As a new foreign trade service provider driven by both technology transformation and foreign trade services, HiSiaddi has established a "1+2+3+4=1" service system and can supply tetraphenylporphyrin from multiple well-known original manufacturers. As a research-and-development-oriented new foreign trade enterprise, HiSiaddi has repeatedly solved customized product demands for tetraphenylporphyrin by virtue of technological transformation cooperation with factories and precise insight into market demands. The following is a case of HiSiaddi addressing customized demands for tetraphenylporphyrin products.
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The buyer, PorphyMed SAS of France, is headquartered in the Science and Innovation Industrial Park of the University of Burgundy in Dijon, France. Spun off from the Molecular Pharmaceutical Research Institute of the University of Burgundy, it is a mid-to-high-end biomedicine enterprise in Europe specializing in the research and development of photodynamic anti-tumor new drugs. It has over 20 years of deep experience in developing porphyrin-based photosensitizer API raw materials, with its product pipeline focusing on API raw materials for photodynamic therapy of solid tumors and in vivo fluorescence imaging probes. Its downstream partners include France’s national oncology clinical research institute and pharmaceutical laboratories of many Grade A tertiary hospitals across the EU, making it a high-end end purchaser in this global niche field.
The enterprise previously purchased long-term supplies of high-purity tetraphenylporphyrin (TPP, CAS: 917-23-7) from Sigma-Aldrich and local PorphyChem. Its standard purchased specification features HPLC purity ≥99.2% with no residual chlorin (chlorine impurity), which is used for pharmacological screening trials of new drugs. Faced with consecutive price hikes from European and American reagent manufacturers and extended customized modified grade production lead times of over 90 days, the client launched a domestic substitution project for customized raw materials from China, with customized special indicators as follows: HPLC purity ≥99.5%, chlorin impurity <0.08%, total lead and cadmium heavy metal content <3ppm, water-insoluble residue <0.1%. The client placed a pilot order of 100g; upon verification of compliance, a framework procurement plan for a cumulative 5kg in batches each year would be signed. All raw materials are used for pilot scale-up R&D of Class I anti-tumor new drugs, and raw material indicators are directly linked to EU new drug application data, with access standards aligned with the control specifications of the European Pharmacopoeia (EP) for API raw materials.
The client previously independently contacted 3 domestic fine chemical synthesis factories but encountered implementation bottlenecks with all of them. Conventional domestic mass-production factories adopt the traditional Adler propionic acid reflux process, which produces a large amount of chlorin by-products (2%–4% residual content) and delivers conventional mass-production purity of only 97%–98%, failing to remove trace chlorine-based impurities. These factories can only produce industrial-grade products per general national standards and lack the capability of targeted customized purification for pharmaceutical-grade materials. While some manufacturers can prepare high-purity samples, they only support gram-level laboratory synthesis and cannot stably scale up production to 100g batches. The client spent 3 months and 18,000 EUR on sample testing, yet all samples failed to meet the internal control indicators for new drug R&D, putting the customization project on hold.
Upon recommendation by France’s Fine Chemical Industry Association, the client fully entrusted Shanghai HiSiaddi Technology (HiSiaddi) to undertake full-process customized delivery services. Supported by HiSiaddi’s team of organic synthesis engineers and pharmaceutical compliance specialists, we resolved all customization challenges from four dimensions: synthetic route adjustment, customized gradient purification processes, mass production process optimization, and item-by-item indicator control. Finally, we delivered a compliant 100g batch of customized high-purity tetraphenylporphyrin in one go, and subsequently finalized a long-term customized supply agreement for 5kg per year.
Product: High-purity pharmaceutical-grade tetraphenylporphyrin, deep purple crystalline powder, vacuum-sealed packaging in light-proof fluorinated bottles, accompanied by full-batch COA test reports, HPLC spectra, REACH documents and raw material traceability lists.
Domestic industrial mass production generally adopts the Adler high-temperature propionic acid reflux synthesis method. High reaction temperatures readily generate cyclic by-product chlorin, with a typical by-product content of around 3% in conventional processes. The client’s new drug R&D explicitly requires this impurity to be ≤0.08%. A single conventional column chromatography purification can only reduce it to 0.5%, failing to meet the ultra-low impurity standard. While the laboratory Lindsey low-temperature synthetic route can be adopted, small domestic workshops only support milligram-level trial production and lack pilot scale-up equipment to stably mass-produce 100g batches of finished products.
