Trade-offs in balancing complexity, patient comfort, and device innovation in complex biotherapeutic delivery

Care is shifting from hospital to home for an increasing number of conditions. Subcutaneous self-administration plays a key role in this trend, driven by the need to reduce the strain on healthcare systems, improve the patient experience, boost adherence and reduce costs. For biopharmaceutical developers and healthcare providers, large volume, highly viscous, and complex biotherapeutics present unique delivery challenges to ensure their safe and effective administration.

Navigating the trade-offs in selecting the optimal delivery method for your formulation can be a complex challenge.

Consider a scenario in which the decision-making process unfolds like a pyramid, each level representing essential factors that must be thoroughly evaluated. Missing a step could lead to potential ‘dead-ends,’ highlighting the need for a thoughtful, all-encompassing approach.

Michelle, who leads a device team, needs to navigate a maze of complex decisions at multiple levels to determine the best way to deliver an exciting new biologic formulation from the drug product team. Each decision is influenced by the decisions she made in the last level.

What will be the best possible way for Michelle to deliver the formulation?
Her journey is one that mirrors the real challenges faced by drug delivery device teams today. Each decision involves balancing patient comfort, practicality, and device capability.

Follow Michelle as she encounters different challenges and considerations during her journey.

Her journey starts in the Formulation Zone, where most device teams are forced to start, as the formulation is still to be decided. For lower volume and low-viscosity formulations (1-2 ml), the delivery is relatively straightforward using existing auto-injectors or prefilled syringes. These formulations flow quickly through the skin’s porous tissues, ensuring a smooth and rapid absorption process.

However, Michelle’s challenge lies in delivering a formulation that is much larger and highly viscous. At viscosities greater than ten centipoise, the skin starts to deform elastically and even fracture to accommodate the formulation—a process often referred to as “fracking.” This is where the biomechanics of the infusion process come into play. Understanding back pressure and tissue deformation becomes critical, especially for pressure-driven devices.

Michelle could consider going slower to avoid fracking, making absorption by the capillary and lymphatic system more predictable.

Decision point: Michelle faces a choice of three formulations as she attempts to advance to the next zone. Her choices will restrict device options later down the line if she selects a less flexible approach. She needs to choose between 5 ml (extremely viscous), 10 ml (slightly less viscous) or 20 ml) (less viscous, but with different device considerations). Each option brings a different set of new challenges, and how she approaches the infusion speed will significantly impact the patient’s experience.

Michelle next enters the Physics Zone, where she must understand how the formulation behaves in the delivery device, by considering factors like delivery time and needle size.

Delivery time is driven by the volume and viscosity of the formulation, but also the bursting pressure of the cartridge. The relationship between needle diameter and delivery time also plays a key role—smaller needles, while more comfortable for the patient, drastically slow down the infusion.

As the needle gauge gets higher (and the inner diameter gets smaller), it takes longer to push the formulation through the needle.

She discovers that smaller needle gauges, while beneficial for patient comfort, significantly increase the delivery time of the viscous formulation.

As Michelle tests different needle sizes, she finds that moving from a 27-gauge extra-thin to a 32-gauge thin needle increases the infusion time significantly—from just 20 seconds to nearly 20 minutes. This insight highlights a key trade-off: while smaller gauges enhance patient comfort, they also substantially lengthen delivery time, making it critical for Michelle to balance comfort with practicality in device design.

It’s not just about comfort—needle selection has real trade-offs in terms of delivery times, and this decision will directly affect the usability of the device.

Decision point: Michelle is faced with a decision. She knows that each option has trade-offs that could restrict subsequent design choices if not considered alongside the broader device goals. She could select a 5 ml formulation, compatible with large auto-injectors, resulting in an infusion time of approximately 20 to 43 seconds. Alternatively, a 10 ml formulation with a thinner needle might offer a balanced solution, providing a manageable 3.5-minute infusion time while maintaining reasonable patient comfort. Lastly, a 20 ml formulation with an ultra-thin needle would increase comfort but extend infusion time to nearly an hour. Each decision involves balancing patient comfort, practicality, and device capability.

In the Usability Zone, Michelle reviews user studies conducted by TTP. She finds that dose frequency and duration are the most important factors in comfort ratings – much more important than device size. Patients’ daily routines and when they prefer to take their medication play a critical role in device design.

She also learns that holding an injector in place for extended periods is physically and psychologically challenging. Stability is a big issue, particularly for those with arthritis, causing fatigue and tension. The physical strain and psychological discomfort can make even the best-engineered device impractical if patient usability isn’t considered.

For example, the studies show that user comfort decreased significantly when they had to hold the auto-injector in place for 60 seconds. These insights are invaluable for designing devices that fit seamlessly into a patient’s life.

Further user-centred insights around injection sites reveal that, on average, the worst sites to administer injections is the arm, followed by the abdomen and then the thigh.

Decision point: Now that Michelle has a better understanding of patients’ preferences, she has a choice of which type of device to choose. For the 5 ml option, she has a choice of two more traditional 2.25 ml auto injectors. Recognising that infusion times are likely to be much longer for the 10 ml option, she could go down the route of an on-body injection platform that infuses over a few minutes. Alternatively, there’s a 20 ml slow infusion option with a personal belt-worn device. Each device comes with its usability trade-offs—balancing longer infusion times with patient comfort and ease of use is critical. Michelle understands that choices here could limit options in the next stages if usability factors aren’t anticipated early on.

Moving to the Adherence Zone, Michelle realises that factors like ease of use and fitting medication into daily routines are crucial for ensuring that patients stick to their treatments. Long-term adherence is complex – patients are more likely to stay on their medication if it doesn’t disrupt their routine or feel overly burdensome.

The number of medications and dose frequency have both been shown to have a strong correlation with adherence and persistence levels in many disease areas. Other things such as convenience habits, ease of use, and feedback are all important as Michelle considers device options.

Michelle is aware that the choices she made in earlier zones about delivery speed and device type can constrain her options here.

Digital health solutions are often introduced here, to help patients track their progress and receive feedback, which can further support adherence.

Finally, Michelle makes her way through the multi-level maze. She understands that making decisions sequentially can often lead to dead-ends where device compatibility or patient comfort might be compromised. Instead, TTP advocates a more holistic approach, encouraging device teams to consider factors from all zones right from the start.

At TTP, we’ve developed a design toolkit to support the design of solutions that take some of these key factors into consideration at the earliest possible development stages. What we advocate is that you should always consider these factors holistically, right from the start, avoiding restrictive decisions to design a solution that aligns seamlessly with both the formulation needs and patient experience. By leaving as many options open as possible for as long as possible, you’ll be better positioned to deliver a device that works well for both the formulation and the patient.

To learn more about how TTP’s drug delivery team can help, get in touch.

At TTP, we transform bold ideas into breakthrough drug delivery solutions, guiding you from a blank sheet to clinical reality. Our interdisciplinary team partners with you to help you address the toughest challenges, leveraging deep engineering, human factors, and scientific expertise. With over 70 successful drug delivery systems commercially available, ranging from injectables to complex infusion pumps, we excel at developing efficient, scalable devices aligned with market demands. Trusted by nine of the world’s top ten pharmaceutical leaders, we drive projects from early exploration through to manufacturing and launch, ensuring high-impact, low-risk solutions that enable the delivery of transformative therapies and enhanced patient experiences.