EP0750488A1

EP0750488A1 - A device and a process for aseptic mixing of liquid products

Info

Publication number: EP0750488A1
Application number: EP19950911514
Authority: EP
Inventors: Lajos Pethö; Ivan Hakansson
Original assignee: HAKANSSON Ivan; Petho Lajos; IMIA Development AB; IMIA Dev AB
Current assignee: IMIA DEVELOPMENT AB
Priority date: 1994-02-28
Filing date: 1995-02-21
Publication date: 1997-01-02
Anticipated expiration: 2015-02-21
Also published as: AU1905295A; ATE179589T1; HUT76713A; DE69509508D1; SE9400681D0; SE9400681L; DE69509508T2; CN1054279C; CA2184249A1; HU9602344D0; EP0750488B1; SE501835C2; PL178101B1; WO1995022954A1; PL316025A1; CN1123521A

Abstract

The invention relates to an apparatus for mixing aseptically three or more liquid products (51, 53, 55) and includes at least two pointed connection devices (1, 21, 41) which are provided with through-passing flow passageways (3, 4, 24, 25, 43, 44) and are connected in series by means of a connecting line (61) and are intended to be inserted through penetrable closure means (58, 59, 60) of product containers (52, 54, 56). A first of these connection devices (1) functions to place the first container (52) in communication with the surroundings via a sterilizing filter (7), and connects the first container with the second container (54) through the connecting line (61), wherein the product containers are mutually connected together successively by means of respective subsequent connection devices down to the last product container (56) in line in which the final mixture of products, including the product (55), is collected. A subpressure prevails in the last container in line, this subpressure constituting the force by means of which the products are driven through the system. The invention also relates to a connection device (21) and to a system for aseptically mixing three or more liquid products, and also to a method of mixing the products. The invention is primarily intended for application when mixing the liquid components of a preparation for parenteral nutrient supply.

Description

A device and a process for aseptic mixing of liquid products

The present invention relates to an apparatus and a method for aseptically mixing liquid products. The invention particularly relates to an apparatus and a method for mixing aseptically three or more liquid products for pharmaceutical or nutritive use. Even more particularly, the invention relates to an apparatus and to method for mixing aseptically liquid products for inclusion in a preparation for adminis¬ tering nutrient parenterally, particularly intravenously. The invention also relates to a connection device and.to a system for mixing aseptically three or more liquid products.

Nutrients are very often administered parenterally to patients who are unable to ingest nutrients in the normal way, for some reason or another. The nutrient supply is com¬ prised primarily of three main types of nutrient, namely carbohydrates, amino acids and fat. However, in order to achieve a good nutrient status it is necessary to supply a patient with approximately fifty different nutrients in total on a daily basis. The carbohydrates and amino acids are supplied in the form of solutions, and the fat in the form of an emulsion. These preparations also contain other necessary nutrients, such as electrolytes, trace elements and water-soluble and fat-soluble -vitamins. However, it is not normally possible to prepare storage mixtures which contain all three liquid components, since such mixtures will not have sufficient storage stability. Unsuitable reaction products are formed as a result of different reaction processes, at times these reaction products can ha harmful to a patient when administered parenterally. For instance, carbohydrates and amino acids may form Maillard reaction products, which can cause toxic secondary effects. The Maillard reaction products often give the solution a yellowish colour, which is undesirable and in many cases unacceptable to the national health authorities. Other components are liable to render fat emulsions unstable and cause the emulsions to break down and form large fat parti¬ cles, i.e. creaming, or a complete separation of the fat phase.

Attempts to avoid the problems have been made by administer¬ ing the three components to the patient separately and by combining the components at a point located only a short distance from the infusion location, with the aid of a branch tube. This method is complicated, however, and it is diffi¬ cult to meter the individual components in their correct dosages.

