Preclinical evaluation of auto-disable (AD) intradermal (ID) adapter: ADID found to increase accuracy and prevent reuse.
Developed by Charles Mantoux at the beginning of 20th century, the Mantoux method has long been the most common technique used to deliver injections into the intradermal realm. Despite the difficulty of correct implementation, the required training, and the resulting variability of the injection efficacy, the Mantoux technique (1) has been used for over 100 years with BCG vaccine given to 100 million newborns each year (2).
ID adapters offer an easy-to-use, low-cost aid for ID injections using Mantoux technique and currently available needles and syringes (3). The adapter sets the depth of the needle as it penetrates the skin and the length of the needle shaft in the skin. The training is minimized and reliability and repeatability of the needle placement increased, which helps to ensure increased injection success rates when using an adapter as compared to unaided Mantoux. Marketed ID adapters are not intended for reuse since the adapter could be contaminated by bodily fluids during the initial use.
UNICEF and healthcare authorities of many developing countries require the use of syringes equipped with an auto-disable (AD) feature to prevent reuse and cross contamination (4). The ADID adapter was developed to be used with a conventional AD syringe and to be used only once. The autodisable feature of the ADID adapter requires activation prior to injection as one of the adapter and syringe merger steps. This feature prevents reuse of the adapter with any new syringe. The adapter remains a single molded plastic component assuring low cost potential, one of the development goals.
We have evaluated the performance of the developed ADID adapters in two usability studies and an animal study. The initial usability study was conducted in the U.S. and was followed by a smaller study in Peru. The results of these usability evaluations and the animal study are detailed below. The preclinical evaluation of ADID adapter is discussed in this article, and the clinical evaluation results have been presented at the second Skin Vaccination Summit in September 20135.
The ADID adapter (Figs IB, 1C, ID) was developed for use with an auto disable syringe by Helm Medical, Gmbl. It has operating characteristics similar to ID adapters developed earlier (Fig 1 A).
The ADID adapter is a disposable, single-use component injection-molded in medical-grade polycarbonate. It fits on an AD syringe with a fixed needle. The syringe is filled with vaccine and merged with the ADID adapter. The adapter is activated by permanently engaging the pivoted integral section hooks to the main adapter body as illustrated in Figs 1C and ID. Furthermore the activation aligns the protruding needle parallel to the skin. The ADID adapter prevents the replacement of the syringe with a new AD or conventional syringe thereby preventing cross contamination.
The main usability study was conducted with 34 nurses from Chicago area. Each injection delivered 0.1 mL of saline solution into a skin model. The ADID adapters were evaluated with both bevel up (BU) and bevel down (BD) lancet orientation. Each nurse made 16 injections into a skin model (pig skin) by injecting saline while the wheal size, a standard measure of successful ID injection, was assessed.
* 8 Mantoux method bevel up (BU)
* 4 with AD ID adapter bevel up (BU)
* 4 with AD ID adapter bevel down (BD)
The usability test results illustrated a substantial increase in the injection success rate with the ADID adapter as compared to unaided Mantoux. The results also confirmed our earlier findings that the performance with the adapter is independent of the bevel orientation.
The use of the adapter substantially increased the average bleb size as well as reduced the STDEV as shown in Table 1.
The adapter increased the success rate of bleb formation with diameter over 6mm by 30 percent as compared to unaided ID injections. These results are similar to our findings for ID adapter without an auto disable feature when used with a conventional syringe (6). In both cases the increase in the success rate in the formation of blebs over 6mm Dia, an accepted threshold for a successful bleb, was close to 30% as shown in Table 2.
There were a few issues limiting the ADID adapter effectiveness at the nurse study in Chicago, IL:
1. Nurses participating in the study were not familiar with AD syringes used only in the developing countries and frequently disabled these syringes during assembly with the adapter.
2. The use procedure required opening of two conventional separate pouches, both of the adapter and the syringe as these were provided separately.
3. Nurses found the axial alignment of the syringe and adapter challenging.
Packaging was the main nurse concern. The adapter use required opening of two pouches resulting in additional steps and time. In comparison, the Mantoux technique involves the use of a syringe only.
Nurses expressed preference for a package containing both the syringe and the adapter.
COMMON PACKAGING EVALUATION
A new common packaging of the adapter and syringe was developed with the intent to minimize the use steps. Furthermore the developed integral blister incorporated features assisting in the correct alignment of the adapter and the syringe during merger. The usability study was repeated in Peru, a country suitable for AD product use.
The common blister for AD ID adapter and AD syringe:
* Provided sterility of the syringe and the adapter
* Retained adapter orientation in shipment (open side up)
* Assisted in the correct syringe and adapter alignment and sterile handling during merger and activation.
The study in Lima was attended by 12 Peruvian nurses and healthcare workers including 6 experienced and 6 novices. Each nurse performed 8 injections into a skin model (pig skin) after training:
* 4 Mantoux method bevel up
* 4 ADID adapter and syringe
Nurses unanimously preferred to use adapters co-packaged with syringes. They perceived main ADID adapter benefits in
* Stability: stable platform and pre-defined angle (children move around a lot)
* Safety: adapter prevents sticking the needle too deep if the child should suddenly move.
