JPS60197287A - Aseptic filter apparatus of liquid - Google Patents

Abstract

PURPOSE:To enable the automation and labor saving in the aseptic filtering of a liquid, by connecting a steam source, a gas source and a distilled water source to primary side piping through a change-over valve and providing a pressure detector to the primary side of a filter housing. CONSTITUTION:When the aseptic filtering of a chemical solution was normally finished, the completeness test of a membrane filter 23 is again conducted. When the completeness test of the membrane filter 23 is finished, a person detaches the membrane filter 23 from a housing 22 and the apparatus is washed with distilled water in the same way as rinsing by distilled water. At this time, a detergent or an org. solvent may be used in place of distilled water. At last, the drying of the apparatus is performed in the same way as air blowing to complete an aseptic filtering process. The constitution of the membrane filter 23 and the filter housing 22 can be adequately altered.

Description

[Detailed description of the invention] TECHNICAL FIELD This invention relates to a liquid V4&1-free device.

Membrane filters (I
A sterile filtration process of the liquid using a PJ III filter is required, which requires integrity testing of the membrane filter and venting of the filter housing. In order to automate the sterile filtration process of liquids, the key is to automate membrane filter integrity testing and filter housing air removal, but as will be described later, these automations are extremely slow.

Next, a conventional sterile filtration process for chemical liquids, particularly a membrane filter integrity test and air venting of a filter housing, will be described.

First, in a semi-sterile room, the chemical solution is passed from the I'll pot through the assembled wire applied filter to the cleaned and sterilized primary receiver (container).
Divide into On the other hand, no rf4iI! A cleaned secondary side receptacle (container) for storing the chemical solution after treatment, and a cartridge-shaped membrane filter (10) installed inside as shown in Fig. 1. A filter housing (13) to which tubes (piping) (11) and (12) are connected to each side is introduced into the sterile room through a sterilizer installed between the focused IM room and the sterile room.

Then, in the sterile room, the membrane filter (10)
Perform an integrity test. △STM-F316-70 is a method that can easily and reproducibly test the integrity of membrane filters without destroying or contaminating them.
The Bubble Point Test (BPT) is standardized in
) is widely used. BPT regards the wire pores of the filter as thin tubes, and uses the relationship between the pressure and the maximum radius of the wire pore, which is expressed by the surface tension equation (1) later, to calculate the maximum radius of the wire pore by measuring the pressure. It is a method of
Conventionally, this has been carried out as follows using a device as shown in FIG. That is, first, the filter housing (
Connect the downstream tube (11) of 13) to the indicating pressure gauge (14).
and a gas It (1B) such as air, nitrogen, carbon dioxide, etc. through a ball valve (15),
) into the water (18) contained in the container (17). On the other hand, prior to the test, the filter (10) is moistened with a liquid such as distilled water to fill the wire holes with the liquid by capillary action, the valve (15) is opened to an appropriate rM degree, and the -next side of the filter (10) is is gradually pressurized with gas. Then, while visually checking for liquid leakage from the housing, a person observes the pressure gauge (14) and the tip of the secondary tube (12). When the downstream side of the filter (10) is pressurized with gas, as long as the pressure is relatively small, this pressure and the liquid in the wire pores are in equilibrium, and the removal of liquid from the wire pores can be ignored. When the pressure reaches a certain value, the liquid in the larger diameter wire holes is expelled from the wire holes to the secondary side, and gas exits through these wire holes to the secondary side. This means that the secondary tube (12)
This can be determined by the generation of bubbles from the tip of the pressure point, and the pressure at this time is referred to as bubble point pressure (hereinafter abbreviated as BP pressure). And this pressure P! :l! There is a relationship between the maximum radius of the hole and the following surface tension equation (1).

