Method for sterilising ports for a medical container

Abstract

The invention relates to a method for sterilising ports for a medical container in an autoclave. The ports comprise a housing having a cavity. In a holding phase, the ports are sterilised in the autoclave using steam at overpressure. Before the holding phase, the autoclave is evacuated to at least 300 mbar in an evacuation phase. Before the evacuation phase, steam is introduced into the autoclave in a steam surge phase, with the result that pressure and temperature are increased. By means of the method according to the invention, the process time can be reduced and at the same time and with the same sterilisation result, the packing density of the ports can be increased.

Description

[0001] Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0002] Method for sterilizing connections for a medical container

[0003] Description

[0004] Field of invention

[0005] The invention relates to a method for sterilizing connectors or connector systems and adapters for a medical container. The invention further relates to a steam-permeable bag comprising medical connectors and a medical container produced using the method according to the invention.

[0006] Background of the invention

[0007] The sterilization of medical products is subject to stringent requirements. A SAL value of 10 is typical. -6This parameter, which serves as a product-determining process parameter, ensures that one in a million products is not sterile. However, this is more of a theoretical value, so in the manufacture of medical devices, it is generally assumed that all products are sterile. Validation is achieved, for example, using the overkill method, which involves sterilization to reduce the number of microorganisms by 12 orders of magnitude.

[0008] Thermal sterilization is particularly suitable for sterilizing medical products. Dry thermal sterilization is generally not possible for heat-sensitive products, especially plastics, as these products cannot be exposed to the required temperatures. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0009] For medical devices, especially plastic packaging and packaging filled with medical fluids, steam sterilization is therefore common. The products are placed in an autoclave into which saturated steam can be introduced. The process parameters of pressure and temperature are controllable. Increasing the pressure raises the boiling point of water. A saturated steam environment is significantly more effective against germs at the same temperature than dry heat.

[0010] In an autoclave, sterilization is carried out by evacuation and subsequent introduction of saturated steam.

[0011] The pressure can be temporarily reduced during the increase and then increased again (fractionated forevacuum).

[0012] A process in which the autoclave is first evacuated, then saturated steam is introduced and the pressure is increased, is known from German patent application DE 30 03 305 A1. The actual sterilization takes place during a holding phase at approximately constant pressure and temperature for a period sufficient to sterilize the product in question. Such sterilization is energy- and time-intensive, but yields good results.

[0013] Medical containers, such as bags that are filled or already filled with a medical fluid, often include ports for introducing and / or draining the medium, particularly medical fluids. Specifically, medical containers are available with an injection port and a drainage port. Each port includes a sealing element that can be pierced with a spike or needle to introduce or drain the medium (Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO) and which reseals itself automatically after the spike or needle is removed.

[0014] To ensure sterility at the insertion site, the sealing element can be closed with a tamper-evident cap, particularly a snap-off cap. This results in a cavity or dead volume between the sealing element and the cap. The connection, especially the upper part of a connector, therefore contains a cavity. When sterilizing a bag already filled with medical fluid, the autoclave cannot be evacuated, as this would cause the gas volume within the bag to expand to such an extent that the bag would be damaged or destroyed. Components of the medical fluid could also evaporate into the gas phase. Therefore, during bag sterilization, it is not possible to replace the air volume present in the cavity of a connector with a fractionated pre-vacuum atmosphere of water vapor.A cavity that is not in fluid contact with the medical fluid is therefore not steam sterilized during the sterilization of the medical bag.

[0015] For such connections, pre-sterilization may therefore be necessary, in which, as described above, the autoclave is first evacuated. During this process, the air volume present in the cavity or dead space, particularly between the seal and the housing, and especially between the upper part of a connector and the sealing element, escapes and can be replaced by a steam atmosphere upon subsequent introduction of steam and pressure increase.

[0016] To achieve a sufficient steam concentration in the dead volume, a low pressure, especially below 100 mbar absolute pressure, is required during evacuation. This is correspondingly time-consuming, as the evacuation time with Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0017] The pressure required increases disproportionately as it approaches zero absolute pressure. The fractionation phases that are then often necessary further increase the energy and time requirements.

