WO1998002129A1

WO1998002129A1 - Method and device for sealing and connecting a container

Info

Publication number: WO1998002129A1
Application number: PCT/SE1997/001094
Authority: WO
Inventors: Percy Bennwick; Olle Ljungquist
Original assignee: Pharmacia & Upjohn Ab
Priority date: 1996-07-11
Filing date: 1997-06-18
Publication date: 1998-01-22
Also published as: PT915692E; ATE222743T1; DK0915692T3; DE69715007T2; JP2000514677A; DE69715007D1; EP0915692B1; ES2183202T3; EP0915692A1; AU3561297A

Abstract

A device for sealing or connecting a container, having at least one opening with an opening axis, comprising (a) a closure member for arrangement in, at or around the opening and having at least one pierceable part, (b) a connector attachable, when oriented at least partially coaxial with the opening, at a proximal end to the container and at a distal end directly or indirectly to a vessel in the form of a second container, a syringe or a duct, and (c) a sharp operable to penetrate at least the pierceable part and to establish a fluid communication between the container and the vessel. The device comprises that the sharp is connected to or integral with the connector so as to follow it in at least its axial movements, that the connector is axially movable in relation to the closure between at least two defined positions, said positions comprising (i) a first position in which the sharp is axially remote from the closure so as not to pierce it and in which the connector bears on the closure so that an axial force applied to the connector is transmitted to an axial force on the closure and (ii) a second position in which the sharp penetrates the closure, and a releasable locking mechanism arranged to prevent, when engaged, and to permit, when disengaged, movement of the connector from the first to the second position. The invention also comprises a method for sealing or connecting a container.

Description

METHOD AND DEVICE FOR SEALING AND CONNECTING A CONTAINER

Technical area The present invention relates to a device for sealing or connecting a container, having at least one opening with an opening axis, comprising (a) a closure member for arrangement in, at or around the opening and having at least one pierceable part, (b) a connector attachable, when oriented at least partially coaxial with the opening, at a proximal end to the container and at a distal end directly or indirectly to a vessel in the form of a second container, a syringe or a duct and (c) a sharp operable to penetrate at least the pierceable part and to establish a fluid communication between the container and the vessel. The invention also relates to a method for sealing or connecting a container.

Background Connection of sealed containers to secondary devices or conduits under highly con- trolled conditions is a common problem, especially in medical applications and with pharmaceutical preparation container contents due to the hazardous or fatal consequences of improper handling, often exaggerated by emergency circumstances or limited operator experience in case of patient self-treatment.

Typical situations are withdrawal of preparation from a vial by use of a syringe type device or the introduction of a solvent or diluent to the vial by similar means, the connection of a container to a conduit e.g. for infusion or the connection of a rigid container to a flexible bag for interchange of their contents. The purpose may be to withdraw a content sample from the container, to add a component to the container for example to dissolve, dilute or mix com- ponents before administration or a more complicated exchange for example when dissolving a container component with a solvent from a vessel or bag for later reintroduction of the dissolved preparation into the vessel. Frequently the container sterility and integrity is secured by a permanent seal including a pierceable septum that has to be penetrated by sharp object such as a needle or cannula to establish the desired fluid communication.

Preparation steps prior to connection, such as container filling and sealing, may re- quire special conditions limiting the possibilities to employ manual manipulation steps and placing special design requirements on the device parts involved. Commonly the container has to be subjected to sterilization, which at least require the parts to sustain sterilization conditions, such as heat, irradiation etc. Most commonly, however, it is also needed that the actual sealing takes place under the special conditions as when access to container interior is a necessity, e.g. when using a sterilizing gas, when introducing a protective or inert gas overlay, when drying, notably freeze-drying or lyophilizing, container content before sealing or when providing an overpressure or vacuum in the container. The access may then be secured in known manners, such as by keeping the sealing parts remote from container opening until the sealing operation or by resting on the container openings sealer elements having channels or cut-outs which are closed by and at the sealing operation.

Problem areas in the above respects are to limit the number of parts and steps the user has to handle and master during connection procedure i order to avoid coupling mistakes, cutting on sharps etc. Often the couplings provided are adapted to the parts to be received and safe connection may not be obtained unless mating parts are connected as intended. Similarly vessels frequently have to be connected in a certain sequence for correct flow, e.g. when vacuum or overpressure are present. Guidance of parts is desirable for safe and leak-proof con- nection, for avoiding bending and weakening of needles, couplings etc. and for preventing release of particles from closures, cappings and septums, which may be carried with the preparations into the body. Maintained sterility and contamination prevention is a major problem in most connection situations. Although each device part may be manufactured and delivered under pure conditions, the interfacing thereof is a notorious cause of contamination. Any design intended to ameliorate these problems also has to take into account the above- mentioned requirements and design restrictions posed in manufacture and container pretreat- ment steps.

Abundant prior art suggestions have been put forward for improved methods and means in the abovesaid problem areas, none of which have been found entirely satisfactory. A common connector type, as represented by e.g. US 3 872 867 and EP 499 481 , relies on an axial compression of the containers against a fixed needle to establish the fluid connection and a similar type, as represented by e.g. US 5 445 631 , EP 570 939 and WO 94/00094, uses a slideable needle for the same purpose. According to EP 533 171 a threaded engagement is used to axially displace a sharp in a corresponding manner for membrane penetration and plug removal . Common to all these devices is that that they give little control over connecting sequence and do not assist in or take any advantage of preceding manufacturing steps but are strictly intended for use with already sealed and capped containers. Other closure systems are known, as exemplified by US 4 286 389, US 5 320 603 and WO 94/04424, providing for both container interior access during lyophilization and complete final sealing but not for controlled or facilitated later connection, but in conventional ways.