r=k(2cr cos θ/P) - (1) where σ is the surface tension, θ is the contact angle, and k is the shape correction coefficient. Therefore, by measuring the BP pressure as described above, the pore diameter of the filter (10) can be determined. However, in the above method, the secondary tip (12
) until air bubbles are generated, a person must constantly observe the pressure gauge (14) and the tip of the tube (12) to read the pressure when air bubbles are generated, which is a cumbersome task and is extremely difficult to automate. be. In addition, as a device to automatically test the integrity of membrane filters, there is a device that measures the flow rate of gas diffusion to the secondary side when a pressure of approximately 80% of the Bl) pressure is applied to the primary side of the filter. It has been proposed to know when the BP pressure has been reached by applying pressure intermittently to the primary side of the filter and measuring changes in the pressure horn. However, in the former case, there is a problem that KwAfi differs depending on the filtration area of the filter, and the error becomes large with a small filter, and in the latter case, there is a problem that the measurement conditions differ depending on the capacity of the housing. In addition, in either case, delicate test conditions must be set as described above, making the equipment complex and expensive.
Maintenance is difficult. Furthermore, although the test itself is performed automatically, the integrity must be determined by humans based on the measurement results.

Therefore, it is extremely difficult to incorporate such a conventional device into a line as a testing device for filters installed in the line, that is, as an in-line testing device.

Once the integrity test of the membrane filter (10) has been completed, the downstream tube (
11) to the primary receiver in the semi-sterile room through the wall between the sterile room and the semi-sterile room, and connect the secondary tube (1
2) to the secondary receiver in the sterile room, and connect the housing (1) to the secondary receiver in the sterile room.
3) Vent the air. This is to exhaust air from the downstream side of the housing (13) in order to secure the filtration area of the filter (10), and with the upper end of the housing (13) open, the housing ( 13)
This is done by sending a chemical solution to the next side. When the chemical liquid is sent to the next side of the housing (13), the air contained therein is discharged from the upper end of the housing (13), and the level of the chemical liquid in the housing (13) gradually rises. A person observes this liquid level, and the liquid level is filtered (1
0), the upper end of the housing (13) is closed to end the air handling. As described above, even when air is removed from the filter housing (13), a person must constantly observe the liquid level within the housing (13), which is a cumbersome task and extremely difficult to automate.

Once the air has been removed from the filter housing (13), remove the housing (13) from the primary receiver.
The medicinal solution is continuously flowed into the secondary receiver through the membrane filter (10) in ) and sterile filtered.

After completing the filtration of the chemical liquid in one primary receiver in this way, the primary receiver and the secondary receiver are connected to the tubes (11) of the filter housing (13).
(12), and the secondary receiver containing the sterile-filtered drug solution is carried to a filling machine in the sterile room and filled with the drug solution.

Then, sterile filtration of the chemical solution is performed in the same way using other primary and secondary receivers, but in this case too, the integrity test of the membrane filter is carried out manually as described above, and the air is vented from the filter housing. It is necessary to do this.

In addition, instead of the above-mentioned secondary side receiver, a buffer tank directly connected to the filling 1 may be used to perform sterile filtration and filling of the chemical solution at the same time, but even in this case, one primary Sterility of the medicinal solution in the side receiver! ! Each time filtration is completed, it is necessary to manually test the integrity of the membrane filter and bleed air from the filter housing as described above.

The purpose of this invention is to solve the above problems and enable automation of the integrity test of membrane filters used in the sterile filtration process of liquids, thus enabling automation and labor saving in the sterile filtration of liquids. Our objective is to provide a sterile filtration device.

The sterile filtration device for liquid according to the first invention includes a filter housing in which a membrane filter is fixed, a primary container into which the liquid before filtration is placed, and primary piping connecting the primary side of the filter housing and the primary container. In a liquid sterile filtration device that includes a secondary container into which the liquid after filtration is placed, and secondary piping that connects the secondary side of the filter housing and the secondary container, a vapor source, a gas source, and A distilled water source is connected to the primary side piping via a switching valve, and a pressure increase rate setting valve is provided between the gas source and the switching valve to maintain the pressure increase rate on the primary side of the membrane filter by gas at a predetermined value. The filter housing is characterized in that an exhaust port that is opened and closed by a valve is provided at the top of the filter housing, and a pressure sensor is provided on the primary side of the filter housing. Further, the colorless liquid filtration device according to the second invention includes:
In addition to the above configuration, the filter housing is characterized in that a liquid level detector is provided above the membrane filter.

The present invention will be described in detail below with reference to FIGS. 2 to 6.

