Preparing for mass vaccination

11 Aug 2020 15min read

There are currently multiple COVID-19 vaccine development programmes running across the world. Hopefully some of these will shortly be approved for use and will have a major impact, not least the recent vaccine developed by Pfizer and BioNTech. In parallel, significant investment is being made by governments and non-profit sources to build adequate capacity for the delivery and administration of such vaccines at national and global scale(1). With potentially hundreds of millions of doses to be administered annually, it is important to think carefully about the platform that will be used for COVID-19 vaccine delivery.

The low cost and ready availability of hypodermic syringes makes them immediately attractive, but the cost burden of needlestick injuries cannot be ignored. Needle-free injection eliminates this risk and, when designed appropriately, enables safe, targeted and reproducible dermal delivery. Furthermore, needle-free delivery is independent of viscosity and hence independent of the flow characteristics of a vaccine. With so many candidate vaccines in development, there is potential to scale needle-free technologies in parallel with ongoing vaccine development programmes, safe in the knowledge that it has maximum potential to reliably deliver whatever vaccine(s) are proven to be effective.

Current status of COVID-19 vaccine developments

According to a report by The Lancet, there were already ten SARS-CoV-2 vaccine candidates in clinical trials as of June 2020(2). These span mRNA vaccines (mRNA-1273 (Moderna and NIAID) and BNT162 (BioNTech and Pfizer)), DNA vaccines (INO-4800 Inovio Pharmaceuticals), inactivated virus (Unnamed (Wuhan Instutitute of Biological Products and Sinopharm)), Protein subunits (NVX-CoV2373 (Novavax)) and Adenovirus vaccine (AZD1222 from the University of Oxford and Astra Zeneca). Operation Warp Speed is underway and many more candidates are now in clinical trials(3).

The Lancet report suggests that the average development time for a vaccine is 10 years, but the hope is that current lifescience tools can shorten the process to allow COVID-19 vaccines to be delivered in 2020. It highlights that the typical success rate for vaccine development is only 6% and that even an 18-month development programme is considered very aggressive by infection experts. The report also warns that “global appetite for any successful vaccines, if and when they are ready, will bring its own difficulties. Developers are starting to scale up production even now, despite the risk that their favoured candidates will fall short. Distribution, delivery and administration need to be worked out”.

Delivery platforms for vaccine administration

Many people will have experienced annual influenza vaccinations being administered by intramuscular injection (generally used for adults) or by nasal delivery (generally used for children). These are the most common methods of vaccine administration and a review of COVID-19 vaccine trials on shows that, for a sample of 17 studies, the following administration methods were cited:

– Intramuscular injection (9 studies)
– Intradermal injection (2 studies)
– Sub-cutaneous injection (2 studies)
– Electroporation via the Cellectra 2000 (1 Study [INO-4800])
– IV Infusions (1 study)
– Not cited (2 studies)

It is clear that parenteral delivery by hypodermic syringe remains the administration method of choice. Although the convenience and cost advantages of hypodermic syringes are undeniable, we believe that a better delivery platform exists to meet the unprecedented demand for rapid, global, mass vaccination against COVID-19.

The case for needle-free injection

When appropriately configured, needle-free injection offers compelling advantages over hypodermic syringe delivery as a platform for mass vaccination. These advantages include a) dose-sparing through intradermal efficiencies b) reliable intradermal delivery, c) elimination of needlestick and re-use d) insensitivity to vaccine flow characteristics and e) attractive healthcare economics. These advantages are described in more detail below:

Illustration of a needle free injection

Dose-sparing through intradermal efficiencies

Intradermal injection is a shallow injection of a substance into the dermis and can be easily and reliably achieved with needle-free technology (see item b below). The dermis and epidermis of human skin are rich in antigen-presenting cells. As such, focusing the delivery of vaccines to these layers – rather than to muscle or subcutaneous tissue – should be more efficient; inducing protective immune responses with smaller amounts of vaccine antigen.

The potential benefit of dose-efficiency through intradermal delivery has long been recognised(4), with the WHO bulletin presciently stating that dose-sparing might also “stretch” the availability of vaccines in cases where supply is limited by manufacturing capacity. This is probably most relevant for pandemic influenza vaccines where global production capacity limits access to a vaccine at the start of a pandemic. In 2009, the H1N1 vaccine was not available in most low-income countries until 8 months after the WHO’s declaration of the influenza pandemic.

