S-HiCon™ is a high-concentration formulation development platform that identifies and mitigates challenges such as pH shifts, high viscosity, and protein aggregation, while enabling the production of stable biologic formulations exceeding 200 mg/mL for subcutaneous administration. S-HiCon™ enables a systematic, rational approach to formulation development by using a structured, step-by-step process to evaluate each molecule’s behavior. S-HiCon™ helps manufacturers conduct comprehensive feasibility studies for the target concentration, including evaluations of all stability aspects and drug-delivery needs. The platform optimizes high-concentration formulations and the manufacturing processes required to produce them and creates customized workflows for different modalities.
Features and Benefits
High-concentration biologics are not simply a scaled-up version of conventional formulation work; they pose a distinct design challenge driven by increasing molecular complexity and the need to achieve concentrations above 100 mg/mL.
As biopharmaceutical programs move toward complex modalities and subcutaneous delivery, platforms like S-HiCon™—coupled with integrated process development and analytical capabilities in a one-team model—demonstrate how coordinated early material generation, structured risk-based workflows, and advanced analytics can compress timelines and reduce technical uncertainty. This structured, data-driven screening matrix provides a repeatable process for optimizing conditions for high-concentration drug production that systematically anticipates pH-shift, aggregation, and viscosity issues early, enabling the successful development of complex biologics.
Applications
The S-HiCon™ platform follows a defined six-step workflow:
- ‘Concentration Gate Check’ through tangential flow filtration
- Surfactant screening
- pH-buffer and basic excipient screening
- Ultrafiltration (UF) and diafiltration (DF) feasibility study
- Excipient screening
- Final formulation determination
Samsung Biologics employs a structured, stepwise approach to high-concentration formulation development, starting with a ‘Concentration Gate Check’. This process serves as an early feasibility decision point, verifying whether the desired concentration is achievable before committing to full-scale development. Programs that pass this step proceed through steps 2–5 before the final formulation is determined. Those that fail at the first step are redirected to alternative strategies, including UF/DF optimization, target concentration adjustment, or engineering-based approaches, before development continues.
S-HiCon™ was used in a high-concentration formulation development program for the mAb-1 (IgG1), an antibody that targets a tumor antigen and is intended for subcutaneous administration. The molecule was received at an initial formulation condition of 10 mg/mL in histidine buffer (pH 6.0) containing sucrose and polysorbate 80, with a monomer purity of 98%, and a high-molecular-weight species content of 2%.
In this case, the S-HiCon™ platform enabled the assessment and successful development of an ultra-high-concentration subcutaneous formulation for the mAb-1 (IgG1) antibody that met the ambitious target profile, reaching a subcutaneously suitable concentration above 200 mg/mL and demonstrating acceptable stability under multiple thermal and stress conditions.
A systematic gate-check assessment of the pH shift during UF confirmed manufacturability and guided formulation selection. Screening across the tested conditions showed that histidine-buffered formulations containing arginine-HCl and sucrose delivered the most favorable purity, aggregation, and charge-variant profiles and enabled concentrations above 200 mg/mL. This buffer-additive combination is therefore a strong candidate for ultra-high-concentration, low-viscosity development of mAb-1, while molecule-specific optimization remains necessary.