Patent Publication Number: US-10766653-B2

Title: Method of packaging sterilized products

Description:
RELATED APPLICATION 
     This application is a continuation of U.S. application Ser. No. 14/068,474, filed Oct. 31, 2013, now U.S. Pat. No. 10,035,615, which claims priority under 35 U.S.C. § 119 to U.S. Provisional Application Ser. No. 61/889,583, filed Oct. 11, 2013, the disclosures of which are incorporated herein by reference in their entirety. 
    
    
     FIELD OF THE INVENTION 
     The invention relates to a method of introducing sterilized products for use in a sterile environment. In particular, the invention provides a method by which sterilized products, namely paper products that are enclosed in four successively sealed layers are introduced into a cleanroom without contaminating the environment with particulates and microorganisms. 
     BACKGROUND OF THE INVENTION 
     Sterile “cleanroom” environments demand that any person or item entering the room be free of a certain level of contaminants. Sterilized environments are most commonly designed for use in manufacturing facilities and medical research and treatment facilities in the pharmaceutical, biotechnology, and healthcare industries, to name a few. Sterile cleanroom environments may be classified under a variety of classification schemes, including the International Organization of Standardization (“ISO”) Cleanroom Standards, whereby the highest level of sterilization is an ISO 1 cleanroom, and normal ambient air (no sterilization) is classified as ISO 9. 
     A variety of products are required to enter cleanroom environments, including paper and paper products used to document manufacturing and testing records within the controlled areas. Such paper products include, but are not limited to, forms, logbooks, tags and batch records. All of these documents are necessary to detail the manufacturing and testing processes so as to ensure that proper procedures are followed and results are documented. Indeed, these documents are subject to review by regulatory agencies, such as the U.S. Food and Drug Administration, and represent the mechanism by which such agencies can review the manufacturing and testing process details after the manufacture, testing, or handling of a drug product, for example, to assure patient safety. 
     However, paper and paper products are a significant contamination source due to shedding fibers, particulates and microorganisms (e.g.,  bacillus  and mold). About 40% of paper products used in sterile environments are standard documents that can be pre-printed, packaged and sterilized by known means. However, the remainder of the documents introduced into sterile environments cannot be pre-printed, sterilized and packaged in a timely fashion. Their preparation requires information that is not readily available until days, or even hours, before the manufacturing or testing is to begin. In some instances, they must be prepared while manufacturing and/or testing is underway. Because of this, these documents are forced to be brought to sterilized areas without prior treatment for the reduction of shedding fibers, particulates and microorganisms. Thus, they represent a significant contamination source. 
     One solution in the industry is to pre-package products that must be introduced into a cleanroom environment. As disclosed in U.S. Pat. Nos. 6,123,900, 6,607,698 and 6,333,006, chemical containers are first pre-sterilized according to the methods set forth therein, and then the containers are enclosed within a first and second layer, and then placed into a carton having a liner. To unpackage, the container (with the two sealed layers and the liner) is removed from the carton on the loading dock. Once transported to a first sterile environment, the liner is removed and the container (now enclosed by two sealed layers) is placed on a shelf for future use. Once it is ready to be used, the second sealing layer is removed and the container (now enclosed by one sealed layer) is moved to a higher-grade sterile environment. In practice, that method requires that the outside of the liner and each sealing layer be sprayed with antiseptic and/or antibacterial sanitizers to remove any contaminants, such as bacteria and mold, before being transported to the next (more sterile) environment. Such an additional step causes vapors from the sanitizing agent to fill the atmosphere of the cleanroom, which introduces particles into the clean room and can be dangerous to the cleanroom operation as well as the workers. Additionally, according to this method, the product is removed from the last layer before it is transported to the final cleanroom where it is to be utilized. 
     To solve this problem, the invention provides for a method of introducing packaged sterilized products, specifically paper products, into a sterile environment. 
     SUMMARY OF THE INVENTION 
     The invention provides a method of introducing a sterilized production to a controlled environment. The sterilized product is enclosed in a substantially hermetically sealed first layer, which is enclosed in a second substantially hermetically sealed layer, which is enclosed in a substantially hermetically sealed third layer, which is enclosed in a fourth substantially hermetically sealed layer to form a packaged product. 
     The method of introducing the sterilized product into a sterilized environment includes removing the fourth layer to expose the third layer in an environment with a first sterility, removing the third layer to expose the second layer in an environment with a predetermined second sterility, the predetermined second sterility being higher than the first sterility, removing the second layer to expose the first layer in an environment with a predetermined third sterility, the predetermined third sterility being higher than the predetermined second sterility, and removing the first layer to expose the sterilized product in an environment with a predetermined fourth sterility, the predetermined fourth sterility being higher than the predetermined third sterility. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       A more complete appreciation of the invention and many of the attendant advantages thereof will be readily obtained as the same becomes better understood by reference to the following detailed description when considered in connection with the accompanying drawings, wherein: 
         FIG. 1  is a block diagram showing the steps for the method of packaging a sterilized paper product; 
         FIG. 2  is a perspective view of a packaged sterilized paper product according to an embodiment of the invention; 
         FIGS. 3A, 3B  are exploded views of the first two layers of the packaged sterilized paper product depicted in  FIG. 2 ; 
         FIGS. 4A, 4B  are exploded views of the packaged sterilized paper product depicted in  FIG. 2  enclosed within a container for shipment; and 
         FIG. 5  is a block diagram showing the steps for the method of introducing paper products into a sterilized environment. 
     
