MXPA97007388A - A lyophilization closure assembly for a medicinal container for use during a liofilization process - Google Patents

Abstract

The present invention relates to a lyophilization closure lensamble for a medicament container having an open top and an edge surrounding said open top portion, comprising: a body secured around the open top of the container, having the body a distal wall disposed on the open top of the container and a skirt surrounding the rim of the container, a central passage provided in the distal wall, the skirt having a distal end, a proximal end and one or more steam passages formed between these, the body including one or more deflectable fingers cooperatible with the container edge and provided in the middle of the distal and proximal ends of the skirt, the body having a first position, wherein the raised body of the open upper part of the container such that the steam passages communicate with the upper part open, and a second position, where the deflecting latches block the At the edge and the steam passages does not communicate with the open top of the container, an elastomeric closure secured inside said body to seal the upper part of the container when the body is in the second position, the elastomeric closure having a stopper for sealing the open upper part of the container, and an upper surface facing the central passage of the distal wall, the plug sized to be spaced from the open top of the container when the body is in the first position such that the open upper communicates with the passages of vapor from the skirt, and a membrane secured removably through the central passage of the distal wall and hermetically enclosing the upper surface of the

Description

A LYOPHILIZATION CLOSING ASSEMBLY FOR A MEDICINAL CONTAINER FOR USE IN A LYOPHILIZATION PROCESS Field of the Invention The invention relates to a lyophilization closure assembly for a medicament container, and more particularly, to a lyophilization closure assembly. for a medication container that is self-supporting with the container and that can be easily sealed to the container within the sterile environment of the lyophilization chamber. Background In order to improve the shelf life of certain drugs, a pharmaceutical manufacturer can subject the drug to a lyophilization process. In the lyophilization process, a liquid medicament contained in a container or bottle is subjected to a freeze-drying process to extract the aqueous content of the medicament, leaving the active components of the medicament in a crystalline state. I-A Figure 11 illustrates a prior art manner for effecting a lyophilization process. A container 600 includes an edge 614 and has an amount of medicament 616 to be lyophilized. Before the container is introduced into the freeze dryer, a lyophilization plug 620 having a plug 626 is partially inserted into the neck 618 of the container. The plug 626 includes a slot 622 which, when the plug is partially inserted in the neck, communicates the interior of the container with the freeze dryer, the vapors generated during the freeze-drying process escaping from the container. After the lyophilization operation, projections provided within the freeze dryer are typically lowered against the flange 624, such that the plug 626 is fully inserted into the neck 618 to seal the medicament within the container. After the sealing operation, the lyophilization plug has to be secured to the container. Typically, in order to do this, the container is removed from the sterile environment of the freeze dryer, and an undulated aluminum lid is applied around the flange 624 and the edge 614 to secure the lyophilization closure to the container. The corrugated lid typically incorporates a removable lug placed over a central area of the lyophilization plug. The removable lug allows a user to have access to the central area and, up to a point, it can serve as an inviolable medium for the container. The removable lug also serves, to some extent, as a means of preserving the cleanliness of the top surface of the lyophilization plug. In practice, the lyophilized medicament is accessed shortly before use by removing the plug from the corrugated lid to access the lyophilization closure. The closure is punctured, and a solvent solution such as a saline introduced into the bottle to reconstitute the powdered or lyophilized medicament. Once reconstituted, the medicine solution is extracted from the bottle to be used. Although in general these assemblies work well to safely store the medication before use, there are certain disadvantages that deserve to be mentioned. The removable studs associated with corrugated aluminum caps have sharp edges, which can pierce safety gloves worn by practitioners if not practiced with proper care. In addition, most of the corrugated lids used with jars of the prior art are not constructed, nor processed in a manner to maintain sterility of the top surface of the closure. As a result, the central area of the lyophilization closure of the prior art must be sterilized, for example, with an alcohol solution, before the closure is punctured. There are additional disadvantages at the level of pharmaceutical manufacturer. Lyophilization is typically conducted in the sterile environment of the freeze dryer. It is the case, sometimes, that the slots provided in the lyophilization closure offer a passage restricted to the vapors generated. Due to the groove, the molds are more complicated than with most standard designs. Also the closure plug is longer than it could be without the slot meaning that more rubber material is needed.

