METHOD FOR CLOSING VIALS, SUPPORTING STRUCTURE FOR VIAL STOPPER MEMBERS AND TRANSPORT OR PACKAGING CONTAINER
FIELD OF INVENTION
The present invention relates in general to the processing of a batch of vials for use in pharmaceutical, medical or cosmetic applications and relates in particular to a supporting structure (also named nest) provided for holding stopper members, such as elastic plugs or plunger stopper members, at predermined positions, for use in a process for closing or stoppering such vials. Further aspects of the present invention relate to a nest and tub assembly accommodating at least one supporting structure supporting a plurality of such stopper members, which can be directly fed on existing filling and stoppering machine set-ups for simultaneously processing a plurality of vials. Further aspects of the present invention relate to a stoppering process and to an integrated filling and stoppering process for processing a plurality of vials.
BACKGROUND OF INVENTION
Conventionally presterilized vials are supplied in tub and nest assemblies that are hermetically sealed to the environment to pharmaceutical customers, who then fill medicine into the presterilized vials and close them under sterile conditions using filling and stoppering machines. In the market there are three types of filling and stoppering machines available, namely 1) manual machines, 2) semi automatic machines and 3) fully automatic machines. There is one tub and nest format available in the market for vials but there are lots of disadvantages to use this existing tub and nest format with existing as well as new filling and stoppering machines because this tub and nest format requires complete setting change from infeed to outfeed for accommodating different height level of vials into the nest. Moreover a complete replacement of filling carriers is required for maintaining the height between the filling nozzles and the vial top level. Further the drawback of two different change parts needs separate validation study as per GMP (Good Manufacturing Practice) guidelines requirements. If one tries to fill the vial nest available in the market on the same machine without changing the machine height setting accidents will happen which may cause damage to the filling nozzles or glass vials may get broken because the height difference between the filling nozzles and the vials is too small.
These disadvantages similarly hold 1) for manual filling and stoppering machines, which are operated electrically and pneumatically and where the processes are triggered by an operator, 2) for semi automatic filling and stoppering machines, which are operated electrically, electronically and pneumatically and where the operator has to remove the outer bag of the tub and nest assembly and then a top lid from the tub along with an inner sheet, and 3) for fully automatic filling and stoppering machines, which are operated electrically, electronically and pneumatically and where whole packets are inserted into the filling and stoppering machine one by one, the machine will automatically remove the outer bag and then remove the top lid from the tub by means of an automatic peeling off unit, then the inner sheet of the tub and nest assembly will be removed automatically and the machine will then automatically pick up the nests by means of a vacuum cup and place them onto transport carriers, which are then moved towards the filling station nozzles for the medicine filling process.
Conventionally, vials are closed by feeding stopper members, such as elastic plugs or plunger stopper members, individually to a closing machine and closing the vials individually, as disclosed e.g. in US 2014/0069062 Al . This often requires removal of the vials from a carrier after filling and re-inserting the vials after closing into the carrier again, as disclosed e.g. in US 8,978,344 B2. Typically the stopper members are singulated using vibratory bowls and transported using vibratory chutes. The vibratory bowl and chutes contact the stopper members, the surfaces of which will eventually be in direct contact with the product inside the vial. To address this problem, it is generally considered necessary to steam sterilize the vibratory bowls and chutes. However, is practically impossible to transfer the stopper bowl and chutes aseptically from the sterilizing autoclave to the processing environment.
US 2012/0248057 Al discloses a capping system method for sealing pharmaceutical vials. A plurality of vials are disposed upright in a tub, which also accommodates a respective stopper member assembly for each vial comprising a preassembled elastomeric stopper and a retainer member, Each stopper member is placed on the neck of its associated vial so that a portion of the stopper partially closes the opening of the vial, Thereafter a force is applied to each of the stopper member assemblies to cause the retainer members to snap-fit on the flanged neck of their associated vial so that portions of their associated stopper seal the opening in their associated vial. This approach makes it easier to seal the vials under aseptic conditions.
For an exact positioning, the outer periphery of the upper tray for stopper members includes a generally V-shaped projection which is arranged to be disposed on a ledge of the sidewall of the bottom tray for vials so that each vial has a respective closure assembly disposed above and axially aligned with it.
A process for filling pharmaceutical containers that uses a similar capping system is disclosed in WO 2015/023924 A2. The process uses nests that are configured to allow multiple stopper members and containers to be simultaneously aligned concentrically, and closed simultaneously. Spring-loaded retaining structures on the stopper member nest allow it to releasably retain multiple stopper members above the corresponding multiple containers. The retaining structures used are, however, still complicated and it is not easy to use this approach in the existing machinery of pharmaceutical fillers. WO 2013/181552 A2 discloses another vial storage and transportation assembly, including a vial tray, a transport lid and a processing lid. The transport lid and the processing lid are interchangeably engageable with the vial tray to house a plurality of vials therein, to shift the assembly between a transport configuration and a processing configuration, SUMMARY OF INVENTION
According to the present invention there is provided a stoppering process or an integrated filling and stoppering process for processing a plurality of vials using a supporting structure for holding a plurality of stopper members. According to a further related aspect of the present invention there is provided a supporting structure for holding a plurality of stopper members (nest for stopper members), such as elastic plugs, at precisely defined positions, for use in the process for closing or stoppering vials. According to a related further aspect of the present invention there is provided a transport or packaging container (nest and tub assembly) accommodating at least one nest for stopper members configured so that the nest accommodating the stopper members can be directly fed on existing filling and stoppering machine set-ups for processing vials.
A supporting structure for stopper members according to the present invention, for use in the stoppering process or an integrated filling and stoppering process, is configured for releasably supporting a plurality of stopper members for closing vials for use in pharmaceutical, medical or cosmetic applications, wherein the stopper members consist of a resilient material and comprise a disk-like cap portion from which a plug projects. The supporting structure for stopper members comprises a planar supporting plate having a plurality of tubular receptacles for accommodating the stopper members at least partially, for concurrently supporting a plurality of stopper members at the supporting plate at precisely defined positions. According to the present invention the receptacles are formed by circumferential side walls disposed in a regular arrangement at the supporting plate and protruding from the supporting plate, wherein the receptacles are configured for accommodating the stopper members at least partially. According to the present invention the receptacles comprise retaining structures for releasably engaging with the disk-like cap portions of the stopper members for retaining the stopper members in the receptacles. The supporting structure for stopper members allows to releasably hold a plurality of stopper members exactly in the same two-dimensional arrangement as a supporting structure used for supporting a plurality of vials, i,e. the same total number of vials. This simplifies a process for closing the vials significantly, because this process only requires disposing the supporting structure for stopper members above the supporting structure for vials, preferably in an environment with reduced pressure, so that the receptacles of the supporting structure for stopper members are aligned with their associated receptacles of the supporting structure for vials, and pushing the stopper members downward out of the receptacles of the supporting structure for stopper members and into the filling openings at the upper ends of the vials while the vials are supported by the supporting devices of the supporting structure for vials.
