JPH05211863A - Germ-free tester of injection - Google Patents

Abstract

PURPOSE:To accurately practice germ-free test by removing bacterial contaminants due to human factor. CONSTITUTION:The objective germ-free tester is provided with a conveying means 1, a table 2 for specimen, a reversing means 10, a sucking means 3, a pump 4 and a filtering vessel 5. The tester is constituted so as to transfer a test specimen 7 fed from the conveying means 1 to the table 2 for specimen, reverse the test specimen 7 by the table 7 for specimen, inject a sample-sucking needle 3A into the reversed test specimen 7, transfer an injection of the test specimen 7 through the sample-sucking needle 3A into a filtering vessel 5 and filter the injection. Thereby, bacterial contaminants due to human factor is removed using a simple structure and germ-free test can surely be practiced.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a sterility test device for an injectable drug filled in a container, and more particularly to a device capable of preventing a bacterial contamination in a manual operation and accurately performing a sterility test.

[0002]

2. Description of the Related Art Injectables in containers are required to be aseptic, and manufactured injectables in containers are shipped after confirming that they are aseptic by a sampling inspection. The sterility test of injections is currently performed according to the Japanese Pharmacopoeia, General Test Method, Membrane Filter Method. In this test method, the test sample is carried in manually into a sterile room and is manually performed. The manual operation has a drawback that it takes a lot of time for a test, and has a fatal defect that false positives due to humans and operations occur. That is, a positive test result
There is a drawback that it is contaminated during the test regardless of the test sample.

An apparatus for eliminating these drawbacks is disclosed in Japanese Patent Laid-Open No. 63-63.
No. 230077. In the device described in this publication, the test sample is placed upright and the containers such as the washing liquid and the culture medium are inverted and placed on the base, and the test sample is pierced above and below the container for the washing liquid and the culture medium which are inverted. Arrange a needle thread,
The two piercing needles are connected by a hose connected to a pump, the piercing needles are pierced through the container for the test sample and the cleaning liquid, and the cleaning liquid is transferred by the pump. Further, a piercing needle is connected to the filtration container via a hose, the piercing needle is pierced into the test sample, and the sample is transferred from the test sample to the filtration container.

[0004]

The sterility test apparatus having this structure can perform a sterility test on a test sample without human intervention. For this reason, there is a feature that a defect caused by manpower can be eliminated. However, this device has a drawback that the structure is complicated and the manufacturing cost is extremely high. Further, there are drawbacks that a mechanism for processing test specimens of various kinds of containers is complicated and that it cannot be applied to flexible plastic bottles and plastic bags at all.

The present invention was developed for the purpose of solving these drawbacks, and the important object of the present invention is to:
It is an object of the present invention to provide an injectable sterility test device capable of removing bacterial contamination caused by human factors and performing an accurate sterility test with an inexpensive mechanism.

[0006]

In order to achieve the above-mentioned object, the injectable sterility test device of the present invention has the following constitution. The sterility test apparatus includes a transport means 1 and a sample table 2
The reversing means 10, the suction means 3, the pump 4, and the filtration container 5 are provided.

The transport means 1 is provided with two parallel guides 6 for continuously transferring a large number of test specimens 7 one after another.

The parallel guide 6 is transported while hooking and sliding the neck portion of the test sample 7 having a collar at the upper end.

The sample table 2 receives the test sample 7 transferred from the transport means 1, and is arranged so as to be connected to the tip of the transport means 1. A holder 8 that holds the test sample 7 and holds it in the inverted state is provided so that the received test sample 7 can be stably held even when it is inverted. The test specimen 7 itself is tiltably arranged so that it can be held and inverted.

The inverting means 10 tilts the sample table 2 so that the cap portion 7A of the test sample 7 held by the sample table 2 faces downward.

The suction means 3 has a sample suction needle 3A for sucking the sample from the inverted test sample 7 and transferring it to the filtration container 5. The suction means 3 pierces the sample suction needle 3A into the cap portion 7A of the test sample 7 to suck the sample from the test sample 7.

The pump 4 is connected to the suction means 3 and forcibly transfers the sample of the test sample 7 to the filtration container 5.

The filtration container 5 contains a membrane filter (not shown) for filtering the sample transferred from the test sample 7. The membrane filter of the filtration container 5 filters the liquid sample to capture bacteria.

In this sterilization test apparatus, the test sample 7 sent from the transport means 1 is transferred to the sample table 2, the test sample 7 is inverted by the sample table 2, and the inverted test sample 7 is attached to the sample suction needle 3A. And the pump 4 transfers the injection of the test sample 7 to the filtration container 5 through the sample suction needle 3A and filters it.

[0015]

The sterility test apparatus of the present invention inspects the sample of the test sample 7 as follows. A test sample 7 is supplied to the carrier 1. The test sample 7 slides along the parallel guide 6 of the transport means 1 and is sent to the sample table 2. The sample table 2 tilts and the test sample 7 is inverted, and the cap portion 7A is set downward. The sample suction needle 3A of the suction means 3 is pierced by the cap portion 7A of the test sample 7. The pump 4 is operated, and the injection of the test sample 7 is transferred to the filtration container 5 via the tube 9. The pump 4 pumps the sample / air into the filtration container 5 to filter the injection. The bacteria remain on the membrane filter of the filtration container 5. The membrane filter is transferred to the culture environment, and the bacteria are cultured and inspected for sterility.

