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Intradermal delivery devices
Source/aims:
Based on 'Intradermal delivery of vaccines' - a review of the literature and the potential for development for use in low and middle-income countries - 27 August 2009 - WHO Optimize webpage: direct link to report (large PDF).
Prepared to support 'Consultation for the Program for Appropriate Technology in Health (PATH) : Intradermal delivery of vaccines for use in low- and middle-income countries - research and development strategy'.
Current standard for intradermal delivery: Mantoux technique
The Mantoux technique, which uses a conventional tuberculin needle and syringe for intradermal (ID) vaccination of BCG (and a few other vaccines such as rabies), requires the vaccinator to judge the angle and depth of needle insertion by eye/feel, which requires careful training and can result in technical errors and variability of dose delivery.
Most ID devices in development (see below) incorporate a mechanism to control the depth of insertion of vaccine into the skin and sometimes also the angle of insertion, thereby ensuring that the vaccine is delivered to the correct layer, e.g. dermis or epidermis.
1. Depth-limited needle & syringe
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An example of a device that incorporates a mechanism to control the depth of insertion into the skin and also the angle of insertion is PATH and SID Technologies' collaboration to develop a plastic depth-limiting ID adaptor that fits over a standard insulin/tuberculin syringe, to limit both the depth and angle of needle penetration. |
2. Intradermal needle & syringe
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These are devices that use a single syringe-mounted needle designed to deliver reliably and easily to the dermis. The Soluvia® device (also referred to as the 'BD microinjection system') is a prefilled syringe with a single 30-gauge, 1.5 mm-long intradermal needle designed to deliver 100–200 µl of fluid. It is now commercially available (Sanofi Pasteur) for trivalent seasonal influenza vaccine in two presentations: for adults and for the elderly. The vaccine presentation for adults < 60 years old contains 9 µg haemagglutinin (HA) per strain rather than the standard 15 µg HA per strain for vaccines for intramuscular (IM) or subcutaneous (SC) delivery. |
3. Disposable syringe jet injector (DSJIs) – pre-filled or end-user (field-) filled
The majority of jet injectors currently being developed for vaccine delivery are disposable syringe (sometimes referred to as 'cartridge') jet injectors (DSJIs). These consist of a re-usable hand-piece containing a propulsion system and a disposable, vaccine-containing needle-free syringe or cartridge (pre-filled or end-user filled), which is replaced before each administration.
End-user filled:
- In response to earlier design requirements shared by WHO for low-cost, manually powered DSJIs, a number of prototype, and soon to be available, commercial devices now meet these requirements including: Zetajet® (Bioject), E-Jet500® (Euroject), PharmaJet® (PharmaJet Inc), and Lectrajet® M3RA (DCI). These devices require the liquid (or reconstituted) vaccine to be transferred from a vial to a syringe at the time of administration before the handpiece is used to administer the vaccine.
- An advantage of end-user filling is that the development of the device is less dependent on the vaccine manufacturer (not requiring a new fill-finish facility), and in case of handpiece failure or a requirement to use a different device/route, the vaccine can still be accessed by needle/syringe. A potential disadvantage is that an additional 'transfer' step is involved, requiring additional training and a potential source of errors.
Pre-filled:
- Prefilled syringes/cartridges are advocated for some applications but will require development of standards to enable their manufacture to be compatible with more than one device. They have the advantage of reducing errors in transfer and possibly reducing training needs.
4. Hollow microneedles with syringe
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Hollow microneedles (usually in arrays of more than one and typically < 1mm in length) can be fitted to the end of a syringe, e.g. Nanoject® (Debiotech) and Micronjet (Nanopass Technologies). This approach has the advantage of employing existing technology to ensure the full dose of vaccine is delivered. A non-prefilled syringe provides greater flexibility and can be filled from a multi-dose vial. These devices aim to give a less painful injection than IM/SC vaccination with more reliability and ease than the standard Mantoux technique. |
5. Hollow microneedles on a patch
Hollow microneedle arrays can also be applied to patches (such as Micro-Trans™, Valeritas) with a liquid vaccine reservoir.
6. Solid, coated microneedles on a patch
In these devices, vaccine (e.g. protein or DNA) is coated by the manufacturer onto solid microneedles in an array on a patch before application to the skin. The microneedles can be metal, silicon or polymer. The patches can contain 100s or 10,000s of microneedles. Examples of this type of device include the Macroflux® system (Zosano Pharma) and MTS® (3M) but other academic-based investigators are also developing solid, coated microneedles for a range of vaccine applications.
7. Solid dissolvable microneedles on a patch
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In this configuration, microneedles are fabricated from the active vaccine plus generally-recognized-as-safe (GRAS) excipients. The feasibility of manufacturing biodegradable microneedles has been demonstrated. Examples include the VaxMAT® technology from Theraject and a number of academic investigators are also pursuing this approach. |
8. Needle-free (transcutaneous) patch/solid uncoated microneedles
For transcutaneous immunization (TCI), some means of disrupting the stratum corneum (top layer of the skin) is usually required to allow large molecules to reach the dermal or epidermal layers.
One approach is the use of solid, uncoated microneedles to prepare or abrade the skin, before the application of vaccine, typically in a patch.
Other needle-free approaches to breach the stratum corneum are being evaluated, such as electromagnetic energy and skin stripping techniques to facilitate delivery of proteins to hair follicles. Examples of this approach include the transcutaneous immunization patch (Iomai, now part of Intercell). Vaxin Inc is also developing TCI patches for use with non-replicating bacterial vectors.
Other useful resources:
- Intradermal delivery
- Benefits of intradermal delivery/desirable attributes of intradermal delivery devices
- Taxonomy of intradermal devices
Last updated: 13 October 2010