It is also possible to mix the three components in desired proportions immediately prior to their administration and then to infuse the supply immediately before any undesirable reactions are able to occur. In this case, however, it is very often necessary to mix the components in a completely aseptic manner without having access to sterilized locations and without the assistance of personnel who have been especially trained for this purpose. The task of mixing these solutions in a manner which is correct both physically and chemically while preventing microbial contamination at the same time has been found to present a serious problem to hospital personnel. Among other things, there has been developed and used hitherto an apparatus which is designed for mixing together two liquid products aseptically. This apparatus has been used to mix aseptically a fat emulsion with a ready mix of amino acids and carbohydrates in aqueous solution. Stock mixtures of amino acids and carbohydrates are not really suitable, however, for the reasons aforeraentioned. No apparatus has been available which will enable three or more liquid products to be mixed aseptically. This drawback is eliminated by means of the present invention.

The present invention provides an apparatus for mixing three liquid products aseptically, said apparatus including a) a first pointed connection device for insertion through a penetrable closure means of a first product container, wherein the connection device includes two separate, general¬ ly parallel through-penetrating passageways of which the first opens at one end into the pointed part of the connec¬ tion device and at the other end communicates with the surrounding atmosphere through a sterilizing filter, and wherein the second passageway also opens at one end into the pointed part of the connection device and is connected to a connection line at its other end; and b) a second, double-pointed connection device, wherein a first pointed part of said device is arranged for insertion through a penetrable closure member of a second product container and includes two separate, generally parallel through-penetrating passageways of which a first passageway opens at one end into the first pointed part and the other end of said passageway is connected to the connection line extending from the first connection device, and wherein the second passageway also opens at one end into the first pointed part and at the other end opens into the second pointed part of the connection device, this second pointed part being arranged for insertion through a penetrable closure means of a third product container in which a mixture of all products is collected.

In the case of one embodiment of the inventive apparatus for mixing aseptically four or more liquid products, the connec¬ tion line between the first and the second connection devices has coupled therein one or more additional, intermediate, pointed connection devices each having a pointed part for insertion through a respective penetrable closure.-..means of a liquid product container, said pointed part including two separate, generally parallel passageways, both of which open at one end into the pointed end of the connection device and the other ends of which are each connected to a respective connection line extending from a preceding or to a subsequent connection device. According to the invention, there is also provided a connec¬ tion device for mixing together three or more' liquid prod¬ ucts, this device including a first, hollow pointed part which is arranged to pierce a penetrable closure means of a liquid product container, wherein the pointed part includes two separate, generally parallel through-penetrating passage¬ ways, both of which open at one end into the pointed part, wherein the first passageway is connected to a connection line for supplying a liquid product or product mixture to be mixed with the liquid product in the container, and wherein the second passageway opens at one end into another pointed part which is arranged to pierce a penetrable closure means of a container which contains another product with which the other liquid products are to be mixed to provide a final mixture.

The invention also relates to a method of mixing three or more liquid products aseptically, each of said products being contained in separate product containers which are connected to each other series, wherein a product or a product mixture is caused to flow initially from the first container in the series under aseptic conditions to the next following container and there be mixed with a product in said container, until a final mixture of all products has been collected in the last container in the series.

According to one preferred embodiment of the method, at least the product in the last container is pre-packed at a pressure beneath atmospheric pressure and the first product container is caused to communicate with the surrounding atmosphere through the medium of a sterilizing filter, so_^_.that the products will be driven or drawn successively through the series of product containers under the influence of the outer atmospheric pressure and mixed mutually together and are finally collected in the last product container as a final mixture. Preferably, all products are packed in their respective containers at a pressure beneath atmospheric pressure. The invention also relates to a system for producing an aseptic mixture of three liquid products, ' this system including

a) a container which contains a first liquid product which is enclosed in the container with the aid of a penetrable closure means;

b) a first, pointed connection device which includes a first through-passing passageway which opens at one end into the pointed part of the connection device and is connected with the ambient atmosphere at its other end through the medium of a sterilizing filter, and which also includes a second, through-passing passageway which is generally parallel with the first passageway spaced therefrom, wherein one end of the second passageway opens into the pointed part of the connec¬ tion device and the other end is connected to a connection line, wherein the pointed part of the first connection device is inserted through the penetrable closure means of the first container to achieve fluid connection therewith;

c) a container which contains a second liquid product, which is enclosed in the container by means of a penetrable closure means;

d) a second, double-pointed connection device which includes a first through-passing passageway which opens at one end into the first pointed part of the connection device and is connected at its other end to the connection line extending from the first connection device, and also includes a second through-passing passageway which is generally parallel with the first passageway and opens at one end into the first pointed part of the connection device and opens at its other end into the second pointed part of said connection device, wherein the first pointed part is inserted through the penetrable closure means of the second product container to achieve fluid connection therewith; and e) a third product container in which the product is con¬ tained at a pressure beneath atmospheric pressure and which includes a penetrable closure means through which the second pointed part of the second connection device is inserted to achieve fluid connection with said product container, wherein the volumetric capacity of the container is sufficient to accommodate the mixture of liquid products.