    
    
     DETAILED DESCRIPTION 
     Referring now to  FIGS. 1-5 , a method of packaging sterilized products so as to ensure their sterility, namely paper products, is provided. A method of introducing sterilized products, namely paper products, into a sterile environment is also provided. While the Figures provided herein are directed to paper products, any sterilized products may be used with the methods of the invention. The four-stage sealing methods described herein provide the benefit of ensuring protection against contamination inside the cleanroom, while maintaining the sterility of the packaged products. Once the products are removed from the successive sealing layers, no additional sanitizing step is needed since the last layer is removed within the cleanroom of the final destination where the product is used. This reduces cost because antibacterial and/or antiseptic sanitizers and sprays are not needed, and the cleanroom and its workers are protected from harmful vapors that are released when sanitizing agents are used on the products. 
     Generally, paper products (or similar printing media) are pre-sterilized and then packaged according to the methods of the invention. They are then shipped in cartons, such as cardboard containers with exterior plastic wrapping, to an end destination. The cardboard containers may be shipped by any known shipping method, such as by truck, rail or air transportation. The packaged products are then introduced into sterile environments according to the methods provided herein. 
     Referring to  FIGS. 1-3 , a paper product or printing medium  200  is first sterilized, according to step  100 . According to one embodiment of the invention, common pulp-based paper may be used. According to a preferred embodiment, a non-shedding paper product, such as plastic, non-shedding Teslin® printing medium (manufactured by PPG Industries of Pittsburgh, Pa.) is used. The term “paper” as used herein includes both common pulp-based paper products as well as other types of printing media (e.g., Teslin® paper) known in the art. The paper may be provided on rolls at a predetermined length, or it may be provided as cut sheets prepared in reams (as shown in  FIGS. 1-4 ). Any sterilization methods known to one skilled in the art may be used, including, but not limited to, steam, heat, chemical treatment, or gamma irradiation. In a preferred embodiment, gamma irradiation is used. The rolls or reams may then be packaged according to the methods of the invention. 
     Specifically, the sterilized paper  200  may undergo a quadruple “bagging” or “layering” process to form a final packaged product  202 , as shown in  FIG. 2 . According to step  102 , the sterilized paper  200  (which may be contained in a sealed paper enclosure, as shown) is enclosed in a first layer  204  ( FIG. 3A ), which may then be sealed to form a substantially hermetically sealed first layer enclosure so as to keep out any contaminants. The first layer enclosure (containing the paper  200 ) is then enclosed in a second layer  206  ( FIG. 3B ) and the second layer  206  is then substantially hermetically sealed to form a second layer enclosure, according to step  104 . This second layer enclosure (containing the first layer  204  and the sterilized paper  200 ) is then further enclosed in a third layer  208 , which is also substantially hermetically sealed, to form a third layer enclosure according to step  106 . Lastly, the third layer enclosure (containing the first and second layers  204 ,  206  and the sterilized paper  200 ) is enclosed in a fourth layer  210  and substantially hermetically sealed to form a fourth layer enclosure, according to step  108 . Any sealing method known to one skilled in the art which forms a hermetic seal may be used for each of the sealing steps. According to a preferred embodiment, heat sealing is used. This process ultimately creates a final packaged product  202 , whereby the sterilized paper product  200  is enclosed within four successive protective layers  204 ,  206 ,  208  and  210  each having a substantially hermetic seal, as shown in step  110 . While not depicted in the Figures, the layering process may involve the use of more than four layers, for example, five or six layers, depending on the level of sterility required. 
     The four sealing layers  204 ,  206 ,  208  and  210  are preferably formed of a single-layer durable, waterproof plastic material. According to one embodiment, polyethylene is used. According to a preferred embodiment, the layers may be in the form of plastic bags. 
