Easier vac­ci­na­tion thanks to microneedle patches

Microneedle patches have the poten­tial to sig­nif­i­cantly sim­plify vac­ci­na­tion cam­paigns. The Aus­tralian start-up VAXXAS and Harro Höfliger have taken the field with enthu­siasm and exper­tise in search of an afford­able, scal­able solution.

The young woman removes a round con­tainer from the pack­aging and places it care­fully on her child’s upper arm. With her thumb, she releases a boost that launches a tiny patch onto the sur­face of the skin. The patch is equipped with thou­sands of nee­dles that are coated with the nec­es­sary vaccine.

According to infor­ma­tion from the World Health Orga­ni­za­tion (WHO), as well as other NGOs, non-­profits and pri­vate groups, con­ven­tional vac­ci­na­tion cam­paigns will be sup­ple­mented with such microneedle array patches (MAPs) in the future. They herald the end of syringes that can only be applied by qual­i­fied spe­cial­ists. The end of liquid vac­cines that require a con­tin­uous cooling chain. Espe­cially in low and middle income coun­tries, simple vac­ci­na­tion using microneedle patch is a promising alter­na­tive. The Aus­tralian start-up VAXXAS and Harro Höfliger have been working to imple­ment this tech­nology, with a view to the cost aspect as well as the upscaling process.

Many paths lead to the summit

Micronee­dles are attrac­tive for a number of mar­kets: vac­ci­na­tion cam­paigns in devel­oping coun­tries are one area, but another is for more upmarket prod­ucts such as migraine reme­dies. A diverse array of microneedle tech­nology devel­op­ment teams and researchers are fol­lowing dif­ferent strate­gies in terms of choice of mate­rial as well as the appli­ca­tion and delivery of the active substance.

Coated micronee­dles

The micronee­dles made of metal or plastic are coated with a liquid active sub­stance that dis­solves later in the skin. To this end, they are either immersed in an active ingre­dient solu­tion or imprinted and then dried.

Self-absorbing micronee­dles

The micronee­dles are formed from a suit­able polymer (PVP, PVOH) and the active ingre­dient to be admin­is­tered. When man­u­fac­tured with a pres­sure process, the nee­dles are already a com­po­nent of the sup­port patch, while in other man­u­fac­turing processes they are glued on in a later step. The nee­dles dis­solve com­pletely once they pen­e­trate the skin, giving off their active ingredient.

Hollow micronee­dles

Hollow micronee­dles (HM) are intended for the admin­is­tra­tion of ­higher doses of active sub­stances. Chan­nels are drilled into the stain­less steel nee­dles, for example with a laser. The active ingre­dient solu­tion stored in a reser­voir on the car­rier film passes through the hollow nee­dles into the skin.

An eye for the possible

The tech­nology com­pany, which came into being as an off­shoot of the Aus­tralian Insti­tute of Bio­engi­neering & Nan­otech­nology of the Uni­ver­sity of Queens­land, con­cen­trates on novel vac­cine delivery tech­nolo­gies. The Nanopatch™ that VAXXAS has devel­oped is mainly designed for well-known vaccines.

Right from the early stages, the inter­dis­ci­pli­nary research team wanted to make sure that the ideas and processes from their lab­o­ra­tory studies would be reli­ably trans­lated into high-volume series pro­duc­tion. Mike Junger, Head of Med­ical Device and Process Engi­neering at VAXXAS, explains: “That’s why we got in touch with Harro Höfliger, and we are really pleased that the experts were quickly ready to assist us in devel­op­ment of the device with a view to sub­se­quent upscaling of the pro­duc­tion process.”

For Stefan Bernsau, Director of Needle Tech­nology at Harro Höfliger, the col­lab­o­ra­tion has been a clear win-win solution:A big part of our phi­los­ophy as a com­pany is guiding our cus­tomers from the lab­o­ra­tory into pro­duc­tion. That is why we often lend our exper­tise and resources to start-ups.” The project with VAXXAS links sev­eral of Harro Höfliger’s tech­nology plat­forms: aseptic assembly, automa­tion, and filling and dosing technology.

Bernsau: “It is a highly demanding process devel­op­ment, since between the coating and sealing you have to include the drying process of the dif­ferent active sub­stances under aseptic conditions.”