Summary of the invention A main object of the present invention is eliminate or reduce the abovesaid deficiencies of the prior art methods and means. A more specific object is to facilitate and reduce the number of steps for the user in making necessary connections. Another object is to increase control over connection sequence. Yet another object is to allow for safe connection without undue release of particles from closure means. Still another object is to facilitate container manufacture and pretreatment steps. A further object is to assist in container closure, sealing and contamination protection. Yet another object is to reduce the number of parts to be handled in the pretreatment and connecting steps.

These objects are reached with the device and method characteristics set forth in the appended claims. By providing connecting means allowing at least two defined positions relative the closure or capping means as stated and a mechanism for control of movement therebetween several of the objects are reached. In a first position the connector may act as integral with the closure or capping. In manufacture and pretreatment steps this allows for treatment of the device as a unit in any chamber process, which obviates additional assembly steps yet permitting all common procedures such as sterilizing and lyophilization of container content as well as final sealing of the container by pushing the unit so as to bring the closure into engagement with the container. When so used the device may be sterilized together with the container and, as no need exists for later separation therebetween, contamination of the interface is prevented. The distal end of the connector may be sealed with a membrane, which can be easily done as the only functional limitation on this part may be to sustain a flat pressure in the abovesaid closing step. In handling, storing and transportation steps following manufacture the integral character in the first position assists in maintaining the device unarmed and secured against unintentional release, which also extends to any sharp attached to the connector. In the connecting procedure the fact that the connector is already safely attached to the con- tainer relieves the user from this step and limits the connecting operation to the secondary device. The mechanism for control of movement to the second position now acts as an important control means for the connecting sequence, allowing the user either to first make the fluid connection to the container or to the secondary device or both substantially simultaneously, in dependence of special conditions such as over or under pressure, which control cannot be obtained in known devices with freely sliding sharps or sleeve parts. Yet the actual coupling movement can still be made substantially axially and does not require threading or twisting actions prone to create particle or debris release. In spite of the advantages offered the invention does not add to complexity. The device only uses standard components, although modified, i.e. closure means and a connector piece with sharp, and the functional requirements of force transfer and axial connection permit a simple part design, easily compatible with the manufacturing conditions mentioned and a material selection free of metal parts, if desired. As said the method steps required represents a simplification in relation to existing procedures. Further objects and advantages will be evident from the detailed description hereinbe- low.

Detailed description of the invention As indicated in the introduction the primary container for the sealing and connecting can take a variety of forms such as any kind of container or vessel, flexible bag, vial, ampoule, cartridge, carpoule, syringe body etc. There are some manufacturing and assembly advantages in using containers that are rigid, at least at its opening but preferably generally rigid, such as vials, ampoules or syringe bodies. There are also some advantages in employing the invention in connection with in-situ sterilization and lyophilization and containers adapted for this pur- pose.

The container has at least one opening to be sealed or connected by means of the invention but may have further openings which can be identical to the at least one opening but which can be entirely different .and for example be adapted for another purpose of e.g. infusion or syringe type with a movable wall or piston. The principles of the invention can with advantage be used for more than one opening on the container. For convenience positional and directional statements herein will be given in relation to the opening "axis" by which shall be understood a line perpendicular to the opening surface or opening cross-section just at its outlet and being centered at its symmetry axis in case of rotation symmetry or momentum center in case of other shapes. Expressed in another way the axis may be directed perpendicu- lar to and centered relative the flow through the opening which in most instances give about the same meaning. There are no severe demands on opening physical structures besides being able to support a sealing. A plain tube shape opening or a hole with rigid rim can be closed with an inserted simple plug or stopper type sealing and the tube type opening also with an external friction fit, possibly supplemented with an adhesive or curing of the sealer part. It is preferred, however, to assist with some kind of physical attachment of the closure means for which purpose it is preferred to provide protruding or recessed structures for cooperation with complementary shaped closure parts. These structures may be located on the opening interior, exterior or both, preferably at least on the exterior when space so permits. Almough threads or bayonet type structures are conceivable it is preferred to use structures allowing engagement with a simple axial relative displacement between container and closure, without requirement for substantial angular motions. Such structures may include circumferential flanges, grooves, undercut etc., continuous or intermittent, around the opening, including the common bottle- type with orifice flange, neck and shoulder parts. Several such structures may be used, e.g. axially displaced for example in order to assist positioning of closure parts in an open posi- tion, allowing gas exchange, and a closed position.

