Patent Abstract:
A method and apparatus for attaching a connector assembly onto a vial is disclosed. The connector assembly features a protective cap, a collar attachable to the rim of the vial, and a locking ring disposed about the collar. A vial access device is contained within the collar. One or more ribs are provided adjacent a distal portion of the collar to seal against the stopper obturating the vial. The collar is provided with one or more slits which render the collar flexible in directions radial and axial to the central axis of the vial to compensate for variations in tolerances or dimensions present in the various components. Locking structure between the locking ring and the collar assures that the collar remains fixed to the vial.

Full Description:
FIELD OF THE INVENTION 
     The invention relates to a method and apparatus for fixing a connector assembly onto a vial, and more particularly, to a method and apparatus for fixing a connector assembly onto a vial which minimizes the number of components in the connector assembly and which reduces the number of microbial barriers necessary to safeguard sterility of the system. 
     BACKGROUND 
     In the art, it is generally known that to reduce inventory space or to increase the shelf life of certain drugs, or both, it is advantageous to reduce these drugs to a dry or powdered form. These dry or powdered drugs are normally stored in a sealed container such as a vial, and reconstituted into liquid form with an appropriate diluent or solvent solution prior to administration to a patient. The vials, typically formed of glass or plastic materials, include an elastomeric stopper sealing the open end of the vial. The stopper includes a portion inserted into the neck of the vial as well as a planar portion which rests on top of the vial, against the vial rim. The planar portion is normally tightly affixed to the vial rim with an aluminum crimp cap. Owing to the malleable nature of aluminum, the crimp cap readily adapts itself any differing dimension or tolerances which may exist between the stopper and the vial. The result is that the crimp cap evenly distributes sealing forces between the stopper and the vial. Thus, it has been generally recognized in the art that the vial/stopper/aluminum crimp cap solution safeguards the sterility of the drug contained within the vial over suitably long storage periods and prescribed conditions. The sizes and dimensions of the various vials and stopper components may be configured to given standards, such as given ISO standards. 
     One way to reconstitute the drug stored in the vial is to introduce the solvent or diluent from a syringe by piercing the stopper sealing the vial. Owing to various considerations, such as the convenience of the healthcare worker charged with reconstituting the drug, the art has recognized ways to transform the standard sealed vial into a system suitable for permitting safe, effective reconstitution of the drug contained within the vial. In these systems, typically, a fluid transfer assembly is connected to the neck of the vial. The fluid transfer system includes structure for connecting the vial to a source of diluent, such as diluent held in bottles, bags or syringes. The transfer assembly is thereafter activated to permit the flow of fluid into the vial to form the source of diluent, thereby reconstituting the drug. 
     In some configurations, the systems are such that standard vial stopper is eliminated in favor of fluid transfer assembly having a rubber stopper which is inserted into the neck of the vial, without the need for a planar portion which rests against the rim of the vial. This stopper remains within the neck until such time as reconstitution of the drug is desired. When the transfer assembly is activated, the stopper is urged towards the interior of the vial to open the neck, thereby permitting fluid to flow through the transfer assembly and into the vial body. Examples of such approaches include the MONOVIAL® line of drug delivery devices manufactured and sold by Becton Dickinson Pharmaceutical Systems of Le Pont de Claix, France and exemplified, for instance, by U.S. Pat. No. 5,358,501. While forming an excellent drug reconstitution system displaying superior properties, particularly convenience of use and sterility maintenance of the drug held in the vial, as typically configured these systems are useful for vial applications where the vial is of a relatively large size, typically 12 milliliters (“ml”) or more. Accordingly, some pharmaceutical companies have expressed the desire for a reconstitution approach where the vial is of a size smaller than the sizes for which the aforementioned system is normally configured. 