As the supporting structure according to the present invention can be easily accommodated and stored or transported in a transport container (tub), the present invention enables using the existing tub and nest format widely used in the market with existing as well as new filling and stoppering machines. Furthermore, the supporting structure according to the present invention can be used to efficiently store and supply a plurality of stopper members in a predetermined geometrical arrangement under sterile conditions, using the tub and nest format widely used in the market. The receptacles may accommodate the stopper members fully or only partially, depending on the circumstances of the further processing of the stopper members and vials. The supporting plate is preferably made of a plastic material, e,g, by plastic injection molding, and offers sufficient strength, stiffness and mechanical stability, although these requirements are usually easy to fulfill, because the stopper members to be accommodated are light-weight and only small forces are usually exerted on the supporting plate during further processing,
The stopper members may be accommodated in the receptacles solely by friction. As the stopper members are made of or comprise an elastic (resilient) material, inserting the stopper members into the receptacles might involve imposing a slight elastic deformation of the stopper members so that the stopper members abut resiliently against the circumferential side walls of the receptacles. As the stopper members are light-weight, a reliably accommodation of the stopper members would usually require only a small degree of deformation of the stopper members, which corresponds to small forces required only for inserting or removing the stopper members into and out of the receptacles. As stopper members for vials usually have a cap portion on their outer circumference, this slight elastic deformation would usually occur only in the region of the cap portions. Thus, the side walls of the receptacles are preferably straight side- walls defining cylindrical receptacles that are not tapered. For more reliably accommodating the stopper members in the receptacles, according to a further embodiment the receptacles comprise retaining structures that releasably engage with the stopper members for retaining the stopper members in the receptacles. Preferably the retaining structures engage with the stopper members in a form-fitting manner. This form- fitting engagement may be implemented at the upper and bottom ends of the stopper members, or at any other suitable positions, such as at the bottom ends and at central portions of the stopper members. For this purpose, the retaining structure may slightly protrude into the interior of the receptacles or may be formed as a recess or groove to retain the stopper members.
According to a further embodiment the protrusions are formed on the inner sides of the circumferential side walls of the receptacles, which may be easily accomplished by integrally forming protrusions or recesses or grooves with the side-walls of the receptacles, e.g. by plastic injection molding,
According to a further embodiment the protrusions may be configured to mate to the outer contour of the stopper members.
According to a further embodiment the protrusions may be formed at equal angular distances along the inner sides of the circumferential side walls of the receptacles, e.g. as small spotlike protrusions. According to an alternative embodiment, however, the protrusions may also be formed as circumferential protrusions on the inner sides of the circumferential side walls of the receptacles. According to a further embodiment upper ends of the receptacles comprise are chamfered, to thereby form a slanted insertion portion facilitating insertion of the stopper members from above the supporting plate into the receptacles thereof.
According to a further related aspect of the present invention there is provided a transport or packaging container for accommodating a plurality of stopper members for closing vials for use in pharmaceutical, medical or cosmetic applications, wherein the transport or packaging container is box-shaped and comprises: a bottom, which is closed or sealed by a seal, upstanding lower side-walls extending essentially perpendicularly from said bottom, a circumferential supporting step extending horizontally from said lower side-walls, and upper side-walls extending upward from said supporting step, wherein a circumferential flange is formed at upper ends of the upper side-walls. According to the present invention at least one supporting structure for stopper members as disclosed in the present application is accommodated in the transport or packaging container, wherein the plurality of stopper members are accommodated in the receptacles of the at least one supporting structure for stopper members.
The transport or packaging container for stopper members enables the storage and transport of a plurality of stopper members in exactly the same format as the existing tub and nest format widely used in the market for the storage and transport of vials so that it may be used easily with existing as well as new filling and stoppering machines without the necessity of changing the whole setup thereof. According to a further embodiment the edge of the bottommost planar supporting plate of the supporting structure for stopper members accommodated in the transport or packaging container may be supported directly on the circumferential supporting step or the transport or packaging container. According to a further embodiment a plurality of supporting structures for stopper members may be accommodated together inside the transport or packaging container stacked one above the other. For this purpose, spacers might be provided on the bottom sides of the supporting plates, for preventing a direct contact of the receptacles (or of the stopper members accommodated in these receptacles) with an underneath supporting stracture or the bottom of the transport or packaging container. However, this is usually not required, because usually the bottom ends of the receptacles of an upper stopper member nest may rest directly on the top surface of another stopper member nest, because the outer diameter of the receptacles is larger than the inner diameter of the receptacles, so that the receptacles of the upper stopper member nest cannot enter the receptacles of another stopper member nest. For this purpose, it might be of advantage if the upper ends of the stopper members are fully accommodated in the receptacles and disposed at a certain minimum distance to the upper ends of the receptacles.
According to a further embodiment the transport or packaging container is closed or sealed by a protective foil against the environment, the protective foil being bonded to the circumferential flange. The protective foil may be impermeable to gas, thus implementing completely sterile conditions during storage and transport of the stopper members.
According to a particularly preferred embodiment the protective foil may be a gas-permeable plastic film enabling a sterilization of the interior of the transport or packaging container through the protective foil by a flow of a sterilization gas, such as ethylene oxide. Particularly the protective foil may be made of a web of synthetic fibers such as polypropylene fibers (PP) or a Tyvek® protective film for this purpose. According to a further related aspect of the present invention there is provided a method for closing a plurality of vials for use in pharmaceutical, medical or cosmetic applications, said vials having a filling opening at an upper end thereof, said method comprising: providing a supporting structure for stopper members as disclosed in the present application accommodating a plurality of stopper members in the receptacles in a regular arrangement, at precisely defined positions; providing a supporting structure for vials comprising a supporting plate having a plurality of openings or receptacles disposed in the same regular arrangement as in the supporting structure for stopper members and a plurality of supporting devices for supporting the vials on the supporting plate as the vials are inserted into the openings or receptacles; disposing the supporting structure for stopper members above the supporting structure for vials, preferably in an environment with reduced pressure, so that the receptacles of the supporting structure for stopper members are aligned with the receptacles of the supporting structure for vials; and pushing the stopper members simultaneously downward out of the receptacles of the supporting structure for stopper members and into the filling openings at the upper ends of the vials while the vials are accommodated in the openings or receptacles of the supporting structure for vials.
The nest accommodating the stopper members can be directly fed on existing filling and stoppering machine set-ups for processing presterilized vials. The method according to the present invention can be implemented easily for vials of different lengths, because this requires just an adjustment of the distance between the supporting structure for stopper members and the supporting structure for vials, which can be accomplished by a simple vertical adjustment of either supporting structure, which does not change the exact alignment of the receptacles of both supporting structures.
According to a further embodiment the supporting structure for vials is held by a bottom holding frame, whereas the supporting structure for stopper members is held by an upper holding frame, wherein the bottom holding frame and the upper holding frame are disposed at a fixed spacing and aligned with each other by alignment devices. For this purpose one of the holding frames may be provided with alignment devices, such as protrusions, rods or the like, that cooperate with corresponding alignment devices, such as holes or recesses, provided on the other holding frame. Thus, an exact, reliable alignment of all receptacles of the supporting structures can be accomplished easily. According to a further embodiment, bottoms of the vials may be supported on a supporting surface interposed between the bottom holding frame and a machine holding frame commonly supporting the bottom holding frame and the upper holding frame. The intermediate supporting surface can be used to adjust the distance between the upper ends of the vials and the bottom ends of the receptacles of the supporting structure for stopper members, but may also serve to transfer forces exerted onto the vials during the stoppering process by pushing down the stopper members into the filling openings of the vials onto the intermediate supporting surface rather than onto the supporting devices of the supporting plate of the supporting structure for vials.