Additional verbalized benefits were related to personal safety (prevent needle pricks) and faster injection critical in children.
The developed co-package approach is also applicable to ID adapter without AD feature.
EVALUATION IN ANIMALS
An animal study was performed to further evaluate the ADID adapter prior to a human saline study. The animal study was conducted in four weeks old Yorkshire (domestic) pigs. The injections were performed by a laboratory technician experienced in ID injections. A total of 60 injections performed using AD syringes were split in three groups:
* 20 by Mantoux method bevel up
* 20 with ADID adapter bevel up
* 20 with ADID adapter bevel down
Mantoux injection performed by the expert technician formed blebs similar in size to that with the adapter, further confirming the adapter's effectiveness when used by novice operators as well as minimizing mistakes by experienced injectors:
* Mantoux: Dia=7.2mm
* Adapter: Dia=7.23mm
ID ADAPTER BENEFITS
One barrier to broad use of ID delivery for new and existing vaccines and other compounds has been the perceived difficulty and lower reliability of ID administration using unaided Mantoux as compared with intramuscular or subcutaneous routes. This is the reason the cost and vaccination time advantages for ID rabies administration have not resulted in a worldwide adoption of this technique.
ID adapters offer a practical, easy-to-use and reliable alternative ID delivery method that has the potential to encourage the advancement of ID delivery of many vaccines by improving the effectiveness, increasing the access, and reducing the cost of some vaccines (7). A device such as the ID adapter could enable clinical research and development of ID delivery of vaccines and make the transition to ID administration more practical for rabies, IPV and other vaccines.
The advantage of the ID adapter is in the device simplicity and low cost. Furthermore the injection basically improves on the Mantoux method successfully used in healthcare for over a century. The device simplifies the use and increases the reliability of an accepted process. The need for a confirmation of the device performance should be limited as the main parameters of Mantoux technique remain unchanged.
The initial ID adapter version is marketed by West (6,8). The developed ADID adapter addresses the need for the prevention of device reuse identified by World Health Organization (WHO) as a critical requirement. The intent is to reduce the risk of adapter reuse and subsequent transmission of bloodbome pathogens; WHO recommends use of auto-disable syringes for all vaccinations (2).
The technology's simplicity and similarity to the conventional Mantoux procedure minimize the required compound development while offering the ID injection reliability and simplicity lacking when using the Mantoux method and a conventional syringe only. In addition, as the ID adapter is compatible with existing presentations of drugs and vaccines, no reformulation or repackaging of medications would be necessary.
The evaluated ADID adapters were designed to place the needle tip at a consistent depth of 0.75 mm beneath the skin's surface. This placement depth is compatible with the variation in skin thickness at typical immunization sites independent of age, gender, ethnic background, or body mass.
Based on the results of preclinical studies, the prototype ADID adapters were found suitable for human studies and were used in evaluating intradermal delivery applications requiring auto disable functionality offered by this adapter. The developed adapter and syringe co-packaging proved to substantially simplify the requirements of device preparation for injection. CP
(1.) Mantoux C. Note sur la tuberculine pour intradermoreaction, par Mantoux. Compt Rend Soc Biol 1909;67:665.
(2.) WHO. BCG vaccine. WHO position paper. Wkly Epidemiol Rec 2004 Jan 23;79(4):27-38.
(3.) Tsais I. Methods and devices for intradermal injection. United States Patent 8556861, 2013
(4.) WHO, UNICEF, UNFPA. WHO-UNICEF-UNFPA joint statement on the use of auto-disable syringes in immunization services. World Health Organization, Department of Vaccines and Biologicals; 2003.
(5.) Tsais I. Improved intradermal injection by auto-disable (AD) intradermal (ID) adapter. Skin Vaccination Summit 2013. September 4-6, 2013; Seattle, WA USA. Arranged by Meetings Management of London, UK.
(6.) http://www.medgadget.com/2013/03/id-adapter-helps-with-safe-delivery-of-intradermal-meds. html
(7.) Hickling J, Jones K, Friede M, Zehrung D, Chen D, Kristensen D. Intradermal delivery of vaccines: potential benefits and current challenges. Bull World Health Organ 2011 Mar 1;89(3):221-6
(8.) Jarrahian C, et al. Clinical performance and safety of the ID adapter, a prototype intradermal delivery technology for vaccines, drugs, and diagnostic tests. Procedia in Vaccinology 6 (2012) 125-133.
TABLE 1: Improvements in bleb formation with ADID adapter Mantoux ADID Bleb average, mm 4.7 6.9 STDEV, mm 3.6 2.6 TABLE 2: Success rate of bleb formation >6mm Dia with increase Device Mantoux adapter by ADID adapter 49.60% 79.40% 29.8% ID adapter 44% 71% 27.0% (earlier study)
|Printer friendly Cite/link Email Feedback|
|Date:||Apr 1, 2015|
|Previous Article:||What is needed from a next-generation inhalation device? Reinventing familiar technologies.|
|Next Article:||Will all tablets and capsules have on-dose physical chemical identifiers soon?|