This century has seen a revolution in healthcare, as biopharma has provided novel treatments for a range of formerly untreatable conditions. However, biologics tend to be vial-based, and their administration initially required complex procedures performed by trained professionals.

The launch of Humira (adalimumab) as a single-dose prefilled syringe (PFS) in 2003 revolutionized the administration of biologics. Strong growth in biopharma has since been mirrored by the development of devices that enable easier, self-administered, subcutaneous (SC) delivery of life-saving medications.¹ For example, Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs), the first and only subcutaneous anti-PD-(L)1 cancer immunotherapy, was approved by the FDA in September 2024. This product, which was developed by Genentech (a subsidiary of Roche) reduces administration time from 30-60 minutes intravenous (IV) infusion to approximately 7 minutes, while minimizing pain and discomfort, addressing key unmet needs in cancer care. Even more recently, in September 2025, Merck (known as MSD outside the US and Canada) received FDA approval for Keytruda Qlex, a SC injection therapy for cancer. 

The transition from IV to subcutaneous (SC) administration has brought multiple benefits, including at-home dosing, enhanced patient compliance, reduced hospital congestion and lowered health care costs. However, the shift to SC administration frequently requires the development of High-Concentration Biologics (HCBs, typically >100 mg/mL) due to the need for large dose volumes. 

As patient preferences and price pressures drive demand for SC biologics, companies face critical challenges in delivery, thanks to three key bottlenecks in their development: excessive viscosity and aggregation; complex integration of drug formulations with delivery devices; and strict regulatory requirements for Clinical-In-Use (CIU) compliance. This article discusses some best-practice solutions to these challenges, with case studies from recent WuXi Biologics platforms to showcase comprehensive Drug Product (DP) capabilities and how they can be applied to accelerate the launch of HCBs, reduce risks and enhance commercial success.  

Reducing Viscosity and Aggregation

A central hurdle in HCB development involves a large increase in viscosity due to greater antibody concentrations.² Viscosity above 20 cP can hinder manufacturing, complicate aseptic filling, and increase injection force, making administration more difficult. Further complications can arise from molecular crowding or co-exclusion effects (proteins blocking the free movement of other proteins), and elevated macromolecular interactions. This leads to aggregation, which can compromise product stability and heighten immunogenicity. 

Addressing viscosity and aggregation is essential for drug performance, safety and patient comfort—enabling the use of smaller needles, easier injections, and supporting robust, scalable manufacturing. Excipients offer the most common solution for both challenges—most often salts and amino acids. However, excipients with viscosity-lowering effects can also impact protein stability, so the discovery of suitable excipient strategies is a crucial step in a biologic’s SC transition journey. 

The WuXiHigh 2.0 technology platform harnesses excipient combinations to address the key challenges of HCBs. Supporting concentrations up to 230 mg/mL, the platform employs exclusive excipients (each listed in the FDA Inactive Ingredient Database) that can reduce viscosity by up to 90%. By pairing organic acids or amino acids with amphiphilic agents, the excipient blends include acids that enhance protein structural stability, while the amphiphilic agents disrupt molecular interactions to lower viscosity and prevent aggregation (Figure 1). To accelerate development, WuXiHigh 2.0 uses dedicated high-throughput (HTP) instruments to rapidly assess viscosity and aggregation risks.³ This predictive, data-driven approach promotes faster, smarter excipient selection from the earliest formulation stages. Internal data from over 100 programs demonstrate that the WuXiHigh platform can empower efficient, scalable DP development for HCB by overcoming viscosity challenges, making material savings, accelerating timelines, and enhancing deliverability (Figure 1).

The platform’s rapid, low-input screening is especially valuable in early development stages, when protein is limited. Traditional formulation screening typically suffers from inefficiencies and resource waste, whether for monoclonal antibodies (mAbs), bispecific antibodies, Fc-fusion proteins, antibody-drug conjugates (ADCs), vaccines or biosimilars. Using HTP technology, the WuXiHigh 2.0 platform significantly reduces protein consumption while expanding the scope of a single screening run and shortening the development cycle by over 50% (Figure 2). 