     In response to the aforementioned concerns, then, one logical way around the dilemma would be to convert, as exactly as possible, the characteristics associated with vial components already in use by the pharmaceutical companies, such as ISO standard vial/stopper/aluminium crimp cap components, and to implement a reconstitution system around these components for use by the healthcare worker. The prior art has considered some attempts in that regard. For instance, as exemplified by PCT Patent Application No. WO 97/10156 to Biodome, SA of Issoire Cedex, France, the aluminum crimp cap which would normally hermetically affix the planar portion of the standard stopper to the vial rim is replaced by a rubber-piercing fluid transfer assembly affixed around the neck of the vial. This rubber piercing fluid transfer assembly is activated by an end user when it is desired to reconstitute the drug held in the vial. The transfer assembly disclosed in this patent application features a fairly rigid, outermost plastic locking ring which, in theory, should lock the plastic transfer assembly firmly against the planar portion of the stopper and, hence, sealing this portion stopper against the vial rim. As has been pointed out, though, in practice, there may be significant variance between the dimensional tolerances of the glass components (the vial), the rubber components (the stopper) and the plastic components (the fluid transfer assembly) forming the system. The malleable nature of the aluminum crimp cap takes into account differences in tolerances. However, owing to the rigid characteristics of the sealing ring, with this approach, there may be the possibility that given a particular vial, stopper, or transfer assembly, the sealing forces realized by the outside sealing ring against the stopper and the vial may not be sufficient or otherwise uniform. Accordingly, the potential contamination of the drug, given the environmental stresses to which the vial may be subject to during manufacture, shipping, or storage, presents a concern. 
     Accordingly, there is a need for a safe and effective drug reconstitution system, wherein a fluid transfer assembly is affixed to a standard vial and stopper arrangement in a manner such that the sealing forces achievable by an aluminum crimp cap are effectively replicated. Such a drug reconstitution system is disclosed herein. 
     SUMMARY OF THE INVENTION 
     The present invention addresses the aforementioned concerns in a convenient and cost-efficient manner. A connector assembly in accordance with the present invention is designed to be employed with a standard vial and stopper so as to be able to be processed by a pharmaceutical manufacturer with standard processing equipment. The connector assembly is fully able to account for dimensional variances or tolerance variances in the vial or stopper components or in the components forming the connector assembly itself, so as to ensure good microbiological barrier characteristics. 
     The connector assembly features a protective cap for covering the open end of the vial neck. The cap includes an open proximal end, a closed distal end, and a shield wall formed therebetween. A collar is provided adjacent the open proximal end of the cap. The collar can be molded with the cap, or it can be separately manufactured and thereafter affixed to the cap. The collar features a proximal end, a distal end, and a sidewall therebetween. One or more rib elements are provided on an interior portion of the collar adjacent the distal end, and the ribs designed to form a tight seal against the stopper as the collar is positioned against the stopper. Interior portions of the collar can be configured to mate with a vial access device provided to pierce the stopper. One or more deflectable latches are provided about the proximal end of the collar. Each of the latches includes locking means deflectable about the rim of the vial for securely attaching the collar to the vial. 
     A defining aspect of the collar is the provision of one or more slits or cuts in the sidewall. These slits or cuts are designed so as to permit the sidewall to flex in axial and radial directions respective of the neck of the vial. In this manner, the sidewall is rendered more flexible respective of the vial neck, allowing the collar to compensate for any dimensional or tolerance variances in the vial, the stopper, or in the connector assembly itself. 
     A ring is provided about the sidewall of the collar. The ring defines an annulus section with an interior surface slidingly placed about the sidewall. The ring is designed to lock the collar to the rim of the vial. As the collar is locked to the rim of the vial, the collar is tightly thrust against the stopper, thereby ensuring a proper seal of the stopper to the vial. Additionally, the ribs provided in the internal portion of the collar form an additional microbiological barrier against the ambient environment. 
     Cooperative locking structure is provided between the ring and the sidewall of the collar to ensure that the collar is not displaced from its tight sealing action with the vial neck. In one embodiment, the cooperative locking structure can be formed as ratcheting teeth provided between the sidewall of the collar and the annulus section of the ring. 
     The connector assembly can be shipped to a pharmaceutical manufacturer such that the ring is retained in an unlocked position respective of the collar. In the cleanroom environment where the vial is filled with a medicament and the stopper is placed against the rim, the connector assembly can be attached to the vial. The connector assembly is transferred from a first position, whereby the collar is placed around the rim and the distal end of the collar spaced from the stopper, to a second position, whereby the deflectable latches of the collar are thrust about the outside surface of the rim and against an underside portion of the rim. By this action also, the ribs provided in the interior of the collar are thrust into sealing relation with the stopper. Thereafter, either in the cleanroom environment or outside of it, as desired, the ring may be urged distally of the collar towards a locked position respective of the collar. The proximal end of the ring is thus urged against the latches, securing the latches in place, and ensuring that the collar is securely locked to the vial. The slits provided in the sidewall of the collar allow the collar to compensate for any dimensional or tolerance variations present in the vial, the stopper, or in the connector assembly itself. 
