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ISO 28823:2018 — Medical devices — Needle-free jet injectors
Requirements and test methods for needle-free liquid jet injection medical devices
ISO 28823:2018 specifies the requirements and test methods for needle-free jet injectors — devices that deliver liquid medication through the skin using a high-velocity jet without the use of a hypodermic needle. These devices eliminate needlestick injury risk and reduce sharps waste, addressing critical safety and environmental concerns in vaccination programmes and chronic disease management.
1. Operating Principles and Classification of Needle-Free Injectors
ISO 28823 defines a needle-free jet injector as a device that creates a fine, high-pressure stream of liquid medication — typically 100–300 μm in diameter — propelled at velocities of 100–250 m/s to penetrate the skin and deliver the drug into the intradermal, subcutaneous, or intramuscular tissue layer. The injection depth is determined by the jet velocity, orifice diameter, and the mechanical properties of the target tissue. Unlike needle-based systems where the needle physically creates a channel, needle-free injectors rely entirely on fluid dynamics to breach the stratum corneum and disperse the drug within the tissue.
The standard classifies needle-free injectors by power source: spring-driven (mechanical energy stored in a compressed spring, typically 50–200 N), gas-powered (compressed CO₂ or nitrogen cartridge delivering pressure of 15–30 bar), and Lorentz-force-driven (electromagnetic coil actuator). Spring-driven devices are the most common in clinical practice due to their simplicity, reliability, and lack of consumable power sources. Gas-powered devices offer more consistent pressure profiles across multiple injections from a single cartridge. Lorentz-force devices provide the most precise control of jet velocity profile but require a battery and electronic control circuitry. Each power source type imposes specific design requirements for pressure regulation, firing reliability, and user safety.
| Power Source | Typical Pressure Range | Advantages | Design Challenges |
|---|---|---|---|
| Spring-driven (mechanical) | 50–200 N spring force → 15–30 MPa | Simple, reliable, no consumables | Force variation over spring displacement, temperature sensitivity |
| Gas-powered (CO₂/N₂) | 15–30 bar regulated output | Consistent multi-dose pressure, scalable | Cartridge disposal, gas regulation accuracy |
| Lorentz-force (electromagnetic) | Programmable up to 40 MPa | Precise velocity profile control, adaptive | Battery life, electronic reliability, cost |
A critical design parameter for needle-free injectors is the “jet stability ratio” — the ratio of jet velocity at the orifice exit to the velocity at the skin surface. As the jet travels through air, aerodynamic drag causes the jet to decelerate and, at sufficient distance, to break up into droplets. The standard specifies that the nozzle-to-skin distance must be controlled to within ±0.5 mm to ensure reproducible jet characteristics. This is typically achieved through a depth-compensating spacer ring that contacts the skin before firing.
2. Performance Requirements and Dose Delivery Validation
ISO 28823 establishes performance requirements specific to needle-free injection technology. Dose accuracy requirements follow the same general framework as needle-based systems (±5 % for ≥ 1 mL, ±10 % for < 1 mL), but the test methods must account for the unique characteristics of jet injection — specifically the potential for splash-back (liquid that bounces off the skin surface and is not delivered), wet-surface injection (liquid pooling on the skin rather than penetrating), and deep-tissue deposition variability. The standard requires that the dose accuracy test be performed using a validated tissue-mimicking material (typically a polyacrylamide gel or ballistic gelatin with calibrated elastic modulus) rather than simple gravimetric collection in air, which does not represent the back-pressure conditions of actual tissue.
The standard introduces the concept of “delivery efficiency” — defined as the ratio of the mass of drug delivered into the tissue-mimicking material to the total mass expelled from the device. A minimum delivery efficiency of 90 % is required, with the balance accounting for splash-back and surface liquid losses. The delivery efficiency must be verified across the full range of intended dose volumes and at three viscosity levels (1 cP, 10 cP, and 100 cP) to cover the range from aqueous solutions to viscous biologics. For each condition, a minimum of 20 consecutive measurements must be performed to establish statistical process control limits.