[0018] Object of the invention

[0019] In contrast, the invention is based on the objective of reducing the energy (steam, electricity, air, etc.) and / or time expenditure during sterilization, in particular during the pre-sterilization of connections for a medical container with a cavity, and / or increasing the capacity of the autoclave.

[0020] Summary of the invention

[0021] The object of the invention is already solved by a method for sterilizing connections according to claim 1.

[0022] Preferred embodiments and further developments of the invention can be found in the subject matter of the dependent claims, the description and the drawings.

[0023] The invention relates to a method for sterilizing connections or connection systems for a medical container or containers in an autoclave, wherein the connections, connection systems, or adapters comprise a housing with a cavity, wherein the connections are sterilized in the autoclave with steam during a holding phase under overpressure, and wherein, prior to the holding phase, the autoclave is evacuated to at least 300 mbar in an evacuation phase, and wherein, prior to the evacuation phase, steam is introduced into the autoclave in a steam pulse phase, thus increasing the pressure and temperature. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0024] The method is particularly useful for the pre-sterilization of connections or connection parts for a medical container, since these cannot be sterilized solely by sterilizing the medical container itself due to their internal cavity. For the purposes of the invention, a connection is understood to be any connection component with a cavity.

[0025] The connectors are specifically designed as the top section for the ports of a medical container. The ports are used for dispensing and / or adding liquid. The sealing element is already inserted into the top section during sterilization, creating a cavity between the sealing element and the top section.

[0026] A port can, in particular, comprise a lower part made of plastic and an upper part made of plastic, wherein a sealing element is inserted between the lower part and the upper part. Preferably, the upper part with the sealing element is sterilized by the method according to the invention, in particular before the upper part is connected to the lower part and the container filled with a medical fluid is sterilized in an autoclave. Thus, disinfection of the port surface is not necessary during initial use.

[0027] In particular, after sterilizing the upper part with the sealing element, the upper part is connected to the lower part, which in turn is already connected to the medical container. The sealing element is specifically fixed between the lower part and the upper part by a form-fit connection. In a further embodiment of the invention, the sealing element is form-fitted into the upper part.

[0028] The sealing element can be designed, in particular, to be pierced with a spike or needle (Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO). After the spike or needle is withdrawn, the sealing element preferably closes itself. Sealing elements, especially for use with a spike, can include a slot that closes after the spike is withdrawn.

[0029] The connectors, which are designed specifically as the upper part of a port, may include a snap-off cap, particularly if they are configured as injection and / or withdrawal ports. After the snap-off cap is removed, the sealing element is exposed for inserting the spike or needle. This ensures sterility during use until the snap-off cap is removed.

[0030] Furthermore, there are also connections designed as blind ports. Such a connection is used to fill the medical container during the manufacturing process. In the case of a blind port, the top part can be designed as a closed cap without a snap-off cap.

[0031] In particular, a cavity may exist between the sealing element located between the upper and lower parts and the upper part itself, forming a dead volume. Such a cavity can only be sterilized during steam sterilization by fractionation, i.e., cyclical evacuation followed by the introduction of steam. Reducing the pressure in the autoclave at least once below atmospheric pressure ensures that a sufficient amount of steam is present in the cavity or dead volume. The steam then flows past the sealing element. This is possible because the upper part for the port is preferably not yet connected to the lower part, and therefore the sealing element is not yet compressed between the upper and lower parts. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0032] Furthermore, there are connectors designed as adapters, particularly for preparing, dissolving, and / or diluting medications, for use with a vial. These include a spike or needle and a valve. The vial is connected to the spike or needle to provide a fluid connection. By opening the valve, the contents of the vial can be diluted, dissolved, and prepared, and the liquid can be transferred from the vial into the medical container, particularly a bag.

[0033] The spike or needle is covered by a protective cap. This cap, which is typically designed as a snap-off cap, creates a cavity. The channel of the spike or needle is also part of this cavity. With such adapters for a vial, the snap-off cap is usually not tightly sealed to the rest of the housing. The snap-off cap may be connected to the housing via ribs, allowing steam to flow between these ribs into the snap-off cap during sterilization, and thus into the cavity beneath the cap, as well as into the spike or needle.

[0034] During the evacuation phase, the autoclave is evacuated to 300 mbar or less. Unless otherwise specified, pressure readings always refer to absolute pressure.

