FILTER ELEMENT WITH IMPROVED TESTABILITY AFTER DRY STEAMING

Description

[0001] The present invention relates to a fusion-bonded filter element, for example in the form of a filter candle, with improved testability after dry vapor deposition or alternatively after sterilization by irradiation, a process for producing the filter element according to the invention, and the use of the filter element for filtering solutions.

[0002] Filter elements, e.g., for use in pharmaceutical production, are typically membranes encased in plastic housings or plastic inserts through which the liquid media to be filtered flows (see, for example, EP 0 096 306 A2). A typical design is flat plastic holders, to which flat polymer membranes are permanently bonded by "thermal joining," i.e., by melting the polymer materials and joining the melt zones. However, the achievable membrane area for this design is small and generally only suitable for laboratory or smaller process scales.

[0003] For use in large-scale processes, other designs have become established in the form of pleated, i.e. folded, membranes which are joined together at both ends of the membrane sheet to form a cylindrical ring. This cylindrical ring of the pleated membrane is open at both end faces. On the one hand, the two ends of the membrane sheet must be joined together, and the two resulting end faces of the pleated membrane sheet must be sealed or connected to a housing. Generally, this is done by directly converting the membranes and / or the housing materials into a polymer melt by heating them in the desired joining area on one or both sides. This polymer melt is at least viscous, which means that both sides of the joint to be joined can be joined using pressure. After the polymer melt has cooled, a stable bond is formed (see, for example, US 3,457,339).

[0004] In special cases, it is not possible to convert both sides of a joint to the melt state. This can particularly apply to membranes if their structure and shape are changed in the melt state to such an extent that a desired function is no longer achieved after the joining process. In these cases, the housing component can be converted into polymer melt on one side in the joining area. In this case, the cold membrane is introduced into the hot polymer melt of the housing component during joining. Such a joint is also sufficiently stable if the joint is designed correctly and a sufficient amount of polymer melt is generated on the housing component.

[0005] Regardless of their design, membranes that are joined to the filter element via a fusion joining process experience thermal stress in the area of ​​the fusion joint. This thermal stress depends on design factors, but in particular on the melting point of the plastic with which the membrane is to be joined. It has been shown that per se Hydrophilic or hydrophilized membranes can be damaged by this thermal stress during joining, resulting in a change in the membrane properties, which may impair wettability in the area of ​​the joint and thus impair the testability of the filter elements. This is particularly the case if the filter element is exposed to further thermal stress, such as through vapor deposition or, even more pronounced, through dry vapor deposition.

[0006] Filter elements within the meaning of this invention are designed to achieve substance separation based on size exclusion. This includes the removal of yeast cells or bacteria (sterile filtration), viruses (virus removal), protein aggregates, or other particulate contaminants. Filter elements achieve this by using membranes through which the solution is passed due to a pressure gradient.

[0007] In these processes, filter elements are typically tested for integrity before and / or after filtration. An integrity test uses a suitable measuring method to determine whether the required pore size of the membrane is not exceeded and whether there are any mechanical defects in the membrane, its seal with the filter housing, or the gas-tight filter housing. Passing the integrity test indicates the functionality of the filter element. The common methods for integrity testing are the bubble point test and / or the gas diffusion test for water-wetted filter elements (DIN 58356-2:08 / 2000, DIN 58355-2). For a positive test result, it must be ensured that the membrane is wetted with water across its entire surface and thickness. Unwetted areas of the membrane lead to convective air currents, which result in a reduced bubble point or increased gas diffusion.As a result, an integrity test is not passed in this case, although the filter element, if it had been fully or sufficiently wetted, would have passed the integrity test and would have shown the expected substance separation, provided that the membrane and its integration into the filter element are otherwise free of defects, i.e. does not have any pores / defects that do not meet the desired substance separation through size exclusion.

[0008] A further requirement for filter elements used for the above-mentioned processes is their ability to be sterilized using steam. For this purpose, the filter elements are usually steamed for a period of 15 to 90 minutes, i.e. steam is passed through at temperatures of up to 140°C, or autoclaved, i.e. the filter element is exposed to steam at temperatures of up to 140°C in a separate step before use to ensure complete sterilization of the unit. This steaming of the filter elements places a high thermal stress on the filter elements. The higher the selected steam temperature, the greater the stress the filter element is exposed to during this step. At the same time, the higher the steaming temperature, the more effectively the filter element is sterilized.Users of these filter elements therefore have an interest in steaming the filter elements at the highest possible steam temperature to achieve the most comprehensive sterilization in the shortest possible time. For example, in Wallhäusser, KH, "Praxis der Sterilisation, Desinfektion, Konservierung, Keimidentifizierung, Betriebshygiene" (Practical Practice of Sterilization, Disinfection, Preservation, Germ Identification, Industrial Hygiene), Georg Thieme Verlag, Stuttgart 1984, representative steaming and autoclaving at 134°C to 140°C for 30 minutes are described.

[0009] A further requirement is that this steaming of the filter elements for sterilization can be carried out without prior wetting / rinsing of the filter elements, i.e., the filter elements can be "dry steamed" and then, after minimal rinsing, an integrity test can be performed. The option of dry steaming eliminates the need for a prior rinsing step for the filter elements. Since the time and material required for the rinsing step can be saved, it is advantageous to provide filter elements that can be dry steamed.

[0010] If sterilization by steaming is preceded by a rinsing step, this entire process is also referred to as "wet steaming." Membranes contained in the filter elements are wetted with water. It has been shown that dry steaming places a higher thermal load on the filter element than wet steaming. It is assumed that, due to evaporative cooling and the heat capacity of the water introduced during the wetting step, "wet steaming" is a less thermally stressful step for the filter elements than the alternative "dry steaming."

[0011] A further requirement is that the filter element's properties and testability remain unchanged by dry steaming. After sterilizing the filter elements with steam, they are rinsed to prepare them for the integrity test. To save time and wetting fluid, it is desirable that the complete wetting of the filter element, necessary for a successful integrity test, be possible with a minimal amount of wetting fluid (< 1 liter of water / m²), with a minimal differential pressure (< 0.1 bar), and in a minimal time (< 120 seconds).

[0012] The testability of fusion-bonded filter elements after dry vapor deposition is only guaranteed with considerable rinsing effort for many filter elements known from the state of the art.