     If desired, the cap and collar can be manufactured in such a manner such that the cap is removable from the collar by a twisting action, permitting a user a convenient way to engage the vial access device held by the connector assembly. In one configuration, the cap can be formed with the collar with a frangible connection formed from a material—such as a thermoplastic elastomer—that is different from the material forming the cap and collar itself, such as polypropylene or polyethylene. The user may simply twist the cap such that the frangible connection shears, allowing the user to remove the cap from the collar to expose the vial access device. One way to achieve this construction is through a co-injection process. All in all, the minimization of the number of components forming the connector assembly results in a concomitant reduction in the number of biological barriers necessary to safeguard the sterility of the vial access device as well as the medicament contained within the vial. 
     In an alternate embodiment, the ring is eliminated in favor of a conventional aluminum crimp cap. The crimp cap is affixed around the collar to secure the collar to the vial rim. If desired, the crimp cap can be supplied to the customer pre-attached to the collar but in an uncrimped state. Thus, the with the connector assembly itself secured to the vial in sealing relation with the stopper, the crimping operation itself need only occur outside of the cleanroom. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     The invention will now be described in detail by way of reference to the appended drawings, wherein: 
     FIG. 1 is an exploded view of a first embodiment of the connector assembly in accordance with the present invention; 
     FIG. 2 is a cross-sectional view of FIG. 1; 
     FIG. 3 is a cross-sectional view depicting placement of the connector assembly against the vial in a first position, wherein the collar is placed around the rim; 
     FIG. 4 is a cross-sectional view depicting placement of the connector assembly against the vial in a second position, whereby the latches provided on the collar are thrust against an underside portion of the rim; 
     FIG. 5 is a cross-sectional view depicting movement of the ring to a locked position respective of the collar; 
     FIG. 6 is a cross-sectional view depicting the cap removed from the collar to expose the vial access device, and the subsequent actuation of the vial access device against the stopper; 
     FIG. 7 is a cross-sectional view of the connector assembly; 
     FIG. 8 is a cross-sectional view depicting locking structure provided between the ring and the collar; 
     FIGS. 9A and 9B depict two manners of configuring a frangible section between the cap and the collar to permit removal of the cap from the collar to expose the vial access device. 
     FIG. 10 is an exploded view of a second embodiment of the connector assembly in accordance with the present invention; 
     FIG. 11 is a cross-sectional view of FIG. 10; and 
     FIG. 12 is a cross-sectional view depicting placement of the connector assembly of FIGS. 10 and 11 against the vial rim. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS 
     A convention used throughout this application is that the term “proximal” denotes a distance closest to rim  14  of vial  10 , while the term “distal” denotes a distance furthest from the rim of the vial. 
     Turning to the drawings, wherein like numerals denote like components, FIGS. 1 and 2 illustrate a first embodiment  30  of a connector assembly for a vial  10  in accordance with the present invention. Vial  10  is characterized by a bottom wall  11 , a sidewall  13 , a neck  12  and an annular rim  14 . Annular rim  14  includes an underside portion  18 , a side portion  20 , and a top surface  16 . A stopper  22  is typically employed to obturate an open end  17  associated with the vial. Stopper  22  features a planar portion  24  covering top surface  16  of the rim, and a plug portion  21  obturating the inside surface  19  of neck  12 . Vial  10  is typically filled with a desired medicament, such as a dry drug or a lyophilized drug, and thereafter affixed with stopper  22 , in a cleanroom environment. For the purposes of this invention, it will be realized that the dimensions and characteristics of vial  10  and stopper  22  can be conformed to various accepted standards, such as ISO standards, governing vials and stoppers intended for medicamental use. 
