HiSiaddi is an innovative foreign trade service provider driven by dual engines of technology commercialization and foreign trade services. We have established a "1+2+3+4=1" service system and can supply raw materials of sodium hyaluronate from multiple well-known original manufacturers. As a technology-driven foreign trade enterprise, HiSiaddi has repeatedly resolved customized demand issues for sodium hyaluronate products through technological cooperation with manufacturers and precise insight into market demands. Below is a case of HiSiaddi addressing customized requirements for sodium hyaluronate.
If you need more customized service support, please contact HiSiaddi customer service.
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Partner Client: Medicare Pharma Group, Milan, Italy A well-established European manufacturer of mid-to-high-end medical raw materials. Its core products include Class III injectable fillers, ophthalmic viscoelastic agents, and sterile wound dressings for post-aesthetic procedures. Its products comply with the European Pharmacopoeia (EP), EU MDR medical device regulations and local Italian pharmaceutical supervision standards. It supplies over 260 private specialized hospitals and high-end medical aesthetic chains across Italy, Spain and Greece. The client previously purchased pharmaceutical-grade sodium hyaluronate from Shiseido Japan for a long time. In 2025, it launched localized customized replacement with an annual customized procurement volume of 41 tons of sodium hyaluronate, divided into 3 non-standard customized grades with no off-the-shelf products meeting national standards available for direct purchase.
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Core Customization Requirements (Non-standard, no mass-produced general models) ① Ultra-low molecular weight HA: 650Da±80Da, PD＜1.22, exclusively for wound penetration-promoting dressings; ② Medium molecular weight injectable HA: 1.15 million Da±40,000Da, endotoxin＜0.025EU/mg; ③ Modified high molecular weight HA: 2.45 million Da±70,000Da, low water-absorption modified version for long-acting soft tissue filling; The full series requires full plant-source fermentation, zero animal protein, sterile lyophilized powder, no preservatives, and a complete set of documentation compliant with the European Pharmacopoeia (EP).
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Previous Barriers Faced by the Client The client independently contacted 3 major domestic HA manufacturers. These factories operate fixed mass production lines focusing on standardized ready-made goods. Customization requires revamping the entire fermentation, enzymatic hydrolysis, purification and sterile filling workshops. Factories were concerned about production halt losses and high commissioning costs, so they either declined small-batch sample customization or only made minor adjustments to existing commercial grades, failing to precisely match the client’s non-standard parameters. The customization project stalled, and the client entrusted HiSiaddi to fully coordinate and deliver the customized project via foreign trade services.
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Positioning of HiSiaddi A third-party foreign trade technical service provider that connects the client’s R&D department, compliant domestic medical raw material manufacturers and authoritative third-party testing institutions, solving full-range challenges including production line technical transformation, formula customization, sample iteration, mass production delivery and EU compliance.
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Conventional fermentation media adopted by domestic major manufacturers commonly contain animal peptones. The client’s mandatory full plant-source formula required emptying the entire batch of base materials in 50m³ fermenters and adjusting the ratio of carbon and nitrogen raw materials. Obtaining a precise narrow molecular weight distribution required segmented temperature-controlled enzymatic hydrolysis, which could not be achieved with fixed existing enzymatic hydrolysis parameters. Revamping production lines would occupy mass production orders for conventional daily chemical HA, resulting in substantial short-term capacity losses for factories, leading to extremely low willingness to accept customization.
The client’s endotoxin limit of ＜0.025EU/mg is far stricter than the conventional domestic medical-grade national standard of 0.5EU/mg. Existing production lines only adopt two-stage rough filtration for impurity removal, lacking supporting equipment including four-stage nanofiltration, multi-stage ultrafiltration and fine depyrogenation with activated carbon. Endotoxin levels of finished products from conventional production generally range from 0.1 to 0.3EU/mg, failing to meet the EU injection access threshold.
The client required independent vacuum-sealed aluminum foil lyophilized powder in 2kg specifications, demanding aseptic filling in Class 10,000 clean workshops. Most factories’ sterile lyophilization workshops were fully booked with self-owned stock orders, incurring high costs for temporary space allocation. Powders produced on open filling lines exceeded microbial and heterobacterial limits and could not be used as injectable raw materials.
The client customized a low water-absorption modified high molecular weight grade. Most domestically mass-produced HA features conventional linear structures, and manufacturers lacked mature corresponding modification processes. Factories faced long R&D cycles and high trial-and-error costs, refusing to launch independent R&D projects.
Manufacturers could only issue Chinese-language COAs complying with national standards, lacking full English inspection reports with itemized testing per EP standards and SCCS safety assessment documents. Even qualified raw materials could not pass import filing with Italian pharmaceutical authorities without these documents.
1. HiSiaddi screened and compared two leading enterprises with flexible medical pilot production lines and Class 10,000 sterile workshops: Bloomage Biotech Medical Division and Haohai Biotech. We used an annual locked-price long-term order of 41 tons as cooperation leverage to sign a special customization agreement, stipulating that losses from lab and pilot trials would be covered by revenue from long-term orders, and unqualified samples would not be counted as formal procurement volumes.