[0013] State-of-the-art filter elements which can be successfully tested for integrity after dry steaming with minimal rinsing effort have one or more of the following characteristics: (1) Discoloration (oxidation) of the membrane due to dry vapor deposition. (2) The membranes themselves are modified in the joining area to become gas-impermeable, for example by melting, filling, or compressing the membrane. (3) Auxiliary materials, such as plastic film strips, are introduced into the joining area to make the membrane gas-impermeable and to improve the bond between the filter element and the membrane while simultaneously minimizing the thermal stress on the membrane in the area of ​​the fusion joint. (4) In the joining area, the membrane surface is modified in such a way that it has sufficient wettability with water after the fusion joining process.

[0014] Therefore, all such filter elements described in the prior art have the disadvantage that the membrane discolors (oxidizes) during dry vapor deposition and / or the joining area has to be modified in an additional process step during production.

[0015] For example, EP 0 096 306 A2, US 4,392,958, US 4,512,892, and US 4,906,371 describe processes for applying plastic film strips to render the porous membrane gas-tight in the joining / edge area. DE 38 033 41 A1 describes the filming of the edge areas of porous membranes through the action of solvents, solvent vapor, or temperature, whereby the membranes treated in this way become gas-tight in the filmed areas. US 5,846,421 describes porous membranes that are filled with high-molecular compounds in the fusion joint area to achieve gas-tightness. What all these processes have in common is that the membrane in the joining area is modified by an additional process step to ensure gas impermeability in order to reliably pass a subsequent integrity test, even if the membrane in the edge area - induced by the joining process - has changed material properties (e.g. changed wettability).

[0016] The following documents describe methods for modifying the membrane surface in the joining region. In contrast to the methods listed above, these methods are characterized in that the membrane remains permeable in the joining region: EP 0 571 871 B1 discloses poly(ether)sulfone membranes with a cross-linked polyvinylpyrrolidone (PVP) coating: Before or after drying the poly(ether)sulfone base membrane, it is passed through an impregnation bath containing PVP, vinylpyrrolidone monomers, and other hydrophobic monomers. An inorganic peroxosulfate is used as the radical initiator for the PVP cross-linking. After drying, the membranes are completely and spontaneously wettable with water and, for example, withstand treatment with steam at 134°C and 2 bar for 1.5 to 2.5 hours without losing this spontaneous wettability with water.This spontaneous wettability is necessarily linked to the presence of hydrophobic monomers in the impregnation bath during production. However, it is not disclosed that a dry-vaporized filter cartridge containing a membrane as described in EP 0 571 871 B1 can be tested after minimal wetting. Only the membrane itself is exposed to the vapor. Furthermore, it is only known that membranes known from the prior art that have not undergone prior thermal stress through fusion bonding can remain hydrophilic.

[0017] WO 2004 / 009201 A2 discloses water-testable filter cartridges with polyethersulfone-based membranes whose embedding areas in the polypropylene end caps are provided with a hydrophilic coating that does not compromise the porosity of the membrane. The hydrophilic coating consists of polyethyleneimine, polyvinyl alcohol, BUDGE (1,4-butanediol diglycidyl ether), or polyepichlorohydrin resins with amine groups. Such cartridges are successfully tested for integrity ("forward flow" or "reverse bubble point" test). However, it is not disclosed that a dry-coated filter cartridge containing a membrane as described in WO 2004 / 009201 A2 is testable after minimal wetting. According to WO 2004 / 009201 A2, cartridges are not dry-coated prior to air diffusion measurements, but are merely rinsed and tested. The strong thermal stress exerted by dry vapor deposition is missing in these experiments.Furthermore, the selective impregnation of the edge areas of the membrane represents an additional process step which is complex.

[0018] DE 43 39 810 C1 describes a process for the partial modification of porous membranes in the joining area. Membranes made of poly(ether)sulfone modified with polyvinylpyrrolidone are modified in the edge regions with a mixture of polyvinylpyrrolidone (PVP) and a copolymer of polyvinylpyrrolidone (PVP) and vinyl acetate (VA) in such a way that an increased concentration of cross-linked PVP or PVP-VA copolymer is present in these edge regions. The selective impregnation of the edge regions of the membrane results in the filter cartridges produced from it being testable for their integrity using air diffusion measurements (pressure retention test or integrity test). However, it is unlikely that a dry-coated candle containing a membrane as described in DE 43 39 810 C1 would be testable after minimal wetting, especially since the coating in the edge region also consists of a thermally unstable PVP-VA copolymer.Furthermore, DE 43 39 810 C1 does not specify the properties of the membrane in the coated edge region, particularly with regard to membrane permeability. The described wetting times of 10 to 30 minutes and the described wetting volumes fall far short of the requirements of a wetting time of less than 120 seconds and a wetting fluid volume of less than 1 L / m² of membrane area, as required for filtration processes with disposable filter elements. Furthermore, additional disadvantageous impregnation, rinsing, and drying steps are described, which are undesirable.

[0019] In summary, all known processes have in common that an additional step is required to further modify the membrane in the joining area. However, dry vapor deposition is not disclosed.

[0020] An alternative sterilization method to the aforementioned dry vapor deposition of filter elements is sterilization by irradiation, in which the filter elements are exposed to high-energy radiation, such as beta, gamma, or electron beams, thereby killing contaminating microorganisms. This process is preferably used for disposable filtration systems in which filter elements are pre-assembled within disposable housings with other disposable components, such as hoses, as a fully operational, closed system. This system is sterilized by irradiation before use and, after sterilization, can be stored until required. Due to the closed nature of this system, its generally small size, and the impermissibility of openly handling fluids during use, the filter elements must be testable using minimal quantities of fluid.

[0021] The present invention is therefore based on the object of providing a filter element which is easy to manufacture and which can be successfully tested for its integrity after dry steaming or alternatively after sterilization by irradiation and subsequent minimal wetting, ie after a time-limited rinsing step carried out with a limited rinsing volume and limited rinsing pressure, and which does not change in its material properties as a result of dry steaming or alternatively as a result of sterilization by irradiation.

[0022] This object is achieved by the embodiments of the present invention characterized in the claims.

[0023] In particular, the invention provides a fusion-bonded filter element with improved testability after dry vapor deposition or alternatively after sterilization by irradiation according to claim 1.