According to one embodiment of the system for obtaining an aseptic mixture of four or more liquid products, one or more additional, intermediate pointed connection devices is/are coupled in the connection line between the first and the second connection devices, each of these additional connec¬ tion devices including two through-passing, generally parallel passageways which open at one end into the pointed part of the connection device, with the other end connected to the connection line, wherein the pointed part of each intermediate connection device is inserted through a penetra¬ ble closure means of an additional liquid product container.

The invention will now be described in more detail with reference to the accompanying drawings, in which Figure 1 is a sectioned view of the first pointed connection device according to the invention; Figure 2 is a side view of the connection device shown in Figure 1; Figure 3 is a sectioned view of the second pointed connection device according to the invention; Figure 4 is a side view of the second connection device; Figure 5 illustrates an additional, intermediate connection device used in accordance with one embodiment of the invention; and Figure 6 illustrates schematically the construction of the inventive system. _^_

Figs. 1 and 2 illustrate the first connection device, generally referenced 1, which includes a pointed part 2 and two mutually separate and generally parallel through-passing passageways 3 and 4. One end of the first passageway 3 opens at 5 into the pointed end 2, while the other end of the first passageway communicates at 6 with the surrounding atmosphere through a sterilizing filter 7. The Figure shows the steril¬ izing filter 7 mounted in a chamber 8 and held in position by a cover member 9 provided with openings 10 in communication with the surrounding atmosphere. The steriliz¬ ing filter may, of course, be arranged in other ways.

The second passageway 4 also opens at one end into the pointed part 2, at 11, while the other end of the second passageway 4 is connected at 12 to a connection line (not shown) by means of a connection 13.

Figs. 3 and 4 illustrate the second connection device, generally referenced 21, which includes a first pointed part 22 and a second pointed part 23, said pointed parts normally extending in mutually opposite directions, although this is not strictly necessary. The second connection device 21 includes two mutually separate and generally parallel passageways 24 and 25. One end of the first passageway 24 opens at 26 into the first pointed part 22, while the other end of said passageway is connected at 27 to a connection line (not shown) from the first connection device 1, by means of a connection 28.

A first end of the second passageway 25 also opens into the first pointed part 22, at 29, and the other end of the passageway opens out adjacent the second pointed part 23, at 30.

Figure 5 is a sectional view of an intermediate, pointed connection device, generally referenced 41, which i.s used in the embodiment of the invention in which four or more liquids are to be mixed together. This intermediate connection device includes a pointed part 42 and two mutually separate and generally parallel through-passing passageways 43 and 44. One end 45 and 46 of respective passageways 43 and 44 opens into the pointed end-part 42, while the other ends 47 and 48 of respective passageways connect with connections 49 and 50 for coupling the intermediate connection device in the connection line (not shown) between the first and the second connection devices 1 and 21.

It will be understood that several intermediate connection devices 41 may be coupled sequentially in the connection line, one such intermediate connection device being required for each additional liquid product to be mixed in accordance with the invention, over and above the first-mentioned three products.

The pointed ends of the connection devices illustrated in Figures 1-5 and the passageways contained therein shall be protected against mechanical damage and primarily against microbial contamination, by means of protective hoods or caps placed over respective points. These protective hoods ^' will preferably be airtight and may also include a means which is destroyed when the hood is removed, so that the hood cannot subsequently be replaced without it being evident that the hood has been removed (tamper-proof) . The design of such protective hoods and such safety devices lies within the competence of one of normal skill in this art. The protective hood shall not be removed from its respective point until immediately prior to inserting the point through the penetra¬ ble product container closure means. The protective hoods have not been shown in the drawings, for the sake of clarity.