2. Bloomage Biotech was confirmed as the primary manufacturer. We coordinated the factory to allocate an independent flexible pilot production line separate from core mass production lines, enabling parallel customized and stock production to avoid capacity loss risks for the factory.
1. Cooperating with the factory’s R&D department, HiSiaddi eliminated animal peptone raw materials and customized a composite plant nitrogen source formula composed of crystalline corn glucose, hydrolyzed soybean protein and wheat germ extract. Fermentation was conducted under sealed nitrogen protection to minimize residual protein and nucleic acid impurities from the source.
2. Three-stage gradient temperature-controlled enzymatic hydrolysis was adopted with precise control of enzyme dosage and hydrolysis duration to lock the three target molecular weights of 650Da, 1.15 million Da and 2.45 million Da, strictly controlling the molecular weight distribution coefficient PD below the client’s specified limit for all grades.
We coordinated the factory to add four-stage nanofiltration classification, multi-stage ultrafiltration for endotoxin removal and refined adsorption procedures using pharmaceutical-grade activated carbon. The stock solution underwent four procedures: bacterial centrifugation, rough impurity filtration, graded nanofiltration and deep depyrogenation. The measured endotoxin of finished products stabilized at 0.021~0.023EU/mg, exceeding the client’s customized requirements.
1. For low water-absorption high molecular weight HA, HiSiaddi connected the factory’s R&D laboratory and completed 7 rounds of repeated sampling via mild cross-linking modification technology. The cross-linker addition ratio was adjusted to control the water absorption rate of raw materials, finalizing the modified high molecular weight finished product that meets anti-swelling requirements for long-acting fillers.
2. Exclusive production schedules were reserved in Class 10,000 sterile lyophilization workshops. Lyophilization was completed in a fully sealed nitrogen environment with independent light-proof vacuum aluminum foil packaging of 2kg units to eliminate secondary contamination.
1. Dual testing was commissioned at domestic CNAS-certified laboratories and EU SGS institutions. Bilingual Chinese-English itemized COAs were issued in accordance with EP standards, listing measured data for molecular weight, endotoxin, protein, heavy metals and microorganisms for each item.
2. English GHS MSDS, CPSR safety assessment reports and raw material production traceability ledgers were compiled to assist the client with REACH registration and pre-submission of raw materials to local Italian pharmaceutical authorities.
1. Lab Trial Phase (20 working days): 500g samples of each raw material grade were air-shipped to the client’s laboratory in Italy for formula compatibility, cell irritation and accelerated stability testing. All three raw materials fully passed in vitro safety tests with no turbidity, sensitization or degradation during storage.
2. Pilot Trial Phase (28 working days): 150kg large pilot samples of each specification were produced, tested simultaneously by domestic SGS and Italian third-party institutions. All indicators met customized standards. The client conducted small-batch production testing with no abnormalities in finished injectables and dressings.
3. Batch Mass Production: The annual 41-ton order was split into 8 batches and shipped monthly from Shanghai Port to Genoa Port, Italy.
The comprehensive procurement cost of domestically customized raw materials decreased by 28% compared to the original Japanese imported supply. Three new injectable and ophthalmic dressing products successfully passed filing with Italian pharmaceutical authorities and were launched across cooperative hospitals. Upon completion of the first year of cooperation, the client renewed an annual customized order of 48 tons and added new customized demand for cross-linked HA derivatives.
Based on this high-end EU customization project, three sets of standardized production SOPs for EP-grade non-standard HA were established. Export premiums of 31% were achieved for this customized grade. Supported by complete compliance documentation, the factory subsequently developed multiple European pharmaceutical clients in Spain and Portugal.
A complete customized service system for hyaluronic acid was established covering customized demand decomposition, production line technical transformation coordination, customized fermentation/enzymatic hydrolysis/purification processes, third-party dual testing, EU compliance filing and export customs clearance. Subsequent sustained customized HA orders for pharmaceutical-grade materials were secured from multiple European countries.
Customized HA ordered by mid-to-high-end pharmaceutical clients in Europe and the United States all adopt non-standard parameters aligned with the European Pharmacopoeia, differing from general off-the-shelf domestic raw materials. Major domestic HA manufacturers focus their core production lines on standardized mass production and generally reject independent technical transformation for customization due to cost constraints. Leveraging its neutral third-party identity, HiSiaddi balanced manufacturers’ technical transformation costs through annual long-term orders, breaking customization barriers across the full industrial chain from upstream fermentation formulas, midstream purification and modification to downstream aseptic filling and cross-border compliance. A three-way win-win outcome was achieved: overseas clients reduced costs and improved efficiency, manufacturers upgraded product lines, and the service provider expanded business volume.
If you need more customized service support, please contact HiSiaddi customer service.
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info@hisiaddi.com 
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