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The unprecedented rapid development and distribution of Covid-19 vaccines worldwide has brought new visibility to how vaccines are produced, packaged, and distributed. The world learned about the vaccine cold chain, for example, as people monitored rollout plans for Covid-19 vaccines and the added logistics that came with keeping them cold.

Since then, many people have asked this question: Why don’t we have more thermostable, easy-to-administer vaccines?


Though a number of pharmaceutical companies are working on advancing these kinds of products, the science is complex and decisions often involve evaluating cascading tradeoffs.

A balancing act between stability and simplicity

Vaccines that don’t need to be kept frozen or refrigerated would be ideal. But because they are biological products, there are no easy methods to make them more thermostable, meaning able to withstand exposure to heat. The more thermostable a vaccine, the less likely it is to lose potency at warmer temperatures.

Each vaccine component has its own inherent stability, and sometimes making one component more stable will destabilize another.


Drying a vaccine is sometimes used to improve its stability. But a dry vaccine must usually be mixed with a liquid before administration. This requires an extra syringe, and reconstitution adds an extra vaccine-handling step, increasing the possibility for contamination and errors.

Adding new ingredients can make a vaccine more thermostable, but this requires significant safety testing to ensure the new ingredients are safe for human use.

Regardless of whether new or existing stabilization methods are used, the testing required to validate higher-temperature storage conditions can slow down the availability of a vaccine. Sometimes manufacturers need to prioritize speed, as was the case during the Covid-19 pandemic. Such testing must occur in real time at the target storage temperature and over the entire shelf life of the product, which is generally two to three years for normal vaccines (though often shorter for vaccines released for emergency use or for seasonal vaccines) and requires approval by the relevant regulatory authority.

This helps explain why the Pfizer/BioNTech team initially released its mRNA Covid-19 vaccine with stringent temperature storage conditions, and then eased the conditions as more data were generated on the vaccine’s potency at higher storage temperatures.

Single-dose syringes versus multi-dose vials

Like thermostable formulas, single-dose, ready-to-use vaccines would offer advantages in nearly every possible situation. These products are not only faster and more efficient to administer, they are often safer as well, as the precise dose is premeasured and minimal handling is required.

The downside is that single-dose products are almost always more expensive. The cost of the container is applied to just one dose of vaccine, rather than spread over the five, 10, or 20 doses a multi-dose vial can hold. Single-dose products also typically require more cold-chain storage space per dose, raising transport and storage costs.

These costs can be somewhat offset by less vaccine waste with single-dose products, another important factor to consider when looking at packaging options. As of now, Covid-19 vaccine wastage has reportedly been low in the U.S. However, once mass immunization slows down and fewer people are vaccinated each day, waste due to multi-dose vials, such as the Pfizer/BioNTech vaccine, will likely increase as opened vials must be discarded if they are not used within six hours.

The pandemic’s impact on vaccine innovation

The world certainly needs more research, and more investment, to harness new technology and improve vaccines. We wouldn’t have mRNA vaccines against Covid-19 were it not for previous investments in other mRNA products.

Despite the global devastation the pandemic has caused, it has created positive momentum around scientific innovation and renewed appreciation for vaccines. This new energy is good news, and I’m hopeful it could accelerate efforts for better vaccine solutions.

For example, the Vaccine Innovation Prioritisation Strategy initiative, which my organization, PATH, is part of, is working to make vaccine innovations more accessible for low- and middle-income countries (though these innovations also have applicability to higher-income countries). Part of this work involves advancing microarray patches, which are applied to the skin like a bandage, to deliver vaccines. Microarray patches use dried vaccine, making them easier to store and transport at ambient temperatures for at least part of their shelf life.

Ideally, microarray patches will provide the benefits of a single-dose, thermostable dried product without the negative tradeoffs. Much work remains to develop and assess this approach, but it is one example of a transformative innovation that could revolutionize the future of immunization.

Debra Kristensen is the director of vaccine technology strategy and policy, within the medical devices and health technologies program at PATH, a nonprofit global health organization.

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