Currently, no country in the world has access to a COVID-19 vaccine and hence developing a delivery system that allows efficient vaccine dosing is a key early consideration.

Reliable intradermal delivery

The traditional procedure for intradermal delivery is needle based injection via the Mantoux procedure. This involves injecting at an angle of administration of 5 to 15 degrees i.e. almost holding the syringe against the skin. With the bevel of the needle pointing upwards the needle is inserted approximately 3 mm into the skin and the injection performed while watching for a small wheal or blister to appear. It is most commonly used in BCG tuberculosis vaccinations.

The degree of needle control necessary in the Mantoux procedure requires careful delivery by the clinician and good cooperation from the patient to ensure reliable intradermal delivery. In needle-free delivery the substance being injected acts as the needle and hence, by controlling the dose volume and skin contact pressure, it is possible to achieve intradermal delivery easily and reliably. One simple approach is the addition of a simple ring around the nozzle of a needle-free injector. This causes a dome of skin to reliably engage the nozzle of the injector and also allows space for the skin to lift up into the characteristic blister or wheal that is generated by successful intradermal delivery. The photographs below show successful intradermal delivery achieved by a DosePro needle-free device modified with a simple polycarbonate intradermal spacer component.

Photo of successful needle free injection and a device

Elimination of needlestick and re-use

A well-recognised advantage of needle-free delivery is the avoidance of needlestick injury and the associated healthcare and societal costs that arise from it. Furthermore, disposable vaccine capsules provide single use advantages such that they cannot be re-used and hence any body fluids picked up from contact with a patient’s intradermal blister will not be transferred to the next patient.

In a recent COVID-19 webinar from PATH(5) it was predicted that, in developing countries, the disruption in services from COVID-19 isolation would knock progress in treating HIV, TB and Malaria back by 5 years. Vaccination programmes for vulnerable groups will be a high priority in these countries. A needle-free injector with single use, dose efficient vaccine capsules offers the potential for safer, more reliable and lower cost vaccination programmes in these vulnerable patient groups.

Insensitivity to Vaccine Flow Characteristics

A further advantage of needle-free injection is that the intradermal delivery performance is independent of the flow characteristics of the substance being delivered. For a conventional hypodermic syringe and needle, flow rate is characterised by the Hagen-Poiseuille equation, where Q=flow rate, D= needle bore, L=needle length, P=drive pressure µ=dynamic viscosity.

Diagram of a needle and syringe

However, for a needle-free injector, delivery is through an orifice, and the flow is characterised by the Bernoulli equation, where Q=flow rate, D= orifice bore, P=drive pressure, ρ=density, Cf=flow coefficient (0.95 for a practical round edged orifice).

Diagram of a needle free injection device

The only fluid property which appears in the Hagen-Poiseille equation is µ, dynamic viscosity.
The only fluid property which appears in the Bernoulli equation is ρ, density.

For a conventional needle and syringe, it can be seen from the Hagen-Poiseuille equation that for any increase in viscosity, µ, an increase in pressure (i.e. an increase in the syringe plunger force) will be required to maintain the same flow rate.

However, if we consider a needle-free injector, there is no viscosity term, and the only fluid property which affects the flow rate is the fluid density, ρ. Since most fluids of interest as injectables have approximately the same density, the pressure to deliver at a given flow rate, and hence the plunger force, will remain unchanged. This unique property makes it viable to scale the technology in parallel to ongoing vaccine development programmes, safe in the knowledge that it will tolerate different vaccine viscosities and hence should be capable of reliably delivering whatever vaccines are proven to be most effective.

Attractive healthcare economics

Needle-free injection relies upon a very high jet velocity hence the pressure and operating force is much higher. All needle-free technologies therefore rely upon a stored energy source rather than unaided manual operation. Although this adds expense to the unit device cost (the unit cost of standard hypodermic syringes will always be cheaper), the potential benefits of reliable, safe, dose efficient, needle-free delivery systems remain compelling from a healthcare economics perspective.

As highlighted in item c), the ability to eliminate needlestick injury is a significant economic benefit. The annual cost of treating needlestick injury in hospital workers alone is as high as $591m in the US, $302m in Japan and $900k in the UK(6). These represent developed countries with the highest levels of training and resource. COVID-19 is a global pandemic, therefore the cost burden of needlestick is likely to be far higher.

