Method and apparatus for manipulating pre-sterilized components in an active sterile field

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Method and apparatus for manipulating pre-sterilized components in an active sterile filed

Baxter International Inc. C.135667

METHOD AND APPARATUS FOR MANIPULATING

PRE-STERILIZED COMPONENTS IN

AN ACTIVE STERILE FIELD

Technical Field

This invention relates generally to the methods and apparatus for connecting, assembling, and filling pre-sterilized medical components in a sterile field. More particularly, the present invention relates to the use of a low voltage electron beam field to create a sterile atmosphere in which connecting, assembling, or filling of pre-sterilized medical components, such as solution delivery sets, medical tubing, drug vials, medical containers, and the like, may occur such that the sterility of the product is continuously maintained.

Background Art

Pre-sterilized, disposable medical products are commonplace in the United States, and other countries throughout the world. One significant restraint on the design, development, and manufacture of such products has been the fact that certain desirable products would include portions or components which are mutually incompatible from a sterilization standpoint. For example, it may be desirable to provide a unitary, pre-sterilized product which has a sealed liquid or powder drug component and a plastic apparatus component, such as a tubing or flow control set

The integral product, however, cannot be sterilized after assembly because not all of the components may be subjected to the same form of sterilization. That is, the plastic apparatus component (e.g., the tubing or flow control device) may only be capable of sterilization with radiation or gas. The drug component on the other hand, may not be sterilized with either gas or radiation—gas sterilization would be ineffective to sterilize a sealed drug, while exposing the drug to radiation may lead to product degradation or otherwise have a deleterious effect on the drug.

Accordingly, efforts have been made to devise a method or means for joining, in a sterile manner, components which are individually pre-sterilized. Such efforts have included the use of electron beam accelerators to sterilize the compromised portion of the assembled components. 1 expensive to use than the present invention because it requires the use of a new disposable knife blade for each connection made.

The apparatus and methods ofthe present invention overcome the disadvantages of other prior art techniques. The present invention is focused on maintaining the sterility of the pre- 5 sterilized components during assembly, connection, and fill, rather than attempting to effect sterilization after such manipulations, like the processes used extensively by those skilled in the art. Additionally, the present invention is focused on processes which are far less expensive than techniques utilizing disposable parts. 10 Summary Of The Invention

In accordance with this invention, a new apparatus and method for forming a connection, and particularly a sterile connection, between two or more pre-sterilized components is disclosed. Preferably, each of the components has at least one closed end suitable for connecting to another component An embodiment of the present method and apparatus requires sterilizing an end of 15 each component to be connected with an active sterile field, then opening the closed ends of the components within the active sterile field. The sterile connection is completed by connecting the opened ends together while in the active sterile field.

It is further an aspect of the present invention to provide an apparatus and method for forming a sterile assembly between two or more pre-sterilized components. Preferably, each of 20 the components has at least one closed end suitable for connecting to another component. An embodiment of the present method and apparatus requires sterilizing an end of each component to be assembled together with an active sterile field, then assembling the ends together while in the active sterile field.

It is still a further aspect of the present invention to provide an apparatus and method for 25 perfoiming a sterile fill of a pre-sterilized container with a pre-sterilized liquid component from a bulk container. Preferably, the empty container has at least one end suitable for accepting the liquid component, and the bulk container has at least one end suitable for delivery of the liquid. An embodiment of the present method and apparatus requires sterilizing a suitable end of each component with an active sterile field, then filling the empty container with an aliquot of liquid 30 from the bulk container while the ends are in the active sterile field.

Specifically, in one embodiment of the present methods, sterilization of the ends of each component is achieved by creating an electron beam field to produce an active sterile field, and 3 FIG. 2 illustrates the assembly line configuration of one embodiment of the present invention; FIGS. 3A through 3D illustrate an embodiment of present method for effecting a sterile connection of two components within an active sterile field; 5 FIG. 4 is an illustration of an electron beam tube used in an embodiment of the present invention; FIG. 5A is one embodiment of a mechanism for supporting the ends of multiple components within an active sterile field; FIG. 5B shows the mechanism of FIG. 5 A as the ends of multiple components are brought 10 into contact with each other within an active sterile field; FIGS. 6A through 6D illustrate an alternative use of the present invention for the sterile assembly of a pre-sterilized vial to a pre-sterilized device; FIGS. 7A through 7E are alternative embodiments and variations on the spike tube and membrane tube configured ends; 15 FIGS. 8A through 8D illustrate an alternative connection using a stream of hot air to soften membrane tubes which are then brought together to join as they cool; FIG. 9 illustrates the sterile fill process of the present invention.

Detailed Disclosure Of Preferred Embodiment 20 While the invention is susceptible of embodiment in many different forms, this disclosure will describe in detail preferred embodiments of the invention with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the broad aspect of the invention to the embodiments illustrated.