The device includes a closure for the container able to seal off container interior and being designed to be penetrable, before or after removal of protective material, by a sharp included in the connector part. "Closure" as used herein shall be understood as a general concept for device parts fulfilling these objects and may be a integral or composite structure to be further explained. A minimum requirement on the closure design for the present purposes is that it shall be able to receive an axial pressure to be pushed into engagement with the opening, which in broad terms only requires that the closure have a suitable part with a surface component, i.e. flat, inclined or curved, transversal to the axial direction. Such surfaces may be provided especially with this object in mind, e.g. a rim surface adapted to the connector or lateral cut-outs for engagement with pushing hooks. An entirely conventional design is also usable, however, as normally including a flange or rim portion or at least a closing top surface. A preferred general design is a sleeve portion extending axially and a closing top surface. The sleeve part may be designed to be inserted in the opening interior but is preferably designed to engage the opening on its exterior when having a tube or neck part. The closure may have structures adapted for cooperation with similar structures on the container for the abovesaid physical attachment purpose, preferably allowing a push fit engagement, either relying on resiliency of the part itself or assisted by a separate locking ring. Similarly, although conceivable that the closure before the sealing is kept remote from the container by entirely independent means and brought into contact with the container at sealing, it is preferred to provide the closure with structures allowing it to rest on the container in a pre-sealing position from which it can be brought to a sealing position. To this end the closure may be provided with at least two axially displaced attachment structures, preferably in an axial sleeve part when present, in addition to or as an alternative to the abovedescribed similar designs placed on the container. When gas exchange between container and surroundings is desirable in the pre-sealing position, slits, channels, holes or cut-outs may be provided in the closure, also preferably in an axial sleeve part when present in a manner known per se. Finally the general closure properties may, but do not have to, include specially designed locking features for cooperation with similar details on the connector part to permit transition from a first position to a second position, with the sharp in non-penetrating and penetrating relationship to the pierceable sealer respectively, which will be further described hereinbelow.

Although a single integral closure structure may be designed so as to act both as a pierceable sealer and a capping part for engagement with the container opening, it is preferred to employ different closure parts for these functions. Accordingly it is preferred that the closure comprises a pierceable sealer part and a capping part at least acting to secure the sealer against displacement from the opening. A "sealer" shall be understood in broad sense as a part being pierceable by the sharp, to be further explained, and may for example include valves, displaceable members in the opening, parts being deformable to an unsealing condition etc. Often preferred is the common soft or resilient type being actually penetrated by the sharp and in this case the sealer can be made in materials common in the art with low disposition for particle release when penetrated and with good ability to again close after penetration and withdrawal of the sharp, e.g. elastic rubber materials. Also the sealer shape may be any con- ventional, such as a more or less flat membrane or septum covering the opening orifice, a cap type shape extending over and around the opening exterior or most preferably a plug or stopper type inserted in the opening. The sealer, especially when of the plug type shape, may have cavities or recesses to limit the penetration depth needed for the sharp to reach container interior. The sealer in itself may be an integral structure or be composed of several layers or parts. The capping shall be able to engage the opening in a releasable or preferably a permanent manner, i.e. with some irreversible destruction necessary for release of the capping. The engagement structures discussed above in relation to the closure in general, which shall not here be repeated, are preferably placed on the capping part when present. To secure sealer positioning the capping should at least cover it partially and optionally also compress it, especially when the sealer covers the opening orifice or exterior parts. It is preferred that the capping leaves at least an area part, and preferably a central area part, of the sealer uncovered to permit access for the sharp during the penetration step, which shall not exclude that said area is covered by a thin penetrable capping part or a part designed to be removed immediately before the penetration step, such as with a tearing weakening or the common flip-off design. The area can be adapted to the sharp type used and can be made small when a needle type sharp is utilized. For the purposes of the invention it is preferred to attach, or provide the capping with means for receiving and fixing, the sealer part to the capping. This in order to offering the option of using in the container sealing step a complete pre-assembled unit having all parts present for closing and sealing the container in a single compression step. The attachment between sealer and capping can be made with any known method, e.g. permanently by for example gluing or welding or releasable by for example a push lock, threads etc. Also the capping can be made as a single integral part or may consist of several discrete parts, e.g. with a separate locking ring, permitting slight capping engagement force while requiring high release force, with additional linings or gaskets, with separate film covering for integrity etc. The capping material can be the conventional metal type, notably aluminum, but preferably comprises or consists of polymers for ease of manufacture and least contamination risks. The connector part of the device in general terms includes a proximal part adapted for cooperation with the closure, a distal part adapted for connection to a secondary container or vessel and an intermediate part comprising at least the sharp. As indicated the connector proximal part cooperation with the closure shall allow the connector to be axially movable in relation- to the closure between at least two defined positions. In a first position the sharp is axially remote from the sealer so as not to pierce it and the connector bears on the closure so that an axial force applied to the connector is transmitted to an axial force on the closure. In a second position the sharp penetrates the sealer. Preferably a releasable locking mechanism is arranged to prevent, when engaged, and to permit, when disengaged, movement of the connector from the first to the second position. Although conceivable that pressure may be ap- plied directly to the closure for the purpose of bringing it to an engagement with the opening to establish sealing, a generally simpler sealing procedure is obtained if the pressure can be applied to the connector part. In order then to transmit the force to the closure any means may o