[0035] During the evacuation phase, the air present in the autoclave is removed and then replaced by a steam atmosphere created by introducing saturated water vapor. Achieving an absolute pressure of zero in an autoclave is technically impossible, and approaching zero pressure requires a disproportionately longer pumping time. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0036] The evacuation phase is followed by a holding phase, whereby at least one fractionation phase may be present between the evacuation and holding phases.

[0037] According to the invention, steam is introduced into the autoclave in a steam pulse phase prior to the evacuation phase, thus increasing the pressure and temperature.

[0038] In particular, the sterilization process begins with the steam injection phase. The process does not start with an evacuation of the autoclave, but rather, before the evacuation phase, pressure and temperature are first increased by introducing steam.

[0039] It has been found that this can significantly reduce the overall sterilization time.

[0040] The inventors explain that this effect is due, among other things, to the displacement of air from the dead space and the autoclave chamber, as well as preheating of the chamber and / or the connections. The initially introduced steam displaces the trapped air, and the dead space is already filled with steam. The connections are warmer during the subsequent evacuation phase, allowing for improved steam flow into the cavity after evacuation.

[0041] The initial steam pulse phase can also be understood as a pre-fractionation phase within the meaning of the invention.

[0042] In one embodiment of the invention, the autoclave is evacuated to 100 to 300 mbar, preferably to 100 to 150 mbar, and particularly preferably to 120 to 140 mbar, during the evacuation phase. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0043] In particular, during the evacuation phase, the pressure at the end of the evacuation phase can reach 120 mbar or higher. This allows the evacuation phase to be shortened compared to evacuating to 50 mbar or less.

[0044] During the steam pulse phase, the pressure in the autoclave is preferably increased to 1200 to 1800 mbar, particularly preferably to 1400 to 1600 mbar.

[0045] The maximum temperature reached during the steam pulse phase is preferably 80 to 120°C, particularly preferably 90 to 110°C.

[0046] The steam pulse phase is preferably carried out over a period of 20 s to 5 min, particularly preferably from 40 to 80 s.

[0047] This period is the period from the start of the introduction of the steam until the start of the evacuation phase, which preferably follows directly after the steam surge phase.

[0048] It has been shown that even a relatively short steam pulse phase leads to the advantages according to the invention.

[0049] Preferably, at least one fractionation phase, i.e., evacuation and subsequent introduction of steam, is carried out between the evacuation phase and the holding phase.

[0050] After the evacuation, there is a further steam pulse phase as well as another evacuation phase, which serves for fractionation.

[0051] Preferably, the pressure is reduced from over 1500 mbar to below 1000 mbar during the fractionation phase. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0052] The fractionation phase therefore starts at a pressure above 1500 mbar and ends at a pressure below 1000 mbar. Since only a single fractionation phase is carried out, the pressure is then increased until the pressure and temperature required for the holding phase are reached.

[0053] However, the minimum pressure in the fractionation phase is higher than the minimum pressure in the evacuation phase.

[0054] In particular, the pressure at the end of the fractionation phase is above 500 mbar, preferably above 700 mbar.

[0055] The holding phase is preferably the longest phase during the sterilization process. Preferably, pressure and temperature are kept essentially constant during the holding phase.

[0056] The temperature during the holding phase is particularly between 110 and 135°C, preferably between 120 and 125°C.

[0057] Preferably, the pressure is maintained between 1750 and 2500 mbar, particularly preferably between 2000 and 2400 mbar, during the holding phase.

[0058] The holding phase is preferably followed by a drying phase. During this phase, the autoclave is evacuated, in particular to below 300 mbar, preferably to below 100 mbar, and in particular to a pressure of above 50 mbar down to below 100 mbar.

[0059] During the drying phase, the steam atmosphere is removed from the autoclave, allowing the connections to dry.

[0060] When the autoclave is vented, the amount of water vapor present in the cavity is so low that the water content is far from the saturation point. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0061] The drying phase is preferably carried out over a period of less than or equal to 20 minutes, in particular from 5 to 20 minutes.

