At the sharp end – What is the best device for 2-5ml dose delivery?

19 May 2026 12min read

An estimated 16 billion injections are administered annually. While the majority of injectable drugs, for dose volumes less than 10ml, are still administered by healthcare professionals (HCPs) via vial and syringe or pre-filled syringe, an increasing proportion are delivered using alternative devices.

Some, like needle-free injectors, micro-needle patches and active oral delivery systems have existed for years but remain, to differing degrees, relatively niche. Newer technologies, such as specialist needle and catheter-based systems or long-term active implants, delivering directly to organs and tissues, are opening up exciting new treatment possibilities, for example in:

Oncology – Inlexzo™ (formerly TAR-200) by Johnson & Johnson is an innovative therapy, recently approved by the FDA for the treatment of high-risk non-muscle invasive bladder cancer (NMIBC).
Neurology – ThecaFlex DRx™ is an implantable drug delivery system developed by Alcyone Therapeutics, acquired by Biogen, designed to improve how therapies, especially antisense oligonucleotides (ASOs), are delivered into the spinal canal (intrathecal space). This offers a new treatment for patients with neurological disorders like spinal muscular atrophy (SMA).
Cell and gene-based therapies – ENCELTO™ is an FDA-approved encapsulated cell therapy developed by Neurotech Pharmaceuticals, Inc. for the treatment of macular telangiectasia type 2 (MacTel), a rare, progressive neurodegenerative retinal disease that causes irreversible vision loss in adults.

These innovations remain a small, albeit high-value, proportion of the overall market. The number of dial-a-dose pen injectors available on or close to market, whether pre-filled and disposable or reusable, has been growing continually since the NovoPen 1 was introduced in 1985. Due largely to the huge increase in diabetes, although also used for other drug products such as growth hormone, annual sales of pen injectors are currently in excess of 2 billion. Given their potential use for delivery of the new blockbuster GLP-1 drugs, these numbers are only likely to increase.

Two other types of drug delivery system, however, are the key focus of this article. Both generally deliver fixed, factory set doses from a small range of standard industry primary packs and both feature a variety of power sources. One is longer established than the pen injector, while the other – in the embodiments that we are most interested in here – is a comparatively recent addition to the landscape.

On-Body Delivery Systems

Infusion pumps can deliver several hundreds of millilitres and near-body/ambulatory pumps, such as those from Becton Dickinson (BD) and Koru Medical Systems, are suitable for delivery of 20-60ml or more. These injections can take minutes and require the patient to be seated or perhaps moving in a very controlled way.

There are also (either commercially available or in late-stage development) many On-Body Delivery Systems (OBDSs) or On-Body Injectors (OBIs), also sometimes referred to as patch pumps, capable of delivering injections smaller than 10ml.These include West Pharma’s SmartDose®, Enable Injection’s enFuse®, the BD Libertas™ and Stevanato’s Vertiva®.

These technologies differ in approaches, including:

The required user steps – transfer of drug from vial/syringe to wearable injector, loading drug-filled container into pump, pre-filled and pre-assembled primary pack
How needle insertion and fluid path are configured
How sterilisation is achieved
Whether or not pumps are single-use, fully disposable or comprised of retained, power pack units and single-use elements containing the primary pack and needle.

So far, OBDSs have not achieved major commercial success. Only a handful have made it to market, most delivering less than 5ml, with the drug manually filled or loaded by the user. One of these – Amgen’s Repatha Pushtronex® device – was subsequently withdrawn (to be replaced by multiple autoinjector injections). The reason cited for this was that Amgen “wanted touphold the high standards that Amgen has set to enable the most optimal patient experience”.

Pumps are able to deliver drugs over a length of time which can, in some cases, provide potential benefit in terms of reduced site injection pain. Other potential advantages include capable power packs, often but not solely electro-mechanical, which can also provide opportunity for rich user feedback, onboard sensing and connectivity.

However, there are a number of downsides of OBDS technologies which may be partially responsible for limiting devices getting on the market. These include high unit cost, poor carbon footprint, user steps and wasted residual drug volume.

So, given these challenges for OBDSs operating in the <10ml range, is there a better alternative?

Autoinjectors

The first autoinjectors, developed for military and emergency use, were introduced in the 1970s. However, the first major embodiments of the spring-powered, pre-filled disposable autoinjector for weekly or bi-weekly use hit the market in the mid-2000s – Enbrel and Humira.

Since then, many other players have entered the market and design configurations have largely converged to a two-step use sequence, delivering 1-2 ml from pre-filled syringe or cartridge primary pack formats. Platform solutions offered by device manufacturers now dominate the market to some extent, with SHL and Ypsomed leading the pack but many other CDMOs offering similar products and platforms.

For a while it looked as though the autoinjector status quo might prevail, but a number of different factors have continued to drive design innovation.

These include:

Interest in emergency use applications
Some pharma companies choosing to develop proprietary devices
A sudden increased interest (now waning somewhat) in device connectivity
The need to respond to increased commercial and regulatory focus on environmental concerns and sustainability
The drive to further refine the autoinjector format to provide optimised, more competitive delivery solutions for GLP-1 (e.g. multiple factory-set fixed doses from a singleuse pre-filled cartridge).Another industry trend has generated even more impetus to push the boundaries of what can be achieved with single-use handheld autoinjectors – the drive to deliver higher volume, higher viscosity payloads.

