Pre-sterilizable carrier system

Abstract

A method for filling dual-chamber systems in pre-sterilizable carrier systems includes providing at least one washed, siliconized and sterilized dual-chamber system in a magazine. The dual-chamber system includes respective separating elements separating the two chambers from each other. The magazine accommodates at least one dual-chamber system and is arranged in a container that is sealed with a closing element. The method additionally includes introducing the container into a clean room; opening the container and filling a first chamber of the at least one dual-chamber system; and closing the first chamber. The method further includes filling a second chamber of the at least one dual-chamber system; closing the second chamber; and removing the system from the clean room.

Claims

1. A method of filling at least one dual-chamber system having a first chamber with a first sealable opening and a second chamber with a second sealable opening, each dual-chamber system further including a separating element separating the first chamber from the second chamber, the method comprising: securely retaining the at least one dual-chamber system in a container with a magazine in a first orientation, such that each dual-chamber system of the at least one dual-chamber system is securely retained in a first configuration relative to the container with the first opening facing upwardly and the second opening facing downwardly; introducing a first solution into the first chamber of the at least one dual-chamber system through the first opening; inverting each dual-chamber system of the at least one dual-chamber system such that each dual-chamber system is securely retained in a second configuration relative to the container with the second opening facing upwardly and the first opening facing downwardly; and introducing a second solution into the second chamber of the at least one dual-chamber system through the second opening; wherein inverting each dual-chamber system of the at least one dual-chamber system includes: removing the magazine from the container with each dual-chamber system securely in the magazine independent of an orientation of the magazine; turning the magazine over to a second orientation; and returning the magazine to the container with each dual-chamber system in the second configuration.

2. The method of filling at least one dual-chamber system of claim 1, wherein the first solution is selected from an active substance, an auxiliary substance and combinations thereof.

3. The method of filling at least one dual-chamber system of claim 2, wherein the second solution is selected from an active substance, an auxiliary substance and combinations thereof.

4. The method of filling at least one dual-chamber system of claim 2, wherein the second solution is selected from a solvent, and a solvent mixture.

5. The method of filling at least one dual-chamber system of claim 2, further comprising sealing the container with a gas-permeable closing element.

6. The method of filling at least one dual-chamber system of claim 5, wherein the gas permeable closing element reversibly seals an upper side of the container with the magazine arranged in both of the first and second orientations.

7. The method of filling at least one dual-chamber system of claim 6, further comprising: introducing the container into a clean room with the at least one dual-chamber system sealed within the container by the gas-permeable closing element; and removing the gas-permeable closing element to provide filling access to the at least one dual-chamber system.

8. The method of filling at least one dual-chamber system of claim 7, further comprising: resealing the container with the gas-permeable closing element after introducing the first solution into the first chamber of the at least one dual-chamber system and before removing the magazine from the container; and lyophilizing the first solution.

9. The method of filling at least one dual-chamber system of claim 8, wherein lyophilizing the first solution occurs within the clean room.

10. The method of filling at least one dual-chamber system of claim 9, further comprising removing the container from the clean room, wherein lyophilizing the first solution occurs outside the clean room.

11. The method of filling at least one dual-chamber system of claim 10, further comprising returning the container to the clean room prior to introducing the second solution into the second chamber of the at least one dual-chamber system.

12. The method of filling at least one dual-chamber system of claim 1, further comprising closing the second chamber of the at least one dual-chamber system after introducing the second solution into the second chamber.

13. The method of filling at least one dual-chamber system of claim 12, wherein closing the second chamber includes closing the second chamber with a plug.

14. The method of filling at least one dual-chamber system of claim 13, wherein each each dual-chamber system of the at least one dual-chamber system such that each dual-chamber system includes a separating element separating the first and second chambers.

15. The method of filling at least one dual-chamber system of claim 14, wherein closing the second chamber includes displacing the plug within the dual-chamber system so that pressure forces are transmitted via the plug into the second chamber and finally into the separating element such that the pressure forces activate the dual-chamber system.

16. The method of filling at least one dual-chamber system of claim 1, wherein the at least one dual-chamber system includes a plurality of dual-chamber systems.

17. The method of filling at least one dual-chamber system of claim 1, wherein the container has an upper side, a lower side, and a shoulder in a middle region between the upper side and the lower side, the lower side being closed by a bottom wall of the container, the upper side being open.

18. The method of filling at least one dual-chamber system of claim 1, wherein the container includes a shoulder having an abutment surface abutting the magazine in both the first orientation and the second orientation.