Beyond the rigid requirements for purity and impurities, the client specified four additional non-standard indicators: total heavy metal residue <3ppm, ignition residue <0.1%, moisture ≤0.2%, and absorbance error ≤2% for the S-band and Q-band of UV characteristic absorption peaks. Most domestic synthetic enterprises only control the main component content and lack complete sets of precision testing equipment including atomic absorption spectrometers, UV spectrophotometers and high-performance liquid chromatographs. Their factory inspection reports only label crude purity and cannot issue bilingual full-item COA test reports formatted for EU new drug filings, meaning the indicator data cannot be used for European pharmaceutical registration.
The 100g order counts as a small-batch pharmaceutical customization order. Large-scale domestic chemical production lines mainly focus on general industrial-grade TPP in batches of kilograms or above. Switching to low-temperature synthesis and multi-stage recrystallization purification processes requires halting production for equipment commissioning and replacing high-purity raw materials (inhibitor-free pyrrole and benzaldehyde free of free aldehyde impurities). From a cost perspective, factories refuse to independently modify processes, either marking up prices by over 65% beyond the client’s budget or only producing general-grade products using outdated processes, creating a severe supply-demand mismatch.
HiSiaddi set up a special project team consisting of organic synthesis specialists, pharmaceutical quality control staff and foreign trade specialists, and collaborated with a domestic pilot synthesis base qualified for pharmaceutical intermediate customization. We split the delivery into four core steps: formula optimization, process modification, multi-stage purification and full-item testing, completing the full cycle of customized product production, full testing and shipment customs clearance within 45 days.
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Improved Synthetic Route: Modified Low-Temperature Lindsey Process to Reduce By-Product Generation at the Source Abandoning the traditional high-temperature propionic acid reflux route, we adopted a modified nitrogen-protected low-temperature synthetic process: anhydrous dichloromethane system, boron trifluoride diethyl etherate low-temperature catalysis at a controlled temperature of 5℃–8℃, precise molar ratio of pyrrole to benzaldehyde at 1:1.03, and full nitrogen sealed environment to isolate air and reduce oxidative side reactions that produce chlorin. After the reaction, DDQ is used for stepwise low-temperature oxidation, limiting by-product generation to within 0.3% from the synthesis source and greatly lowering subsequent purification pressure. HiSiaddi engineers stationed at the factory supervised the entire feeding and temperature control process, strictly controlling raw material grades by specifying the procurement of pharmaceutical-grade rectified pyrrole (monomer purity ≥99.9%, free of peroxide impurities) and recrystallized benzaldehyde to eliminate heavy metals and organic impurities introduced by raw materials.
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Customized Multi-Stage Gradient Purification to Achieve the Ultra-Limit Indicator of Chlorin <0.08% Based on crude products, we designed a three-stage purification scheme: low-temperature recrystallization + silica gel gradient column chromatography + solvent cyclic refining.
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1. Step 1: Low-temperature recrystallization with mixed dichloromethane-methanol solvent to remove macromolecular viscous impurities;
2. Step 2: 200–300 mesh chromatographic silica gel with gradient polarity elution to fractionally collect target components and separate chlorin isomers;
3. Step 3: Secondary short-path recrystallization after vacuum low-temperature drying. The final finished product achieved an HPLC measured purity of 99.57% with chlorin residue of 0.062%, better than the client’s upper customized limit of 0.08%.
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Establish EU-Standard Full-Item Quality Control System to Generate Test Documents for New Drug Filing HiSiaddi partnered with third-party testing laboratories holding CNAS and EU GLP qualifications to conduct tests in accordance with European Pharmacopoeia customized testing methods specified by the client:
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1. HPLC: Quantification of total component content and chlorin impurities;
2. Atomic Absorption Spectroscopy: Limit testing of heavy metals including lead, cadmium and arsenic;
3. UV-Vis Spectrophotometry: Calibration of absorbance for characteristic absorption peaks;
4. Drying method + Muffle furnace: Testing of moisture and ignition residue. All complete test data were compiled into a three-language (French, English, Chinese) COA inspection certificate, attached with original HPLC chromatograms and raw UV spectral data. The format complies with new drug raw material filing requirements of France’s ANSM pharmaceutical regulatory authority, filling the gap that domestic factories cannot issue compliant test documents.
