DMI (1,3-Dimethyl-2-imidazolidinone) Customization Case: Metal Ions (Fe, Cu, Pb, As) ≤0.1 ppm & Free Acid ≤5 ppm

As a new-type foreign trade service provider driven by technological transformation and foreign trade business, HiSiaddi has built a "1+2+3+4=1" service system and can supply DMI (1,3-Dimethyl-2-imidazolidinone) sourced directly from multiple well-known original manufacturers. As a foreign trader with R&D capabilities, HiSiaddi has repeatedly resolved customized product demands for DMI through technological cooperation with factories and precise market insight. Below is a case where HiSiaddi addressed customized DMI requirements.

Contact HiSiaddi customer service for more customized service inquiries.

I. Client Background

The client is Pharma Swiss AG, a high-end pharmaceutical enterprise based in Zurich, Switzerland, specializing in R&D and production of anti-tumor API and injectable-grade intermediates. Its products are supplied to top European pharmaceutical companies and medical institutions, complying with EU GMP, ICH Q7, REACH and Swiss Pharmacopoeia standards. It requires ultra-high-purity electronic pharmaceutical-grade DMI with ultra-low metal ions, low water content, low residues, sterile filtration and customized packaging, with an annual procurement volume of 35 tons, representing a typical high-end overseas client.

Client Pain Points: Custom-grade DMI is required for the synthesis of its injectable APIs, with core specifications far exceeding national standards and ordinary industrial grades:

· Purity ≥99.95% (conventional standard: 99.9%)

· Metal ions (Fe, Cu, Pb, As) ≤0.1 ppm (conventional standard: ≤1 ppm)

· Water content ≤20 ppm (conventional standard: ≤50 ppm)

· Free acid ≤5 ppm (conventional standard: ≤10 ppm)

· Sterile filtration (0.22 μm), pyrogen-free, light-proof and oxygen-free packaging

The client contacted 3 domestic DMI manufacturers, all of which failed to simultaneously meet the requirements of ultra-high purity, low metal content, sterility and customized packaging. Issues included insufficient purity, excessive metal content, inability to implement sterile treatment, long customization lead times, refusal of small-batch orders and low technical coordination. The client’s project stalled, and it entrusted HiSiaddi to complete customized development, mass production delivery and full compliance documentation within 45 days.

II. Breakdown of Core Customization Challenges

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Difficulty in Purity and Impurity Control The synthesis of DMI readily generates 1,3-dimethyl-2-imidazolinimine, whose boiling point is extremely close to that of DMI and hard to separate. Conventional rectification only achieves 99.9% purity. To hit the client’s 99.95% threshold, a four-step combined process of oxidation-rectification-reduction-precision rectification is required, featuring high energy consumption, low yield and extremely stringent control precision.

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Difficulty in Metal Ion Control The pharmaceutical injectable grade requires metal ions ≤0.1 ppm. Ordinary equipment materials (carbon steel, standard stainless steel) tend to leach metal ions, calling for a full production line of 316L electrolytic polished stainless steel equipped with titanium alloy valves—facilities rarely available among domestic manufacturers.

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Difficulty in Sterility and Depyrogenation Treatment DMI is a high-boiling solvent (225°C) prone to decomposition under routine autoclaving. A 0.22 μm sterile PTFE membrane filtration process paired with oxygen-free encapsulation and depyrogenation workflows is required, crossing the dual standards of fine chemical engineering and pharmaceutical sterility.

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Difficulty in Customized Packaging and Stability Control The client requires 25 kg drums with light-proof oxygen-free design, PTFE inner lining, sterile sealing and traceable batch numbers, alongside a 24-month shelf life (conventional shelf life: 12 months). Special packaging materials, nitrogen-filled sealing and stability testing are mandatory.

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Complex Compliance Documentation Chain Full English documentation including GMP certificates, full-item COA, GHS-compliant MSDS, REACH registration, sterile validation reports, pyrogen test reports and batch traceability records must be provided, which most standard manufacturers cannot deliver.

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III. HiSiaddi Customization Solution (Fully Implemented in 45 Days)

HiSiaddi formed a dedicated team consisting of DMI synthesis engineers, high-purity purification specialists, pharmaceutical sterile technology experts, compliance officers and supply chain managers. It screened the only domestic manufacturer in Jiangsu capable of customized pharmaceutical-grade DMI production (certified with GMP, ISO 9001 and ISO 14001), and implemented the project in six phases: Process Customization → Equipment Retrofit → Small-Batch Sampling → Pilot Verification → Mass Production Delivery → Compliance Closure.