19. The method of filling at least one dual-chamber system of claim 1, wherein the magazine includes a first planar side and an opposing second planar side, and further wherein the first planar side faces upward in the first configuration and the second planar side faces upward in the second configuration.

Description

(1) The invention is illustrated in more detail hereinafter by means of the drawings. In the figures:

(2) FIG. 1 shows a schematic view of a pre-sterilizable carrier system;

(3) FIG. 2 shows a schematic illustration of the step of filling a first chamber of the dual-chamber systems with a method according to the invention;

(4) FIG. 3 shows a schematic view of the closing process of the first chamber of the dual-chamber systems with the method;

(5) FIG. 4 shows a schematic illustration of the filling process of a second chamber of the dual-chamber systems with the method; and

(6) FIG. 5 shows the closing process of the second chamber of the dual-chamber system with the method.

(7) FIG. 6A illustrates an alternative closure with attachable needle.

(8) FIG. 6B illustrates another alternative closure with attached needle.

(9) FIG. 1 shows schematically an exemplary embodiment of a pre-sterilized carrier system. The pre-sterilizable carrier system 1 comprises at least one washed, siliconized and sterilized dual-chamber system 3 with two chambers 5, 5′ which are separated from each other by a separating element 7. The dual-chamber systems 3 are accommodated by a magazine 9 which in turn can be arranged in a container 11. The latter is sealed with a closing element 13.

(10) The container 11 can comprise plastic and preferably consists of plastic. The magazine 9 too can comprise plastic and preferably consists of plastic. In this manner, both elements can be provided for a one-time use so that to each batch of dual-chamber systems 3, one magazine 9 and one container 11 are allocated.

(11) The closing element 13 for the container 11 is preferably configured in a gas-permeable manner so that the fully loaded and sealed container 11 can be sterilized in the closed state by introducing the container into an atmosphere which comprises a gas intended for sterilization or a vapor intended for sterilization. The gas or the vapor can penetrate through the closing element 13 into the interior of the container 11 and thus can sterilize in particular the interior of the container 11 and the dual-chamber systems 3 and the magazine 9 contained therein.

(12) The different methods are now illustrated in more detail by means of the FIGS. 2 to 5.

(13) First, the pre-sterilizable carrier system 1 is provided and introduced into a clean room. Then, the closing element 13 is removed so that the dual-chamber systems 3 are accessible.

(14) FIG. 2 shows the step of filling a first chamber 5 of the dual-chamber systems 3. Identical and functionally identical elements are indicated with identical reference numbers so that in this respect, reference is made to the preceding description. A dispensing device 15 is provided through which a first solution L1 of an active and/or auxiliary substance can be introduced into a first chamber 5 of the dual-chamber systems 3.

(15) After filling the first chamber 5 of the dual-chamber systems 3, the first chamber can be closed as shown in FIG. 3. Identical and functionally identical elements are indicated with identical reference numbers so that in this respect, reference is made to the preceding description. A first closing device 17 is provided by means of which the first chamber 5 of the dual-chamber systems 3 can be closed in each case with one closure 19. The closure 19 can be a flanged cap, a tamper-proof closure, a closure with attachable needle or a closure with attached needle. In principle, other types of closures can also be used; it is essential, however, that the first chamber 5 of the dual-chamber system 3 is tightly sealed by a closure 19.

(16) Instead of closing the first chamber 5 of the dual-chamber systems 3 directly after filling it is also possible to integrate a lyophilization step for the active substance and/or auxiliary substance contained in the solution L1. For this purpose, the container 11 is closed after filling the first chamber 5 of the dual-chamber systems 3 with a gas-permeable closing element, preferably a gas-permeable membrane film. The container 11 sealed in this manner can be introduced into a lyophilization device where the solution contained in the first chamber 5 sublimates through the gas-permeable closing element so that the active substance and/or auxiliary substance present in the dual-chamber systems 3 is lyophilized. Since the container 11 is hygienically sealed by the gas-permeable closing element 13, it is possible to provide the lyophilization device outside of the clean room. Thus, the container 11 can be removed from the clean room and can be introduced into an external lyophilization device. The latter does not have to be sterile and/or aseptic because no germs, viruses or bacteria can pass through the closing element 13 and get into the interior of the container 11. In this manner, in particular the dual-chamber systems 3 remain sterile or aseptic even if the lyophilization is carried out in a non-sterile and/or non-aseptic environment. After lyophilization, the container 11 can be introduced again into a clean room in which the further method steps take place.

(17) Of course, it is also possible to arrange the lyophilization device in the clean room itself so that removing and re-introducing the container 11 is eliminated. It is obvious that here also the lyophilization device itself has to be sterile and/or aseptic.

