JPH04142445A - Completeness testing method - Google Patents

Abstract

PURPOSE:To perform the completeness test for a precision filtration film filter and a filter cartridge by measuring diffusion flows by pressure at two or more points and using an anisotropic film inspected on the measured values and differentiated values between measurement points as the inspection standard. CONSTITUTION:The relation between the size (radius (r)) of a defect existing on a filter or a filter cartridge and the pressure P that a test liquid contained in the defect is blown out is expressed in the equation I. If the defect exists on the filter or the filter cartridge, air is blown out at the specific pressure P. The quantity of the air flowing out from the defect is obtained by the Hagen- Poiseuille's equation as shown by the equation II. The measured pressure must be set at two or more points in the range containing the defect. Diffusion flows by pressure or pressure hold values at two or more points are measured in the pressure range 4kg/cm<2> or below on an anisotropic sterilization grade filter, a completeness test is performed on the measured values and differentiated values between measurement points, and sensitivity can be most increased.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a method for testing the integrity of filters and filter cartridges used in fluid filtration. More specifically, the present invention relates to a method for testing the integrity of microfiltration membrane filters and filter cartridges.

The filters and filter cartridges referred to here are used to filter and collect particulates and microorganisms present in fluids, and are used in semiconductor manufacturing processes, pharmaceutical manufacturing processes, food, drinking water, alcoholic beverage manufacturing processes, etc. .

[Conventional technology]

Various types of filters and filter cartridges are used in the above fields depending on the purpose of the manufacturing process in each field, but those that play an important role in performance are usually 1 μm or 0 μm or less. This is a filter or filter cartridge using a sterilization grade microfiltration membrane that captures and removes microorganisms with a size of 1 μm. A sterilizing grade filter is defined as a sterilizing grade filter that is normally tested under the most severe conditions expected to be encountered in the sterilization process, i.e. 10' filter elements per effective filtration area lal of the test filter element. In the test conducted by challenging the above-mentioned index teeth, it passed the strict test that no bacteria was found in the filtrate. The indicator tooth here is Pseudomonas deiminuta, a Durham-negative bacillus with polar flagella.
Diminuta ATCC 19146) is commonly used. In 1967, Bowman et al. isolated bacteria that were not quantitatively captured by 0 and 45 μm filters, which were considered sterile filtration grade at the time, and were quantitatively captured by 0.2 μm or 0.22 μm filters. It was called Pseudomonas diminuta (ATCC19146). According to the Systemic Bacteriology Manual (1984), its size is 0.
．． The size is 5 x 2 to 3 μm, but it varies depending on the culture conditions, and for the purpose of examining the filtration sterilization performance of filter elements, non-agglomerated particles with a size of about 0.3 x 1 μm are generally used.

These filters or filter cartridges are used for direct filtration of products or semi-finished products, filtration of liquids that are product components, filtration of process washing water, etc. in pharmaceutical manufacturing processes, food, drinking water, and alcohol manufacturing processes. The filtration membrane that performs this filtration function is microporous, and has a sponge structure with minute pores inside, or a structure with a layer with pores on one side and a dense layer on the other side, and the pores are In some cases, the rate is up to 90%. The filter cartridge referred to here is a pleated microporous membrane for filtration that has been processed into pleats and is creased to form a cylindrical filtration membrane structure that has a height in the direction parallel to the pleat folds. Examples include a type filter cartridge and a disk-stacked filter cartridge, which is formed by stacking filtration units in which filtration membranes are adhered to both upper and lower surfaces of a flat support that grows fluid passages. When such filters or filter cartridges are used, leakage of microorganisms and particulates contained in the filtration stock solution to the permeate side is not allowed. If microorganisms or particulates are present on the permeate side, harmful pharmaceutical or food products will be produced. In particular, in the case of microorganisms, even if only one microorganism leaks, it will multiply during storage or transportation, resulting in pharmaceuticals and foods containing a large number of microorganisms. Needless to say, such medicines and foods are harmful to the human body. To prevent this from happening, manufacturers of filters and filter cartridges carry out careful manufacturing process control and quality control. In addition, users of filters and filter cartridges should also confirm before and after use that the filter or filter cartridge they intend to use has the desired level of ability to trap and inhibit microorganisms and particulates.

The integrity test (Integrity Te5t) is a method of testing the ability to capture and prevent microorganisms and particulates.

Broadly speaking, there are three types of integrity testing methods currently in use: (1) bubble point method;
2) diffusion flow rate method, and (3) pressure hold method. The principle of each of these methods is that a liquid (test liquid) is applied to the filtration membrane of the filter or filter cartridge to be tested.
The primary side of the membrane containing this test liquid is loaded with gas at a higher pressure than the secondary side, and the flow behavior or flow rate of this gas to the secondary side is measured to detect serious defects in the filter or filter cartridge. Determine the existence of. Each test method will be explained in more detail below.

