Abstract:
Devices and methods for intradermal (ID) administration of diagnostic and therapeutic agents, vaccines and other compounds into the dermal layer of the skin are disclosed. The devices and the methods simplify the ID injection process and increase the consistency of the placement of the needle tip in the dermal space close to the skin surface allowing for a shallow cannula placement in the dermis. Furthermore, the devices and methods broaden the number of sites suitable for ID injection and make the ID injection possible with limited training.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     This application is a section 371 of International Application No. PCT/US2008/061331, filed Apr. 23, 2008, which was published in the English language on Oct. 30, 2008 under International Publication No. WO 2008/131440 A1, which claims the benefit of U.S. Provisional Patent Application No. 60/925,609, filed Apr. 23, 2007 and U.S. Provisional Patent Application No. 60/928,423, filed May 10, 2007, the disclosure of which is incorporated herein by reference. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates to methods and devices for intradermal injection of drugs, vaccines and other compositions. Specifically, adapter devices and needle assemblies are described that are attachable to, or form a part of, a drug delivery system such as a syringe to facilitate intradermal injection. 
     BACKGROUND 
     Intradermal injections are used for delivering a variety of diagnostic and treatment compositions into a patient. Substances may be injected intradermally for diagnostic testing, such as to determine a patient&#39;s immunity status against tuberculosis and the status of allergic diseases. Vaccines, drugs and other compounds may also be delivered intradermally. In many instances, intradermal delivery is preferred because it generally requires a smaller volume dose of the diagnostic or treatment compound than other delivery techniques. An intradermal injection is made by delivering the substance into the epidermis and upper layer of the dermis. There is considerable variation in the skin thickness, both between individuals and within the same individual at different sites of the body. Generally the outer skin layer, or the epidermis, has a thickness between 500-200 microns and the dermis, the inner and thicker layer of the skin, has a thickness between 1.5-3.5 mm. 
     Making intradermal injections is difficult and generally requires an experienced nurse or medical professional. Incorrect placement of the tip of the needle cannula leads to a failed injection. The placement of the needle tip deeper than about 3.0 mm has the potential of delivering the injection into the subcutaneous region, where the intradermal dosage may be insufficient. Incorrect placement of the needle cannula may also puncture the skin again after being inserted into dermis, with the delivered compound being lost on the surface of the skin. Injection is often followed by a jet effect, with the compound exiting the injection site through the needle puncture track. The jet effect is even more pronounced for injections through a needle placed perpendicular to the injection site and in particular for shallow delivery. The success of intradermal injections is often determined by the experience of the healthcare professional. The preferred intradermal injection technique (using a standard needle) requires the healthcare professional to stretch the skin, orient the needle bevel to face upward, and insert a short bevel needle cannula at an angle of around 10-15 degrees, assuring that 2 to 3 mm of the needle cannula are located in the skin. The needle tip ends up positioned in the dermis or close to epidermis boundary. The compound is slowly injected into the skin of the patient, forming a blister or wheal. The insertion of the needle at an incorrect angle and/or depth results in a failed intradermal injection. Intradermal (ID) injection has been considered for immunization in the past, but has generally been rejected in favor of more reliable intramuscular or subcutaneous routes of administration because of the difficulty in making a successful ID injection. 
     Administration into the region of the intradermal space has been routinely used in the Mantoux tuberculin test, in which a purified protein derivative is injected at a shallow angle to the skin surface using a 27 or 30 gauge needle and a standard syringe. The technique is known to be quite difficult to perform and requires specialized training A degree of imprecision in the placement of the injection results in a significant number of false negative test results. As a result, the Mantoux approach has not led to the use of intradermal injection for systemic administration of substances, despite the advantage of requiring smaller doses of substances. 
     There have been attempts to develop devices that would assure a precise needle penetration depth during ID injection which tends to vary due to tissue compliance, penetration angle, skill level and other factors. These are detailed in U.S. Pat. Nos. 4,393,870 20 and 6,200,291 and US Published Patent Applications no. 2003/0093032, 2004/0147901. These devices employ complex constructions that tension the skin by vacuum, expanding the mounting surface prior to the needle insertion. 
     Alchas et al. developed a unique intradermal needle assembly for the delivery of compounds into the intradermal space by penetrating the dermis perpendicularly to its surface. A limiter supporting the needle is placed on the skin, the needle inserted, and the compound delivered. The penetration depth is in the 0.5 to 3 mm range, with a device limiter setting the penetration depth. There is a broad range of patents, issued and pending, defining different features of the system. U.S. Pat. Nos. 6,494,865, 6,569,123, 6,689,118, 6,776,776 and others, and U.S. Patent Publication no. 2003/0199822 describe such systems. The main limitation of the systems developed by Alchas et al. is the broad range of deposit depth due to assembly tolerances, needle bevel and the variations in skin properties. Another concern is back flow through the needle channel from the deposit pool to the surface of the skin due to a short direct channel formed by the needle. The jet effect further limits the performance when a shallow delivery is attempted. 
     Shielding and disposal of the contaminated needle cannula is a primary concern upon completion of an injection. It is preferable to cover the contaminated needle as soon as the intradermal injection is completed. A number of different approaches to shielding the contaminated needle are discussed in U.S. Pat. Nos. 4,631,057, 4,747,837, 4,801,295, 4,998,920, 5,053,018, 5,496,288, 5,893,845 and others. 
     The lack of suitable devices to accomplish reproducible delivery to the epidermal and dermal skin layers has limited the widespread use of the ID delivery route. Using conventional devices, ID injection is difficult to perform, unreliable and painful to the subject. There is thus a need for devices and methods that will enable efficient, accurate and reproducible delivery of agents to the intradermal layer of skin. 
