Title of Invention	IMPROVEMENTS IN OR RELATING TO THE STERILIZATION BY AUTOCLAVING OF COMPLEX BLOOD BAG SYSTEM
Abstract	A method for sterillizing a complex blood bag sustem having atleast one blood bag containing an aqueous solution within the bag, and including filters covered with corresponding permeable sealed sealed filter covers, which sterilized blood bag system shall be free from moisture on its outer surface, the method comprising the steps of

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Field of Invention: The invention relates to sterilization of complex blood bag system, comprising blood bags and other devices like fiUers which may have been more complex in construction with folds of filter material etc. Prior Art: Indian Patent No, 179473 (1992) relates to a process for the sterilization of intravenous or other solutions intended for introduction into the blood steam, which are held in autoclavable plastic containers. Contamination of the outer surface of such containers with microorganisms such as bacteria or fungi is an ever-present danger. The above-mentioned patent ensures the sterility of such plastic containers by autoclaving such containers with or without labels in an outer protective pouch made of autoclavable transparent polymers. A problem encountered in the application of this process is the accumulation of some quantity of water in the space between the inner container and its outer protective plastic covers. The water is derived from two sources - the aqueous solution in the inner plastic container and from the steam from the autoclave, which penetrates the outer protective covers. The actual quantity of the water, which accumulates within the annular space between the two bags, varies depending upon the dimensions of the irmer and outer covers, their thicknesses and also the water vapour permeabilities of the materials used. The removal of such condensed water is covered by two Indian Patents Nos. 179474 (1992) and 179475 (1992). Objects of Invention: The main object of the invention is to sterilizing the devices such as filters also alongwith sterilization of complex blood bag systems and a means with a method to ensure sufficient steam enters even the most difficult to access spots in the system. This main object is to further guarantee the sterilization of special blood bag system with complex structure having devices such as leucocytes filters offering a general resistance to easy penetration of steam by making available sufficient amount of steam to enter all the recesses on all such complex structure. The main object being to provide sufficient steam for the thorough sterilizing of complicated devices like filters and other attachments in blood bag systems, the second object is to ensure that the hold time is not unnecessarily increased for the purpose of supplying the desired sufficient steam to the area of sterilization, it is attempted to reduce the hold time but supply sufficient steam when sterilizing the complex blood bag system having filters and other devices which time would be longer than for sterilization of normal blood bag systems. The third object of the invention is to hasten the process of water entry to the filter or other devices during autoclaving. The fourth object of the invenfion is to assist the process of water entry to the filter or other devices during autoclaving by making available a ready supply of predetermined quantity of water for the generation of steam. The fifth object of the invention is to reduce the loss of moisture from the aqueous solution contained within the blood bag systems to prevent composition change of this solution during the autoclaving process of the blood bag system. The sixth object of the invention is to form a multi layer outer protective cover having a high permeability to moisture in relation to the permeability of the covers enclosing the filters and the permeability of the blood bag. The seventh object of the invention is to produce sufficient steam for the thorough sterilization of complicated devices as defined above by using a more permeable protective outer cover which shall assist and enhance the availability of steam in sufficient quantity during the process of autoclaving due to its nature of high permeability. Brief Description of Invention: When the blood bag system becomes more complex as in the case of double, triple, quadruple blood bags or blood bags, which incorporate a filter or other, closed devices, guaranteeing the sterility of such devices becomes more complex. A difficult case in point is blood bag systems incorporating filters or such complex devices, which have an outer protective cover. In such cases, sterilization by steam should ensure that steam from the autoclave should enter the outer protective plastic cover in sufficient quantity, then penetrate the outer protective plastic cover of the filter or other devices to build up sufficient steam within such devices and penetrate the inner most recesses of such devices to destroy any micro organisms present. To enable the easy entry of sufficient steam and without the use of made available water in the annular space, the protective outer cover shall be made to have a suitable higher permeability than the permeability of the blood bag and filter covers so as to allow sufficient steam for the purposes of sterilization of the said filters. A filter usually is built up of a number of folds of filter material of pre-determined porosity having large surface area to present the minimum possible pressure drop across the system. The sterilization parameters have to be so adjusted to ensure that steam enters the devices such as filters in quantities sufficient to reach even the most difficult to access spots within. Description of the drawings: The invention is now descried with reference to figures 1 to 