[0024] According to the invention, the term "filter element" encompasses all filtration devices whose purpose is to achieve substance separation based on size exclusion or different affinity. For example, the filter element according to the invention is suitable for removing yeast cells or bacteria (sterile filtration), viruses (virus removal), protein aggregates, or other particulate contaminants. According to a preferred embodiment of the present invention, the filter element is a filter candle.

[0025] For the purposes of the present invention, "irradiation" means beta, gamma or electron radiation.

[0026] The term "improved testability after dry vapor deposition" is understood according to the invention to mean that the filter element according to the invention can be successfully tested for integrity after dry vapor deposition with minimal rinsing effort (minimal wetting), without degradation of the polymer membrane in the filter element occurring due to the dry vapor deposition. "Degradation" is understood according to the invention to mean any thermally induced oxidative material change, in particular discoloration. The term "successful integrity testing" is understood according to the invention to mean that an integrity test consisting of a bubble point and / or diffusion test produces a positive result. This is the case when the membrane and its integration into the filter element are flawless, i.e., when it has no pores / defects that do not meet the desired substance separation through size exclusion / affinity, and when the entire filter element is completely wetted.

[0027] The term "minimal wetting" is understood according to the invention to mean that a filter element or membrane within a housing with appropriate line connections can be completely wetted with a minimal amount of wetting fluid and minimal wetting pressure. For this purpose, a peristaltic pump (hose pump), such as those typically used in pharmaceutical processes with disposable filter elements, can be used with a maximum pressure of 0.1 bar upstream of the filter element. The wetting time is a maximum of 120 seconds, and the amount of water is a maximum of 1 liter / m² < nominal filter area. The nominal filter area is understood to be the filter area of ​​a filter element that is effectively subjected to flow. Furthermore, several layers of filter membrane can be arranged one behind the other in the filter element, although in this case only the first layer subjected to flow counts.

[0028] The term "complete wetting" is understood according to the invention to mean that the entire interface separating the unfiltrate side of the filter element from the filtrate side of the filter element is either impermeable to liquid or filled with test liquid. The liquid-impermeable interface includes, for example, the end caps of the filter element made of solid plastic. The areas of the interface filled with test liquid primarily comprise all pores of the embedded membrane structure, but also any gaps that may have remained when the membrane was joined to the filter element. If complete wetting is present, a bubble point test and / or diffusion test will not be falsely negatively influenced by residual gas in the interface separating the unfiltrate side of the filter element from the filtrate side of the filter element. This means that after more intensive wetting, e.g.Due to upstream steps such as temperature application (e.g. autoclaving) or wetting with liquids with lower surface tension (e.g. alcohol) and after a subsequent integrity test, no higher bubble point pressures or a lower diffusion flow can be measured.

[0029] An integrity test, for example, involves testing the integrity of a filter element by determining the bubble point or the level of gas diffusion (pressure hold test) at a specified test pressure (DIN 58356-2:08 / 2000, DIN 58355-2) below the bubble point. The bubble point is the bubble point or gas diffusion at a specified pressure (DIN 58356-2:08 / 2000, DIN 58355-2). An integrity test consisting of a bubble point and diffusion test can be performed, for example, as described in the examples.

[0030] According to the invention, the term "porous polymer membrane" refers to a porous structure having a mean pore size ("mean flow" pore size) in the range of 0.001 to 10 µm, preferably 0.01 to 5 µm, and most preferably 0.1 to 1 µm. The "mean flow" pore size is the pore size of a membrane below which 50% of the gas flow through pores occurs < the "mean flow" pore size. The "mean flow" pore size can be measured, for example, according to ASTM F316 03 (2011) ("Standard Test Methods for Pore Size Characteristics of Membrane Filters by Bubble Point and Mean Flow Pore Test").

[0031] The material of the polymer membrane in the filter element according to the invention is not subject to any restrictions. According to a preferred embodiment, the polymer membrane comprises at least one plastic selected from the group consisting of polysulfone, polyethersulfone, cellulose acetate, cellulose nitrate, polyvinylidene fluoride, polypropylene, polyethylene, polytetrafluoroethylene, polyamide, and copolymers thereof, as well as mixtures thereof. Corresponding membranes are known in the art. According to a particularly preferred embodiment, the membrane comprises polyethersulfone.

[0032] The thickness of the polymer membrane in the filter element according to the invention is not subject to any restriction. According to a preferred embodiment, the thickness of the polymer membrane is in the range of 5 to 500 µm, more preferably in the range of 50 to 300 µm, and most preferably in the range of 80 to 200 µm.

[0033] The polymer membrane in the filter element according to the invention is a permanently hydrophilized polymer membrane. "Hydrophilic" in the context of the present invention refers to polymer membranes whose surface tension at 20°C is greater than 72 mN / m, or whose contact angle with water is less than 10°. The contact angle defined in the context of the present invention is the static contact angle in degrees [°] with ultrapure water. The contact angle θ can be determined analogously to ASTM-D5946-09 using a commercially available goniometer by applying a drop of ultrapure water (1 to 2 µL) to the surface to be analyzed and subsequently evaluating it according to Equation 1, where θ denotes the contact angle, B denotes half the width of the drop, and H denotes the height of the drop. The evaluation can be performed using software (for example, PG Software from FIBRO system AB). θ = 2 arctan H / B

[0034] For practical applications of polymer membranes, it is usually desirable for the membrane to be mechanically stable, thermally and chemically resistant, and insoluble in common (organic) solvents. Against this background, polymers are often used as membrane materials whose surface properties, such as hydrophilicity, wettability with water, or nonspecific binding (e.g., of proteins), do not meet the requirements of subsequent use and whose surfaces must be chemically or physically modified before filtration.

[0035] Therefore, the polymer membrane integrated into the filter element according to the invention is a permanently hydrophilized polymer membrane. The term "permanently hydrophilized" is understood according to the invention to mean that the polymer membrane is permanently hydrophilically modified, i.e., resistant to mechanical, thermal, and chemical influences. The method of permanently hydrophilizing the polymer membrane is not subject to any restrictions according to the invention, as long as the permanent hydrophilization of the polymer membrane is achieved by chemically or physically modifying an unmodified polymer membrane with a single hydrophilizing agent whose degradation temperature is at least 270°C.

