oryzae (for example, rProbuminAF), is being developed specifically for industrial cell culture use. Used as an ingredient in mammalian
cell culture, such recombinant albumins can deliver quality, regulatory benefits, and performance benefits for both research
and commercial-scale applications.
ANIMAL-FREE RECOMBINANT SUPPLEMENTS—A STEP IN THE RIGHT DIRECTION
New animal-free cell culture ingredients derived from microbial expression systems (such as those described above) offer a
valuable solution to the quality and performance limitations of supplement regimes currently used with serum-free and protein-free
media formulations for industrial-scale mammalian cell culture. Such ingredients, designed and manufactured exclusively to
support biopharmaceutical manufacturing, bypass many regulatory hurdles and offer a secure, consistent supply for commercial-scale
production.
ANIMAL-FREE TECHNOLOGY: THE MICROBIAL OPTION
Mammalian expression systems historically have been characterized as slow and expensive vehicles for the large-scale manufacturing
of therapeutic proteins. They are, however, essential for the production of therapeutics that require complex post-translational
modifications (PTMs), particularly glycosylation. O-linked and N-linked glycosylation patterns can influence protein stability,
ligand binding, immunogenicity, and serum half-life, and they are significant in the context of efficacy of a wide range of
biopharmaceuticals.1
On the other hand, microbial systems as models for the animal-free production of recombinant proteins on an industrial scale
have much to offer the biopharmaceutical industry.
Unlike mammalian-based technology, microbial systems are typically grown in simple, chemically defined media. And, in the
case of the proprietary E. coli and S. cerevisiae systems (which enabled the development of the recombinant ingredients described above) the entire production process is free
from the use of animal- or human-derived materials.
With faster growth rates, high yields, and well understood genetics, microbial systems remain the obvious choice for expression
of non-glycosylated peptides and proteins. Of the 31 therapeutic proteins approved since 2003, nine are produced in E. coli.15 However, in spite of this prokaryote lacking the ability to perform eukaryote -specific PTMs, it is widely used for the
production of insulin, growth hormones, and growth factors. Yeast-based systems confer the advantages of high expression levels,
easy molecular manipulation, and low costs of goods; in addition, as eukaryotes, yeast can perform PTMs, such as proteolytic
processing, folding, disulphide bond formation, and glycosylation.
Since the 1980s, yeasts have been used for the large-scale production of recombinant proteins of human, animal, and plant
origin. The brewer's yeast S. cerevisiae is an extremely well characterized eukaryotic system with "generally regarded as safe" (GRAS) status, and it was widely used
for early protein production, including the first commercialized recombinant vaccine.16
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