Figure 1 – Illustration of delivery energy requirements for 2ml and 5ml (2ml delivered in 10 seconds, Ø8.65mm syringe bore, 1N stopper glide force 5ml in 30 seconds, Ø11.85mm bore, 5N stopper glide force)

Implications for formulation changes on device requirements

Much has been written about the desire to move from very large volume intravenous (IV) delivery to delivery of smaller volumes subcutaneously (SubQ). The FDA approval in September 2025 of the Merck (MSD) KEYTRUDA QLEXTM anti-cancer drug for SubQ injection is one example, whereby a treatment previously undertaken as a 30-minute IV infusion can now be delivered as a 2.4 ml injection lasting one minute. In this case the injection will still be carried out by a healthcare professional, but there will be more flexibility over the location and environment where the injection will be administered.

Moving care from HCP delivery in hospitals or clinics to self-injection at home by the patient, where appropriate, can provide many potential benefits. Key to this change, and the shift from IV to SubQ, is the need to re-formulate the drug product.

Drug formulation is not a topic best suited to detailed examination and explanation by a device engineer (not this one anyway!). What is clear from current conversations within the industry though is that such re-formulation, as drug concentration increases, will result in delivery payloads with increasing volumes and/or viscosities. Volumes of 3 to 5ml as opposed to 1 or 2ml can be expected, with viscosities increasing from 1 or 2cP to 20, 40, 60cP or higher. Such payloads will exceed what current commercially available autoinjectors can deliver and may be beyond what is physically possible for a device which must remain usable – safely and effectively – by the patient.

Figure 1 shows how the energy level required to deliver the dose increases significantly as viscosity and volume increase, particularly for smaller needle gauges. This is true even when allowing for some increase in injection time which also has potential implications for usability.

These increases in force/energy requirements are driving innovations in another aspect of autoinjector design – the power pack. Pre-loaded springs stored over long periods of time can only provide so much energy before demands on the device’s robustness, and possible impact on usability such as delivery time and activation forces, become unreasonable.

Devices such as the YpsoMate 5.5 (5ml delivery, up to 30cP) and GX Inbeneo® (3ml up to 100cP) show what can be achieved by mechanical means (springs). However, there has been a recent increase in devices utilising alternative power sources, such as pre-filled gas canisters (e.g. Kaleo’s AerioTM, SMC’s Bios, Aktiv’s Penpal®) or electro-mechanical drive systems (Phillips-Medisize’s Aria, SHL’s ElexyTM and Portal Instruments’ PRIME Nexus).

With many future formulations likely to land in the 2-5ml volume range, with potentially high viscosities, the medium-term device landscape appears to be giving companies a choice between
OBDSs and hand-held autoinjectors. So, which are likely to be best suited?

Table 1 – Examples of OBDSs and autoinjectors delivering between 2 & 5ml

Is there a preferred device type for self-injection of 2-5ml?

Table 1 shows a selection of currently available on-body and autoinjector delivery systems which cover the dose volume range of 2-5 ml.

From a commercial perspective, mechanical autoinjectors have a number of upsides. They generally provide both lower cost per dose and better environmental impact than single-use, on-body injectors, most of which contain expensive, high carbon footprint electronics.

Onboard technology does provide pump systems with scope to offer potentially commercially attractive functionality, but the value proposition of onboard monitoring and connectivity has not yet been widely demonstrated.

Cost and environmental impact can be reduced by moving to systems that use retained, reusable drive systems and single-use disposable primary packs, fluid paths and needles. Autoinjectors too can be configured in this way. For both types however, this approach can have an adverse impact on usability, due to the increased number of use steps. Autoinjectors that employ the well-established two-step use sequence offer intuitive ease-of-use which, if well designed, is hard to match.

This is almost certainly true for patients accustomed to weekly or bi-weekly self-injection who then move to dosing regimes of one or two injections per year i.e. a familiar process, just less frequent. However, patients who are used to treatments based on long infusions in clinics might feel more at home, so to speak, moving to delivery via on-body systems. User preference may depend on familiarity and the treatment journey that the patient has been on to get to a 2-5 ml bolus injection.

Also important of course is the physical – not cognitive – challenge of carrying out self-injection. Human Factors studies carried out by Ypsomed indicated that users were able to sustain a hold time consistent with a 5ml injection of over 60 seconds, but whether this can consistently be achieved – or is preferred – across different user groups is not yet known.

Perhaps the key factor influencing user preference for different delivery systems is injection site pain. A review of literature presented at a recent conference indicates that injection rates >1 ml per minute (as delivered by most autoinjectors) are more painful than delivery rates of <1 ml per minute (by most pumps). Also, injection into the arm or thigh (a common injection site for autoinjectors) is scored as being more painful than injection into the abdomen (both autoinjectors and OBDSs). Other factors influencing pain, such as drug volume, temperature and viscosity, are also reported but do not distinguish between the two device types.

Conclusion

As demand for self-injection continues the industry will innovate with new devices, both on-body delivery systems and autoinjectors, and the 2 to 5ml delivery volume range will be an important area of attention. Pros and cons of different device types to cover this range are discussed above, but no definitive best route is identified.

Many factors are at work which need to be considered for each application. The needs of the user must always be considered as a priority and solutions optimised to support safe and effective use. This does not mean direct patient preference or patient choice can always be applied, however, and the reality of commercial constraints will always dictate what can be offered. Optimum solutions will vary case by case, but device companies will strive to offer viable options from which the most appropriate system can be chosen.