In pharmaceutical development, several major trends are shaping the future of drug delivery. For decades now, the industry has been slowly but surely shifting towards higher value biologic drugs. In 2021, 2022, 2023, and 2024, there were more approvals for biologic new molecular entities (NMEs) than small molecule NMEs according to GlobalData’s New Drug Approvals and Their Contract Manufacture: 2025 Edition report. There was also a surge in the number of biosimilar approvals in 2024, improving patient access to cost-effective treatments and increasing the use of biologics.

According to Paolo Ferrigno, Product Manager, Prefilled Syringes and Cartridges, Datwyler, who presented on a recent webinar titled “The New Subcutaneous (SC) Landscape: Adapting Drug Delivery for Biologics Administration at Home”, biologics developers have historically favoured intravenous administration routes for better bioavailability. However, this comes with several disadvantages that are prompting sponsors to consider other options on an increasing basis.

Intravenous vs subcutaneous – the pros and cons

“Intravenous delivery has to be managed in a clinical environment with the assistance of healthcare professionals,” states Ferrigno. “That means high total cost for the therapy and less comfort for the patient, leading to higher risk of patients abandoning the treatment. The subcutaneous route of administration, especially when paired with user-friendly devices that allow the patient themselves to administer their therapies in the comfort of a domestic environment, can often support and solve such negative points.”

However, the subcutaneous route brings reduced bioavailability. According to Ferrigno, it’s roughly in 60 to 80% less bioavailable than intravenous administrations, meaning higher dosing needs to be considered when switching therapies to this route.[i] The high viscosity of biologics also requires formulations to be diluted in order to be delivered through the thinner needles used in subcutaneous devices. “So again, even larger volumes,” Ferrigno adds.

Self-delivery of small volume biologics via subcutaneous devices is already well established thanks to the introduction of pen injectors, auto-injectors, and safety syringes with smaller, almost painless needles.

The new challenge comes with the industry’s transition of larger volume biologics, such as oncology therapies, to subcutaneous delivery formats. Doses can be increased and formulations diluted, but how should this be balanced against the patient’s need for a shorter infusion time, as well as the sizing limitations of parenteral packaging systems?

Transitioning large volume biologics to subcutaneous devices

As the benefits of transitioning to subcutaneous delivery continues to grow, innovative companies are exploring new “co-formulation technologies” aimed at increasing the available subcutaneous space, allowing tissue to absorb increased volumes in shorter times. Others are investigating oily solutions with microbiological suspension technology as a way of increasing the formulation’s concentration and reducing its overall volume.

Meanwhile, on-body delivery systems or wearable injectors such as Amgen’s well known Onpro device have been introduced. Ideal for larger volume drugs with longer infusion times, these allow patients to receive their therapy more comfortably and conveniently, with hands-free, on-the-go administration supported by automated injections and smart tracking features.

The impact on primary packaging components

For primary packaging providers, the changing landscape also necessitates innovation. Ferrigno explains that while single-dose auto injectors are currently more common at 1mL to 2.25mL volumes, this limit is now stretching over 5mL. And wearable/on-body systems are looking at 10mL and above.

The first implication is obviously larger components – larger barrels, larger cartridges, and larger plungers. At the same time, there are very important requirements when it comes to safety and performance.

“Being in contact with more sensitive molecules, the requirements for [packaging material] formulation, chemical compatibility, and interactions for reduced particulate, both visible and subvisible, are even stricter,” explains Ferrigno. “[Packaging components] are also required to have a consistent functionality in order to obtain an accurate dose delivery, minimising the need for overfilling in order to reduce dead volume as much as possible.”

For elastomeric plungers, all of this places high demands for quality, performance, and a wide range of size options. Sponsors can find the answers to all of these challenges in Datwyler’s recently expanded range of NeoFlex™ plungers, which are fully coated with a lubricious fluoropolymer spray for low and consistent break-loose and glide force behaviour.

Datwyler’s risk-free solution

According to Ferrigno, the overarching goal behind the NeoFlex™ range is to provide a “risk-free environment and the best experience for the patient”, and several factors go into achieving this.

“The rubber substrate is made with our most advanced formulation characterised by an ultra-low level of extractables,” he begins. “Also, the manufacturing is exclusively performed at our FirstLine® plants – our most advanced solution – to guarantee the highest level of quality.”  

In the same plants, the fluoropolymer spray coating is applied in a thin and flexible layer, with limited risk of peeling or delamination. The coating provides a completely inert barrier to reduce any risks of the drug product interacting with the elastomer formulation, with no further need for siliconisation. Importantly, the coating is applied after the trimming step, mitigating the risk of loose particulates generated during the die cut.

Between 2024 and 2026,  Datwyler expanded its NeoFlex™ range, introducing new plungers engineered to fit into larger syringe and cartridge formats commonly used as containers for large auto-injectors and wearable devices. The largest of these is now suitable for a 20mL cartridge, providing an advanced, risk-free solution for the dynamic and growing market of large-volume injectables.

To learn more on this topic, please download the whitepaper below.

[i] https://pmc.ncbi.nlm.nih.gov/articles/PMC11225035/