     As previously explained, a drawback in the art is ensuring that proper sealing forces exist between stopper  22  and vial  10 . It would also be advantageous to incorporate a solution to this problem in a vial connector assembly that is easily processed by the pharmaceutical manufacturer and which, desirably, can be fully processed in the cleanroom environment where medicaments are processed, introduced into the vial, and stoppered within the vial. 
     With the foregoing in mind then, a first embodiment  30  of the connector assembly of the present invention is provided. Connector assembly  30  is formed of three principal components, namely, a cap  32 , a collar  42 , and a ring  60 . 
     Cap  32  is characterized by a closed distal end  34 , an open proximal end  36 , and a shield wall  38  therebetween. Cap  32  is provided adjacent collar  42 . Cap  32  and collar  42  can be formed together, such as by a co-injection process, or they can be separately formed and joined together by mechanical means, welding, or the like. In a preferred construction, cap  32  and collar  42  are formed together and connected by a frangible section  100 , as will be hereinafter discussed. 
     Collar  42  is designed to mate with rim  14  of the vial. Collar  42  is located adjacent open proximal end  36 . Collar  42  includes an upstanding tubular section  38  defining an interior portion  35 . Interior portion  35  serves to engage a vial access device, as will be more fully explained hereinbelow. Adjacent tubular section  37  there is provided a vial attachment section  39 . Vial attachment section  39  of the collar displays a distal end  44 , an open proximal end  46 , and a sidewall  48  therebetween. One or more sealing ribs  40  are provided, on an interior portion of vial attachment section  39 , adjacent distal end  44 . Ribs  40  can take any shape appropriate to their sealing function such as rounded, peaked, square, or other geometries. 
     One or more deflectable latches  52  are provided about the proximal end of collar  42 . Deflectable latches  52  feature a proximally facing, outwardly canted surface  53  and a distally facing, inwardly canted surface  54 . Outwardly canted surface  53  facilitates movement of collar  42  over the outside portion of rim  14  for movement of the collar from a first position, wherein sealing ribs  40  are spaced from planar portion  24  of stopper  22  (FIG.  3 ), to a second position, where sealing ribs  40  are engaged in surface contact with the planar portion of stopper  22  (FIG.  4 ). Inwardly canted surface  54  serves to lock the collar against underside portion  18  of the rim in the second position. In effect then, by properly configuring the dimensions of the various components, latches  52  of the collar will lock onto the underside of the rim, causing a sealing force to be applied by sealing ribs  40  against stopper  22 . 
     A distinguishing feature of the collar is its ability to compensate for dimensional or tolerance variances between the stopper, the vial, or the connector assembly itself, so as to ensure that uniform sealing forces are applied over the surface of stopper  22 . To this end, collar  42  is formed such that a plurality of slits  50 A and  50 B (collectively, slits  50 ) are disposed throughout sidewall  48  of the vial attachment section. Referring to FIGS. 1,  2  and  7 , one or more slits  50 A are formed in sidewall  48  in a direction radial to a central axis “X” defined by collar  42 . As best seen in FIG. 1, slits  50 A take the appearance of circumferential cuts about sidewall  48 , and preferably, they do not extend about the entire circumference of sidewall  48 . In addition, one or more slits  50 B are formed in sidewall  48  in a direction parallel to central axis X. As best seen in FIG. 1, preferably, slits  50 B are placed adjacent open proximal end  46  of the collar. The effect of slits  50  is to impart a degree of elasticity or flexibility to collar  42 , allowing it to account for dimensional or tolerance variances in the various components. 
     For instance, the existence of slits  50 A imparts a degree of flexibility to vial attachment section  39  of the collar in an axial direction parallel to central axis X. Thus, if for some reason the thickness “C” of planar portion  24  of the stopper or the thickness “B” of side portion  20  of the rim (FIG. 1) is not uniform, the vial attachment section of collar  42  can flexibly respond in an axial direction to account for those variances. That is to say, the distance measured between ribs  40  and inwardly canted surface  54 —the two principal structures of collar  42  that engage stopper  22  and rim  14 , respectively—will be adapted to the thicknesses “B” and “C” displayed by the rim and stopper, respectively. Similarly, slits  50 B impart a degree of flexibility to the collar in directions radial to central axis X. Thus, for instance, if the shape of side portion  20  of the rim is not uniformly round, collar  32  may flexibly respond in a direction radial to central axis X to compensate. It is important to note, too, that the hardness displayed by the materials forming either of stopper  22  or vial  10  may affect the ultimate combined thicknesses “B” and “C” of the rim and stopper and, thus, the sealing force ultimately exerted by ribs  40  against the stopper. Thus, the provision of slits  50  help to compensate for such variances as well. All in all, then, the sealing force imparted by ribs  40  will be constant from one connector assembly  30  to another. 
