Following our previous series interpreting FDA's definition, regulatory guidelines and safety risks for microneedle products, many industry practitioners reached out to share observations that FDA's regulatory framework for microneedles has exerted tangible influence over domestic product review in China. Most domestic Class II metal microneedle devices are registered under rolling needles (20‑03‑05), a sub‑category of traditional Chinese medical instruments in the Classification Catalogue of Medical Devices. Some products are registered under the name "microneedle transdermal patch", also following the regulatory pathway for traditional Chinese medical instruments.

Several readers mentioned single‑crystal‑silicon microneedles developed overseas. One product manufactured by NanoPass (Israel) obtained China import Class III medical device approval in 2019, representing one of the few commercially available single‑crystal‑silicon microneedle products worldwide. This device was cleared by the FDA in 2009 as a Class II medical device under the trade name MicronJet 600, formally designated as a single‑lumen intradermal needle. Its physical form differs substantially from cosmetic microneedles familiar to the public; functionally it resembles a short‑needle intradermal injector. During the FDA 510(k) clearance, traditional intradermal syringes from Terumo and BD were selected as predicate devices to demonstrate substantial equivalence.

In clinical‑research circles, the review article Microneedle‑enabled therapeutics delivery and biosensing in clinical trials (DOI:10.1016/j.joonrel.2023.07.023) is the first comprehensive review dedicated exclusively to microneedle clinical trials. Drawing core insights from this publication, this article systematically outlines technical categories, clinical scenarios, key trial findings and industry trends of microneedles investigated in clinical research.

Microneedle‑Enabled Therapeutics Delivery and Biosensing in Clinical Trials

Abstract

Microneedles (MNs) are micron‑scale protrusion arrays integrated onto diverse device platforms. They are widely studied for therapeutic delivery as well as in‑vivo and ex‑vivo biosensing. Benefiting from prominent merits including minimally invasive pain‑free administration, potential for self‑application, and compatibility with diverse therapeutic payloads, microneedles hold great promise for both local and systemic drug delivery. This review summarizes global microneedle clinical trials initiated since 2007. Tested microneedle devices are grouped into five categories: hollow microneedles, microneedle patches, radio‑frequency microneedles, microneedle rollers and other special‑purpose microneedles. Systematic analysis is performed covering microneedle configurations, trial timelines and geographical distribution.

Keywords: microneedles; clinical trials; drug delivery; diagnostic technology; innovative therapeutics; polymeric materials

Introduction

Microneedles are micron‑scale protrusions typically several hundred micrometers long. They can be mounted on rollers, pen‑type therapeutic handles, patch substrates or conventional syringes. Their core mechanism relies on generating numerous transient microchannels across the skin barrier to facilitate penetration of therapeutic agents into viable skin layers; certain designs can achieve direct drug entry into systemic circulation. Characterized by low pain profiles, easy operation, home‑use feasibility and favorable safety profiles, multiple microneedle devices have completed clinical testing and achieved commercialization.

This study searched the public ClinicalTrials.gov database and identified 127 clinical trials directly relevant to microneedle technology. Tested devices were classified into five groups: hollow microneedles, microneedle patches, radio‑frequency microneedles, microneedle rollers and miscellaneous microneedles. Hollow microneedles are further subdivided into micro‑injection and non‑injection biosensing types; microneedle‑based patches cover dissolvable patches, coated patches and bare patches intended solely for skin pre‑treatment.

Categories of Microneedles Deployed in Clinical Trials

2.1 Hollow Microneedles

Hollow microneedles represent the most frequently adopted modality in clinical trials, accounting for 33.6 % of all included studies. They are divided into micro‑injection and non‑injection biosensing variants according to intended use.

Micro‑injection type: delivers diverse therapeutic agents intradermally into target tissue sites;

Non‑injection type: primarily for interstitial‑fluid sampling to enable minimally‑invasive biosensing of biomarkers.

Representative device: MicronJet 600 developed by NanoPass Technologies (Israel). It is a sterile single‑use instrument equipped with three 600 μm single‑crystal‑silicon hollow microneedles, compatible with administration of all drugs approved for intradermal injection.

