Cleaning method and storage method of ultrafiltration membrane package

Abstract

The application discloses a kind of cleaning method of ultrafiltration membrane package, preservation method.The cleaning method includes the following steps: ultrafiltration membrane package is sequentially cleaned by first water, 0.5M NaOH solution, then first 0.1M NaOH solution cleaning or second water cleaning, namely obtained.Ultrafiltration membrane package can be stored in 0.1M NaOH solution after using the above cleaning method, namely obtained;Or, after the second water cleaning of ultrafiltration membrane package, it is cleaned again with 0.1M NaOH solution, and stored in 0.1M NaOH solution.In the application, by using 0.1M NaOH solution, ultrafiltration membrane package is temporarily stored in ultrafiltration system, which can well solve the problem of production connection, and cannot clean ultrafiltration membrane package in time, leading to irreversible damage to membrane package.In the application, long-term storage of ultrafiltration membrane package is realized by using 0.1M NaOH solution.

Description

Technical Field

[0001] This invention relates to a method for cleaning and storing ultrafiltration membrane packs. Background Technology

[0002] The mechanism of ultrafiltration refers to the combined effects of mechanical sieving at the membrane surface, pore blockage, and adsorption at the membrane surface and pores, with sieving being the primary mechanism. Ultrafiltration membrane packs are the optimal tangential flow filtration devices for the separation of monoclonal antibodies and therapeutic protein drugs. This technologically advanced, high-performance membrane pack is ideally suited for today's high-concentration therapeutic antibodies.

[0003] Applications of ultrafiltration membrane packs include: bacterial collection, cell clarification filtration, concentration of biological macromolecules, removal of impurity molecules, separation, continuous dialysis of equal volume, and removal of pyrogens from culture media.

[0004] Ultrafiltration membrane packs are typically stored in 0.1M NaOH solution. However, if the membrane pack is exposed to a dirty environment for an extended period after the ultrafiltration dialysis process, it may cause pore blockage and affect the membrane pack's permeability.

[0005] Therefore, how to improve the cleaning method of ultrafiltration membrane packs to maintain good permeability is a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0006] The technical problem to be solved by the present invention is to overcome the technical defects of the existing ultrafiltration membrane pack preservation or cleaning methods, which either cannot clean the ultrafiltration membrane pack in time, resulting in irreversible damage to the membrane pack, or after long-term storage, problems such as membrane hydrolysis, microbial erosion, freezing and shrinkage deformation failure occur. The present invention provides a cleaning method and preservation method for ultrafiltration membrane packs.

[0007] In existing technologies, ultrafiltration membrane packs are typically stored using 0.1M NaOH solution. However, prolonged exposure to a contaminated environment after ultrafiltration dialysis can cause pore blockage and affect membrane permeability. Therefore, this invention provides a method for storing ultrafiltration membrane packs using 0.1M NaOH solution.

[0008] During the research and development process, the inventors discovered that in the ultrafiltration dialysis process, if short-term storage of the ultrafiltration membrane pack is required, the entire tangential flow filtration system can be rinsed with 0.1M NaOH solution, and then the ultrafiltration membrane pack can be stored on the tangential flow filtration system for a short period of time. Afterwards, the membrane pack is rinsed with WFI (water for injection), the water flux after use is tested, and finally the membrane pack is rinsed with 0.1M NaOH solution. Then the membrane pack is removed / disassembled from the tangential flow filtration system and soaked in 0.1M NaOH solution for long-term storage.

[0009] This invention provides a method for cleaning an ultrafiltration membrane pack, comprising the following steps:

[0010] The ultrafiltration membrane pack is first washed with water, then washed with 0.5M NaOH solution, and then washed with 0.1M NaOH solution or water for the second time.

[0011] In this invention, the ultrafiltration membrane pack can be a conventional ultrafiltration membrane pack in the art.