These mechanisms enable the delivery of stable, scalable, and patient-friendly formulations for SC injection. Size-exclusion high performance liquid chromatography (SE-HPLC) has confirmed that WuXiHigh 2.0 maintains high main peak percentages post-stress, indicating minimal degradation and aggregation. 

The WuXiHigh platform is complemented by a dedicated program that has been launched to tackle the unique challenges of high-concentration, high-viscosity formulations during GMP filling production. With a strong focus on practical GMP execution and operations, assessments include:

• Aggregation under shear stress
• Start–stop and hold time assessments for the filling process
• Needle clogging risk analysis
• Filling accuracy and precision evaluations
• Robustness testing of critical filling parameters
• Characterization of fluid properties under real production temperature and humidity conditions in a GMP facility.

By leveraging this program alongside the WuXiHigh platform, it is possible to proactively identify risks in filling production, define a reliable process window, and minimize uncertainties during scale-up. This integrated approach ensures that HCBs transition seamlessly from the development lab to GMP production – smoothly, reliably, and with greater confidence.

Hyaluronidase Co-Formulation

Hyaluronidase can catalyze the degradation of hyaluronan in the extracellular matrix to allow large-volume subcutaneous injections, resulting in increased dispersion and absorption of the co-administered therapeutic protein. Hyaluronidase co-formulation is an emerging strategy that combines hyaluronidase with other therapeutic agents. 

Hyaluronidases are a family of enzymes that mainly catalyze the hydrolysis of hyaluronic acid (HA). Among the hyaluronidase family, the recombinant human PH20 (rHuPH20) appears to be the most reliable candidate with excellent efficacy and safety for co-formulation development. When administered subcutaneously, rHuPH20 depolymerizes HA in the extracellular matrix, thereby reducing the HA barrier in the SC space and increasing tissue permeability (Figure 3). Because the action of rHuPH20 is transient and local, and HA has a fast turnover, the SC tissue can be restored within 1-2 days after rHuPH20 injection.⁴ We provide all-inclusive services for rHuPH20 co-formulation products, covering feasibility, development, manufacturing, analytical testing, clinical supply services, and regulatory support.

Integration of Drug Delivery Devices

While SC administration offers convenience and ease to end-users, for the companies producing the delivery devices, the approach offers no such simplicity. The integration of drug formulations with delivery devices can be highly complex, raising challenges from design and specification, through development and testing, to filling and assembly.⁵ Our initial solution to overcoming bottlenecks caused by these challenges is to combine formulation development, device engineering and combination product development. 

Unlike standalone device suppliers, WuXi Biologics offers fully integrated support spanning formulation development through combination product development, with a focus on formulation-device compatibility to ensure optimal performance of final drug-device combination product. This minimizes risks and delays associated with formulation–device mismatches. For example, post‑market experience with GLP‑1 autoinjectors has highlighted that, without robust early‑stage formulation–device compatibility assessment, high‑viscosity biologics can be more prone to needle-related delivery issues such as activation failures or clogging.⁶ FDA published event reports further document real world cases of injection failures, including needles failing to penetrate the skin or medication leaking externally. While such spontaneous reports do not establish causality, the incident patterns are consistent with the types of needle related risks described in the literature, reinforcing the importance of thorough early compatibility assessments for SC HCBs. At WuXi Biologics, our drug-device combination product development (DDCD) platform can provide end-to-end support to proactively mitigate such risks and safeguard the full lifecycle of combination products. 

Covering the full life-cycle needs of these products, an integrated drug-device combination platform offers full-scenario coverage for all project stages. For example, at the early clinical phase, PFS and safety PFS cater to small-batch, rapid validation needs. At more advanced commercial stages, autoinjectors, cartridge pens, next-generation on-body delivery systems and dual-chamber designs can be adapted for large-scale production and long-term patient use.