As has been explained, in order to ensure closure to the bottle, additional equipment is necessary, such as equipment to apply the corrugated lid to the edge of the bottle. The undulation operation is normally carried out separately to the lyophilization operation and outside the sterile environment of the lyophilization area. This adds time and expense to the manufacturing operation. In addition, because the upper surface of the lyophilization closure is exposed to a non-sterile environment during the corrugation operation, an end user must sterilize the upper surface of the lyophilization closure such as with an alcohol solution before the medicine can be accessed.

Summary of the Invention A lyophilization closure assembly is described for a medication container, such as a bottle or flask. The lyophilization closure assembly, which is self-supported in the container, can be attached to the container while the medication is subjected to a lyophilization process, to provide an unobstructed passage, free of vapors generated during the lyophilization process. The lyophilization closure assembly after this can be sealed against the container and attached thereto while in the sterile environment of the lyophilization chamber. The lyophilization closure assembly thus allows the lyophilization operation and the subsequent complete seal operation to occur in one step, eliminating the need for an additional process outside of the sterile environment in which the lyophilization operation takes place. The lyophilization closure assembly includes a body supported around the edge of the container. The body includes a distal wall facing the open top of the container and a skirt that is placed around the edge. The skirt includes one or more deflectable arms engageable with the edge and one or more steam passages through which the vapors generated during a lyophilization process can escape. The body is positioned around the edge between a first position, wherein the medicament in the container is subjected to a lyophilization process, and a second position, wherein the lyophilization closure assembly is sealed to the container. An elastomeric closure for sealing the open top of the container is retained within the body. The elastomeric closure has a cap for sealing the open top of the container, and an upper surface facing towards and away from the open top of the container. The distal wall of the body defines an opening on the upper surface of the elastomeric closure that defines an access area. A membrane is removably secured to the body above the access area on the upper surface of the elastomeric closure. The membrane includes a pull-tab that allows the practitioner to remove the membrane from the body when it is desired to have access to the medication. In use, the lyophilization closure assembly is secured to the container in a first position, wherein the elastomeric closure is spaced from the open top of the container. The vapors generated during the lyophilization process can escape from the container via the vapor passages provided in the body. Subsequent to the lyophilization operation, and while the container remains in the lyophilization chamber, the lyophilization closure assembly can be urged to the second position, where the body is locked to the container's edge and the elastomeric seal is positioned to seal the open top of the container. Accordingly, lyophilization and complete seal operations can occur in a single process within the sterile environment of the freeze-drying chamber, obviating the need for an additional sealing operation outside the sterile environment in which lyophilization takes place. The elastomeric closure can be formed of various rubber materials, the body can be formed of various rigid materials such as plastic materials, and the membrane can be formed of various plastic materials, composite materials, paper materials, sheet metal materials, TYVEK materials, or the like. The various components can be separately supplied to a pharmaceutical manufacturer in a sterile state, for the pharmaceutical manufacturer to assemble the components in a lyophilization closure assembly. Alternatively, the lyophilization closure assembly can be supplied to a pharmaceutical manufacturer in a pre-assembled sterile condition, for the pharmaceutical manufacturer to apply the pre-assembled sterile assembly to the medication container. The sterile membrane hermetically encloses the access area of the elastomeric closure, eliminating the need to sterilize the upper surface, such as with an alcohol solution, before using the medicament. Also, the sterile membrane provides evidence of tampering for the contents held within the container. If desired, a washer may be incorporated in the upper surface of the elastomeric closure. The washer includes an opening disposed on the upper surface of the closure which defines an access area on the upper surface of the elastomeric closure. The membrane can be removably secured to the washer, and if desired, extended to a portion of the body. BRIEF DESCRIPTION OF THE DRAWINGS The invention will now be described in greater detail by reference to the accompanying drawings, in which: Figure 1 is a perspective view of the sterile closure for a container or flask according to the present invention.; Figure 2 is a cross-sectional view of one embodiment of a sterile closure according to the present invention; Figure 2a represents an alternate form for configuring a sterile closure according to the present invention; Figure 2b represents an alternate form for configuring a sterile closure according to the present invention; Figure 3 is a cross-sectional view of one embodiment of a sterile closure according to the present invention incorporating enhancer-of-sterility ribs; Figure 4 is an alternative embodiment of the sterile closure shown in Figure 3; Figure 5 is a top view of an elastomeric closure usable with a sterile closure according to the present invention; Figure 6 depicts a cross-sectional view of a washer for a sterile closure according to the present invention; Figure 7 depicts an alternative embodiment of a washer for a sterile closure according to the present invention; Figure 8 is a cross-sectional view of a lyophilization closure assembly for a medical container in accordance with the present invention; Figure 8a depicts a transfer body usable with the lyophilization closure assembly of Figure 8; Figure 9 depicts the lyophilization closure assembly of Figure 8 subsequent to a lyophilization process; Figure 10 depicts an alternate embodiment of a lyophilization closure assembly according to the present invention; and Figure 1 represents a prior art manner for effecting a lyophilization process.