[0012] In this invention, before the ultrafiltration membrane pack is first washed with water, the system and the membrane pack can be equilibrated with dialysis buffer. Then, the protein feed solution is added and ultrafiltration is performed twice to increase the protein concentration to a suitable concentration for dialysis. Subsequently, the high-concentration protein is subjected to a 7-11 fold dialysis operation.

[0013] In this invention, before the first water wash, the fouling environment of the ultrafiltration membrane pack may be as follows: the system and the membrane pack contain a small amount of protein (e.g., trace protein) as well as impurities such as HCP (host cell protein), DNA, aggregates and fragments.

[0014] In this invention, the first water cleaning is a mechanical cleaning of the ultrafiltration membrane pack, which can initially remove water-soluble dirt from the system and the membrane pack.

[0015] Generally speaking, in order to ensure the removal of soluble residues from the membrane pack and equipment as much as possible, the retention time for dirty equipment should be ≤2 hours.

[0016] In this invention, water for injection (WFI) can be used for the water cleaning process.

[0017] In this invention, when the reflux end of the ultrafiltration membrane pack is rinsed with water for the first time, the feed flow rate of the water rinsing can be 200-360 LHM.

[0018] In this invention, when the return end of the ultrafiltration membrane pack is rinsed with water for the first time, the rinsing volume of the water rinse can be ≥32L / m³. 2 .

[0019] In this invention, when the reflux end of the ultrafiltration membrane pack is rinsed with water for the first time, the inlet pressure of the reflux end can be ≤2.0 bar.

[0020] In this invention, when the reflux end of the ultrafiltration membrane pack is rinsed with water for the first time, the pressure at the reflux end can be ≤1.0 bar.

[0021] In this invention, when the permeate end of the ultrafiltration membrane pack is rinsed with water for the first time, the feed flow rate of the water rinsing can be 200-360 LHM.

[0022] In this invention, when the permeate end of the ultrafiltration membrane pack is rinsed with water for the first time, the rinsing volume of the water rinse can be ≥32L / m³. 2 .

[0023] In this invention, when the permeate end of the ultrafiltration membrane pack is rinsed with water for the first time, the inlet pressure of the permeate end can be ≤2.0 bar.

[0024] In this invention, when the permeate end of the ultrafiltration membrane pack is rinsed with water for the first time, the pressure at the reflux end can be ≤1.0 bar.

[0025] In this invention, cleaning with 0.5M NaOH solution can be used to circulate and sterilize the ultrafiltration membrane pack.

[0026] In this invention, the washing time with 0.5M NaOH solution can be ≥30 min.

[0027] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with 0.5M NaOH solution, the feed flow rate of the 0.5M NaOH solution can be 200-360 LHM.

[0028] In this invention, when using a 0.5M NaOH solution to clean the reflux end of the ultrafiltration membrane pack, the rinsing volume of the 0.5M NaOH solution can be ≥22 L / m³. 2 .

[0029] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with 0.5M NaOH solution, the inlet pressure of the reflux end can be ≤2.0 bar.

[0030] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with 0.5M NaOH solution, the pressure at the reflux end can be ≤1.0 bar.

[0031] In this invention, when the permeate end of the ultrafiltration membrane pack is cleaned with 0.5M NaOH solution, the feed flow rate of the 0.5M NaOH solution can be 200-360 LHM.

[0032] In this invention, when using a 0.5M NaOH solution to clean the permeate end of the ultrafiltration membrane pack, the rinsing volume of the 0.5M NaOH solution can be ≥22 L / m³. 2 .

[0033] In this invention, when the permeate end of the ultrafiltration membrane pack is cleaned with 0.5M NaOH solution, the inlet pressure of the permeate end can be ≤2.0 bar.

[0034] In this invention, when the permeate end of the ultrafiltration membrane pack is cleaned with 0.5M NaOH solution, the pressure at the reflux end can be ≤1.0 bar.

