Abstract:
In one embodiment, there is provided a method for producing a sterilized and pyrogen-free bag for storing fluids. The method includes providing a bag comprised of polymeric film and heating the bag to at least approximately 253 degrees Celsius for at least approximately 30 minutes for sterilization and pyrogen removal. The polymeric film is a polymer selected from the group of poly(oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-phenylene) (PEEK); polytetrafluoroethylene (PTFE); a perfluoroalkoxy (PFA) polymer; poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) (MFA); polyperfluoro(ethylene-co-propylene)(FEP); poly(ethylene-alt-chlorotrifluoroethylene) (ECTFE); poly(ethylene-co-tetrafluoroethylene) (ETFE); poly(vinylidene fluoride) (PDVF); tetrafluoroethylene-co-hexafluoropropylene-co-vinylidene fluoride terpolymer (THV); poly(bisphenol A-co-4-nitrophthalic anhydride-co-1,3-phenylenediamine) (PEI); poly(4-methyl-1-pentene) (PMP); and suitable mixtures thereof.

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S)  
       [0001]     This application is related to and a divisional of application Ser. No. 10/658,034, filed on Sep. 9, 2003, and entitled “Sterile Pyrogen-Free Polymeric Film-Based Heating Bag”, now abandoned. 
     
    
     TECHNICAL FIELD  
       [0002]     This invention generally relates to a method of heating a bag. More particularly, the invention relates to a method for producing an essentially sterile, pyrogen-free, polymeric film-based heating bag. The polymeric film can include a polymer selected from the group of poly(oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-p-henylene) (PEEK); polytetrafluoroethylene (PTFE); a perfluoroalkoxy (PFA) polymer; poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) (MFA); polyperfluoro(ethylene-co-propylene) (FEP); poly(ethylene-alt-chlorotrifluoroethylene) (ECTFE); poly(ethylene-co-tetrafluoroethylene) (ETFE); poly(vinylidene fluoride) (PDVF); tetrafluoroethylene-co-hexafluoropropyl-ene-co-vinylidene fluoride terpolymer (THV); ultra-high molecular weight polyethylene (UHMW PE); (poly(bisphenol A-co-4-nitrophthalic anhydride-co-1,3-phenylenediamine) (PEI); poly(4-methyl-1-pentene) (PMP); and suitable mixtures thereof.  
       BACKGROUND OF THE INVENTION  
       [0003]     The storage of fluids and liquids that are essentially free of contaminants and bacteria is important across a number of different industries. For example, in the medical field, the storage of bodily fluids, such as blood, in containers that are free of pyrogen are important. In particular, pyrogen is a substance or agent that produces fever. Pyrogen may be present in containers that store bodily fluids. Accordingly, such containers may contaminate the bodily fluids stored therein with this pyrogen. A current requirement from a number of government agencies (including the Federal Drug Administration (FDA)) is that such containers are to be heated to at least 253 degrees Celsius for at least approximately 30 minutes to one hour (to remove pyrogen therefrom) prior to storage of the fluids.  
         [0004]     A conventional approach is to use glass containers because such containers may withstand the required temperature. However, the use of glass containers can be problematic. In particular, the glass containers may break if dropped. Moreover, such containers, which cannot typically be reused in certain applications (storage of bodily fluids), are relatively expensive.  
         [0005]     A typical application of storage of fluids that are to be sterilized and pyrogen free includes the transfer of blood from a first individual to a second individual. In particular, the blood is drawn from the first individual and stored in a glass container (that has been sterilized and free of pyrogen). Subsequently, the blood is transferred into the second individual. However, when glass containers are used in such an application, air is typically trapped in the glass container along with the blood. Therefore, when the blood is transferred into the second individual, if such transfer is not closely monitored, the air in the glass container can be transferred into the second individual as well. A conventional approach to preclude the introduction of the air into the second individual during the blood transfusion is to include an electronic monitoring. Accordingly, when the transfer of the blood is completed, the electronic monitoring detects that air is in the connector (coupling the glass container to the body). The electronic monitoring then closes a shutoff valve inside the connector to preclude the transfer of air from the glass container into the body. However, such equipment that allows for the electronic monitoring is relatively expensive and must be unique for each individual receiving a blood transfusion.  
       BRIEF SUMMARY OF THE INVENTION  
       [0006]     There is provided a method for producing a sterilized and pyrogen-free bag for storing fluids. The method includes providing a bag comprised of polymeric film and heating the bag to at least approximately 253 degrees Celsius for at least approximately 30 minutes for sterilization and pyrogen removal. The polymeric film is a polymer selected from the group of poly(oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-phenylene) (PEEK); polytetrafluoroethylene (PTFE); a perfluoroalkoxy (PFA) polymer; poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) (MFA); polyperfluoro(ethylene-co-propylene)(FEP); poly(ethylene-alt-chlorotrifluoroethylene) (ECTFE); poly(ethylene-co-tetrafluoroethylene) (ETFE); poly(vinylidene fluoride) (PDVF); tetrafluoroethylene-co-hexafluoropropylene-co-vinylidene fluoride terpolymer (THV); poly(bisphenol A-co-4-nitrophthalic anhydride-co-1,3-phenylenediamine) (PEI); poly(4-methyl-1-pentene) (PMP); and suitable mixtures thereof. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0007]     Embodiments of the invention may be best understood by referring to the following description and accompanying drawings which illustrate such embodiments. The numbering scheme for the Figures included herein are such that the leading number for a given reference number in a Figure is associated with the number of the Figure. For example, a polymeric film-based bag  100  can be located in  FIG. 1 . However, reference numbers are the same for those elements that are the same across different Figures. In the drawings:  
         [0008]      FIG. 1A  illustrates parts of a bag comprised of a polymeric film, according to one embodiment of the invention.  
         [0009]      FIG. 1B  illustrates a manufactured bag comprised of a polymeric film, according to one embodiment of the invention.  
         [0010]      FIG. 2  illustrates an apparatus for manufacturing a bag comprised of a polymeric film, according to one embodiment of the invention.  
         [0011]      FIG. 3  illustrates a flow diagram for manufacturing a polymeric film-based bag, according to one embodiment of the invention.  
         [0012]      FIG. 4  illustrates a flow diagram for storing fluids in a polymeric film-based bag that is essentially sterile and pyrogen free, according to one embodiment of the invention.  
     