Figure 2 shows a sterile filtration device in an automatic drug filling facility, and this device consists of a semi-sterile room (20) and a sterile room (20) as shown below.
21).

A filter housing (22) is installed in the semi-sterile room (20), and a cartridge-shaped membrane filter (23) is installed and fixed inside the housing (22). A remotely operated exhaust valve (25) is connected to the upper end of the filter housing (22) via an exhaust pipe (24), and the exhaust valve (25) is provided with an exhaust port (2G) that is opened and closed by this. . A liquid level detector (27) using an optical fiber (67) and a pressure detector (28) are attached to the exhaust pipe (24). Note that the configurations of the membrane filter (23) and filter housing (22) themselves are the same as those of the conventional ones.

Preparation pot (-next side container) into which the chemical solution before filtration is placed (29
) is installed in the semi-sterile room (20), and this and the downstream side of the filter housing (22) are connected by a primary side pipe (31) equipped with a first remote control switching valve (30). ing. The chemical solution in the preparation pot ('29) is connected to the primary side piping (3
A first compressed air source (32) for pumping through the filter housing (22) through the semi-sterile room (2)
0), and a sixth remote control switching valve (33) is installed between this compressed air source (32) and the preparation pot (29).
and a first regulating valve (34).

The semi-sterile room (20) also has a steam source (35) for steam sterilization, an air blower and a membrane filter (23).
A second source of compressed air (gas source) for integrity testing of
6), and rinse and membrane filter (23
) A source of distilled water (37) is installed for integrity testing. The steam source (35) is connected to a second remotely operated switching valve (38).
) and a third remote-controlled switching valve (39), it is connected to the part of the downstream side piping (31) between the first switching valve (30) and the filter housing (22), and the steam is A pressure gauge (4) is installed between the source (35) and the third switching valve (39).
0), the seventh remote control switching valve (41) and the filter (
42) is provided. The second compressed air source (36) is connected to the third switching valve (43) via the fourth remote control switching valve (43).
39), and an eighth remote control switching valve (43) is connected between this compressed air source (3G) and the fourth switching valve (43).
44), Pressure increase speed setting valve using a needle valve (45)
, a second regulating valve (46) and a filter (47). A ninth remote control switching valve (68) is provided in parallel with this pressure increase speed setting valve (45), and an exhaust valve (48) is provided between the regulating valve (4G) and the filter (47). ing. A source of distilled water (37) is connected to a fourth switching valve (43) via a fifth remotely controlled switching valve (49).

The sterile room (21) is equipped with a buffer tank (secondary side container) <50) into which the filtered chemical solution is temporarily stored, and the secondary side of the filter housing (22) and this tank (5o) are installed. are connected by a secondary pipe (51). This piping (51) is connected to the semi-sterile room (20) and the sterile room (21).
), and a chemical solution inlet pipe (53) and a fluid ejection pipe (54) are connected in parallel to the part within the sterile room (2) via a tenth remote control switching valve (52). and,
The tip of the chemical solution introduction pipe (53) faces the upper inner wall surface in the tank (5o), and the lower end of the fluid ejection pipe (54) faces the upper inner wall surface in the tank (5o).
) is located in the upper medium heat. A temperature detector (55) is provided at the top of the tank (50), and an exhaust valve (56) is connected via a filter (57). A chemical solution delivery pipe (58) is connected to the bottom of the tank (5o), and the tank (5o) is connected to this pipe (58) by hydraulic pressure.
A liquid level detector (59) is attached to detect the height of the liquid level in the tank 5o. The chemical solution delivery pipe (58) is connected to the filling 1 (path shown) via the eleventh remote control switching valve (60), and is connected to the steam exhaust pipe (through the twelfth remote control switching valve (61)). 62) and a drain pipe (63). The steam exhaust pipe (62) and the drain pipe (63) are arranged in the semi-sterile room (20), and the steam exhaust pipe (62)
) is provided with a thirteenth remote control switching valve (64) and a steam trap (65), and the drain pipe (63) is provided with a fourteenth remote control switching valve (66).

Although not shown, the above-mentioned 11 equipment is equipped with a control device that controls the entire system using a microcomputer. .

