MARKET INSIGHT

Needle-Free Nanopatch Smaller Than A FingernailCould This Be The Future Of Vaccines?

By Swathi Allada; Research Analyst, Medical Devices, Healthcare

Frost & Sullivan

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Vaccine Industry: A Sneak Preview

The vaccine industry has diverse profiles on the basis of three fundamental parameters—geography, technology, and disease type. Research and development (R&D) for novel vaccine technologies is moreprominent in developed economies, particularly in the US, due to a greater number of startup companiesand better financial support. New vaccine delivery technologies such as needle-free transdermal andintradermal systems (patches and degradable implants), edible vaccines, intranasal formulations, and pulmonary delivery methods will be used increasingly to improve access to vaccines and the overall efficacy of the vaccine delivery process. The development of thermostable vaccines with a long shelf lifeis an area of focus for many vaccine developers, especially for those marketing to nations where cold-chain storage is an issue. The following factors presented in exhibit 1 highlight the necessity forneedle-free (NF) delivery of vaccines.

Exhibit 1: Factors Influencing Growth in the Vaccine Industry, Global, 2014

Has the Time Finally Arrived for Needle-free Delivery of Vaccines?

Drug delivery technologies are becoming an essential part of the entire drug development process.Pharmaceutical companies are recognizing the significance of drug delivery technologies during the primary stages of drug development. Pharmaceutical companies are also investing billions of dollars inresearch to not only develop new molecules, but to understand the application of drug delivery technologies to these molecules. As a result, drug delivery technologies are being used to enhance pharmacodynamic and pharmacokinetic profiles, and also to increase patient comfort and compliance.A targeted delivery of drugs is also being used to help reduce the adverse side effects of many drugs.The needle-based approach is one of the oldest vaccine delivery techniques employed to achieve thedesired result; however, this procedure is associated with a lot of risk. It is prone to cause needle-stickinjuries to healthcare workers, can be painful, and at times also be associated with excruciating pain; itcan also be a potential agent for the spread of dangerous infections such as hepatitis and HIV.

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Immediate alternatives for NF vaccination are auto disable andsafety syringes, which are alreadyin use in LMICs. Prefilled syringesand reconstitution devices are

emerging alternatives.

Due to the conservative mindsetof manufacturers and the need forincentives and supporting clinicaldata, needle-based vaccines willdrive the industry until 2020.

Significant development costs ofsuitable vaccine formulations idealfor needle-free device technologymay delay their availability until

2020.

Delivery techniques that are incorporated in the early stages ofnew vaccine development are expected to have fast growth.

The global vaccine market wasonce valued at US $24 billion in2009 and is expected to reach

$47 billion by 2015, with emergingmarkets in South America andAsia expected to drive growth.Emergence of novel delivery

techniques will further bolster thissector.

Vaccine availability is expected toincrease in low and middle incomecountries (LMICs) from 2015 to2020, and become globalized by

2025.

Global health issues such as pan-demics (for example, H1N1 –Swine Flu) keep vaccines as a key

focus for manufacturers.

Vaccines are a major revenuesource for top-tier firms. Hence,companies are expanding their investments into vaccines and vaccine delivery technologies.

Central Conclusion

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Needle-free delivery: The drug is injected without the use of any needles and is delivered into the systemic circulatory system. The delivery of drugs through needle-free devices is gaining acceptancebecause of technology upgrades as well as availability of more formulations for needle-free deliveries.

One of the injectable delivery types—needle-free technology—offers a substitute to needles traditionally associated with injectable drug delivery. Currently, the size of needle-free delivery sectormakes up only a very small fraction of the total drug delivery market. Furthermore, the major factorsdriving the growth of NF deliveries are estimated to be an increased awareness of such products, patient acceptance, and the introduction of new devices.

Significant advancements have been made in needle-free injection technology, most of which have focused on addressing patient comfort levels and increasing the adoption of self-injectable therapies.Although the concept of needle-free drug delivery existed from the 1940s, it is only now that the concept is becoming implemented into reality. Needle-free technology can be applied by healthcareprofessionals for mass vaccinations and insulin delivery; it can also be made available for home use. Theearly forms of this technology were developed to address and eliminate multi-use systems, which increased the risk of disease transmission. Today, the goal of needle-free injection technology has changedfrom merely improving patient comfort, to increasing the adoption of the self-injection at home. Exhibit2 presents the factors influencing needle-free vaccine delivery technology.

Exhibit 2: Factors Driving Needle-Free Vaccine Delivery Technology, Global, 2014

Vaccine Delivery Market Is Ripe for Technological Innovation

Vaccine technologies have garnered increased interest from pharmaceutical companies and biotechcompanies in the last few years. Companies are not just working on newer vaccine types, but also onplatform technologies for delivery, production, and adjuvants. Live vaccines containing active viruses orbacteria are extremely hard to deliver in resource-deprived areas because they must be properly andcontinually refrigerated to keep them viable. The present mode of delivering vaccines into human tissuelocations using a needle and syringe has several limitations. Such limitations include administering vaccines to candidates who are needle phobic, accidental needle-stick injuries, and the improper andunsafe usage of needles that may lead to the rapid spread of infectious diseases.

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Needle-free or painless vaccines bring about enhanced

occupational safety for vaccinators and other healthproviders, and hence can beeasily accepted, with a possibility of becoming essential in the future.

Developing nations faceshort supply of vaccines,which require cold storageand extended refrigeration.Painless or NF vaccinesmay eliminate such issues,and thus ease and speed upvaccine supplies for the

needy.