[0036] For example, US 4,618,533 describes the permanent modification of membranes made of polymers with a prioriFor unsuitable hydrophobic surfaces, it has been proposed to impregnate porous, hydrophobic membranes based on poly(ether)sulfone or polyvinylidene fluoride with a solution of a monomer (hydroxyalkyl or aminoalkyl acrylates) and an initiator, and then to initiate the polymerization of the monomer by applying energy, e.g., by heating (thermal initiation) or UV irradiation (using a photoinitiator). The polymerization forms long-chain, cross-linked polymer chains inside the porous matrix. These polymers cannot be washed off the membrane and are partially grafted onto the membrane, resulting in a permanent modification.

[0037] An alternative to the use of initiators is the initiation of polymerization using electron beams. In this case, the membrane to be modified is impregnated with a solution containing monomers derived from acrylic acid derivatives and subsequently exposed to electron beams, which initiates the reaction of the monomers. The described impregnation solutions often also contain crosslinkers, i.e., doubly or generally polyfunctional monomers (see US 4,944,879, EP 1 390 087 B1, EP 1 381 447 B1, and WO 2005 / 077500 A1) or mixtures of several monomers and crosslinkers (EP 1 390 087 B1, EP 1 381 447 B1, and US 7,067,058 B2). In addition, variants of thermally induced modification with a homopolymer and a crosslinker (WO 2005 / 077500 A1) orwith an oligomer, with a monomer, and optionally with a crosslinker, whereby US 6,039,872 discloses hydrophilic membranes that can be produced from a hydrophobic poly(ether)sulfone membrane and a crosslinkable polyalkylene glycol diacrylate and a hydrophilic monoacrylate. DE 10 2009 004 848 B3 discloses microporous membranes on whose outer and inner surfaces a crosslinked hydrophilic polymer is fixed by the action of electron beams. JP 2011-156533 A discloses the hydrophilization of polysulfone-based hollow fiber membranes, e.g., with polyethylene glycol or polyvinylpyrrolidone. By controlling the temperature during production and by selecting a suitable ratio between the average molecular weight of the polysulfone polymer and the polymer selected for hydrophilization, membranes are obtained that combine high oxidation resistance with low binding capacity for hydrophobic proteins.

[0038] The housing of the filter element according to the invention comprises a plastic or a plastic mixture, wherein the melting point of the plastic or plastic mixture of the housing component, which is melt-bonded to the polymer membrane, is at least 125°C lower than the degradation temperature of the hydrophilizing agent with which the polymer membrane is permanently hydrophilized. According to a preferred embodiment, the melting point of the plastic or plastic mixture of the housing component, which is melt-bonded to the polymer membrane, is at least 140°C, more preferably at least 155°C lower than the degradation temperature of the hydrophilizing agent.

[0039] According to a preferred embodiment, the housing comprises at least one plastic selected from the group consisting of polyolefins, polysulfones, fluorinated or partially fluorinated polymers, polyamides, polyesters, and cellulose derivatives, as well as mixtures thereof. According to a particularly preferred embodiment, the housing comprises polypropylene.

[0040] In the filter element according to the invention, the polymer membrane is connected to the housing via fusion joints using a fusion joining process. The term "fusion joint" refers to the joint through which the housing is connected to the polymer membrane. Such fusion joining processes are known in the art.

[0041] The filter element according to the invention is advantageously dry-vaporized, does not change its material properties as a result of dry vaporization or alternatively as a result of sterilization by irradiation, and can be tested for integrity after minimal wetting.

[0042] This requirement is met by ensuring that the membrane is stable against the thermal stress during fusion bonding or subsequent dry vapor deposition. The membrane is stable against these thermal stresses if all membrane components that determine the material properties of the membrane are stable against these thermal stresses. The membrane properties are largely determined by the polymer material from which the membrane is made, or by the hydrophilizing agent, which determines the surface properties of the permanently hydrophilized membrane. Furthermore, the lower the melting point of the filter element housing material, the lower the thermal stress on the membrane during fusion bonding.

[0043] For the purposes of the present invention, the "melting point of a plastic or plastic mixture" is understood to mean the melting point determined on the plastic or plastic mixture using dynamic differential scanning calorimetry (DSC) according to DIN EN ISO 11357-1:2009. Differential scanning calorimetry is performed, for example, as described in the examples.

[0044] As shown in Table 1, typical filter element housing materials show various exemplary melting point ranges: Tabelle1: material Melting point range [°C] Polypropylene (PP) 140 - 170 Polysulfone (PSU) 170 - 190 Polyvinylidene fluoride (PVDF) 180 - 220 Polyamide (PA) 200 - 260 Polyethylene terephthalate (PET) 230 - 260

[0045] In technical melt-joining processes, however, the melt reaches temperatures far higher than the melting point of the filter element housing material. As can be seen from Table 1, polypropylene, as a plastic base material, has a melting point range of 140–170°C that is most suitable for the invention, since the membrane experiences the lowest thermal stress when joined to this material. Polypropylene is also suitable for short-term vapor deposition at 105–140°C. In technical melt-joining processes, polypropylene actually reaches melt temperatures of approximately 220–300°C at the moment of joining. This difference between the melting point and the melt temperature actually reached during joining in a technical process applies equally to other filter element housing materials and is determined by the technical nature of these processes.In order to melt the housing component to be joined to a depth of several millimeters in an economically viable time, the housing component is heated, at least on its surface, to a temperature significantly higher than the melting point of the filter element housing material. Consequently, the surface of the housing component to be joined facing the heat radiator in particular will reach a temperature significantly above the melting point of the filter element housing material. The membrane immersed in this melt is exposed to temperatures elevated relative to its melting point. Furthermore, it is known that polymer melts have a relatively high specific heat capacity, which means that the cooling of the melt occurs relatively slowly, and thus the membrane is subjected to greater thermal stress than melts with a lower specific heat capacity.

[0046] A measure of a material's thermal stability is its degradation temperature. This is determined, for example, using dynamic thermogravimetric analysis (TGA) conducted in an air atmosphere, in which the weight of the sample is measured as the sample temperature increases. When thermal decomposition begins, the weight of the sample decreases. In this way, materials can be examined with regard to their thermal stability and a degradation temperature can be determined. The term "degradation temperature" is understood to mean the temperature in a TGA measurement at which the mass loss (TG %) is equal to 2% and the weight of the sample has thus fallen to 98% of the initial weight. The sample is heated at a rate of 10 K / min.