Figure 6 is a schematic illustration of an inventive system for mixing three liquid products aseptically. The first product 51 is contained in the first product container 52, and the second product 53 is contained in the second product container 54. The third product 55 is contained in a product container 56 whose empty volume 57 is sufficiently large to accommodate the products 51 and 53 arriving from the contain¬ ers 52 and 54 respectively. The three containers 52, 54 and 56 are closed by means of penetrable closure means 58, 59 and 60 respectively. These closure means may be of a conventional kind, consisting in a rubber membrane which closes the container opening and which is held in place by a metal capsule. This capsule contains in the central region of the closure an opening which exposes the rubber membrane so as to enable said membrane to be pierced by a pointed connection device. The opening in the metal capsule can be protected from damage and from bacterial contamination during storage and transporta¬ tion with the aid of a metal or plastic protective covering. It will be obvious to those skilled in this art that other penetrable closure means are conceivable.

Figure 6 shows schematically a first pointed connection device 1 according to Figures 1 and 2 inserted through the penetrable closure means 58 of the container 52. The passage¬ ways 3 and 4 of the connection device 1 connect at one end with the interior of the container 52 at the pointed end 2 of the device. The other end of the passageway 3 communicates with the surrounding atmosphere through a sterilizing filter at 6, while the other end of the passageway 4 connects at 12 to a connection line 61 extending to a second connection device 21 of the kind illustrated in Figures 3 and 4.

The pointed end 22 of the connection device 21 is inserted into the container 54 through the penetrable closure means 59, while the pointed end 23 of said connection device 21 is inserted into the container 56 through the penetrable closure means 60. The orifice 27 of the first passageway 24 of said connection device connects with the connection_,, line 61 extending from the first container 52. The second passageway 25 connects the interior of the second container 54 with the interior of the third container 56. Thus, there is obtained an open connection from the surrounding atmosphere through the sterilizing filter 7 (Figure 1) and successively through the containers to the third, and in the illustrated case the last container 56. Thus, when subjected to the influence of a suitable driving force, liquid product 51 is- able to flow from the container 52 and through the container 54 while mixing with the liquid product 53 contained therein, and finally into the conductor 56 in which all three products are mixed together to form a final mixture.

When four or more liquid products are to be mixed together, one or more intermediate connection devices of the kind shown in Figure 5 are coupled in the connection line 61 with the aid of their two connectors 49 and 50. The pointed part 42 of this connection device, which includes the passageways 43 and 44, is then inserted through a penetrable closure means of a product container of similar type to the containers 52 and 54.

The last container 56 in line which accommodates the final mixture of said liquid products, including the product 55, shall have a volumetric capacity sufficient to accommodate the final mixture. The final container 56 will thus have a significant empty volume 57 prior to the mixture components having been transferred to this final container. This empty volume shall be under a vacuum or a pressure beneath atmo¬ spheric pressure. It is this subpressure that generates the driving force in the mixing process, as will be described in more detail below.

The products contained in the containers 52 and 54, and also in any other additional container arranged upstream of the final container 56 will also preferably be contained under a vacuum or a subpressure. However, subpressure conditions are not necessary in the case of these containers, and the containers may be under atmospheric pressure or a moderate overpressure. When an overpressure or subpressure prevails in one or more containers, with the exception of the last container, this overpressure must be equalized through the sterilizing filter. In order to achieve this, it is necessary for the pointed ends of the connection devices to lie above the surfaces of the liquid in respective containers. The products are often packed under some suitable protective gas, such as nitrogen, and not under air, in order to prevent the oxidation of sensitive components.

The connection line 61 extending between the two connection devices 1 and 21 may have the form of a hose connection between the connectors 13 and 28 of respective connection devices, optionally with additional, intermediate connection devices 41 coupled in the connection line. However, it is preferred that the connection line 61 and the two connection devices 1 and 21 are permanently connected together in the manufacture of the mixing apparatus, such as to form a unit. This combination of connection devices and connection line can then be combined with a suitable container holding device which functions to hold the three product containers 52, 54 and 56 and their respective connections and connecting line in the form of a unit. Such a unit can be handled more easily in the mixing process than separate product containers.