The need for mass inoculationsof vaccines recommended bythe World Health Organization(WHO) is critical in developingcountries. Producing new andsafer vaccines could preventmillions of childhood deathscaused by the use of poorly

preserved vaccines.

Demand in Developed CountriesDemand in Developing Countries

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Furthermore, in most cases the needle does not place the vaccine doses in the body sites that areknown to elicit optimal immune response. Clinical data evolved over the years show that both theneedle and syringe place the vaccine dose in muscles wherein immunologically sensitive cells are presentat a much lower density. However, clinicians theorize that the thinner and viable upper skin layers containa greater population of antigen-presenting cells (APCs) than what is required for potential immune responses.

Forms of Needle-Free Vaccine Delivery

• Jet injectors

• Micro needles

• Transdermal patches

• Oral/nasal sprays and inhalers

• Vaccine implants

• Fast-dissolving tablets

Vaxxas Technology: A Classic Example of the Future of Needle-Free Delivery

The introduction of vaccine delivery using physical targeting methods, such as liquid jet injection, geneguns, and micro needles is used to facilitate vaccine delivery through the skin; however, the inability toconsistently and directly deliver vaccines to these cell types and the minimal cell damage caused duringadministration, renders such delivery methods incapable and inefficient. This inefficiency opens new opportunities for vaccine developers to create and commercialize a needle-free vaccine delivery systemthat is not fraught with challenges.

Enchasing on this potential market opportunity is a biotechnology start-up called Vaxxas, which had itshumble beginnings in the Australian Institute for Bioengineering and Nanotechnology (AIBN), a multi-disciplinary research institute that is an undertaking of the University of Queensland, Brisbane(Australia). A team of researchers under the able guidance of Professor Mark Kendall have found a delivery method to administer a dried live vaccine directly to the skin in a needle-free manner, whichwould also remain effective at room temperatures. This development can effectively address the issueof vaccine refrigeration or ‘cold-chain’ supply, which can be a challenge in remote areas of developingand underdeveloped nations with little or no infrastructure. Overall, it will eliminate needle-stick injuriesknown to cause around 1.3 million deaths per year, according to statistics from the World Health Organization. The needle-free vaccine delivery platform will also eliminate other issues such as the elimination of pain associated with needle pricks, risk of contamination through needle pricks withblood-borne illnesses like HIV [human-immunodeficiency virus], and also the cost of doing away withhypodermic needles.

The Nanopatch is a class of device for needle-free delivery of vaccines. It is a micro-needle patch, whichis comprised of very small and densely packed micro-projections with a defined geometry. It is capableof directly depositing vaccine to thousands of skin immune cells, while not causing potential damage tothe cell membrane in the process. The Nanopatch device is roughly about 5 millimeters (mm) × 5 mmin size and is made up of 1 square centimeter of solid silicon, dry-coated with antigen, adjuvant, and/orDNA payloads that could be used for a range of indications. The surface of the patch has around 20,000micro-projections on its surface, invisible to the naked eye and in an ultra-high density array. Early stagetests conducted on mouse models, have shown that the Nanopatch delivered flu vaccine is effectivewith just 1/150th of the dose as compared to the traditional syringe.

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More importantly, the use of the Nanopatch eliminates the requirement of adjuvants to boost the immunogenicity of vaccines, which unlike traditional inoculation methods would mean a more efficientdelivery of vaccine to produce the required immunological response and better patient compliance.Furthermore, being smaller than a postage stamp, the Nanopatch offers a host of benefits and alsoachieves precise, controlled, and consistent skin penetration along with rapid dissolution and diffusionof the vaccine. The Nanopatch also eliminates the need for refrigeration as the vaccine is formulated indry form and is thermostable; this makes transportation and storage significantly cheaper as comparedto traditional needles. In addition, the Nanopatch is painless and could be used for patients who areneedle phobic; it also improves patient convenience and reduces complications.

This device elicits minimal skin response through its usage and does not cause bleeding, inflammation,or bruises; it accommodates the accurate delivery of the drug into the underlying tissue wherein thedrug dissolves and is present for action in the blood stream. Although the technique has only beentested on rodents, the results have been very promising. Researchers have been able to identify for thefirst time, a group of cells in the skin capable of detecting the type of vaccine being injected and puttingthe body’s immune system on alert. Using these specialized cells, room-temperature vaccines can beproduced to create the same level of immune response as that of traditional liquid medicine stored ina freezer. However, with the animal model testing complete with successful results, scientists will nowhave to look at scaling up their production and seeking FDA approval once the clinical trials on humanshave been completed.

Conclusion

Several other ways of drug and vaccine delivery would include PharmaJet Stratis Needle-Free InjectionSystem, SeroJet, Mhi-500, cool.click, Recojet, Intraject technology, Biovalve Mini-Ject, Antares Medi-JectorVISION, Needle-free, auto and pen injectors, MadaJet XL Needle Free Injector, BiojectZetaJet, INJEX30 Injex needle-free injections for infiltration anesthesia, and others. Over the next five to ten years itis estimated that a number of vaccine products will migrate to skin delivery moving away from needlesand syringes. The vaccine industry will be fundamentally changed with these newer technologies suchas needle-free injections, fast-dissolving tablets, patches, and inhalers, which will disrupt the vaccine industry. As more companies realize the potential benefits of needle-free drug delivery, this technologywill gain its traction, both among patients and physicians, ultimately enhancing the adoption of needle-free injectable drugs or vaccine deliveries.

Swathi Allada is the Research Analyst for the Medical Devices Healthcare business unit at Frost & Sullivan.

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