[0035] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with a first 0.1M NaOH solution, the feed flow rate of the 0.1M NaOH solution can be 200-360 LHM.

[0036] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with a first 0.1M NaOH solution, the rinsing volume of the 0.1M NaOH solution can be ≥22L / m³. 2 .

[0037] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with a first 0.1M NaOH solution, the inlet pressure of the reflux end can be ≤2.0 bar.

[0038] In this invention, when the reflux end of the ultrafiltration membrane pack is cleaned with a first 0.1M NaOH solution, the pressure at the reflux end can be ≤1.0 bar.

[0039] In this invention, when the permeate end of the ultrafiltration membrane pack is cleaned with a 0.1M NaOH solution for the first time, the feed flow rate of the 0.1M NaOH solution can be 200-360 LHM.

[0040] In this invention, when using 0.1M NaOH solution to clean the permeate end of the ultrafiltration membrane pack, the rinsing volume of the 0.1M NaOH solution can be ≥22 L / m³. 2 .

[0041] In this invention, when the permeate end of the ultrafiltration membrane pack is cleaned with a first 0.1M NaOH solution, the inlet pressure of the permeate end can be ≤2.0 bar.

[0042] In this invention, when the permeate end of the ultrafiltration membrane pack is cleaned with a first 0.1M NaOH solution, the pressure at the reflux end can be ≤1.0 bar.

[0043] In this invention, the process conditions for the second water cleaning can be the same as those for the first water cleaning described above.

[0044] In one embodiment of the present invention, the cleaning method of the ultrafiltration membrane pack includes the following steps:

[0045] 1. Use WFI (water for injection) to flush the ultrafiltration membrane pack, feed tank, manifold, and other pipelines to remove soluble residues from the equipment, and then drain the WFI (water for injection) from the equipment.

[0046] 2. Perform online cleaning (CIP, circulation ≥30 min) on the ultrafiltration membrane pack, feed tank, manifold, and other pipelines using 0.5M NaOH solution; after CIP, drain the 0.5M NaOH solution from the feed tank.

[0047] 3. Use 0.1M NaOH solution to flush the ultrafiltration membrane pack, feed tank, manifold, and other pipelines. After flushing, the ultrafiltration membrane pack can be temporarily stored in the tangential flow filtration system.

[0048] In one embodiment of the present invention, if the ultrafiltration membrane pack is to be stored for a short period of time, the 0.1M NaOH solution in the equipment can be drained after step 3 above, and then the ultrafiltration membrane pack, the equipment feed tank, the manifold, and other pipelines can be flushed with WFI (water for injection), and then the WFI (water for injection) in the equipment can be drained.

[0049] In one embodiment of the present invention, the cleaning method of the ultrafiltration membrane pack includes the following steps:

[0050] 1. Use WFI (water for injection) to flush the ultrafiltration membrane pack, feed tank, manifold, and other pipelines to remove soluble residues from the equipment, and then drain the WFI (water for injection) from the equipment.

[0051] 2. Perform online cleaning (CIP, circulation ≥30 min) on the ultrafiltration membrane pack, feed tank, manifold, and other pipelines using 0.5M NaOH solution; after CIP, drain the 0.5M NaOH solution from the feed tank.

[0052] 3. Use WFI (water for injection) to test the standard water flux of the membrane pack to check whether the filter membrane is clean, and then drain the WFI (water for injection) from the equipment;

[0053] 4. Use 0.1M NaOH solution to store the ultrafiltration membrane pack in the system. Then drain the 0.1M NaOH solution from the equipment, remove the membrane pack, fill the membrane pack box with 0.1M NaOH solution, and immerse the ultrafiltration membrane pack in the 0.1M NaOH solution for long-term storage.

[0054] This invention provides a method for preserving an ultrafiltration membrane pack, comprising the following steps:

[0055] The ultrafiltration membrane pack is cleaned using the aforementioned cleaning method, first cleaned with 0.1M NaOH solution, and then stored in 0.1M NaOH solution to obtain the final product.