4. Fig- 1. Illustrates quadruple bag with filter and other accessories sealed within a first outer protecfive cover (1) and packaged within a multilayered outer cover, which is impermeable to moisture. The figure shows the entire blood bag system as packaged. Fig-2. Illustrates a quadruple blood bag system as available incorporating leur adopter (5) diversion bag (6), needle injury protector (7), outer port (8), break off valve and sleeve (9) label (10), holder with lid (11) L A sleeve (12), tube (13), Y-connector (14), hard tube (15), tube (16), robert clamp (17), tube (18), needle holder assembly (19), SAGM fill tube (20), T R sleeve (22), and leukocyte filter (CRC filter) (21). Fig-3. Illustrates a quadruple blood bag system as available incorporating leur adopter (5) diversion bag (6), needle injury protector (7), outer port (8), break off valve and sleeve (9) label (10), holder with lid (11) L A sleeve (12), tube (13), Y-connector (14), hard tube (15), tube (16), robert clamp (17), tube (18), needle holder assembly (19), SAGM fill tube (20), T R sleeve (22), and buffy bag (23). Fig-4. Illustrates a quadruple blood bag system as available incorporating leur adopter (5) diversion bag (6), needle injury protector (7), outer port (8), break off valve and sleeve (9) label (10), holder with lid (11) L A sleeve (12), tube (13), Y-connector (14), hard tube (15), tube (16), robert clamp (17), tube 18, needle holder assembly (19), SAGM fill tube (20), T R sleeve (22), and leukocyte filter (save platelet filter) (25). The water in predetermined quantity is introduced in the annular space between the protective plastic container and the outer cover. Description of the Invention: The complex Blood Bag systems envisaged in this invention includes multiple bag with safety features and leukocyte filters. Further the process consist of a) The blood bag system - Double, Triple, Quadruple or higher configurations. and/or b) The filter or other devices incorporated with the above described blood bag system having their own cover, which is permeable. c) The blood bag system filters and other devices all sealed within a protective outer cover, which is also permeable. Our studies have shown that at least 0.15 to 0.30 gm of steam should get inside the filter system to ensure its sterility. This means that the hold time in a sterilizer should be longer than for the normal blood bag systems. Typical hold times as determined by us are at least 35 minutes at 117-118*'C or 50 minutes at 114-115°C. The sterilization condifions described above are applicable only if filters are made of a material such as PVC, polyolefin's or polycarbonate, which have high permeability to water/steam. As per the invention, we have found a method for sterilizing a complex blood bag system having atleast one permeable blood bag containing an aqueous solution within the bag, and including filters covered with corresponding permeable sealed covers, which sterilized blood bag system shall be free from moisture on its outer surface, the method comprising the five steps, the first step involves an outer protecfive cover with higher permeability enclosing the complex blood bag system including the filters within and thereby forming an annular space therein between the blood bag system and the outer cover, then introducing predetermined quantity of water if so desired in the annular space for generating steam, and sealing the said outer protective cover to form a sealed assembly. Autoclaving the sealed assembly wherein the steam formed from the water in the annular space enters into the recesses of filters. Then, drying process involving heat treating the assembly for removing the excess moisture collected in the annular space during autoclaving, through the highly permeable outer cover. An alternative method of sterilizing the complex blood bag system is also envisaged wherein there is no introducfion of predetermined quanfity of water in the hollow annular space for generating addidonal steam but instead , the protective outer cover itself is so pemieable to allow sufficient and desired steam to the area of sterilization in the filters. In this alternative method, there is no dependence on the water made available in the annular space as in the first method. This alternative is solely dependent on the material used as protective outer cover and its permeability. The protective plastic outer cover should have a water vapour permeability of at least 4-g/square meter/24 hrs. at 30C The protective outer cover should have sufficient strength to hold the complex bag system and attachments without getting damaged or developing scratches, tears or pinholes. The outer surface of the protective outer cover should be fairly tough and resist abrasion. Polyamide and Polyester sheets have good scratch and abrasion resistance. These materials however have poor scalability characteristics. Hence such materials will have to be used in multi layer systems where the polyester or polyamide fonns the outer protective layer, which is co-extruded with or bonded to easily sealable, films made of polyethylene or polypropylenes which may also be multi-layered as for example co extruded cast propylene. The permeability of the outer protective cover is so selected to be higher than the permeability of the said corresponding filter covers and the permeability of the blood bags. The said protective filter cover of said filters shall have a water vapour permeability of atleast 8g/square meter/ 24hrs at 30° C at atmospheric pressure. The best materials for the outer protective cover according to our studies in multi-layered films such as at least 12 microns thick polyester or polyamide bonded to or co-extruded with one or more layers of propylene or high-density polyethylene or combinations thereof Various other possibilifies exist as for example