     SUMMARY OF THE INVENTION 
     The present invention relates to devices and methods for the administration of compositions into the intradermal layer of the skin. An adapter device is provided, according to one aspect of the present invention, that facilitates intradermal delivery and can be used with minimal training Specifically, the adapter device minimizes the user skill required for correct insertion of the needle and accurate administration of an intradermal dosage. 
     In one embodiment, the adapter device of the present invention is intended for use with a conventional drug delivery system, such as a syringe, with the adapter and the syringe being arranged in a sliding relationship. Alternatively, a needle assembly may be provided integrally with the adapter device, eliminating the need for a needle integral with a syringe. In one embodiment of the adapter device, the user is able to observe the drug injection process. After the injection is completed, the user removes and discards the syringe and the adapter. In some embodiments, the user shields the needle by placing the adapter in a discard position following injection. 
     Adapter devices and needle assemblies of the present invention have surfaces that contact and deform the skin to provide an injection site at which the needle cannula can be inserted and then extended generally parallel to, but below, the surface of the skin. Adapter devices generally have first and second primary skin contacting surfaces provided on generally different, adjacent planes and positioned at an angle of less than 180° relative to each other, which act to deform a target tissue site when the adapter is applied to the skin. In use, the skin conforms to the first and second primary skin contacting surfaces of the adapter, and the needle cannula penetrates through the epidermis and dermis at a shallow angle to the surface of the skin, for example at an angle of 10° to 70°, preferably 15° to 6°. The cannula is further extended into the dermis along a path generally parallel to the second primary skin contacting surface for a distance, and the injectite is deposited in the dermal layer at a distance from the cannula penetration site. The adapter may include a first secondary skin contacting surface positioned proximal to the first primary skin contacting surface and/or a second secondary skin contacting surface positioned distal to the second primary skin contacting surface which act to limit tissue distortion. 
     The arrangement and configuration of the first and second primary skin contacting surfaces, and the angle at which the needle cannula exits the adapter device, facilitate extension of the cannula into the dermal layer at a depth, and for a distance, that allows deposition of the injected compound in the dermis and far enough away from the cannula penetration site to prevent loss of the injected composition. The structure of the adapter device provides a path for the cannula to enter the skin at a shallow angle to the surface of the skin, ensuring that the composition is delivered to the dermal layer rather than subcutaneously, and also limits the distance the cannula travels, ensuring that the composition is deposited in the dermal layer at an appropriate distance from the injection site. 
     The eventual placement of the needle tip closely follows the results of a well performed manual ID needle placement technique. The deformation of the skin and the underlying tissue during the application of the adapter and syringe assembly blocks the needle pathway to the surface of the skin after the assembly is removed. This technique resembles a Z-track approach used for intramuscular injections where the tissue layers are shifted prior to injection to minimize the backflow through the cannula channel after injection. 
     The positioning of the cannula tip in the dermis, and the length of the cannula extending into the dermis is controlled by the design and manufacture of the adapter. The cannula length in the dermis is selected to facilitate delivery to the dermis and to minimize the back flow and is generally set in the 0.25 mm to 8 mm range and, in some embodiments, the depth of the cannula orifice in the dermis may be as shallow as 0.25 mm or as deep as 3.00 mm. A shallow positioning is further facilitated by the opportunity to use fine gauge needles. The use of fine gauge cannulas is possible because minimal deflection forces act on the cannula during insertion and is also facilitated by the conventional lancet geometry minimizing the forces acting on the cannula and cannula deflection. 
     The cannula may be positioned at a slight angle to the second primary skin contacting surface in order to increase or decrease the orifice placement depth in the dermis while the cannula is being inserted. The cannula orifice placement depth can also be set by the curvature of the second primary skin contacting surface of the adapter. 
     Various features and advantages of this invention will become apparent to those skilled in the art from the following detailed description of the currently preferred embodiments. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a side perspective view of one embodiment of an adapter according to the invention; 
         FIG. 2  is a top view of the device in  FIG. 1 ; 
         FIG. 3  is a top perspective view of the device in  FIG. 1  during merger with a syringe; 
         FIG. 4  is a cross sectional view of the device in  FIG. 3  with the syringe placed further into the adapter in a pre-injection position; 
         FIG. 5  is a cross sectional view of the device in  FIG. 4  after extension of the needle into dermis and prior to compound injection; 
         FIG. 5A  is an enlarged view of the device and injection shown in  FIG. 5 ; 
         FIG. 6  is a cross sectional view of the device in  FIG. 4  placed on a skin surface and illustrating the bulging of the dermis into the skin observation opening. 
         FIG. 7  is a top perspective view of another embodiment of an adapter according to the invention, having a safety ring; 
         FIG. 8  is a top perspective view of the device in  FIG. 7  during merger with a syringe; 
         FIG. 9  is a cross sectional view of the device in  FIG. 8 ; 
         FIG. 10  is a cross sectional view of the device in  FIG. 9  with the cannula in a pre-insertion position in the adapter prior to insertion into dermis; 
         FIG. 11  is a cross sectional view of the device in  FIG. 10  after cannula extension and insertion into dermis and prior to compound injection; 
         FIG. 12  is a cross sectional view of the device in  FIG. 11  after the cannula is withdrawn from the dermis and shielded; 
         FIG. 13A  is a bottom view of the device in  FIG. 7  (from the skin side) during merger with the syringe; 
         FIG. 13B  is a cross sectional view of the device in  FIG. 13A  along the surface AA; 
         FIG. 14A  is a bottom view of the device in  FIG. 13A  with the needle permanently shielded by the ring in discard position; 
         FIG. 14B  is a cross sectional view of the device in  FIG. 14A  along the surface AA; 
         FIG. 15  is a top view of yet another embodiment of an ID adapter having an alternative latch, syringe support and wall thickness implementation; 
         FIG. 16  is another perspective view of the ID adapter of  FIG. 15 ; 
         FIG. 17  is a side perspective view of an ID needle assembly according to the invention as stored; 
         FIG. 18A  is a side perspective view of the device in  FIG. 17  as merged with a partially illustrated syringe, with the safety clip removed and shown in  FIG. 18B ; 
         FIG. 19  is a cross sectional view of the device in  FIG. 17  as applied to the skin in a pre-insertion position with a partial view of an attached syringe; 
         FIG. 20  is a cross sectional view of the device in  FIG. 18  during injection after activation with a partial view of an emptied syringe; 
         FIG. 21  is an enlarged cross sectional view of the needle area of the device in  FIG. 20 ; 
         FIG. 22  is a partially cross sectional side perspective view of the syringe and the adapter of the device in  FIG. 17  after the needle has been placed into discard position; 
         FIG. 23  is an enlarged, cut-away perspective view of the device in  FIG. 17  illustrating the safety clip and portions of the adapter in proximity to the safety clip. 