[0062] According to one embodiment of the invention, the entire sterilization process, beginning with the introduction of the steam pulse phase and continuing until the autoclave is vented, is carried out over a period of less than or equal to 100 min, in particular from 60 to 100 min, preferably from 85 to 95 min.

[0063] According to one embodiment of the invention, the holding phase is carried out over a period of 30 to 90 minutes, preferably 40 to 50 minutes.

[0064] In one embodiment of the invention, the connections are sterilized in a steam-permeable bag.

[0065] In particular, it is planned that vapor-permeable bags, for example made of a polyethylene fleece, will be provided, which will be filled with a variety of connections.

[0066] To carry out the process according to the invention, the autoclave is loaded with the steam-permeable bags.

[0067] After the autoclave has been ventilated, the vapor-permeable bags are removed. The connectors can be removed for further processing.

[0068] If further processing takes place at a different location, the vapor-permeable bags can also be packaged in secondary packaging, in particular in film. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0069] According to one embodiment of the invention, the connections are connected to a medical container after sterilization.

[0070] In particular, the connectors designed as the upper part for a port are connected to the lower part, which in turn is connected to the medical container or is already connected.

[0071] The medical container is filled with a medical fluid. At least one of the container's connections can be used for filling.

[0072] The medical container can then be packaged, in particular in a secondary packaging, for example a tear-off bag, and sterilized, in particular in an autoclave.

[0073] The invention further relates to a vapor-permeable bag which includes a plurality of connections that have been sterilized using the method described above.

[0074] The invention further relates to a medical container manufactured using the method described above. In particular, the invention relates to a medical container comprising a connection manufactured, and in particular sterilized, using the method described above.

[0075] Brief description of the drawings

[0076] The subject matter of the invention will be described below with reference to the

[0077] Drawings Fig. 1 to Fig. 6 are explained in more detail. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0078] Fig. 1 is a flowchart of an embodiment of a method according to the invention.

[0079] Fig. 2 is a graph of the pressure and temperature profile during the execution of the process.

[0080] Figs. 3a to 3c are sectional views of connections for a medical container that can be sterilized using the method according to the invention.

[0081] Fig. 3d and Fig. 3e are longitudinal sections of an adapter for a vial, which can also be sterilized using the method according to the invention.

[0082] Fig. 4 is a schematic representation of a medical container.

[0083] Fig. 5 is a schematic representation of the connections arranged in a vapor-permeable bag.

[0084] Fig. 6 shows a schematic of an autoclave.

[0085] Detailed description of the drawings

[0086] Fig. 1 is a flowchart of an embodiment of a method according to the invention.

[0087] First, a large number of connectors are packaged in vapor-permeable bags. These bags can be made of a polyethylene nonwoven fabric and are sealed after the connectors are inserted.

[0088] The autoclave is then loaded with the bags. In particular, an autoclave with an insert (Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO) can be used, which forms several levels on which the vapor-permeable bags are placed.

[0089] After the autoclave is closed, it is not immediately evacuated, in contrast to the prior art described above, but the sterilization process starts with a steam pulse phase in which the pressure increases to 1200 to 1800 mbar and the temperature to 80 to 120°C.

[0090] After the steam surge phase, the evacuation phase takes place to a pressure of 100 to 150 mbar.

[0091] Then another steam pulse phase takes place, during which steam is introduced until the pressure reaches 1400 to 1800 mbar.

[0092] Before reaching the holding phase, fractionation is carried out, whereby the pressure is reduced to 800 to 1000 mbar and then a further steam pulse phase takes place until a pressure of 2000 to 2400 mbar and a temperature of 120 to 125°C is reached.

[0093] Then a holding phase follows, during which pressure and temperature remain essentially constant.

[0094] For drying, the autoclave is evacuated during a drying phase, achieving a pressure of less than 100 mbar.

[0095] The autoclave is then ventilated by introducing air through sterile filters.

[0096] The vapor-permeable bags can then be removed.

[0097] The connectors can then be further processed, in particular they can be designed as a top part for a Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0098] The port or adapter for a vial can be further processed into a medical container, in particular a foil bag.

[0099] Fig. 2 includes a curve of the pressure profile p and the temperature profile, where T2 is the temperature in the autoclave at the steam inlet and TI is the temperature in the autoclave chamber. Unless otherwise specified, the temperature values ​​referred to in the context of the invention are TI.