Particularly, in such an embodiment the vials may be supported directly on the supporting surface rather than on the supporting devices of the supporting plate of the supporting structure for vials such that the upper ends of the vials are released by the supporting devices in an elevated processing position during the stoppering process. This offers a high degree of freedom when selecting the specific type of supporting structure for supporting the vials on the supporting plate.
According to a further embodiment, the supporting devices are holding tabs formed at upper ends of resilient holding arms, wherein the holding tabs are matched to the vials such that the vials rest loosely on upper sides of the holding tabs with widened upper rims formed at upper ends of the vials, or wherein the holding tabs embrace the widened upper rims formed at upper ends of the vials, preferably so that the via!s are held by the holding tabs with a radial clearance or with radial and axial clearance. Various different types of supporting types may be used as well for this purpose.
According to a further embodiment the upper holding frame may be disposed at such a distance to the bottom holding frame that the upper ends of the vials are in direct contact with or at a small distance to bottom ends of the tubular receptacles of the supporting structure for stopper members so that the stopper members may be directly guided into the open upper ends of the vials if pushed down out of the receptacles of the supporting structure for stopper members. Furthermore, this configuration during processing helps to further minimize the risk of dust and pollutants entering the interior of the vials via the filling openings at upper ends thereof. In this method, the supporting structures for stopper members and/or the supporting structures for vials may be supplied under sterile conditions, e,g. to a pharmaceutical filler, in transport and packaging containers as outlined in the following in more detail.
Of course, the method according to the present invention may involve additional processing steps, particularly a step of filling the plurality of vials with a pharmaceutical, medical or cosmetic product, which can be performed in any suitable sequence, particularly row-wise or simultaneously for all vials supported by a supporting structure. According to a further embodiment this step of filling the plurality of vials with the pharmaceutical, medical or cosmetic product may be performed while the supporting structure for vials is held in the same bottom holding frame used during stoppering. According to a further embodiment of the process, after closing the vials with the stopper members in a gas-tight manner, the vials may be protected further against the intrusion of contaminants into the vial, for example by crimping a metal protective foil, as is known from the prior art. This crimping process may be performed while the vials are accommodated in the openings or receptacles of the supporting plate of the supporting structure for vials.
OVERVIEW ON DRAWINGS
Hereinafter, the present invention will be disclosed in exemplary manner and with reference to the drawings, wherein:
Figs, 1a - lc show details of a supporting structure for stopper members for vials according to a first embodiment of the present invention;
Figs. 1d - 1f show the accommodation of stopper members in the receptacles of a supporting structure for stopper members for vials according to a further embodiment of the present invention;
Figs, 1g - lh show perspective exploded views of a supporting structure for stopper members for vials with stopper members according to two preferred embodiments of the present invention;
Fig. 1i shows a perspective top view of a supporting structure for stopper members for vials with stopper members being accommodated in receptacles thereof;
Figs. 2a - 2d show a transport or packaging container together with the supporting structure of Fig. la (tub and nest assembly for stopper members) for accommodating a plurality of stopper members for vials, at various stages of providing the transport or packaging container for stopper members;
Fig. 3a is a perspective view of a vial and of a stoppering member before performing the stoppering process;
Fig. 3b is a perspective view of a vial sealed by a stoppering member after performing the stoppering process according to the present invention;
Fig. 4a is a perspective top view of a supporting structure for vials for use in a method according to the present invention;
Fig. 4b is a top view of the supporting structure of Fig. 4a;
Fig. 4c is a bottom view of the supporting structure of Fig. 4a; Fig. 4d is an exploded perspective view of the supporting structure of Fig. 4a together with vials to be supported;
Fig. 4e is a perspective top view of the supporting structure of Fig. 4a showing how the vials are supported;
Fig. 4f is perspective top view of a tub and nest assembly for vials, in which the supporting structure of Fig. 4a is accommodated, with a sealing lid removed;
Fig. 4g is an exploded perspective view of the tub and nest assembly for vials of
Fig, 4f with the supporting structure for vials inserted and a sealing lid to be bonded on an upper edge of the transport or packaging container;
Fig. 4h is a sectional view of the supporting structure of Fig. 4e showing how the vials are supported inside the receptacles of the supporting structure for vials;
Fig. 5 shows a method according to the present invention for simultaneously closing (stoppering) a plurality of vials in a schematic sectional side view;
Fig, 6 is a schematic top view of a processing station for processing and sealing vials using the supporting structure for stopper members according to the present invention in a filling process; and
Fig. 7 is a perspective top view showing the supporting structure for vials with sealed vials after processing in a process according to the present invention as shown in Fig, 5.
Throughout the drawings, the same reference numerals designate identical or substantially the same components or groups of components.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
A supporting structure (in the following nest for vials or vial nest) in the sense of the present invention is used for concurrently supporting a plurality of vials, preferably of pre-sterilized vials or sealed vials, for use in pharmaceutical, medical or cosmetic applications, Such vials, including pen vials, by-pass vials and dental vials, are a commonly-used packaging solution for drug delivery systems, e.g. insulin administration, pen systems, pump systems, auto- injectors and needle free injectors. For special requirements such as by-pass and chemically strengthened vials, personalized designs are available on the market. Vials available on the market may be made of glass material, particularly of Fiolax® glass from SCHOTT AG, or of plastic material and offer fixed volumes for drug delivery of e.g. 1.0 ml, 1.5 ml and 3.0 ml, Different volumes usually correspond to different axial lengths of the vials. An example of such medication containers embodied as vials is schematically shown in Fig. 3a in a perspective view. These have a cylindrical basic shape, having a cylindrical side wall 50 with - within tolerances - constant inner and outer diameters, which project vertically from a flat vial bottom 50a, and is followed by a shoulder portion 51 , which merges in a constricted neck portion 52 of a relatively short axial length near the upper open end of the vial and then merges in an expanded upper rim 53 (so-called rolled edge), which has a larger outer diameter than the associated neck portion 52 and is configured for connection to a closure member 200. As can be concluded from Fig. 3 a, the underside of the rolled edge 53 may extend basically in horizontal direction or may be slanted and extend downward under a small acute angle and towards the constricted neck portion 52.
The neck portion 52 can be formed with smooth walls and without an external thread or may be provided with an external thread for screwing on a closure member. Such vials are radially symmetric and are made of a transparent or colored glass or of a suitable plastic material by blow molding or plastic injection molding techniques, and in general can be internally coated so that the material of the vial emits minimal impurities to the agent to be received.