         FIG. 24  is a top perspective view of another embodiment of an ID needle assembly according to the invention as merged with a partially illustrated syringe; 
         FIG. 25  is a top perspective view of the device of  FIG. 24  with the safety clip removed during cannula insertion as merged with a syringe; 
         FIGS. 26A-B  illustrate cross sectional views of the device in  FIG. 24  as merged with a syringe in a pre-insertion position ( FIG. 26A ), as applied to the skin with the cannula inserted into dermis ( FIG. 26B ), and after injection with the cannula withdrawn ( FIG. 26C ); 
         FIGS. 27A-B  illustrate perspective views of an adapter of the device of  FIG. 24 , with a top perspective view shown in  FIG. 27A  and a bottom perspective view shown in  FIG. 27B ; 
         FIGS. 28A-B  illustrate perspective views of the cannula assembly of the device of  FIG. 24 , as viewed facing the luer in  FIG. 28A  and facing the cannula in  FIG. 28B ; 
         FIG. 29  is a side view of yet another embodiment of an ID needle assembly having a dermis sensor according to the invention; 
         FIG. 30  is a side view of the device in  FIG. 29  as merged with a syringe with the sensor turned by the contact with the dermis; 
         FIG. 31  is a side view of the device in  FIG. 29  with the cannula inserted into dermis; 
         FIG. 32A-C  illustrate cross sectional views of the device of  FIG. 29  as merged with a syringe ( FIG. 32A ), as applied to the skin with the cannula inserted into dermis ( FIG. 32B ), and after injection with the cannula withdrawn ( FIG. 32C ); 
         FIG. 33  illustrates a perspective view of an adapter of a device of  FIG. 29  as viewed from the top ( FIG. 33A ) and the bottom ( FIG. 33B ) of the component; and 
         FIG. 34  illustrates a perspective view of the dermis sensor of the device of  FIG. 29 . 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     An adapter for an intradermal (ID) injection is intended for use with a syringe or another drug delivery system. One embodiment is shown in and described with reference to  FIGS. 1-6 . An alternative embodiment incorporating a safety system is described in  FIGS. 7-14 . As used herein, “proximal” refers to the assembly end positioned towards the user or the drug delivery device, while “distal” defines the opposite end of the assembly positioned towards the skin of the patient. 
     The external view of an adapter is illustrated in  FIG. 1 . The adapter  100  has a main body  101  and a distal section  103 . The adapter main body  101  has finger grips  102  for ease of handling. The distal section of the adapter  103  has a first skin contacting surface  104  and a second skin contacting surface  105  positioned at an angle  123  relative to each other. Skin contacting surfaces  104  and  105  may be generally planar and connected to each other along one edge as shown in  FIG. 1 . Angle  123  is selected to allow for skin conformance to surfaces  104  and  105  when adapter  100  is applied to the dermis. Angle  123  is below 180° to allow for an adapter needle opening  110  to be positioned in the plane of skin contacting surface  104 . In some embodiments, angle  123  is preferably less than about 165° and more than about 120°. This allows for penetration of the dermis by a needle of a drug delivery device upon the needle being forwarded through adapter needle opening  110 . It also allows the needle to be advanced into the dermal space generally parallel to (e.g., at a shallow angle to) and below the skin surface. Skin contacting surfaces  104  and  105  may be arranged with an area of a gradual transition from surface to surface. 
     During use, skin contacting surface  105  is positioned on the surface of the skin above the site where the composition is deposited during injection and covers the bleb area formed when a compound is injected through the needle into the dermal space. To improve the skin visibility and to allow for skin distension, a skin observation window  112  may be provided in skin contacting surface  105 . 
     Conformance of the dermis to the skin contacting surfaces  105  and  104  is improved when pressure is applied to an upper surface  118  of the adapter distal section  103 . The conformance of the dermis to the skin contacting surfaces  104  and  105  may also be improved by minimizing deformation of the dermis and the underlying tissue. This can be achieved by providing a distal contact surface  116  and a proximal contact surface  117  of the adapter  100  arranged in proximity to the skin contacting surfaces  105  and  104 , respectively, to minimize the tissue distortion during positioning of the adapter device on the skin and injection. Proximal contact surface  117  adjoins a proximal edge of first skin contacting surface  104  and may slope away from first skin contacting surface in a generally downwards direction with respect to needle opening  110  when the adapter is in the orientation shown in  FIG. 1 . Distal contact surface  116  adjoins a distal edge of second skin contacting surface  105  and may slope away from second skin contacting surface  105  in a generally opposite, upwards direction with respect to needle opening  110  when the adapter is in the orientation shown in  FIG. 1 . Tissue distortion may be reduced, desirably, when contact surfaces  116  and  117  are arranged in substantially similar planes. 