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Flexible Production Line Coordination to Realize Scaled Production of Small-Batch Custom Orders Leveraging long-term chemical supply chain resources, HiSiaddi coordinated cooperating factories to allocate small pilot reaction kettles for separate production scheduling, adopting a progressive production workflow of 5g small trial → 50g pilot test → 100g mass production. First, 5g sample batches were sent to the client’s French laboratory for initial screening; mass production was only launched after the client’s laboratory verified eligibility via NMR and liquid chromatography, avoiding losses from unqualified one-time mass production. Meanwhile, we optimized vacuum low-temperature light-proof drying and vacuum fluorinated bottle packaging processes, strictly controlling humidity in the packaging environment to meet the client’s light-proof low-temperature storage requirements.
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On-Time Delivery of 100g Customized Products to Smoothly Advance the Client’s New Drug Pilot Scale-Up After full testing of customized finished products, HiSiaddi completed UN classification per EU dangerous goods specifications, organized full customs clearance documents including SDS chemical safety data sheets, REACH component lists, COA reports and certificates of origin, and shipped goods via international cold-chain air freight from Shanghai Pudong to Paris Charles de Gaulle Airport with full-process temperature control of 2–8℃ and light shielding. French customs cleared the goods within 3 working days with complete compliant documents. After raw materials arrived at the client’s factory, full re-testing by their pharmacological laboratory showed purity of 99.54%, chlorin content of 0.065%, and total heavy metals of 2.1ppm, all meeting customized requirements. The raw materials were smoothly applied to pilot formula development of third-generation photodynamic sensitizers, and data submission to France’s national oncology research institute was completed on schedule. The client cut 42% of original procurement costs for imported European and American raw materials, and delivery lead time was shortened from the original 90 days to 48 days.
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Signing of a Long-Term Framework for Annual 5kg Customized Procurement 40 days after acceptance of the initial 100g sample order, France’s PorphyMed formally signed a framework agreement with HiSiaddi for annual customized procurement of 5kg in batches. The agreement stipulates on-demand customization in 6 batches each year based on the progress of new drug R&D, retaining the customized indicators set in this project. For subsequent development of new grades such as halogenated phenyl modified tetraphenylporphyrin derivatives and metal-coordinated zinc porphyrin (TPP-Zn), all new process customization development and production delivery will be entrusted to HiSiaddi. HiSiaddi established an exclusive raw material file for this client, synchronizing updates on domestic synthetic process iterations and raw material price fluctuations in real time, and predicting indicator adjustments brought by updated EU regulations in advance.
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Expansion of High-End European Porphyrin Niche Market Supported by This Benchmark Case This successful high-end pharmaceutical customization case built a positive reputation within France’s biomedicine circle. Relying on the client’s industry resources, HiSiaddi subsequently connected two high-end research procurement clients: the Drug R&D Center of the University of Amsterdam in the Netherlands and the Max Planck Institute for Materials Science in Germany, delivering customized orders for multiple specifications of high-purity porphyrin series products. We formed a standardized customized service model for high-end fine chemicals: front-end demand decomposition → customized process improvement → graded purification → full-process quality control → cross-border customs clearance and export.
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Tetraphenylporphyrin is a key fine chemical for high-end biomedicine and optoelectronic catalysis fields. There is an essential process gap between pharmaceutical-grade customization and general industrial mass production. Most domestic synthetic factories focus on mass-produced industrial-grade products and lack capabilities for refined customization for new drugs, ultra-limit impurity control, and supporting EU-compliant testing. Raw material indicators of European and American mid-to-high-end pharmaceutical R&D clients are tied to new drug filings, leading to extremely strict control over impurities, purity and test documents. Independent raw material sourcing often traps clients in procurement dilemmas including unqualified factory processes, excessively high customization modification costs and massive sample testing losses.
Breaking the traditional foreign trade model limited to supply matching, HiSiaddi takes technical customization as the core and full-process quality control as the starting point, connecting the entire industrial chain of formula improvement, purification process optimization, third-party compliant testing and cross-border customs clearance. We make up for the lack of refined customization capabilities among domestic chemical manufacturers, helping overseas high-end pharmaceutical enterprises achieve cost reduction and faster delivery with domestic raw materials, while supporting domestic high-end customized fine chemical products to enter Europe’s high-end pharmaceutical supply chain, emerging as a key technical service provider for domestic export of special porphyrin chemicals.
If you need more customized service support, please contact HiSiaddi customer service.
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info@hisiaddi.com 
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