(1) Bubble point method A liquid (usually water or alcohol) is added to the secondary side of the filtration membrane to be tested, and the secondary side is filled with gas. This pressure is gradually increased, and the size of the largest pore or void in the filter or filter cartridge is determined based on the pressure at which bubbles are generated on the secondary side, and the completeness of the trapping ability of the filter or filter cartridge is determined. It's a method.

- When the pressure on the downstream side is low, no bubbles are seen in the liquid on the secondary side, but when the pressure exceeds a certain value, the largest pores exist in the filtration membrane, the filtration membrane, and the filter cartridge parts. It is observed that air bubbles are generated through the largest pores or voids among the voids existing at the bonded portion with the filter cartridge, voids existing in the filter cartridge parts, etc. This pressure is called the bubble point. The bubble point is proportional to the size of the hole or void through which the gas passes.

Therefore, the size of the hole or gap through which the gas has passed can be determined from this pressure.

(2) Diffusion flow method A test liquid is filled into the microporous filtration membrane of a filter or filter cartridge to form a liquid membrane. - The size of the largest pore or void existing in a filter or filter cartridge is estimated by making gas exist on the downstream side, applying pressure, and measuring the amount of gas flowing to the secondary side. . - As the pressure on the liquid surface in the downstream filter membrane increases, the amount of primary gas dissolved in the liquid increases. A gas concentration gradient occurs in the liquid film, and the dissolved gas moves to the secondary side by diffusion. - When the pressure of the gas on the downstream side is small, the amount of gas that moves to the secondary side through the filtration membrane is only due to diffusion, but as the pressure is gradually increased, the bubble point mentioned above is reached, and the pores or voids Through this, gas becomes a viscous flow and can flow to the secondary side with relatively small resistance. That is, when this bubble point is reached, the flow rate of gas flowing to the secondary side increases rapidly.

By measuring the gas flow rate flowing to the secondary side, it is possible to estimate the size of the largest pore or void present in the filter or filter cartridge. Determine in advance the size of the pores and voids that will not leak microorganisms and particulates, and check that the gas flow rate flowing to the secondary side at a pressure lower than the pressure calculated from these values is only a diffusion flow, then install the filter or filter cartridge. Confirm that it has the ability to capture the desired microorganisms or particulates.

(3) Pressure hold method Similar to the diffusion flow method, this method fills the filtration membrane with the test liquid, allows gas to exist on the -next side and the secondary side, and keeps the gas volume and pressure on the -next side constant and the test liquid Measures the pressure of the primary gas, which decreases with the amount of fluid flowing over time through a filtration membrane filled with Confirm that it has the same gender.

Users of filters and filter cartridges should:
The integrity test was conducted according to the method recommended by the manufacturer from among the three methods mentioned above.

In either test, the test solution is water, alcohols such as methanol, ethanol, isopropyl alcohol, or a mixed test solution of water and the above alcohols.
Alternatively, various types of liquid can be used, such as the liquid itself to be filtered, but generally water is often used as the test liquid.

In addition, any test gas can be used, such as air, oxygen, nitrogen, helium, or a mixture of these gases, but air or nitrogen is usually used from the viewpoint of solubility, diffusion coefficient, and cost. many.

<Problems to be Solved by the Invention> However, if the flow rate of gas from a defect that leaks bacteria or particles to be captured is sufficiently small, the above test method may miss the presence of the defect. In particular, JP-A-56-154051 and JP-A-62-27006
In a microporous filtration membrane having anisotropy such as that described in 2007, when the surface with large pores is used as the primary side, the higher the pressure of the gas on the downstream side, the more the gas will be retained in the filter. The thickness of the test liquid becomes thinner, and as a result, the observed pressure reduction value and diffusion flow rate in the pressure hold method become larger, and the probability of missing defects also increases.

In addition, if there are large variations in the wetting of the filter or filter cartridge or in the membrane forming process, and the viscous flow flowing out from these defects is small enough, the viscous flow will be hidden within the range of the variation. There was a risk that it would happen.

Furthermore, it is generally required that the filtration work be carried out in a short period of time. Particularly when used in pharmaceutical manufacturing processes, short-term filtration is required to prevent bacterial contamination of the filtrate. Therefore, in order to increase the amount of filtration per unit time, a filter or filter cartridge with a large filtration area is preferably used.

However, when the filtration area is increased, in the integrity test mentioned above, the value of the diffusion flow rate flowing out from the entire membrane surface and the pressure hold value become relatively large compared to the flow rate flowing out from the defect to be detected, making it difficult to detect. There are some concerns.

The present invention provides a method for solving such problems. In other words, the present invention provides an integrity test for detecting defects in the structural parts of filters and filter cartridges with higher accuracy in the integrity test of sterilization grade filters and filter cartridges using a membrane that develops anisotropy. The purpose is to provide a method.