     Adapter  100  has an internal cavity  106  as illustrated in  FIG. 2 . Cavity  106  is arranged to accept a drug delivery device equipped with a cannula, such as a conventional syringe  50 . Internal cavity  106  is arranged to accommodate syringe  50  in a sliding relationship. Syringe  50  slides on the internal adapter surface  107 . Adapter body  101  is provided with an opening  111  allowing for the direct observation of merger of syringe  50  with adapter  100 . An integral syringe support  124  is provided on adapter body  101  to guide syringe  50  during merger. 
     Syringe  50  is placed into the adapter in a radial direction through opening  111  as illustrated in  FIG. 3 . The distal end of the syringe barrel  59  is placed on syringe support  124  which provides a guiding surface. Adapter opening  111  is formed to not interfere with the syringe cannula during the merger. The adapter body is provided with an integral latch  113 . Latch  113  is separated from the body  101  by a slit  114  except for on its distal end where latch  113  is attached to the adapter body  101 . Syringe  50  is pushed in a distal direction until a distal end  60  of the syringe barrel  59  contacts latch  113 . 
     The internal cavity  106  of the adapter has a cylindrical section  122  that accommodates syringe barrel  59 , a reduced diameter section  108  that accommodates needle hub  63 , and a needle opening cone section  109  that ends at first skin contacting surface  104  and adapter needle opening  110 . The needle cannula  55  has a forward tip  58  with a bevel. The adapter is sized such that cannula  55  is enclosed in the adapter  100  when distal end  60  of syringe barrel  59  contacts adapter latch  113  as illustrated in  FIG. 4 . 
     In use, adapter  100  is applied to and held in contact with the dermis, as detailed below. An axial force is then applied to syringe barrel  59  causing the latch  113  to deflect when acted upon by the distal end  60  of barrel  59 . The barrel  59  moves forward after the latch  113  is deflected. Cannula  55  then extends through needle opening  110  and is inserted into the dermis parallel to the skin surface. The needle insertion stops when a distal end  64  of needle hub  63  contacts the adapter  100  as shown in  FIG. 5 . 
       FIG. 5A  illustrates details of the adapter design. The first  104  and second  105  skin contacting surfaces are positioned at a relative angle  123 . The angle allows for tissue deformation and for bringing the dermis into contact with these adapter primary surfaces. The position of needle opening  110  and the cannula orientation in the adapter are selected to result in cannula  55  being inserted parallel to the dermis surface at a desired depth  115  from the cannula center line. 
     The compound is expelled from the drug delivery device into the dermis by pushing on syringe rod  61  and advancing the stopper  62 . The injection may be performed while the adapter is applied to the skin with some pressure. Alternatively, the pressure on the adapter towards the skin may be reduced during injection allowing for more dermis distention and welt formation. In another technique, the adapter may be somewhat elevated above the skin while maintaining the needle tip position in the dermis, in order to further improve the dermis distension. 
     Cannula  55  may be extracted from the skin and the cannula and syringe discarded while the adapter  100  remains in contact with the dermis. Alternatively, the adapter  100  may be removed from the skin together with the syringe and subsequently discarded. 
     Adapter finger contact surface  118  may be shaped to provide an indication to the user of where to apply pressure on contact surface  118  during insertion of cannula  55  into the dermal space. Adapter  100  may also be provided with a recess  119  to minimize the plastic volume of the device. 
     The skin tends to form a slight bulge  251  and protrude into observation opening  112  when the adapter is pushed toward the dermis  250  as illustrated in  FIG. 6 . The adapter may have an adapter body extension that extends into the opening  112 . This extension, which would be positioned above the cannula  55 , would support the dermis and prevent bulging of the skin thereby maintaining the desired depth of the needle forward tip during needle insertion. The skin will further bulge and protrude into the window during injection as a result of the bleb formation. 
     It is desirable to minimize distortion of the dermis and the underlying tissue during ID injection. This is accomplished through the design of the primary first and second skin contacting surfaces  104  and  105  and the secondary distal  116  and proximal  117  contact surfaces of the adapter. The orientation of secondary distal and proximal contact surfaces  116  and  117  is selected to form a surface with minimal distortions when considered together with the first skin contacting surface  104  and the second skin contacting surface  105 . 
     It is also desirable to have a taut skin area in contact with the adapter to minimize the bulging of the skin into the observation opening  112 . Areas of the skin contacting surfaces could have properties assisting in increasing adherence toward skin when the adapter is applied, such as sticky or rubbery surfaces. The skin contacting surfaces may be substantially flat, or they may be grooved or ridged, or they may be curved or provided in another configuration. The part of the adapter skin contacting surfaces  104  and  105  in the plane of the needle may be elevated compared to peripheral sections of the skin contacting surfaces. The resulting protruding parts of the contact surfaces in the plane of the cannula contact the skin during the initial phase of the adapter application resulting in a taut skin. 
     The distal  116  and the proximal  117  contact surfaces may be provided as extensions of the primary first and second skin contacting surfaces, and they may be equipped with ridges  120  and  121 . The distal contact surface  116  may be placed into contact with the dermis first, allowing for skin tensioning. Subsequently, the second contact surface  117  may be brought into contact with the dermis, allowing the retention of the skin tensioning during the injection process. 
     In another embodiment, an adapter for an intradermal (ID) injection is equipped with a safety feature. This embodiment, which is also intended for use with a syringe or any other drug delivery system is illustrated in  FIGS. 7-14 . 
     An external view of the device is illustrated in  FIG. 7 . Adapter assembly  200  has an adapter body  201  and a safety ring  230 . The features of adapter body  200  are similar to those of the adapter illustrated in  FIGS. 1-6 . The adapter body  201  has finger grips  202  for ease of handling and a syringe support  224 . The adapter is also equipped with a delivery device opening  211  simplifying the adapter and syringe merger. 