Detailed Description of the Preferred Modalities Although the description and figures herein refer to a bottle or bottle, it will be understood and appreciated by the skilled artisan that any type of container normally employed in the field of attempt, such as capsules, bottles or similar containers are easily sensitive to the advantages described herein. In addition, although described herein in relation to containers having a quantity of dry drug or drug for reconstitution by liquid obtained from an external source, it will be appreciated by the skilled artisan that the invention is not so limited. For example, the invention can be applied to containers containing therein a quantity of liquid medication. For the purpose of simplification, a sterile closure assembly according to the present invention will be described first, followed by a description of how the features of the sterile closure assembly according to the present invention can be implemented in a lyophilization closure assembly. . Turning now to Figures 1 and 2, the sterile closure assembly 20 according to the present invention can be applied to a medical container 10, such as a bottle or bottle, having a distal end 12, and a proximal end 14 , and that contains a load of medication 16 in it. As will be further described below, the loading of medicament 16 may involve, for example, a loading of medicament subject to a lyophilization process. The medication container 10 includes a neck 18 characterized by an open top 15. The open top 15 is surrounded by an edge 17 having an upper surface 13 and a lower surface 19. The sterile closure assembly 20 according to present invention includes an elastomeric closure 22 for sealing the open top 15 of the medication container. The elastomeric closure, which may be configured from a rubber material, includes a plug 24 preferably having a diameter "A" at least equal to, if not slightly larger than, the diameter "B" of the neck 18 to comfortably close the open top 15. The elastomeric closure 22 further includes a flange portion 28 configured to rest on the upper surface 13 of the edge 17, and preferably, structured and otherwise arranged to substantially cover the entire area of the surface 13 of the edge. An upper surface 26 is provided in the elastomeric closure which faces towards and away from the open top of the container. The upper surface 26 includes an access area 26a intended to be accessed by a practitioner who wishes to employ the medicament 16 contained within the container 10. As previously explained, in the closures of the prior art, a practitioner was typically forced to sterilize the surface upper 26, such as with an alcohol solution, before using the bottle. The reason for this is that in the prior art the corrugated aluminum caps typically employed to retain the closures in the bottle were not constructed or otherwise processed to maintain sterility of the upper surface of the closure. An advantage of the sterile closure assembly 20 according to the present invention is that it can be constructed in such a way that the closure 20 is presented in a sterile state, ready-to-use at the end-user level. One way to ensure the sterility of the closure 20 is to remove a conventional corrugated aluminum lid incorporating a removable lug, in favor of the construction described herein. A washer 30 is configured to be placed on the upper surface 26 of the elastomeric closure 22. The washer 30 includes a bottom surface 30A which contacts the upper surface 26 of the elastomeric closure along an interface 37. Preferably, the interface 37 covers the entire area of the bottom surface 30A. The washer 30 defines an opening 32 disposed on the upper surface 26 that delimits the access area 26A provided on the upper surface 26. Figure 2 illustrates a membrane 34 which is removably secured to the washer 30 along an upper surface 35 of the washer. The membrane 34 protectably encompasses the access area 26A of the upper surface 26 in a sterile manner and is preferably fixed to the washer to hermetically seal the access area 26A of the elastomeric closure. The membrane 34 preferably includes a leg-of-throw 36 which allows a user to separate the membrane 34 from the washer when it is desired to have access to the elastomeric closure.