    
     DETAILED DESCRIPTION  
       [0013]     Methods, apparatuses and systems for different embodiments for an essentially sterile, pyrogen-free, polymeric film-based heating bag are described. References in the specification to “one embodiment”, “an embodiment”, “an example embodiment”, etc., indicate that the embodiment described may include a particular feature, structure, or characteristic, but every embodiment may not necessarily include the particular feature, structure, or characteristic. Moreover, such phrases are not necessarily referring to the same embodiment. Further, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of one skilled in the art to affect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described.  
         [0014]     As used herein, “polymeric” or “polymer” refers to poly(oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-phenylene) (PEEK); polytetrafluoroethylene (PTFE); a perfluoroalkoxy (PFA) polymer; poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) (MFA); polyperfluoro(ethylene-co-propylene) (FEP); poly(ethylene-alt-chlorotrifluoroethylene) (ECTFE); poly(ethylene-co-tetrafluoroethylene) (ETFE); poly(vinylidene fluoride) (PDVF); tetrafluoroethylene-co-hexafluoropropyl-ene-co-vinylidene fluoride terpolymer (THV); (poly(bisphenol A-co-4-nitrophthalic anhydride-co-1,3-phenylenediamine) (PEI); poly(4-methyl-1-pentene) (PMP); and suitable mixtures thereof.  
         [0015]     Poly(oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-phenylene) (PEEK) is a non-fluorinated polymer that has a repeat unit that comprises oxy-1,4-phenylene-oxy-1,4-phenylene-carbonyl-1,4-phenylene. PEEK is commercially available from Victrex (http://www.victrex.com/us/) and is shown below:  
                         
 
         [0016]     Polytetrafluoroethylene (PTFE) is a fluorinated polymer in which the film typically has a thickness of about 0.0115 inches to about 0.25 inches (as commercially sold). PTFE is commercially available from Saint-Gobain Performance Plastics and Aldrich Chemicals (Aldrich entry # 43,093-5), has a CAS Reg. No. of # 9002-84-0, and is shown below:  
                         
 
         [0017]     A perfluoroalkoxy (PFA) polymer resin is a fluorinated polymer in which the film typically has a thickness of about 0.0005 inches to about 0.030 inches (as commercially sold). PFA&#39;s are commercially available from Saint-Gobain Performance Plastics and are shown below:  
                         