The inventive method of aseptically mixing three liquid products is carried out in the following manner:

The two connection devices 1 and 21 will have been connected together by means of the connecting line 61 and all pointed parts 2, 22 and 23 of respective connection devices will have been covered with protective hoods (not shown) which are impervious to air and bacteria and therewith prevent air and bacteria from entering the passageways 3, 4 and 24, 25 of respective devices 1 and 21, as before described. The protective hood is now removed from the pointed part 2 of the connection device 1 and the point is inserted through the penetrable closure means 58 of the product container 52. If the product 51 in the container 52 is under subpressure, the interior of the container will now assume atmospheric pressure by virtue of ambient air being able to flow into the device 1, through the sterilizing filter 7 and the passageway 3.

The protective hood covering the pointed part 22 of the connection device 21 must not be removed before the subpres¬ sure in the container 52 has been equalized. This is impor¬ tant in ensuring aseptic conditions in the container 52. If the hood covering the point 22 is removed prematurely while a subpressure still prevails in the container 52, unfiltered air will be sucked in through the passageway 24 and the connection line 61 and enter the container 52 and therewith contaminate the container contents 51.

When the subpressure in the container 52 has been equalized, the hood covering the point 22 of the connection device 21 is removed and the point is inserted through the penetrable closure means 59 of the container 54. The subpressure prevailing in this container is thereafter equalized by air that flows into the connection device 1 through the steril- ized filter 7 and from there into the product container 52, while displacing part of its content 51 into the container

54. The hood covering the point 23 of the connection device

21 may not be removed before the pressure has been equalized.

This is important in preventing unfiltered air from flowing into the product container 54 through the passageway 25 and contaminating the content 53 of said container.

When the subpressure in the container 54 has been equalized, the hood is removed from the point 23 of the connection device 21 and said point is inserted through the penetrable closure means 60 of the last container 56 in „lάne. The subpressure prevailing in the mixing chamber 57 in the container 56 will now draw in product 53 from the container 54 by suction, at the same time as the product 51 from the container 52 will pass through the container 54 and enter the final container 56, in which the three products are mixed. The subpressure prevailing in the final container 56 will also be equalized by air drawn by suction through the sterilizing filter 7 and passing through the 'containers 52 and 54 and the connection line 61.

When four or more liquid products are to be mixed together, the mixing process is analogous with that described above. The containers are connected successively by means of the pointed connection devices, it being ensured that the subpressure in a connected container has been equalized before removing the protective hood from the point of the next following connection device and a liquid connection is established with the next following container.

As mentioned earlier, it is only necessary for a subpressure to prevail in the final container. This subpressure must be of sufficient magnitude to drive the remaining liquid products into the final container. The pressure in the preceding containers may initially be atmospheric pressure, whereby there is no danger of non-filtered air being sucked into the containers. Notwithstanding, it is preferable to remove the protective hood from a respective point on a connection device immediately prior to the point being inserted through the penetrable closure means of the contain¬ er concerned. This gives added assurance against non-filtered air coming into contact with anyone of the products and contaminating the same.

When the mixing of the products has been completed and the pressure in the final container 56 has been equalized, the container can be removed from the connection device 21 and the finished mixture administered in a conventional manner, for instance by infusion or by injection. For added safety, it is recommended that the mixture is administered as quickly as possible after being produced, in order to reduce the risk of reactions taking place between the component products, these reactions possibly giving rise to undesirable reaction products. Furthermore, the finished mixture will preferably be stored in a dark and cool environment, until it can be administered.

Naturally, it is necessary to carry out the mixing process under hygienically and unimpeachable conditions. Thus, the penetrable closure means will preferably be washed with a disinfectant, e.g. alcohol, prior to inserting the point of a connection device therethrough. The actual connection devices and associated connecting line will preferably be disposable, i.e. intended for one-time use only and stored in a sterilized package prior to use, for instance a package that has been sterilized by ionizing radiation. The simple method and apparatus provided by the invention enable the products to be mixed by hospital personnel who have no particular training in this regard without any appreciable risk of bacterial contamination.

The components of the inventive apparatus may be made of a material that is normally used within known techniques for the aseptic handling of liquids. The product containers are conveniently conventional glass or plastic bottles intended for injection or infusion preparations. The pointed connec¬ tion devices are conveniently made of a metal and/or plastic material conventionally used in this field. It is important that the materials can be sterilized, for instance by autoclaving or with the aid of gas or radiation. Since the components will preferably be intended for one-time use only, the cost of the components is also important. A skilled person who has knowledge of the invention will find no difficulty in choosing suitable materials and determining the construction of the components in detail.