That is, first, from the steam ITI (35), the 38th and second switching valves (39) (38), and the next side piping (31)
, a membrane filter (23) in the filter housing (22), a secondary pipe (51), a tenth switching valve (5
2), chemical liquid introduction pipe (53) and liquid ejection pipe (54),
Six valves are operated so that steam flows through the buffer tank (5G), the chemical solution delivery pipe (58), and the twelfth switching valve (61) to the steam exhaust pipe (62), thereby performing steam sterilization. At this time, the exhaust valve (25) of the filter housing (22) and the exhaust valve (56) of the buff 1 tank (50)
) are both closed. Also, during steam sterilization, the temperature of the steam is monitored by a temperature sensor (55) in the buffer tank (50), and the steam i
l! (35) The opening degree of the seventh switching valve (41) is controlled.

Next, the second compressed air source (36) is connected to the ninth switching valve (6).
8), fourth, third and second switching valves (43) (39
) (3B>, - Outgoing side piping (31), membrane filter (23) in filter housing (22), secondary side piping (51), W410 switching valve (52), chemical liquid introduction pipe (53), and liquid Six valves are operated so that the GC air flows through the drain pipe (63) through the ejection pipe (54), the buffer tank (50), the chemical solution delivery pipe (58), and the twelfth switching valve (61), and the air blowing This air removes the steam condensed water remaining in each part and cools the membrane filter (23).At this time, the exhaust valve (22) of the filter housing (22)
25) is closed, but the exhaust valve (56) of the buffer 1 tank (50) is opened to an appropriate degree. Also, during air blowing, the temperature of the air is determined by the temperature sensor (55) of the buffer tank (50), that is, the temperature of the membrane filter (22).
Sfl! is monitored and air blowing is terminated when the desired temperature is lowered.

Next, from the distilled water source (37), the fifth, fourth, third and second switching valves (49) (43) (39) (38),
- Outgoing side piping (31), membrane filter (23) in the filter housing (22), secondary side piping (51),
The drain pipe ( 6 valves are operated so that distilled water flows into 63),
Rinsing is performed. Then, each part is rinsed with this distilled water, and the membrane filter (23) is moistened with the distilled water. At this time, the exhaust valve (25) of the filter housing (22) is idle, but the buffer tank (50)
) is opened to an appropriate opening degree.

Next, the pressure increase speed setting valve (
45), fourth, third and second switching valves (43) (3
9) (38), - Outgoing side piping (31), membrane filter (23) in filter housing (22), secondary side piping (51), 10th switching valve (52), chemical liquid introduction pipe (53) Six valves are operated so that air flows to the drain pipe (63) through J3, the liquid ejection pipe (54), the buff 7 tank (SO), the chemical delivery pipe (58), and the twelfth switching valve (61). , an integrity test of the membrane filter (23) is performed.

As a result of repeated research on integrity testing of membrane filters, the inventors discovered the following fact. In other words, when the pressure on the primary side of a defect-free filter moistened with liquid is increased with gas at a predetermined rate, the BP pressure on the downstream side is reached by the gas supply m and the second side from the negative side. A balance is maintained between the discharge of gas to the next side, and the pressure on the next side is maintained constant. In this case, the time it takes for the primary side of a defect-free filter to reach the BP pressure is approximately constant, determined by the BP pressure of this filter and the pressure increase rate, and therefore, after a longer predetermined time elapses, the primary side pressure will increase. The integrity of the filter can be automatically and accurately tested by checking whether a predetermined criterion value is reached. The above test is based on this principle,
There is no error in the measured values compared to the conventional BPT results,
It has been confirmed through experiments that the integrity of the filter can be determined quantitatively.

Next, the operation of the above-mentioned apparatus will be explained by taking as an example a case where a membrane filter having a pore diameter of 0.2 μm is subjected to an integrity test. In addition, cellulose ester, nylon 6
In the case of a hydrophilic membrane filter such as -6 or polyvinylidene fluoride, the BP pressure is about 3.5 ko/cm' with a 0.2 μm pore diameter and no defects.

Before the start of the test, the eighth switching valve (44) of the second compressed air source (36) is closed, and prior to the test, a person sets the setting valve (27) to obtain a predetermined pressure increase rate. In this case, 0.1 kg/aI per second.
Boost the pressure at a rate of . Further, during the test, the exhaust valve (25) of the filter housing (22) is closed, but the exhaust valve (56) of the buffer tank (50) is opened to an appropriate degree.