be used for bearing on the closure. Friction between the parts may be used, e.g. by radially pressing connector parts, such as a sleeve pushed over a similarly shaped closure part, against each other, which allows for force transmission with only axially arranged abutting surfaces. In this case the locking mechanism may include means for providing and releasing respec- tively said radial compression between the parts, e.g. a compression/expansion ring or wedges acting on slits, possibly cooperating with resilient parts. It is generally preferred, however, to provide both the closure and the connector with abutting surfaces, having at least a component perpendicular to the axis, such as either flat, inclined or curved. When abutted, such surfaces may safely transmit even strong forces. The abutment may either be direct, as when the sur- faces on closure and connector are contacted, or indirect, as when a separate member is positioned between and in contact with the surfaces on closure and connector. The locking mechanism may here include means for axially aligning and disaligning respectively the surfaces. To achieve this one option is to laterally displace at least the surface or surfaces on one of the parts, preferably the connector part, or a separate member when present, radially away from engagement with the corresponding surface on the other part, e.g. by placing the surface bearing parts on flexible or removable tongues which may be manually influenced. Another option is to place the surfaces, preferably inclined, on a resilient part or support in such a way that at a certain axial force the resilient part yields to allow the surfaces to ride out of engagement in a push lock manner. The resilient part should be adapted to sustain the sealing step force but be overridden by a larger force in the connecting step. Still another and preferred option is to align and disalign the surfaces by a relative rotation between closure and connector, which method is safe, yet convenient to the user. One implementation of this option is to provide at least one, preferably several and most preferably a number of evenly and circum- ferentially distributed alternating surfaces and spaces on both the closure and connector parts in such a way that in certain angular positions the surfaces overlap and in other angular positions the surfaces can cross each other through the spaces. It is sufficient that the parts comprises a flange or rim part with the alternating structures, provided no device details behind interferes with the desired axial displacement, which sufficiency may be utilized to allow for angular dislocations of the parts after crossing of the surfaces, e.g. for final locking after completed axial displacement. Contrary hereto the surfaces and spaces on at least one of the parts may be extended to longitudinal ridges and grooves, for example in order to completely guide the parts during the movement from the first to the second position, which does not ex- elude a similar final locking in the second position. It is to be understood that the requirement that after releasing the locking mechanism the parts shall be able to axially displace in relation to each other, as well as the option of guiding the parts, applies with equal significance to the other embodiments mentioned. Apart from any rotation for release of the locking mechanism it is preferred that the movement from the first to the second position is substantially axial for reasons already given. A preferred general outline for these purposes is to arrange the closure and connector parts in a telescopic manner, preferably with the connector part outermost. With advantage the locking mechanism can be biased towards a default position, preferably towards the locked position preventing sharp penetration, by any known means, either re- versibly by a resilient part or a spring or irreversibly through a rupturable member.

The proximal connector part may be designed with other optional features. It may be desirable to provide an additional locking between closure and connector designed to prevent axial separation of these parts. This in order for example to avoid unintentional disassembly, to assist in treating these parts as a unity or to maintain sterility. For the latter purpose the connection may be sealed, either by means of the mating parts themselves or by for example an additional adhered film or paste. Another optional feature is to extend a shroud part of the connector over the closure, when exteriorly engaging the opening by a sleeve part, to act as a protection or a locking ring for the closure.

The intermediate connector part should at least have a length corresponding to the ax- ial distance for the sharp when penetrating the sealer or when going from the first to the second position plus a possible additional length corresponding to an axial movement for connection of the distal connector part to the secondary container or vessel. Besides possible structures for attachment or receipt of the sharp the physical structure of the connector intermediate part is not critical and may for example be reduced to any spacer bridging said neces- sary length, and uniting the proximal and distal ends and in a manner permitting transmission of the desired force. It is preferred to make the part substantially closed, among others to maintain sterility and avoid contamination, and preferably with a substantially tubular form wherein the interior size and shape with advantage may be adapted to the exterior of the closure for simplest overall design. The sharp can be of an known type able to open up the closure to give access to container interior and "sharp" shall be understood to cover devices in broad sense for these purposes. The sharp may be the mating part of a valve mechanism in the opening, a pusher for opening a one-way valve, a pusher for displacing e.g. a stopper or plunger into the container or to a non-sealing section on the stopper or container, a member displacing a sealing part of the closure such as a sealing pin, a part deforming a sealer into a non-sealing form etc. The flow channel may be provided by a part separate from the sharp, e.g. a duct surrounding the sharp or the connector itself may act as the channel when it has a closed design. In this case the sharp could open the closure in a manner allowing flow around shaφ exterior, e.g. by having a non-uniform exterior. It is preferred, however, that the sharp not only performs penetration but also provides the flow channel for which puφose the shaφ should contain at least one channel with one opening placed so as to be positioned within the container after the penetration step and the other opening outside the container and preferably ending so as to allow conduit connection to the secondary devices. Two or more channels may be provided in an known manner, e.g. for allowing liquid flow in one channel and gas pressure equalizing through the other. One preferred shaφ is the needle-type designed as conventional in metal but preferably in a plastic. The shaφ is positioned within the intermediate part in a manner admitting closure penetration at an axial movement. The shaφ can be arranged slideably within the connector for example on a piston or movable wall type carrier or in any other known way as exemplified in the introduction. It is preferred, however, to affix the shaφ to the connector allowing it to be axially displaced together with the connector. It may still be allowed to rotate relative the connector housing, e.g. to even out rotational movements of the connector housing, to allow separate locking of the shaφ part, to perform an opening deformation on a closure or to assist in locking the secondary containers or vessels. For simplest design the shaφ is preferably fixed to the connector also in respect of rotational movements. A preferred construction is to arrange a wall across and substantially peφendicular to the device axis to which wall the shaφ is attached, preferably substantially centrally. The distance between the wall and the closure should be sufficient to allow the axial movement during penetration and may preferably act as a final stop for that movement. The wall can be perforated, for example to allow venting of the proximal volume e.g. during evacuation, or can be continuous or sealed, for example to maintain sterility or to prevent any fluid communication but through the shaφ channel. The connector distal part for connection to secondary devices should at least comprise conduit completion means for the flow between the primary and secondary containers as exemplified but may with preference also comprise fixation means for physical attachment of the secondary device. These means may need adaptation to the specific secondary device to be received, either by modification of the distal connector part itself or by use of separate and different inserts or adapters for use with the same main connector design. The secondary devices can be any of the types enumerated for use as primary devices but may also a simple tube, duct or catheter. The conduit completion means may be another shaφ in case the secondary device has a pierceable sealer, a female luer taper or other needle connector part in case of a syringe type secondary device, a push pin in case of one way valve mechanism, a thread in case of screw type opening etc. Such conduit completion means should have fluid communication with the shaφ part and may preferably be designed integral therewith. Preferably conduit completion is attained by an axial movement relative the secondary device although an angular movement component may also be present as when threads are part of the means. When the shaφ is fixed to a transverse wall as described it is preferred that the shaφ extends therefrom towards the proximal device end and that the conduit completion means extends from the wall in the opposite direction towards the connector distal end, whereat said wall may act also as a stop for the secondary device at reception thereof. If the conduit completion means does not provide physical fixation for the secondary device the abovesaid additional fixation means may be included, which preferably are located at the connector main housing rather than at the conduit completion means. The fixation means may include any known type of fit, such as friction by wedging surfaces or otherwise, threads, bayonet, push lock, under- cut, camming surfaces etc. In most instances a simple and convenient design is obtained if the connection is made so that the secondary device opening axis, as defined, becomes oriented substantially coaxial with the primary container opening axis. Other orientations are conceivable, however, for example more or less laterally in relation to connector axis e.g. to meet special administration demand situations or to avoid that the connection requirements for the secondary device interferes with the optimal design of the connector distal end for other purposes.