[0056] Alternatively, the ultrafiltration membrane pack can be cleaned using the aforementioned cleaning method, followed by a second water wash and then a second wash with 0.1M NaOH solution to obtain the final product.

[0057] In this invention, after the first rinse with 0.1M NaOH solution, the tangential flow filtration system and the ultrafiltration membrane pack can be temporarily stored in 0.1M NaOH solution. When the cleaning process is restarted, the 0.1M NaOH solution in the equipment can be drained.

[0058] The short-term storage time is generally ≤24h.

[0059] The advantage of short-term storage is that it allows for prioritizing more critical process operations in subsequent steps. Generally, systems and membrane packs have a dirt retention time (≤2 hours). If this time is exceeded, dirt becomes difficult to remove, potentially causing irreversible damage to the tangential flow filtration system and ultrafiltration membrane pack. Therefore, short-term storage methods hold great promise for ultrafiltration dialysis processes.

[0060] In this invention, the 0.5M NaOH solution can be removed from the equipment and membrane pack after a second water rinse, and after a second 0.1M NaOH solution rinse, the ultrafiltration membrane pack can be soaked in 0.1M NaOH solution for long-term storage.

[0061] The process conditions for the second water cleaning can be the same as those for the first water cleaning.

[0062] The process conditions for the second 0.1M NaOH solution cleaning can be the same as those for the first 0.1M NaOH solution cleaning.

[0063] After the second 0.1M NaOH solution cleaning, it can be further cleaned with water and dried a third time.

[0064] The process conditions for the third water wash can be the same as those for the first water wash.

[0065] The third water wash may also include rinsing the equipment's feed tank, manifold, and other pipelines with WFI (water for injection) to remove residual 0.1M NaOH solution from the equipment.

[0066] The drying process can be a conventional drying process in the field, such as connecting a CDA and adjusting it to 2.0 bar, and using a 2.0 bar CDA to continuously purge the liquid tank, manifold, and other pipelines in sections.

[0067] After drying, the air valve can be closed, and then all inlets and outlets can be sealed to complete the cleaning process.

[0068] In this invention, TMP, or average pressure difference across the membrane, is defined as: TMP = (feed pressure + concentrate pressure) / 2 - product water pressure.

[0069] In this invention, WFI refers to water for injection.

[0070] In this invention, CDA refers to clean and dry air.

[0071] In this invention, LMH refers to liters per square meter per hour; where "square meter" is the area of ​​the membrane pack.

[0072] In this invention, L / m 2 It refers to liters per square meter; where "square meter" is the area of ​​the membrane package.

[0073] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of the present invention.

[0074] The reagents and raw materials used in this invention are all commercially available.

[0075] The positive and progressive effects of this invention are as follows:

[0076] In this invention, the ultrafiltration membrane pack is temporarily stored in the ultrafiltration system using a 0.1M NaOH solution. This effectively solves the problem of irreversible damage to the membrane pack caused by the inability to clean it in a timely manner due to production continuity issues. Furthermore, the use of a 0.1M NaOH solution for long-term storage effectively prevents membrane hydrolysis, microbial erosion, freezing, and shrinkage / deformation failure.

[0077] Therefore, the ultrafiltration membrane package preservation technology of the present invention can be used for short-term and long-term preservation of ultrafiltration membrane packages in tangential flow filtration systems. Attached Figure Description

[0078] Figure 1 The results of TOC (Total Organic Carbon) testing of the system and membrane pack after the cleaning procedure in Example 2 are shown.

[0079] Figure 2 The TOC (Total Organic Carbon) test results of WFI (water for injection) used in the cleaning procedure of Example 2 are shown. Detailed Implementation

[0080] The present invention is further illustrated below by way of embodiments, but the invention is not limited to the scope of the embodiments described herein. Experimental methods in the following embodiments that do not specify specific conditions were performed according to conventional methods and conditions, or as selected according to the product instructions.