They are sealed with a stopper 200 of a resilient material, e.g. rubber, with a piercing area 202 (septum or puncture rubber), The stopper 200 generally comprises a disk-like cap portion 201 from which a plug 203 projects, which may be inserted into the filling opening of the vial. The disk-like cap portion 201 is connected with the upper rim 53 of the vial in a gas-tight manner and protected against the intrusion of contaminants into the vial, for example by crimping a metal protective foil (beaded cap or cramp), often made from an aluminum sheet. More specifically, the cap portion 201 may be formed by a cylindrical side- wall 201a of a predetermined axial length, from which two leg portions 203 project substantially perpendicularly, forming the plug of the stopper 200, wherein a recess 202 is formed between the two leg portions 203 for facilitating piercing of the stopper 200 and enabling venting the interior of the vial via the recess 202 if the stopper 200 is only partially inserted into the filling opening of the vial. A semi-circular radial protrusion 204a can be formed on the outer side of the two leg portions 203 for enhancing the sealing tightness if the stopper 200 is inserted into the filling opening of the vial. Fig. 3b shows the vial with the stopper 200 inserted into the filling opening thereof. Fig, la shows a supporting structure for stopper members (in the following nest for stopper members or stopper nest) in a perspective bottom view, which comprises a planar supporting plate 60 having rounded corners 64 and a plurality of tubular receptacles 61 disposed in a regular arrangement, which extend downward from the bottom side of the planar supporting plate 60. The tubular receptacles 61 are formed by circumferential side-walls 62 protruding from the bottom side of the supporting plate 60. Preferably these side-walls 62 are of cylindrical shape for accommodating the stopper members 200, although other shapes, such as elliptic shapes might also be possible. These receptacles 61 are disposed in the same regular two-dimensional arrangement as for the supporting structure for vials set forth below, preferably at equidistant spacing.
Fig. lb shows the supporting structure for stopper members in a perspective top view,
Fig. lc shows how the stopper members 200, such as elastic plugs, are accommodated in the receptacles 61 of the stopper nest 2. For this purpose, the stopper members 200 are inserted from above or below into the receptacles 61 to a desired extent, preferably until they are fully accommodated in the receptacles 61 and the bottom ends of the stopper members 200 are substantially flush with the bottom ends of the side- walls 62 of the receptacles 61 as defined by the retaining structures inside the receptacles 61, which will be explained in more detail hereinafter.
As shown in the enlarged partial cross-section on the right-hand side of Fig. lc, the receptacles 61 are of cylindrical shape, wherein the upper rim 65 may be chamfered to ease insertion of the stopper members 200 into the receptacles from above the supporting plate 60. Below the chamfered upper rim 65 the side-walls of the receptacle 61 may extend perpendicularly to the top surface of the supporting plate 60 to form a cylindrical insertion portion 66, which may have the same diameter as the receptacles 61 at their bottoms ends. As shown in Fig. lc, a radial protrusion 67, preferably a circumferential radial protrusion 67, is formed below the insertion portion 66, which forms a constriction having a smaller inner diameter than the inner diameter of the receptacle 61. The radial protrusion is followed by a circumferential groove or recess 68 formed on the inner side of the side-walls 62. The axial length of the groove 68 corresponds to the axial length of the cap portion 201 of the stopper member 200 to be accommodated. For retaining the stopper members 200 reliably in the receptacles 61, particularly for avoiding that the stopper members 200 simply slide out of the receptacles 61 during handling of the stopper member nest which might include reversing the orientation of the stopper nest, the receptacles 61 comprise retaining structures 67, 68 for j-eleasably engaging with the stopper members 200 for retaining the stopper members 200 in the receptacles 61. More specifically, the retaining structures correspond to the radial protrusion 67 and to the circumferential groove 68 respectively formed on the inner sides of the circumferential side walls 62 of the receptacles 61 and configured to cooperate with the disk-like cap portions 201 of the stopper members 200 in a form-fitting manner. The axial lengths and/or the inner diameters of the grooves 68 may be equal to or slightly larger than the axial lengths and/or outer diameters of the cap portions of the stopper members
200 so that the stopper members 200 may also be retained loosely, i.e. even with radial and/or axial play, by the two retaining structures 67, 68 or at least with minor friction only.
Upon insertion of a stopper member 200 into a receptacle 61 from above the supporting plate 60, the bottom rim of the disk-like cap portion 201 first abuts with the chamfered upper rim 65. Upon further insertion of the stopper member 200 the side- wall 201a of the cap portion
201 slides over the radial protrusion 67 and into the groove 68. Finally the disk-like cap portion 201 is fully accommodated in the groove 68 to be secured in axial direction by the edges of the groove 68 and by the radial protrusion 67 in a form-fitting manner. In the position shown in the enlarged partial cross-section on the left-hand side of Fig. lc the circumferential side-wall of the cap portion 201a abuts to the inner side-wall of the groove 68. Figs. Id and I f show how further embodiments of stopper members 200 for vials are retained in the stopper nest. As shown in the. enlarged sectional view of Fig. Id, the stopper member 200 may further comprise a circumferential radial protrusion 204a and a circumferential groove 204b formed on the central plug portion 205 of stopper member 200, which is chamfered at a bottom end thereof. As shown in the enlarged sectional view of Fig. le, the central plug portion may also be formed by two leg portions 203 disposed on diametrically opposite sides, each having a chamfered bottom end 203a, a central recess 202 being formed between the two leg portions 203, e.g. for venting the interior of a vial if the stopper member 200 is only partially inserted into the filling opening of a vial. Additional recesses 201b my also be formed on the upper surface of the stopper member 200, e.g. to render the cap portion 201 more flexible. As shown in the enlarged sectional view of Fig. If, the central plug portion may also be provided with an additional horizontal venting channel 206 for venting the interior of a vial if the stopper member is only partially inserted into the filling opening of a vial. Figs, 1g to 1h show perspective exploded top views of a supporting structure for stopper members for vials with stopper members according to two different embodiments of the present invention. Fig. 1 i shows a perspective top view of a supporting structure for stopper members for vials with stopper members being accommodated in receptacles thereof. As shown in Fig. li, when the stopper members 200 are accommodated in the receptacles 61, there exists a gap in axial direction between the top surfaces of the stopper members 200 and the upper surface of the supporting plate 30 of stopper nest 2. For the transport, storage and packaging of a stopper nest 2 as outlined above together with the stopper members accommodated therein a transport or packaging container 3 a (hereinafter also named tub for stopper members) is used as schematically shown in Fig. 2a. According to Fig. 2a, the transport or packaging container 3a has basically the same configuration as described below with reference to Fig. 4f and is essentially box-shaped or tub-shaped and has a base 30a, a circumferential side wall 31a protruding essentially in vertical direction therefrom, a supporting step 32a protruding essentially rectangular therefrom, a circumferential upper side wall 33a and an upper rim 34a which is formed as a flange. The corners 35a of the transport or packaging container 3a are suitably formed rounded, particularly near the supporting step 32a. Preferably, the upper side wall 33a is formed inclined at a small angle of inclination with respect to a vertical to the base 30a in order to ease the insertion of the stopper nest 2. Such a transport or packaging container 3a is preferably formed from a plastics material, particularly by plastic injection molding, and is preferably formed of a clear transparent plastic in order to enable a visual inspection of the nest 2 accommodated in the transport or packaging container 3 a and of the stopper members accommodated in it. The rounded corners 64 of the supporting plate 60 mate to the inner rounded corners 36a of the tub 3a, at least if disposed at the bottom end of the upper side walls 33 a. As shown in Fig. 2a, a plurality of stopper nests 2 (in this example five stopper nests 2) can be accommodated inside the same transport or packaging container 3 a stacked one above the other, in the stacked configuration, the lower ends of the side-walls of an upper of two adjacent supporting plates 60 may rest directly on the upper surface of the lower of two adjacent supporting plates 60. If the outer diameter of the receptacles 61 is larger than the inner diameter of the receptacles 61, the side-walls 62 will not penetrate into the insertion portions 66 of the receptacles 61. Thus, no spacers are required between adjacent supporting plates 60, which contributes to optimizing the packing density.