As a result of intensive consideration of the above-mentioned problems, we have detected defects large enough to leak bacteria and particles that should be captured, which were difficult to detect using any of the above integrity testing methods. To do this, 4
Within the pressure range of kg/a1 or less, the diffusion flow rate or pressure hold value is measured at two or more pressure points, and the measurement value and the differential value between the measurement points are used as inspection standards.A membrane with anisotropy is used. We have discovered that this can be achieved by a method for testing the integrity of sterilizing grade filters or filter cartridges. Further details will be explained below. The relationship between the size (radius r) of a defect existing in a filter or filter cartridge and the pressure P at which the test liquid contained in the defect is blown out is r = 2σ cos θ/
It is expressed as P. That is, if there is a defect in the filter or filter cartridge, air will blow out at a certain pressure P. Further, the amount of air flowing out from the defect is determined by the No. 1-Gemboisouille equation as shown below.

QL=15πd4ΔP/32Lη In the present invention, the pressures measured at two or more points need to be set in a range that includes the above defects.

However, JP-A-56-154051 and JP-A-62
In a microporous filtration membrane with anisotropy such as that described in 27006, when the surface with large pores is used as the primary side, the higher the pressure of the gas on the downstream side, the more the filter becomes The thickness of the test liquid being held becomes thinner, and as a result, the observed pressure reduction value and diffusion flow rate in the pressure hold method become observed to be large. Therefore, in a high pressure range, the sensitivity for detecting defects in the structural parts of the filter or filter cartridge is reduced.

For this reason, it is necessary to find an appropriate pressure range and conduct an integrity test within that range. As a result of intensive study regarding this appropriate pressure range, we measured the diffusion flow rate or pressure hold value at two or more pressure points in a pressure range of 4 kg/cm2 or less for an anisotropic sterilization grade filter. By conducting a completeness test using the measured value and the differential value between measurement points as the inspection standard,
I discovered that the sensitivity can be maximized. The differential value is obtained by dividing the difference in measured values by the difference in measured pressure. If there is a defect in the filter or filter cartridge that allows bacteria or particulates to pass through, air will be blown out at a specific pressure depending on the pore size. Before that specific pressure, there is only a diffusion flow flowing out from the entire membrane surface, and in areas higher than that specific pressure, two types of flow are observed: a diffusion flow from the entire membrane surface and a viscous flow. Once we measured the flow rate of gas through the membrane before and after this particular pressure,
By calculating the amount of change, that is, the differential value, it becomes easy to discover the existence of defects. In addition, it is necessary to set the measurement pressure range to a range that includes defects that may leak bacteria or particulates.

This pressure range may be any pressure below 4 kg/al, but preferably, it is appropriate to measure at three points within the range of 2.5 kg/al to 4.0 kg/al.

This improved integrity testing method can be applied to any type of filter cartridge, but this effect is most pronounced when the incorporated membrane area is large. For example 0.
4rr! Single oven end or double oven end type pleated filter cartridges with an effective membrane area of 2.1rd to 2.1rd, and disk laminated filter cartridges with an effective membrane area of 0.05trf to 0.2nf can be mentioned. .

Example Polysulfone precision filtration membrane with an average pore size of 0.2 μm (
Bubble point value 5. 5kg/cd) to 0°2rIi
Integrity testing of the assembled disc-stacked filter cartridge I and filter cartridge II was carried out according to the method of the present invention. Test pressure is 2.5kg/at,
The test liquid was water at 3.25 kg/cof and 4.0 kg/cd, and the test liquid was filled into the filtration membrane by attaching the filter cartridge to the filter housing and sending ultrapure water at 25°C at a constant flow rate for 5 minutes. This was done by draining the liquid. The results are shown in column I of Table 1. Furthermore, the results of a sterilization filter test based on the method specified by ASTM are shown. (However, Pseudomonas Deminutor ATCC 19146 was used as the index surface.) As shown in Table 1, no abnormality was observed in the diffusion flow rate and the differential value of the diffusion flow rate in Sample I. On the other hand, in sample ■, no abnormality is observed in the diffusion flow rate value, but the differential value of the diffusion flow rate is 3, . 25 kg/ci value or 4.0 kg/cXl
is larger than the value of , which is abnormal. This suggests that sample (2) has a defect that causes air to blow out in the pressure range between 2.5 kg/cd and 3.25 kg/a+f. In addition, the sterilization results confirm that sample ■ had a defect.

As a result of disassembling the cartridge, it was found that sample (2) had a small defect.

Patent applicant: Fuji Photo Film Co., Ltd. 1990 2019/, Otsu month ends on 3rd

Claims (1)

[Claims] (1) Measure the diffusion flow rate or pressure hold value at two or more pressure points within a pressure range of 4 kg/cm^2 or less, and check the anisotropy using the measured value and the differential value between the measured points as the inspection standard. Integrity testing method for sterile grade filters or filter cartridges using membranes with