     As shown in step  112  of  FIG. 1 , the final packaged product  202  may then be enclosed within a container  212  for shipping. According to one embodiment, the container  212  is a standard cardboard shipping container. The container  212  may have an internal liner  218  (see  FIG. 4A ) that lines the walls of the container  212  and acts as yet another sealing layer. The internal liner  218  may be formed of a plastic material (i.e., polyethylene bag) similar to sealing layers  204 ,  206 ,  208  and  210 . Multiple packaged products  202  may be placed inside the internal liner  218  of the container  212 . The internal liner  218  may then be closed via tying (e.g., twist tie) or some other known closure mechanism (e.g., rubber band) such that the packaged products  202  are enclosed therein. According to another embodiment, the internal liner  218  can be substantially hermetically sealed. Referring now to  FIGS. 4A, 4B , the cardboard container  212  may then be closed in the standard manner, using flap closures  214 . The cardboard container  212  may also have an exterior layer of plastic wrapping  216 , or “shrink wrap,” so as to protect the surface of the cardboard container  212  from outside contaminants. The cardboard container  212  may then be sterilized according to known methods in the art, such as, for example, gamma irradiation. Multiple cardboard containers  212  may then be placed on skids (not shown) for ease of transportation. The closed and sterilized cardboard containers  212  are then prepared for shipping and are transported for operational use downstream. 
     Referring now to  FIG. 5 , the cardboard container  212  arrives at the end destination and, inevitably, the plastic wrapping  216  is contaminated with many types of bacteria (e.g.,  bacillus ), mold, and other microorganisms, as shown in step  300 . Thus, the plastic wrapping or “shrink wrap”  216  is removed from the cardboard containers  212 , as shown in step  302 . The exterior of the cardboard container  212  and the transportation skids (not shown) are also contaminated with various microorganisms. Thus, as shown in step  304 , the cardboard container  212  and internal layer  218  are opened, and the packaged product  200  located within the internal layer  218  is removed from the cardboard container  212  and placed on a vehicle, such as a cart, for transfer to the Grade D, C, B and A areas. 
     According to the invention, Grade A areas demand that all products entering the cleanroom be sterilized via steam, heat, chemical treatment, or gamma irradiation and packaged in multi-layer packaging configurations. “Grade B” areas are adjacent to Grade A areas and also demand sterilization and the use of multi-layer packaging configurations. Grade C and Grade D are consecutively adjacent to Grade B areas, such that any products bound for a Grade A area must pass through Grades C and D, which also demand low “bioburden,” or contamination, to be present. The use of a multi-layer packaged product reduces the bioburden that may exist on the exterior of the packaging, while keeping the inner packaged produce free of particulates and microorganisms. 
     The classification of Grade A, B, C and D sterile environments are measured based upon the number and size of particles permitted per volume of air. Specifically, the ISO Cleanroom Standards correspond to the allowed number of particles having a minimum particle size per cubic meter. The ISO classification is set forth in Table 1 below. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 ISO Cleanroom Standards 
               
            
           
           
               
               
            
               
                   
                 Maximum number of particles per cubic meter 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 ≥0.1  
                 ≥0.2  
                 ≥0.3 
                 ≥0.5 
                 ≥1 
                 ≥5 
               
               
                 Class 
                 μm 
                 μm 
                 μm 
                 μm 
                 μm 
                 μm 
               
               
                   
               
               
                 ISO 5 
                 100,000 
                  23,700 
                   10,200 
                    3,520 
                     832 
                    29 
               
               
                 ISO 6 
                 1.0 ×  
                 237,000 
                   102,000 
                    35,200 
                    8,320 
                    293 
               
               
                   
                 10 6   
                   
                   
                   
                   
                   
               
               
                 ISO 7 
                 1.0 ×  
                 2.37 ×  
                 1,020,000 
                   352,000 
                   83,200 
                  2,930 
               
               
                   
                 10 7   
                 10 6   
                   
                   
                   
                   
               
