Many biologics rely on cold-chain storage and injection by trained professionals, which ultimately adds further costs and complexities to these already expensive drugs. In my view, the industry should be more open to considering microneedle array patches (MAPs). Unlike the more familiar transdermal patch, their mechanism of action is fundamentally different. Transdermal patches work by passive diffusion, delivering small molecule drugs slowly through the skin's outermost barrier, the stratum corneum. MAPs, in contrast, use microscopic needles to physically and painlessly bypass this barrier, actively delivering large molecule biologics directly into the underlying skin layers. This is the difference between relying on a substance to slowly seep through a barrier wall versus creating precise microscopic gateways to deliver it directly past that wall.
The dermis is rich in antigen-presenting cells, making it an ideal target for immunogenic products. By accessing this layer, microneedle patches can support dose sparing and may reduce the need for adjuvants. These benefits may be particularly compelling for vaccines, glucagon-like peptide-1 receptor agonists (GLP-1s), and chronic therapies that require regular dosing.
Know your needles
The two primary MAP platforms in development are solid-coated microneedles and hollow microneedles.
Solid-coated microneedles deliver a dry formulation directly into the skin. These systems could be particularly well-suited for heat- and moisture-sensitive biologics. Because the formulation is applied as a dry coating, these patches avoid cold-chain requirements and offer long-term room temperature stability. The manufacturing process allows precise control over dose loading by adjusting the formulation properties and coating process parameters. These microneedles are also compatible with a broad range of actives, including proteins, peptides and vaccines. Provided the formulation can be stabilized in solid form, this platform is the leading candidate for near-term regulatory approval and commercial deployment.
Hollow microneedles are designed to deliver liquid formulations through micro-scale channels in the needle itself. These systems can accommodate molecules that may not be amenable to solid-state formats, such as those requiring specific excipients or aqueous stability. Hollow microneedles can also support higher dose volumes and offer greater formulation flexibility for certain biologic programs. This flexibility stems from their ability to:
deliver a liquid formulation that allows for the inclusion of stabilizing excipients that are only active in an aqueous environment
accommodate molecules that are too sensitive to undergo the drying process required for solid-coated needles
enable the delivery of larger total drug volumes than can be applied as a thin coating.
However, they also introduce greater challenges in terms of formulation stability and device engineering.
For both solid-coated and hollow systems, the microneedle patch can be customized by adjusting the number of needles, the spacing, the geometry and the length of the microneedles to suit a given drug or therapeutic goal. This tunability is a key engineering advantage. For example, needle length determines the precise depth of delivery, allowing developers to target the dermis for vaccines to maximize immune response. The number and density of needles directly impact the total dose capacity and the speed of delivery. Finally, needle geometry is optimized to ensure reliable skin penetration and efficient drug release from the needle surface into the tissue.
Co-development cooperation
Developing a successful MAP for biologics is a complex process that requires true co-development, where the formulation and device evolve together. This principle extends from initial design to scalable, high-quality manufacturing. Biologic molecules are inherently sensitive, so the entire manufacturing process, including array molding, drug coating, and applicator assembly, must be designed around the needs of the drug. Choices around excipients and drug concentration directly inform applicator design and material selection. To ensure consistency and quality at high volumes, this integrated process relies on essential technologies like machine vision, robotics, and in-line inspection.
The core formulation task is to transfer a biologic from a stable liquid vial to a microscopic needle tip and ensure it remains potent through storage and administration. For solid-coated MAPs, the key challenge is protecting the molecule’s delicate structure during the drying and coating process. This requires a deep understanding of protein chemistry and the selection of specific stabilizing excipients that form a protective scaffold around the molecule.
Success here also hinges on the co-development principle. For example, if initial tests show a protein is losing activity during coating, the formulation team must work closely with device engineers. Together, they iteratively adjust both the chemical stabilizers in the formula and physical manufacturing parameters such as drying temperature and humidity. Advanced analytical techniques are then essential to confirm that the biologic on the final patch is structurally identical to the original drug.
Paving the path to market
While the regulatory path is still being paved, the industry is moving forward by focusing on these fundamental challenges. No biologic MAP has yet received regulatory approval, but clinical programs are progressing. At least one microneedle technology has reached phase III, offering valuable insights for the entire field. Successfully advancing to this stage provides a critical proof-of-concept for the platform, demonstrating the ability to manufacture MAPs reproducibly at a large GMP-compliant scale. It also establishes a viable pathway for long-term room-temperature stability of a biologic on a patch. From a regulatory perspective, this progress helps create a roadmap for future submissions by clarifying agency expectations around clinical endpoints, safety data, and the chemistry, manufacturing and controls (CMC) documentation required for a novel combination product.
As microneedle technologies mature, some developers are forming partnerships to support the transition to commercial-scale manufacturing. This includes companies working on dissolvable or alternative microneedle designs that require GMP-compliant, high-volume production. As clinical programs advance, collaboration around process design tooling and analytical validation may play a critical role in bringing these technologies to market.
MAPs represent a potential solution to some of the most persistent challenges in biologic drug delivery. As the regulatory path becomes clearer and manufacturing capabilities expand, the opportunity for MAPs will only grow. Biopharma innovators looking to differentiate their products and serve patients more effectively would be wise to explore the platform early. The skin may be a thin barrier, but it holds immense potential for the future of medicine.
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