The test is started in this state, and during the test, the housing (22
) is recorded in the record fi+ (not shown) as shown in FIGS. 4 to 6. In addition, Figures 4 to 6
In the figure, the horizontal axis represents time (sec), and the vertical axis represents the pressure (ko/am') on the downstream side of the housing (22).

When the test starts, first, the eighth switching valve (44) is opened, and the second compressed air source (36) passes through the pressure increase speed setting valve (45) to the next side of the housing (22). If air is supplied to the membrane filter (23) and there is no damage or improper installation of the membrane filter (23), the pressure on the negative side will be as shown in Figures 4 and 5.
As shown by straight line (a) in the figure, it increases at the above rate.

Then, when the pressure on the negative side reaches 2ka/a11', the pressure increase is stopped for a certain period of time (t2-20sec).
9. If there is a seal failure in the housing (22) or piping, or a wetting failure in the filter (23), the primary pressure will decrease from 2 ka/d while the pressure increase is stopped, so an alarm will be issued and the test will be stopped. is interrupted. If there is no such abnormality, the pressure on the negative side will be maintained constant as shown by the straight line (b) in Figures 4 and 15, and the valve pressure will be restarted after the above time (t2) has elapsed. . Then, when a certain period of time (t3=60 sec) has elapsed after restarting the pressure increase, it is automatically checked whether the pressure on the negative side is greater than a predetermined determination value (3 ka/ba).

In the case of a defect-free filter with a pore diameter of 0.2 μm, the pressure on the primary side after restarting pressure increase increases at the above rate as shown by the straight line (Ci) in Figure 4, and the BP pressure (3,5k17/CI
'), it remains constant as shown by the straight line (d) in the figure. Then, the pressure (3.5ko/cm') when the above time (t3) has passed after restarting pressurization is judgment 1 (3kM (!11')
Since it is larger, it is determined to be normal and the test ends.

If the pore diameter of the filter is larger than 0.2 μm, for example, if a filter with a pore diameter of 0.45 μm is installed by mistake, the pressure on the primary side after increasing the pressure again will be shown by the straight line (e) in Figure 5.
As shown in , the BP pressure (2,4k
lJ/ff1l'), it is maintained constant as shown by the straight line (f) in the figure. Then, the pressure (2, il ko/
an') is smaller than the judgment value (3ko/csa'), so it is determined that there is an abnormality and an alarm is issued.
sec) Pressure is maintained and the test is terminated.

If the filter is damaged or improperly installed, the pressure on the primary side after the initial pressure increase will be determined by the curve (0) shown in Figure 6.
), the pressure rises as shown by t 1 =
Since it does not reach 2 ko/C12 even after 40 seconds), it is determined that there is an abnormality. After the alarm is issued, the test ends.

After completing the integrity test of the membrane filter (23),
If the result is normal, the first compressed air source (32
) is sent to the preparation pot (29), and its pressure horn causes the chemical solution in the preparation pot (29) to flow through the primary side piping (31) and the membrane filter (23) in the filter housing (22).
), secondary piping (51), tenth switching valve (52),
Eight valves are operated so that the liquid flows to the filling machine through the chemical liquid introduction pipe (53), the buffer tank (50), the chemical liquid delivery pipe (58), and the eleventh switching valve (60). , the filter housing (22) is vented, and then the medicinal solution is sterile filtered. During this time,
The exhaust valve (56) of the buffer tank (50) is set to an appropriate IF.
I have heard this before, but the filter housing (2
2) When air bleeding starts, the housing (22)
The cheerful valve (25) is open. When the chemical solution is sent from the primary side piping (31) to the housing (22) in this state, the air on the negative side of the housing (22) flows into the exhaust pipe (22).
4) and is discharged from the exhaust port (26) through the exhaust valve (25), and the liquid level of the chemical liquid in the housing (22) gradually rises. When the liquid level reaches the liquid level detector (21), this is detected as follows, the exhaust valve (25) is closed, and air venting is completed. As shown in FIG. 3, the tip of the optical fiber (61) constituting the liquid level detector (21) is slightly inserted into the exhaust pipe (24), and the optical fiber (
A part of the light transmitted through the optical fiber (61) is reflected at its tip and returns to the optical fiber (67). When the liquid level of the chemical solution has not reached the optical fiber (61), that is, when air is present around the tip of the optical fiber (61), and when the liquid level has reached the optical fiber (67) and the area around the tip is When a chemical solution is present in the optical fiber (6
1) Since the light deflection rate at the tip is different, the light stone returning into the optical fiber (61) changes. Based on this change, it is detected that the liquid level has reached the optical fiber (67). The liquid level detector (27) using such an optical fiber (61) has an extremely fast response time, so when the liquid level reaches the detector (27), the exhaust valve (25) can be immediately closed. . In addition, the filter housing (22
) may be manually vented as in the conventional manner.