It is desirable that the connector distal end is made so that it can securely receive a flat force coaxial with the device for transmission to the closure part. For this puφose the distal end preferably has surface components transversal to the device axis and most preferably substantially symmetrically arranged to avoid twist and tilt, although conceivable that the force is applied via an equalizing intervening part. In order to maintain device sterility and integrity it is also desirable that the openings for the secondary device can be closed off before the connecting operation, e.g. by a cover or preferably a tearable or rupturable membrane. The main device parts can be made in metal but are preferably manufactured in a plastic such as ABS, polycarbonate or preferably polypropylene and optionally the plastic materials contains a fiber reinforcement of for example glass. For cost efficiency, handling and assembly reasons it may be desirably to manufacture the device in as few pieces as possible. In broad terms at least the closure and the connector are manufactured as separate parts.

The manner of using the device and the corresponding method for sealing and connecting the container has been given hereinabove in relation to each device feature described. Below some additional comments in relation to a possible process. Preferably the device parts including a capping, sealer, connector, shaφ and possible sealing membranes are preassem- bled and possibly sterilized. The primary container with a pharmaceutical preparation content is placed in a chamber and the preassembled unit is positioned coaxial on top of the container in a resting position allowing gas exchange with the container interior. In the chamber a steril- izing step can be conducted with irradiation, heat, oxidizing gas etc., optionally with over or undeφressure, the gas exchange also allowing evening out of pressure differences. Another useful chamber process is a lyophilizing step on an initially liquid preparation, which may include cooling to freezing temperatures, chamber evacuation to create vacuum, preparation drying under moisture release and evacuation and oxygen purge or introduction of an inert gas overlay of for example nitrogen. Closing and sealing of the container can now take place by pressing the device unit towards the container, which will result in that the sealer is brought to or into the container opening, the capping is engaged and locked to the opening, possibly also resting with its lower end on a shoulder part of the container, and location of the connector in position for connection. This step is preferably made within the chamber by compression of the shelves on which containers with device units are standing. The chamber may now be pressure equalized and opened. The combined sealed container and connector can from now on be treated as an inseparable unit during optional post-treatment, transport, storage or other handling up to the connection thereof to a secondary device. In that process the operator removes or ruptures any sealing at the connector distal end and any similar sealing on the sec- ondary part to be received. Depending on the nature of the preparations in the containers and the fluid interchange desired the operator can decide either first to open the fluid connection to the primary container or the secondary device or both simultaneously by influencing the locking mechanism, by rotation or any of the other movements described, and axially compressing the relevant parts. If the primary container is first to be connected the operator releases the locking mechanism and pushes the connector part towards the container for penetration of the shaφ and then introduces and pushes or threads, as the case may be, the secon- dary device opening into the distal connector part. The reverse connection sequence is equally possible. A substantially simultaneous connection may be obtained by for example first releasing the locking mechanism, but not compressing container and connector, then inserting the secondary device into the connector and compressing the secondary device relative the primary container to axially displace both the connector towards the primary container and the secondary device towards the connector. Unless the devices are pre-treated with over or un- deφressure to assist fluid flow, it is assumed that the operator actively orient the devices and take any other necessary measure to secure the desired flow. In a typical situation the primary container contains a lyophilized solid or syrup and a residual vacuum from the lyophilizing step and the secondary device is a bag containing a solvent for the solid. The operator first connects the bag to the connector to create a fluid communication therewith, then releases the locking mechanism and pushes the connector towards the primary container to pierce the closure with the shaφ and establish fluid communication also here. The vacuum in the container will now suck solvent from the bag into the container to dissolve the solid. After dissolution the operator may turn the entire aggregate of connected parts to a position with the primary container high and allow the solution to drain down into the bag for mixing with the main volume thereof and for subsequent administration of the combined preparations to a patient.

Although the invention has been described mainly in terms of pharmaceutical applications it shall not be regarded as restricted thereto.

Summary of drawings Figures 1A, IB and 1C show in section an embodiment of the device in three different positional stages relative a container in plan view.

Figure 2A shows a top plan view of the closure from Figure 1 and Figure 2B shows a bottom plan view of the connector from Figure 1.

Figures 3 to 6 show in schematic form alternative locking mechanism principles. Figure 7 shows schematically a connector with alternative distal connecting means.

Figure 8 shows schematically a connector design with a movably arranged shaφ.

