Table of Contents
1. Fundamentals of Hyaluronic Acid
Hyaluronic acid is a natural polysaccharide composed of N-acetyl-D-glucosamine and D-glucuronic acid. Its exceptional viscoelasticity, biocompatibility, and water-binding capacity make it essential in applications such as dermal fillers, ophthalmic solutions, wound healing, and skin hydration. It is used across pharmaceutical, cosmetic, and nutraceutical industries for its moisturizing, lubricating, and regenerative properties.
Historically, hyaluronic acid was extracted from animal tissues such as rooster combs. However, hyaluronic acid is now primarily obtained through microbial fermentation using bacterial strains like Streptococcus zooepidemicus. Fermentation allows for controlled molecular weight, higher purity, and animal-free sourcing. Synthetic routes exist but remain limited due to their cost and complexity. Nowadays, precision fermentation is also used to produce hyaluronic acid, especially when specific variants are required.
Microbial fermentation ensures consistent quality, scalability, and regulatory compliance. It eliminates zoonotic risks and allergen concerns linked to animal-derived materials, while enabling precise control of hyaluronic acid’s molecular weight and yield.
2. Fermentation Process & Challenges
Streptococcus zooepidemicus remains the primary microorganism used for industrial hyaluronic acid production, though recombinant strains of Bacillus, Corynebacterium, and Lactococcus are emerging for improved safety and process control by precision fermentation.
Key challenges include high broth viscosity limiting oxygen transfer, lactic acid accumulation inhibiting cell growth, and metabolic competition between cell growth and hyaluronic acid synthesis pathways.
Yeast-based nutrients are critical for supplying amino acids, vitamins, and growth factors. Optimized yeast extracts like NuCel® and ProCel® improve yield, reduce lag phase, and enhance molecular weight control compared to standard casein or soy peptones and other commercially available nitrogen sources.
Industrial hyaluronic acid fermentation processes can achieve yields between 7–10 g/L under optimized conditions with appropriate yeast-based nutrients and phosphate buffering. Depending on the strain used and process development employed, the selection of specific yeast based nutrients is critical for achieving the desired yield.
3. NuCel® – Cosmetic & Nutra Applications
NuCel® enhances hyaluronic acid yield by up to +62% while reducing fermentation time by approximately 4 hours. Its high solubility and balanced nitrogen profile improve cell metabolism and reduce downstream processing variability.
NuCel® supports hyaluronic acid production across low to medium molecular weights (0.5–2 MDa), ideal for topical and oral beauty formulations focused on hydration and elasticity.
Yes. NuCel® is produced from yeast-based raw materials and is free from animal, allergen, gluten, and GMO components, compliant with Halal and Kosher certifications.
By increasing yield and process efficiency, NuCel® lowers the cost per kilogram of hyaluronic acid produced, reduces energy use through shorter fermentation cycles, and eases downstream processes (Purification and formulation steps).
4. ProCel® – Pharma-Grade Applications
ProCel® ensures pharmaceutical compliance through ultra-low endotoxin levels, strict batch-to-batch reproducibility, and comprehensive QA documentation packages including Certificates of Analysis, TSE/BSE statements, and allergen-free declarations.
Pharma-grade hyaluronic acid typically ranges from 1 to 3 MDa, with high viscosity and purity required for ophthalmic and injectable applications.
Procelys ProCel® range products are manufactured under GMP like standards and provide complete ISO, Halal, and Kosher certifications, along with audit support and technical dossiers suitable for regulatory submissions.
5. Batch-to-Batch Consistency & Quality
Consistency ensures reproducible molecular weight and rheological behavior, which are essential for pharmaceutical efficacy and cosmetic performance.
Their formulations are standardized and produced under controlled conditions with tight specifications on amino acid profiles and molecular weight distribution.
Each batch is delivered with a detailed CoA including nitrogen content, solubility, endotoxin level, and trace element profile, plus optional technical data packages on performance validation.
6. Downstream Processing & Purity
Downstream processing typically involves cell removal, precipitation, purification, and drying. Different filtration techniques areused to isolate hyaluronic acid from the fermentation broth, followed by concentration and sterilization steps to ensure pharmaceutical purity.
Impurities from poorly defined nutrients can increase broth turbidity and viscosity, complicating both filtration and recovery. NuCel® and ProCel® minimize such variability by offering high solubility and low particulate load, leading to cleaner supernatants and faster DSP cycles.
By reducing variability and organic residue, yeast-based nutrients simplify purification and enhance final hyaluronic acid recovery. Users report faster filtration and improved hyaluronic acid precipitation quality when switching from animal-derived peptones to NuCel® or ProCel®.
Pharma-grade hyaluronic acid exceeds 99% purity with endotoxin levels below 0.5 EU/mg, while cosmetic-grade hyaluronic acid typically targets ≥95% purity.
7. Regulatory & Compliance
Pharma-grade hyaluronic acid must comply with pharmacopeial standards (e.g., EP, USP) and GMP manufacturing, while cosmetic and nutraceutical grades follow ISO and food-grade safety standards.
Both nutrient ranges are produced under ISO 9001 and ISO 22000 standards and comply with Halal and Kosher requirements. ProCel® specifically meets GMP and audit-readiness expectations for pharmaceutical applications.
Procelys provides full documentation packages, including TSE/BSE statements, allergen-free declarations, Certificates of Origin, and detailed CoAs to support global compliance and audit needs.
8. Applications & Market Insights
NuCel®-based hyaluronic acid is primarily used in cosmetic serums, nutricosmetic supplements, and functional foods where hydration, elasticity, and clean-label attributes are key.
ProCel®-based hyaluronic acid serves high-purity applications such as ophthalmic solutions, dermal fillers, wound care, and osteoarthritis injections requiring pharma-grade safety.
The hyaluronic acid market is expanding alongside collagen in skin health, joint support, and aesthetic medicine. Precision fermentation and animal-free sourcing are accelerating innovation across cosmetic and pharma sectors.
Demand for animal-free hyaluronic acid is rising as manufacturers seek sustainable, ethical, and regulatory-compliant alternatives to animal-derived materials.
9. Technical Support & Co-Development
Procelys offers hands-on assistance from its application labs and experts in microbial fermentation to help optimize nutrient integration and fermentation parameters.
Yes. Tailored nutrients can be developed as co-creation project to match strain-specific nitrogen requirements, process kinetics, and desired molecular weight targets. We engage in extensive co‑creation with our partners to meet customer needs, leveraging our R&D resources and formalizing collaborations through NDAs.
Procelys provides access to Design-of-Experiments (DoE) tools, lab-scale models, and joint R&D programs to validate performance before industrial implementation.
10. Practical Aspects for Buyers & Engineers
NuCel® and ProCel® are available as fine powder and/or microgranulated powder, light-colored powders with excellent solubility and stability across a wide pH range.
Both ranges offer higher yield per batch and reduced fermentation time compared to casein or soy peptones, delivering superior cost-in-use performance.
Procelys benefits from Lesaffre’s global production footprint, ensuring reliable dual sourcing, consistent supply, and scalability for industrial hyaluronic acid producers worldwide.
Through multiple certified production sites and aligned quality systems, Procelys guarantees supply continuity and technical support for projects.