[0081] In the following embodiments, the terms are explained as follows:

[0082] Chemical cleaning (CIP): A prepared cleaning solution or bactericide / chemical agent is introduced into the ultrafiltration system from the influent side and then returned to the cleaning tank from the concentrate and permeate sides for soaking and circulation to effectively remove ultrafiltration contaminants. For example, the 0.5M NaOH solution in step 2 of Example 1 is used as the chemical cleaning agent.

[0083] TMP, or average pressure difference across the membrane, is calculated as: TMP = (feed pressure + concentrate pressure) / 2 - product water pressure.

[0084] WFI: Water for Injection.

[0085] CDA: Clean and dry air.

[0086] LMH: Liters per square meter per hour; where "square meter" refers to the area of ​​the membrane pack.

[0087] L / m 2 : Liters per square meter; where "square meters" refers to the area of ​​the membrane package.

[0088] The models and structures of tangential flow filtration systems commonly used in ultrafiltration membrane packs in this field are applicable to the cleaning and preservation methods described in this application.

[0089] In the following examples, prior to CIP (Clean-In-Place), the system and membrane pack were equilibrated with dialysis buffer. Then, the protein feed solution was added and subjected to two ultrafiltrations to raise the protein concentration to a suitable level for dialysis. Subsequently, the high-concentration protein was subjected to fold-up (7-11 times) dialysis. Contamination environment: The system and membrane pack contain small amounts of residual protein (typically trace amounts), as well as impurities such as HCP (host cell protein), DNA, aggregates, and fragments.

[0090] Example 1

[0091] Short-term storage method for ultrafiltration membrane packs

[0092] 1. Pre-CIP water flushing. Use water for injection to flush the return end: feed flow rate: 200-360 L / min, flushing volume: ≥32 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeation end with water for injection: feed flow rate: 200-360 L / min, flushing volume: ≥ 32 L / m³ 2 Inlet pressure ≤ 2.0 bar, return pressure ≤ 1.0 bar.

[0093] 2. CIP sterilization. Rinse the reflux end with 0.5M NaOH solution: feed flow rate: 200-360 L / m³, rinsing volume: ≥22 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeate end with 0.5M NaOH solution: feed flow rate: 200-360 L / m³, flushing volume: ≥ 22 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar. Cleaning time with 0.5M NaOH solution ≥ 30 min.

[0094] 3. Store temporarily. If necessary, flush the reflux end with 0.1M NaOH solution: feed flow rate: 200-360 L / m³, flushing volume: ≥22 L / m³2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeate end with 0.1M NaOH solution: feed flow rate: 200-360 L / m³, flushing volume: ≥ 22 L / m³ 2 The inlet pressure should be ≤2.0 bar, and the reflux pressure ≤1.0 bar. At this point, the tangential flow filtration system and ultrafiltration membrane pack can be temporarily stored. When the cleaning process restarts, drain the 0.1M NaOH solution from the equipment.

[0095] Example 2

[0096] Long-term preservation method of ultrafiltration membrane pack

[0097] 1. Pre-CIP water flushing. Use water for injection to flush the return end: feed flow rate: 200-360 L / min, flushing volume: ≥32 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeation end with water for injection: feed flow rate: 200-360 L / min, flushing volume: ≥ 32 L / m³ 2 Inlet pressure ≤ 2.0 bar, return pressure ≤ 1.0 bar.

[0098] 2. CIP sterilization. Rinse the reflux end with 0.5M NaOH solution: feed flow rate: 200-360 L / m³, rinsing volume: ≥22 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeate end with 0.5M NaOH solution: feed flow rate: 200-360 L / m³, flushing volume: ≥ 22 L / m³ 2 Inlet pressure ≤ 2.0 bar, return pressure ≤ 1.0 bar.