The present invention thus provides a simple technical solution to the problem of mixing three or more liquid products under aseptic conditions without risk of contamina¬ tion. This is of particular value when, e.g., mixing all of the nutrients required for a complete intravenous nutrient supply.

It will be understood that the exemplifying embodiments of the invention described in detail here and shown in the drawings are merely examples and have no limiting signifi¬ cance. Further variants and modifications of the invention are possible within the scope of the following Claims and will be apparent to the skilled person who has knowledge of the fundamental inventive concept.

Claims

1. An apparatus for mixing three liquid products together aseptically, characterized by a) a first pointed connection device for insertion through a penetrable closure means of a first product container, wherein the connection device includes two separate, general¬ ly parallel through-penetrating passageways of which the first opens at one end into the pointed part of the connec- tion device and at the other end communicates with the surrounding atmosphere through a sterilizing filter, and wherein the second passageway also opens at one end into the pointed part of the connection device and is connected to a connection line at its other end; and

b) a second, double-pointed connection device, wherein a first pointed part of said device is arranged for insertion through a penetrable closure member of a second product container and includes two separate, generally parallel through-penetrating passageways of which a first passageway opens at one end into the first pointed part and the other end of said passageway is connected to the connection line extending from the first connection device, and wherein the second passageway also opens at one end into the first pointed part and at the other end opens into the second pointed part of the connection device, this second pointed part being arranged for insertion through a penetrable closure means of a third product container in which a mixture of all products is collected.

2. An apparatus for aseptically mixing four or more liquid products, characterized by a) a first, pointed connection device for insertion through a penetrable closure means of a first product container, wherein the connection device includes two separate, general¬ ly parallel through-passing passageways of which a first opens at one end into the pointed part of the connection device and at the other end communicates with the surrounding atmosphere through a sterilizing filter, and wherein the second passageway also opens at one end into the pointed part of the connection device and is connected to a connection line at its other end;

b) a second, double-pointed connection device, wherein a first pointed part of said device is arranged for insertion through a penetrable closure member of a second product container and includes two separate, generally parallel through-penetrating passageways of which a first^"passageway opens at one end into the first pointed part and the other end of said passageway is connected to the connection line extending from the first connection device, and wherein the second passageway also opens at one end into the first pointed part and at the other end opens into the second pointed part of the connection device, this second pointed part being arranged for insertion through a penetrable closure means of a third product container in which a mixture of all products is collected, and

c) one or more additional, intermediate, pointed connection devices each having a hollow point for insertion through a penetrable closure means of an intermediate liquid product container, wherein each said point includes two separate, generally parallel passageways which both open into the pointed end of the connection device and which are connected at their other open ends to a respective connecting line extending from a preceding or to a subsequent connection device.

3. A connection device for mixing three or more liquid products, characterized by a first, hollow pointed part which is arranged to pierce a penetrable closure means of a liquid product container, wherein the pointed part includes two separate, generally parallel, through-passing passageways, both of which open into the end of the pointed part, wherein the first passageway is connected to a connecting line for the supply of liquid product or product mixture to be mixe with the liquid product in said container, and wherein the second passageway opens into the end of a second pointed part which is arranged to pierce a penetrable closure means of a terminal container for an additional liquid product with which the other liquid products are to be mixed finally to form a final mixture.

4. A system for aseptically mixing three liquid products, characterized in that the system includes

b) a first, pointed connection device which includes a first through-passing passageway which opens at one end into the pointed part of the connection device and is connected with the ambient atmosphere at its other end through the medium of a sterilizing filter, and which also includes a second, through-passing passageway which is generally parallel with the first passageway and separate therefrom, wherein one end of the second passageway opens into the pointed part of the connection device and the other end is connected to a connection line, wherein the. pointed part of the first connection device is inserted through the penetrable closure means of the first container to achieve fluid connection therewith;

d) a second double-pointed connection device which includes a first through-passing passageway which opens at one end into the first pointed part of the connection device and is connected at its other end to the connection line extending from the first connection device, and also includes a secon through-passing passageway which is generally parallel wit the first passageway and opens at one end into the first pointed part of the connection device and opens at its other end into the second pointed part of said connection device, wherein the first pointed part is inserted through the penetrable closure means of the second product container to achieve fluid connection therewith; and

e) a third product container in which the product is con¬ tained at a pressure beneath atmospheric pressure and which includes a penetrable closure means through which the second pointed part of the second connection device is inserted to achieve fluid connection with said product container, wherein the volumetric capacity of the container is sufficient to accommodate the mixture of liquid products.

