A Novel Intradermal Adapter to Address the Growing Use and Demand of Safe, Reliable, and Repeatable Intradermal Delivery of Vaccines
Over the past few years, there has been a growing awareness of the unique benefits of delivering vaccines intradermally. Potential benefits include improved vaccine safety, increased vaccine effectiveness, and enhanced immunogenicity in hard to vaccinate populations such as the elderly. The immunogenicity benefits of intradermal delivery include equivalent response from patients to a vaccine when a lower dose of the vaccine is given intradermally than when the same vaccine is given at a higher dose subcutaneously or intramuscularly. Also, intradermal delivery has been effective in generating an immune response to vaccines in patient populations that typically are considered non-responders to traditional subcutaneous and intramuscular vaccines. In addition, intradermal delivery of vaccines may allow for lower volumes of vaccine to be used in comparison to subcutaneous or intramuscular delivery, and thus dose sparing of vaccines can assist in cost reduction and increase access to vaccines.
According to the U.S. Food and Drug Administration (FDA), there are over 80 intradermal vaccine clinical trials ongoing as of September 2011.[i] Increasingly, current vaccines available on the market are being evaluated for intradermal delivery. In the future, other vaccines in development such as therapeutic cancer vaccines, new generations of tuberculosis (TB) and influenza vaccines, live attenuated yellow fever vaccines, Dengue vaccines, and hepatitis A and B vaccines may also be given intradermally. Intradermal delivery also is being used today for allergy testing and evaluated for delivery of anesthetics and cosmetic agents.
Conventional Intradermal Delivery
The traditional method of intradermal delivery of vaccines has been done using the Mantoux method, which is fraught with limitations. Since 1907, the Mantoux technique has been in use for TB testing and vaccinations. To perform the standard Mantoux technique, the syringe needle is inserted into the skin, with needle bevel oriented up at a 5 to 15 degree angle from the surface, to a depth of 1mm. As the fluid is injected into the intradermal space, a bleb (wheal) is formed. The bleb is typically between 6 to 10 mm in diameter and is regarded as a visual confirmation that a successful intradermal injection has been completed. The Mantoux technique requires significant training and experience, and even among experienced clinicians, a bleb is not always formed by using the Mantoux technique. With intradermal injections, improper injection technique can impact the results of the vaccination. There is a growing need in the market for a safe, easy-to-use system that would allow for consistent, repeatable injection into the intradermal space. To answer this market demand, West has collaborated with SID Technologies LLC and PATH to address these challenges by developing an intradermal adapter. In October 2011, West presented the results of a Phase I trial that was conducted by PATH on the use of the intradermal adapter at the World Vaccine Congress in Lyon, France.
Novel Intradermal Adapter
As the use of intradermal delivery has begun to grow, there is a market need for a better method to allow the clinician to safely, consistently and repeatably deliver an intradermal injection. Ideally, an intradermal adapter would:
· allow for consistent injection into the intradermal space
· ensure it is safe and well-tolerated by patients
· ensure it is convenient and easy to use for clinicians
· require minimal end-user training
· work in all age ranges and skin types
· not require reformulation of vaccine or drug
· use current vaccine vials and disposable syringes
To this end, in collaboration with SID and PATH, West has designed an intradermal adapter that sits on a standard tuberculin syringe that will allow the clinician to perform a successful intradermal injection. Currently the only two commercially available options for intradermal injections are either use of the traditional Mantoux technique or the Becton Dickinson Soluvia™ device, which is only approved for use with Sanofi Aventis’s flu vaccine. The traditional Mantoux technique is very user-skill dependent and the Becton Dickinson Soluvia™ device is currently approved for adults only. Successful usage of the adapter is not dependent on end-user skill level.
The Phase I performance and safety evaluation of the intradermal adapter was conducted by Path, West’s collaborative partner, in Seattle in May 2011. The Phase I trial data of the intradermal adapter showed that when the intradermal adapter was used, the nurse achieved a 100% success rate in delivering intradermal injections based upon bleb formation. Twenty healthy volunteers between the ages of 18 to 55 years were injected intradermally with a saline solution into the upper region of the arm. Two injections per participant were done using the intradermal adapter, one bevel up and one bevel down. Intradermal administration was evaluated by measuring the diameter of the bleb, weighing the quantity of fluid remaining on the skin and outside the delivery system following injection, and confirmation of delivery depth to the intradermal layer by ultrasound. The success of injection was determined by both ultrasound showing delivery into the intradermal space and by bleb formation on the skin. There was no difference due to bevel orientation. Safety was evaluated in the Phase I study up to 48 hours post-injection. There were no adverse events, other than five minor skin abrasions out of the total of 40 injections observed. These skin abrasions were between 2-9mm in length and required no medical treatment. No other safety events were observed. A pain scale was used to evaluate the pain associated with each intradermal injection. The majority of participants reported feeling little or no pain with the intradermal injection using the intradermal adapter, with a mean pain score of 2.6 on a scale of 1 to 10 with 1 being the least painful.
The intradermal adapter shown above is an investigational prototype that was evaluated in the recent Phase I trial. The goal with the development of the intradermal adapter is to make intradermal injections easier and more reliable by controlling depth, length and angle of needle insertion. This is a simple, easily manufactured, low-cost solution to allow for successful intradermal delivery of vaccines. The intradermal adapter snaps onto a standard tuberculin syringe and limits the depth and angle of the needle’s penetration into the skin. The intradermal adapter holds the needle at a depth of 0.75mm to allow for a correct and consistent intradermal injection. Using the intradermal adapter does not significantly change the conventional method of administering an intradermal injection.
In the past, the use of intradermal injections has been limited due to the low reliability of the Mantoux method and the difficulty of administration for nurses. The intradermal adapter had a 100% success rate of delivering intradermal injections in a recent Phase I trial. Often, when intradermal injections are performed, a bleb is not created and thus it is theoretically possible that part of the dose has been delivered intradermally and part of the dose has been delivered subcutaneously. This was not the case when using the intradermal adapter, where every injection in the Phase I trial produced a bleb and every injection was proven by ultrasound to have been delivered to the intradermal space. With the shift from higher volume subcutaneous vaccines to lower volume intradermal vaccines, it is critical that the full dose of the intradermal vaccine be delivered to the intradermal space and not to a deeper tissue depth. If intradermal vaccines are not delivered completely to the intradermal space, the benefit of dose sparing is lost. The patient in this situation may not receive an effective vaccination. The intradermal adapter offers the following cumulative benefits in comparison to the currently commercially available options:
· It is a platform technology that can be further developed into multiple formats such as prefilled syringes
· It works with standard tuberculin syringes
· It requires minimal end-user training
· It does not require additional reformulation of vaccines
· It allows for simple manufacturing at a low cost
· It can be incorporated into standard packaging
· Use of the intradermal adapter does not significantly disrupt current clinical practices
The intradermal adapter has demonstrated its reliability in this Phase I trial, and it appears to be well-tolerated by patients. The intradermal adapter's Phase I trial results confirm its suitability for use in future intradermal trials. Use of the intradermal adapter does not require any change to current components used for intradermal injections. The intradermal adapter is expected to enter additional clinical trials and preclinical studies in 2012.