According to further embodiments (not shown), spacers may be provided on the upper surface of lower surface of the supporting plates 60 to thereby prevent a direct contact betweeen the bottoms ends of the receptacles of an upper supporting plate 60 and the upper surface of an underneath supporting plate 60 in the stacked configuration.
Fig. 2b shows the tub and nest assembly 4a for stopper members with all stopper nests inserted into the tub 3a for stopper members, i.e. in the stacked configuration. For reasons of clarity, the stopper members are omitted in Figs. 2a and 2b. As shown in Fig. 2b, a gap 39a is formed between the edges of the supporting plate 60 and the upper side- walls 33a of tub 3a by spacer webs 38a, which will ease insertion and removal of the stopper nests. Fig, 2 c shows a further stage of sealing the tub and nest assembly 4a of Fig. 2b , by sealing the upper end of tub 3a with a protective foil 6a, which may be bonded to the circumferential flange 34a and may be gas-impermeable. Preferably, however, the protective foil 6a is a gas- permeable plastic film, in particular a web of synthetic fibers such as polypropylene fibers (PP) or a Tyvek® protective film, which enables a sterilization of the interior of the transport or packaging container 4a by a flow of a sterilizing gas through the protective foil 6a.
Fig. 2d shows the tub and nest assembly 4a of Fig. 2c sterile sealed against the environment. In this condition the stopper members may be stored and transported under sterile conditions. For this purpose, the tub and nest assembly 4a for stopper members may be packaged additionally in at least one gas -impermeable sterile plastic bag (not shown).
Referring to Figs. 4a to 4e, a supporting structure for vials 1 (in the following nest for vials or vial nest) comprises a planar supporting plate 10 having a plurality of openings or receptacles 11 disposed in a regular arrangement. As shown in the cross-sectional view of Fig. 4h, the receptacles 11 may be formed by cylindrical side- walls 14, which extend downward from the bottom side of the planar supporting plate 11. Preferably these side- walls 14 are of cylindrical shape for accommodating the vials, although other shapes, such as polygonal shapes, are also possible, These receptacles 1 1 are disposed in a regular two-dimensional arrangement, at equidistant spacing. As shown in the top view of Fig. 4b, virtual connecting lines between the centers of directly adjacent receptacles 1 1 respectively may form a hexagon with a further receptacle 11 disposed at a center of the respective hexagon. According to other embodiments, the receptacles may also be disposed at equidistant spacing along two mutually orthogonal directions. The inner diameter of the receptacles 1 1 is slightly larger than the outer diameter of the vials to be accommodated.
As shown in Fig. 4a, the supporting plate 10 comprises rounded corners 12. Furthermore, extensions 13 extend beyond two opposite edges of the earner plate 10, which may be used as spacer members to ensure a proper spacing between the supporting plate 10 and side-walls of the transport and packaging container if inserted therein.
As shown in Fig. 4a, resilient holding arms 17 are associated with respective receptacles 61 in a configuration with a three-fold point symmetry. This results in a symmetrical force distribution when holding the vial by means of the holding arms 17. The holding arms 17 thus result in an advantageous three-point bearing of the vials in the openings or receptacles 1 1 , so that the vials are automatically supported centered with respect to a center line of the respective opening or receptacle 11. Holding tabs 17a which are flag-like are formed at the upper ends of the holding arms 17. These holding tabs 17a are each provided with a holding nose 17b protruding inward in radial direction, as shown in more detail in the cross-section through this holding structure shown in Fig. 4h. According to Fig. 4h, the holding tabs 17a are connected with the supporting plate 10 via a resilient base 17 protruding perpendicularly from the upper side of the supporting plate 10. In use the bottom side of the widened upper rim 53 of a vial rests on the holding nose 17b protruding into the aperture of the supporting plate 10. The holding nose 17b passes over into a slanted insertion surface extending slanted upward, which connects with the upper end of the holding arm 17. Due to the slanted insertion surface on the upper side of the holding tab 17a and due to the shape of the bottom end of the holding tab 17a, which is open towards the bottom, the vials can be inserted selectively either from above or from below into the apertures of the supporting plate 10 and taken out again,
As the vials are inserted from above into the apertures, at first the bottoms or bottom ends of the vials get in contact with the slanted insertion surfaces of the holding tabs 17a. Upon further insertion of the vials the bottom ends or the bottoms of the vials slide downwards along the slanted insertion surfaces and thereby resiliently spread the holding arms 17 increasingly apart or flap or pivot them back. Upon further insertion of the vials finally the cylindrical side walls 50 of the vials (see Fig. 4h) get in contact with the holding noses 17a and slide there along, until eventually the undersides of the expanded upper rims 53 of the vials rest loosely on the holding noses 17b of the holding tabs 71a. Afterwards, the vials can be removed from the apertures of the supporting plate 10 upward with reversed motion sequence and with resilient bending of the holding arms 17. As the containers are inserted from below into the apertures, at first the upper ends of the vials get in contact with the curved portions on the bottom side of the holding tabs 17a. Upon further insertion of the vials the uppers ends of the vials slide upwards along the curved portions and thereby resiliently spread the holding arms 17 increasingly apart or flap or pivot them back. Upon further insertion of the vials the undersides of the expanded upper rims 53 of the vials slide beyond the holding noses 17b of the holding arms 17 and finally rest loosely on the holding noses 17b. Afterwards, the vials can be removed from the apertures of the supporting plate 10 e.g. upward without resilient bending of the holding arms 17.