5. A system for aseptically mixing four or more liquid products, characterized in that the system includes

b) a first, pointed connection device which includes a first through-passing passageway which opens at one end into the pointed part of the connection device and is connected with the ambient atmosphere at its other end through the medium of a sterilizing filter, and which also includes a second, through-passing passageway which is generally parallel with the first passageway and separate therefrom, wherein one end of the second passageway opens into the pointed part of the connection device and the other end is connected to a bypass line, wherein the pointed part of the first connection device is inserted through the penetrable closure means of the first container to achieve fluid connection therewith; c) a container which contains a second liquid product, which is enclosed in the container by means of a penetrable closure means;

d) a second double-pointed connection device which includes a first through-passing passageway which opens at one end into the first pointed part of the connection device and is connected at its other end to the connection line extending from the first connection device, and also includes a second through-passing passageway which is generally parallel with the first passageway and opens at one end into^" the first pointed part of the connection device and opens at its other end into the second pointed part of said connection device, wherein the first pointed part is inserted through the penetrable closure means of the second product container to achieve fluid connection therewith;

e) a third product container in which the product is con¬ tained at a pressure beneath atmospheric pressure and which includes a penetrable closure means through which the second pointed part of the second connection device is inserted to achieve fluid connection with said product container, wherein the volumetric capacity of the container is sufficient to accommodate the mixture of liquid products; and

f) one or more additional, intermediate pointed connection devices, each having a hollow pointed part for insertion through a penetrable closure means of an intermediate liquid product container, wherein each said pointed part includes two separate, generally parallel passageways which both open into the pointed part of the connection device and whose other end-openings are each connected to a respective connecting line extending from a preceding or to a subsequent connection device, and wherein the pointed part of each of said intermediate connection devices is inserted through a penetrable closure means of an additional, intermediate liquid product container to provide a liquid connection with said product container.

6. A method for aseptically mixing three or more liquid products, characterized in that each of the products is contained in an individual product container, wherein the containers are connected together in series and product or product mixture from each of the containers, beginning with the first container in the series, is caused to flow succes¬ sively under aseptic conditions to the next container in line and there mix with the product in said container, until a final mixture of all products has been collected ^"in the last container in the series.

7. A method according to Claim 6, characterized in that at least the product in the last product container in line is pre-packed in the container at a pressure beneath atmospheric pressure; and in that the first product container is placed in communication with the surrounding atmosphere via a sterilizing filter, such that the products will be driven through the series of product containers through the influ¬ ence of the surrounding atmospheric pressure while mutually mixing the contents of the containers, said products being collected finally as a final mixture in the last product container in line.

8. A method according to Claim 7, characterized in that the products of all product containers are pre-packed therein at a pressure beneath atmospheric pressure.

9. A method according to any one of Claims 6-8, character¬ ized in that the first product container is first_^connected to the connecting line extending to the second container and to the surrounding atmosphere, and the first container is brought to atmospheric pressure while the connecting line to said second container is closed, whereafter the connecting line to the second container is opened after the pressure in the first container has assumed atmospheric pressure, and the second container is brought to atmospheric pressure while the connecting line to the third container is 'held closed, whereafter the connecting line to the following container is opened when the second container has assumed atmospheric pressure and said following container is brought to atmo¬ spheric pressure, wherein the process is repeated successive¬ ly for each of the product containers in the series down to the last product container in line, wherein the atmospheric pressure prevailing in the preceding product containers is caused to drive the products from said containers to the final product container in line so as to obtain a final product mixture in said container.

10. A method according to any one of Claims 6-9, character- ized by mixing together three liquid products.