Vaccine delivery has long been a hot topic and only got hotter in the ongoing push to vaccinate against COVID-19 around the world.
Most would probably associate vaccines with the standard “jab” injection with a syringe. Over the past year and more, companies have touted ideas for other avenues. Inovio has a “smart” delivery device for a COVID-19 vaccine, while Intravacc is developing a nasal COVID-19 vaccine, plus there are many more in between.
Whether it’s standard delivery devices or the innovative ones various companies are trying to bring to the market, there are difficulties in creating the vessels for the potentially life-saving therapeutics they deliver.
Drug Delivery Business News spoke with Scott Thielman — chief technology officer at Product Creation Studio, a company that offers insights to deliver designs for a range of entities, including medical device companies — to learn about some of the biggest design challenges in the hot field of vaccine delivery.
“The vaccine delivery space was active before COVID-19, it’s no fluke that researchers were able to pivot quickly to produce candidate vaccines,” Thielman said. “We had ongoing work in the space and that interest continues.
“Much of the work lies with the microbiologists, chemists and drug formulators. The lipid nanoparticle (LNP) delivery mechanism utilized in the Moderna and Pfizer vaccines is an amazing story. But there are also exciting opportunities to move past the syringe administration and introduce novel devices for the delivery of next-generation vaccines. Oral administration would be the holy grail, bypassing patient fears of discomfort. But transdermal patches, intranasal and biolistic solutions are just a few options where device innovators will continue to have influence.”
Here are four major design challenges in creating vaccine delivery devices, according to Thielman:
1. Matching distribution and administration model to the technology (and vice versa)
ST: As with any drug delivery challenge, it’s important to match a workflow to the realities of the technology and also meet the needs of the users. For instance, the Pfizer-BioNTech vaccine requires specific cold-chain storage and two doses administered by intramuscular injection, requirements introduced by the LNP formulation. The chain of delivery from factory, storage, logistics, preparation to injection is driven by the need for mass vaccination at large clinics; a workflow that mitigates the challenges of storage and dose management. Additionally, the syringe-based delivery process is recognizable and well understood by healthcare clinicians.
A remote distribution model with intermittent dosing schedules and limited cold storage may drive the need for alternate distribution models and delivery technologies. There is room for medical device innovators to take up the challenges along the way. Designers need to zoom in to get the final step of administration and delivery — from package to patients’ cells — right. But they also need to zoom out to look at all the other aspects of production, distribution and disposal.
2. The hypodermic needle shouldn’t be the end of the discussion. We need more delivery technologies.
ST: The success of LNP formulations delivering mRNA vaccines is fantastic, but doesn’t mean we should close the book on other delivery mechanisms and administration techniques. Poor patient compliance due to fear of needles can be a major drag on mass vaccination efforts. Additionally, cross-contamination from reused syringes and unwanted disease transmission from inadvertent needle sticks are also significant downsides.
If DARPA is to be believed, there is a need for systems that can rapidly produce and deliver customized vaccines to fight local outbreaks and variants. In such a future, potential epidemics could be stopped in their tracks by rapid local responses, saving lives and economies. Platforms that provide flexible and adjustable genetic payloads with fewer storage and logistics constraints should be developed. Even if unit costs are significantly higher than the ubiquitous hypodermic needle, the benefits of rapid vaccine response worldwide would be a boon for the larger population.
3. The tissues targeted can make a difference.
ST: The entryway for most pathogens is through the skin and mucosa. Many infections start in the tissues of our nasal passages, lungs or sexual organs. While the intramuscular injections for COVID-19 have been shown to mount strong immune responses, a direct challenge to the mucosal tissues may be beneficial in vaccinations for other diseases such as HIV or for those with weakened immune systems. This is where innovators need to look beyond the ubiquitous vial-and-syringe combo for methods that deliver to alternate tissues.
Opportunities for administration via transdermal patch, intranasal spray and biolistics are all being pursued. Each has its own set of technical challenges and strategies to get past the barrier effects of the tissues. For instance, in our work with Orlance on their biolistic administration via gene gun, we’ve seen that there is a sweet spot for particle distribution and velocity to attain proper immunogenicity in dermal cells.
Alternate techniques to bypass the barrier characteristics of the skin and cell membranes include iontophoresis and electroporation. These involve the application of electrical potentials to the skin to assist in the introduction of vaccine molecules. You can begin to imagine the need for electrical engineers to join the bioengineers and mechanical engineers on these development efforts.
4. Get the user experience right.
ST: These alternative delivery opportunities are where it gets interesting for the medical device designers and engineers. Establishing a new administration method can have ripple effects throughout the workflow. It is up to device teams to capture the user needs and translate novel delivery technologies into understandable processes for the administrators.