PROCESS AND APPARATUS FOR TRANSFERRING AND STERILIZING A SOLUTION

Abstract: Process and apparatus for the transfer of a parenteral solution into an extensible plastic bag (32) and the sterilization of that solution during such transfer. The apparatus includes a hydrophilic, bacterial organism retentive, sterilizing filter (20), such a bag (32), and tubing (18) connecting same, which have been combined and sterilized as a unit, which unit is labeled for sale as being sterile. A container (10, 12) holding the solution to be transferred and tubing (18) associated therewith are provided for delivery of the solution to the sterile unit. A vacuum chamber (34) is also provided by which the solution may be rapidly drawn through the filter (20), as it is sterilized, and into the bag (32) upon the creation of a pressure differential between the inside and outside of the bag in the vacuum chamber (34). A transparent portion of the sterile unit provides a means by which the sterility of the transfer process can be determined. The process includes delivering the solution to the sterile unit, transferring the solution through the filter (20) for sterilization and into the bag by creating the pressure differential, terminating solution transfer and directing a gas through the unit, observing the transparent portion for the presence of gas bubbles, which would indicate a loss of filter integrity, and consequently sterility of the unit, and hermetically sealing off the bag (32), if no such bubbles are present.

Description: PROCESS AND APPARATUS FOR TRANSFERRING AND STERILIZING A SOLUTION David Bellamy John L. Quick BACKGROUND OF THE INVENTION The present invention pertains to a process and apparatus for the transfer and sterilization of a solu¬ tion. More particularly, it pertains to such a process and apparatus useful for the compounding of hyperali- mentation solutions. Hyperalimentation therapy is the intravenous feed¬ ing of, for example, a protein-carbohydrate mixture to a patient. It is used primarily to meet' his protein and caloric requirements which are unable to be satis- fied by oral feeding. The protein may be in the form of free-amino acids or protein hydrolysate and the carbohydrate commonly used is dextrose. In addition to the protein and carbohydrate, vitamins (water-soluble and fat- soluble) and electrolytes can also be supplied in this therapy. Each of these parenteral ingredients and the combination thereof are particularly susceptible to the growth of deleterious organisms and it is desirable that they be administered to the patient in a sterile condition. Thus, because these protein and carbohydrate solutions cannot be precompounded by the manufacturer, but must be combined at the time of their use, their compounding must be performed under sterile conditions to avoid organism growth. A known apparatus and process for compounding hyperalimentation solutions utilizes a solution trans¬ fer system including a plastic receiving container and a Y-transfer set. A plastic container found to be particularly useful is one manufactured by Travenol Laboratories, Inc., of Deerfield, Illinois and marketed under the trademark VIAFLEX®. A known Y-transfer set includes two separate tubes, each having an end attached to a common juncture by which solutions delivered through the tubes will pass through the juncture into the attached plastic container. The other end of one tube of the set is attached to a protein holding con¬ tainer and of the other tube of the set to a carbohy¬ drate holding container. The desired volume of each solution being transferred to the receiving container is controlled by a roller clamp placed on each tube. Each solution may be allowed to flow into the plastic container by gravity flow. However, it has been found to be useful to transfer same under the influence of a vacuum applied to the receiving container, which vacuum is created in a vacuum chamber into which the container is placed, such as the one manufactured by Travenol Laboratories, Inc., of Deerfield, Illinois and marketed under the trademark VIAVAC®. It has been known in the past that to maintain sterility during the compounding of hyperalimentation solutions, compounding should be perform under a laminar flow hood. Laminar flow hoods are useful for reducing the risk of airborne contamination of such solutions. These units operate by taking room air and passing it through a prefilter to remove gross contaminants, such as dust and lint. The air is then compressed and channeled through a bacterial retentive filter in the hood in a laminar flow fashion. The purified air flows out over the entire work surface of the hood in parallel lines at a uniform velocity. This type of filter is designed to remove essentially all bacteria from the air being filtered. Compounding under a laminar flow hood aids is pre¬ venting airborne contamination, but it is relatively cumbersome and expensive. When using such a hood the operator might inadvertently perform the work at the edge or outside of the hood and not at least 6 inches within the hood to insure the benefits of the air being purified. Time must be taken and care must