In recent years, oligonucleotide therapeutics have been widely recognized as the "third wave" of the global pharmaceutical industry, following small-molecule drugs and antibody medicines. Boasting abundant druggable targets, precise molecular design, and long-lasting therapeutic effects, oligonucleotide drugs are seeing a continuous surge in globally approved products and domestic preclinical & clinical pipelines, driving the industry to rapidly transition from an R&D boom to large-scale commercial manufacturing.
While the industry’s focus largely rests on pipeline advancement and business development transactions, the supporting value of upstream manufacturing infrastructure is growing increasingly prominent. Oligonucleotide production features lengthy workflows and stringent precision requirements, with scalable manufacturing and quality control standing as widely acknowledged core industry bottlenecks. Relying merely on equipment sourced from disparate suppliers fails to meet the full-cycle demands of drug development spanning early-stage laboratory research to commercial mass production.
As a leading domestic enterprise in separation and purification technology, Hanbon Technology delivers an industry-wide solution: taking self-developed equipment and matching proprietary processes as dual growth drivers, the company covers the entire workflow of oligonucleotide solid-phase synthesis, chromatographic separation & purification, and ultrafiltration concentration. It establishes a complete industrial pathway from lab-scale R&D and pilot scale-up to commercial production, delivering actionable integrated manufacturing solutions for partners.
I. Oligonucleotide Drugs and Their Full Manufacturing Workflow
If human cells are likened to a factory, DNA serves as the master blueprint storing genetic information, mRNA acts as the construction instruction slip that transmits genetic commands, and oligonucleotide therapeutics function as precision tools that regulate these instructions. Some block the synthesis of disease-causing proteins, while others replenish defective gene functions, enabling disease treatment at the genetic level with the potential to address both root causes and symptoms.
Mainstream oligonucleotide therapeutics currently include antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). With their versatile targets, accurate design, and sustained efficacy, they exhibit immense application potential for chronic conditions such as hypertension, hyperlipidemia, and hepatitis B. The production of qualified oligonucleotide active pharmaceutical ingredients (APIs) consists of three tightly linked core stages:
Solid-phase Synthesis: Starting from phosphoramidite monomers, cyclic reactions of deprotection, coupling, oxidation, and capping assemble oligonucleotide strands of specific sequences. As the starting point of production, reaction precision directly determines crude product purity and overall yield.
Separation & Purification: Crude synthesis products contain abundant truncated fragments and reaction impurities. Reverse-phase chromatography or ion-exchange chromatography is applied to remove contaminants and achieve purity standards for pharmaceutical-grade APIs, forming the core quality control stage.
Ultrafiltration & Concentration: This step completes buffer exchange and product concentration, further eliminating small-molecule impurities and adjusting the final material to the concentration and solution system required for formulation, serving as a critical finishing procedure prior to filling.
The coordination of the full workflow directly governs final production efficiency, product quality, and comprehensive manufacturing costs. This explains why the fragmented, multi-supplier equipment procurement model is increasingly unable to support industrial-scale commercialization.
II. Common Pain Points of Oligonucleotide Manufacturing Amid Industrial Acceleration
As an increasing number of drug pipelines advance to clinical stages and move toward commercialization, manufacturing bottlenecks are becoming more pronounced, representing universal challenges for pharmaceutical companies and CDMOs alike:
1.**Patchwork Equipment Procurement Creates Disconnected Process InterfacesEquipment for each oligonucleotide production stage is typically sourced from different manufacturers, featuring inconsistent control logics and mismatched parameter standards. Frequent iterative debugging is required to connect upstream and downstream processes, drastically extending project timelines. Scenarios also arise where upstream testing yields qualified results yet downstream production suffers plummeting yields. Clear accountability boundaries disappear when faults occur, complicating troubleshooting.