[0047] It has been shown that a difference between the melting point of the plastic or plastic mixture of the building component and the degradation temperature of the hydrophilizing agent of at least 125°C, preferably at least 140°C, and most preferably at least 155°C, produces favorable testability results due to the significantly reduced thermal stress on the hydrophilizing agent in technical processes. In this case, the melting point is then below the degradation temperature by the specified difference. If a plastic or plastic mixture with a higher melting point is used for the housing component, a hydrophilizing agent with a similarly higher degradation temperature must be used to maintain the specified temperature difference. In this way, thermal stress on the hydrophilizing agent is reduced.

[0048] According to the state of the art, hydrophilizing agents are either applied directly as a polymer to the membrane surface, or monomeric agents are polymerized in the presence of the membrane and applied to it.

[0049] According to the present invention, a single hydrophilizing agent is used that is thermally stable, i.e., has a degradation temperature of at least 270°C, preferably at least 295°C, and most preferably at least 315°C. This ensures that the permanently hydrophilized polymer membrane has suitable thermal stability.

[0050] When using polymeric hydrophilizing agents, the degradation temperature refers to the polymer itself. When using monomeric hydrophilizing agents, which are only polymerized during the membrane hydrophilization process, the degradation temperature refers to the resulting polymer. This polymer is produced using the same process as for membrane hydrophilization, with the difference that the membrane is removed from the process and only the impregnation solution is used.

[0051] According to a preferred embodiment, the hydrophilizing agent comprises a polymer, more preferably a water-soluble polymer. According to a particularly preferred embodiment, the hydrophilizing agent is selected from the group consisting of hydroxyalkylcellulose, polyvinylpyrrolidone, and poly-2-ethyloxazoline. The hydrophilizing agent is most preferably poly-2-ethyloxazoline.

[0052] The permanently hydrophilized membrane contained in the filter element according to the invention is not further modified in the joining area, apart from the hydrophilization described above. The term "not further modified" is understood according to the invention to mean that the permanently hydrophilized membrane is neither further physically or chemically modified in the joining area, nor is it further modified by auxiliary materials introduced into the joining area, such as plastic film strips.Since the filter element according to the invention, in contrast to filter elements known in the prior art, does not require such additional modification of the membrane in the joining area due to the high degradation temperature of the hydrophilizing agent relative to the melting point of the housing material joined to the membrane, a time-consuming and costly work step is advantageously eliminated in the manufacturing process of the filter element according to the invention compared to known filter elements.

[0053] A further subject of the present invention relates to a method for producing the filter element according to the invention according to claim 10.

[0054] In the first two steps of the process according to the invention, a porous, permanently hydrophilized polymer membrane and a housing, as already characterized above, are provided.

[0055] In the next step, the polymer membrane and the housing are melt-joined to connect the polymer membrane to a component of the housing via melt joints. This melt-joining step is carried out according to methods known in the art.

[0056] In the process according to the invention, the polymer membrane is not further modified in the joining area. This advantageously eliminates the additional modification step in the joining area, which is always necessary in the prior art to ensure the integrity of a filter element.

[0057] A further object of the present invention relates to the use of the filter element according to the invention for the filtration of solutions, for example for sterile filtration or virus depletion.

[0058] The inventive combination of low-melting filter element housing material and a thermally stable polymer membrane, which has been permanently hydrophilized with a single thermally stable hydrophilizing agent, makes it possible to provide a filter element, for example in the form of a filter candle, which can advantageously be dry-coated without changing its material properties and which can be tested for integrity after minimal wetting. Due to these advantageous features, the filter element according to the invention is ideally suited for use in filtration in the pharmaceutical and biotechnological sectors, where high demands are placed on the stability and sterility of the filter material.In addition, in the manufacturing process of the filter element according to the invention, advantageously no additional step for modifying the polymer membrane in the joining area is necessary in order to be able to successfully carry out a subsequent integrity test, whereby the filter element can be manufactured more cost-effectively than filter elements previously known in the prior art.

[0059] The present invention is further illustrated by the following non-limiting examples. Examples General procedures Determination of the melting point of a thermoplastic or plastic mixture according to the present invention by means of DSC:

[0060] Differential scanning calorimetry (DSC) is used to determine the melting point of a thermoplastic. The determination is based on DIN EN ISO 11357-1:2009.

[0061] For crystalline or semi-crystalline plastics, the melting point is defined as the "peak melting temperature" T pm, as described in section 10 of DIN EN ISO 11357-3:2011(E). The determination of T pm is also carried out according to this DIN standard. If the DSC curve of the plastic exhibits several T pm values, the T pm with the highest value is chosen as the measure of the plastic's melting point.

[0062] For amorphous or semi-crystalline plastics, the melting point is defined as the "midpoint temperature" T mg, as described in section 3 of DIN EN ISO 11357-2:1999(E). The determination of T mg is also carried out according to this DIN standard. If the DSC curve of the plastic shows several T mg values, the highest T mg is chosen as the measure of the plastic's melting point. Preparation of polymers for TGA analysis from monomers used for hydrophilization:

[0063] The monomers are used in the same concentration and solvent as in the membrane hydrophilization process (see Example 1). Polymerization then takes place under the same conditions as in the membrane hydrophilization process, except in the absence of the membrane: In particular, the temperature, oxygen content, layer thickness, if applicable, the intensity or dose of irradiation, and / or the concentration and type of initiator are adjusted or used analogously to the membrane manufacturing process.