[0100] The horizontal axis shows the time in minutes, and the vertical axes show the pressure in mbar and the temperature in °C.

[0101] After the autoclave is closed, the process starts with a steam burst (up to position 1), during which the pressure increases from atmospheric pressure to 1400 to 1600 mbar. Simultaneously, the temperature rises to 90 to 110°C.

[0102] This steam burst phase is carried out over a fairly short period of 40 to 80 seconds.

[0103] The evacuation phase then follows (starting with position 1), which serves to replace the atmosphere in the autoclave and especially in the dead space of the connections with a saturated steam atmosphere.

[0104] During this phase, the pressure in the autoclave is reduced to 120 to 140 mbar until saturated steam is introduced back into the autoclave via another steam burst (starting with position 2).

[0105] The evacuation phase can last from 5 to 10 minutes. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0106] Upon reaching the desired minimum pressure (position 2) in the evacuation phase, a second steam surge phase follows, in which the pressure increases to 1600 to 1800 mbar. Simultaneously, the temperature rises to 90 to 110°C.

[0107] The fractionation process then takes place in a fractionation phase (Pos. 3 to 4), during which the pressure is reduced from 700 to 1000 mbar.

[0108] The temperature drops to between 85 and 105°C during this phase.

[0109] The process according to the embodiment shown here includes only a single fractionation phase.

[0110] Upon reaching the minimum pressure in the fractionation phase, another steam burst occurs (starting with position 4), which increases the pressure and temperature to approximately the values ​​or parameters required during the holding phase (positions 5 to 6).

[0111] The temperature during the holding phase is preferably 120 to 125°C (unless otherwise specified, the information refers to the temperature in the autoclave).

[0112] The apparent peak at the beginning of the holding phase is due to a lag or overshoot of the sensors.

[0113] A heating device in the autoclave keeps the temperature approximately constant during the holding phase, particularly at a value of 120 to 125°C.

[0114] In this embodiment, the holding phase is carried out over a period of 40 to 50 minutes. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0115] At the end of the holding phase, a drying phase (items 6 to 7) takes place by evacuating the autoclave to a pressure of less than 100 mbar. This evacuation removes the water vapor atmosphere from the autoclave. The water vapor also escapes from the cavities.

[0116] At the end of the process, the autoclave is vented and the connections can be removed.

[0117] Figures 3a to 3c are sectional views of exemplary ports that can be sterilized using the method according to the invention. In each case, the upper part of a port with an inserted sealing element is sterilized using the method according to the invention.

[0118] Fig. 3a shows a connection 1 designed as a withdrawal port. This comprises a housing formed from a lower part 10 and an upper part 20. The upper part 20 includes a groove which is already engaged on a collar 12 of the lower part 10. A sealing element 30, which can be pierced with a needle or a spike, is inserted between the upper part 20 and the lower part 10.

[0119] The sealing element 30 consists of an elastic material, in particular polyisoprene. In this embodiment, the sealing element 30 comprises a circumferential collar 31, which is positively engaged in a groove 22 of the upper part and in a groove 11 between the lower part 10 and the upper part 20.

[0120] In this embodiment, the upper part 20 is closed with a snap-off cap 21.

[0121] After breaking off the snap-off cap 21, the sealing element 30 is accessible for piercing with a spike or needle. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0122] Due to this design, the cavity A is located between the sealing element 30 and the upper part 20, which can only be sterilized by steam sterilization if a sufficient amount of water vapor penetrates into the cavity A after evacuation past the sealing element 30.

[0123] According to the invention, preferably only the upper part 20 with the inserted sealing element 30 is sterilized. Since the sealing element 30 is not yet pressed between the upper part 20 and the lower part 10 during sterilization or pre-sterilization, steam can easily flow into the cavity A. Pre-sterilization of the lower part 10 is not strictly necessary, as its channel-shaped cavity comes into contact with the medical fluid during the subsequent sterilization of the medical container, so that a steam atmosphere forms in this cavity during the sterilization of the filled container.

[0124] Fig. 3b shows an embodiment of a connection 1, which is designed as a blind port. The design essentially corresponds to Fig. 1a, with the upper part 20 being designed as a closure cap without a snap-off cap. Such a blind port serves to fill the medical container during its manufacture and is therefore not used by the user for introducing or draining liquid.