Once the exhaust valve (25) of the filter housing (22) has been closed and the air flow has ended, the chemical solution is subsequently sterilized and filtered from the preparation pot (29).
Pass through the next piping (31) to the filter housing (22)
The chemical solution sent to the next side is passed through a membrane filter (23
) and flows to the secondary side, and the filtered chemical liquid passes through the secondary side piping (51) and enters the buffer tank (50) from the chemical liquid introduction pipe (53). Buffer tank (50
) has four levels of liquid level, from the bottom to the lower limit of the allowable value,
A target value lower limit, a target value upper limit J3, and an allowable value upper limit are set. Immediately after sterile filtration is started, the 11th
The switching valve (60) is closed, and when the liquid level in the tank (50) reaches the upper limit of the target value, the switching valve (60) opens. Thereby, the chemical liquid in the tank (50) is supplied to the filling machine through the chemical liquid delivery pipe (58) and the eleventh switching valve (60). In addition, m of the drug solution supplied into the tank (50) from the drug 1llll introduction tube (53) is the same as the drug solution delivery tube (
When the liquid level in the tank (50) reaches the upper limit of the target value, the first switching valve (30) closes and the liquid is sterilized. Filtration is interrupted. When the liquid level in the tank (50) falls to the lower limit of the target value, the first switching valve (30) is turned on and sterile filtration is restarted. The liquid level is maintained between the upper and lower target limits.

All of the chemical solution in the preparation pot (29) is removed from the filter housing (2
After being sent to 2) and sterile filtered, the m-made pot (29),
- The next side of the next side piping (31) and the housing (22) is filled with air. However, this air [31
) Since the pressure is lower than the pressure, the membrane filter (23)
Therefore, the membrane filter (23) remains wet with the chemical solution. The chemical solution after filtration is kept in a buffer tank (50
), and the liquid level in the tank (5o) gradually decreases. Then, when the liquid level reaches the lower limit of the allowable value, the eleventh switching valve (60) is closed immediately or after a certain period of time has passed, and the non-filtering operation is completed. At this time, the preparation pot (29)
If no chemical solution remains, it is determined that sterile filtration has been completed normally as described above. If the liquid level in the tank (5o) falls to the lower limit and there is some chemical remaining in the preparation pot (29), it is assumed that an abnormality has occurred somewhere in the device, and an alarm is issued. emanate.

Also, when the liquid level in the tank (50) reaches the upper limit of the allowable value, it is determined to be abnormal and w! issue a report.

When the sterile filtration of the drug solution is completed normally, the integrity test of the membrane filter (23) is performed again. At this time,
Since the membrane filter (23) is wetted with the chemical solution as described above, various values are different compared to the previous test using distilled water, but the operation itself is the same.

Once the integrity test of the membrane filter (23) has been completed, a person must attach the membrane filter (23) to the housing (
22) and rinse the device with distilled water as in the previous distilled water rinse. At this time, detergent J: or an organic solvent may be used instead of distilled water.

Finally, do the same thing as the previous air blow and i! The sterile filtration process is completed by drying the container.

In the above embodiment, the integrity test of the membrane filter (23) is carried out only before and after the start of m-less filtration.
At an appropriate time during sterile filtration, for example, one tank of buff (5
When the liquid level in 0) reaches the upper limit of the target value and sterile filtration is interrupted, an integrity test using a chemical solution similar to that described above can be performed. In this way, reliability can be further improved by 1 degree.

