Small-size virus removal filter

Abstract

The utility model discloses a hollow fiber virus removal filter assembly with a very small cavity volume before filtration. The assembly comprises a liquid inlet joint (1), a hollow pipe (2), an outlet joint (3) and hollow fiber membrane filaments (4). The two ends of the hollow pipe (2) are connected with the liquid inlet connector (1) and the outlet connector (3) to form a closed cavity. And one end of the hollow fiber membrane filament (4) in the hollow tube (2) is hermetically connected with the inner connector (5) through glue and is opened on the end surface, and the other end is self-sealed. The volume of the cavity can be smaller than 0.1 ml before filtration, no residue exists, and feed liquid is saved; only two connectors are arranged, the hollow fiber membrane filaments are only sealed with the liquid inlet, production is simple, and operation is convenient.

Description

Technical Field

[0001] The utility model belongs to the technical field of filters, and specifically relates to a virus removal filter. Background Art

[0002] Viral contamination of therapeutic biological products is a significant risk to drug safety. ICH Q5A is the most important international guideline for viral safety of biological products, providing crucial guidance and reference for the viral safety evaluation of biotechnology products derived from human or animal cell lines. Domestic regulations and guidelines also govern this, such as the "Control of Viral Safety of Biological Products" in Part III of the Chinese Pharmacopoeia, published in 2020; and the "General Principles for Technical Review of Viral Safety Evaluation of Products Extracted from Biological Tissues and Products Expressed in Eukaryotic Cells," published in 2005.

[0003] With the approval of more gene therapy products, their safety issues are receiving greater attention. At the same time, as the pipeline layout, which started with rare diseases and cancer, has now shifted to common diseases, the risks and benefits need to be reassessed. On September 29, 2022, ICHQ5A released a new draft for comment, ICHQ5A (R2). In this draft, biologics were redefined, and genetically engineered viral vectors and viral vector-derived products were included in ICHQ5A for the first time. CGT products, which have developed rapidly in recent years and are mainly based on viral vectors such as AAV and LV, will also need to incorporate a viral clearance step into the process as required.

[0004] After nearly 20 years, this revision of the IC H5A is designed to adapt to industry development and the evolving needs of new technologies. The "General Principles for Technical Review of Viral Safety Evaluation of Biological Tissue Extracts and Eukaryotic Cell Expression Products," published in China in 2005, already considers viral safety risks for all eukaryotic cell-expressed products.

[0005] However, viral vector-based gene therapy drugs have unique production processes. They do pose potential safety risks from both endogenous and exogenous viruses. Furthermore, the current immature viral vector production system and high production costs contribute to high drug prices. (Zolgesma, an AAV-based drug for the treatment of SMA launched in 2019, costs a staggering $2.12 million per dose, significantly hindering drug accessibility.) Regulatory oversight also prohibits currently marketed gene therapy drugs from requiring dedicated viral clearance processes.

[0006] With the approval and marketing of multiple AAV gene therapy drugs in 2022, the viral risks of gene therapy products have attracted increased attention. Simultaneously, ICH Q5A has been updated. This has posed greater challenges to the CMC of viral vector-based gene therapy drugs, with viral clearance processes being a major challenge. This is particularly true for many AAV drugs, which have low production yields, high costs, small dosages, and complex process development. Adding a viral clearance step during process development will increase the demand for costly feed solutions.

[0007] Chinese utility model patent CN216321131U discloses a virus removal filter including an upper shell, a lower shell and a filter chamber, wherein the filter chamber has an upwardly inclined guide surface connected to the exhaust channel. The patent takes into account the problems of sealing and exhaust in its design. However, there is not much description of the correspondence between the volume of the upper chamber and the effective filtration area. When reducing the overall volume of the filter, the diameter and surface area of ​​the filter membrane will be reduced simultaneously. When filtering and removing viruses from complex biological product liquids, such as purified AAV liquid, when selecting a suitable effective filtration area, there will be residues of high-cost liquid. Summary of the Invention

[0008] The utility model provides a virus removal filter, which solves the problems of an oversized cavity upstream of the filter and residual liquid by improving the internal structure of the filter.