use of pouches in which one side is made up of co-extruded polyamide - poly ethylene / polypropylene and the other side is made of polyester / polyethylene / polypropylene co-extruded / bonded films. The outer protective layer shall be preferably multilayered. There shall be two layers. The outer layer exposed to the atmosphere and the inner layer towards the blood bag. The inner layer is generally further multilayered to enhance the permeability. The outer layer is tougher and anti-abrasive. The permeabilities of the inner layer and the outer layer are different from one another. The permeability of inner layer and outer layer are determined in accordance with the desired permeability of the protective outer cover. The tensile strength of the inner layer and the outer layer are different from one another. The thickness of the inner layer and the outer layer may also be different from one another. The inner layer and the outer layer together compositely form the outer protective layer possessing the determined permeability. As described above, the said outer protective cover shall comprise of atleast two layers, an inner layer and an outer layer, the inner layer and the outer layer comprising of, said outer layer with tensile strength of not less than 1,700 kg/cm^ and water vapour permeability not less than 30 gm/m^ in 24 hours at 25°C at atmospheric pressure, and said inner layer comprises of atleast two layers of sheets co-extruded or bonded together, with tensile strength of not less than 250 kg./cm2 and water vapour permeability not less than 6 gm/m in 24 hours at 25°C at atmospheric pressure. Our studies have also shown that when sterilizing complex blood bag systems by autoclaving, instead of waiting for 0.15 - 0.30 gm water to enter the filter or other devices, we could hasten the process by placing a quantity of water for injection in the outer protective plastic cover before the autoclaving operation. During autoclaving, this water is converted to steam and gains entry into the filter or other devices. This procedure provides two distinct advantages. Firstly the duration of the hold time in the autoclave could be reduced. Secondly, the loss of moisture from the aqueous solutions held within the blood bag systems is reduced thereby preventing undesirable changes in the composition of the solutions. The presence of made available water definitely assist to ensure that this readily available water is converted to steam and gains early entry into the filter area and other devices during autoclaving. Further, the sufficient steam may be made available alternatively instead of introducing water and using this introduced water for generating steam in the annular space by designing and configuring the outer protective cover with a permeability which is very high, thereby allowing higher entry level of steam to the area of sterilization. Further due to the presence of this made available water in the novel process of sterilization of complex blood bag systems, leads to formation of sufficient amount of moisture in the annular space between the blood bag system and the protective outer cover, thereby reducing the loss of moisture from the aqueous solution contained within the blood bag. This retards the composition changes of the aqueous solution during the autoclaving. As has been indicated earlier there is some accumulation of water in the annular space between the blood bag system and the outer protective cover, the actual quantity being decided by the water vapour permeability of the blood bag and its outer protective cover. The removal of this condensed water in the subject of the two Indian Patents mentioned earlier. These processes involve the subjecting of blood bags in their outer covers to heat treatment at temperatures in the range of 40-70oC with air circulation for periods up to 24 hours. Further this accumulated moisture formed in the annular space after autoclaving is made to rapidly escape out during the drying process which may be by applying heat treatment for drying the blood bag system and the escape of this moisture is hastened by using an outer protective cover having a higher permeability. This further prevents the loss of moisture from the aqueous solution contained within the blood bag thereby retarding the composition changes of the aqueous solution during the drying process. As explained above, the filters and devices described above will have their own covers which are permeable in nature. The filters are also permeable. However, the outer protective cover enclosing all the above will have permeability much higher than the permeability of the covers enclosing the filters and devices individually. The blood bag itself are made of permeable material. The rate of moisture escape could be hastened if the outer protective plastic cover has higher permeability to water. We found that using the preferred packaging covers discussed earlier it is possible to reduce the time required for moisture removal to around five hours. As described above it is attempted to sterilize complex blood bag systems, including complex filters by generating and using sufficient quantity of steam within very nominal duration but without disturbing the composition of aqueous solution contained within the blood bags, by introducing intentionally predetermined quantity of water during the step of autoclaving process and then removing the formed excess moisture during the steps of the drying process, thereby resulfing in a completely and efficiently sterilized complex blood bag system, which is almost totally free from moisture on its outer side. The visible accumulated water in the annular space after the process of autoclaving is undesired even though it is considered inert and harmless. Further presence of unnecessary and unrequired quantity of water will not be appreciated