     The distal section of the adapter  203  has two skin contacting surfaces  204  and  205  positioned at an angle  223  relative to each other similar to the adapter discussed above and illustrated in  FIGS. 1-6 . Angle  223 , which has to be below 180 degrees to allow for the adapter needle opening  210  to be positioned in the plane of the skin contact surface  204  is selected to allow for skin conformance to these surfaces when the adapter is applied to the dermis. This arrangement allows for the penetration of the dermis by the needle of a drug delivery device upon the needle being forwarded through the needle opening  210 . It also allows the needle to be advanced into the dermal space parallel to the skin surface and the adapter plane  205 . The primary skin contacting surfaces  204  and  205  may be arranged with an area of a gradual transition from surface to surface. The adapter contact surface  205  covers the bleb area formed when the compound is injected. To improve the skin visibility and to allow for the skin distension a skin observation window  212  can be formed in the contact surface  205  of the adapter body distal section  203 . 
     Conformance of the dermis to the adapter surface is improved when pressure is applied to the surface  218  of the adapter distal section  203 . Conformance of the dermis to the adapter surfaces  204  and  205  is also improved by minimizing deformation of the dermis and the underlying tissue during application of the adapter to the skin This is achieved by the introduction of distal  216  and proximal  217  contact surfaces designed to minimize the tissue distortion during injection. 
     The adapter  200  has an internal cavity  206  as illustrated in  FIGS. 7 and 8 . This cavity is arranged to accept a drug delivery device equipped with a cannula.  FIGS. 7-14  illustrate a safety adapter intended for use with a conventional syringe  80  provided with an undercut  94  (such as, for example, Terumo SurGuard safety insulin or allergy syringes). 
     The adapter  200  has a safety ring  230  in a sliding relationship with adapter body  201 . The ring  230  is initially in a most distal position as illustrated in  FIGS. 7-10 . Ring  230  has an observation window  231  coinciding with the window of the adapter body  211 , and a latch  232 . Latch  232  has a protrusion  233  for engaging the syringe. Ring  230  also has an undercut  234  in the latch area that retains ring  230  in the most distal position during the initial steps of the operation. 
     The internal cavity  206  of the adapter  200  is arranged to accommodate a syringe  80  in a sliding relationship. Syringe  80  slides on the internal surface  207  of the adapter body  201 . The adapter body  201  is provided with an opening  211  that facilitates the merger of the adapter with syringe  80  by allowing the cannula passage and observation of the merger process. Adapter body  201  also has an integral syringe support  224  to simplify the adapter  200  and the syringe  80  merger by the user. 
     The syringe  80  is placed into the adapter  200  through the adapter body opening  211  as illustrated in  FIGS. 8 and 9 . The distal end of the syringe barrel  89  is placed on the syringe support  224  which provides a guiding surface for further insertion. The adapter opening  211  does not interfere with the syringe cannula during the merger step. 
     The adapter body  201  has an integral latch  213 , which is separated from body  201  by a slit  214  except for at its distal end where the latch is attached to the adapter body  201 . The syringe is pushed in a distal direction until the distal end of the syringe hub leading edge  95  contacts the latch protrusion  226  and deflects the latch  213  with the protrusion  226  jumping into the undercut  94  of the syringe needle hub  93  as illustrated in  FIG. 10 . The internal adapter cavity  206  has a cylindrical section  222  that accommodates the syringe barrel  89 , a reduced diameter section  208  that accommodates the needle hub  93 , and a needle opening cone section  209  ending at adapter needle opening  210 . 
     Needle cannula  85  has a forward tip  88  with a bevel. The cannula  85  is held within the adapter  200  when the syringe barrel  89  contacts and engages the adapter latch  213  as illustrated in  FIG. 10 . 
     In use, the adapter  200  is applied to and held in contact with the dermis. An axial force is applied to the syringe barrel  89  causing the adapter latch  213  to deflect when acted upon by the barrel distal end  96 , thereby enabling barrel  89  to move forward. The cannula  85  penetrates the skin through the needle opening  210  and is automatically inserted into the dermis parallel to the skin surface in contact with the second primary surface  205  for a preset cannula shaft length. The needle insertion stops when the distal end  95  of the syringe hub  93  contacts adapter body  201  as illustrated in  FIG. 11 . 
     Prior to the needle hub leading edge  95  contacting the adapter body, the ring latch  232  contacts the needle hub and gets deflected. The latch protrusion  233  simultaneously engages the syringe with the distal motion of the syringe being stopped by contact of the needle hub with the adapter body  201 . 
     The details of the adapter  100  design illustrated in  FIG. 5A  are applicable to the safety adapter  200 . The syringe needle penetrates adapter first contact surface  204  and is further inserted parallel to the second contact surface  205 . The relative angle between the first and second surface allows tissue deformation, bringing the dermis in contact with the adapter. The position of the needle opening  210  and the cannula orientation in the adapter are selected to result in the needle being inserted parallel to the dermis surface at a desired depth from the cannula center line. 
     The compound is expelled from the drug delivery device into the dermis by pushing on the syringe rod  91  and advancing the stopper  92 . The injection may take place while the adapter is applied to the skin with some pressure. Alternatively, the pressure on the adapter toward the skin may be reduced allowing for more dermis distention and bleb formation. In another technique, the adapter may be somewhat elevated above the skin while maintaining the needle tip position in the dermis, thereby further improving the dermis distension. 