The configurations of the membrane filter (23) and filter housing (22) are not limited to those of the above embodiments, and can be modified as appropriate. Figure m7 and Figure 8 respectively show a housing (22) of the cartridge-shaped membrane filter (23) that is different from the above embodiment, and Figure 9 shows a disc-shaped membrane filter (23) and its housing (22) that are different from the above embodiment. It shows. Note that in FIGS. 7 to 9, the same components as those in the above embodiment are designated by the same reference numerals. In addition, a membrane filter (23
) integrity testing may be performed using a suitable gas other than air.

The sterile filtration device does not necessarily have to be directly connected to the filling machine as in the above embodiment. Furthermore, the present invention can of course be applied to liquids other than medicinal liquids.

According to the liquid sterile filtration device of the first invention, as described above, it is possible to automate the integrity test of the membrane filter in the liquid sterile filtration process, and therefore, the liquid
A: It is possible to automate filtration, save labor, reduce costs, and improve reliability. Furthermore, the integrity of the membrane filter can be tested any number of times at any time during the process, and by doing so, reliability is further improved. Furthermore, according to the second aspect of the liquid filtration device, in addition to automating the integrity test of the membrane filter, it is possible to automate the air removal of the filter housing, thereby achieving a higher degree of automation of the sterile filtration of liquids. becomes possible.

[Brief explanation of drawings]

Figure 1 is a pipe system diagram showing a conventional device for performing bubble point tests on membrane filters, Figures 2 to 6
The figure shows one embodiment of the present invention, Figure 2 is a pipe system diagram of a sterile filtration device for chemical solutions, Figure 3 is an enlarged side view of the main parts of the liquid level detector, and Figures 4 to 6 are membrane diagrams. Graphs showing three examples of filter integrity test results, Figures 7-
FIG. 9 is a vertical sectional view showing a modified example of a membrane filter and a filter housing, respectively. (22)...Filter housing, (23)...Membrane filter, (25)...Exhaust valve, (26)...
...Exhaust port, (21)...Liquid level detector, (28)...
・Pressure detector, (29)...Preparation pot (-next side container),
(30) (38) (39) (43) (49)...
・Switching valve, (31)...-Next side piping, (35)...
Steam source, (36)... Compressed air source (gas source), (37
)... Distilled water source, (45)... Striking pressure speed r! 1 setting valve, (50)...1 buff tank (secondary side container), (5
1)...Secondary side piping. 4 people other than the above Figure 5 Figure 6

Claims (2)

[Claims] (1) A filter housing in which a membrane filter is fixed, a primary container into which the liquid before filtration is placed, a primary pipe connecting the primary side of the filter housing and the primary container, and into which the liquid after filtration is placed. a secondary container;
In a liquid sterile filtration device including a secondary side piping connecting a secondary side of a filter housing and a secondary side container, a steam source, a gas source, and a distilled water source are connected to the primary side piping via a switching valve, A pressure increase rate setting valve of t=th is provided between the gas source and the switching valve to maintain the pressure increase rate of the primary side of the membrane filter by gas at a predetermined value, and an exhaust port that is opened and closed by the valve is located at the top of the filter housing. A sterile filtration device for liquid, characterized in that the device is provided with a pressure sensor on the primary side of the filter housing. (2) A filter housing into which a membrane filter is fixed, a primary container into which liquid before filtration is placed, primary piping connecting the primary side of the filter housing and the primary container, and into which liquid after filtration is placed. a secondary container;
In a liquid sterile filtration device including a secondary side piping connecting a secondary side of a filter housing and a secondary side container, a steam source, a gas source, and a distilled water source are connected to the primary side piping via a switching valve, A pressure increase rate setting valve is provided between the gas source and the switching valve to maintain the pressure increase rate on the primary side of the membrane filter by gas at a predetermined value, and an exhaust port that is opened and closed by the valve is provided at the top of the filter housing. A liquid sterile filtration apparatus characterized in that a liquid level detector is provided above the membrane filter of the filter housing, and a pressure detector is provided on the primary side of the filter housing.