by the end user. This left over water in the annular space being visible to the user is not desired. Further the presence of water even in a sealed area may cause some contamination problems, which too needs to be eliminated. So though as much as it was found necessary to introduce consciously readily available water for sterilizing a complex blood bag system to generate sufficient steam quickly, it was equally important that this desired water during autoclaving was to be removed thereafter immediately after autoclaving. So it has to be attempted to use a highly permeable outer cover, which will assist during the process of heat treatment in high rate of moisture escape away from the annular space. The presence of introduced water generates the necessary steam during autoclaving proportionate to the quantity of water so introduced, complexity of the blood bag system used and the temperature developed during autoclaving. This means that the quantity of water can be predetermined based on these factors for the purpose of calculation. The invention has achieved a means and an improved method to sterilize a complex blood bag system containing aqueous solution within and including permeable filters enclosed in corresponding permeable covers, the said blood bag system enclosed further within an outer cover having higher permeability, to form an annular space having a desired quantity of water introduced during the process of autoclaving. The invention has definitive inventive steps in atleast two manner. The first being the step of introducing water in the annular space for the purpose of generating sufficient quantity of steam within a desired duration to enable thorough sterilization of complex components like filters but without prolonging unnecessarily autoclaving duration. Further the second inventive step includes the elimination of the introduced water during autoclaving, the elimination being efficiently conducted during the heat treatment following the autoclaving. This inventive step is achieved by using a multi layer highly permeable material for preparing the protective outer cover, resulting in a moisture fi'ee outer surface of the sterilized dried assembly but which has not disturbed the composition of the aqueous solution. The invented process consists in the packaging and sealing of complex blood bag systems, which include a filter or other devices in their own cover within a permeable transparent outer protective cover made of films such as polyester or polyamide co extruded or bonded to easily sealable films made of polyolefins such as polyethylene or polypropylene or combinations thereof and subjecting the system to sterilization by autoclaving with or without the introduction of specified quantities of water for injection in the space between the blood bag system and into outer protective cover. WE CLAIM- 1. A method for sterilizing a complex blood bag system having atleast one blood bag containing an aqueous solution within the bag, and including filters covered with corresponding permeable sealed filter covers, which sterilized blood bag system shall be free from moisture on its outer surface, the method comprising the steps of:- a. a multilayered outer protective cover having permeability of atleast 4 g/m /24 hours at 30oC at atmospheric pressure enclosing the complex blood bag system including the filters within and thereby forming an annular space thereinbetween the blood bag system and the outer cover. b. sealing the said outer protective cover to form a sealed assembly. c. autoclaving the sealed assembly wherein the steam from beyond the sealed assembly, penetrating through the outer protective cover into the recesses of filters, and d. heat treating the assembly for drying and removing the excess moisture collected in the annular space during autoclaving, through the highly permeable outer cover. 2. A method as claimed in Claim 1, wherein the step of autoclaving may further include a prior step of introducing pre-determined quantity of water in the annular space for generating steam. 3. A method as claimed in claim 1, wherein the permeability of the outer protective cover is higher than the permeability of the said corresponding filter covers and the permeability of the blood bags. 4. A method as claimed in claim 1, wherein the said outer protective cover shall comprise of atleast two layers, an inner layer and an outer layer, the inner layer and the outer layer comprising of: a. the said outer layer with tensile strength of not less than 1,700 kg./cm and water vapour permeability not less than 30 gm/m in 24 hours at 25°C at atmospheric pressure, and b. the said inner layer further comprising of atleast two layers of sheets co-extruded or bonded together, with tensile strength of not less than 250 kg./cm2 and water vapour permeability not less than 6 gm/m in 24 hours at 25°C at atmospheric pressure. 5. A method as claimed in claim 1, wherein the said protective filter cover of said filters shall have a water vapour permeability of atleast 8g/square meter/ 24hrs at 30° C at atmospheric pressure. 6. A method as claimed in claim 1, wherein the step of autoclaving is performed such that atleast 0.15 to 0.30 gms of steam reaches the filter recesses. 7. A method as claimed in claim 1, wherein the step of heat treating is performed such that the time required for moisture removal is not more than 5 hours.

Documents:

0679-che-2003 claims-duplicate.pdf

0679-che-2003 description (complete)-duplicate.pdf

0679-che-2003 drawings-duplicate.pdf

679-che-2003-claims.pdf

679-che-2003-correspondnece-others.pdf

679-che-2003-correspondnece-po.pdf

679-che-2003-description(complete).pdf

679-che-2003-description(provisional).pdf

679-che-2003-drawings.pdf

679-che-2003-form 1.pdf

679-che-2003-form 3.pdf

679-che-2003-form 4.pdf

679-che-2003-form 5.pdf