(18) During lyophilization, the dual-chamber systems 3 are embedded in the container 11 and are reliably protected against interfering radiation or other disturbing influences.

(19) If such a lyophilization step is integrated between the filling of the first chamber 5 of the dual-chamber systems 3 and the closing of said first chamber, it is obvious that the container 11—if necessary, after re-introducing into a clean room—has to be opened again so that the dual-chamber systems 3 are accessible. After closing the first chamber 5 of the dual-chamber systems, a second chamber 5′ is filled. This is possible in a particularly simple manner by turning the magazine 9 over. In this case it is provided that the magazine 9 encompasses the dual-chamber systems 3 in such a manner that the latter are securely retained in the magazine 9, independent of the orientation of the same. In this manner it is ensured that the dual-chamber systems 3 do not slip out of the magazine, not even when turning it over. After turning the magazine 9 over, the same is preferably introduced again into the container 11, wherein now a second chamber 5′ of the dual-chamber systems 3 is accessible through the opening of the container 11.

(20) FIG. 4 shows schematically the filling of the second chamber 5 of the at least one dual-chamber system 3. Identical and functionally identical elements are indicated with identical reference numbers so that in this respect, reference is made to the preceding description. Here too, a dispensing device 15 is provided through which a second medium L2 can be introduced into the second chamber 5′ of the dual-chamber systems 3. The second medium L2 can involve the solution of a further active substance and/or auxiliary substance; however, it can also involve a—preferably pure—solvent or solvent mixture.

(21) After filling the second chamber 5′ of the dual-chamber systems 3, said chamber can also be closed.

(22) FIG. 5 shows schematically the step of closing the second chamber 5′ of the dual-chamber systems 3. Identical and functionally identical elements are indicated with identical reference numbers so that in this respect, reference is made to the preceding description. The second chamber 5′ is closed by means of a second closing device 21 with a closing element which is exemplary configured here as plug 23. The latter is preferably displaceable in the dual-chamber system 3 so that pressure forces can be transmitted via the plug into the second chamber 5′ and finally into the separating element 7, wherein the pressure forces result in an activation of the dual-chamber system 3. It is preferred that the plug 23 is configured as threaded plug. In this manner, it can act as plunger element, wherein a non-illustrated plunger rod can be engaged by means of an external thread with the internal thread of the threaded plug 23. Thus, pressure forces can be transmitted in a very simple manner into the second chamber 5′ and therefore indirectly into the separating element 7, wherein the pressure forces result in an activation of the dual-chamber systems 3.

(23) After closing the second chamber 5′, the container 11 can be closed again and can be removed from the clean room. It is also possible to omit the closing of the container 11 and to selectively remove the container in its open state from the clean room or to remove only the magazine 9 or even the individual dual-chamber systems 3 from the clean room. Since both chambers 5, 5′ of the dual-chamber systems 3 are tightly sealed, it is not required to keep the dual-chamber systems 3 any longer in a sterile and/or aseptic environment.

(24) Overall, it is apparent that the production method according to the invention and the pre-sterilizable carrier system according to the invention are advantageous over the known methods and devices for filling dual-chamber systems. According to the invention it is possible for a producing pharmaceutical company to use a standardized packing directly on standardized filling lines. Here, it is also possible to fill products intended for lyophilization on plants which are configured for pre-sterilizable systems. In known methods, specifically for filling dual-chamber systems in connection with materials intended for lyophilization, heavy and expensive metallic magazines are used which are re-used and therefore have to be autoclaved in a costly manner. In the present case, instead of such magazines, a standardized packing form is used during the entire filling process, wherein the packing form is used only once and is disposed of afterwards. Since the carrier system according to the invention is gas-permeable but can be sealed to be impenetrable for germs, viruses or bacteria, it is possible to arrange the filling area and the lyophilization area decentralized with respect to each other which, moreover, allows to carry out the lyophilization in a non-sterile environment. The content of the carrier system according to the invention thus remains sterile at any time. Furthermore, in known methods it is necessary to close each individual chamber 5, 5′ of the dual-chamber systems 3 prior to the lyophilization step with a so-called lyo closure, whereby the selection of the closure of the first chamber is limited. In contrast, in the present method it is possible to select any closure system. This is achieved by the fact that the container 11 itself is closed by a gas-permeable closing element 13 so that an individual closing of the first chamber 5 of the dual-chamber systems 3 is not necessary for the lyophilization step. Since during the semi-automatic, automatic or manual loading and unloading of the lyophilizer, hygienically closed containers are handled, there is again a significantly lower contamination risk as this is the case with known methods.