As biologics increasingly shift toward self-administration, the demand for high-concentration formulations compatible with prefilled syringes and on-body devices continues to rise. These delivery formats improve patient adherence but pose unique developability and manufacturability challenges. With deep expertise in high-concentration formulation development, drug–container compatibility, and collaborative drug product development involving multiple stakeholders, Coriolis Pharma helps drug developers transform complex biologics into stable, patient-friendly therapies that are ready for real-world use.
Why Self-Administration Matters: Improving Experience and Adherence
The vast majority of biologic drugs must be delivered by injection. Traditionally, this has meant intravenous administration in clinical settings, typically under the supervision of a healthcare provider. Many biologics also require frequent dosing, making regular trips to hospitals or infusion centers time-consuming, disruptive, and, for many patients, unsustainable. This burden is one of the most common causes of treatment discontinuation.
Shifting from intravenous to subcutaneous delivery opens the door to self-administration, enabling patients to receive their medications at home or even while traveling. This change significantly improves convenience, comfort, and autonomy, all of which contribute to better treatment adherence, and with that ultimately to treatment success. As a result, self-administrable formats — especially prefilled syringes, autoinjectors, and on-body devices — have become a growing focus in drug product development.
These advanced application systems offer psychological as well as practical benefits. Because the needles are often hidden inside the device, patients are spared the stress of visually being confronted with the injection process, an important factor for individuals with needle anxiety. This design can make a profound difference in whether patients feel confident enough to administer their medication independently.
In addition to ease of use, subcutaneous delivery typically involves smaller injection volumes, often at higher drug concentrations, to achieve similar therapeutic drug levels compared to an intravenous injection. On-body devices take this a step further by enabling delivery of larger volumes over extended periods, requiring even less effort from the patient (hands-off application of the drug), which can further contribute to prolonged dosing frequencies. For people managing chronic conditions, such as autoimmune diseases or cancer, this hands-off approach can dramatically reduce treatment burden.
On-body devices also offer particular advantages for patient populations with physical limitations or psychological barriers. Children, for example, can receive treatment without even realizing it is occurring — while playing, attending school, or resting. Similarly, elderly patients or those with reduced dexterity may find on-body systems more accessible than handheld devices.
Ultimately, the design of the delivery system is not just a technical matter; it’s central to the patient experience. Formulations optimized for self-administration empower patients to stay on treatment and live more independently, making them a vital component of modern biologic drug development.
Formulating with the Device in Mind
When developing biologic drug products, the route of administration is a fundamental driver of formulation design. For subcutaneous injection via autoinjectors or on-body devices, the physical and mechanical constraints of the device have a direct impact on formulation parameters, including excipient selection, concentration, viscosity, and compatibility with the container closure system.
Because autoinjector volumes are limited — typically 1–3 mL — formulations must often be developed at higher drug concentrations to achieve the required therapeutic dose. However, increasing concentration tends to raise viscosity, which can pose challenges during manufacturing (e.g., tangential flow filtration) and require higher injection forces during administration. To address this, viscosity-reducing excipients are systematically screened as part of the optimization process.
Higher concentrations can also increase protein–protein interactions, heightening the risk of aggregation, which may compromise both stability and efficacy. This necessitates careful selection of stabilizing excipients, guided by deep knowledge of the molecule’s aggregation pathways and the formulation’s stress response profile.
Autoinjector design further influences formulation requirements. For example, multi-dose autoinjectors may necessitate the inclusion of antimicrobial preservatives to maintain product integrity over repeated uses. These agents must be selected and validated carefully to avoid interference with protein stability or patient tolerability.
Container closure system compatibility is equally critical. Protein adsorption to syringe or cartridge surfaces can reduce dosing accuracy and contribute to degradation. Additionally, particulate contamination often stemming from formulation–material interactions — must be mitigated. One particular concern is the use of siliconized glass barrels in prefilled syringes. Over time, silicone oil droplets may leach into the formulation and might result in higher aggregation rates due to interactions with the drug. Alternatives, such as crosslinked siliconization techniques or silicone-free container materials, may be explored when warranted.
Ultimately, successful formulation development for advanced drug containment solutions requires a holistic view that integrates physicochemical understanding of the drug substance, device-specific constraints, and a proactive strategy to minimize risk throughout the product’s life cycle.
Balancing Volume, Viscosity, and Compatibility
Formulating biologics for autoinjectors and on-body delivery systems requires careful navigation of overlapping challenges, most notably the need for high drug concentrations, acceptable viscosity levels, and device-specific stress tolerances. While both systems are designed to enable subcutaneous self-administration, the technical requirements and formulation constraints can vary significantly between them.
In both cases, high concentration formulations are typically needed to deliver effective doses within the volume limits dictated by the device. However, while prefilled syringes/autoinjectors usually accommodate volumes up to 3 mL (newer developments also enable 5 mL), on-body devices can deliver much larger volumes — up to 10–20 mL — by extending the injection time. This makes on-body systems ideal for newer, more complex biologics, such as multispecific antibodies, fusion proteins, and antibody–drug conjugates, which require high doses but cannot be formulated at ultra-high concentrations due to viscosity or aggregation risks.