The entire bottle closure 20 can be secured to the edge 17 of the bottle, for example, by a corrugated lid 38. The corrugated lid 38 can be formed of any suitable rigid material, such as plastics, metals or the like. As illustrated therein, the corrugated lid 38 engages the upper surface 35 of the washer and the lower surface 19 of the edge 17, thereby pressing the washer 30 tightly against the flange 28 of the elastomeric closure, and securing both to the edge 17 of the bottle. In addition to the characteristics for maintaining sterility, the material selected for the membrane 34 preferably avoids sharp edges to avoid the problems with conventional corrugated aluminum covers, previously described. Also, it will be appreciated by the skilled artisan that in addition to ensuring the sterility of the access area 26A, the membrane 34 provides evidence of forcing for the contents held within the container 10. It will be appreciated and understood by those skilled in the art that the elastomeric closure 22, washer 30 and membrane 34 can be supplied separately to the pharmaceutical manufacturer in a sterile condition, and assembled by the pharmaceutical manufacturer in a bottle closure assembly 20 during processing of the medication container. Alternatively, the sterile closure assembly 20 can be supplied to the pharmaceutical manufacturer in a pre-assembled sterile condition, allowing the pharmaceutical manufacturer to process the vial closure assembly 20 as a single unit. The elastomeric closure 22 may be formed from various rubber materials, while the washer 30 may be formed from suitable rigid materials, including various plastic materials. The membrane 34 may be designed from another suitable material, such as plastic materials, composite materials, paper materials, sheet metal materials, TYVEK materials or the like, which provide maintenance of sterility of the elastomeric seal. The membrane 34 can be secured to the washer 30 by means of adhesives, heat sealing, adhesion or other suitable methods to the materials used for the membrane and the washer. It will be understood by the skilled artisan that the elastomeric closure 22 and the washer 30 can be jointly formed such by a co-injection process.

Similarly, the washer 30 and the membrane 34 can be formed together as by a co-injection process, if desired. Alternatively, the three components, the elastomeric closure, the washer and the membrane, can be formed together by an appropriate co-injection process, if desired. It is preferable that the washer 30 and the elastomeric closure 22 are arranged in full surface contact with each other to effect a good seal between these components. Particularly when the washer 30 is supplied separately from the elastomeric closure 22, a structure can be incorporated in the interface 37 to improve the sealing contact between the washer 30 and the upper surface 26 to account for any molding irregularities, tolerance irregularities or Similar. As seen in Fig. 3, one or more sealing ribs 42 can be formed in the washer 30. With the help of the force of the corrugated lid 38, the sealing ribs 42 will press on the upper surface 26 of the elastomeric closure to improve the sealing contact between them. Alternatively, as seen in Figs. 4 and 5, the sealing ribs 27 can be provided on the upper surface 26 of the elastomeric closure, also to improve the sealing contact between the washer and the elastomeric closure. It will also be appreciated that the sealing ribs (not shown) may be incorporated into the interface 39 between the flange of the elastomeric closure and the rim of the container, and these sealing ribs provided either on the flange or on the rim., to improve the sealing contact between the two. In the preceding Figures 3-5, it will be seen that the sealing ribs 27 and 42 are illustrated with rounded cross sections. Fig. 6 illustrates a modality 230 of the washer, wherein the sealing ribs 242 are formed with a square cross section. Alternatively, as seen in FIG. 7, the washer 330 may have sealing ribs 342 formed with pointed cross sections. It will be apparent to the skilled artisan that any of these cross sections can be applied to the sealing ribs formed on the upper surface 26 of the elastomeric closure. Fig. 2 illustrates a variant 120 of a sterile closure assembly according to the present invention. The elastomeric closure 122 includes a plug 124 and a flange 128. The washer 130 is retained with the elastomeric element 122 by a clamp 129 defining a recess 131 in which the washer 130 is retained securely. One or more sealing ribs 144 can be provided on the top surface 126 of the elastomeric closure 122 to improve the sealing contact between the washer 130 and the top surface 126, as previously described. A membrane 134 is secured to the washer 130 in a manner previously described. Here, bottle closure 120 is retained to neck 17 of a medication container (not shown) securing a corrugated lid (not shown) around clamp 129 and the rim of the container. Although the above sterile closure assemblies 20, 120 have employed a washer 30, 130 as part of their structure, it is also within the skilled artisan's field to forgo a washer and pre-attach a membrane 734 directly on a corrugated lid 738. See Fig.2b. The corrugated lid 738 and the membrane 734 can then be placed on the elastomeric closure 722 and the edge 717 while the elastomeric closure and the edge are in a sterile environment. To ensure that the membrane 734 and the corrugated lid 738 are not altered or detached from the top of the container during handling operations between the sterile area and the corrugation area, if desired, a structure such as a rib 780 may be provided between the membrane 734 and the elastomeric closure 722. This provides a second area in which the membrane 734 can adhere, such that the membrane and the corrugated lid are not altered or detached from the container during handling. As previously described, one of the difficulties with bottle closures of the prior art is that they are not designed to allow a lyophilization operation and a sealing operation to occur in a single step, thus necessitating an additional sealing operation, such as a waving operation, which takes place outside the sterile environment of the lyophilization chamber. Depending on the construction of the lyophilization chamber and the structures provided by the lyophilization chamber, the sterile closure assembly 20 of the present invention could be applied to the container 10 within the sterile environment of the lyophilization chamber. For example, the structure can be provided within the lyophilization chamber to retain the sterile closure assemblies while the medicament is being lyophilized in the containers, and which could then be used to seal the closure assemblies in the containers subsequent to the lyophilization. Even with a waving operation outside the lyophilization chamber, the membrane characteristic of the sterile closure assembly obviates the need to sterilize the closure access area, such as with an alcohol solution, before it is desired to have access to the medicament. . However, it would be beneficial to incorporate the features of the sterile closure of the present invention into a lyophilization closure assembly which is self-retained in the container. Such a lyophilization closure assembly could ideally be finally sealed to the container, inside the sterile environment of the lyophilization chamber and after the lyophilization process, without the need to incorporate costly modifications to the lyophilization. The lyophilization closure assembly would therefore facilitate concurrent lyophilization and complete seal operations, the net result being reduced process costs and particularly, the elimination of an additional process operation, such as a corrugation operation, out of the sterile environment in which lyophilization takes place.