[0064] After polymerization, the resulting polymeric hydrophilizing agent is washed with the solvent of the impregnation solution and dried at 110°C to constant weight. The resulting polymer is pulverized, and a sample is taken for TGA. Determination of the degradation temperature of a hydrophilizing agent according to the present invention by means of TGA:

[0065] Dynamic thermogravimetry (TGA) is used to determine the degradation temperature of the hydrophilizing agent. The determination is carried out in accordance with DIN EN ISO 11358:1997. The change in the mass of a sample of the hydrophilizing agent is recorded under a flowing air atmosphere as a function of the temperature increasing at a constant rate of 10 K / min. Before the TGA measurement, the hydrophilizing agent is pre-dried at 110°C until constant mass is reached. As described in the DIN standard, ms is defined as the mass of the sample before heating. The degradation temperature defined according to the invention is the temperature at which the sample mass has lost 2% of its weight, i.e., only 98% of the mass before heating remains, i.e., sample mass = 0.98 × ms . Dry steaming:

[0066] A filter element, for example a 10" filter candle, is inserted dry into a stainless steel housing, and the housing is connected to a steam supply. The steam supply is opened, steam flows through the filter element in the housing, and a control valve arranged downstream of the housing is used to set a steam pressure of 2 bar, corresponding to a steam temperature of 134°C. A steam supply control is used to set a differential pressure of 0.05 to 0.1 bar between the inlet and outlet of the filter housing. After 30 minutes, the steam supply is closed, and the housing is cooled with ambient air at room temperature until temperatures of < 30°C are reached. Wet steaming:

[0067] Wet steaming corresponds to the steaming process of dry steaming, however the 10" filter element is wetted with water for 90 seconds before being inserted into the filter housing and then inserted wet. Since steam cannot flow through the water-wetted membrane when the steam supply is opened, the steam supply is only opened minimally and the steam on the filter housing is released through vent valves until the housing and filter element reach a temperature > 100°C and steam can pass through the filter element. The steam pressure never exceeds a differential pressure of 0.5 bar between the inlet and outlet of the housing. The differential pressure after a temperature > 100°C is reached and the steam has thus passed through the filter element is 0.05 to 0.1 bar. Integrity test, bubble point and diffusion test:

[0068] The integrity test, consisting of a bubble point and diffusion test, is performed using a Sartockeck®< 3 and Sartocheck®< 4 integrity test device (Sartorius Stedim Biotech GmbH). The setting parameters are 3 minutes of stabilization time, 3 minutes of test time for the diffusion test, and the diffusion test pressure specified by the manufacturer for the corresponding filter element (2.5 bar for the filter elements according to the invention described here). Porometer:

[0069] PMI measuring device, Porous Materials Inc., USA, Capillary Flow Porometer Commercially available comparison filter elements:

[0070] For comparison, the following commercially available filter elements were tested: Pall, Typ: Supor EKV 0,2 µm, Prod.code: AB1EKV7PH4, Ch. IR7867, (2-lagig PES Membran); Pall, Typ: Fluorodyne EX EDF 0,2 µm, Prod.code: AB1UEDF7PH4, Ch. IR8838, (je 1 Lage PES u. PVDF Membran); Pall, Typ: Fluorodyne II 0,2 µm, Prod.code: AB1DFL7PH4, Ch. IR8255, (2 Lagen PVDF Membran); Millipore: Typ Durapore 0,22 µm, Prod.code: CVGL7TP3, Ch. F1KA97385, (1 Lage PVDF Membran); Millipore, Typ: Express SHC, Prod.code: CHGE01TS3, Ch. C1EA82133, (2 Lagen PES Membran); 3M Cuno, Typ: Cuno 3M Life Assure, PNA020F01BA,Ch. M01812-002, (1 Lage PES Membran). Examples of implementation 1. Permanent hydrophilization of membranes:

[0071] A starting membrane type 15407 (Sartorius Stedim Biotech GmbH), a sterile filter membrane made of polyethersulfone with an average pore size of 0.2 µm, was wetted with an impregnation solution containing the hydrophilizing agent used for permanent hydrophilization (see Table 2 below). In the examples described, the hydrophilizing agent is a polymer. The concentration of the hydrophilizing agent in the impregnation solution ranges from 0.5 to 6.0 weight percent, with water being used as the solvent. After contacting the membrane with the impregnation solution, the membrane was placed between two polyethylene (PE) films, and excess impregnation solution was either expelled from the membrane with a roller or squeezed off between two rubberized rollers.The impregnated membrane was then exposed to electron beam irradiation (EC-Lab 400, Crosslinking AB, Sweden) using an accelerating voltage of 190 kV and doses of 25 to 75 kGy. The irradiation zone was inerted with nitrogen, i.e., any existing oxygen was displaced by nitrogen. After irradiation, the membrane was extracted with suitable solvents to dissolve any non-permanently bound hydrophilizing agent and demonstrate the durability of the hydrophilization. The modified membrane was then dried in a drying cabinet and tested for its properties. Table 2: abbreviation Name, CAS No., Molecular weight MW Polymer concentration in the impregnation solution Irradiation dose PVP Polyvinylpyrrolidone, 9003-39-8, 50,000 1.3% by weight 50 kGy POZ Poly-2-ethyloxazoline, 25805-17-8, 0.5% wt 75 kGy 5000 PEG Polyethylene glycol, 25322-68-3, 4,000 0.7% by weight 70 kGy PVP-VA (VA: vinyl acetate) 630S Polyvinylpyrrolidone-co-vinyl acetate S630 25086-89-9, 51,000 1.0% by weight 50 kGy 2. Thermoanalytical investigations of polymers (TGA):

[0072] The investigations were carried out using the STA 449 F3 "Jupiter" simultaneous thermal analysis device (Netzsch-Gerätebau GmbH) under flowing air atmosphere at a heating rate of 10 K / min. The polymers were pre-dried at 110°C. The analyzed temperature range was from 10 to at least 500°C. The execution and evaluation of the results were based on DIN EN ISO 11358. To compare different polymers, the degradation temperature was defined as the temperature at which the mass loss is equal to 2%. The TGA data for Aquazol ®< 5 (poly-2-ethyloxazoline, MW 5,000; CAS No. 25805-17-8) are illustrated as an example ( Figure 1 ). Table 3: Degradation temperatures of the hydrophilizing agents used in the examples abbreviation Name, CAS No., Molecular weight MW Degradation temperature POZ Poly-2-ethyloxazoline, 25805-17-8, 5,000 328°C PVP Polyvinylpyrrolidone, 9003-39-8, 50,000 300°C PEG Polyethylene glycol, 25322-68-3, 4,000 275°C PVP-VA 630S Polyvinylpyrrolidone-co-vinyl acetate S630, 25086-89-9, 51,000 250°C 3. Construction of filter elements using the fusion joining process

[0073] Filter elements are constructed by pleating a membrane permanently hydrophilized with POZ, PVP, PEG, or PVP-VA according to Example 1. A polypropylene spunbond is arranged on the top and bottom of the permanently hydrophilized membrane on a knife pleating machine. The pleated membrane composite is placed in a 10" polypropylene outer and inner housing (Sartorius Stedim Biotech GmbH). Polypropylene end caps with a melting point T pm of 166°C measured by DSC (see "General Procedures") are melted and attached. For this purpose, a metal block is heated to a temperature above the melting point of the housing components used for melt joining and positioned 8 to 12 mm in front of the end caps for 60 seconds to create the melt. The membrane composite with inner and outer housings is then inserted into the polymer melt.The end cap and connection adapter are then joined by melting and joining polypropylene end caps and connection components on both sides. The finished candles undergo a 90-second water rinse, autoclaving at 134°C for 30 minutes, a (re)similar rinse, an integrity test, and drying for 12 hours at 80°C in a convection oven. 4. Integrity test on filter elements after dry and wet steaming

[0074] Table 4 compares the results of an integrity test of commercially available filter elements with filter elements according to the invention after dry steaming. Filter elements are known that fail the integrity test after dry steaming (134°C, 30 minutes) with subsequent minimal wetting due to insufficient wetting: Table 4: Integrity test after dry steaming Product, Prod.code, Lot.No Diffusion / limit [ml / min] Bubble point / limit [bar] Integrity test passed commercially available filter elements Millipore Express SHC, CHGE71TS3, Ch. C1EA82133 18,4 / < 28,2 5,44 / > 4,0 Yes Millipore Durapore®<, CVGL71TP3, Ch. F1KA97385 12 / < 13,3 3,36 / > 3,45 no Pall Supor ®< EKV, AB1EKV7PH4, Ch. IR7867 168 / < 17 3,29 / > 3,2 no Pall Fluorodyne ®< EX EDF, AB1UEDF7PH4, Ch. IR8838 42,5 / < 30 3,44 / > 3,2 no Pall Fluorodyne ®< II, AB1DFL7PH4, Ch. IR8255 16,2 / < 12 3,23 / > 3,2 no Cuno 3M Life Assure, PNA020F01BA, Ch. M01812-002 nb / < 51 nb / > 3.2 no filter elements according to the invention Inventive element PES / POZ, 10", Ch. 11022083 (membrane according to Table 2) 16,8 / < 25 4,03 / > 3,5 Yes Element according to the invention 12,5 / < 13 4,15 / > 3,5 Yes PES / PVP, 10", Ch. 120008583 (membrane according to Table 2) Comparative examples of filter elements not according to the invention Comparison example: Element PES / PEG, 10", Ch. 09005883 (membrane according to Table 2) 16,1 / < 13 3,81 / > 3,5 no Comparison example: Element PES / PVP-VA, 10", Ch. 09011983 (membrane according to Table 2) 17,4 / < 13 3,90 / > 3,5 no

[0075] Comparatively, filter elements successfully pass the integrity test after wet steaming (134°C, 30 minutes) with subsequent minimal wetting (Table 5): Table 5: Integrity test after wet steaming Product, Prod.code, Lot.No Diffusion / limit [ml / min] Bubble point / limit [bar] Integrity test passed commercially available filter elements Millipore Express SHC, CHGE71TS3, Ch. C1EA82133 17,5 / < 28,2 5,5 / > 4,0 Yes Millipore Durapore®<, CVGL71TP3, Ch. F1KA97385 10,8 / < 13,3 3,29 / > 3,45 no Pall Supor ®< EKV, AB1EKV7PH4, Ch. IR7867 13,5 / < 17 3,45 / > 3,2 Yes Pall Fluorodyne ®< EX EDF, AB1UEDF7PH4, Ch. IR8838 23,3 / < 30 4,38 / > 3,2 Yes Pall Fluorodyne ®< II, 10,3 / < 12 3,88 / > 3,2 Yes AB1DFL7PH4, Ch. IR8255 Cuno 3M Life Assure, PNA020F01BA, Ch. M01812-002 43,3 / < 51 4,54 / > 3,2 Yes filter elements according to the invention Inventive element PES / POZ, 10", Ch. 11022083 (membrane according to Table 2) 18,1 / < 25 3,83 / > 3,5 Yes Inventive element PES / PVP, 10", Ch. 120008583 (membrane according to Table 2) 12,7 / < 17 3,95 / > 3,5 Yes Comparative examples of filter elements not according to the invention Comparison example: Element PES / PEG, 10", Ch. 09005883 (membrane according to Table 2) 11,1 / < 13 4,47 / > 3,5 Yes Comparison example: Element PES / PVP-VA, 10", Ch. 09011983 (membrane according to Table 2) 10,4 / < 13 4,05 / > 3,5 Yes

[0076] Millipore Express SHC filter elements are manufactured with foil strips as an aid in the cap sealing area and do not meet the above requirements. Millipore Durapore ®< filter elements generally exhibit bubble point values ​​that are too low, even with wet vapor deposition or with sub-minimal wetting, and therefore do not meet the requirements. Pall Fluorodyne ®< II and EX filter elements exhibit degradation under the applied thermal stresses and do not meet the requirements. The microfiltration membranes contained in these products discolor / oxidize due to vapor deposition (see Example 6).

[0077] The diffusion results of the integrity test can be plotted as a function of the degradation temperature. The lower the degradation temperature of the hydrophilizing agent, the greater the damage to the hydrophilization during thermal bonding during filter element production. Thus, the greater the damage, i.e., the lower the degradation temperature, the larger the non-wettable membrane areas and, consequently, the greater the diffusion currents. This results in a sequence of decreasing degradation temperatures compared to increasing diffusion values ​​normalized to the nominal filter area: Temperature: 328 300 275 250°C Diffusion value: 16,8 20,8 26,8 29 ml / min / m 2< , which is shown in Table 6 with reference to the other data. Table 6: Integrity test after dry vapor deposition and diffusion result versus degradation temperature of the hydrophilizing agent Product, Prod.code, Lot.No Diffusion [ml / min / m 2< ] Average per batch Integrity test passed Degradation temperature filter elements according to the invention Inventive element PES / POZ, 10", Ch. 11022083 (membrane according to Table 2) 16,8 Yes 328°C Inventive element PES / PVP, 10", Ch. 120008583 (membrane according to 20,8 Yes 300°C Table 2) Comparative examples of filter elements not according to the invention Comparison example: Element PES / PEG, 10", Ch. 09005883 (membrane according to Table 2) 26,8 no 275°C Comparison example: Element PES / PVP-VA, 10", Ch. 09011983 (membrane according to Table 2) 29 no 250°C 5. Degradation / discoloration of the membranes of filter elements after thermal treatment

[0078] For the Durapore®< 0.22 µm product, degradation is observed, visible by the brownish discoloration of the polymer membrane. For the Fluorodyne®< II and Fluorodyne®< EX EDF products, degradation is also observed, visible by the brownish discoloration of the polymer membrane.