Key clinical applications

Vaccine delivery: A trial (NCT01304563) conducted by the University of Hong Kong administered trivalent influenza vaccine via MicronJet 600, confirming favorable safety and immunogenicity.

Insulin delivery: Research from Emory University Diabetes Center demonstrated that hollow microneedles can achieve effective and pain‑free intradermal insulin delivery for children and adolescents with type 1 diabetes mellitus.

Ocular therapy: SCS Microinjector® developed by Clearside Biomedical employs hollow microneedles to inject triamcinolone acetonide suspension into the suprachoroidal space for treatment of posterior‑segment inflammatory diseases such as uveitis.

2.2 Microneedle Patches

• 2.2.1 Dissolvable microneedle patches

Fabricated from hydrophilic polymers. Upon skin penetration, needle tips dissolve locally and release loaded drugs into target tissue.

An influenza‑vaccine patch trial (NCT02438423) led by Emory University utilized a patch carrying 100 water‑soluble polymer microneedles of 650 μm length.

SkinJet conducted a clinical trial (NCT03646188) investigating doxorubicin‑loaded dissolvable microneedle patches for basal‑cell carcinoma therapy.

• 2.2.2 Coated microneedle patches

Non‑dissolvable substrates with therapeutic agents coated onto microneedle tips.

Qtrypta™ (M207), a microneedle patch for acute migraine treatment, contains 1987 titanium microneedles each 340 μm long.

Abaloparatide‑coated microneedle patches are explored for transdermal therapy of postmenopausal osteoporosis.

• 2.2.3 Bare microneedle patches

Carry no payload themselves. They are designed for skin pre‑treatment only, generating microchannels to enhance skin permeability of subsequent topical formulations. The 3M Microchannel Skin System (MSS) exhibited excellent safety and subject tolerability across multiple clinical studies.

2.3 Radio‑Frequency (RF) Microneedles

RF energy (3 kHz‑300 GHz) is delivered into the dermis through microneedle electrodes to induce dermal coagulation and trigger collagen remodeling, mainly applied in aesthetic rejuvenation and scar management.

The Endymed PRO Intensif handpiece has obtained FDA clearance for facial aesthetic indications.

Lutronic Infini is equipped with a 49‑pin interchangeable cartridge with insulated gold‑plated microneedles delivering focused radio‑frequency energy. Interchangeable cartridges of different sizes adapt to lesions of varying dimensions.

2.4 Microneedle Rollers

Hand‑held roller‑type devices with stainless‑steel microneedles mounted on the roller drum, suitable for treating large skin areas. The MTS Roller™ system by Clinical Resolution Laboratory provides multiple needle‑length specifications ranging from 0.2 mm to 2.0 mm and has been widely used in skin‑repair‑focused clinical trials.

Trends Observed in Microneedle Clinical Trials

3.1 Statistical profiles of clinical trials

• Geographical distribution: The United States hosted the largest number of microneedle clinical trials (57 studies), followed by Europe and East Asia.
• Timeline evolution: The world's first microneedle clinical trial was initiated in 2007; the annual number of trials peaked in 2018.
• Device parameters: Average microneedle length varies substantially across modalities; RF microneedles have the longest average length at approximately 1560 μm.

3.2 Therapeutic application directions

• Drug delivery: small‑molecule chemicals, peptide and protein therapeutics, cell‑based preparations and others;
• Vaccination: intradermal delivery research targeting influenza, COVID‑19, measles, polio and other vaccines;
• Biosensing: minimally‑invasive real‑time monitoring of in‑vivo analytes such as penicillin, lactose and levodopa.

Conclusion

Thanks to its minimally‑invasive nature and user‑friendly operation, microneedle technology demonstrates broad prospects in therapeutic delivery, vaccination and minimally‑invasive biosensing. Technical bottlenecks still remain. Future research priorities include improvement of drug‑loading capacity and optimization of wearability and real‑time analytical performance for wearable microneedle‑based sensors. Commercially FDA‑cleared microneedle products to date include MicronJet 600, SkinPen® Precision System and the MTS Roller™ series.