[0125] Fig. 3c shows another embodiment of a connection 1, which in this embodiment is designed as an injection port. In this embodiment, the predetermined breaking point of the snap-off cap 21 is approximately aligned with the sealing element 30. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0126] In this embodiment, the sealing element 30 is fully inserted into the upper part 20, with the lower part 10 engaging in the upper part 20 to enclose the sealing element 30. In this embodiment, the sealing element 30 is cup-shaped.

[0127] In this connection 1 as well, preferably only the upper part 20 with the inserted sealing element 30 is sterilized using the method according to the invention.

[0128] Fig. 3d is a longitudinal section of a connection 1 which is designed as an adapter for a viol.

[0129] The connector comprises a housing consisting of an upper part 20 and a lower part 10. The upper part 20 is designed as a vial receptacle and includes a spike 23 for establishing a fluid connection with the vial. The lower part 10 serves for connection to a medical container, in particular a bag, filled with a medical fluid.

[0130] Furthermore, the connection 1 includes a valve. In this embodiment, this is formed by arranging the spike 23 on a base 24 that is rotatable together with the violet.

[0131] Between the upper part 20 and the lower part 10 there is a sealing element 30 with a channel.

[0132] As shown in Fig. 3e, the sealing element 30 can be brought into intersection with a channel 25 through the base 24 by rotating the spike 23 with the base 24, thus providing a fluid connection. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0133] Such an adapter for a viol is described in detail in document EP 3 747 421 Al.

[0134] The spike 23 is covered by the snap-off cap 21, which serves as a contact guard or protection against injuries. The snap-off cap 21 forms the cavity A in which the spike 23 is located; the channel of the spike 23 is also part of this cavity A.

[0135] The snap-off cap 21 is not fluid-tightly connected to the housing or the upper part 20. This allows water vapor to flow into the cavity A.

[0136] The connection 1, designed as an adapter for a violet, is preferably sterilized including the lower part 10.

[0137] Fig. 4 shows a schematic representation of a container produced using the inventive method, which is designed as a foil bag 40.

[0138] The foil bag 40 is filled with a medical fluid and includes a withdrawal port 1a and an injection port 1b as connections.

[0139] The lower parts of ports a1a, b are welded into the weld seam of the foil bag 40. Similarly, the lower part of the adapter for a vial shown in Fig. 3d / 3e can also be welded into the foil bag 40 (not shown).

[0140] The foil bag 40 is sterilely packaged in a secondary packaging 41. The secondary packaging 41 can be designed, in particular, as a tear-open pouch. Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO

[0141] Fig. 5 is a schematic representation of a vapor-permeable bag 50. This bag is filled with a plurality of ports 1. In this embodiment, the ports 1 are designed as top parts 20 for a port with an inserted sealing element 30. Due to the vapor-permeable bag 50, the ports 1 can be easily inserted into the autoclave and removed again under sterile conditions.

[0142] In this embodiment, the vapor-permeable pouch 50 is packaged in a foil package as secondary packaging 51. If the medical containers are manufactured at a different location, the pre-sterilized connectors 1 can be shipped in a sterile state.

[0143] Fig. 6 schematically shows an autoclave 60 as it is used to carry out a process according to the invention.

[0144] The vapor-permeable bags 50, filled with connections 1, are placed in the autoclave 60 in several layers, one above the other. The layers can be designed as perforated shelves. This ensures that the flow of water vapor into the bags 50 is not obstructed from either the top or the bottom.

[0145] In particular, the bags 50 can be placed on a movable shelf into the autoclave 60. The autoclave 60 is then closed and the connections 1 are sterilized, starting with a steam pulse phase.

[0146] The inventive method allows, in contrast to a

[0147] Sterilization without an initial steam burst significantly reduces the process time, in particular by 15 to 21%. At the same time, with the same sterilization result, the packing density of the connections in the steam-permeable bags can be increased, in particular by 5 to 15%.

[0148] The method according to the invention thus leads to a significant increase in efficiency. The increased number of cycles per day results in cost savings while simultaneously reducing energy consumption. Furthermore, packaging material in the form of vapor-permeable bags can be saved.