     After injection, the syringe cannula  85  is extracted from the skin by removing the adapter and the syringe from the site. At this point the adapter safety ring  230  and the syringe  80  are engaged. The cannula is than permanently shielded by pulling the barrel in respect to the adapter or by pulling the safety ring toward the finger grips  202 . The discard position of the adapter  200  engages with the syringe  80  as illustrated in  FIG. 12 . The needle forward tip  88  is thus permanently hidden in the adapter body  201 . 
     The adapter  200  latches retain the cannula in the discard position as illustrated in  FIGS. 12 and 13 . The safety ring  230  has a bottom opening which allows for unobstructed deflection of the adapter latch  213  during operation. The safety ring is further equipped with two discard latches  337  separated from the safety ring  230  by a slit  238 . 
     The adapter finger contact surface  218  may be shaped to provide an indication to the user as to where to apply pressure on the surface during needle insertion into the dermal space. For example, the surface may be curved to match the finger tip profile and have a different texture from the rest of the adapter. The adapter  200  may also have a recess  219  to minimize the plastic volume as illustrated in  FIG. 7 . 
     It is desirable to minimize the distortion of the dermis and the underlying tissue during ID injection. This goal is accomplished by the distal  216  and the proximal  217  contact surfaces of the adapter. The orientation of contact surfaces  216  and  217  is selected to form a surface causing minimal distortions of the dermis when considered together with the first skin contacting surface  204  and the second skin contacting surface  205 . 
     It is also desirable to have a taut skin area in contact with the adapter to minimize bulging of the skin into the opening  212 . Areas of the skin contacting surfaces may have properties assisting in increasing adherence toward skin when the adapter is applied, and the contacting surfaces could be substantially curved as discussed above. The part of the adapter contacting surfaces in the plane of, and in proximity to the needle may be elevated compared to the peripheral sections of the skin contacting surfaces. The protruding peripheral parts of the contact surfaces would contact the skin during the initial phase of the adapter application resulting in a taut skin. 
     The secondary distal  216  and proximal  217  skin contacting surfaces of the adapter may be equipped with ridges  220  and  221  or other surface protrusions. The rigged distal contact surface  216  may be placed into contact with the dermis first, allowing for skin tensioning. Subsequently the second contact surface  217  is brought into contact with the dermis allowing for the skin tension to be retained during the insertion process. 
     The ID adapter illustrated in  FIGS. 1-6  may be modified, for example, as shown in  FIGS. 15 and 16 , to improve manufacturability of the ID adapter. ID adapter  260  has the same essential features as the ID adapter illustrated in  FIGS. 1-6  and has a reduced wall thickness in the area of recesses  279 . Syringe support  284  was formed as a direct extension of the adapter body  261 . In this embodiment of ID adapter  260 , latch  273  protrudes from the proximal surface of the body  261 , providing improved manufacturability. 
     Alternative needle assemblies for intradermal (ID) injection employing the ID adapter and intended for use with a syringe or any other drug delivery system are illustrated in  FIGS. 17-34  with a first embodiment being shown in  FIGS. 17 through 23 ; a second embodiment being shown in  FIGS. 24 through 28 ; and a third embodiment being shown in  FIGS. 29 through 34 . The adapter geometry features are detailed for the first preferred embodiment but are implemented in all three embodiments. 
     A side perspective view of the first preferred embodiment of the device is illustrated in  FIG. 17 . The main components include an adapter  310 , a needle cannula assembly  330  and a safety clip  360 . The adapter  310  is in a sliding relationship with the needle cannula assembly  330  and partially surrounds it. The safety clip  360  retains the relative position of the adapter  310  to the needle cannula assembly  330  during storage and during the attachment to a drug delivery device. 
     The needle cannula assembly  330  has a hub portion  331  to connect to a syringe  350  or another drug delivery device as illustrated in  FIG. 18 . The hub portion  331  could have a female luer  332 . In designs employing a luer lock the hub portion would have luer lock wings  335 .  FIGS. 18 through 22  do not illustrate the thread of the syringe luer lock design. 
     The adapter  310  is equipped with two skin contacting surfaces  311  and  323  positioned at an angle  324  relative to each other. The angle is selected to allow for skin conformance to the adapter when the adapter is applied to the skin surface. The angle has to be below 180 degrees to allow for the adapter needle opening  325  to be positioned in the plane of the skin contact surface  311 . This allows for the penetration of the dermis by the needle upon the needle being forwarded from its storage position. It also allows the needle to be advanced into the dermal space in general parallel to the skin surface. The contact surfaces  311  and  323  have been arranged with an area of a gradual transition from surface to surface. 
     The adapter contact surface  311  covers the welt area formed when the compound is injected. To improve the skin visibility and to allow the skin distension a skin observation window  317  can be formed in the contact surface  311  of the adapter  310 . 
     The adapter  310  and the needle cannula assembly  330  are arranged in a sliding relationship. The adapter  310  has an internal cavity  312  to accommodate the needle assembly  330  and to prevent the exposure of the needle cannula  345  prior and after injection. The needle cannula has a forward tip  348  with a bevel  347 . The cannula outer diameter is illustrated as  346  in the attached figures. 
     The needle cannula assembly  330  has protrusions  336  and  337  to maintain the alignment of the assembly and the adapter  310  during storage, use and in discard position. Furthermore the assembly has a protrusion  333  to maintain the desired bevel  347  position in respect to the skin surface. The protrusion  333  has a proximal slope  334  to accommodate the placement of the assembly into a discard position. The needle cannula is affixed to the hub portion using adhesion, interference fit or any other of the commonly used techniques. 
     The adapter  310  has two openings, an operation opening  315  and a discard opening  316  to accommodate the needle assembly protrusion  333 . During storage and integration with the syringe the protrusion  333  is positioned in the storage opening section  313  of the operation opening  315 . The storage opening section  313  is separated from the operation opening  315  by elevations  314 . These elevations retain the adapter to needle assembly position prior to needle deployment. 