“It is a great tech­nology which is going to sim­plify vac­ci­na­tion.“ Stefan Bernsau, Director Needle Tech­nology at Harro Höfliger

Harro Höfliger has been engaged in the topic of microneedle patches for quite some time and Stefan Bernsau reg­u­larly par­tic­i­pates in con­fer­ences on this topic, including those of the WHO. He has built up a world­wide net­work that is working together to find prac­tical solu­tions for this tech­nology of the future.

Bernsau: “It is a great tech­nology with many chal­lenges and it is going to sim­plify vac­ci­na­tion con­sid­er­ably. The con­sis­tent approach to new processes and devel­op­ments together with ­VAXXAS, taking into account aseptic require­ments, cor­re­sponds exactly to Harro ­Höfliger’s philosophy.”

Tar­geted protection

Recent studies have shown that intra­dermal vac­ci­na­tion may have advan­tages over the pre­vi­ously cus­tomary admin­is­tra­tion of vac­cines into the sub­cutis or muscle. In con­trast to the sub­cutis and the muscle, where only a few defense cells of the immune system are located, defense cells of the den­dritic type are very common in the upper skin layer (dermis). These cells are respon­sible for ini­ti­ating the immune defense.

If the vac­cine active ingre­dient is admin­is­tered here, it ensures a stronger immune response and thus improved vac­cine pro­tec­tion. Microneedle patches also follow this approach. VAXXAS aims to achieve a more tar­geted admin­is­tra­tion of lower vac­cine doses in order to opti­mize their effectiveness.

Going skin deep

The Nanopatch™ from VAXXAS con­sists of a one-cen­timeter polymer square that con­tains sev­eral thou­sand micro pro­jec­tions, each just 0.25 mil­lime­ters high. These are coated with the vac­cine, which they inject directly into the sub­cu­ta­neous layers that are rich in immune cells. Thanks to the appli­cator, the Nanopatch™ can be applied quite easily, even by non-spe­cial­ists. The spe­cial design ensures that the vac­cine is con­sis­tently admin­is­tered, regard­less of age- and sex-related dif­fer­ences in skin struc­ture. Cooling the active sub­stance is not ­nec­es­sary, thanks to its solid phys­ical form.

“In future, nan­otech­nology will be the norm in sterile man­u­fac­turing.“ Mike Junger, Head of Med­ical Device and Process Engi­neering bei VAXXAS

“We have a ‘do it your­self’ cor­po­rate phi­los­ophy,” says Mike Junger. “I trust my employees’ abil­i­ties. They under­stand our product and they have the tools to do their job better than anyone else. ­We there­fore didn’t expect Harro Höfliger to solve all the prob­lems on their own. It was impor­tant for us to develop our ideas fur­ther by col­lab­o­rating with the machine building spe­cial­ists with all of their expe­ri­ence, which guar­an­teed prac­tical imple­men­ta­tion in the end.”

The hard facts

When devel­oping an upscalable
process for future series pro­duc­tion of the device, VAXXAS relies on the know-how of Harro Höfliger’s mechan­ical engi­neering specialists.

VAXXAS has now had their vac­cine ­coating process for the micronee­dles patented. The next chal­lenging task is to build a system on which the VAXXAS tech­nology can be auto­mat­i­cally and cost-effec­tively real­ized in large-scale pro­duc­tion. The largest chal­lenges are the ­highly pre­cise coating of the nee­dles with vac­cine, the sub­se­quent drying process and the sealing, all of which have to be car­ried out under aseptic con­di­tions. According to Bernsau, “in order to apply a large enough amount of active sub­stance, the nee­dles need to be coated mul­tiple times. To do this, we need a non-con­tact, highly pre­cise, auto­mated and camera-mon­i­tored dosing system that works in a sterile environment.”

This work is in progress. The ­VAXXAS brain trust and the spe­cial­ists at Harro Höfliger are in con­stant con­tact to resolve issues as they arise. Junger explains: “We believe that in the future, micro- and nan­otech­nology will be the norm in sterile man­u­fac­ture. But we still need to con­vince the reg­u­la­tory author­i­ties and the industry so that guide­lines and stan­dards can be adapted. Our Nanopatch™ is an impor­tant con­tri­bu­tion to the process.”


VAXXAS is a tech­nology start-up founded in 2011 based on research at the Aus­tralian Insti­tute of Bio­engi­neering & Nan­otech­nology at the Uni­ver­sity of Queens­land and is engaged in improving the per­for­mance of vac­cines by delivery into the skin by the Nanopatch.

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Photos: Group, Janine Kyofsky, Harro Höfliger