Description of drawings In Figures 1A to 1C position 1 indicates a rigid bottle with an attached device according to the invention. Bottle 1 has a neck 2, a rim 3 and an opening 4. A closure member 5 comprises a pierceable sealer 6 of stopper type, having a cylindrical part 7, adapted to the opening interior, with a cavity 8 for limitation of necessary needle penetration, and a flange part 9 for abutment against bottle rim 3. Closure 5 further comprises a capping 10, having a substantially cylindrical sleeve part 11, with internal rest and lock projections 12, and a closing top surface 13, with a hole 14 for needle penetration. A connector 15 comprises a cylindrical housing 16, having a proximal end 17, with an internal flange part 18 for rest against the top surface 13 of capping 10, an intermediate part 19, with a fix wall 20 carrying a shaφ in the form of a hollow needle 21 , and a distal end 22 for pressure application and connection to a secondary vessel. Stopper 6 is attached to the capping 10 to form a closure 5 unit and connector 15 and closure 5 are united by friction to form a device assembly. A locking mechanism between closure 5 and connector 15 is not shown but will be described in relation to Figure 2. Figure 1 A shows an initial stage in which the device assembly has been placed on bottle 1 so that stopper 6 cylindrical part 7 only partially extends into bottle 1 opening 4 and without contact between flange 9 and rim 3. The sleeve part 1 1 of capping 10 rests on rim 3 in a first push lock position stabilized by first and second projections 12 above and under rim 3. The positions in this stage may be useful when communication between bottle interior and surroundings is desirable, as for any of the puφoses previously described, and to assure such a communication lateral openings (not shown) may be present for example in sleeve 1 1 of capping 10 and in cylindrical part 7 of stopper 6. The not shown locking mechanism between closure 5 and connector 15 is assumed to be in the locked state that prevents axial displacement of connector 15 in relation to closure 5. In this stage an axial pressure applied to connec- tor 15 distal end 22 will be transferred to closure 5. Figure IB shows a second stage in which such a pressure has brought the device assembly as a whole down towards the bottle 1 and in which position the closure is in full engagement with bottle opening 4. Stopper 6 cylindrical part 7 is fully accommodated in opening 4 and its flange 9 in contact with bottle rim 3. Capping 10 is in a second push lock position stabilized by third and fourth projections 12 above and under rim 3. The push lock and stopper friction may be sufficient for final retention of the closure but if desired additional means may be used such as a crimp under rim 3, a locking ring preventing sleeve 11 from flexing out or the push lock engagement or any other means. Figure 1C shows a stage in which the locking mechanism has been disengaged to allow relative axial displacement between connector 15 and closure 5 and such a displacement has taker- place to let needle 21 pass through hole 14 and penetrate stopper 6 upper part into cavity 8 to establish fluid communication. A second container, syringe or duct may now be attached to the distal end 22 of connector 15.

Figure 2 shows a preferred locking mechanism for the device of Figure 1. Figure 2A is a top plan view of closure 5 with its closing top surface 13 and hole 14 for needle 21. At regular intervals along the closure periphery are recesses or cut-outs 23 extending axially along sleeve 1 1 a distance at least corresponding to the desired movement between the two defined positions for the connector 15 and ending in shelves 24. Figure 2B is a bottom plan view of the connector 15 with cylindrical housing 16, proximal end 17, flanges 18, wall 20 and needle 21. The diameter of inner surface 25 corresponds to the outer surface size of closure 5, allowing it to slide over the closure. The flanges 18 projects inwardly from inner surface 25 a bit up from proximal end 17, to permit an initial engagement between closure and connector, and are distributed and sized in a manner corresponding to the recesses 23 of closure 5. By relative rotation between these parts flanges 18 and recesses 23 may be brought either in alignment or disalignment. When disaligned flanges 18 rests on capping top surface 13 between the recesses 23 and the connector cannot be displaced further towards the capping but may transfer a pressure applied at its distal end 22 to capping 5. When aligned flanges 18 may travel along recesses 23 to allow connector 15 to approach capping 5 in the shaφ penetration step until wall 20 abuts the capping top surface 13 or until flanges 18 abut shelves 24. Additional optional features may be included on the parts, e.g. a lock for the connector 15 at the end of its travel for example lateral undercuts close to the shelves for slightly hook shaped flanges or means for giving distinct stops at the aligned and disaligned positions respectively. Figures 3 to 6 show in schematic form alternative locking mechanism principles. As in

Figure 1 the main parts shown is a closure 5 and a connector 15 with sleeve 11 and shaφ 21 attached to rigid wall 20. The embodiment of Figure 3 relies on friction for locking and a locking ring 30 is arranged to compress the lower part of sleeve 1 1 against closure 5, which may take place by locking ring resilience, by slightly conical ring or sleeve surfaces or in any other way. To facilitate compression lower part of sleeve 1 1 may be axially slitted. In the embodiment of Figure 4 a number of tongues 40 or a continuous flange extends inwardly from the inner wall of sleeve 1 1. The tongues normally bears on top surface 13 of the closure 5 and are rigid enough to sustain the necessary pressure for pushing the closure into engagement with the container but are designed to yield under higher pressure to a second position indicated at 41, allowing the connector to move into its second position. In Figure 5 similar tongues 50 are arranged on arms 51 hinged to the sleeve 1 1. When the arms are flush with sleeve 1 1 the tongues 50 bear on closure 5, as shown in Figure 5A, but the arms 51 may be flexed out, as shown in Figure 5B, to free the connector for displacement relative closure 5. Flexing of arms 51 may be made manually but preferably the arms are resilient and biased towards one of the positions, suitably to the open position shown in Figure 5B and may be retained in the closed position of Figure 5A by an axially displaceable ring or tearable strip 52. In Figure 6 similar tongues 60 are provided on an openable or tearable strip 61 with a generally T-shaped cross-section. In the connecting step the strip 61 is removed to allow relative displacement between connector 15 and closure 5. It is clear that the locking mechanism can be designed in a multitude of ways. The embodiments of Figure 3 to 6 have the advantage of not requiring any particular locking structures on the closure 5 and accordingly being com- patible with many standard closure designs.