With the foregoing in mind, FIGS. 8-10 represent a modality 400 of a lyophilization closure assembly according to the present invention. The lyophilization closure assembly 400 incorporates a sterile bottle closure 420 with the characteristics of the sterile closure assembly 20 previously described. The sterile vial closure 420 is incorporated within a body 460 that is constructed and arranged to allow lyophilization of a medicament 16 contained within the container 10 while the sterile vial closure is retained in the container. After lyophilization, although the container 10 is placed within the sterile environment of the freeze dryer, the body 460 can be self-attached to the container 10 to allow the sterile bottle closure 420 to seal the open top of the container, eliminating the need for an additional process operation, such as a corrugation operation. The body 460 includes a distal wall 462 disposed on the open top portion 15 of the container. The distal wall 462 engages a skirt 464 that surrounds the edge 17 of the container. The skirt 464 includes one or more deflection boundaries 470 having an L-shaped grip at a proximal end of the skirt. One or more deflectable latches 472 are formed intermediate the L-shaped grips 471 and the distal wall 462. As will be seen in Fig.8, the deflectable latches 472 are inclined internally toward the interior of the skirt 464. The body 460 may be initially attached around the edge 17 by driving the deflection boundaries 470 around the edge 17. The various dimensions of the components are selected such that in a first position, the edge 17 is retained between the one or more L-shaped grips. 471 of the diverting boundaries and the one or more deflecting latches 472. One or more steam passages 474 are formed in the skirt 464. When the body 460 is disposed in its first position, the steam passages 474 communicate with the open top portion. 15 of the bottle, allowing the vapor "V" generated during the lyophilization process to escape from the interior of the container 10. As before, the sterile closure 420 for the bottle includes a elastomeric closure 422 which is retained within the body 460. As before, the elastomeric closure 422 includes a plug 424 configured to completely block the neck 18 to seal the open upper portion 15 of the container when the lyophilization closure assembly 400 is placed, with respect to edge 17, in its second position (Fig. 9). As before, the elastomeric closure 422 includes an upper surface 426 for the purpose of being accessed by an end user when access to the medicament 16 contained within the medication container 10 is desired. The upper surface 426 is accessible through the body 400 via a central passage defined in the distal wall 462. If desired, the elastomeric closure may also include a flange 428 disposed in surface contact with interior portions of the distal wall 462 of the body. The flange 428 is designed to cover the upper surface of the edge 17 when the body 460 is disposed in its second position (Fig. 9). One or more sealing ribs 427 may be provided on flange 428 to improve the sealing contact between flange and distal wall 462. Alternatively, sealing ribs may be provided on the interior portion of distal wall 462. Sealing ribs 427 may assume any suitable shape, such as the shapes illustrated in Figs.3-7. As seen in Fig. 8, the elastomeric closure 422 can include a vertical projection 450. The upper surface 426 of the elastomeric closure can thus be provided on the vertical projection 450. The body 460 can include a tubular extension 468 coming from the wall distal 462. Tubular extension 468 terminates in a support 467 defining a central passage 466. Vertical projection 450 of elastomeric closure 422 can be retained within tubular extension 468 by providing a lip 456 which is housed within notch 469 defined within the tubular extension 468. The lip 456 is captured within the notch 469 and is sealingly retained against the interior portions of the support 467. One or more sealing ribs 452 may be provided in the vertical projection 450 of the elastomeric closure, for sealing contact with the inner portions of the tubular extension 468. Alternatively, these sealing ribs may be provided in inner portions of the tubular extension 468. In any case, the sealing ribs 452 may assume any suitable shapes, such as the illustrated shapes in Figs.3-7. A membrane 434 may be fixed on the lyophilization closure assembly 400 to protectively enclose the upper surface 426 of the elastomeric closure 422 in a sterile manner. The membrane 434 includes a pull-tab 436. Fig. 8 illustrates that the membrane 434 is attached to the flange 467 of the body, to protectively close the upper surface 426. Alternatively, if desired, Fig. 10 illustrates that a washer 530 can be provided against the upper surface 526 of the elastomeric closure 522. The washer 530 includes an opening 532 which delimits an access area 526A on the upper surface. The washer 530 is retained on the upper surface of the elastomeric closure and may be dimensioned such that its outer edge rests adjacent to the central passage 566 defined by the flange 567 of the body. Alternatively, if desired, the washer can be dimensioned in a manner to be retained between the upper surface of the elastomeric closure and the flange 567, analogous to the constructions illustrated, for example, in Figs.2-4. The membrane 534 can be secured in surface contact with the washer 530 to protectively enclose the access area 526A of the elastomeric element 522. If desired, the membrane 534 is extended and further secured in surface contact with the flange 567 of the body 560.

