Techno-Economic Analysis of a Hyaluronic Acid Production Process Utilizing Streptococcal Fermentation

Abstract

Hyaluronic acid (HA) is a polysaccharide of alternating d-glucuronic acid and N-acetyl-d-glucosamine residues present in the extracellular matrix of connective, epithelial, and nervous tissues. Due to its singular hydrating, rheological and adhesive properties, HA has found numerous cosmetic and medical applications. However, techno-economic analyses of high value-added bioproducts such as HA are scarce in the literature. Here, we present a techno-economic analysis of a process for producing HA using Streptococcus zooepidemicus, simulated in SuperPro Designer. In the baseline scenario, HA is produced by batch fermentation, reaching 2.5 g/L after 24 h. It is then centrifuged, diafiltered, treated with activated carbon and precipitated with isopropanol. The product is suitable for topical formulations and its production cost was estimated as 1115 $/kg. A similar scenario, based on fed-batch culture and assuming a titer of 5.0 g/L, led to a lower cost of 946 $/kg. Moreover, in two additional scenarios, 10% of the precipitated HA is diverted to the production of a highly pure and high-molecular weight HA, suitable for injectable applications. These scenarios resulted in higher capital and operating costs, but also in higher profits, because HA for injectable use has a higher selling price that more than compensates for its higher production costs.

Hyaluronic Acid-Conjugated Carbon Nanomaterials for Enhanced Tumour Targeting Ability

“…Currently, the price is unaffordable for any significant application, with HA costing approximately 150 EUR for every 10 mg [ 100 ]. It is predicted that this price could become less than half in a study by Ferreira et al [ 101 ].…”

Comprehensive review on biotechnological production of hyaluronic acid: status, innovation, market and applications

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Figure 4. General representation of unit’s operations evolved in HA production by fermentation pathway (Modified and adapted from[ 77 , 78 ].

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“…Modern strategies are found in the literature involving simulations and techno-economic analysis to guide the industries for HA production ( Table 3 ) [ 61 , 77 , 78 ]. 1 pointed out the impact of various sources and extraction methods on HA production.…”

“…Application of HA in medical applications suitable for injectable applications like osteoarthritis requires HA of extremely high purity, which settles prices up to 30-fold higher than topical or dietary HA [ 29 ]. Based on reports from the US International Trade Commission and Scientific Literature, the average selling price of ‘topical’ HA is 2000 $/Kg for and for ‘injectable’ HA is 50,000 $/Kg [ 78 ].…”

Production of Hyaluronic Acid from Molasses by Streptococcus thermophilus TISTR 458

“…Streptococci are fastidious lactic acid bacteria [10] which demands nutritional enrichment in culture medium for cell growth and HA production [11]. Using of the chemically defined medium (CDM) [10] and the addition of amino acids such as arginine and lysine in the culture medium help supportive for cell growth and HA production [12]. These lead to high production cost which was the obstacle of commercial competitiveness on HA production.…”