2.**Hardware-Only Suppliers Fail to Provide Scalable Processes, Creating the "Valley of Death" for Scale-UpScalable manufacturing and quality control constitute the most recognized core bottlenecks of oligonucleotide production. Most equipment vendors only supply hardware without mature, validated scale-up processes. Parameters delivering stable performance at lab scale often lead to reduced purity and uncontrolled impurities when transferred to pilot or industrial-scale equipment. Pharmaceutical enterprises must conduct repeated trial runs using costly phosphoramidite monomers, risking missed market launch windows.
3.**Evolving GMP Compliance Standards Raise Risks for Multi-Supplier CollaborationAs pipelines progress to late-stage clinical trials and commercial production, projects face heightened requirements for GMP compliance, audit trails, and consistent delivery. Collaborating with multiple suppliers means managing separate compliance systems and enduring repeated client audits, driving up operation and management costs. Fault diagnosis becomes inefficient, and overall project schedules are difficult to guarantee.
III. Dual-Driven Development: Hanbon Technology’s Integrated Full-Chain Solutions
Hanbon Technology’s core competitive differentiation lies in its positioning beyond a standalone equipment supplier. Rooted in "equipment as the framework, proprietary processes as the core soul", the company delivers a unified package of fully self-developed full-workflow hardware and validated matching processes to provide truly integrated solutions.
Hanbon Technology boasts a complete matrix of self-developed equipment spanning lab to industrial scales, covering the three core stages of synthesis, purification, and ultrafiltration. All equipment shares unified control logics and native cross-process compatibility, fundamentally resolving the industry’s fragmented equipment pain point.
(1) Oligonucleotide Synthesis Platform: Full-Scale Coverage Enables Seamless Scale-Up
The company supplies a full lineup of oligonucleotide synthesis instruments and matching consumables for all R&D and production phases, supporting scale ranges from micromole to mole level.
*Lab-Scale Systems: Oligo-Lab 25 (50 μmol–500 μmol), Oligo-Lab 100 (200 μmol–9 mmol), Oligo-Lab 150 (500 μmol–12 mmol). Modular design paired with intelligent software aligns with standard industry operation habits, ideal for early-stage process development.
*Pilot-Scale Systems: Bio-Oligo 36L (4 mmol–48 mmol), stably producing hundreds of grams of oligonucleotide raw material per batch; Bio-Oligo 180L (20 mmol–150 mmol), delivering nearly kilogram-scale output per batch. All models feature professional explosion-proof design that meets GMP production standards, laying a compliant foundation for clinical-grade raw material manufacturing.
*Commercial Production-Scale Systems: Bio-Oligo 480L (50–400 mmol), Bio-Oligo 1800L (100–900 mmol), Bio-Oligo 3000L (300–1800 mmol), fully meeting mass commercial production demands. Equipped with explosion-proof construction for GMP workshop deployment, the embedded software complies with FDA 21 CFR Part 11 regulations.
Matching Self-Developed Synthesis Columns: A full spectrum of proprietary synthesis columns ranges from fixed-volume 6.3 mL columns to 800 mm inner-diameter production-grade columns. Fabricated from stainless steel resistant to organic reagents, their optimized flow channels ensure even solution distribution, adapting to synthesis requirements across all manufacturing stages.
(2) Separation & Purification Platform: Dual Technical Routes with Natively Matched Chromatography Systems & Stationary Phases
Drawing on over two decades of chromatography expertise, Hanbon Technology offers two mainstream purification workflows: reverse-phase chromatography and ion-exchange chromatography, paired with self-developed chromatographic stationary phases. This native matching eliminates trial-and-error costs caused by incompatibility between third-party equipment and packing materials.
Reverse-Phase Chromatography Workflow: From lab-scale high-performance liquid chromatography (HPLC) systems to the CS-Prep series industrial preparative HPLC platforms paired with DAC dynamic axial compression columns. Featuring high throughput and full automation, all hardware complies with GMP/cGMP and FDA 21 CFR Part 11 standards, with complete validation documentation available.
Ion-Exchange Chromatography Workflow: Bio-Lab lab-scale chromatography systems support microgram to gram-level purification for early process development; the fully automated Bio-Pro pilot & production chromatography systems are integrated in accordance with ASME BPE and GMP standards, enabling full automation of equilibration, sample loading, elution, and fraction collection.