As shown in Fig. 4a recesses 20 and/or corresponding protrusions 21 are formed along the side edges of the supporting plate 10. The recesses 20 have a frustro-tri angular shape, if viewed in a top view, and are formed by upright side-walls projecting perpendicularly from the top surface of the supporting plate 10, namely by a central side- wall 20a and two inclined side-walls 20b, which intersect the central side-wall 20a under an acute angle, The inclined side- walls 20b are followed by lateral extensions 20c. The protrusions 21 have a corresponding frustro-triangular shape, if viewed in a top view, and are formed by upright side- walls projecting perpendicularly from the top surface of the supporting plate 10, namely by a central side-wall 21a and two inclined side- walls 21b, which intersect the central side- wall 21a under an acute angle. The inclined side- walls 21b are followed by lateral extensions 21c. The protrusions 21 are disposed along an opposite side edge of the supporting plate 10. By means of the recesses 20 and protrusions 21 a positive-fit can be established between directly adjacent vial nests 1 to define and stabilize the mutual positions of the vial nests 1 during the processing or handling. Fig. 4c shows the vial nest of Fig. 4a without vials in a perspective bottom view. The honeycomb-like, hexagonal configuration of the circumferential side walls 14 of the receptacles 11 can be seen, which prevent a contact of vials accommodated in directly adjacent receptacles 11 with each other. For stiffening the supporting plate 10, stiffening webs 26, 27 may be provided on the bottom side of the supporting plate 10, connecting the side- walls 14 of the receptacles 1 1. More specifically, the stiffening webs 26 extend perpendicular to the long sides of the supporting plate 10, whereas the stiffening webs 27 extend perpendicularly therefrom, Additional stiffening webs may extend under an acute angle, to thereby interconnect the side -walls 14 of the receptacles 1 1. The central portion of the supporting plate 10 including all receptacles 1 1 is enclosed by a circumferential side- wall 25 projecting perpendicularly from the bottom side of supporting plate 10. Around the access apertures the short sides of the side- wall 25 is curved, The short sides of the side- wall 25 are interconnected with each other by undulated stiffening webs 28 projecting perpendicularly from the bottom side of supporting plate 10, for further stiffening the supporting plate 10. In a preferred embodiment, such a nest 1 will be made of a plastic material using plastic injection-molding techniques. Despite the afore-mentioned stiffening measures, the supporting plate 10 may still be flexible to a certain extent, if required.
Fig. 4d is an exploded perspective view of the supporting structure of Fig, 4a together with vials to be supported. Fig. 4e is a perspective view of the supporting structure of Fig. 4a showing how the vials are supported. Fig. 4h is a sectional view of the supporting structure of Fig. 4e showing how the vials are supported inside the receptacles of the vial nest 1. In the holding position shown in Fig. 4e the bottoms 50a of the vials project beyond the bottom ends of the side- walls 14 of the supporting plate and the circumferential side- wall 25 so that the bottoms 50a are freely accessible from the bottom side of the vial nest 1 for handling or processing while the vials are supported on the vial nest, Further, in the holding position shown in Fig. 4e the upper rims 53 of the vials do not extend beyond the front ends of the holding arms 17, but are slightly displaced downward, In this position the vials can be displaced easily in axial direction upward toward a raised position and without bending of the holding arms 17 by a distance that corresponds basically to the axial length of the neck portion 52 of the vials. As shown in Fig. 4e, in this holding position the upper ends and the filling openings 53 of the vials are freely accessible for processing, e.g. for performing a filling operation as shown in Fig. 5.
For the transport, storage and packaging of a vial nest 1 as outlined above together with the vials accommodated therein a transport or packaging container 3 (hereinafter also named tub for vials) is used as schematically shown in Fig. 4f. According to Fig, 4f, the transport or packaging container 3 is essentially box-shaped or tub-shaped and has a base 30, a circumferential side wall 31 protruding essentially in vertical direction therefrom, a supporting step 32 protruding essentially rectangular therefrom, a circumferential upper side wall 33 and an upper rim 34 which is formed as a flange. The corners 35 of the transport or packaging container 3 are suitably formed rounded, particularly near the supporting step 32. Preferably, the upper side wall 33 is formed inclined at a small angle of inclination with respect to a vertical to the base 30 in order to ease the insertion of the vial nest 1. Such a transport or packaging container 3 is preferably formed from a plastics material, particularly by plastic injection molding, and is preferably formed of a clear transparent plastic in order to enable a visual inspection of the vial nest 1 accommodated in the transport or packaging container 3 and of the vials 5 supported by it.
In this manner, the nest I can be positioned precisely in the transport or packaging container 3 and thus the plurality of vials 5 can be positioned and held in a regular array and at precisely defined positions in a transport or packaging container 3 with standardized dimensions. In particular, it can be ensured in this way that all bottoms or bottom ends of the vials are positioned in a plane defined jointly and in parallel to the base 30 and that all upper ends are positioned in a plane defined jointly and parallel to the upper rim 34 of the transport or packaging container 3. As shown in Fig. 4f, the upper ends of the vials 5 do not extend beyond the upper rim 34 of the transport or packaging container 3 but are spaced apart to the upper rim 34.
As shown in Fig. 4g a packaging unit (also named tub and nest assembly) formed by the transport or packaging container (tub) 3 and the nest 1 with the vials 5 accommodated therein is closed or sealed at least on the upper side by means of a protective foil or packaging foil 6 bonded onto the upper flange-like edge 34 of the tub 3. Thus, it is ensured that the interior of tub 3 is hermetically sealed from the environment, from manufacture until the time when access is to be gained to the interior of the tub 3 for further processing of the vials 5. The protective foil 6 may be in particular a gas-permeable plastic film, in particular a web of synthetic fibers such as polypropylene fibers (PP) or a Tyvek® protective film, which enables a sterilization of the vials accommodated therein through the film 6. As will become apparent to a person skilled in the art, the bottom side of the transport or packaging container (tub) 3 may also be formed open, e.g. in the manner of the tub 3 shown in Fig. 4g, i.e. in the manner that also the bottom side of the tub is provided with a flange-like bottom rim in the manner of the upper rim 34 so that the bottoms of the vials 5 may be freely accessible for processing steps also from the underside of the tub 3 if required.
As shown in Figs. 4a and 4f5 for enabling an easy insertion of vial nest 1 into tub 3 and removal from the latter, access apertures 15 are formed on two longitudinal sides of the supporting plate 10, via which gripping arms or the like may grab the vial nest 1. As shown in Fig. 4a, the access apertures 15 are partially surrounded by upright side- walls 16 projecting perpendicularly from the upper side of the supporting plate 10 to prevent a collision of the gripping arms or the like with the vials 5 accommodated. As shown in Fig. 4a, the access apertures 15 are displaced relative to each other, e.g. by one row, which further facilitates an unambiguous positioning of vial nest 1 in tub 3,
A packaging unit as shown in Fig. 4g accommodating presterilized prefillable vials can be stored under save and sterile conditions and then supplied to pharmaceutical customers for further processing. Particularly, the pharmaceutical customers will then fill medicine or other liquids into the presterilized nested vials via the filling openings using conventional filling and stoppering machines, which may be any of the three following types of filling and stoppering machines: 1) manual machines, 2) semi automatic machines and 3) fully automatic machines. An example of such a filling operation is shown in Fig. 5 in a schematic cross- sectional view. At the time of delivery under sterile conditions, the packaging unit will be sealed by a lid or protective foil as outlined above (not shown), while the nest 1 will be supported on the supporting step 32 of tub 3. At the time of delivery under sterile conditions, the packaging unit may be packaged further in at least one sterile plastic bag. The vials 5 will be accommodated upside-down in the receptacles of nest 1 so that their filling openings 54 face toward the upper end of tub 3 and the lid or protective foil (not shown). The height level of the upper ends of vials 5 is thus precisely defined in relation to the level of the supporting plate 10, which is essentially equal to the level of supporting step 32 of tub 3, because the supporting plate 10 rests directly on supporting step 32.
The exemplary filling process shown in Figs. 5 and 6 considers that the supporting plate 10 rests directly on a rectangular holding frame 40 after removal from tub 3, As an alternative, the inner free width of the holding frame 40, however, may also allow for a direct support of the outer side of supporting step 32 of tub 3 on the holding frame 40. In either case the height level of the upper ends of vials 5 is precisely defined in relation to the level of the holding frame 40.
For performing the filling process, the holding frame 40 is transferred at a precisely defined height level to a filling station 110 comprising a row of filling nozzles supported by a holding arm used for injecting a liquid, e.g. a medicine, via the filling openings into the vials supported by a vial nest. Also the height level of the bottom ends of filling nozzles is precisely defined so that a non-zero gap of well defined width Δζ will be ensured between the upper ends of the vials and the bottom ends of filling nozzles. Usually, the width Δζ of this gap will be precisely adjusted before performing the process and will be part of the general settings of a processing station. The width Δζ of this gap will be adjusted in accordance with general safety regulations, in particular in accordance with GMP (Good Manufacturing Practice) guidelines requirements. As can be concluded from Fig. 4h, for a given length of the vials 5 to be supported in a vial nest, the height level of the upper ends of the vials 5 will be precisely defined by the axial lengths of the holding aims 17 of a vial nest. Thus, if different types of vials 5 with different axial lengths are to be processed by one and the same processing .station, according to the present invention no change of the general settings of the processing station is required. Thus, it is ensured that different types of vials with different axial lengths will be fed to the processing station at the same height level of the upper ends of the different type vials.
As the same type of vial nest 1 may be used for different types of vials 5 together with the vials 5 accommodated therein and they can be inserted into the packaging unit in the same manner and as the whole packaging unit and can be sealed and transported under sterile conditions to the pharmaceutical customers, according to the present invention it can be ensured that also the different types of vials may be processed under the same settings and conditions without the need of adjusting the general settings of the processing station. Furthermore, no additional hygienic permissions will be required for this purpose. Thus, according to the present invention different types of vials involving different axial lengths may be processed in the same way and under the same general conditions and settings. Thus, the present invention enables a cost-efficient processing of presterilized, sealed vials.
As will become apparent to the person skilled in the art, replacement of one type of vial nest by a different type of vial nest may be performed for compensating for different outer diameters of batches of different types of vials. More specifically, if a first batch of vials having a first outer diameter and a second batch of vials having a second outer diameter different to the first outer diameter needs to be processed by the same processing station, according to the invention only a first type of vial nest used for the first batch of vials and having receptacles of a diameter corresponding to the first outer diameter needs to be replaced by a second type of vial nest to be used for the second batch of vials and having receptacles of a diameter corresponding to the second outer diameter. As will become apparent to the person skilled in the art upon studying of the above, the aforementioned principle may also be applied if access to the bottom ends of the vials is required, because also the height level of the bottom ends of all vials accommodated by a vial nest is precisely defined in relation to the height level of the holding frame 40. This even applies if the tub 3 should be supplied to the pharmaceutical customer with an open bottom sealed by a lid or protective foil.
Referring to Figs. 5, a general setup for filling and closing (stoppering) vials according to the present invention will be described. For supporting and aligning a supporting plate 10 of a vial nest in a predetermined position and orientation, a bottom holding frame 80 is used, which comprises a central opening 84, whose contour corresponds exactly to the outer counter of the circumferential side-wall 25 on the bottom side of the vial nest (see Fig. 4c). By means of the bottom holding frame 80 the upper ends of the vials 5 are positioned at a precisely defined height level relative to the machine holding frame 70, which may be part of a processing machine for the processing of containers and may be provided in a cleanroom or under sterile conditions, e.g. at a pharmaceutical company or filler.
As shown in Fig. 5, several spacer rods 72 are disposed on the machine holding frame 70 for precisely defining the position and orientation of the bottom holding frame 80, For this purpose, alignment tips may be provided at the front ends of the spacer rods 72 that engage with alignment holes formed in the bottom holding frame 80,
Fig. 5 further shows how the vial nest is accommodated and positioned in the central opening 84 of the bottom holding frame 80,
Several spacer rods 82 are disposed on the upper side of bottom holding frame 80 for precisely defining the position and orientation of an upper holding frame 90 used for positioning and aligning a stopper nest above and relative to the underneath vial nest. Alignment tips may be provided at the front ends of the spacer rods 82 that engage with alignment holes formed in the upper holding frame 90 for proper alignment.
A plurality of openings or receptacles 92 formed as through holes are formed in the upper holding frame 90 in exactly the same geometric arrangement as the receptacles of the underneath vial nest. More specifically, the receptacles 92 are formed by side-walls 93 whose inner profile exactly match the outer profile of the side-walls 62 forming the receptacles 61 of the stopper nest. At the bottom ends of side-walls 93 protrusions 94 project radially inward enabling a firm support of the bottom ends of the receptacles 61 of the stopper nest.
As an alternative, if the supporting plates 60 of the stopper nests are sufficiently stiff, a central opening may be formed in the upper holding frame 90 so that the outer rim of a supporting plate 60 may rest directly on the upper holding frame 90 while the receptacles 61 extend through the central opening of the upper holding frame 90 in precise alignment with the filling openings of the underneath vials 5.
Fig, 5 shows how the supporting plate 60 of a stopper nest is put onto the upper holding frame 90. As shown in Fig. 5, the supporting plate 60 of the stopper nest is put onto the upper holding frame 90 in such a manner that the bottom ends of the side-walls 62 of the receptacles 61 are in direct contact with or disposed slightly above the upper rims 53 of the vials.
Furthermore, in this position the chamfered bottom ends of the side-walls 93 of the upper holding frame 90 substantially enclose the upper rims 53 of the vials 5 to thereby prevent any dust or pollutants from entering the vials 5 via the filling openings. More specifically, as shown in Fig. 5, the bottoms 50a of the vials 5 are directly supported on a supporting plate 76 that is disposed above the machine holding frame 70 at a distance precisely defined by the length of the spacer rods 75. The lengths of the spacer rods 75 may be adjustable in order to lift the vials 5 from a position, in which the upper rims 53 of the vials 5 directly rest on the holding noses 17b of the holding tabs 17a, in axial direction upward toward the raised working position shown in Fig. 5, in which the upper rims 53 of the vials 5 are spaced apart from the holding noses 17b of the holding tabs 17a.
In the condition of Fig. 5 all receptacles 61 of the supporting plate 60 of the stopper member nest are precisely aligned with the filling openings of the vials 5 supported by the vial nest.
The set-up shown in Fig. 5 may be accomplished in a stoppering machine or in a combined filling and stoppering machine, in which case the bottom holding frame 80 could be identical with the holding frame 40 shown in Fig. 6 and the whole set-up will be disposed under reduced pressure or vacuum conditions at least while performing the stoppering process.
As shown in Fig. 5, the lower ends of the cylindrical side- walls 93 of the receptacles 92 of the upper holding frame 90 are beveled inwards so that they can snuggle to the open upper ends of the vials 5, if required. These lower ends may be coated with a resin or plastic to reduce tension in this region. During the stoppering process, preferably a very narrow gap exists between the upper ends of the vials 5 and the lower ends of the cylindrical side-walls 93 of the receptacles 92 of the upper holding frame 90.