     Preferably, to ensure uniform sealing forces between the stopper and the rim, the collar is configured such that the height “D” (FIG. 7) between ribs  40  and inwardly canted distally facing surface  54  of the latches is at least equal to, if not slightly less, than the combined thickness B+C of rim  14  and planar portion  24  of the stopper, respectively, when collar  32  is in an unflexed condition. Similarly, inside diameter “E” measured between diametrically opposite latches  52  (FIG. 7) should be chosen such that it is at least equal to, or slightly less than, outside diameter “F” of rim  14  (FIG. 3) when the collar is in an unflexed condition. By unflexed condition, what is meant is that slits  50 A are not compressed or expanded axially, and that slits  50 B are not compressed or expanded radially, from their original configuration on sidewall  48 . 
     Ring  60  is disposed about collar  32 . Ring  60  serves to lock the collar to the rim in the second position. Ring  60  includes a proximal end  64 , a distal end  62 , and an annulus section  66  therebetween. Annulus section  66  preferably displays an inside diameter “G” at least equal to, if not slightly less than, outside diameter “H” of sidewall  48  (FIG.  2 ). Ring  60  includes an internally projecting rib  70  adjacent proximal end  64 . An inwardly canted, distally facing locking surface  72  is provided on rib  70 . Locking surface  72  is designed to mate with a cooperating outwardly-canted, proximally facing locking surface  55  provided on an exterior surface of latches  52  of the collar. 
     Cooperating locking structure is provided between the ring and the collar. This locking structure, denoted by numeral  68   b  for the collar and numeral  68   a  for the ring, can be structured in a variety of manners. Referring to FIGS. 2 and 8, locking structure  68   a  and  68   b  can take the form of cooperating ratcheting teeth formed about the respective circumferences of sidewall  48  of the collar ( 68   b ) and annulus section  66  of the ring ( 68   a ). Each of the sets of ratcheting teeth are placed adjacent the respective distal ends  62 ,  44  of the ring and collar, respectively. Alternate structure can also be envisioned for the locking structure. For instance, cooperative threads can be substituted for the ratcheting teeth. Other structure within the realm of the skilled artisan is also possible. 
     Connector assembly  30  typically encloses a vial access device  80 . Vial access device  80  is structured to pierce stopper  22  so as to gain access to the medicament held by vial  10 . While not limited in scope, in general vial access device  80  may feature a body  82  in frictional engagement with an interior surface  35  associated with tubular section  37  of the collar. A distally facing piercing element  84  is mounted to the body. A connector end  86 , attached in fluid communication to piercing element  84 , is provided to mount the vial access device to an external component such as a syringe, a rigid bottle, a flexible bottle, or the like. It will be realized by the skilled artisan that piercing element  84  can take various configurations, such as a pointed metallic or plastic needle, a spike, or any pointed structure serving to pierce stopper  22 . Similarly, connector end  86  can be configured as a spike, a needle, as a luer connector, or any other desirable configuration to mate with the various external components, such as rigid fluid bottles, luer lock or luer slip syringes, flexible fluid bags, or the like, with which an end user will want to employ with the connector assembly. 
     Operation of the connector assembly will now be explained, referring principally to FIGS. 3-6. 
     In practice, the pharmaceutical customer would process or otherwise fill a desired medicament in vial  10 , thereafter applying stopper  22  to the vial neck. Both of these operations would occur in a cleanroom environment. As illustrated in FIG. 3, the component manufacturer would normally supply connector assembly  30  to the pharmaceutical manufacturer in a pre-assembled sterile state, ready to apply to an already stoppered vial. 