As before, the elastomeric closure 422 may be formed of a suitable rubber material while the body 460 may be formed of a suitable rigid material such as a plastic material. The membrane 434 may be formed of various plastic materials, composite materials, paper materials, sheet metal materials, TYVEK materials, or the like. The various components can be supplied to a pharmaceutical manufacturer in a sterile state, for the pharmaceutical manufacturer to assemble as part of its processing operation.

Alternatively, the various components may be pre-assembled by the manufacturer of components and sterilized, so that a sterile, pre-assembled, lyophilization closure assembly 400 is provided to the pharmaceutical manufacturer. If desired, the body 460 and the elastomeric closure 422 can be formed together by a co-injection process, the membrane 434 and the body 460 can be formed together by a co-injection process, or the entire body 460, closure Elastomeric 422 and membrane 434 can be formed together in a co-injection process. If a washer 530 (see Fig.10) is used, it can be formed together with any of the preceding components, separately or in its entirety, in a co-injection process. The lyophilization closure assembly 400 according to the present invention allows a pharmaceutical manufacturer to perform a lyophilization operation on a medicament and a complete sealing operation on the sterile environment of a freeze dryer, without the need for a sealing operation additional, such as a ripple operation, outside the sterile environment of the freeze dryer. Fig.8 illustrates the lyophilization closure assembly 400 in its first position, wherein the medicament 16 contained within the container can be subjected to a lyophilization process. The lyophilization closure assembly can be adjusted over the edge 17 in the position of Fig.8 after the medication 16 is inserted into the container 10. As can be seen, in this position, the cap 424 is not inserted in the neck of the container, but rather, it is positioned away from the open top 15 of the container. The filled container can be introduced into an appropriate lyophilization chamber, such as a freeze dryer, for lyophilization of the medicament 16. As the lyophilization closure assembly 400 is self-supported in the container, no additional structure is required in the lyophilization chamber to support the closing assembly d lyophilization during the lyophilization process.

