Spray for Success

Vaccines have a huge impact on global health. According to the World Health Organization, measles vaccinations alone have saved over 17 million lives since 2000 (1), and some diseases, such as polio and small pox, have almost been eradicated from many countries because of vaccination. Today, companies are developing vaccines for emerging healthcare threats, including Zika and Ebola, as well as bioterrorism threats, such as anthrax.

Vaccine development, however, is a time- and cost-intensive process. Determining new, viable viral targets involves consideration of a range of factors, including the frequency of disease, virulence, mortality, access to healthcare administrators, location, and socioeconomic impacts. And many vaccines have to be stockpiled (particularly with bioterrorism), which creates additional challenges.

Most vaccines are delivered by the parenteral route, using a needle and syringe. Such vaccines are often delivered in liquid form, which typically requires cold chain storage, or are lyophilized into a powder that is reconstituted upon delivery. Injections are a well-established form of drug delivery (although not always well-accepted by patients) and are easy to administer for specialized healthcare professionals. But is this the best delivery method for a vaccine? In developing countries, for example, where vaccines have the potential to save millions of lives, there aren’t always enough professionals to administer the vaccine – and training in remote locations can also be difficult. Additionally, delivery to Zone 4 locations may require temperature excursions or long term storage at 35 °C or beyond for effective delivery to impacted populations.

In terms of manufacturing, the current processes for liquid and lyophilized formulations are still very much based on batch production – not the most flexible processing technology in an epidemic. And the range of excipients and adjuvants suitable for lyophilization can be limited when it comes to high glass transition polymers or aluminum adjuvants, which can be enabling for high-temperature stabilization or efficacy. Furthermore, certain antigens can be damaged during the ice nucleation and drying step despite the low temperature of lyophilization processing.

There is a growing opportunity in vaccine development to explore the potential of intranasal or inhalation vaccines, particularly as these vaccines can take advantage of the manufacturing benefits offered by spray drying. For parenteral vaccines, spray drying is limited because of a lack of aseptic spray drying infrastructure globally, but dry powders for intranasal/inhalation delivery do not require aseptic processing. Spray drying consists of a liquid feedstock being prepared and fed continuously to an atomizer inside a spray dry chamber. The spray plume is contacted by drying gas, converted to a dry powder and continuously collected. Powder aliquots are also removed during the process. Cycle times are short, and if more material is needed, the process is simply run longer. The continuous nature allows manufacturing volumes to be adjusted rapidly, which is useful given the uncertainties associated with supply chain predictions. The ability to ramp up production quickly in case of an epidemic is also a key advantage.

Spray drying can be used for a variety of purposes in the pharma industry. But the key point for vaccine developers is its ability to produce free-flowing particles in a range of particle sizes, particularly those suitable for inhalation (2-5µm) or intranasal (>30µm) delivery. In targeted vaccine delivery to the nose or lung – the point of entry for many viruses – there are notable opinions that the method may produce an enhanced antigen response (2).  Moreover, such vaccine administration can be handled through passive devices that are controlled by inspiration, which requires less healthcare professional training and observation than 
needle injections.

Another benefit of spray drying is that it can process a broad range of excipients with a range of physical-chemical properties, including high molecular weight and high glass transition temperature excipients for improved shelf-life. In collaboration with vaccine development companies, my colleagues have demonstrated stability of a vaccine for up to six months at 50°C (3). Spray drying also allows for the incorporation of adjuvants, which may have compatibility challenges with lyophilization.

Spray drying isn’t suitable for all vaccines, but it’s a good technique for the toolbox – especially when traditional vaccine delivery routes aren’t working out. The development and commercialization of a vaccine can require years – or even decades – but some epidemics take shape in only a few months. Vaccine development will continue to be a unique challenge, so the more tools we have at our disposal the better.