 
         [0018]     Poly(tetrafluoroethylene-co-perfluoromethyl vinyl ether) (MFA) is a fluorinated polymer in which the film typically has a thickness of about 0.0005 inches to about 0.03 inches (as commercially sold). MFA is commercially available from Saint-Gobain Plastics and is shown below:  
                         
 
         [0019]     Polyperfluoro(ethylene-co-propylene) (FEP) is a fluorinated polymer commercially available from Saint-Gobain Plastics and is shown below:  
                         
 
         [0020]     Poly(ethylene-alt-chlorotrifluoroethylene) (ECTFE) or ethylene-chlorotrifluoroethylene is a fluorinated polymer that is commercially available from Saint-Gobain Performance Plastics and Aldrich (Aldrich entry # 42,721-7) and has a CAS Reg. No. 25101-45-5. ECTFE is shown below:  
                         
 
         [0021]     Poly(ethylene-co-tetrafluoroethylene) (ETFE) or ethylene-tetrafluoroethylene is a fluorinated polymer that is commercially available from Saint-Gobain Performance Plastics and Aldrich (Aldrich entry # 42,719-5) and has a CAS Reg. No. 25038-71-5. The structure of ETFE is shown below:  
                         
 
         [0022]     Poly(vinylidene fluoride) (PVDF) is a fluorinated polymer that is commercially available from Saint-Gobain Performance Plastics and Aldrich (Aldrich entry # 42,715-2) and has a CAS Reg. No. 24937-79-9. The structure of PVDF is shown below:  
                         
 
 and has an average molecular weight of about 180,000 g/mol or about 275,000 g/mol from gas permeation chromatography (GPC); or an average molecular weight of up to about 534,000 from Aldrich. 
 
         [0023]     Tetrafluoroethylene-co-hexafluoropropylene-co-vinylidene fluoride terpolymer (THV) or tetrafluoroethylene-hexafluoropropylene-vinylidene fluoride terpolymer is a fluorinated polymer that is commercially available from Saint-Gobain Performance Plastics and Aldrich (Aldrich entry # 45,458-3). THV has a CAS Reg. No. of 54675-89-7 and is shown below:  
                         
 
         [0024]     Poly(bisphenol A-co-4-nitrophthalic anhydride-co-1,3-phenylenediamine (PEI) or polyether imide is a non-fluorinated polymer that is commercially available from Saint-Gobain Performance Plastics and Aldrich (Aldrich entry # 43,229-6) and has a CAS Reg. No. 61128-46-9. The structure of PEI is shown below:  
                         
 
         [0025]     Poly(4-methyl-1-pentene) (PMP) or polymethyl pentene is commercially available from Saint-Gobain Performance Plastics and Aldrich (Aldrich entry # 19,099-3) and is shown below:  
                         