Due to the space of the cap 424 with respect to the open top of the container, any vapors "V" generated during the lyophilization process can freely exit the container 10 via the vapor passages 474 provided in the body 460. Subsequent to the lyophilization of the medicament 16, the container 10 must be sealed in order to seal the medicament. Fig. 9 illustrates the lyophilization closure assembly 400 driven to a second position wherein the elastomeric closure 422 has been urged toward sealing contact with the open top 15 of the bottle, subsequent to the lyophilization process, while the container 10 is retained within the sterile environment of the freeze dryer. An "F" force exerted, for example, by shelves conventionally provided in the freeze dryer, is applied to the body 460. The body 460 is propelled proximally from the edge 17, while the deviable latches 472 are pressed outwardly from their orientation toward inward so that they can pass on the side 21 of the edge 17. After the divertable latches 472 pass around the side 21, they are free to re-assume their original inward inclined position, so that the disposable latches engage in blocking contact with the bottom surface 19 of the edge. Therefore, the body 460 is locked in its second position to firmly secure the lyophilization closure assembly to the container. The elastomeric closure 422 seals the open top portion of the container 15, with the vapor passages 474 blocked from communicating with the open top 15. Therefore, the medicament is securely sealed within the container 10 in a sterile manner. It will be seen that various components may be dimensioned or otherwise configured such that when the lyophilization closure assembly 400 is driven to the second position, the cap 24 is urged toward the neck 18 to seal the open top 15 of the bottle. The lower surface 429 of the flange is engaged in surface contact with the upper surface 13 of the edge, such that a seal is made between these components. If desired, it will be understood that the sealing ribs (not shown) can be provided between the lower surface 429 of the flange and the upper surface 13 of the edge to improve the sealing contact between them. In addition, it will be seen that the vapor passages 474 are blocked from the open top 15 of the medicament container, such that the medication container is perfectly sealed by the lyophilization closure assembly while in the sterile environment in which Lyophilization occurs. The membrane 434 hermetically protects the upper surface 426 of the elastomeric closure. When it is desired to use the medicament, an end user needs only to remove the membrane 434 without the need to sterilize the access area, such as with an alcohol solution. It will be appreciated and understood by those skilled in the art that further and further forms of the invention may be conceived without departing from the spirit and scope of the appended claims, the invention not being limited to the specific embodiments shown.

Claims (18)