Viscosity is a critical constraint for both device types. Prefilled syringes are designed for rapid injections, typically completed within 30 seconds or less, and rely on human or spring-assisted force. On-body devices, on the other hand, use miniature pumps to deliver the drug over an extended period — minutes up to hours — and have their own force limitations. In both scenarios, formulations must be optimized to meet viscosity thresholds compatible with the device’s mechanical tolerances to ensure consistent and precise delivery while maintaining comfort for the patient.
Another important distinction lies in supply chain flexibility. Prefilled syringes and cartridges are widely used, and multiple standardized formats are available from several vendors. This broad availability gives formulation developers a relatively high degree of freedom when selecting container materials and configurations. In contrast, the on-body device market is still emerging, with fewer commercialized systems and more proprietary designs. As a result, developers may face greater constraints in terms of packaging compatibility, component selection, and regulatory familiarity.
In-use stability and compatibility requirements also differ. The rapid injection delivered by a prefilled syringe or an autoinjector subjects the formulation to a brief, high-shear event, while the slow, prolonged administration via an on-body device exposes the product to extended contact with device materials, body heat, and ambient conditions. This means the formulation must remain stable at room or skin temperature for the entire delivery duration — in some cases, this might be a period of several hours. These stressors must be evaluated during development — not only from the device side, but also from the drug side — to ensure that the product maintains its critical quality attributes throughout the delivery window.
As the range of biologic modalities expands and patient preferences shift toward more convenient, at-home treatment options, both prefilled syringes, autoinjectors, and on-body devices will play an increasingly important role. Successful formulation development hinges on understanding and addressing the distinct requirements of each.
Adapting Formulations to Fit Evolving Delivery Needs
Regardless of the delivery route, successful formulation development begins with a deep understanding of the drug itself: its structure, physicochemical properties, and potential liabilities. This foundational knowledge not only informs excipient selection and formulation design but can also help guide the choice of the most appropriate route of administration and delivery system.
In an ideal scenario, formulation development begins in the early stages of drug development, allowing for developability assessments and pre-formulation studies to proceed in parallel with evaluations of potential delivery options, such as prefilled syringes, autoinjectors, and on-body devices. During this phase, many feasibility and optimization studies are conducted, often using vial-based formulations, including for high-concentration products. Specific adaptations for device-based delivery, such as optimization for a particular syringe or cartridge, and screening of compatible packaging materials, are often performed later, once more is known about the dosing requirements and delivery context.
This phased approach is particularly effective when supported by a strong foundation of prior experience. At Coriolis, broad familiarity with a range of injection systems allows formulation teams to anticipate common device-related challenges, even before a specific device has been selected. This knowledge helps shape early study designs and mitigates the risk of surprises later in development.
However, there are cases where formulation flexibility is limited — for example, when the route of administration is fixed due to the target patient population or clinical indication. Pediatric patients, oncology settings, or products intended for self-administration may impose strict constraints from the outset. In these instances, formulation scientists must adopt a more reverse-engineered approach, tailoring the formulation to suit the chosen device or administration route from the very beginning.
Ultimately, formulation development is rarely linear. It requires adaptability, early cross-functional collaboration, and the ability to pivot between feasibility, optimization, and final device integration as new information emerges. The ability to operate fluidly within this dynamic landscape is what enables teams to deliver effective, patient-friendly therapies, on time and on target.
From Vial to Device: Navigating the Transition
Biologic products are often first developed in vial-based formulations for early-stage clinical studies, particularly phase I and II trials, where the primary goal is to determine drug safety, optimal dosing and therapeutic exposure levels. Once a viable dose is established, the focus often shifts to improving patient convenience and adherence, prompting a transition to prefilled syringes, autoinjectors, or on-body delivery systems.
In some instances, the original vial formulation may already meet the requirements for subcutaneous delivery. More commonly, however, reformulation and optimization are needed to adapt the product for use in a device.
The first step in this transition typically involves increasing the protein concentration of the IV vial formulation to deliver the full dose within the volume constraints of a subcutaneous injection. This can trigger a cascade of formulation challenges, including mitigation strategies to control elevated viscosity, increased aggregation risk, and potential changes in thermal and colloidal stability. To evaluate these effects, accelerated stability and stress studies are performed, examining the impact of the higher protein concentration on these parameters in detail. It is frequently necessary to introduce viscosity-reducing or stabilizing excipients to ensure both flowability and stability at higher concentrations.
After the initial adjustments in formulation composition, developers often conduct material compatibility studies across different container closure systems to evaluate performance and potential risks.
New container materials, as present when switching from vials to prefilled syringes or cartridges, can introduce new leachables and extractables, such as silicone oil droplets or tungsten residues, which can impose incompatibilities with the drug. If such incompatibilties are detected, root cause analysis is essential to identify appropriate mitigation strategies, such as switching to crosslinked siliconized barrels to reduce exposure to silicone oil or syringes manufactured without contact to tungsten pins during their manufacturing to avoid tungsten residues.