[0099] 3. Post-CIP water rinsing. Rinse the return end with water for injection: feed flow rate: 200-360 L / min, rinsing volume: ≥32 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeation end with water for injection: feed flow rate: 200-360 L / min, flushing volume: ≥ 32 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar. Cleaning time with 0.5M NaOH solution ≥ 30 min.

[0100] 4. Water Flux Test. Keep both the return and permeate lines fully open. Adjust the pump speed and valves to maintain the TMP transmembrane pressure and ΔP within a suitable range. TMP transmembrane pressure: 0.8 ± 0.2 bar; ΔP (ΔP = P1 - P2) (P1 is the inlet pressure, P2 is the return pressure): 0.5 ± 0.2 bar. After the flow rates at the return and permeate ends stabilize, record the weight and temperature of the WFI permeated through the permeate end for a period of time (generally 2 minutes).

[0101] Standard water flux = (WFI weight at the end - WFI weight at the beginning) * temperature correction factor at WFI temperature during testing / (duration * total membrane area * TPM). The standard water flux needs to be compared with the water flux before use. If the ratio of "standard water flux after use / water flux before use" is between 0.8 and 1.2, it indicates that the cleaning was effective. If it is outside this range, it indicates that the cleaning may have been incomplete or the membrane pack may have been damaged.

[0102] 5. Storage. Rinse the reflux end with 0.1M NaOH solution: feed flow rate: 200-360 L / m³, rinsing volume: ≥22 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeate end with 0.1M NaOH solution: feed flow rate: 200-360 L / m³, flushing volume: ≥ 22 L / m³ 2 The inlet pressure is ≤2.0 bar, and the reflux pressure is ≤1.0 bar. Then, drain the 0.1 M NaOH solution from the equipment, remove the membrane pack, fill the membrane pack box with 0.1 M NaOH solution, and immerse the ultrafiltration membrane pack in the 0.1 M NaOH solution for long-term storage.

[0103] 6. Rinse with water before drying. Rinse the return end with water for injection: feed flow rate: 200-360 L / m³, rinsing volume: ≥32 L / m³ 2 Inlet pressure ≤ 2.0 bar, reflux pressure ≤ 1.0 bar; flush the permeation end with water for injection: feed flow rate: 200-360 L / min, flushing volume: ≥ 32 L / m³ 2 The inlet pressure is ≤2.0 bar, and the return pressure is ≤1.0 bar. This flushing step is for the ultrafiltration system equipment.

[0104] 7. Drying. Open the level control pump cover (peristaltic pump cover), connect the CDA and adjust it to 2.0 bar. Use the 2.0 bar CDA to continuously purge the feed tank, manifold, and other pipelines in sections.

[0105] 8. After drying, close the air valve and then seal all inlets and outlets.

[0106] Example 1

[0107] In alkaline solutions, proteins can be hydrolyzed into soluble oligomers or free amino acids. Therefore, during the cleaning validation process for biopharmaceuticals, limits for active substances are not directly set or detected; instead, analytical methods such as TOC (Total Organic Carbon) are used to detect protein residues (or fragments thereof). If non-specific methods such as TOC are used to detect active substance-related residues, it should be noted that the "true" value of protein residues after cleaning may be significantly lower because TOC measures all sources of organic carbon, not just active protein residues.

[0108] In this invention, the residues of active substances and degraded pollutants can meet the following standards: TOC rinsing: ≤ blank TOC (WFI TOC) + 1 ppm.

[0109] TOC was measured using a Sievers 500RL TOC analyzer.

[0110] Figure 1 The test results for the system and membrane pack after cleaning with WFI (water for injection) are as follows: After the ultrafiltration membrane pack in Example 2 is rinsed with water after CIP in step 3. Figure 2 The blank control group used the same batch of water for injection (WFI) as the one used in Example 1 to clean the membrane pack. This WFI had not been used to clean the system before and therefore served as a blank control for the WFI used to clean the membrane pack. If the total organic carbon (TOC) was ≤ blank control group + 1 ppm, the cleaning was considered successful. Figure 1 and Figure 2 As can be seen, 289ppb≤166ppb+1ppm, therefore, the cleaning result is passed, that is, the cleaning expectation is achieved.