Figure 7 shows schematically how the distal end 22 of connector 15 can be redesigned depending on the nature of the secondary vessel to be connected. In this embodiment the double-tipped needle 21 of the previous embodiments is replaced with a single needle 71 in the proximal end of the connector and ending in a luer taper 72 formed in the wall 73 e.g. to receive a syringe with a corresponding luer.

Figure 8 shows schematically a connector having a substantially cylindrical sleeve part 81 in which a slideable wall 82 is arranged carrying a shaφ 83. The wall is locked in position by pegs 84 penetrating the sleeve 81 and at least partly into the wall 82 and being accessible from the sleeve 81 outside. Other locking means, such as similar to those shown in Figures 2 to 6, can be used. In use the device as shown may carry pressure from its distal end to closure 5. The locking means provides at least two defined position for the shaφ and allow the connecting sequence to be controlled, e.g. by first making the connection to the secondary- vessel with retained locking means, by first making the connection to the primary container by removal of the lock and pushing of wall 82 towards the container or substantially simulta- neously by removal of the lock and axial compression of container and vessel.

The invention is not restricted to the embodiments shown but can be varied within the limits of the appended claims.

Claims

Claims 1. A device for sealing or connecting a container, having at least one opening with an opening axis, comprising (a) a closure member for arrangement in, at or around the opening and having at least one pierceable part, (b) a connector attachable, when oriented at least par- tially coaxial with the opening, at a proximal end to the container and at a distal end directly or indirectly to a vessel in the form of a second container, a syringe or a duct and (c) a shaφ operable to penetrate at least the pierceable part and to establish a fluid communication between the container and the vessel, charact erized in the improvement comprising that the shaφ is connected to or integral with the connector so as to follow it in at least its axial movements, that the connector is axially movable in relation to the closure between at least two defined positions, said positions comprising:

(i) a first position in which the shaφ is axially remote from the closure so as not to pierce it and in which the connector bears directly or indirectly on the closure so that an axial force applied to the connector is transmitted to an axial force on the closure and (ii) a second position in which the shaφ penetrates the closure, a releasable locking mechanism arranged to prevent, when engaged, and to permit, when disengaged, movement of the connector from the first to the second position.

2. The device of claim 1, characterized in that the closure has a surface com- ponent transversal to the opening axis.

3. The device of claim 1, characterized in that the closure general design includes a sleeve portion, extending substantially axially, and a closing top surface.

4. The device of claim 3, characterized in that the sleeve part is designed to engage the exterior of an opening having a tube or neck part.

5. The device of claim ^characterized in that the closure includes means for physical attachment to the opening.

6. The device of claim 5, characterized in that the attachment means includes such means for attachment in a pre-sealing position and in a sealing position.

7. The device of claim 1, characterized in that the closure comprises the pier- ceable part in the form of a pierceable sealer and further comprises a capping part adapted to secure the sealer against displacement from the opening.

8. The device of claim 7, characterized in that the sealer includes a membrane or septum.

9. The device of claim 7, characterized in that the sealer includes a plug or stopper for at least partial insertion in the opening.

10. The device of claim 7, characterized in that the capping is designed to engage the opening at least partly on the opening exterior.

11. The device of claim 1, characterized in that the connector is arranged to bear on the closure by means of friction and that the locking mechanism includes means to provide friction and to reduce or remove the friction respectively.

12. The device of claim 1, characterized in that the connector is arranged to bear on the closure over abutting surfaces therebetween, having at least a component peφen- dicular to the axis.

13. The device of claim 12, characterized in that the locking mechanism includes aligning means for aligning and disaligning respectively the surfaces.

14. The device of claim 13, characterized in that the aligning means are arranged to move the abutting surfaces lateral to the axis.

15. The device of claim 13, characterized in that the aligning means are arranged to mutually rotate the abutting surfaces at least partially around the axis.

16. The device of claim 1, characterized in that axially extending parts of capping and connector are connected in a telescopic manner.

17. The device of claim 1, characterized in that the shaφ is one of a mating part of a valve mechanism in the opening, a pusher for opening a one-way valve, a pusher for displacing e.g. a stopper or plunger into the container or to a non-sealing section on the stopper or container, a member displacing a sealing part of the closure such as a sealing pin or a part deforming a sealer into a non-sealing form.

18. The device of claim 1, characterized in that the shaφ comprises a needle.

19. The device of claim 1, characterized in that the shaφ comprises a conduit for establishing fluid communication.

20. The device of claim 1, characterized in that the shaφ is arranged at least axially fixed in the connector.

21. The device of claim 1, characterized in that the connector distal end comprises conduit completion means for the flow between container and vessel.

22. The device of claim ^characterized in that the connector distal end comprises means for physical attachment of the vessel.