be exercised to maintain a direct open path between the filter and the compounding area. Solution bottles and other non- sterile objects cannot be placed at the back of the hood work area next to the filter because these objects could contaminate everything downstream and disrupt the laminar flow pattern of the purified air. Also, in using a laminar flow hood, it is necessary to routinely clean the work surface of the hood before any compounding is performed. Therefore, it is the object of the present inven- tion to.provide a process and apparatus for transferring a solution from a holding container to a receiving con¬ tainer, such as a receiving bag of the type above identified, while also sterilizing such solution. Another important object of the present invention is to provide a readily available process and apparatus for transferring and sterilizing the solution being transferred without the necessity of a laminar flow hood. Other objects and advantages of present inventions will become apparent from the description of this inven¬ tion that follows. SUMMARY OF THE INVENTION In accordance with the present invention, an apparatus is provided for transferring at least one solution into at least one solution receiving container and for also sterilizing the solution during the trans¬ fer process. The apparatus includes a solution receiv¬ ing container; a filter capable of sterilizing the solution, the filter having means by which the solution can be directed into the sterilizing portion of the filter and an outlet; and tubing connected between the filter outlet and the container for transfer of the sterilized solution from the filter into the container. At least the sterilizing portion of the filter, the filter outlet, the tubing, and the container are combined and labeled for use as a sterile unit. In one embodiment of the invention means are pro¬ vided for determining whether the integrity of the filter, and consequently the sterility of the unit, has been maintained during the transfer process. Such means preferably include an inlet into the filter by which a pressurized gas may be introduced and a trans¬ parent portion in the sterile unit through which the presence of gas bubbles can be determined, which would indicate a loss of filter integrity and unit sterility. in another embodiment of the invention, the apparatus includes a vacuum source operable on the container to create a pressure differential between the inside and outside of the container, thereby facilitating solution transfer to the container. T e process of this invention includes the steps of delivering the solution from a solution source to the sterile unit, sterilizing the solution by trans¬ ferring it through the filter, and transferring the sterilized solution through the filter outlet and tubing _ . A into the container. In one embodiment of this inven¬ tion, the above mentioned pressure differential is created by the operation of a vacuum chamber into which the container has been placed. Upon the successful completion of the transfer and sterilizing operation, the container is hermetically sealed by the application of external compression to the tubing, heat sealing of the tubing, or heat sealing of the container at a point adjacent the connection of the tubing to the container. A more detailed explanation of the invention is provided in the following description and claims, for which reference to the accompanying drawing should be made. BRIEF DESCRIPTION OF THE DRAWING FIG. 1 is a perspective view of a preferred embodiment of the apparatus of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT An apparatus of the present invention for compound¬ ing hyperalimentation solutions generally includes a filter, a plastic, extensible, parenteral solution bag, and tubing connecting the outlet of the filter to the bag. Once these elements are connected, the combination is sterilized and made available as a sterile unit, which unit is labeled for sale as being sterile. Briefly, in the transfer operation, the solutions to be transferred are selected and a vacuum chamber is made available. The filter of the sterile unit is connected to the containers holding the solutions and the bag to be filled is placed in the vacuum chamber. The solutions, prior to their transfer, may or may not be sterile. However, once they are transferred through the sterilizing filter into the bag, there is no need for resterilization of the resultant, sterilized solu¬ tion. The solutions are transferred through the filter and into the bag under the influence of a vacuum created in the vacuum chamber, which accelerates the transfer process. The bag is then sealed. However, it has been found to be advantageous to verify the integrity of the sterile unit, and the sterility of the transferred solu¬ tion, prior to the bag being sealed. This is accomplishe by the introduction into the filter of either air or another gas to ascertain if such gas passes through the filter, which is indicated by the presence of bubbles in a transparent portion of the sterile unit. If such bubbles are present, because sterility of the trans- ferred solution has not been