Claims

1. A method for preserving an ultrafiltration membrane pack, characterized in that, It includes the following steps: The ultrafiltration membrane pack is sequentially washed with water, then with 0.5M NaOH solution, and then with 0.1M NaOH solution. After the first 0.1M NaOH solution wash, it is stored in 0.1M NaOH solution to obtain the final product. Alternatively, the ultrafiltration membrane pack can be sequentially washed with the first water wash, then with the 0.5M NaOH solution, followed by a second water wash, and then a second wash with the 0.1M NaOH solution to obtain the final product. Before the first water wash, trace amounts of protein, HCP, DNA, aggregates, and fragments remain in the ultrafiltration membrane pack. When the reflux end of the ultrafiltration membrane pack is rinsed with water for the first time, the feed flow rate for the water rinsing is 200-360 LHM. When the permeate end of the ultrafiltration membrane pack is rinsed with water for the first time, the feed flow rate for the water rinsing is 200-360 LHM. When cleaning the reflux end of the ultrafiltration membrane pack with 0.5M NaOH solution, the feed flow rate of the 0.5M NaOH solution is 200-360 L / m³, and the rinsing volume of the 0.5M NaOH solution is ≥22 L / m³. 2 The inlet pressure of the reflux end is ≤2.0 bar, and the reflux end pressure is ≤1.0 bar; When cleaning the permeate end of the ultrafiltration membrane pack with 0.5M NaOH solution, the feed flow rate of the 0.5M NaOH solution is 200-360 L / m³, and the rinsing volume of the 0.5M NaOH solution is ≥22 L / m³. 2 The inlet pressure at the permeation end is ≤2.0 bar, and the pressure at the return end is ≤1.0 bar; When using a 0.1M NaOH solution to clean the reflux end of the ultrafiltration membrane pack for the first time, the feed flow rate of the 0.1M NaOH solution is 200-360 L / m³, and the flushing volume of the 0.1M NaOH solution is ≥22 L / m³. 2 The inlet pressure of the reflux end is ≤2.0 bar, and the reflux end pressure is ≤1.0 bar; When using a 0.1M NaOH solution to clean the permeate end of the ultrafiltration membrane pack for the first time, the feed flow rate of the 0.1M NaOH solution should be 200-360 L / m³, and the flushing volume of the 0.1M NaOH solution should be ≥22 L / m³. 2 The inlet pressure at the permeation end is ≤2.0 bar, and the pressure at the return end is ≤1.0 bar; The process conditions for the second water cleaning are the same as those for the first water cleaning.

2. The method for preserving the ultrafiltration membrane pack as described in claim 1, characterized in that, When the return end of the ultrafiltration membrane pack is rinsed with water for the first time, the rinsing volume of the water rinse is ≥32L / m³. 2 The inlet pressure of the reflux end is ≤2.0 bar, and the reflux end pressure is ≤1.0 bar.

3. The method for preserving the ultrafiltration membrane pack as described in claim 1, characterized in that, When the permeate end of the ultrafiltration membrane pack is rinsed with water for the first time, the rinsing volume of the water rinse is ≥32 L / m³. 2 The inlet pressure at the permeation end is ≤2.0 bar, and the pressure at the return end is ≤1.0 bar.

4. The method for preserving the ultrafiltration membrane pack as described in any one of claims 1-3, characterized in that, The process conditions for the second 0.1M NaOH solution cleaning are the same as those for the first 0.1M NaOH solution cleaning. And / or, after the second 0.1M NaOH solution cleaning, a third water cleaning and drying are performed; the process conditions for the third water cleaning are the same as those for the first water cleaning.

Images