The compound, which finished ahead Dr Reddy’s precatalyst fabrication technology and Pierre Fabre’s “green” formulation processes, is being developed for a wide range of solubility applications in the pharmaceutical sector.
HyaCare is free of both animal proteins and bacterial endotoxins and is produced by a strain of the organism Bacillus subtilis that has been modified to synthesize both the enzyme required to produce HA and the precursor sugars from which the polysaccharide is built.
The Bacillus strain, which is owned by Novozymes, is a well-characterised, endotoxin free organism that is generally regarded as safe by the US Food and Drug Administration (FDA).
Novozymes’ science manager Fanny Longin told in-PharmaTechnologist.com that the firm’s method of production has several advantages of existing methods of HA manufacture.
Dr Longin explained that: “traditionally, hyaluronic acid is derived from rooster combs or from genetically modified strains of pathogenic Streptococcal bacteria, which allows for a high degree of contamination by animal proteins, viruses and endtoxins present in the bacterial genome.
“HA produced by our, non-pathogenic strain of B.subtilis sidesteps the risk of viral and endotoxin contamination,” she added, going on to say that unlike Streptococci, Novozymes’ modified bacteria can be fermented in an animal product-free environment.
Organic solvent-free process
Another innovative feature of HyaCare is related to its collection after the fermentation stage. While both rooster comb and Streptococcus derived HAs must be recovered using powerful organic solvents, Novozymes’ product is secreted outside the bacterial cell and can be collected using only water.
Longin commented that, in addition to completely removing the risk of solvent contamination of the final product, the technology yeilds a highly pure compound.
In addition, Novozymes’ spray drying system produces a fine powder final product that has a uniform particle size, which the firm believes will expedite its customers manufacturing steps.
Longin went on to say that: “having established both the B.subtilis strain and production technology, Novozymes is now in the process of upgrading the product [which already meets cosmetic and ophthalmology quality standards] to pharmaceutical grade”
She added that the firm intends to set up a new manufacturing facility and work with industrial partners to scale up production of drug grade HyaCare and anticipates that the whole process will be completed over the next three years.