Serially linked containers for containing a sterile solution

Abstract

The invention relates to a system which can be sterilized, for preparing individual containers to be filled with a substantially accurately predetermined volume of a sterile solution, which comprises at least one string of containers comprising at least two containers which are: serially linked or serially pre-attached to one another to form a single tubing, predefined to regulate individual container fill volume either by partial partition of said single tubing or by specification which is indicative of the boundaries of the individual containers, and made of a substantially non-deforming material, one extremity of each of the at least one string of containers comprising a single inlet for the sterile solution and the other extremity comprising a single outlet for air and/or for the sterile solution, said single tubing being the exclusive flowing means for the sterile solution and for air, when present, from the single inlet to the single outlet of the string of containers.

1 . A system which can be sterilized, for preparing individual containers to be filled with a substantially accurately predetermined volume of a sterile solution, which comprises at least one string of containers comprising at least two containers which are: 
 serially linked or serially pre-attached to one another to form a single tubing,    predefined to regulate individual container fill volume either by partial partition of said single tubing or by specification which is indicative of the boundaries of the individual containers, and    made of a substantially non-deforming material,    one extremity of each of the at least one string of containers comprising a single inlet for the sterile solution and the other extremity comprising a single outlet for air and/or for the sterile solution,    said single tubing being the exclusive flowing means for the sterile solution and for air, when present, from the single inlet to the single outlet of the string of containers.    
   
   
       2 . The system of  claim 1 , further comprising means for air displacement and connecting means, said means for air displacement being connected to the single outlet of each of the at least one string of containers via said connecting means.  
   
   
       3 . The system of  claim 2 , wherein said means for air displacement comprise at least one pre-sterilized venting bag or at least one sterile barrier filter.  
   
   
       4 . The system of one of  claims 1  to  3 , further comprising at least one reservoir for sterile solution, said at least one reservoir of sterile solution being optionally connected to the single inlet of each of the at least one string of containers.  
   
   
       5 . The system of  claim 1  to  4 , characterized in that, when the sterile solution is present inside the system and in particular when the reservoir for sterile solution is full, said system is closed relative to the ambient environment, so that there is no contact between the sterile solution and air, when present, inside the system on the one hand and the ambient environment outside the system on the other hand.  
   
   
       6 . The system of one of  claims 1  to  5 , comprising a single string of containers, means for air displacement and a single reservoir for sterile solution, the means for air displacement being connected to the single outlet of the single string of containers via connecting means, and the single reservoir for sterile solution being optionally connected via additional connecting means to the single inlet of the single string of containers.  
   
   
       7 . The system of one of  claims 1  to  5 , comprising at least two strings of containers, means for air displacement and a single reservoir for sterile solution, the at least two strings of containers being placed in parallel, the means for air displacement being connected to the outlets of all the strings of containers via connecting means, and the single reservoir for sterile solution being optionally connected to the inlets of all the strings of containers via additional connecting means.  
   
   
       8 . The system of one of  claims 1  to  5 , comprising N strings of containers (N≧2), N individual means for air displacement, and a single reservoir for sterile solution, the N strings of containers being placed in parallel and each of the N individual means for air displacement being connected to the outlet of one single string of containers among the N strings of containers via connecting means, and the single reservoir for sterile solution being connected to the inlets of the N strings of containers via additional connecting means.  
   
   
       9 . The system of one of  claims 1  to  8  wherein said substantially non-deforming material is a substantially rigid material.  
   
   
       10 . The system of one of  claims 1  to  8  wherein said substantially non-deforming material is a flexible material whose deformation is limited by applied forces such as framing means or an externally applied mold which regulates the container volume.  
   
   
       11 . The system of one of  claims 1  to  10  wherein said substantially non-deforming material is sufficiently non-deforming in order for each container to be filled with a predetermined volume of said sterile solution with a better accuracy than 20%, in particular with a better accuracy than 10%, and in particular with a better accuracy than 5%.  
   
   
       12 . The system of one of  claims 1  to  11 , comprising at least one reservoir for sterile solution and wherein said at least one reservoir for sterile solution is made of a flexible material.  
   
   
       13 . The system of one of  claims 2  to  12 , wherein the means for air displacement comprise at least one venting bag and wherein said at least one venting bag is made of a flexible material.  
   
   
       14 . The system of one of  claims 1  to  13  wherein all containers have the same volume.  
   
   
       15 . The system of one of  claims 1  to  13  wherein at least some of the containers have different volumes.  
   
   
       16 . The system of one of  claims 1  to  15  wherein the volume of each individual container independently ranges from about 0.1 mL to about 200 mL.  
   