If the volume needed to reach the required dose cannot be brought below the ~3-mL limit typical of autoinjectors and prefilled syringes, the use of an on-body injector may be warranted. These systems support larger injection volumes by delivering the drug slowly over time, but they also introduce new formulation requirements, such as extended room-temperature stability during administration.
No matter which device is ultimately selected, this phase of development is best managed through a three-way collaboration between the drug sponsor, the formulation development team, and the device manufacturer. Each partner brings unique expertise that helps ensure a seamless transition from vial to device, minimizing risk while optimizing patient experience and clinical success.
Exciting Opportunities on the Horizon
While the pharmaceutical industry is often viewed as conservative — driven by the imperative to ensure patient safety — it is also deeply rooted in scientific and technological innovation. Nowhere is this more evident than in the evolving field of subcutaneous biologic drug delivery, where continuous advances in formulation science and injection device technology are reshaping the possibilities for patient care.
For high-concentration formulations, researchers are actively exploring methods to push the boundaries even further, developing ultra-high concentration formats that can deliver potent doses in minimal volumes without compromising stability or usability. At the same time, device manufacturers are rising to meet this challenge, introducing higher-volume syringes and autoinjectors capable of delivering up to 5 mL subcutaneously, significantly expanding the range of biologics that can be self-administered.
Innovative formats like dual-chamber syringes may soon enable sequential delivery of multiple components in a single injection, reducing burden and increasing convenience. While some of these technologies remain on the horizon, their development reflects a growing industry consensus: the future of biologics depends not only on what is delivered, but also on how it is delivered.
The industry has already made remarkable progress in enabling self-administration of complex therapies. As formulation strategies and device capabilities continue to co-evolve, the next generation of treatments promises to be even more patient-centric, adaptable, and effective.
Excipient Challenges in High-Concentration Formulations
One of the most significant hurdles in developing high-concentration biologic formulations is the limited availability of regulatory-approved excipients. Few novel excipients are introduced to the market because of the high regulatory risk and lack of a dedicated approval pathway. Currently, excipients are only approved in the context of a drug product — not as standalone components — meaning any new excipient must undergo full safety evaluation as part of the overall product submission.
The use of a novel excipient introduces greater regulatory complexity and data requirements, including extensive toxicology and safety studies. As a result, such excipients are typically only considered when no approved alternatives exist, and the therapeutic benefit of the drug — often a breakthrough therapy — justifies the added risk and investment.
Formulators of biosimilars face a related, but distinct challenge. In many cases, key excipients used in reference biologics are protected by patents. For example, the antioxidant methionine is widely recognized for its stabilizing properties but may be excluded from use in biosimilar formulations due to proprietary claims. In such cases, developers must identify alternative excipients that can deliver comparable performance, which can be a difficult task, particularly when stability, solubility, and aggregation resistance are already being pushed to the limits by high drug concentrations.
As formulation complexity increases, these excipient constraints — regulatory, legal, and scientific — underscore the importance of deep experience, innovative problem-solving, and early risk assessment in the development process.
Extensive Experience and Strategic Collaborations Advance Self-Administered Therapies
Developing high-concentration formulations for self-administration requires deep scientific expertise and a nuanced understanding of both formulation science and device compatibility. For drug developers pursuing these complex therapies, choosing an experienced outsourcing partner is essential to minimizing risk and accelerating progress from early development to clinical success.
With nearly two decades of experience, Coriolis Pharma has established itself as a leader in high-concentration formulation development. Our expertise spans the full spectrum of project needs — from early-phase programs focused on developability and high-concentration feasibility to later-stage efforts involving the transition from vial-based formulations to those compatible with autoinjectors and on-body delivery systems.
Our approach begins with a detailed evaluation of the physicochemical characteristics of the drug substance, including its behavior under varying formulation conditions, such as pH, ionic strength, and concentration and storage conditions, such as temperature. These insights inform the development of formulations that balance stability, manufacturability, and device compatibility, often through comparative studies across different container materials and delivery formats — all while aligning with the target product profile.
Once formulation candidates are shortlisted, we conduct rigorous excipient screening, considering both well-established excipients and novel options when appropriate and desired by the client. This scientific, methodical process ensures that each formulation is optimized not just for today’s development needs, but for future manufacturability and life cycle flexibility.
A hallmark of Coriolis’ success is our unbiased approach to formulation. We prioritize scientific integrity and flexibility over pre-commitment to any specific platform. At the same time, we recognize the value of strategic collaboration, not only with our clients but also with device manufacturers. When appropriate, we facilitate three-way confidentiality agreements between sponsors and primary packaging/device partners to enable open, collaborative data sharing — an essential step in selecting the most suitable delivery solution.
Coriolis is also committed to staying ahead of the curve by familiarizing ourselves with the latest developments and ongoing innovation, so we can better support clients pursuing next-generation delivery technologies.
Above all, our formulation development programs are anchored in a client-centric philosophy. Through our integrated, collaborative approach, we help drug developers advance even the most complex biologics with confidence. From candidate selection and stability testing to primary packaging selection, late-stage optimization, and device integration, our goal is to enable success at every stage—delivering high-quality, stable, patient-friendly products that meet the demands of a rapidly evolving market.