 
         [0026]     In one embodiment of the invention, the polymer or polymeric film can include PEEK. In another embodiment of the present invention, the polymer or polymeric film can include a fluorinated polymer described above. In another embodiment of the present invention, the polymer or polymeric film can include a non-fluorinated polymer described above.  
         [0027]     A number of figures show diagrams of systems and apparatuses of a polymeric film-based bag, in accordance with embodiments of the invention. A number of figures show flow diagrams illustrating operations for manufacture and use of a polymeric film-based bag (that is essentially sterile and pyrogen free). The operations of the flow diagrams will be described with references to the systems/apparatus shown in the diagrams. However, it should be understood that the operations of the flow diagrams could be performed by embodiments of systems and apparatus other than those discussed with reference to the diagrams, and embodiments discussed with reference to the systems/apparatus could perform operations different than those discussed with reference to the flow diagrams.  
         [0028]      FIG. 1A  illustrates parts of a bag comprised of a polymeric film, according to one embodiment of the invention.  FIG. 1A  illustrates a polymeric film-based bag  100  that includes a first polymeric film  102 , a second polymeric film  104  and a connector  106 . In one embodiment, the connector  106  is made of polymeric. The first polymeric film  102  has an edge  108 A, an edge  108 B, an edge  108 C and an edge  108 D. The second polymeric film  104  has an edge  110 A, an edge  110 B, an edge  110 C and an edge  110 D. As shown, the connector  106  is approximately perpendicular to the side  108 C and the side  110 C. In an embodiment, the thickness of the first polymeric film  102  and/or the thickness of the second polymeric film  104  may be in a range of approximately 15 to 50 microns.  
         [0029]     In one embodiment, the first polymeric film  102  and/or the second polymeric film  104  has a viscosity in a range such that the film is of a pharmaceutical grade and may reach mechanical constraints regarding the application. For example, the first polymeric film  102  and/or the second polymeric film  104  may be of BC3-WH type.  
         [0030]      FIG. 1B  illustrates a manufactured bag comprised of polymeric film, according to one embodiment of the invention. As shown,  FIG. 1B  illustrates the parts illustrated in  FIG. 1A  that have been coupled together to form the polymeric film-based bag  100 . The edge  108 A of the first polymeric film  102  is coupled to the edge  110 A of the second polymeric film  104 . The edge  108 B of the first polymeric film  102  is coupled to the edge  110 B of the second polymeric film  104 . The edge  108 C of the first polymeric film  102  is coupled to the edge  110 C of the second polymeric film  104 . The edge  108 D of the first polymeric film  102  is coupled to the edge  10 D of the second polymeric film  104 . Accordingly, the connector  106  is between the edge  108 C and the edge  110 C after the edge  108 C is coupled to the edge  110 C.  
         [0031]     In one embodiment, the edges  108 A- 108 D are coupled to the edges  110 A- 110 D, respectively, through a welding process. In one such embodiment, the edges  108 A- 108 D are welded to the edges  110 A- 110 D by heating such edges to a predefined temperature and pressing the edges together. In one embodiment, the predefined temperature is at least approximately 3300 Celsius.  FIG. 2  illustrates an apparatus for manufacturing a bag comprised of a polymeric film, according to one embodiment of the invention. As shown, an apparatus  200  includes a first press  202  and a second press  206 . The first press  202  includes a press edge  204 A, a press edge  204 B, a press edge  204 C and a press edge  204 D. The second press  206  includes a press edge  208 A, a press edge  208 B, a press edge  208 C and a press edge  208 D. The remaining part of the first press  202  (that is interior to the press edge  204 A, the press edge  204 B, the press edge  204 C and the press edge  204 D) is recessed. The remaining part of the first press  202  (that is interior to the press edge  208 A, the press edge  208 B, the press edge  208 C and the press edge  208 D) is recessed.  
         [0032]     The press  202  includes a first slot  215 A in the press edge  208 C. The press  206  includes a second slot  215 B. The first slot  215 A and the second slot  215 B allow for the placement of the connector  106  approximately perpendicular to the press edge  204 C and the press edge  208 C during the weld operation.  
         [0033]     The first polymeric film  102  is placed in the first press  202  and the second polymeric film  104  is placed in the second press  206 . The edge  108 A is aligned with the press edge  204 A. The edge  108 B is aligned with the press edge  204 B. The edge  108 C is aligned with the press edge  204 C. The edge  108 D is aligned with the press edge  204 D. The edge  110 A is aligned with the press edge  208 A. The edge  10 B is aligned with the press edge  208 B. The edge  110 C is aligned with the press edge  208 C. The edge  110 D is aligned with the press edge  208 D. In operation, the first press  202  is pressed into the second press  206 . Accordingly, the edges  108 A- 108 D are pressed to the edges  110 A- 110 D, respectively. However, the remaining part of the first polymeric film  102  and the remaining part of the second polymeric film  104  are not in contact with each other. In an embodiment, the press, edges  204 A- 204 D and the press edges  208 A- 208 D are heated to a predefined temperature. In one embodiment, the predefined temperature is at least approximately 330 degree. Celsius. In an embodiment, the press edges  204 A- 204 D and the press edges  208 A- 208 D comprise a covered liquid (e.g., an oil). Accordingly, the temperature is more homogenous across the press edges  204 A- 204 D and the press edges  208 A- 208 D.  