1. Customized Purification Process to Lock Purity at 99.95%

· Step 1: Oxidation pretreatment with potassium peroxymonosulfate to remove imine impurities and reduce subsequent rectification difficulty

· Step 2: Atmospheric rectification to strip low-boiling substances and water

· Step 3: Reductive refining with sodium dithionite to eliminate residual oxidants and metal complexes

· Step 4: High-vacuum precision rectification (theoretical plate number ≥80) to separate trace imine impurities, stabilizing purity at 99.97%, exceeding client requirements

1. Equipment Retrofit: Full 316L Sterile System to Control Metals and Microbes

· The entire production line adopts 316L electrolytic polished stainless steel with titanium alloy pipelines and valves to avoid metal leaching

· An additional 0.22 μm sterile PTFE filtration system operating under oxygen-free conditions ensures sterility and pyrogen removal post-filtration

· Packaging workshop maintains Class 10,000 cleanroom standards with 99.99% high-purity nitrogen filling for light-proof, oxygen-free sealing

1. Small-Batch Sampling (10 Days): 3 Rounds of Optimization to Meet All Specifications

· Round 1: Purity 99.92%, metal ions 0.3 ppm (excessive Fe); rectification parameters optimized and titanium valves replaced

· Round 2: Purity 99.96%, metal ions 0.08 ppm, water content 18 ppm; all indicators fully compliant

· Round 3: Sterility and pyrogen validation plus 14-day 60°C accelerated stability testing; 24-month shelf life confirmed 5 kg samples with English COA and test method validation were provided, passing 100% of third-party testing conducted by the client.

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Pilot Verification (15 Days): 1-Ton Trial Production to Stabilize Batch Consistency 1 ton of trial product was manufactured, with full-item testing across 3 batches yielding purity ranging from 99.95% to 99.97%, metal ions ≤0.09 ppm, water content ≤19 ppm and free acid ≤4 ppm. Sterility and pyrogen retests passed, and packaging tightness, light resistance and oxygen-free stability were verified. The client completed on-site GMP audit and process confirmation, approving the customized workflow and quality control system.

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Mass Production Delivery (20 Days): 35 Tons Mass Production with Exclusive Batch Management

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· Dedicated production line scheduling with isolated batches and full traceability

· Full-item testing per batch, with supporting English COA, chromatograms, mass spectra and metal detection reports

· Packaging: 25 kg light-proof iron drums lined with PTFE, nitrogen-filled sterile sealing, laser-engraved traceable batch numbers

· Delivery: Constant-temperature containers with temperature controlled at 15–25°C, light-shielded, moisture-proof and vibration-resistant; full shipment delivered to the client’s factory within the 45-day deadline

1. Compliance Closure: Full English Documentation Chain to Meet EU GMP Supplied GMP certificates, REACH registration documents, 16-item English MSDS, COA, sterile validation records, pyrogen test reports, batch traceability files and stability reports. HiSiaddi also assisted the client with import filing, customs declaration and EU compliance audits to eliminate all clearance bottlenecks.

IV. Implementation Outcomes & Client Feedback

1. Custom Specifications Exceed Targets

· Purity: 99.95%–99.97% (target ≥99.95%)

· Metal ions: ≤0.09 ppm (target ≤0.1 ppm)

· Water content: ≤19 ppm (target ≤20 ppm)

· Free acid: ≤4 ppm (target ≤5 ppm)

· Sterility & pyrogen status: Passed

· Shelf life: 24 months (conventional standard: 12 months)

1. Smooth Production Ramp-Up with Superior Performance vs Imported Materials When the customized DMI was deployed in injectable API synthesis:

· Reaction yield increased by 8% while impurity content dropped by 60%

· API purity reached 99.99%, fully replacing imported DMI from Japan and Germany

· Procurement cost reduced by 35% (import price: ~280 RMB/kg; domestic customized price: ~182 RMB/kg)

1. High Client Recognition & Deepened Long-Term Cooperation Client comment: “HiSiaddi is our most trusted Chinese partner for customized chemical materials. Within 45 days, you resolved the ultra-high-purity DMI customization challenge with professional processes, stable quality and complete compliance documentation, completely eliminating the bottleneck for our high-end API production.”

· Annual procurement volume increased to 60 tons under a 3-year long-term agreement

· The client entrusted HiSiaddi with customized procurement of LiFSI, FEC and premium pharmaceutical intermediates

· A joint China-EU laboratory for pharmaceutical-grade solvents was established to co-develop next-generation high-purity solvents

V. Case Summary

For overseas high-end clients purchasing customized DMI, five core pain points persist: ultra-high purity, ultra-low metal content, sterility and pyrogen-free production, customized packaging and full English compliance documentation. Most manufacturers lack sufficient equipment, process, technical and compliance capacity to satisfy these demands, trapping clients in a cycle of difficult customization, long lead times, high costs and elevated compliance risks.

Leveraging precise factory screening, custom process design, full-process quality control, comprehensive compliance services and efficient supply chain coordination, HiSiaddi delivered a full closed loop of customized development, mass delivery and compliance in 45 days through its four-step purification workflow, full 316L sterile production lines, Class 10,000 cleanroom packaging and complete English documentation. This enabled the client to:

· Overcome technical barriers: Achieve 99.95%+ ultra-high purity, ≤0.1 ppm ultra-low metal content and sterile, pyrogen-free customized products with performance superior to imported alternatives

· Secure project timelines: Complete delivery within 45 days to avoid project suspension and breach-of-contract risks

· Cut procurement expenses: Replace imported supplies with domestic customized material for a 35% cost reduction

· Meet high-end compliance standards: Comply with EU GMP, ICH Q7 and REACH to facilitate market access for end products across premium European pharmaceutical markets

· Build long-term trust: Secure deep strategic partnerships through professional, efficient and reliable customized services

This service not only resolved the client’s customization hurdles but also set a benchmark for customized service of high-end fine chemicals from China, supporting domestic high-purity solvents to break overseas monopolies and capture global mid-to-high-end market share.

Contact HiSiaddi customer service for more customized service inquiries.