   
       17 . The system of one of  claims 1  to  16  wherein the number of individual containers per string of containers independently ranges from 2 to about 100.  
   
   
       18 . The system of one of  claims 1  to  17  wherein the number of strings of containers ranges from 1 to about 20.  
   
   
       19 . The system of one of  claims 1  to  18  wherein the containers are selected among the group composed of vials, formed containers, pouches, or bags.  
   
   
       20 . The system of one of  claims 1  to  19  wherein at least one of the individual containers further comprises at least one individual port per container for extracting sterile solution and optionally at least one other individual port per container for letting in air when sterile solution is extracted.  
   
   
       21 . The system of one of  claims 1  to  20  wherein the at least one string of containers is made of a single tube of constant cross-section, the containers being predefined by a specification which is indicative of the boundaries of the individual containers, each container optionally comprising one or two individual ports such as capped ports and in particular such as capped female Luer ports.  
   
   
       22 . The system of one of  claims 1  to  20  wherein the at least one string of containers is made of a single tubing comprising portions of tube alternated with flow-through couplings and in particular male-female Luer connections, the containers being partly predefined by a specification which is indicative of the boundaries of the individual containers and by said flow-through couplings, each container optionally comprising individual ports in particular for attachment to a capped sterile vent.  
   
   
       23 . The system of one of  claims 1  to  20  wherein the at least one string of containers is made of a single tubing comprising alternated portions of tubing of respectively larger and smaller cross-section, and wherein the individual containers are substantially predefined by the alternation of said portions of tubing and each individual container optionally comprises an individual port such as a capped port.  
   
   
       24 . The system of one of  claims 1  to  20  wherein the at least one string of containers is made of a substantially rigid material and the individual containers are substantially predefined as strings of formed containers by partial partition of the single tubing and optionally comprise at least one individual port such as a capped port.  
   
   
       25 . The system of one of  claims 1  to  24  wherein the containers are designed with materials and shapes which are resistant to cracking when cycled through freezing and thawing and which does not entrap air pockets within the containers their access ports or the fill ports.  
   
   
       26 . A method for preparing individual containers to be filled with a substantially accurately predetermined volume of a sterile solution comprising the steps of: 
 providing a system according to any one of  claims 1  to  25  comprising at least one reservoir for sterile solution and additional connecting means, said at least one reservoir for sterile solution being connected to the single inlet of each of the at least one string of containers via said additional connecting means;    injecting the sterile solution from said at least one reservoir filled with sterile solution into the at least one string of containers via the single inlet of the at least one string of containers, so as to provide individual containers filled with a predetermined volume of sterile solution;    sealing the at least one string of containers by sealing means at a plurality of positions, so as to provide filled, separate, individual containers; and    optionally detaching each individual container from the at least one string of containers by detaching means, so as to provide filled, separate, detached, individual containers.    
   
   
       27 . The method of  claim 26 , wherein the system remains closed relative to the ambient environment during the steps of injecting the sterile solution into the at least one string of containers and of sealing the at least one string of containers, so that there is no contact between the sterile solution and air, when present, inside the system on the one hand and the ambient environment outside the system on the other hand.  
   
   
       28 . The method of  claim 26 , wherein the system remains open relative to the ambient environment until the sealing of the at least one string of containers, the sterility of the sterile solution being maintained at all steps via at least one filtering means.  
   
   
       29 . The method of one of  claims 26  to  28 , wherein the system comprises at least one venting bag for displaced air which is connected to the outlets of the at least one string of containers and which is mostly empty prior to injecting the sterile solution into the at least one string of containers.  
   
   
       30 . The method of one of  claims 26  to  29 , wherein the injection of the sterile solution into the at least one string of containers is made from the top to the bottom or from the bottom to the top by means of hydrostatic pressure or of filling means such as a peristaltic pump.  
   
   
       31 . The method of one of  claims 26  to  30 , wherein the injection of the sterile solution is made from the bottom to the top, whereby air bubbles in the containers are substantially avoided.  
   
   
       32 . The method of one of  claims 26  to  31 , wherein the sealing of the containers of each of the at least one string of containers is carried out by sealing means either after the filling of said string of containers, or after the complete filling of all of the at least one string of containers.  
   
   
       33 . The method of one of  claims 26  to  32 , which comprises the additional final step of freezing and optionally thawing the sterile solution inside the containers, optionally more than once, without stress fractures appearing on said containers.  
   
   
       34 . The method of one of  claims 26  to  33 , wherein the individual containers filled with a predetermined volume of sterile solution obtained after the step of injecting the sterile solution or the filled, separate, individual containers obtained after the step of sealing or the filled, separate, detached, individual containers obtained after the optional step of detaching are subsequently used for cellular or clinical applications.