         [0034]     Embodiments for the manufacture of the polymeric film-based bags are not limited to the weld operation illustrated in  FIG. 2 . For example, in an embodiment, the edges  108 A- 108 D are coupled to the edges  110 A- 110 D, respectively, through ultrasonic sealing.  
         [0035]     One embodiment for the manufacturing of a polymeric film-based bag is now described. In particular,  FIG. 3  illustrates a flow diagram for manufacturing a polymeric film-based bag, according to one embodiment of the invention.  
         [0036]     In block  302  of the flow diagram  300 , the edges of a first polymeric film are aligned with the edges of a second polymeric film. With reference to the embodiment of  FIG. 1A , the edges  108 A- 108 D are aligned with the edges  110 A- 110 D, respectively. Control continues at block  304 .  
         [0037]     In block  304 , a connector is placed approximately perpendicular with one edge of the first polymeric film and one edge of the second polymeric film. With reference to the embodiment of  FIG. 1A , the connector  106  is placed approximately perpendicular to the edge  108 C and the edge  110 C. Control continues at block  306 .  
         [0038]     In block  306 , the edges of the first polymeric film are coupled to the edges of the second polymeric film. With reference to the embodiment of  FIG. 1B , the edges  108 A- 108 D of the first polymeric film  102  are coupled to the edges  110 A- 110 D of the second polymeric film  104 . As described above, such coupling may be performed by a number of different operations, including a welding operation, ultrasonic sealing, etc. The operations for manufacturing a polymeric film-based bag are complete.  
         [0039]     One embodiment for using a polymeric film-based bag is now described. In particular,  FIG. 4  illustrates a flow diagram for storing fluids in a polymeric film-based bag that is essentially sterile and pyrogen free, according to one embodiment of the invention. While described with reference to storage of fluids, embodiments of the invention are not so limited. For example, in other embodiments, different types of solids and gases may be stored therein. In an embodiment, the polymeric film-based bag may store different types of bodily fluids. For example, the fluids may be blood. In one embodiment, the fluids may be bodily fluids that include at least one of macrophages, B lymphocytes, cytotoxic T lymphocytes, plasma cells, helper cells, B lymphocytes, antibodies, erythrocytes, leukocytes, red blood cells, white blood cells, and platelets. In one embodiment, the fluids may be bodily fluids that include arterial blood, banked blood, cord blood, defibrinated blood, laky blood, oxalated blood, or whole blood.  
         [0040]     In block  402  of the flow diagram  400 , the polymeric film-based bag is heated to at least approximately 253 degrees Celsius. As described above, current requirements by the FDA for the sterilization and removal of pyrogen from containers, bags, etc include that the interior lining be heated to at least 253 degrees Celsius. In an alternative embodiment, the polymeric film-based bag is heated to a lesser or greater temperature depending on the application. Control continues at block  404 .  
         [0041]     In block  404 , the heating of the polymeric film-based bag is maintained for at least 60 minutes. Current requirements by the FDA for the sterilization and removal of pyrogen from containers, bags, etc. include that the interior lining of such container, bags, etc. be heated to at least 253 degrees Celsius for at least 60 minutes. In an alternative embodiment, the heating of the polymeric film-based bag is maintained for a lesser or greater amount of time depending on the application. Control continues at block  406 .  
         [0042]     In block  406 , fluids are stored in the polymeric film-based bag after heating the bag to at least 253 degrees Celsius for at least 60 minutes. Accordingly, fluids (essentially sterile and free of pyrogen) that are stored in this polymeric film-based bag stay essentially sterile and free of pyrogen. In other words, the polymeric film-based bag that has been treated as described above does not contaminate the fluids stored therein, because the inner lining of the bag is essentially sterile and free of pyrogen. With reference to  FIG. 1B , the fluids are stored in the polymeric film-based bag through the connector  106 . Control continues at block  408 .  
         [0043]     In block  408 , the polymeric film-based bag is sealed after storing the fluids in the bag. With reference to  FIG. 1B , the connector  106  is sealed after storing the fluids therein. In an embodiment, the polymeric film-based bag  100  may be incorporated into a kit. For example, the kit may include the polymeric film-based bag  100  (subsequent to sterilization and removal of pyrogen) along with packaging material and instructions or indicia located on the packaging material or inside the packaging material. In one such embodiment, fluids may be included in such a kit (stored either external or internal to the polymeric film-based bag  100 ).  
         [0044]     Thus, methods, apparatuses and systems for an essentially sterile, pyrogen-free, polymeric film-based heating bag have been described. Although the present invention has been described with reference to specific exemplary embodiments, it will be evident that various modifications and changes may be made to these embodiments without departing from the broader spirit and scope of the invention. Therefore, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense.