A method for verifying the filterability of a virus-removing filter material

Abstract

The application relates to the field of filter equipment detection, in particular to a virus-removing filter material filterability verification method, which comprises the following continuous steps: S1, setting a calibration sample; S2, determining a standard pressure according to a production process, and performing constant-pressure filtration on a filter containing a filter material to be detected by using the calibration sample under the standard pressure; S3, adjusting an inlet pressure to simulate a pressure burst situation experiment on the basis of step S2, containing at least one group of pressure interruption experiments and at least one group of pressure repetition experiments; in steps S2-S3, a detection point is arranged in any detection test group or downstream of the experimental group, and whether the filter material is broken through is detected. The above method can better simulate the burst situation of the filter material in the actual filtration process, and can better verify the membrane material leaving the factory, so as to reflect the basic state of the membrane material in the use process.

Description

Technical Field

[0001] This application relates to the field of filtration equipment testing, specifically to a method for verifying the filterability of virus-removing filter materials. Background Technology

[0002] In modern industrial production and numerous experimental settings, filter materials, as a crucial component, are widely used in various precision filtration processes. For example, they are employed in the pharmaceutical industry to ensure the purity of drug solutions and in chemical experiments to separate specific components. Particularly in the biopharmaceutical field, virus-removing filter materials (such as filter membranes) play a vital role, significantly impacting the cleanliness and safety of biological products.

[0003] As production scale continues to expand and process requirements become increasingly refined, it is becoming increasingly important to verify membrane materials in advance. Otherwise, if the membrane material is punctured or damaged during use due to various reasons, it can easily lead to large-scale pollution and damage of raw materials, resulting in huge economic losses. Therefore, it is necessary to fully verify the puncture resistance of membrane materials in advance.

[0004] Existing methods for validating filter materials typically involve two aspects: first, routine filtration tests on the filter material under specific sample solutions; and second, testing the filter material under special conditions to evaluate its performance under high concentrations, different pH values, pressure interruptions, backwashing, and other conditions. These approaches have several shortcomings in practical application. Firstly, conventional validation methods often only test filter materials under single, relatively ideal conditions, failing to comprehensively simulate the real-world performance of filter materials under complex and variable operating conditions, such as high-load filtration tasks and sudden pressure fluctuations. In particular, they struggle to accurately assess potential breakdown performance issues. Secondly, the complex manufacturing process of filter materials, including the equipment used at each stage and potential accidents during operation, can impact the filter material itself. This makes it difficult to control the intensity of actual testing. At lower testing intensities, inherent problems with the filter material may be overlooked, while at higher intensities, an overemphasis on strength performance can occur, leading to insufficient assessment of flux, load capacity, and permeability. Summary of the Invention

[0005] This application provides a method for verifying the filterability of a filter material, which can better simulate the sudden situations encountered by the filter material during the actual filtration process, and can better verify the membrane material leaving the factory to reflect the basic state of the membrane material during use.

[0006] First, a method for verifying the filterability of a virus-removing filter material, characterized by comprising the following sequential steps:

[0007] S1. Set up the calibration sample;

[0008] S2. Determine the standard pressure according to the production process, and use the calibration sample to perform constant pressure filtration on the filter containing the filter material to be tested under the standard pressure.

[0009] S3. Based on step S2, adjust the inlet pressure to simulate a sudden pressure event experiment, including at least one set of pressure interruption experiments and at least one set of pressure repetition experiments.

[0010] In steps S2 to S3, a detection point is set in any test group or downstream of the test group to detect whether the filter material is punctured.

[0011] In the above solution, the filter media is first tested in a one-time integrated manner. During the test, the filter media can be installed and then a continuous testing process is carried out. In the one-time process, various situations can be fully simulated, and at the same time, it has better fitting performance for the unexpected situations encountered by the actual product during use.

[0012] Based on the above, and considering that as the load on the filter material increases during the filtration process, the filter material itself becomes more susceptible to external pressure fluctuations and more prone to breakdown after a certain period of filtration. Therefore, in this scheme, the pressure surge test is conducted after constant pressure filtration. Conducting the surge test after the initial constant pressure filtration better reflects the actual state of the filter material during filtration and facilitates simulation of real-world conditions. Furthermore, by verifying repeated pressure and pressure interruptions in consecutive steps, this experiment better simulates actual conditions. Overall, this scheme allows for better differentiation between filter materials with and without quality issues, thus enabling better product verification at the factory.

[0013] Preferably, in step S3, a pressure interruption experiment is performed first, followed by a pressure repetition experiment. The pressure interruption experiment and the pressure repetition experiment are further separated by a transition section for filtration under standard pressure. The load of the transition section is 0.1 to 0.2 times the total load of steps S1 to S3.

[0014] In the above scheme, the pressure interruption test is performed first, followed by the pressure repetition test, with a transition section added in between. The reason for this is that, compared to the pressure interruption test, the pressure repetition test will put more pressure on the filter material. Filter materials that are prone to breakdown after long-term interruption are more likely to have similar problems in the pressure repetition test. Therefore, performing the pressure interruption test first and then the pressure repetition test can better evaluate the overall performance and reduce the verification time.

[0015] Based on the above scheme, a transition section with a certain load is set in the pressure interruption test and the pressure repetition test. The transition section can provide testing space and also allow the filter material to recover its filtration state after the pressure interruption, so as to more accurately measure the actual situation of the filter material.

[0016] Preferably, the load of the transition section before the detection point is not less than 50% of the total load of the transition section.

[0017] In the above scheme, filtration is carried out for a period of time in the transition section before testing. The reason is that after the interruption test, the filter material needs to be filtered for a period of time before it can be seen whether it will be broken down. Filtration is carried out for a period of time in the transition section before verification, which can better detect the test results of the pressure interruption test.

[0018] Preferably, in step S3, the pressure repetition test includes 5 to 30 test cycles. For any test cycle, it includes at least a high-pressure section and a low-pressure section. The pressure of the high-pressure section is not less than 0.8 times the standard pressure, and the pressure of the low-pressure section is not higher than 5 psi.

[0019] In the above scheme, repeated pressure is mainly used to simulate the pressure fluctuation phenomenon that occurs during the use of a peristaltic pump. The repeated pressure rise and fall process can easily cause fatigue of the filter material, leading to damage. This phenomenon often occurs during the filtration process. In this application, by conducting repeated pressure tests after constant pressure filtration, the fatigue strength of the filter material can be tested after it has withstood pressure for a certain period of time. This can provide a higher degree of simulation of the problems encountered in the actual production and preparation of the filter material.

[0020] More preferably, the test cycle of repeated pressure experiments includes a normal test cycle and a high-pressure test cycle, wherein the high-pressure section of the high-pressure test cycle has a pressure of 1.2 to 2 times the standard pressure.

[0021] In the above scheme, an additional high-pressure test process is added to the pressure repeated test experiment. The single high pressure can simulate the sudden high pressure phenomenon caused by airflow fluctuation, power fluctuation and liquid flow fluctuation during the normal pressure repeated process of the peristaltic pump. Considering that the normal operation of the peristaltic pump and the sudden situation of it have different effects on the filter material, the above operating pressure setting can better simulate the pressure fluctuation in the actual production process, and thus more objectively evaluate the performance of the filter material during filtration.

[0022] More preferably, the number of high-voltage test cycles is 2 to 5, and at least 2 ordinary test cycles are set between adjacent high-voltage test cycles.

[0023] Under normal circumstances, sudden increases in pressure will not occur repeatedly during use. Therefore, high-pressure test cycles are intermittently performed using ordinary test cycles to prevent excessive pressure on the filter material, which could cause the filter material, which has good strength under normal use, to break down during testing.

[0024] Preferably, in all test cycles of the pressure repetition experiment, at least three atmospheric pressure test cycles are performed before the high-pressure test cycle.

[0025] In the above approach, a high-pressure test cycle is not performed at the very beginning of the pressure fluctuations because a sudden high-pressure test cycle would make the filter material more susceptible to breakdown, which does not reflect reality. In actual filtration processes, sudden high-pressure phenomena are rare; they are usually accidental occurrences during repeated pressure oscillations. Therefore, performing at least three atmospheric pressure test cycles before the high-pressure test cycle better simulates the process of the filter material under actual conditions.

[0026] More preferably, the duration of the low-pressure section is 20-60 seconds, the duration of the high-pressure section is no more than 10 seconds, and each pressurization and depressurization process does not exceed 10 seconds.

[0027] In the above scheme, maintaining a low-pressure period before the pressurization process, and controlling the pressurization and depressurization time within 10 seconds, allows for better application of filtration pressure to the filter material. This simulates the pressure state of the filter material during actual production, making its internal defects more easily exposed. The results also better simulate the more frequent pressure fluctuations encountered in actual use. Using a faster pressure adjustment speed during the pressurization and depressurization phases reduces the stress adaptation process of the filter material during testing, further improving the accuracy of the verification.

[0028] Preferably, the duration of the pressure interruption experiment in step S3 is 12 to 48 hours.

[0029] The above time range can better simulate the dwell time in the actual production and preparation process, and can also fully reflect the problems of filter materials.

[0030] Preferably, in step S2, the filter load is 0.5 to 0.8 times the total filter load.

[0031] By employing advanced constant-pressure filtration in step S2 to load the filter material to a certain capacity, the pressure interruption or repeated pressure test in step S3 is then conducted. After the filter material itself has undergone a high load, it is more prone to breakdown or leakage under sudden conditions. Therefore, this method better simulates the extreme conditions the filter material experiences in actual production, ensuring higher reliability during use. Simultaneously, the load in the above process should generally not be too large. This provides a margin for subsequent processing and allows the filter material to be replaced once the filtration process has progressed to a certain stage, at which point additional attention to the filter material's durability is unnecessary.

[0032] Preferably, the method further includes step S4, which involves top-washing the filter material with a blank buffer solution. The top-wash load is 0.1 to 0.2 times the total filter load in steps S1 to S3, and at least one detection point is set up during the top-washing process for verification.

[0033] In the above scheme, the top-washing conditions were verified. In actual production processes, top-washing refers to rinsing the filter material with a blank buffer solution after filtration to elute residual proteins and other target products from the filter material. Since the filter material has already undergone pressure interruption and pressure repetition experiments in the aforementioned steps, the top-washing experiment is essentially a process of continuing to rinse the filter material without further increasing the viral load. This step tests the filter material's ability to withstand continuous rinsing with the buffer solution without being broken down when it is already close to full load.

[0034] Preferably, an intermittent period is provided between step S3 and step S4, in which the filtration pressure is reduced to 0, and the duration of the intermittent period is not less than 10 minutes.

[0035] In the above scheme, setting an intermittent period before the topwash experiment better reflects the actual experimental procedures. Since solution replacement and other steps are required before the topwash stage, there is often a pause time. Therefore, setting an intermittent period can simulate actual working conditions. In the above scheme, the duration of the intermittent period is at least 10 minutes. This time allows for sufficient release of internal stress and also conforms to the actual time intervals in actual production processes. A longer interval would not affect the verification process.

[0036] In a further preferred embodiment, step S3 includes a recovery section before the intermittent section, wherein the calibration sample is subjected to constant pressure filtration at standard pressure, and the load of the recovery section is 0.1 to 0.2 times the total load under the initial constant pressure filtration state.

[0037] In the above scheme, the recovery section is used to restore the state of the filter material to a certain extent after repeated pressure and pressure interruption, so that it is freed from the special stress state after pressure interruption and pressure repetition. Considering that the overall state of the filter material is relatively stable between the backwashing stages of S4, setting up intermittent and recovery sections is more conducive to the simulation accuracy of the subsequent topwashing experiment.

[0038] Preferably, in step S4, several detection points are set, wherein the top wash load at the first detection point is 10-50 L / m. 2 At least one detection point is set at the end of the top washing stage.

[0039] In the above scheme, the sites detected at the first and last detection points are different. The main purpose of the first detection point is to test the durability of the filter material during the initial top washing process, while the last detection point is to verify the breakdown resistance of the filter material after all residual proteins in the filter material have been washed away. Since the proteins have been washed away, its internal stress structure is different from that in the first test, so two tests are required.

[0040] In summary, this application provides a method for verifying the filterability of filter materials, which can perform overall verification of filter materials in an integrated process. It can identify potential problems of filter materials in actual processes through a single experiment and simulate various unexpected situations in actual filtration, thereby better determining the performance of filter materials. Attached Figure Description

[0041] Figure 1 This is a flowchart of the detection process in Embodiment 1 of the present invention.

[0042] Figure 2 This is a flowchart of the detection process in Embodiment 2 of the present invention. Detailed Implementation

[0043] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0044] In the description of this invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0045] In the description of this invention, it should be noted that, unless otherwise explicitly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this invention based on the specific circumstances.

[0046] In the biopharmaceutical field, during the preparation of protein samples such as monoclonal antibodies, recombinant proteins, and vaccines, the removal of viruses primarily relies on filtration due to the inherent sensitivity of the feed solution to external factors. Virus removal filtration materials are typically nanofiltration membrane systems formed from PVDF, PES, regenerated cellulose, or other copolymers, designed for high throughput, low protein adsorption, and high chemical stability. Overall, the dynamic and static spatial distribution of virus removal filtration materials is approximately 20–50 nm.

[0047] In the process of achieving virus removal filtration, the load-bearing capacity and breakdown resistance of filter materials (especially membrane materials) are crucial. If membrane breakdown occurs during filtration, viruses from upstream can enter downstream, leading to filtration failure and contamination of the target product. Current technologies typically verify filter materials through experimental procedures such as high pressure, low pressure, high pH, ​​low pH, high conductivity, and high concentration. However, in practical use, it has been found that even if filter materials pass these verification methods, they still experience some damage during actual use, indicating that existing methods for testing filter membranes still have certain shortcomings.

[0048] Based on the above, the following embodiments are designed to validate various virus-removing filter membranes. In these embodiments, the actual filter material used for validation is a virus-removing needle. Considering that load capacity is required as the unit of measurement during validation, using a needle with a smaller actual membrane area can save feed solution, and its performance is similar to other filter materials, such as membrane packs. It should be noted that the experiments in this embodiment are only for validating the filter material itself and do not verify defects that may exist in the equipment after it has been manufactured.

[0049] Example 1: This example provides a method for verifying the filterability of virus-removing filter materials, which includes the following sequential verification steps:

[0050] S1. Set up the calibration sample;

[0051] S2. Determine the standard pressure according to the production process, and use the calibration sample to perform constant pressure filtration on the filter containing the filter material to be tested under the standard pressure.

[0052] S3. Based on step S2, adjust the inlet pressure to simulate a sudden pressure event experiment, including at least one set of pressure interruption experiments and at least one set of pressure repetition experiments.

[0053] S4. Based on step S3, use a different top washing solution for the top washing experiment.

[0054] The calibration samples are prepared according to the protein samples, antibodies or other samples involved in actual production and buffer solutions, and the corresponding concentration of spiked virus is added.

[0055] In this embodiment, the change in filtration pressure with load is as follows: Figure 1 As shown, the specific steps are as follows:

[0056] S2, constant pressure filtration pressure is 30psi, load capacity is 1000L / m 2 And with a load capacity of 800L / m 2 Set detection point 1.

[0057] S3. After step S2 is completed, a pressure interruption test, a transition section, and a pressure repetition test are sequentially set. In the pressure interruption test, the pressure is adjusted to 0 psi and maintained for 24 hours, then restored to 30 psi. Subsequently, in the transition section, filtration continues at a pressure of 30 psi to 1250 L / m³. 2 Then, repeated pressure tests were conducted until the filter reached 1200 L / m³. 2 At that time, set up detection point 2.

[0058] In the pressure cycling test, 10 pressure cycles were performed, including a normal cycle test and a high-pressure cycle test. In the normal cycle test, the pressure was gradually adjusted to 0 psi within 5 seconds, maintained for 30 seconds, and then the pressure was restored to 30 psi within 5 seconds. In the 4th and 9th cycles, a high-pressure cycle test was set up, in which the pressure was gradually adjusted to 0 psi within 5 seconds, maintained for 30 seconds, and then the pressure was adjusted to 45 psi within 5 seconds.

[0059] Between steps S3 and S4, a recovery section and an intermittent section are set, wherein filtration is continued at 30 psi in the recovery section until the filtration rate reaches 1500 L / m³. 2 The load is set, and a detection point 3 is set at the end of the recovery section. The intermittent section is after the recovery section, and the pressure is adjusted to 0Psi and maintained for 1 hour.

[0060] S4. During the topwash step, after the interval period, replace the buffer solution with a blank buffer solution for the topwash step. The total topwash volume is 200 L / m², and the buffer solution is 20 L / m². 2 100L / m 2 and 200L / m 2 Detection points 4, 5 and 6 are set up at each location.

[0061] Regarding the test samples, the spiked virus sample used was mouse parvovirus MVM with a viral titer of 1×10⁻⁶. 6 PFU / ml. Test samples were prepared according to the target product in actual production and adjusted to the corresponding pH value using phosphate buffer, TRIS buffer, or other buffer solutions.

[0062] For each detection point, the corresponding filtrate was collected, and titers were measured at all collection points according to the MVM virus plaque assay standard operating procedure. In addition, an interference experiment was set up to avoid affecting the evaluation of the virus clearance process. At the beginning of the interference experiment, the test sample was serially diluted with serum-free EMEM / HEPES medium. Three different concentrations of virus stock solution (0.1% v / v) were added to each dilution of the interference test sample. Additionally, three aliquots of serum-free EMEM / HEPES medium with approximately 0.1% v / v of virus stock solution (three concentrations) were added as positive controls. Serum-free EMEM / HEPES medium without added virus served as a negative control. Each generated test sample was analyzed in triplicate according to the corresponding interference experiment procedure.

[0063] Example 2: This example, based on Example 1, swaps the pressure interruption experiment and the pressure repetition experiment in step S3. Specifically, the change in filtration pressure with load is as follows: Figure 2 As shown.

[0064] Example 3: In this example, some experimental groups were set up to test and adjust the pressure repeatedly. Specifically, the pressure settings for the repeated pressure experiments in different experimental groups are shown in Table 1.

[0065] Table 1

[0066]

[0067] Example 4: In this example, the difference from Example 1 is that a recovery section is not set. Considering that the recovery section cannot be completely eliminated in order to set up the detection point, the load of the recovery section is actually set to 20L / m. 2 .

[0068] Example 5: In this example, the difference from Example 1 is that no additional intermittent period is set. It should be noted that in this step, since the feed liquid needs to be replaced before the top washing step, a short pause still exists, and the overall intermittent period time does not exceed 5 minutes.

[0069] Example 6: The total load of constant pressure filtration and the load of subsequent recovery section in step S2 were adjusted. The specific experimental groups are shown in Table 2.

[0070] Table 2

[0071]

[0072]

[0073] To address the filter material issues reported by customers in the above embodiments, testing was conducted on each batch of filter membranes. Ten parallel tests were performed in each experimental group, and the number of samples showing breakdown at different test points was counted. Specific samples are shown in Table 3.

[0074] Table 3

[0075] A PVDF Dual resistance 0.9 No problem B RC Fusion protein 4.0 It is prone to breakdown after pressure interruption. C PES monoclonal antibodies 12.0 Repeated pressure can easily cause breakdown. D PES Fusion protein 3.9 The top wash stage is prone to breakdown.

[0076] For the samples in Example 3, the experimental groups in Examples 1 to 6 were used to conduct verification experiments on the samples in the above groups. The number of samples that were detected to have breakdown at each detection point is shown in Table 4.

[0077] Table 4

[0078]

[0079]

[0080] Additionally, the following comparison example is provided:

[0081] Comparative Example: In this comparative example, constant pressure filtration testing, top-wash filtration testing, pressure interruption testing, and repeated pressure testing were conducted using separate experiments, as detailed below:

[0082] Constant pressure filtration test: directly at 30psi and 1500L / m 2 The load is filtered, and detection point 1 is set at the end of the detection.

[0083] Top-wash filtration test: Following the constant pressure filtration test, a top-wash test is performed directly afterward. The pressure during top washing is 30 psi and 20 L / m. 2 100L / m 2 and 200L / m 2 Detection points 2 to 4 are set at the locations respectively.

[0084] Pressure interruption detection: The sample is first filtered at 30 psi at a rate of 200 L / m³. 2 The load was initially set, then the pressure was interrupted for 24 hours, then restored to 30 psi, and filtration continued at 200 L / m³. 2 And set up detection point 5.

[0085] Repeated pressure experiments: The sample was first filtered at 30 psi at a rate of 200 L / m³. 2 The load capacity was then tested repeatedly with the pressure as described in Example 1, and then the pressure was restored to 30 psi for filtration of 200 L / m³. 2 The load capacity was measured, and 6 detection points were set.

[0086] In the above experiments, each group of experiments used 10 samples for parallel testing, and the number of downstream breakdown samples was recorded.

[0087] The membrane breakdown phenomenon of samples A, B, C, and D in the control example is shown in Table 5.

[0088] Table 5

[0089]

[0090] In Tables 4 and 5, blank spaces indicate that no breakdown samples occurred during the process.

[0091] Through the above experiments, it is clear that compared to testing each stage individually, the integrated testing method shown in Example 1 can better reflect the breakdown effect of the filter material during actual production. Compared to the separate testing method used in the comparative example, it can better measure the membrane's performance under various extreme conditions, and thus better reflect the actual problems of the membrane.

[0092] Specifically, in the comparison between Example 1 and Example 2, it can be seen that, compared to testing each experimental group separately, the continuous testing process in this application can better simulate the problems encountered by the membrane materials of the four samples in actual production. For example, in Example 1 and the control example, sample B, after undergoing constant pressure filtration, more fully reflects the problems encountered in actual production during pressure interruption. In Example 6-2, it can be seen that when the loading of the preceding constant pressure filtration is too low, the membrane itself does not receive sufficient pressure during pressure interruption, failing to fully demonstrate the defects inherent in the membrane. For sample D, by comparing Example 1 and the control example, it can also be seen that after the continuous state simulation in Example 1, the problems encountered by the membrane during the top washing process are more easily reflected. In Control Example 1, although the loading before top washing is the same, it is all in an ideal state beforehand, failing to fully reflect the problems encountered by the filter material in actual use, thus its detection rate during the top washing stage is significantly reduced.

[0093] For sample C, it can be seen that compared to comparative example 1, example 1 has a higher detection rate for the problems present in the sample. Comparing examples 1 and 3-1 to 3-9, it can be seen that adding high-pressure test cycles in the pressure repetition experiment better reflects the actual problems. In example 3-3, which does not include high-pressure test cycles, the detection rate in the pressure repetition experiment is significantly reduced, failing to fully simulate the problems that occur in the membrane itself during actual production. In example 3-2, it can be seen that when two high-pressure test cycles are directly connected, the membrane itself is subjected to excessive pressure in a short period of time, causing even a filter membrane that would not be punctured under normal conditions to puncture under this state. In examples 3-6 and 3-7, it is equivalent to a sudden high-low pressure oscillation under normal pressure. This situation is relatively rare in actual production and can easily lead to excessive pressure on the membrane itself, thus easily causing a qualified filter membrane to be detected as punctured during testing.

[0094] Example 7: Based on Example 1, this example further verifies sample A through the following experiments:

[0095] 1. High-pressure filtration experimental group and low-pressure filtration experimental group: The samples were filtered at high pressure of 60 psi and low pressure of 10 psi respectively, to a filter density of 1500 L / m³. 2 At loading, collect and analyze the downstream filtrate, then rinse with buffer solution until the solution reaches 20 L / m³. 2 The downstream filtrate was collected and tested.

[0096] 2. High conductivity filtration experimental group and acid-base filtration experimental group: Prepare 4 groups of samples A, then adjust the pH of two of them to 4.5 and the pH of the other two to 8.0 using buffer solution; for each test sample, take one sample each of pH 4.5 and pH 8.0, and adjust the conductivity to 5 mS / cm with 4M NaCl; then take one sample each of pH 4.5 and pH 8.0, and adjust the conductivity to 50 mS / cm with 4M NaCl. The virus-spikened samples were then filtered at a pressure of 30 Psi to 1500 L / m³. 2 Collect the downstream filtrate and stop filtration. Then, perform a top wash with buffer solution until the solution reaches 20 L / m³. 2 The downstream filtrate was collected and tested.

[0097] 3. High-concentration filtration experimental group: For sample A, use three times the initial concentration (in the actual experiment, since the raw material solution of sample A needs to be prepared by dilution, it is only necessary to reduce the amount of buffer solution used during the dilution process), filter at a filtration pressure of 30 Psi to 1500 L / m2, collect the downstream filtrate and stop filtration, then use buffer solution for top washing, top wash to 20 L / m2, collect the downstream filtrate and test.

[0098] The above experimental steps are a supplement to Example 1, which can verify the performance of the filter membrane under further extreme conditions.

[0099] The above embodiments are merely preferred embodiments of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-substantial changes and substitutions made by those skilled in the art based on the present invention shall fall within the scope of protection claimed by the present invention.

Claims

1. A method for verifying the filterability of virus-removing filter materials, characterized in that, It includes the following consecutive steps: S1. Set up the calibration sample; S2. Determine the standard pressure according to the production process, and use the calibration sample to perform constant pressure filtration on the filter containing the filter material to be tested under the standard pressure. S3. Based on step S2, adjust the inlet pressure to simulate a sudden pressure event experiment, including at least one set of pressure interruption experiments and at least one set of pressure repetition experiments. In step S3, a pressure interruption test is performed first, followed by a pressure repetition test. The pressure interruption test and the pressure repetition test include a transition section for filtration under standard pressure. The load of this transition section is 0.1 to 0.2 times the total load of steps S1 to S3, and at least one detection point is set in the transition section. The pressure repetition test includes 5 to 30 test cycles. For any test cycle, it includes at least a high-pressure section and a low-pressure section. The pressure of the high-pressure section is not less than 0.8 times the standard pressure, and the pressure of the low-pressure section is not higher than 5 psi. The test cycles of the pressure repetition test include ordinary test cycles and high-pressure test cycles. The pressure of the high-pressure section in the high-pressure test cycle is 1.2 to 2 times the standard pressure. In steps S2 to S3, a detection point is set in any test group or downstream of the test group to detect whether the filter material is broken down; The method also includes step S4, which involves top-washing the filter material with a blank buffer solution. The top-wash load is 0.1 to 0.2 times the total filter load in steps S1 to S3, and at least one detection point is set for verification during the top-washing process. Between steps S3 and S4, an intermittent section is set, in which the filter pressure is reduced to 0, and the duration of the intermittent section is not less than 10 minutes. Before the intermittent section in step S3, a recovery section is set, in which the calibration sample is filtered at a constant pressure using a standard pressure, and the load of the recovery section is 0.1 to 0.2 times the total load.

2. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, The load on the transition section before this detection point shall not be less than 50% of the total load on the transition section.

3. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, The number of high-voltage test cycles is 2 to 5, and at least 2 normal test cycles are set between adjacent high-voltage test cycles.

4. The method for verifying the filterability of a virus-removing filter material according to claim 3, characterized in that, In all test cycles of the pressure repetition experiment, at least three atmospheric pressure test cycles are performed before the high pressure test cycle.

5. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, The duration of the low-pressure section is 20 to 60 seconds, the duration of the high-pressure section is no more than 10 seconds, and each pressurization and depressurization process does not exceed 10 seconds.

6. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, The duration of the pressure interruption experiment described in step S3 is 12 to 48 hours.

7. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, In step S2, the filter load is 0.5 to 0.8 times the total filter load of steps S1 to S3.

8. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, In step S4, several detection points are set, wherein the top wash load at the first detection point is 10-50 L / m2, and at least one detection point is set at the end of the top wash stage.

9. The method for verifying the filterability of a virus-removing filter material according to claim 1, characterized in that, The verification method also includes any number of experimental groups among the high-pressure filtration experimental group, low-pressure filtration experimental group, acid-base filtration experimental group, high-concentration filtration experimental group, and high-conductivity filtration experimental group.

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