     As illustrated in FIG. 3, in the pre-assembled state, ring  60  is positioned about collar  42  such that ring  60  is in an unlocked position respective of the collar. That is to say, proximal end  64  of the ring is displaced proximally way from proximal end  46  of the collar, such that locking surface  72  of internally projecting rib  70  on the ring is displaced from contact with outwardly canted surface  55  of latches  52 . Latches  52  are thus free to flex respective of sidewall  48 , particularly along slits  50 A,  50 B. Locking structure  68   a ,  68   b  retains the ring to the collar. Vial access device  80  is enclosed inside cap  32  and collar  42 . Pre-assembled connector assembly  30  is thus placed over vial  10  directly in the cleanroom, with open proximal end  64  of the ring passing around side portion  20  of rim  14 . It will also be seen that outwardly facing, proximally directed surface  53  of the latches have engaged against the periphery of planar portion  24  of the stopper at this time. 
     FIG. 4 illustrates placement of the connector assembly in its second position relative to vial  10 . Here, outwardly facing, proximally directed surfaces  53  have been urged over outside portion  20  of the rim, and inwardly facing, proximally directed surfaces  54  of the latches have engaged underside  18  of the rim. At the same time, ribs  40  provide adjacent distal end  44  of cap  42  have descended upon stopper  22  such that they are engaged in tight sealing contact with planar portion  24 . At this time also, ring  60  continues to be displaced in an unlocked position relative to collar  42 . Note that ring  60  continues to be located in an unlocked position relative to collar  42 . Thus, as the collar is displaced to its second position relative to the vial rim, the sidewall can flex both radially and axially to accommodate any dimensional or tolerance variances, as previously described. Equal forces will be exerted by the collar across the surface of the stopper, ensuring a proper seal between the stopper and the vial. 
     Once the connector assembly has been urged to the second position such that it has locked against the rim and a seal has been formed between ribs  40  and planar portion  24  of the stopper, the connector assembly and vial can be removed from the cleanroom environment for the final assembly step, represented by FIG.  5 . Of course, it will be understood that this step can take place in the cleanroom, if desired. In FIG. 5, ring  60  is displaced distally respective of collar  42  until a locked position is reached. In the embodiment shown, ratcheting teeth  68   b  of the ring are displaced distally of ratcheting teeth  68   a  of the collar, until such time as locking surface  73  of internally projecting rib  70  of the ring presses tightly against outwardly canted surface  55  of latches  52 , and inwardly canted, proximally facing surface  54  mates tightly with underside portion  18  of the rim. Continued distal displacement of the ring relative to the collar also causes ribs  40  to bite tightly into planar portion  24  of the stopper, thereby ensuring a good microbiological seal between the ribs and the stopper. At the same time, stopper  22  is also pressed into good sealing contact with rim  14 , ensuring a good microbiological seal between the two. The effect is that two microbiological barriers are created—one between the sealing ribs and the planar portion of the stopper, and one between the planar portion of the stopper and upper surface  16  of the rim—in a uniform manner across the entire planar portion of the stopper. Vial access device  80  is thus secured in microbiological isolation within connector assembly  30 , and stopper  22  tightly sealed to vial  10  so as to isolate the drug held by the vial. Locking structure  68   a ,  68   b  between the ring and the collar will retain the two in locked position. Connector assembly  30  is now securely affixed to the vial, and the pharmaceutical manufacturer may ship the filled vial to the end user. 
     To employ the vial, cap  32  must be removed from collar  42  so as to expose vial access device  80 . While various ways can be configured to so remove the cap, FIGS. 9A and 9B illustrate forming cap  32  and collar  42  together and connecting them by a frangible section  100 . Frangible section  100  permits a user to apply a twisting force to cap  32  so as to remove the cap from the collar to expose vial access device  80 . Cap  32  and collar  42  may be formed together by a co-injection process, wherein a material having a low shear resistance is employed for frangible section  100 , and a material having a higher shear resistance is employed for the rest of the cap and the collar. For instance, frangible section  100  can be formed by employing various thermoplastic elastomers (“TPE”) displaying low shear resistance, and which display good adhesion properties to the material chosen for the rest of the cap, which typically can be polypropylene or polyethylene. 