     The adapter openings are positioned on a latch  319 . The latch  319  is a part of the adapter  310 , is separated from the adapter by slits  320  while connected to the body of the adapter at the distal end of the latch. The latch is able to deflect away from the center of the adapter during the integration of the needle cannula assembly  330  with the adapter  310 . Furthermore the latch is deflected outward when the protrusion proximal slope impacts the latch bridge  326  during the assembly transition from inject to discard position. Slits  320  also allow the tangential deflection if the side walls of the latch  319  when these are impacted by the protrusion  333 . 
     The dimensions of the adapter cavity  312 , the adapter needle opening  325 , the outer diameter of the hub portion  331  and protrusions  336  and  337  are selected to assure the forward needle tip is stable and moves parallel to the first contact surface  311  when deployed. Furthermore the adapter has a needle opening cone  321  to assist in the assembly of the adapter and the needle cannula assembly. 
     The adapter could also have a finger rest  318  for applying some pressure on the surface during the needle insertion into the dermal space. The adapter  310  could also have a recess  327  to minimize the plastic volume. The needle is inserted into the dermal space in general parallel to the skin and the skin contact surface  311 . The thickness of the skin layer above the needle is set by the adapter design and the method of use and is illustrated as  322  in  FIG. 21 . 
     Prior to injection the skin tends to slightly bulge and protrude into the window  317  as illustrated in  FIG. 19 . The window  317  could have an extension  328  to support and prevent bulging of the skin above the needle and to maintain the desired depth of the needle forward tip during needle insertion. The skin will further bulge and protrude into the window during injection as illustrated in  FIG. 20 . 
     It is desirable to have a taut skin in contact with the adapter. This is accomplished by the properties of the skin contacting surfaces  311  and  323  and the shape of these surfaces along with the appropriate application techniques. Areas of the skin contacting surfaces could have properties to increase adherence toward skin when the adapter is applied. Furthermore the contacting surfaces could be substantially curved. The part of the adapter contacting surfaces in the plane of the needle (as illustrated in  FIG. 19 ) could be elevated comparing to the peripheral sections of the skin contacting surfaces  311  and  323 . These protruding parts of the contact surface would contact the skin during the initial phase of the adapter application resulting in a taut skin. 
     The needle assembly could be equipped with a safety clip  360  as mentioned above. The safety clip  360  illustrated in  FIGS. 17 ,  18 B and  23  has a body  361 , ridges  362 , clip protrusion  363  and extension  364 . The clip is engaged to the needle cannula assembly by ridges  362  interacting with the needle assembly undercuts  338 . Furthermore the clip protrusion  363  engages the discard opening  316  of the adapter. The safety clip prevents the relative displacement of the needle assembly and the adapter until the clip removal as illustrated in  FIG. 18 . The clip can be removed by pulling on the extension  364 . 
     ID injection is substantially simplified when the ID needle assembly is employed. Furthermore, many additional skin sites may be used for intradermal delivery when this needle assembly is used. The assembly assures the injection is consistent in regards to the needle tip placement. The needle assembly is initially connected to the drug delivery device, which may be a pre-filled syringe or a single use syringe filled by the caregiver prior to injection. The system might be primed if required. The needle assembly is applied to the skin at any one of a broad range of suitable sites. These could be conventional sites recommended for ID injection or curved sites offering a curvature compatible with the relative position of the adapter contact surfaces. 
     The assembly is applied to the skin with some pressure, resulting in tissue deformation and the desired skin compliance with the adapter contact surfaces. The needle is subsequently inserted into the tissue while the contact is maintained. The hub protrusion  333  deflects the latch side walls and is moved into the distal part of the operations opening  315 . The needle penetrates into the dermis through the opening  325  in surface  323  and is further advanced substantially parallel to the skin surface. 
     The compound is expelled from the drug delivery device into the dermis. The injection could take place while the adapter is applied to the skin with some pressure. Alternatively the pressure on the adapter toward the skin could be minimized allowing for more dermis distention and welt formation. Furthermore the adapter could be somewhat elevated above the skin while maintaining the needle tip position in the dermis. This technique could further improve the dermis distension. 
     The needle could be extracted from the skin while the adapter remains in contact with the dermis. Alternatively the adapter could be removed from the skin with the needle tip exposed and subsequently put into a discard position with the needle being shielded. The placement of the needle assembly into a discard shielded position takes place while the adapter is pushed in the distal direction by a pressure against a table edge or any other protruding element while holding on to the syringe. Subsequently the needle assembly and the syringe are discarded. 
     Another embodiment  400  is illustrated in  FIGS. 24-28 . The external view of the embodiment of the device  400  is illustrated in  FIG. 24 . The main components include an adapter  410  and a needle cannula assembly  430 . The needle cannula assembly  430  has a hub  436  retaining the cannula  431 . The hub  436  has a protrusion  432  engaging the adapter opening  411 . The hub  436  also has another protrusion  433  positioned on a lever  434  and also engaging the adapter  410 . 
     The adapter  410  is in a sliding relationship with the needle cannula assembly  430  and partially surrounds it. The protrusion  432  engages the opening  411  of the adapter  410  whereby in storage the protrusion  432  is positioned at the proximal end  413  of the opening  411 . The protrusion  432  and the shape of the proximal end  413  of the opening  411  prevent the distal motion of the needle cannula assembly relative to the adapter during the merger with a luer. 
     The ID needle  400  is merged with a drug delivery device such as a syringe. The hub of the needle cannula assembly  430  is exposed for merger with say a syringe  350 . The syringe has a rod with a stopper  352  and a male luer  354  for merger with the ID needle  400 . The syringe could also have a thread component  353  engaging the needle assembly  400  through hub wings  435 . 