[0079] The discoloration is measured using a reflection densitometer D186, manufactured by Greteg, Althardstr. 70, CH-8105 Regensdorf.

[0080] The membrane material is taken from a filter element in its as-delivered condition and a filter element that has undergone dry vapor deposition. The D186 densitometer is calibrated using the provided calibration color chart. All membranes are wetted and lie flat on the same PP base plate, allowing the meter to be placed flat on the membrane and measured. The calibration for the color yellow is 1.48 units. The results of the yellow content measurement are shown below: Sample 1: Fluorodyne ®< II, 10" cartridge, main filter membrane, material as specified

[0081] Output membrane after dry steaming 0,42 0,63 0,42 0,62 0,44 0,62

[0082] After thermal treatment, the membrane material shows a discoloration in the yellow / brown range, which indicates thermal oxidative degradation of the membrane material. Sample 2: Fluorodyne ®< EX EDF, 10" main filter membrane, material as specified

[0083] Output membrane after dry steaming 0,42 0,61 0,44 0,62

[0084] After thermal treatment, the membrane material shows a discoloration in the yellow / brown range, which indicates thermal oxidative degradation of the membrane material. Sample 3: Durapore ®< 0.22, 10" membrane, material as specified

[0085] Output membrane after dry steaming 0,24 0,56 0,24 0,59

[0086] After thermal treatment, the membrane material shows a discoloration in the yellow / brown range, which indicates thermal oxidative degradation of the membrane material. Sample 4: inventive filter element PES-POZ, 10" main filter membrane,

[0087] Output membrane after dry steaming 0 0 0 0 0 0

[0088] The membrane material shows no yellow / brown discoloration after thermal treatment. There is no evidence of thermal oxidative degradation of the membrane material. Sample 5: inventive filter element PES-PVP, 10" main filter membrane,

[0089] Output membrane after dry steaming 0 0 0 0 0 0

[0090] The membrane material shows no yellow / brown discoloration after thermal treatment. There is no evidence of thermal oxidative degradation of the membrane material.

[0091] Figure 1 shows a thermogram of Aquazol ®< 5 (poly-2-ethyloxazoline, MW 5,000; CAS No. 25805-17-8).

Claims

1. Melt-joined filter element with improved testability after dry steaming or alternatively after sterilization by irradiation, comprising a housing that comprises a plastics material or a plastics material mixture, and a porous, hydrophilically modified polymer membrane resistant to mechanical, thermal and chemical influence, whose surface tension at 20°C is greater than 72 mN / m, wherein the hydrophilization of the polymer membrane is accomplished by chemical or physical modification of an unmodified polymer membrane with a hydrophilization agent, the polymer membrane is connected to the housing by a melt-joining process via melt-joining, the polymer membrane in the join area is not additionally modified physically or chemically or by auxiliary materials introduced into the join area apart from the hydrophilization with the hydrophilization agent, wherein the melting point of the plastics material or of the plastics material mixture of the housing component, which is melt-joined to the polymer membrane, is at least 125°C lower than the degradation temperature of the hydrophilization agent, with which the polymer membrane is hydrophilized to be resistant to mechanical, thermal and chemical influence, wherein the surface tension and the degradation temperature are determined as stated in the description, and wherein the melting point is determined in accordance with DIN EN ISO 11357-1:2009 as stated in the description, characterized in that the degradation temperature of the hydrophilization agent is at least 270°C.

2. Filter element according to claim 1, wherein the melting point of the plastics material or of the plastics material mixture is at least 140°C lower than the degradation temperature of the hydrophilization agent.

3. Filter element according to any of claims 1 to 2, wherein the housing comprises at least one plastics material selected from the group consisting of polyolefins, polysulfones, fluorinated or partially fluorinated polymers, polyamides, polyesters and cellulose derivatives, as well as mixtures thereof.

4. Filter element according to any of claims 1 to 3, wherein the housing comprises polypropylene.

5. Filter element according to any of claims 1 to 4, wherein the polymer membrane comprises at least one plastics material selected from the group consisting of polysulfone, polyethersulfone, cellulose acetate, nitrocellulose, polyvinylidene fluoride, polypropylene, polyethylene, polytetrafluoroethylene, polyamide and copolymers of these, as well as mixtures thereof.

6. Filter element according to any of claims 1 to 5, wherein the polymer membrane comprises polyethersulfone.

7. Filter element according to any of claims 1 to 6, wherein the hydrophilization agent comprises a polymer.

8. Filter element according to any of claims 1 to 7, wherein the hydrophilization agent comprises a water-soluble polymer.

9. Filter element according to any of claims 1 to 8, wherein the hydrophilization agent is selected from the group consisting of hydroxyalkylcellulose, polyvinylpyrrolidone and poly-2-ethyloxazoline.

10. Method for producing a filter element according to any of claims 1 to 9, comprising the steps: - providing a porous, hydrophilized polymer membrane resistant to mechanical, thermal and chemical influence; - providing a housing; and - subsequently melt-joining the polymer membrane and the housing in order to connect the polymer membrane to a component of the housing via melt-joining; wherein the polymer membrane in the join area is not additionally modified physically or chemically or by auxiliary materials introduced into the join area apart from the hydrophilization with the hydrophilization agent, wherein the melting point of the plastics material or of the plastics material mixture of the housing component, which is melt-joined to the polymer membrane, is at least 125°C lower than the degradation temperature of the hydrophilization agent, with which the polymer membrane is hydrophilically modified to be resistant to mechanical, thermal and chemical influence, wherein the degradation temperature is determined as stated in the description, and wherein the melting point is determined in accordance with DIN EN ISO 11357-1:2009 as stated in the description, characterized in that the degradation temperature of the hydrophilization agent is at least 270°C.

11. Use of the filter element according to any of claims 1 to 9 for the filtration of solutions.