Abstract:
Apparatus for filling sterile containers is disclosed which defines an elongated but narrow sterile zone in which a number of operating stations are disposed. An elongated vertical wall is carried by an elongated frame and a cabinet type enclosure cooperates with the vertical wall to define the sterile zone. The plurality of operating stations are disposed in sequential relation over the length of the sterile zone, and an elongated container conveyor is disposed within the sterile zone to convey the containers through the plurality of operating stations. The conveyor is vertically oriented, consisting an endless belt mounted on end wheels that rotate on horizontal axes. Each of the operating stations includes an operating portion disposed within the sterile zone. Actuating means are included for each of the operating stations as well as the elongated conveyor, each of which is disposed outside the sterile zone. Connecting means operabably connect each of the actuating means outside the sterile zone through the vertical wall to the associated operating station within the sterile zone. By orienting the conveyor vertically and disposing the various actuating means outside the sterile zone in side-by-side relation, the effective width of the sterile zone is significantly reduced. As a result, the sterile zone is more easily accessed, and also more easily drained after washdown operations. In addition, the sterile zone of reduced size results in an apparatus that much easier to manufacture and maintain in a sterile state.

Description:
This is a Continuation of application Ser. No. 08/205,041, filed Mar. 2, 1994, and now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     The invention broadly relates to container filling apparatus and is specifically directed to an improved apparatus for rapidly filling containers in a sterile environment. 
     Many pharmaceutical preparations produced by the pharmaceutical industry are dispensed in relatively small containers. Among these are injectable drugs and medicines which, by the nature of their use must be dispensed with a high level of sterility assurance. Elaborate techniques and apparatus are employed to maintain this high level of sterility. 
     To limit contamination, current container filling apparatus, which tends to be quite large, is placed in a clean room environment with the apparatus operators required to wear sterile attire, including gowns, gloves, headwear, masks and the like. The clean room itself must be maintained in a low contamination level, with conventional precautions taken as the operating personnel enter, observe and make adjustments to the equipment and leave. The apparatus itself must be periodically sterilized by steam cleaning and/or washed down with decontaminating liquid cleaners. It is difficult, time consuming and expensive to maintain the container filling apparatus and the clean room in a low level contamination. 
     This is particularly true with respect to the filling apparatus itself. A typical filling machine includes a number of operating stations; e.g., a container accumulator that dispenses empty (usually pre-sterilized) containers onto a lengthy container conveyor in sequential order through the use of a container transfer mechanism, a pre-fill check weigh station, a filling station which consists of a series of dispensing nozzles each of which is connected to a precision metering pump with associated control apparatus, a post-fill check weigh station, a stoppering or plugging mechanism (if required for the particular container configuration) including appropriate stopper feeder apparatus, and an eject and outfeed station that transfers the filled and sealed containers to an outfeed conveying system. Each component of the container package must be maintained in a sterile state through-out each of these operations. Conversely, the contamination of any single component may cause the finished package to become contaminated and unusable. 
     The primary source of contamination in a clean room environment is from individuals within the room who operate and/or monitor the filling apparatus. The air inside the room is brought in at a high rate thorough special filters that remove virtually all of the contaminants. Any liquids brought into the room such as cleaners or the drug product itself are filtered through high quality filters that again remove virtually all of the contaminants. Contamination is considered to be anything foreign to the drug product itself. This includes not only living microorganisms that are removed through filtration, steam sterilization, chemical sterilants, or other techniques, but also any particle matter that may enter the product container, including particles that carry no living organisms. An example of sources for organism free or “sterile” particles are particles of matter that enter the air when two sterile containers or two sterile machine parts rub together. 
     Equipment operators or other people that may enter the sterile environment contribute high levels of contaminants to the environment both in the form of microorganisms and particles. Because of this, elimination of the entry of people into the sterile zone is a significant improvement. 
     The subject invention is the result of an effort to produce apparatus that is less difficult as well as less costly to operate and maintain, including the ease of contamination control. Specifically, it has been found that the apparatus itself can be designed in such a way that it includes a smaller isolation or sterile zone including only those components which are directly essential to the filling and sealing process with all other components as well as equipment operators disposed outside the zone. By creating such a sterile zone and providing it with operator access ports, the need for a clean room is obviated, as is the need for the apparatus operators to be in sterile attire. 
     A preliminary approach to the problem was to build an isolation barrier around the upper “clean” portion of an existing filling apparatus. This resulted in a number of problems, the primary of which were inaccessibility to and extreme difficulty in cleaning and sterilizing the zone interior including the housed components, and the sealing of the components that pass from the inside to the outside of the sterilize zone. 