1. CLAIMS 1. A lyophilization closure assembly for a medication container having an open top and an edge surrounding said open top, comprising: a body secured around the open top of the container, the body having a wall distal disposed on the open top of the container and a skirt surrounding the edge of the container, a central passage provided in the distal wall, the skirt having a distal end, a proximal end and one or more steam passages formed therebetween, the body including one or more deflectable latches cooperable with the container rim and provided in the middle of the distal and proximal ends of the skirt, the body having a first position, wherein the body is elevated from the open top of the container such that the steam passages communicate with the upper part open, and a second position, where the deflecting latches block the body to the edge and the steam passages do not communicate with the open top of the container; an elastomeric closure secured inside said body to seal the open upper part of the container when the body is in the second position, the elastomeric closure having a cap for sealing the open top of the container, and an upper surface facing the central passage of the container. the distal wall, the plug sized to be spaced from the open top of the container when the body is in the first position such that the open top communicates with the vapor passages of the skirt; and a membrane removably secured through the central passage of the distal wall and hermetically enclosing the upper surface of the closure. The lyophilization closure assembly of claim 1, wherein the body includes a tubular extension surrounding the central passage of the distal wall and the elastomeric closure includes a vertical projection securely retained within the tubular extension, the upper surface of the closure provided in the vertical projection 3. The lyophilization closure assembly of claim 1, wherein the elastomeric closure includes a flange portion retained against the distal wall of the body. The lyophilization closure assembly of claim 3, further comprising one or more sealing ribs disposed between the flange portion of the closure and the distal wall of the body. The lyophilization closure assembly of claim 2, further comprising one or more sealing ribs disposed between the vertical projection of the elastomeric closure and the tubular extension of the body. The lyophilization closure assembly of claim 2, wherein the elastomeric closure includes a flange portion retained against the distal body wall, further comprising one or more sealing ribs disposed between the rib portion of the closure and the wall distal of the body. 7. A lyophilization closure assembly for a medicament container having an open top and an edge surrounding said open top portion, comprising: a body secured around the open top of the container, the body having a distal wall arranged on the open top of the container and a skirt surrounding the rim of the container, a central passage provided in the distal wall, the skirt having a distal end, a proximal stranger and one or more vapor passages formed therebetween, the body including one or more deflectable latches cooperable with the container rim and provided in the middle of the distal and proximal ends of the skirt, the body having a first position, wherein the body is raised from the open top of the container such that the passages of steam communicate with the upper part open, and a second position, where the deflecting latches block the body to the edge and pass them steam jets do not communicate with the open top of the container; an elastomeric closure secured within said body to seal the open upper part of the container when the body is in the second position, the elastomeric closure having a cap for sealing the open upper part of the container, a flange portion retained against the distal wall of the container; body, and an upper surface facing the central passage of the distal wall, the plug sized to be spaced from the open top of the container when the body is in the first position such that the open top communicates with the vapor passages of the body. Skirt; a washer secured in surface contact with the upper surface of the closure, the washer defining an opening facing the central passage of the distal wall? and a membrane removably secured through the opening of the washer and hermetically enclosing the upper surface of the closure. 8. The lyophilization closure assembly of claim 7, wherein the membrane is furthermore removably secured through the central passage of the distal wall. The lyophilization closure assembly of claim 7, wherein the body includes a tubular extension surrounding the central passage of the distal wall and the elastomeric closure includes a foot projection securely retained within the tubular extension, the surface top of the closure provided in the vertical projection. The lyophilization closure assembly of claim 7, further comprising one or more sealing ribs disposed between the flange portion of the elastomeric closure and the distal body wall. The lyophilization closure assembly of claim 9, further comprising one or more sealing ribs disposed between the foot projection of the closure and the tubular extension of the body. The lyophilization closure assembly of claim 7, wherein the elastomeric closure is formed of a rubber material and the washer is formed of a plastic material. The lyophilization closure assembly of claim 12, wherein the elastomeric closure and the washer are formed together in a co-injection process. The lyophilization closure assembly of claim 7, wherein the washer is formed with a plastic material and the membrane is formed of a sheet metal material. 15. The lyophilization closure assembly of claim 14, wherein the washer and the membrane are formed together in a co-injection process. The lyophilization closure assembly of claim 7, wherein the elastomeric closure is formed of a rubber material, the washer is formed of a plastic material, and the membrane is formed of a sheet metal material. 17. The lyophilization closure assembly of claim 16, wherein the elastomeric seal, the washer and the membrane are formed together in a co-injection process. 18. The lyophilization closure assembly for a medication container having an open top and an edge surrounding said open top, comprising: a body secured around the open top of the container, the body having a distal wall disposed on the open top of the container and a skirt surrounding the rim of the container, a central passage provided in the distal wall, a skirt having a distal end and a proximal end, and one or more vapor passages formed therebetween, the body having one or more latches deviable latches cooperable with the edge of the container and provided in the middle of the distal and proximal ends of the skirt, the body having a first position, wherein the body is raised from the open top of the container such that the steam passages communicate with the upper part open, and a second position, where the deflecting latches block the body to the bord e and the vapor passages do not communicate with the open top of the container; a rubber closure secured inside said body to seal the open top of the container when the body is in the second position, the rubber closure having a stopper to seal the open top of the container, a flange portion retained against the wall distal of the body, and a top surface facing the central passage of the distal wall, the plug sized to be spaced from the open top of the container when the body is in the first position such that the open top communicates with the passages of steam skirt; a plastic washer secured in surface contact with the upper surface of the closure, the washer defining an opening facing the central passage of the distal wall; and a sheet metal membrane removably secured through the opening of the washer and hermetically enclosing the top surface of the closure.