achieved, the solution would be discarded. The following is a more detailed description of the structural elements shown in FIG. 1. Referring to FIG. 1, there is shown a first solu¬ tion container 10 and a second solution container 12. Generally these solution containers are made of glass and have means by which they may be connected to tubing for transfer or administration purposes. As shown in FIG. 1, the containers each have a stopper 14 into which a spike 16 is inserted. Each spike is attached to one end of a tubing 18 by which the solution in each of these solution holding containers can be transferred to a filter 20. A roller clamp 22 is provided for con¬ trolling the flow of solution through each tubing 18. The other end of each tubing is inserted into a Y-con- nector 24 which is attached to an inlet 26 of filter 20. Herein, inlet encompasses any means by which the solution to be transferred is presented to and may pass through the filter, such as an opening in the filter by which the solution is presented to the filtering and sterilizing media of the filter. Filter 20 is a sterilizing filter by which the solution passing through the filter is made essentially bacteria free prior to its further transfer. Preferably, the filter is a hydrophilic, bacterial organism retentive filter having a membrane surface area that is greater than one centimeter and a maximum pore size of about 0.22 microns. Filters found to be particularly useful in the present invention are manufactured by the Milli- pore Corporation of Bedford, Massachusetts under the trademark MILLIPORE. Proceeding downward in FIG. 1 from filter 20, the filter has an outlet 28 to which is attached a triple- branch, connector 30. Tubing similar to tubing 18 described above is inserted into each branch of con¬ nector 30. Again, a roller clamp 22 is utilized on each tubing 18 to control the flow therethrough. The other end of each tubing 18 is attached to a flexible, plastic bag 32 in a manner well known in the art. As shown in FIG. 1, bag 32 is placed in a vacuum chamber 34 to be filled in the manner discussed below. A vacuum chamber found to be particularly useful in accordance with the present invention is disclosed in U.S. Pat. No. 3,722,557, the disclosure which is incorporated by reference herein. Such a vacuum chamber includes a base 36, a support post 38, and top and bottom members, 40 and 42, which are hinged together. The vacuum drawn in the chamber is sourced through a vacuum hose 44. The solutions contained in holding containers 10 and 12 are generally sterilized during their manufacture and packaging. However, to transfer these solutions to another container or administer them, the holding con¬ tainers must be open to the environment so air can enter therein for affecting solution flow. Once this occurs the possibility of contamination exists. Further, in handling spikes 16 and the other apparatus connected to containers 10 and 12, touch contamination is also possible. Therefore, whatever the condition of sterility of the solutions, filter 20 sterilizes the final solution being transferred into bag 32. In the transfer operation, filter 20, bags 32, the tubing 18 connecting the filter and bags, and the roller clamps 22 associated therewith are combined and presente for use as a sterile unit. Solution holding containers 10 and 12 and the elements associated therewith are connected to an inlet 26 of filter 20. The first bag 32 to be filled is placed in vacuum chamber 34. The actual operation of the various clamps and vacuum chambe by which the solutions are transferred into the bag is well known and need not be further discussed. Of course it should be understood that the bags can be filled in sequential order or all at one time by the use of multiple vacuum chambers. Once the bag is filled, it has been found to be advantageous to check the integrity of filter 20 and determine whether any leaks or other conditions have arisen during the transfer process by which the sterility of the transferred solution may have been compromised. Preferably, with the aid of the applica- tion of a vacuum on the filled bag, air or another gas is introduced into filter 20. By directing such a gas into inlet 26 (after the tubing 18 associated with hold¬ ing containers 10 and 12 has been disconnected there¬ from) or another opening in filter 20, the operator can determine from gas bubbles in a transparent portion of the sterile unit whether the integrity of the filter, and consequently the sterility of the transferred solu¬ tion, has been maintained. Of course, if a vacuum chamber is not used in the operation the gas can be pressurized instead. If no such bubbles appear in the solution being sterilized, bag 32 is hermetically sealed by either external compression of tubing 18 connected thereto, heat sealing of this tubing, or heat sealing of the bag itself adjacent a point where the tubing connects to the bag. Although only preferred embodiments of the present invention have been shovm in FIG. 1 and described with respect thereto, various modifications to and other improvements in this invention will be apparent to one skilled in the art.