Self-Manufactured Stationary Phases via Subsidiary Hedeera Technology: Silica-based and agarose separation media are independently developed by wholly-owned subsidiary Hedeera Technology. The stationary phases are co-engineered and optimized alongside purification systems to maximize separation efficiency and product yields from the source.
(3) Ultrafiltration & Concentration Platform: Low-Shear Design Preserves Molecular Integrity
Addressing the vulnerability of oligonucleotides to degradation, all ultrafiltration systems adopt optimized flow channel architecture to reduce shear force, fully protecting molecular integrity and maximizing product recovery rates.
*Lab-Scale: Bio-Lab TFF automated tangential flow filtration (TFF) systems deliver automatic cross-flow pressure control, supporting automated concentration, constant-volume diafiltration, sample collection, and data logging for streamlined lab R&D operations.
*Industrial-Scale: Bio-TFF automated TFF systems feature split circulation tank design, enabling minimal operating volumes, high concentration ratios, and excellent product recovery. Compatible with CIP cleaning protocols, they fully satisfy pilot and full-scale industrial manufacturing requirements.
Equipment forms the hardware foundation, while proprietary processes constitute the core competitive advantage. Unlike other equipment vendors, Hanbon Technology delivers not only hardware but also fully validated, immediately deployable manufacturing processes that enable clients to rapidly commission equipment and achieve stable, qualified production output.
1.**Optimized Synthesis Processes Improve Crude Product Quality at the Source
Customized validated solid-phase synthesis parameter sets are provided for oligonucleotides of distinct sequences and modification types. Precisely controlled reaction conditions for each step boost phosphoramidite coupling efficiency and minimize impurity generation.
Take Inclisiran, a classic siRNA therapeutic, as an example: using the Oligo-Lab 100 lab-scale synthesizer paired with optimized proprietary processes, the sense strand crude purity reaches 86.2% and antisense strand crude purity hits 84.4%, with an average monomer coupling efficiency of 99%. Mass spectrometry confirms molecular weights fully match theoretical values, delivering high-quality crude material that simplifies downstream purification.
Embedded UV detectors monitor deprotection progress in real time, while conductivity sensors track coupling and oxidation reactions for end-to-end process control and consistent batch-to-batch performance.
2.**Custom Purification Process Development Delivers Optimal Separation Schemes
Tailored reverse-phase or ion-exchange purification workflows are designed based on molecular characteristics and quality specifications, including stationary phase selection, elution condition optimization, and impurity removal strategies. Solutions balance target purity and product yield, drastically shortening clients’ independent process development cycles.
3.**Validated Scale-Up Processes Smoothly Cross the "Valley of Death"
All equipment lines share unified design logic and control architectures, enabling linear translation of process parameters between scales. Hanbon Technology provides complete scale-up validation datasets and full technical support, allowing seamless transfer of lab-scale processes to pilot and industrial production. This drastically mitigates scale-up failure risks and cuts costly trial runs with expensive raw materials.
The synchronized R&D and native compatibility of equipment and processes are far more than bundled multi-unit equipment sales. Hanbon delivers a complete manufacturing ecosystem that is "plug-and-play and immediately produces qualified material". Clients only need to engage Hanbon as a single point of contact to resolve all manufacturing challenges from synthesis to ultrafiltration, truly unlocking a seamless industrial pathway from laboratory research to commercialization.
IV. Conclusion
China’s domestic oligonucleotide industry stands at a pivotal inflection point, shifting from R&D catch-up to large-scale industrial commercialization. Stable, efficient, scalable manufacturing capacity has become enterprises’ core competitiveness to navigate industry cycles.
Hanbon Technology will continue its dual-driven strategy of integrated equipment and proprietary process innovation, deepening full-chain technical expertise for oligonucleotide manufacturing. The company aims to accelerate partners’ drug R&D and commercial launch timelines, collectively advancing high-quality development of China’s oligonucleotide industry.
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