     As illustrated in FIG. 9A, frangible section  100  can be configured as a series of TPE pockets, or “teeth”,  110  that are molded into an interior section  112  defined between cap  32  and collar  42 . Teeth  110  are interspersed with intervening sections  116  of the section  100 , the intervening sections formed from the more shear resistant material that makes up the remainder of cap  32  or collar  42 . The resulting frangible section  100  allows a user to exert a moderate twisting force “TF” against the cap to remove it. At the same time, the presence of intervening sections  116  strengthen the frangible section against inadvertent removal of the cap caused, for instance, by jostling during shipment, inadvertent opening by an end user, or the like. Alternately, as illustrated in FIG. 9B, if desired, frangible section  100  can be formed as a solid section  120  of TPE material across interior section  112 . In any event, by forming cap  32  and collar  42  as a single unit, an additional, portential area for microbiological contamination—the juncture between the cap and the collar—is eliminated, leading to a concomitant reduction in the number of microbiological barriers needed. 
     It will also be realized that cap  32  and collar  42  can be formed separately and attached by various means, such as by welding, adhesives, or the like. That will safeguard integrity of the connection between the cap and the collar, but that will provide a reasonable force to permit a user to remove the cap. 
     In use then, cap  32  is removed from collar  42 , and vial access device  80  exposed. FIG. 6 illustrates activation of the vial access device. An external component (not shown) is attached to connector end  86 , and a proximally directed force applied. Piercing element  84  is urged through stopper  22  and in communication with the interior of the vial. 
     Body  82  is slidably disposed with respect to interior surface  35  of shield wall  38 . The engagement between body  82  and interior surface  35  can be by frictional engagement, via mechanical engagement such as by threaded engagement or by a lot and follower arrangement, or by other arrangements within the realm of the skilled artisan, If desired, body  82  can be retained against inadvertent removal from shield wall  38  by providing a stop  88  adjacent a proximal end of body  82  that is arrested by a shoulder  89  inside shield wall  38 . 
     FIGS. 10-12 illustrate a second embodiment  230  of a connector assembly in accordance with the present invention. In describing this embodiment, like components are described as for the embodiment of FIGS. 1-5 above, except that a prefix “2” is supplied to the numerical designation for those components. Accordingly, detailed description of those like components need not be repeated for embodiment  230 . 
     Here, connector assembly  230  is substantially as before described, except that the ring  60  of the prior embodiment  30  is replaced by a conventional aluminum crimp cap  260 . Cap  232  and collar  242  are formed as their counterparts in embodiment  30 , except that locking structure  68   a  is omitted from the collar as no ring is required. 
     As before, connector assembly  230  is supplied to a pharmaceutical manufacturer in a pre-assembled, sterile state, with vial access device  280  engaged in the interior of shield  232 . In the confines of the cleanroom, collar  242  is placed in one operation over vial rim  214 , such that latches  252  engage underside  218  of the vial rim. Ribs  244  engage planar portion  224  of the stopper to form a tight seal, with collar  242  flexibly accommodating the stopper and rim via slits  250 A,  250 B. Thereafter, with the connector assembly attached to the vial in a sealing manner, the connector assembly and vial can be removed from the cleanroom so that crimp cap  260  can be applied about distal end  244  and proximal end  246  of the collar, locking the collar to the vial. As before a frangible section (here again denoted by numeral  100 ) can be incorporated between cap  232  and collar  242 . 
     If desired, the connector assembly can be supplied with crimp cap  260  pre-attached to collar  242  in an uncrimped condition, such that connector assembly  230  together with the uncrimped crimp cap  260  are applied to the vial in the cleanroom. Thus, the only operation which need occur outside of the cleanroom is the actual crimping operation. 
     The various components can be constructed from materials standard in the art. For example, the cap, the collar, and the ring can be injection molded from various thermoplastics (the construction of the frangible section having been already explained). The vial access device can be made from various medical grade plastics, medical grade stainless steels, combinations of these materials, or the like. Various rubbers or elastomers can be chosen for the stopper, and the vial can be made from suitable glass or plastics materials adapted to the drug held therein. If desired, various tamper evidence means, such as heat shrunk plastic strips, can be incorporated between the vial and the collar. 
     It will be appreciated and understood by those skilled in the art that further and additional forms of the invention may be devised without departing from the spirit and scope of the appended claims, the invention not being limited to the specific embodiments shown.

Technology Classification (CPC): 0