Drug delivery devices are designed and developed to enable convenient self-administration with smaller injection volumes and proven compatibility between the formulation and the device. Using patient-centric design logic as a basis for product design, we aim to enhance patient adherence and confidence through ergonomic design (e.g. non-slip grips), precise dose feedback, and reduced injection discomfort. 

Aligned with WuXi Biologics’ DDCD R&D and manufacturing capabilities, we have established an end-to-end quality management system covering design, development, and manufacturing, compliant with 21 CFR Part 4 and ISO 13485, enabling us to provide global pharmaceutical partners with high-quality, end-to-end combination product development and manufacturing services. 

Clinical Supply Service

In the complex global drug development landscape, a seamless link between efficient clinical trial management and supply chain connection is critical to successful launch. Pharma clients often face challenges such as fragmented supply, global deployment hurdles, strict cold chain requirements, time and cost pressures, as well as internationalization needs of local biotechs.

WuXi Biologics offers a one-stop Clinical Supply Service (CSS), covering full-process support from Phase I to III clinical trials. Compliant with international GMP standards, CSS integrates drug substance and drug product production, ensuring seamless connection across clinical stages. A seamless platform extends through clinical and commercial labeling and packaging, and global distribution to clinical centers via regional depots—providing a single accountable partner from development to delivery. This end-to-end offering significantly reduces risks to quality and compliance, while guaranteeing efficient, continuous, stable supply.

To date, CSS has supported 94 batches of clinical samples, serving clients across Asia, Oceania, Europe and North America—complementing our DP capabilities to form a complete biological drug product service ecosystem.

Conclusion

By leveraging the WuXiHigh 2.0 development and manufacturing platform, hyaluronidase co-formulation, integrated drug-device combination solutions, one-stop CSS and global end-to-end capabilities, WuXi Biologics is helping partners from early clinical development through commercialization to accelerate the launch of new HCBs. This full-lifecycle support enables better patient access to high-quality, patient-friendly, manufacturable products that deliver safe and effective SC doses, while mature technology platforms, regulatory proficiency, and global manufacturing footprint minimize technical failures, supply disruptions and approval delays. 

Complemented by a global DP footprint, with manufacturing sites in China, the US and Singapore, WuXi Biologics’ regional manufacturing hubs are fully compliant with multi-regional regulatory standards (FDA/EMA/NMPA), ensuring integrated capabilities that meet localized supply requirements for global partners.

As these advances continue to address common challenges in SC delivery device development and unlock the full potential of HCBs, we look forward to collaborating with biopharmaceutical partners worldwide to accelerate clinical translation and bring transformative therapies to more patients globally.

References

1. Guo J et al. A review of recent FDA-approved biologic-device combination products. J Pharmaceut Sci 2024;113:866-879.

2. Mijangos LRR et al. Developing high-concentration monoclonal antibody formulations for subcutaneous administration to improve patient treatment. Biophys Rev 2025.

3. Zhai Y et al. Low-field NMR works as a rapid, automatic, non-invasive and wide-scale coverage technique for aggregates indication in biomacromolecule development. J Pharm Sci 2024;113:3034-3044. 

4. Guo J, Weng J, Zhou F, Gu X. An industry perspective on hyaluronidase co-formulated biopharmaceuticals. J Control Release. 2025;381:113573. doi:10.1016/j.jconrel.2025.02.069

5. Guo G. Addressing the pain points of making drug-device combination products. Contract Pharma 2025;1:28–31.

6. U.S. Food and Drug Administration. (2023). MAUDE Adverse Event Report: Wegovy (semaglutide) 2.4 mg single-dose prefilled pen (MDR Report Key: 17052477). Retrieved from www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/detail.cfm?mdrfoi__id=17052477&pc=NSC, January 6, 2026.

Jeremy Guo, PhD, is Senior Vice President and Head of Drug Product Development and Clinical Drug Product Manufacturing at WuXi Biologics. He has over 20 years of industry experience in formulation, process and device development for biologics over a range of modalities.