     The assembly is applied to the skin with some pressure, resulting in tissue deformation of the underlying skin and compliance to the adapter contact surfaces. The needle cannula  431  could be inserted into the dermis by slightly turning the needle hub CCW with the protrusion  432  moving along the adapter opening  411 . Forward thrust on the syringe after the CCW turn results in the protrusion  432  moving toward the distal end of the adapter opening  412 . The cannula position in storage is illustrated in  FIG. 26A . At the end of the distal travel the cannula is fully inserted into the dermis  370  as illustrated in  FIG. 25  and  FIG. 26B . The compound is then injected into dermis forming a drug pool illustrated as  371  in  FIG. 26C . The hub protrusion  433  located on the lever  434  of the hub is shown in  FIG. 28 . In the cannula assembly  410  the protrusion  433  is engaged with an axial slot  415  of the inner adapter cavity  416  of the adapter  410  illustrated in  FIG. 27 . The lever  434  integral with the hub  436  maintains the cannula and the adapter angular orientation during the device operation. The rotation of the hub in respect to the adapter requires a turning moment to deflect the lever  434 . This prevents unintended cannula exposure. The adapter has also another short slot  414  to facilitate the merger of the adapter  410  and the needle cannula assembly  430 . The embodiment  400  shields the cannula when not in use preventing needle pricks. This mechanism does not disable the device and allows multiple ID injection as required. 
     Yet another embodiment of the device  500  is illustrated in  FIGS. 29 through 34 . The main components include an adapter  510 , a needle cannula assembly  530  and a dermis sensor  550 . The needle cannula assembly  530  has a hub  536  retaining the cannula  531 . The hub  536  has a retention step  532  engaging the adapter lever  211  in storage position. The hub  536  also has an extension  533  with a protrusion  535  positioned on the end of  533 . 
     The adapter  510  is in a sliding relationship with the needle cannula assembly  530  and partially surrounds it. The hub  536  has side protrusions  534  engaging the guiding openings  517  of the adapter  510  whereby in storage the protrusions  534  are positioned at the proximal end of the opening  517 . The protrusions  534  and opening  517  assure the angular orientation of the needle cannula assembly  530  relative to the adapter  510  through the device operation. The lever  511  is merged with the adapter  510  through an integral hinge on the proximal end of the lever. 
     The adapter  510  has a lever  511  as illustrated in  FIGS. 29 through 33 . The lever has an end protrusion  512  engaging the hub retention step  532  of the cannula assembly  530  during storage and merger with a syringe. The side walls  514  of the lever  511  prevent accidental contact during use. 
     The dermis sensor  550  has side levers  554  connected by a cross bar  552 . The lever pivots  553  engage the adapter  510  through pivot openings  516 . The crossbar  552  rests on the bar rest  515  of the adapter  510  when in storage. The dermis contacts the central sections  551  of the side levers  554  of the sensor  550  during the application of the assembly to the skin. The contact forces acting on the side lever section  551  result in the rotation the sensor  550 . 
     When the needle assembly is applied to the dermis the sensor is rotated by the dermis contact as illustrated in  FIG. 30 . The cross bar  552  acts on the middle protrusion  513  of the adapter lever  511  and elevates the lever  511 . This lever displacement enables the distal motion of the hub  536  and the cannula  531  insertion into dermis  370 . The hub  536  is moved forward with the hub extension protrusion  535  bypassing the sensor  550  as shown in  FIG. 31 . 
     The sequential injection steps are illustrated in  FIG. 32 . The lifting of the adapter lever  511  by the bar  552  of the sensor  550  is shown in  FIG. 32A . The cannula in then inserted into dermis illustrated as illustrated in  FIG. 32B . After injection the cannula assembly is pulled in the proximal direction further rotating the sensor  550  and permanently shielding the needle. The adapter  510  and sensor  550  component designs are shown in  FIGS. 33 and 34 . 
     The execution of ID injection is substantially simplified when the ID needle is employed. The tip of the needle cannula is repeatable placed at a desired depth below the dermis surface. Furthermore many additional sites become viable while using the adapter. The adapter could be applied to the skin to any one of the broad range of sites. The assembly assures the injection is consistent in regards to the needle tip placement and compound delivery. 
     EXAMPLE 1 
     An ID adapter evaluation was conducted with a machined adapter prototype and a single use syringe. The adapter prototype was sized to accommodate in a sliding relationship BD PLASTIPAK syringe with 1 ml volume, 0.5″ long needle and cannula gage  28 . The cannula lancet had a conventional subcutaneous bevel. The injection procedure was as follows: 0.1 or 0.5 ml WFI was aspirated into the syringe; the syringe was placed in the adapter with the needle tip positioned in the cannula passageway; the adapter was applied to the desired injection site; the needle was inserted into dermis; the contents were injected; and the needle was withdrawn and the syringe discarded. The needle placement depth was adjusted to locate the cannula center line at about 0.5 mm from the dermis surface. The needle cannula length in the dermis was set at 4.5 mm. WFI volumes of 50 μl and 100 μl were tested. 
     The initial evaluation in volunteers with the injection of 0.1 ml of WFI produced blebs customarily observed during conventional ID injections. The blebs rapidly diffused. The lancet orientation did not appear to impact the injection results. 
     While the present invention has been described with reference to the specific embodiments thereof, it should be understood by those skilled in the art that various changes may be made and equivalents may be substituted without departing from the true spirit and scope of the invention. In addition, many modifications may be made to adapt a particular situation, material, composition of matter, method, method step or steps, for use in practicing the present invention. All such modifications are intended to be within the scope of the claims appended hereto. 
     All of the publications, patent applications and patents cited in this application are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent application or patent was specifically and individually indicated to be incorporated by reference in its entirety.