               
                 ISO 8 
                 1.0 ×  
                 2.37 ×  
                 1.02 ×  
                  3,520,000 
                   832,000 
                  29,300 
               
               
                   
                 10 8   
                 10 7   
                 10 7   
                   
                   
                   
               
               
                 ISO 9 
                 1.0 ×  
                 2.37 ×  
                 1.02 ×  
                 35,200,000 
                 8,320,000 
                 293,000 
               
               
                   
                 10 9   
                 10 8   
                 10 8   
               
               
                   
               
            
           
         
       
     
     Normal ambient air is classified as ISO 9. According to the invention, Grade A areas correspondence to ISO 5, Grade B areas correspond to ISO 6, Grade C areas correspond to ISO 7, and Grade D areas correspondence to ISO 8. The methods provided below ensure that sterilized paper can be consecutively introduced from Grade D to Grade A, minimizing the level of contaminants between each Grade area until little to no contaminant is present when the product is introduced to the Grade A area. 
     Once the packaged product  202  arrives near the Grade D area, the fourth layer  210  (outermost layer) is removed and discarded by a first operator wearing protective gloves, as shown in step  306 . As set forth above, the exterior of the fourth layer  210  inevitably has some amount of contamination. The packaged product  202  is then transferred to the Grade D area. Once the packaged product  202  arrives at the Grade D area, the third layer  208  is removed by a second operator (also wearing protective gloves) and discarded, as shown in step  308 . This packaged product  202  is then transferred to the Grade C area. Once the packaged product  202  arrives at the Grade C area, the second layer  206  is removed by a third operator (also wearing protective gloves) and discarded, as shown in step  310 . This packaged product  202  is then transferred to the Grade B area. Once the packaged product  202  arrives at the Grade B area, the first layer  204  (innermost layer) is removed by a fourth operator (also wearing protective gloves) and discarded, as shown in step  312 . At this point, each of the layers  204 ,  206 ,  208  and  210  has been successively removed and the packaged product  202  should have little to no bioburden on its exterior surface. The paper rolls or reams  200  are then transferred to the Grade A area for their end use. The paper rolls or reams  200  may be inserted into the feed roller (for roll paper) or the paper tray (for ream paper) of a printing device within the Grade A area (not shown in  FIG. 5 ), with the assurance that the paper  200  has been maintained in a sterilized state. 
     According to another embodiment, the first three steps of the method of  FIG. 5  are performed, namely steps  300 ,  302  and  304 . However, once the packaged product  202  is removed from the cardboard containers  212  and transported to the Grade D area, the fourth layer  210  (outermost layer) is removed by a first operator and discarded in the Grade D area (as opposed to outside of the Grade D area). Next, the third layer  208  is removed and discarded by a second operator in the Grade C area, and the second layer  206  is removed and discarded by a third operator in the Grade B area. The sterilized paper  200  contained within the first layer  204  (innermost layer) is then stored in a cabinet within the Grade A area until it is ready for use. When it is needed, the first layer  204  is removed and discarded by a fourth operator in the Grade A area, and the sterilized paper  200  is inserted into the feed rollers or paper tray as set forth above. 
     It is noted that the invention is described as having four sealing layers  204 ,  206 ,  208 ,  210 , each of which successively encloses a single product. Each of the sealing layers  204 ,  206 ,  208 ,  210  can be a polyethylene bag that is sized to fit the single product and earlier layers, and is hermetically sealed such as by heat. However, it should be appreciated that other variations of the sealing layers  204 ,  206 ,  208 ,  210  can be provided within the spirit and scope of the invention. For instance, one or more of the outers sealing layers  208  and/or  210  can instead be a bag that receives two or more product and which is tied or otherwise closed using known mechanisms, such as, for example, a rubber band or twist tie. In one exemplary embodiment, the first layer  204  and second layer  206  are hermetically sealed, while the third layer  208  and fourth layer  210  are closed via the alternative methods discussed herein. According to yet another embodiment, the fourth layer  210  may be in the form of a bag liner  218  that lines the shipping container  212  used to transport the packaged product  202 . 
     Although this invention has been described in connection with specific forms and embodiments thereof, it will be appreciated that various modifications other than those discussed above may be resorted to without departing from the spirit or scope of the invention. For example, equivalent elements may be substituted for those specifically shown and described, certain features may be used independently of other features, and in certain cases, particular locations of elements may be reversed or interposed, all without departing from the spirit or scope of the invention as defined in the appended Claims.