     The existing filling machine used for this preliminary approach is constructed in a manner with a large flat horizontal table top to which clean zone devices are mounted in the upward direction and to which the mechanical drive components are mounted in a downward direction from the horizontal table top. A stainless steel sheet metal cover is placed on the top side of the horizontal table top plate and serves as the division between the upper clean area and the lower mechanical space. When the concept was proposed to surround the upper clean space with an isolation barrier, several problems arose. First, the horizontal table top was relatively wide and, when surrounded by a barrier, would not allow for access to all points within the clean space with conventional techniques using glove port access. Second, since the significant amount of water and/or chemical may be used in a process to clean and/or sterilize the interior sterile zone, a simple and clean drainage system would be required. Because the conventional horizontal table top was large and flat, not allowing for good drainage, and since many mechanical devices pass through from the upper clean zone, now the sterile zone inside the isolator, to the lower mechanical space, the problems of drainage and sealing of the bottom of the sterile zone became a major problem. 
     In the subject invention an apparatus has been created the frame and main mounting plate of which are oriented vertically, defining sterile and non-sterile zones in side-by-side relation. Those components which are directly essential to the actual processing of the containers are disposed on one side of the plate (sterile zone) with the supporting components disposed on the opposite side (non-sterile zone). The plate, together with sterile cabinetry, encloses the essential components and defines the sterile zone. For example, the dispensing nozzles are disposed within the sterile zone, whereas the pumping devices are located within the non-sterile zone and connected to the nozzles by tubes that pass through the plate or barrier in sealed relation. The container conveyor itself, which of necessity is located in the sterile zone, also has been oriented from horizontal to vertical to significantly reduce its width. The drive means for the conveyor, however, is located in the non-sterile zone. 
     The result is a sterile zone that is of significantly reduced size, and an apparatus which is much more easily operated and maintained. The smaller sterile zone and the internally disposed components are easily accessed through glove ports and, since the zone is much smaller, it is easily cleaned. In addition, the absence of any mechanical devices passing through the bottom of the sterile zone enclosure allows for an extremely clean and drainable collection pan without the associated sealing problems. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 is a view in top plan of a prior art container filling apparatus; 
     FIG. 2 is a transverse sectional view of the prior art container filling apparatus taken along the line  2 — 2  of FIG. 1; 
     FIG. 3 is a schematic representation of a container filling apparatus embodying the invention, showing in particular a sterilization zone of reduced size; 
     FIG. 4 is a view in top plan of the inventive container filling apparatus; 
     FIG. 5 is a transverse sectional view of the inventive container filling apparatus taken along the line  5 — 5  of FIG. 4; 
     FIG. 6 is a fragmentary perspective view of the prior art container conveyor; 
     FIG. 7 is a fragmentary perspective view of a container conveyor used in the inventive container filling apparatus; 
     FIG. 8 is an enlarged perspective view of a conveyor cleat used on the container conveyor of FIG. 7; and 
     FIG. 9 is a transverse sectional view of a mechanism for adjusting the container conveyor and associated apparatus. 
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     With initial reference to FIGS. 1,  2  and  6 , a typical prior art filling apparatus is represented generally by the numeral  11 . Apparatus  11  comprises a large table or frame  12  that is horizontally disposed and supports all of the various components of apparatus  11 . With particular reference to FIG. 1, these components include an accumulator disk  13  which is filled with a plurality of vials  14  received from a conveyor not shown. Vials  14  are transferred from accumulator disk  13  to a transfer disk  15 , and a star wheel  16  individually picks up vials  14  from the transfer disk  15  and carries them to a vial conveyor  17 . 
     With reference to FIGS. 1,  2  and  6 , conveyor  17  includes drive sprockets  18 ,  19  at opposite ends with a sprocket type conveyor belt  21  operably connected therebetween. A plurality of cleats  22  are mounted on and carried by conveyor belt  21 , each having a V-shaped frontal recess  23  that is capable of receiving and carrying vials  14  of different diameter. The sequentially carried vials  14  slide along a horizontal carrier rail  24  disposed therebelow, and a side rail  25  (FIGS. 2 and 6) retains each vial  14  within the V-shaped projection  23  and on the carrier rail  24 . The position of conveyor  17  and side rail  25  may be horizontally adjusted separately by the mechanism bearing reference numeral  26  in FIG. 2, which enables the apparatus to accommodate vials of different diameter and ensures that the vials travel along the proper line of machine operation. 
     The vials  14  are sequentially carried by conveyor  17  to a pre-fill check weigh mechanism  27 , a filling apparatus  28  consisting of a plurality of nozzles connected to a like number of pumps  29 , a post-fill check weigh mechanism  31 , a stoppering head  32  supplied by a stopper feeder  33 , and a vial eject station  34 . 
     Prior art vial filling apparatus  11  is open to the surrounding environment, and is conventionally disposed in a large clean room the environment of which is maintained in a decontaminated or sterile state as is known in the art. Conventional techniques are also used to prevent contamination as operating personnel enter and leave the room, including the wearing of sterile attire such as gowns, gloves, headwear and masks. 
     With reference to FIGS. 3-5, a vial filling apparatus embodying the invention is represented generally by the numeral  41 . The apparatus  41  of the preferred embodiment is intended for use in the sequential filling of continuously fed vials for injectable drugs, but the invention contemplates the filling of any type of container in a sterile environment. 
     With particular reference to FIG. 4, apparatus  41  includes a sterilized infeed enclosure  42  through which vials  14  pass on a conveyor  48 . Infeed enclosure  42  represents the inlet to a sterile zone, discussed below, and it is essential that the vials  14  entering at this point be in a sterilized condition. To that end, enclosure  42  is connected to a conventional vial washer/sterilizing tunnel  50  that receives unsterilized vials, performs a multiple step procedure that sterilizes the vials, generally including depyrogenization, and delivers sterilized vials to the conveyor  48  of sterilized infeed enclosure  42 . At this point, the sterilized vials are transferred to an oscillating belt infeed station  43  that moves the vials to a transfer star wheel  44 , which sequentially loads the vials  14  onto a principal vial conveyor  45  the basic function of which is the same as conveyor  21  of the prior art apparatus  11 . However, as specifically discussed below, conveyor  45  is structurally different and operates in an improved and advantageous manner. 
     Conveyor  45  sequentially moves the vials  14  to a pre-fill check weigh station  46  that randomly removes a vial to establish a reference pre-fill weight. The vials are then carried by conveyor  45  through a filling station  47  which comprises a plurality of nozzles  49 . Nozzles  49  are supplied by a plurality of pumps  51  described in further detail below. 
     After filling, the vials  14  are moved by conveyor  45  past a post-fill check weigh station  52 , which removes each of the randomly selected empty vials previously weighed at pre-fill check weigh station  46 . This comparative weighing ensures that the specific amount of pharmaceutical preparation has been metered and dispensed into each vial. 
     Conveyor  45  then moves the vials through a stoppering station  53  at which each of the filled vials is closed and sealed with a stopper. Vials  14  then move into an eject and outfeed station  54 , where the vials are removed from conveyor  45  and carried by means not shown to a packing station. 
     With reference to FIG. 5, apparatus  41  comprises an elongated frame certain components of which are shown in this transverse sectional view. These include vertical leg members  55 , a vertical cross rail member  56 , a mounting plate  57  and a vertical frame support member  58  that extends between the lower and upper cross rail member  56  and plate  57 , at an intermediate point between the vertical leg members  55 . It is will be understood that the various components  55 - 58  repeat over the length of the apparatus frame. 
     A vertically disposed mounting plate  59  is secured to the several frame support members  58 , extending longitudinally over the length of the apparatus  41  (see also FIG.  4 ). A portion of vertical mounting plate  59  extends above the upper cross rail members  57 . A thin stainless steel sheet  61  corresponding in size to vertical mounting plate  59  is mounted thereto in spaced relation, defining an air gap  62 . The stainless steel sheet  61  defines the elongated barrier or back plate of a stainless steel cabinet bearing general reference numeral  63 , which in turn defines an internal sterile zone  64 . The area outside cabinet  63  (i.e., that portion on the left side of barrier plate  61  as viewed in FIG. 5) constitutes a non-sterile zone bearing the general reference numeral  70 . 
     With continued reference to FIGS. 3 and 5, sterile cabinet  63  further comprises a front plate  65  that is shown as corresponding generally in size to the back plate  61  in the schematic representation of FIG.  3 . However, and as shown in FIG. 4, the front plate  65  includes several outward steps to accommodate various of the components described above. A cabinet top  66  and cabinet bottom  67  interconnect the back plate  61  and front plate  65 , and the cabinet ends are enclosed by end plates  68 ,  69 . 
     The primary inlet to sterile zone  64  is the sterile tunnel  42  as discussed above. The stoppering station  53  also includes a stopper inlet or docking port  53   a  through which sterilized stoppers are admitted in a sterile manner as is known in the art. The sole outlet from sterile zone  64  is the eject and outfeed station  54 , which in the preferred embodiment comprises a plurality of conventional star wheels, the first of which is disposed within sterile zone  64  and the second of which is disposed outside zone  70 . Vials  14  are transferred between these first and second star wheels through a small opening in cabinet  63 . Sterile zone  64  is preferably maintained at a pressure higher than that of the ambient surroundings to cause an outflow of air through the vial outlet between the star wheels, thus resisting contaminant entry. The means for maintaining such pressure, which is not shown, is conventional and typically includes a supply of air that is filtered to remove contaminants. 
     Preferably, cabinet  63  includes a plurality of conventional glove ports  80  or other conventional means for permitting sealed access to the sterile zone  64 . Preferably, glove ports  80  are disposed at spaced points to permit operators of the apparatus  41  to have access at all points along the line of vial movement. 
     With reference to FIG. 3, a drain portion  71  of the cabinet  63  projects downwardly below the filling station  47 . The respective bottom portions  67  adjacent the drain portion  71  are inclined downwardly toward the drain portion  71 . The bottom of drain portion  71  defines a plurality collecting drain pans  71   a-c  which respectively lead to drains  72   a-c.  Each of the drains  72   a-c  is connected through a sealed coupling  73  to a common drain pipe  74 . The purpose of these drain components is discussed in further detail below. 
     With reference to FIGS. 4 and 5, each of the series of pumps  51  is of the rolling diaphragm type, such as that disclosed in U.S. Pat. No. 3,880,053, and is capable of dispensing a precise amount of liquid. Each of the pumps  51  is horizontally disposed as shown in FIG. 5, and the rolling diaphragm is actuated by a reciprocating rod  75 . The rod  75  is reciprocated by a pivoted linkage member  76  that is connected between the rod  75  and an actuating rod  77 . The several rods  77  for the respective pumps  51  are actuated in a precisely timed manner by a controlling mechanism  78  which is known in the art. 
     Each of the pumps  51  has an inlet  81  to which an inlet tube  82  is connected. The several inlet tubes  82  are commonly connected to a manifold that supplies the liquid to be dispensed and filled into the vials  14 . 
     Each of the pumps  51  has an outlet  83  from which the precise amount of liquid is dispensed or pumped. Each pump outlet  83  has an outlet tube  84  connected thereto that leads to one of the nozzles  49 . The series of nozzles  49  are mounted on a walking beam  85  that linearly reciprocates in a timed sequence relative to the moving vials  14 . The apparatus which controls the walking beam  85  bears general reference numeral  86  and is known in the art. 
     With reference to FIGS. 4,  5  and  7 , conveyor  45  includes a conveyor belt  87  having a row of sprocket holes  88  disposed along each edge. Conveyor belt  87  is endlessly driven by a pair of opposed sprocket wheels  89 ,  90  (only sprocket wheel  89  is shown in FIG.  7 ). In contrast with the drive sprocket wheels  18 ,  19  of conveyor  17 , which rotate about vertical axes, the sprocket wheels  89 ,  90  are turned 90 degrees and rotate about a horizontal axis as shown by reference numeral  91  in FIG.  5 . For purposes of simplicity in FIG. 5, the horizontal shafts upon which drive sprocket wheels  89  rotate are not shown. Such shafts extend through appropriate seals in the stainless steel sheet  61  and mounting plate  59  and are driven as discussed below. With such a configuration, the width of conveyor  45  is significantly reduced, as compared with the prior art conveyor  17 . Further, since the drive means for conveyor  45  is located outside sterile cabinet  63  as discussed below, cabinet  63  and sterile zone  64  are significantly reduced in size from the standpoint of width. 
     With continued reference to FIGS. 7 and 8, a plurality of vial carrying cleats  92  are mounted on the conveyor belt  87 , each of which has a width that substantially corresponds to the width of belt  87 . With reference to FIGS. 7 and 8, each of the cleats  92  comprises a lower body  93  and an upper body  94 . Lower body  93  includes a base  95  the underside of which defines a grooved track  96  that is sized and configured to overlie and be supported by conveyor belt  87 . A counter-sunk bore  97  extends through the center of lower body  93  to receive a mounting screw (not shown) that fastens each of the cleats  92  to the conveyor belt  87 . The top surface of lower body  93  defines a platform  98  on which one of the vials  14  may rest. 
     The upper body  94  of each of the cleats  92  is offset relative to the lower body  93  to permit a vial  14  to rest in centered relation on the lower body  93 . Upper body  94  defines lower and upper lateral supports which respectively define V-shaped recesses  100 ,  102 , respectively. The recesses  100 ,  102  are centered relative to the lower body  93 , and in the preferred embodiment are formed at a 90 degree included angle. This angle, coupled with the size of platform  98 , permits each of the cleats  92  to accept vials  14  having a range of diameters. For vials having diameters that do not fall within such range, cleats  92  of a different size or a different included angle may be substituted. 
     With reference to FIG. 7, conveyor  45  includes a stationary guide rail  103  that is positioned relative to the moving cleats  92  to retain the vials  14  as shown in FIG.  7 . The lateral position of guide rail  103  may be adjusted, as described in further detail below, based on the diameter of the vials  14 . 
     In comparing the prior art conveyor  17  of FIG. 6 with the improved conveyor  45  of FIG. 7, it will be appreciated that the effective operating width of conveyor  45  is significantly less than that of conveyor  17 , and corresponds essentially to the width of the cleats  92  and belt  87 . The prior art conveyor  17  has a width that includes not only the diameter of the drive sprocket  19  and thickness of conveyor belt  21 , but twice the width of the cleats  22  as well (bearing in mind the fact that the cleats  22  project laterally from both the front and back flights of the conveyor belt  21 ). Further, the effective operating width of conveyor  17  is increased by the vials  14  which project laterally outward of the conveyor  17 , whereas the vials  14  are carried in centered overlying relation to the conveyor belt  87 . It will also be noted that the prior art conveyor  17  requires a carrier slide rail  24 , which comprises additional structure, adds to the overall size of the conveyor  17  and requires the vials  14  to slide as they are moved forwardly. In the improved conveyor  45 , the vials  14  rest directly and are supported in their entirety by the cleats  92 , eliminating the need for the bottom slide rail  24  of the prior art and conveyor  17 , avoiding friction, vibration and particle generation. 
     With reference to FIGS. 5 and 9, it is essential that the center of each of the vials  14  pass directly below the nozzles  49 , and it will be appreciated that adjustments must be made to container carrying and guiding apparatuses to maintain a constant centerline of the vials. The adjustment mechanism shown in FIG. 9 permits independent adjustment of the conveyor  45  as well as the guide rail  103  to accommodate vials  14  of differing diameters and to maintain the constant centerline. 
     More specifically, the drive sprocket wheel  89  is carried by a mounting bracket  104  which in turn is carried by an annular mounting flange  105 . Mounting flange  105  is secured to a telescoping adjustment tube  106  that projects through stainless steel sheet  61  and mounting plate  59 . Telescoping adjustment tube  106  is carried for such telescopic movement by a stationary mounting tube  107  that is secured to an annular mounting collar  108 . An annular ring  109  and annular seal  110  disposed in the air gap  62  in encircling relation to mounting collar  108  serve to maintain the sterile zone  64  in a decontaminated state. 
     Bearings  111 ,  112  disposed between adjustment tube  106  and mounting tube  107  permit relative telescoping movement of the tube  106 , and a flexible bellows  113  extends between stationary tube  107  and mounting flange  105  to permit such relative movement while sealing against contamination. 
     Guide rail  103  is carried by a mounting bracket  114  that is mounted to a telescoping adjustment shaft  115 . Shaft  115  telescopically slides within adjustment tube  106  relative to a pair of bearings  116 ,  117 . A flexible bellows  118  is secured at one of its ends to the adjustment shaft  115  with the other end secured to the end of adjustment tube  106 , also for the purpose of preventing the entry of contaminating matter into sterile zone  64 . 
     A control plate  119  is mounted to the outer end of adjustment tube  106 , and a similar mounting plate  121  is mounted to the outer end of adjustment shaft  115 . Separate actuator means  122 ,  123  are respectively connected to the control plates  119 ,  121  to effect separate adjustment of the adjustment tube  106  and shaft  115 . The actuator means  122 ,  123  may be interrelated for adjustment to vials of predetermined diameter, and may also include automated means to ensure centering of the vials  14  relative to the nozzles  49 . 
     With reference to FIG. 4, each of the operating stations disposed within the sterile zone  64  is driven by an actuating means that is disposed outside the sterile zone  64  (i.e., within the nonsterile zone  70 ). These various actuating means, although separate, are interrelatably driven because the various operations performed within sterile zone  64  must be synchronous. An electric motor  131  serves as the primary drive means for the various actuating means. Separate servomotors are used for other actuating means as described below, which are operated in synchronous relation to primary drive motor  131 . Motor  131  includes drive pulleys  132 ,  133  at each end. Drive pulley  132  drives a driven pulley  134  through an endless drive belt  135 . Driven pulley  134  is operably connected to the bank of  16  pumps  51  in a conventional manner. 
     Drive pulley  133  is connected through a drive belt  136  to a driven pulley  137 , which in turn is mounted to a common drive shaft bearing the general reference numeral  138 . Drive shaft  138  comprises a plurality of interconnected drive shaft segments  138   a-e.    
     Drive shaft segment  138   a  is connected through a right angle gear drive  139  to a pulley/timing belt configuration. A drive connection  142  extends through the wall of cabinet  63 , connecting the pulley/timing belt  141  to the oscillating belt infeed station  43 . The seal in the wall of cabinet  63 , which bears reference numeral  143 , is of the same type as the seal consisting of components  108 - 110  used for the lateral conveyor belt/rail adjustment of FIG.  9 . 
     Drive shaft segment  138   a  is connected to shaft segment  138   b  through a right angle drive  144 . A right angle drive  145  is connected between drive shaft segments  138   b-c,  the purpose of which is to drive the star wheel  44  through a pulley/belt configuration  146  and a drive connection  147 . Drive connection  147  extends through mounting plate  59  of cabinet  63  through a seal of the same type as seal  143 . 
     Drive shaft segment  138   c  is connected through a pulley/belt configuration  148  to a right gear drive  149  having a drive pulley  151  (see also FIG.  5 ). Drive pulley  151  is connected to drive the walking beam  85  through actuators  86  as described above, each of which extends through the mounting plate  59  through a seal similar to seal  143 . 
     The pre-fill check weigh station  46  and post-fill check weigh station  52  are separately driven by servomotors (no shown for purposes of clarity), which are operated in synchronous relation to the primary drive motor  131 . Pre-fill check weigh apparatus  46  includes a drive connection  152 , and post-fill check weigh apparatus  52  includes a drive connection  153 . 
     Shaft drive segment  138   d  is connected through a pulley/belt configuration  154  to a right angle gear drive  155  which in turn drives a pulley/belt configuration  156 . This in turn is connected to a drive connection  157  that actuates a portion of the stoppering station  53 . Other components of the stoppering station are driven by a separate variable speed motor. 
     Shaft drive segment  138   d  is also connected through a gear drive  158  that drives a pulley/belt configuration  159 . A drive connection  161  interconnects the configuration  159  through a seal, similar to seal  143 , to the eject and outfeed station  54 . 
     Shaft drive segment  138   e  is connected to a right angle gear drive  162  which in turn drives a pulley/belt configuration  163 . A drive connection  164  extends through a seal and mounting plate  59  and connects configuration  163  with drive sprocket wheel  89 . Sprocket wheel  90  is a driven wheel and does not include a direct drive. 
     The lateral adjustment mechanism shown on FIG. 9 is included in the drive connection  164 . This adjustment mechanism is provided at a plurality of points over the length of conveyor  45 , each of which is represented by reference numeral  165 . The actuating means for effecting lateral adjustment is not shown in FIG. 4 for purposes of clarity. 
     FIG. 4 particularly emphasizes the significantly improvement in filling apparatus  41  of a sterile zone that is significantly reduced in size, with only those components that are directly essential to the filling process located within the sterile zone. All other components, including machine drive elements, pumps, controls and the like are located outside the sterile zone. By effectively reducing the size of the essential components within the sterile zone and focusing on decontaminant sealing techniques, the resulting sterile zone is considerably smaller in size, shortens the operator&#39;s reach into the operating area while excluding potential contamination by the operator, and significantly reduces the periodic cleaning and sterilizing task. 
     In this latter regard, and with particular reference to FIGS. 3 and 5, the sterile zone  64  within the sterile cabinet  63  can be periodically cleaned and sterilized by techniques utilizing steam and/or a disinfecting liquid wash with all of the internal components in place. As a result, clean zone  64  may be effectively sterilized and decontaminated on a periodic basis in a manner which is far easier than decontaminating an entire room or much larger zone. This also results in a significant decrease in the cost of operating and maintaining the apparatus  41 .