The present invention involves methods and apparatus for joining plastic components in 25 a sterile manner. The term “joining” in this application includes the processes of: 1) connecting components, where a fluid pathway is created at the time of joining; 2) assembling components, where a fluid pathway is not complete at joining, but may be completed at a later time; and, 3) filling at least one component from a bulk container. Particularly, the invention permits the joining together of tubing to container, tubing to tubing, tubing to connector, vial to connector, 30 container to connector, and even sheet/film stock to itself, in a sterile field. 5

The arranged components 10, 12 are first optionally conveyed to a labeling station 40 where important batch, lot, and date codes may be applied. Components 10,12 are then conveyed to the active sterile field station 50 where a sterile connection between the pre-sterilized components may be effected. This process is better illustrated in FIGURES 3A through 3D. 5 FIGURES 3A - 3D show an electron beam (e-beam) field 60 created within station 50.

Electron beam 60 is created by the tube 54 as illustrated in FIGURE 4. Tube 54 comprises a vacuum tube 55 shrouding filament 56 on all sides, except at base 57. Base 57 has various electrical connectors 58 for plugging into a low voltage source. Opposite base 57 is a thin film window 59 which discharges the electron beam toward the desired location, Window 59 is 10 approximately 3 microns thick, and through it a beam of approximately 2 mm x 25 mm (0.08" x 1") area is discharged. Arrays of tubes 54 could be set up to increase the collective area of the e-beam discharge. An example of this arrangement is illustrated in U.S. Patent No. 5,414,267 (or Re. 35,203) to Wakalopulos, the disclosure of which is hereby incorporated by reference.

Tube 54 is preferably about 5 cm (2") from the area in which an active sterile field is 15 desired and operates at about 60 KeV. Higher voltages may allow a greater gap, and a lower voltage might require a lesser gap. FIGURE 3 A shows the pre-sterilized components 10, 12 arranged prior to connection. Tube 54 creates the spherical-shaped e-beam field 60 having approximately a two-inch diameter. Other diameters of the sterile field are certainly possible, however manipulation of the joining of components requires very little space. Where a greater 20 space is required, field 60 could be made larger by conventional methods.

Referring to FIGURE 3B, the ends 14 of components 10,12 are conveyed into the sterile e-beam field 60. While maintained within sphere 60, ends 14 of each component 10,12 may be cut-off, as shown in FIGURE 3C, to create opened ends. The mechanism for opening these ends may be a mechanical blade, which may be held permanently within the e-beam field 60 to 25 maintain its sterility, or any other suitable cutting or opening mechanism. FIGURE 3D shows that once the ends 14 are cut-off, the resulting open ends are connected together while still within the field 60.

While, the use of an electron beam field is a preferred source for creating the active sterile field, applicants ofthe present invention have anticipated the use of alternative sources, such as 30 a chemical vapor atmosphere. A chemical vapor atmosphere can be created through known methods, and the chemical may be selected from the group comprising hydrogen peroxide, 7

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especially where it is anticipated that the assembled components may be stored for a period of time. A suitable connection (i.e., creation of a fluid pathway) may be readily achieved in the field (e.g., hospitals, clinics, etc.) by trained personnel prior to use

Alternatives to and variations ofthe spike and membrane tubes, shown in FIGURE 5B and

5 used in a preferred embodiment ofthe present invention, are abundant in the art. Some of these alternatives which do not require end cut-off are illustrated in FIGURES 7A-7E. For example, FIGURE 7A shows the spike end having a tip protector. FIGURE 7B illustrates removable plugs in each end. These plugs may insert into the inner diameter of the ends, or, as illustrated, over the outer diameter of the ends. FIGURE 7C shows seal tabs used as closures on the ends. FIGURE 10 7D illustrates another variation of the spike and membrane configuration. FIGURE 7E, also a variation of the spike and membrane configuration, introduces a dual end spike component. Generally, the illustrated configuration may be varied where one component may have a larger inner diameter of the sealed terminal end than the outer diameter of the sealed terminal end of the other component, such that the smaller fits snugly into the larger. Also, the ends 14 may be of an 15 identical diameter, but be brought together to abut each other within a collar (not shown). To the extent that such alternative designs, too numerous to illustrate, allow pre-sterilized ends to be brought together within a sterile field, creating a sterile connection between the ends, such alternatives are considered to fall within the scope of the present invention.

Regardless of the design configuration of terminal ends 14, a permanent seal between the 20 contacting ends will need to be effected. The final permanent connection is preferably made outside the sterile field, but, if necessary, can also be accomplished while the contacting ends are exposed within the e-beam field sphere 60. This connection can be made using a radio frequency sealer (such as a HEMATRON™), a heat sealer, solvent bonding techniques, or the like.

In an alternate method, shown in FIGURES 8A-8D, a device to vial assembly (similar to 25 the assembly shown in FIGURE 6D) connection is illustrated with some variation to the methods previously discussed. FIGURE 8A shows device 110 and vial assembly 112, both having membrane tubes 114, positioned for sterile connection. The membrane tube 114 of each component is subjected to a hot air stream, as shown in FIGURE 8B. The membrane of each tube 114 becomes semi-amorphous, and the tubes 114 are moved toward one another, as shown in 30 FIGURE 8C, within e-beam field sphere 160. FIGURE 8D shows the final connection, where the membrane tubes have been held together until cool enough to form a proper seal. 9