23. A method for sealing or connecting a container, having at least one opening with an opening axis, to a vessel in the form of a second container, a syringe or a duct, c h a r a c t e r i z e d i n that it comprises the steps of positioning a closure, having at least one pierceable part and being adapted to close the container when pushed into an engagement position relative to the container, in, at or around the opening substantially coaxial with the opening but distally displaced from the engagement position, abutting a connector, containing a shaφ operable to penetrate at least the pierceable part and to establish a fluid communication between the container interior and the surrounding, ddirectly or indirectly against the closure for axial force transmission, applying an axial pressure on the connector to move the connector and the closure towards the container and to push the closure into the engagement position relative the container and moving the shaφ towards the container to penetrate the pierceable part and to establish said fluid communication.

24. The method of claim 23, characterized in that it comprises the step of preassembling closure and connector and performing said placing and abutting steps by posi- tioning the preassembled parts as a unit relative the container.

25. The method of claim 23, characterized in that the closure comprises the pierceable part in the form of a pierceable sealer and a capping part adapted to secure the sealer against displacement form the opening.

26. The method of claim 25, characterized in that it comprises the step of preassembling and retaining the sealer with the capping and moving the sealer together with the capping during at least one of said steps.

27. The method of claim 25, characterized in that it comprises the step of resting at least the capping on the container during at least part of said positioning step.

28. The method of claim 23, characterized in that it comprises the step of se- curing fluid exchange conditions between container interior and surroundings at least some time between positioning of the closure and application of pressure.

29. The method of claim 28, characterized in that it comprises the step of performing under said fluid exchange conditions a sterilizing step.

30. The method of claim 28, characterized in that it comprises the step of performing under said fluid exchange conditions a lyophilizing step.

31. The method of claim 28, characterized in that it comprises the step of maintaining the container in a treatment chamber and performing the pressure application step when in the treatment chamber.

32. The method of claim 23, characterized in that it comprises the step of performing during said shaφ moving step a relative axial displacement between connector and shaφ.

33. The method of claim 32, characterized in that it comprises the step of releasing, before said axial displacement, an at least axial locking of the shaφ to the connector to thereby allow the shaφ to perform the axial displacement.

34. The method of claim 23, characterized in that it comprises the step of moving connector and shaφ axially together relative the container during said shaφ moving step.

35. The method of claim 34, characterized in that it comprises the step of performing said combined movement substantially axially without substantial rotational component.

36. The method of claim 34, characterized in that it comprises the step of disengaging, before said combined movement, said abutment relationship between closure and connector to allow relative axial motion therebetween.

37. The method of claim 36, characterized in that said disengagement of abutment relationship includes the step of relative rotation between closure and connector.

38. The method of claim 36, characterized in that said disengagement of abutment relationship includes the step of laterally displacing abutting surfaces between closure and connector.

39. The method of claim 23, characterized in that the movement of connector and shaφ together includes the step of displacing a skirt portion of the connector over the closure to act as a locking ring therefore.

40. The method of claim 23, characterized in that it comprises the step of establishing said fluid communication through a channel in the shaφ.

41. The method of claim 23, characterized in that it comprises the step of connecting the vessel to the connector to establish fluid communication with container interior.

42. The method of claim 41, characterized in that the connecting step being performed before movement of the shaφ.

43. The method of claim 41, characterized in that the connecting step is performed after movement of the shaφ.

44. The method of claim 41, characterized in that the connecting step is performed about simultaneous with the movement of the shaφ.

45. The method of claim 41, characterized in that the connecting step includes penetrating a pierceable vessel member by a second shaφ in fluid communication with the first shaφ.

46. The method of claim 41, characterized in that it comprises the step of moving the vessel substantially coaxial with the opening.

47. The method of claim 41, characterized in that it comprises the step of attaching a syringe to the connector.

48. The method of claims 46 or 47, characterized in that it comprises the step of attaching a luer taper in flow communication with the shaφ.

49. The method of claim 41, characterized in that it comprises the step of performing a reconstitution step after the connecting step.

50. A device for connecting a container, having at least one opening defining an opening axis, to a vessel in the form of a second container, bag, syringe or duct, comprising (a) a closure member for the opening having a pierceable part, (b) a connector being axially displaceable in relation to the closure member and (c) a shaφ, able to penetrate a pierceable container sealer part, connected to or integral with the connector to accompany the connector in its axial movements, charact erized in the improvement comprising that the closure member has at least one resting surface extending transversely to its axis, that the connector has at least one stop surface extending transversely to its axial di- rection, that the resting surface and stop surface when in at least partial axial direct or indirect alignment and abutment prevents axial displacement of the connector in relation to the closure member and that the resting surface and stop surface can be brought out of axial alignment to allow axial displacement of connector and shaφ in relation to and towards the closure member.

51. The device of claim 50, characterized in that it comprises any one of the characteristics of claims 2 to 22.

52. A method for connecting a container, having at least one opening defining an opening axis, to a vessel in the form of a second container, bag, syringe or duct, comprising (a) a closure member for the opening, (b) a connector being axially displaceable in relation to the closure member and (c) a shaφ, able to penetrate a pierceable container closure part, connected to or integral with the connector to accompany the connector in its axial movements, charact erized in that it comprises the steps of bringing or maintaining at least one resting surface on the closure member, having at least one surface component transversal to its axis, and at least one stop surface on the connector, having at least one surface component transversal to its axis, in direct or indirect alignment and abutment to prevent axial displacement of the connector in relation to the closure member, applying force to the connector to thereby move the closure member and connector to- gether, with the closure member leading, disaligning the resting surface and stop surface and displacing axially connector and shaφ in relation to and towards the closure member.

53. The method of claim 52, characterized in that it comprises any one of the characteristics of claims 24 to 49.