[0149] Reference symbol list

[0150] A cavity

[0151] I connection la extraction port

[0152] 1b Injection port

[0153] 10 Lower part

[0154] II Nut

[0155] 12 collars

[0156] 20 tops

[0157] 21 Snap-off cap

[0158] 22 Nut

[0159] 23 Spike

[0160] 24 sockets

[0161] 25 Channel

[0162] 30 sealing element

[0163] 31 collars

[0164] 40 foil bags

[0165] 41 Secondary packaging

[0166] 50 vapor-permeable bags

[0167] 51 film packaging / secondary packaging

[0168] 60 Autoclaves

Claims

Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO Claims:

1. Method for sterilizing connections (1) for a medical container (49) in an autoclave (60), wherein the connections comprise a housing with a cavity (A), wherein the connections (1) are sterilized in the autoclave (60) in a holding phase under overpressure with steam, and wherein, prior to the holding phase, the autoclave (60) is evacuated to at least 300 mbar in an evacuation phase, characterized in that, prior to the evacuation phase, steam is introduced into the autoclave (60) in a steam pulse phase, so that pressure and temperature are increased.

2. Method according to the preceding claim, characterized in that the method starts with the steam pulse phase.

3. Method according to one of the preceding claims, characterized in that the cavity (A) is located between a housing part and a sealing element (30), and / or in a fluid channel which preferably does not have direct contact with the contents of the container during sterilization of the already filled medical container.

4. Method according to one of the preceding claims, characterized in that the autoclave (60) is evacuated to 100 to 300 mbar, preferably to 100 to 150 mbar, particularly preferably to 120 to 140 mbar, during the evacuation phase.

5. Method according to one of the preceding claims, characterized in that the pressure in the steam shock phase is increased to 23 Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO 1200 to 1800 mbar, preferably to 1400 to 1600 mbar, and / or that the temperature in the The steam pulse phase is increased to 80 to 120 °C, preferably to 90 to 110 °C, and / or the steam pulse phase is carried out over a period of 20 s to 5 min, preferably from 40 s to 80 s.

6. Method according to one of the preceding claims, characterized in that between the steam pulse phase and the reaching of the holding phase in a fractionation phase, pressure and temperature are first increased again by a further steam pulse phase and pressure and temperature are reduced again by a further evacuation phase, preferably in a single fractionation phase, wherein in particular the pressure in the fractionation phase is reduced from over 1500 mbar to under 1000 mbar.

7. Method according to one of the preceding claims, characterized in that during the holding phase the temperature is maintained between 110 and 135 °C, preferably between 120 and 125 °C, and / or that during the holding phase the pressure is maintained between 1750 and 2500 mbar, preferably 2000 and 2400 mbar, and / or that the holding phase is carried out for a period of 30 to 90 min, preferably 40 to 50 min.

8. Method according to one of the preceding claims, characterized in that after the holding phase the autoclave (60) is evacuated in a drying phase to dry the connections (1), in particular to below 300 mbar, preferably to below 100 mbar.

9. Method according to one of the preceding claims, characterized in that the drying phase is carried out over a Fresenius Kabi Deutschland GmbH FK24055-05-PAT-WO The procedure is carried out over a period of 20 minutes, particularly from 5 to 20 minutes.

10. A method according to one of the preceding claims, characterized in that the entire method is carried out over a period of time from 100 min, in particular from 60 to 100 min, preferably from 85 to 95 min.

11. Method according to one of the preceding claims, characterized in that the connections (1) are sterilized in a steam-permeable bag (50).

12. Method according to one of the preceding claims, characterized in that the connections (1) are sterilized, which are designed as the upper part (20) of a port with an inserted sealing element (30) or as an adapter for a vial.

13. Method according to one of the preceding claims, characterized in that the connections (1) are connected to a medical container (40) after sterilization, wherein the medical container (40) is filled with a medical liquid, which is then packaged and, preferably terminally, sterilized, in particular in a secondary packaging (41).

14. Vapor-permeable bag (50) comprising a plurality of connections (1) sterilized according to one of the preceding claims .

15. Medical container (40) , manufactured by a method according to claim 13.

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