[0009] In order to solve the above technical problems, the utility model provides a virus removal filter with the following structure, which is characterized by comprising a liquid inlet connector (1), a hollow tube (2), an outlet connector (3), and a hollow fiber membrane (4) with one end connected to the inlet connector in the hollow tube and the other end being self-sealed.

[0010] The liquid inlet connector (1) comprises an internal connector (5) and an external locking thread (6).

[0011] The outer locking thread (6) of the liquid inlet connector (1) is limitedly clamped on the inner connector (5).

[0012] The external locking thread (6) of the liquid inlet connector (1) is rotatable.

[0013] The liquid inlet connector (1) is connected to the hollow tube (2) and can be integrally formed by welding, casting or stretching.

[0014] The liquid inlet connector (1), hollow tube (2), and outlet connector (3) can be made of stainless steel or polymer materials.

[0015] The liquid inlet connector (1), the hollow tube (2), and the outlet connector (3) can withstand irradiation sterilization and high-pressure steam sterilization.

[0016] The hollow fiber membrane (4) is sealed and connected to the inner connector (5) by glue.

[0017] The hollow fiber membrane (4) is flush with the outer end surface of the inner connector (5).

[0018] The hollow fiber membrane (4) opens at the outer end surface of the inner connector (5).

[0019] The hollow fiber membrane (4) is sealed at the outlet end by glue or hot melt.

[0020] The hollow fiber membrane (4) is made of a polymer material, which may be PES, PVDF, regenerated cellulose, or a modified material thereof.

[0021] The inner diameter of the hollow fiber membrane (4) may be 0.2 mm to 1 mm.

[0022] The wall thickness of the hollow fiber membrane (4) can be 20um-100um.

[0023] The inner diameter of the hollow tube (2) is 0.5-2.5 cm.

[0024] The hollow tube (2) has a length of 5-25 cm.

[0025] The outlet joint (3) is connected to the hollow tube (2) and can be integrally formed by welding, casting or stretching.

[0026] The outlet connector (3) comprises an inner connector (7) and an outer locking thread (8).

[0027] The external locking thread (8) is fixedly welded to the internal connector (7).

[0028] The cavity volume of the virus removal filter before filtration is the inner cavity volume of the fiber membrane filament, which is the effective filtration area / 2*inner diameter; the cavity volume of the virus removal filter before filtration can be less than 0.1 ml.

[0029] The virus removal filter is filled with sterile water for injection, can be sealed with a double-layer breathing bag, and is sterilized for use. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a schematic diagram of the structure of the utility model, which consists of the following components: 1: liquid inlet connector; 2: hollow tube; 3: outlet connector; 4: hollow fiber membrane.

[0031] Figure 2 This is a schematic cross-sectional view of the structure of the utility model, which comprises: 1: liquid inlet connector; 2: hollow tube; 4: hollow fiber membrane.

[0032] Figure 3This is a cross-sectional view of the structure of the utility model, which comprises: 1: liquid inlet connector; 2: hollow tube; 4: hollow fiber membrane. DETAILED DESCRIPTION

[0033] The virus removal filtration process has the following steps: filter wetting and exhaust, NWP detection, integrity test before use, buffer balance, feed liquid filtration, post-filtration flushing, and post-filtration integrity test.

[0034] The utility model performs virus removal filtration as follows: in a controlled area, the plastic package of the virus removal filter is opened, and the liquid inlet (1) is fixed on an iron frame with the liquid inlet facing upward. Pipelines, three-way valves, pressure gauges and pressure tanks are connected to the interfaces at both ends.

[0035] Exhaust: Connect the liquid inlet to the waste liquid bottle and the outlet to the WFI tank, slowly adjust the pressure of the WFI tank to 15psi, open the inlet and outlet valves, and let the water for injection enter the hollow tube (2) from the outlet (3). Possible bubbles in the inner cavity of the hollow fiber membrane (4) are discharged from the fiber tube to the waste liquid bottle. The process lasts for 10 minutes to facilitate the full discharge of gas.