Claims: AMENDED CLAIMS (received by the International Bureau on 23 March 1981 (23.03.81)) 13 1. Apparatus for transferring and sterilizing a solution, which comprises: at least one flexible plastic solution bag, having an inlet; a sterilizing filter capable of sterilizing the solu¬ tion and having a maximum pore size of about 0.22 micron, said filter having an outlet; flexible tubing connected to the inlet of said flexi- ble plastic solution bag and to the outlet of the steriliz¬ ing filter, to provide a flexible fluid path between the filter and the flexible plastic solution bag; said flexible tubing being heat sealable whereby the tubing may be heat sealed after the solution is trans- ferred to said flexible plastic solution bag; said sterilizing filter, flexible tubing and flexible plastic bag being presterilized as a unit and carrying a label thereon indicating that said unit is sterile; and an inlet connected to said sterilizing filter for coupling to the solution to be transferred and sterilized. 2. The apparatus of Claim 1 further comprising means for determining whether the integrity of the filter, and consequently the sterility of the unit, has been main¬ tained during the transfer process. 3. The apparatus of Claim 1 further comprising means for creating a pressure differential between the inside and outside of the container, thereby facilitating solu¬ tion transfer through the apparatus. 4. The apparatus of Claim 1 wherein the filter has a membrane surface area of at least one centimeter. 5. The apparatus of Claim 1 wherein the filter is hydrophilic, bacterial organism retentive filter. 6. The apparatus of Claim 2 wherein said means in¬ cludes an inlet into the filter by which a pressurized g may be introduced and a transparent portion in the steri unit through which the presence of gas bubbles can be determined, which would indicate a loss of filter integr and unit sterility. 7. The apparatus of Claim 6 further comprising mea for creating a pressure differential between the inside and outside of the container, thereby facilitating solu¬ tion transfer through the apparatus. 8. A process for transferring and sterilizing a solution, which comprises the steps of: providing at least one flexible plastic solution ba having an inlet; providing a sterilizing filter capable of steriliz¬ ing the solution and having a maximum pore size of about 0.22 micron, said filter having an outlet; providing flexible tubing connected to the inlet of said flexible plastic solution bag and to the outlet of the sterilizing filter, to provide a flexible fluid path between the filter and the flexible plastic solution bag sterilizing said sterilizing filter, flexible tubin and flexible plastic bag as a unit; providing a label on said unit indicating that said unit is sterilized; connecting, to an inlet to said sterilizing filter, a source of solution to be transferred; and sterilizing the solution by transferring it from th source, through the sterilizing filter and to the plasti bag via said flexible tubing. 9. The process of Claim 8 further comprising the step of determining whether the integrity of the filter, and consequently the sterility of the unit, has been ain- tained during the transfer process. 10. The process of Claim 8 further comprising the steps of introducing a pressurized gas into the filter and observing through a transparent portion in the sterile unit for gas bubbles, which would indicate a loss of filter integrity and unit sterility. 11. The process of Claim 8 further comprising the step of creating a pressure differential between the in¬ side and outside of the container to facilitate solution transfer from the filter into the container. 12. The process of Claim 8 further comprising the step of hermetically sealing the container after termina¬ tion of the transfer process. 13. The process of Claim 9 further comprising the step of creating a pressure differential between the in- side and outside of the container to facilitate solution transfer from the filter into the container. 14. The process of Claim 9 wherein the pressure differential is created by the operation of a vacumm chamber into which the container is placed. 15. The process of Claim 9 wherein the gas is directed into the filter in the same manner as is the solution being transferred. ■ βU EΛ ^ _0λ-PI v ΛilPO ? TlO 16. The process of Claim 10 wherein the gas is directed through a reclosable opening in the filter. 17. The process of Claim 12 wherein the container is hermetically sealed by the application of external compression to the tubing. 18. The process of Claim 12 wherein the container is hermetically sealed by the heat-sealing of the tubing 19. The process of Claim 12 wherein the container is hermetically sealed by being heat-sealed at a point adjacent the connection of the tubing to the container. U O.V. A V?. r - STATEMENTUNDERARTICLE19 The above-identified revised claims have been added to the specification in order to overcome indefiniteness and to add subject matter in the claims. Applicant's attorney states that the entire subject matter of these claims is disclosed in the specification of the interna¬ tional application as filed. These revised claims are identical to the now pending claims in the priority application in the United States. OMPI xA

Inventors: BELLAMY D, QUICK J
Applicants: BAXTER TRAVENOL LAB, BAXTER TRAVENOL LAB INC
Application year: 1980
Main classification: B01D31
IPC codes: A61J1, A61J3, A61L2, A61M1, B01D35, B01D61