Fremont, Calif.–based Zosano Pharma created a ZP Patch, which uses an applicator device to push the microneedles into the skin, while St. Paul, Minn.–based 3M is developing a Microstructured Transdermal System. Neither is licensed for vaccine delivery.
In 2011, the Soluvia prefilled microinjection system, manufactured by BD Medical of Franklin Lakes, N.J., was approved in the United States for administering a new Fluzone Intradermal vaccine (Sanofi Pasteur) in adults aged 18-64 years. In 2009, it was licensed in the European Union for administration of the same company’s Intanzaand IDfluinfluenza vaccines. The device features a 30-gauge minineedle staked onto a prefilled glass syringe. "The outer diameter of the needle is 0.305 mm, and it projects 1.5 mm outside of the syringe," Dr. Weniger said. "Sanofi Pasteur purchased exclusive worldwide rights to the technology for all commercially sold vaccines."
Another hollow microneedle system under investigation is the MicronJet, manufactured by NanoPass Technologies of Nes Ziona, Israel. This device features an array of 250-mcg-tall microneedles on a Luer-slip syringe adapter. One human trial found that intradermal delivery of 3 or 6 mcg of influenza hemagglutinin yielded similar hemaglutination inhibition antibody titers as intramuscular delivery of 15 mcg (Vaccine 2009;27:454-9).
• Dissolving microneedles. In this approach pioneered at the Georgia Institute of Technology, the antigen/drug is formulated within a solid dissolvable matrix on a patch using biocompatible and nontoxic components, such as carboxymethylcellulose. "Upon dissolution into the body, all the sharps are gone, so there is less of an issue of expensive sharps waste and the cost of disposing of them," Dr. Weniger said. "Other research groups are pursuing this approach, as well."
Other cutaneous vaccine delivery methods are "a bit more futuristic," he said, including kinetic deposition of propelled microparticles, thermoporation, laser light ablation, iontophoresis, chemical enhancers, and sound waves.
Although some of the novel cutaneous delivery systems he discussed might use off-the-shelf liquid products, "others may require extensive, expensive reformulation efforts," Dr. Weniger cautioned.
"Also, regulatory criteria to license annual influenza vaccines may not be biologically relevant for novel nonparenteral routes/antigens. This means that phase III field-efficacy trials may be required to tease out and validate new immunologic correlates of protection."
Even so, the minimally invasive nature of delivering antigen onto or into the skin "means it’s easier to monitor and treat local adverse reactions," he said. "You can see them. You can put topical steroids or other treatments on them to reduce them, and you can hypothesize fewer unanticipated serious adverse events than we’ve seen with other routes."
Another advantage of the cutaneous route is that it’s less dependent on patient cooperation than other novel routes.
"Think of a squirming, uncooperative child unable to swallow capsules, retain oral doses, activate inhalers, or quietly breathe a vaccine mist for an extended time." Dr. Weniger offered. He added that the cutaneous route provides "a relatively sure and certain delivery, compared with oral and respiratory administration."
Dr. Weniger disclosed that he holds stock in Pfizer.