For closing the upper ends of the vials 5, the stopper members 200 are pushed downward out of the receptacles 61 of the stopper nest and into the filling openings 54 at the upper ends 53 of the vials 5, while the vials 5 are accommodated in the receptacles 61 of the vial nest. The stopper members 200 are pushed down by means of a plurality of adjustable pushing rods 121 of the stoppering machine 120. This stoppering process may be performed row- wise but can also be performed simultaneously for all stopper members 200 and vials 5 held by the nests. For this purpose, both the supporting plate 10 of the vial nest and the supporting plate 60 of stopper nest are sufficiently stiff to ensure the above precise alignment of the stopper members 200 and vials 5 at all stages of the stoppering process.
Fig. 6 shows in a schematic top view an example of a processing apparatus or station for performing a process according to the present invention, as outlined above, under sterile conditions. The processing apparatus 100 has a sterile inner volume 101 with an infeed section at the left-hand side and an outfeed section at the right-hand side thereof. For processing, sterile packaging units as outlined above are fed, via the infeed section, into,the sterile inner volume 101. During this infeed step the lids or protective foils of the packaging units are removed so that the tub and nest assemblies accommodating the presterilized vials and presterilized stopper members finally are disposed near the infeed position indicated by reference numeral 102. For processing, the tub and nest assemblies are conveyed by a conveyer 106 along the direction of the arrow shown in Fig. 6 until finally reaching the outfeed position indicated by reference numeral 103. For conveying the nests either the nests are accommodated by holdings frames 40 or similar holding tables or the tubs respectively accommodating a nest are accommodated by holdings frames 40 or similar holding tables. In any case, the upper ends of the vials are fed to the processing stations 101 at precisely defined height levels. The infeed and outfeed sections for the vials nests and the stopper member nests might be at different positions and particularly might be disposed at different height levels.
As an example for a process step, Fig. 6 shows the filling and stoppering of the vials accommodated by nests in the holding frames 40. For the filling and stoppering, the nests or tub and nest assemblies for vials and for stopper members are first conveyed to the waiting position 104 and then to the filling and stoppering station 110, where the filling and stoppering process is usually performed row-wise, but may also be performed simultaneously for all vials and stopper members, After filling and stoppering the nests holding the filled and stoppered vials or the tub and nest assemblies accommodating the filled and stoppered vials are finally conveyed to the outfeed position indicated by reference numeral 103.
Fig. 7 is a perspective view showing the supporting structure for vials 1 with sealed vials 5 after processing in a process according to the present invention as shown in Fig. 5. After removal of the supporting structure for vials 1 out of the processing station shown in Fig. 5 the upper rims of the stoppered vials 5 rest again directly on the holding noses 17b of the holding noses 17a (see Fig. 4h). During stoppering of the vials, when usually large axial forces will be exerted from above onto the vials, the direct support of the vials 5 on a stable supporting surface 76 (see Fig. 5) ensures that both the precise centering and the height levels of the vials 5 will be maintained.
Besides filling the sealed vials via the filling openings at the upper ends and/or stoppering the vials at their upper ends using resilient stopper members, the above procedure may equally be performed for pre gassing or post gassing the vials. For this purpose, gaps or flow channels may be provided to further support a proper gas flow for pre gassing or post gassing of the vials when the nest is accommodated in a tub, because a sterilizing gas may flow essentially unhindered from the upper side of the nest towards the bottom side of the nest, if accommodated in a tub.
It will be appreciated that according to the present invention the pre-sterilized vials are entirely of a known form and require no modification as compared to conventional pre- sterilized vials. Equally the tub is as currently employed in a known pre-sterilized vial handling system and it is only the nest for stopper members which has been modified properly. Moreover, as the pre-sterilized vials allows to use the same height setting of a prefillable syringe filling machine table, the down stand socket of the receptacles ensure that the pre-sterilized viais are held at the same level of pre-sterilized vials in a conventional nest, Thus, the supporting structure for vials and stopper members according to the present invention may be used equally for a manual, semiautomatic or fully-automatic filling and stoppering process, as summarized below:
While specific embodiments of the invention have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of the invention which is to be given the full breadth of the appended claims and any and all equivalents thereof. List of Reference Numerals
1 supporting structure for vials (also named vial nest)
2 supporting structure for vial stopper members (also named stopper nest)
3 transport or packaging container for vials (also named tub)
3 a transport or packaging container for stopper members (also named tub)
4 tub and nest assembly (for vials)
4a tub and nest assembly (for stopper members)
5 vial
6 sealing lid (of tub for vials)
6a sealing lid (of tub for stopper members)
10 (planar) supporting plate of vial nest 1
11 receptacle
12 rounded corner
13 extension
14 side wall of receptacle
15 gripping aperture
16 side wall of gripping aperture 15
17 holding arm
17a holding tab
17b holding nose
18 side wall on upper surface of supporting plate 10
20 recess
20a central side wall of recess 20
20b inclined side wall of recess 20
20c lateral extension
21 protrusion
21a central side wall of recess 21
21b inclined side wall of recess 21
21c lateral extension 25 side wall on bottom surface of supporting plate 10
26 stiffening web
27 traverse stiffening web
28 stiffening web 30 bottom (of tub for vials)
30a bottom (of tub for stopper members)
31 lower side wall (of tub for vials)
31 a lower side wall (of tub for stopper members) 32 supporting step (of tub for vials)
32a supporting step (of tub for stopper members)
33 upper side wall (of tub for vials)
33a upper side wall (of tub for stopper members)
34 upper flange (of tub for vials)
34a upper flange (of tub for stopper members)
35 rounded corner (of tub for vials)
35a rounded comer (of tub for stopper members)
36a inner rounded corner (of tub for stopper members)
37a indentation (of tub for stopper members)
38a spacer web (of tub for stopper members)
39a gap
40 holding frame
42 holding arm for filling array of nozzles
43 holding arm for stoppering devices
50 cylindrical body of vial 5
50a bottom
51 shoulder portion
52 neck portion
53 widened upper rim
54 filling opening
60 supporting plate of stopper nest 2
61 receptacle
62 side wall of receptacle 61
64 rounded corner of supporting plate 60
65 chamfered upper rim
66 inserting portion
67 protrusion
68 retaining groove
70 machine holding frame 72 spacer rod 75 spacer rod
76 supporting surface 80 bottom holding frame
82 spacer rod
84 opening of bottom holding frame 80 90 upper holding frame
92 receptacle
93 cylindrical side wall
94 bottom protrusion
100 processing apparatus
101 sterile inner volume
102 tub and nest assembly at infeed
103 tub and nest assembly at outfeed 104 nest assembly at waiting position
105 nest assembly at filling station
106 conveyor
1 10 process station for filling and stoppering 1 11 downstream processing station
120 stoppering machine
121 pushing rod 200 stopper
201 cap portion
201a side wall of cap portion 201
201b recess
202 piercing area
203 leg portion
203a chamfered front end of leg portion 203
204 side wall
204a protrusion
204b recess 205 central plug portion 206 venting channel