When developing a needle-free injector for viscous biologics (> 20 cP), consider that jet penetration depth decreases approximately as the square root of viscosity — doubling the viscosity halves the penetration depth for the same jet pressure. To compensate, you may need to increase the peak jet pressure or extend the injection duration. CFD simulation using the Carreau-Yasuda model for non-Newtonian fluids can accurately predict penetration depth for shear-thinning biologics before building hardware prototypes.
| Performance Parameter | Requirement | Test Condition | Test Method |
|---|---|---|---|
| Dose accuracy (≥ 1 mL) | ±5 % | Tissue-mimicking gel, 20 °C | Gravimetric after gel extraction |
| Dose accuracy (< 1 mL) | ±10 % | Tissue-mimicking gel, 20 °C | Gravimetric after gel extraction |
| Delivery efficiency | ≥ 90 % | All viscosities: 1, 10, 100 cP | Mass balance per injection |
| Penetration depth (intradermal target) | 0.5–2.0 mm | Gel with layered modulus | Dye tracking + optical sectioning |
| Penetration depth (subcutaneous target) | 2.0–8.0 mm | Gel with layered modulus | Dye tracking + optical sectioning |
| Splash-back loss | ≤ 5 % of dose | High-speed video recording | Image analysis + gravimetric |
| Dispersion volume | Reproducible per design spec | Post-injection gel dissection | Volumetric analysis of stained region |
3. Safety Features — Cross-Contamination Prevention and Single-Use Lockout
ISO 28823 places strong emphasis on cross-contamination prevention because needle-free injectors operate without a needle that is physically replaced between uses. For multi-use devices, the standard requires that the fluid pathway be designed to prevent back-flow of tissue fluid or blood into the device — typically through a one-way check valve at the nozzle, a physical fluid path separation between the drug reservoir and the nozzle assembly, or a single-use disposable nozzle cartridge that is replaced for each patient. The single-use disposable approach is strongly preferred for clinical settings where multiple patients are treated sequentially.
The standard requires that single-use lockout mechanisms be tested for reliability: after the first firing cycle, the device must be rendered inoperable through a physical or electronic interlock that prevents a second firing. The lockout mechanism must be tested through 100 attempted re-fire cycles with a test force 20 % above the normal firing force to ensure that the lockout cannot be defeated by brute force. For reusable nozzle cartridges (limited to single-patient use), the standard requires that the nozzle be designed for cleaning and sterilisation per the manufacturer’s instructions, and that the cleaning efficacy be validated per ISO 17664.
Cross-contamination between patients was a documented issue with early-generation needle-free injectors used in mass vaccination campaigns, leading to cases of hepatitis B transmission. Although modern injectors incorporate robust one-way fluid path designs, the risk of “splash-back contamination” — where tissue fluid expelled during injection contacts the device nozzle and is transferred to the next patient — must be specifically addressed in the risk management file. The standard recommends using single-use disposable nozzle caps that are ejected after each injection, combined with an automatic retraction mechanism that isolates the nozzle face after firing.
Frequently Asked Questions
Q1: How does the injection pain of needle-free injectors compare to conventional needles?
Clinical studies consistently show that needle-free injectors produce less injection-site pain than conventional hypodermic needles for most patients, primarily because the pain stimulus is distributed over a larger area of the dermis rather than concentrated at a single point. However, some patients report a different sensation — a brief “pressure-pop” feeling rather than the sharp prick of a needle. The standard encourages manufacturers to include user experience data in the design validation documentation.
Q2: What jet velocity is needed to penetrate human skin?
The stratum corneum (the outermost layer of the skin, approximately 10–40 μm thick) has a puncture strength of approximately 10–25 MPa. To reliably breach this barrier, the jet must achieve a stagnation pressure exceeding this threshold. For a typical 150 μm orifice, this corresponds to a jet velocity of approximately 140–200 m/s at the skin surface. The standard recommends that manufacturers determine the minimum effective pressure through dose-response testing in cadaver skin or validated tissue models.
Q3: Can needle-free injectors be used for all types of medications?
Most aqueous-based medications can be delivered by needle-free injection. Limitations apply to: highly viscous formulations (> 200 cP), large-volume injections (> 3 mL per site), and medications that require very precise tissue targeting (e.g., certain ocular therapies). The drug formulation must also be stable under the shear stresses encountered during jet injection — the standard recommends that the manufacturer verify drug stability after passage through the jet orifice using appropriate analytical methods (HPLC, particle size analysis, bioassay).
Q4: What is the required quality system for needle-free injector manufacturing?
ISO 28823 requires that manufacturers operate a quality management system compliant with ISO 13485. The standard specifically requires process validation for: nozzle orifice dimension (critical for jet formation), power source calibration (spring force or gas pressure), assembly of single-use disposable components, and sterilisation process (typically ethylene oxide or gamma irradiation for single-use components).