[0036] NWP detection: Connect the liquid inlet to the WFI tank, collect the filtrate with a beaker at the outlet, slowly adjust the WFI tank pressure to 15psi, open the inlet and outlet valves, continue filtering for 10 minutes, measure the filtrate temperature, calculate the temperature-calibrated NWP, and confirm that the NWP value is within the qualified range.

[0037] Integrity test before use: Connect the liquid inlet to the air tank, collect the filtrate at the outlet with a beaker, slowly adjust the air tank pressure to 60psi, open the inlet and outlet valves, and wait for 5 minutes after no liquid is filtered out of the fiber, and observe whether there are continuous large bubbles on the outer wall of the fiber.

[0038] Buffer balance: Connect the liquid inlet to the waste liquid bottle and the outlet to the buffer tank. Slowly adjust the WFI tank pressure to 15psi, open the inlet and outlet valves, and the buffer enters the hollow tube (2) from the outlet (3). The hollow fiber membrane (4) is soaked, and any bubbles in the inner cavity are discharged from the fiber tube to the waste liquid bottle. The process lasts for 10 minutes to ensure that the filter is fully wetted and the gas is discharged.

[0039] Liquid filtration: Connect the liquid inlet to the liquid tank, connect the outlet to the liquid receiving tank, slowly adjust the sample tank pressure to 30psi, open the inlet and outlet valves, and start the filtration process.

[0040] Post-filtration flushing: Connect the liquid inlet to the buffer tank and the outlet to the liquid receiving tank. Slowly adjust the buffer tank pressure to 30psi, open the inlet and outlet valves, and perform the flushing process. End the flushing after flushing the appropriate volume according to the filtration rate.

[0041] Post-filtration integrity test: Connect the liquid inlet to the air tank, collect the filtrate at the outlet with a beaker, slowly adjust the air tank pressure to 60psi, open the inlet and outlet valves, and wait for 5 minutes after no liquid is filtered out of the fiber, and observe whether there are continuous large bubbles on the outer wall of the fiber.

[0042] The above is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with this technical field can make equivalent replacements or changes within the technical scope disclosed by the utility model based on the technical solution and concept of the utility model, which should be covered by the protection scope of the present invention.

Claims

1. A small-volume virus removal filter, characterized by: The invention comprises a liquid inlet connector (1), a hollow tube (2), and an outlet connector (3); the hollow tube contains a hollow fiber membrane (4) with one end connected to the inlet connector and the other end being self-sealing; the liquid inlet connector (1) comprises an inner connector (5) and an outer locking thread (6), the outer locking thread (6) is limitedly clamped on the inner connector (5), the outer locking thread (6) of the liquid inlet connector (1) is rotatable, the liquid inlet connector (1) is connected to the hollow tube (2), and the outlet connector (3) is connected to the hollow tube (2), which can be welded, cast or stretched into one piece, and the material can be made of stainless steel or polymer material.

2. The small-volume virus removal filter according to claim 1, characterized in that: The hollow fiber membrane (4) is sealed and connected to the inner connector (5) by glue.

3. The small-volume virus removal filter according to claim 1, characterized in that: The hollow fiber membrane (4) is sealed at the outlet end by glue or hot melt.

4. The small-volume virus removal filter according to claim 1, characterized in that: The hollow fiber membrane (4) is made of a polymer material, which may be PES, PVDF, regenerated cellulose, or a modified material thereof.

5. The small-volume virus removal filter according to claim 1, characterized in that: The inner diameter of the hollow fiber membrane (4) may be 0.2 mm to 1 mm.

6. The small-volume virus removal filter according to claim 1, characterized in that: The wall thickness of the hollow fiber membrane (4) can be 20um-100um.

7. The small-volume virus removal filter according to claim 1, characterized in that: The hollow tube (2) has an inner diameter of 0.5-2.5 cm and a length of 5-25 cm.

8. The small-volume virus removal filter according to claim 1, characterized in that: The cavity volume of the virus removal filter before filtration can be less than 0.1 ml.

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