Based on work by Team Consulting, it is feasible to develop mass vaccination needle-free injectors where the cost of re-use is limited to a pre-filled single shot vaccine cartridge. One concept involves vaccines being dispensed from the low volume single-shot, non-reusable capsule using a robust, high duty cycle, multi-use actuator device.

The Sumavel DosePro is a factory-filled, single-use needle-free injection product, which was approved in the US, UK and Germany for needle-free delivery of sumatriptan for migraine relief. The image below shows a self-powered variant based on a system developed and proven in clinical trials in the early 2000s by Team Consulting – alongside a leading veterinary medicine company – for vaccination of farm animals. It is powered by a small reservoir of butane/propane fuel, similar in size to a cigarette lighter. The farm animal version was much like a power drill in size and appearance, but a scaled down human use version was built and tested. The images show the operational sequence of the system with cartridges (capsules) configured for subcutaneous injection.

Drawing of a cartridge injection device

Mass vaccination device (with on-board fuel tank)

An alternative approach is a mass vaccination system powered by pressurised nitrogen (see images below). The nitrogen-powered concept is simpler to use than the self-contained butane/propane fuelled device, but is dependent on the availability of a compressed nitrogen supply (typically a standard cylinder).

Drawing of pressurised nitrogen injection device

Compressed nitrogen powered vaccination system

The self-contained nature of the butane/propane fuelled device – though requiring more user effort to prime the system – may be preferred in areas with limited infrastructure/logistics. The nitrogen-powered systems may be more widely accepted in developed countries.

Challenges and risks

Clearly the decision to adopt needle-free technology is a significant one and not without risk. In addition to the development and scaling risks (applicable to any new medical technology) there is also the question of whether all vaccines will actually be suited to the efficiencies of intradermal delivery.

In terms of technical development and scaling, Team, in its 30+ years, has investigated needle-free platforms and seen encouraging clinical results, as well as approvals obtained. With sufficient investment it is very feasible to scale the technology to be ready to deliver novel vaccines at large scale. The key challenge will be the availability of large-scale filling systems and indeed the supply of a custom vaccine cartridge. It is very likely that existing, available filling systems will all be configured for filling ‘standard’ prefillable syringes or vials. It will take 18 months and significant investment to set up the high-volume manufacturing and filling capacity for needle-free capsules, but this is still commensurate with the 18 months that vaccine experts consider likely for a COVID-19 vaccine to be developed(7).

In terms of vaccine efficacy under intradermal administration, the WHO bulletin from 2011(8) states that “Live-attenuated vaccines have been successfully delivered intradermally and should be good candidates providing that appropriate formulations can be developed. Reduced doses of inactivated whole-virion vaccines have also shown satisfactory immunogenicity when delivered intradermally. Inactivated whole virion influenza vaccines might also be suitable because they have intrinsic immune-stimulating sequences, which might avoid the need for addition adjuvants”. With timely investment, a low volume needle-free system could be developed more quickly for researchers to use in vaccine trials, allowing vaccine efficacy under intradermal needle-free delivery to be demonstrated from the outset.

Governments, international agencies and technology companies are already investing significant sums of money into vaccine development programmes and associated delivery systems. With sufficient coordination across stakeholders, a reliable, needle-free, dose efficient vaccine delivery system is a very viable concept that should be considered.


1. “Industry Builds Fill/Finish Capacity for Pandemic Response”, July 15, 2020
2. Covid-19 vaccine development pipeline gears up, Vol 395, June 6 2020 pp 1751 to 1752,
3. “COVID-19 vaccine tracker”, Regulatory Focus,
4. “Intradermal delivery of vaccines: potential benefits and current challenges”, Bulletin of the World Health Organisation, 2011, 98, 222-226
5. Continuing Essential Service Delivery in a Pandemic: HIV, TB and Malaria Solutions in Action []
6. “Estimating the national cost burden of in-hospital needlestick injuries among healthcare workers in Japan<” PLoS One 2019, 14(11) pp 1-21 7. Covid-19 vaccine development pipeline gears up, Vol 395, June 6 2020 pp 1751 to 1752, 8. “Intradermal delivery of vaccines: potential benefits and current challenges”, Bulletin of the World Health Organisation, 2011, 98, 222-226

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