[0016]

Embodiments of the present invention will be described below with reference to the drawings. However, the examples shown below are examples of a sterility test apparatus for embodying the technical idea of the present invention, and the sterility test apparatus of the present invention is made of materials, shapes, structures, and arrangements of components. It is not specific to the structure below. The sterility test apparatus of the present invention can be modified in various ways within the scope of the claims.

Further, in this specification, for easier understanding of the claims, the numbers corresponding to the members shown in the embodiments are referred to as "claims" and "means for solving the problems." It is added to the members shown in "Column". However, the members shown in the claims are not limited to the members of the embodiment.

The sterility test apparatus shown in FIGS. 1 to 5 has a carrying means 1, a sample table 2, an inverting means 10, and a suction means 3.
And a pump 4 and a filtration container 5.

The transporting means 1 is provided with two parallel guides 6 for continuously transferring a large number of test specimens 7 one after another. The parallel guide 6 is transferred while hooking and sliding the neck portion of the test sample 7 having a collar at the upper end. Therefore, the distance between the parallel guides 6 is larger than the outer diameter of the neck of the test sample 7,
It is designed to be narrower than the width of the brim at the tip of the cap portion 7A. The parallel guide 6 is inclined downward so that the test sample 7 slides under its own weight and is transferred. Inclination angle is 10-35
Adjusted to a range of degrees.

A stopper 11 for stopping the transfer of the test sample 7 is provided at the front of the transport means 1. Stopper 11
Is for sending out the test specimens one by one, and two rods are arranged in the passage of the test specimens 7 so that they can freely move in and out. The interval between the two rods is one test specimen 7 between them.
It is designed so that the neck can be inserted. The two rods cannot be retracted at the same time. The stopper 11 performs the following operation to send out the test specimens 7 one by one.

The rod on the front end side is pushed out to the transfer path of the conveying means 1, and the rod on the rear side is retracted. In this state, the test sample 7 supplied to the transport means 1 slides down to the position where it hits the rod at the tip. The rear rod is pushed out into the passage of the transport means 1.
In this state, the neck of one test sample 7 is inserted between the two rods. The rod at the front end is pulled in from the passage of the conveying means 1 without pulling in the rod at the rear part. The test sample 7 between the rods is sent out. After discharging the test sample 7, the operations from to are repeated,
The test sample 7 is sent in units of one.

As shown in the figure, the transport means 1 capable of sliding the test sample 7 by its own weight has the feature that the structure can be most simplified. However, the present invention does not specify a mechanism for sliding and moving the parallel guide 6 in this structure. Although not shown, a mechanism or the like may also be adopted that provides a member forcibly transferring the test sample with a chain along the parallel guide 6 and transfers the test sample.

The sample table 2 is provided with a base 12, a table 13 and a holder 8. The sample table 2 receives the test sample 7 transferred from the transport means 1, inverts the received test sample 7 upside down, and holds the cap portion 7A downward. Therefore, the sample table 2 is arranged at the tip of the transport means 1. The mounting table 13 has a plate shape with both sides bent upward so as to stably receive the test sample 7 sent from the transporting device 1 in a vertical posture.

With the sample table 2 in a substantially vertical posture,
FIG. 4 is a plan view of the holder 8 seen from above, and FIG.
Is shown in. In the holder 8 shown in this figure, the neck portion of the test sample 7 is clamped by two clamping pieces 8A and held at a fixed position. The clamp piece 8A clamps the neck portion of the test sample 7 at a fixed position in order to make the needle stick position of the test sample 7 placed on the mounting table 13 constant. Therefore, the sandwiching piece 8A of the holder 8
4, the left sandwiching portion is curved in an arch shape, and the right sandwiching piece 8A is provided with a protrusion. Left and right sandwiching piece 8A
(Not shown) is opened and closed by an air chuck.
The test sample 7 is supplied from the parallel guide 6 to the holder 8 with the sandwiching piece 8A opened, and then the sandwiching piece 8A is closed to sandwich the neck portion of the test sample 7. When the test sample 7 is discharged from the mounting table 13, the sandwiching piece 8A of the holder 8 is opened. As shown in FIG. 1, the sandwiching piece 8A of the holder 8 is located above the upright mounting table 13 and extends in a direction orthogonal to the mounting table 13 or at a certain angle. There is. Further, the holder 8 is arranged so that the test sample 7 is supplied from the parallel guide 6 in a state where the mounting table 13 is erected.
It is disposed below the parallel guide 6.

Further, as shown in FIGS. 1 and 4, the mounting table 13 extends to the tip to fix the lifting arm 14. The mounting base 13 completes the suction of the injectable agent, and in order to discharge the empty container of the test sample 7 in which the sample suction needle 3A is pulled out from the cap portion 7A, the base 12 can be raised through the discharge cylinder 15. Is linked to. The holder 8 is fixed to the base via an air chuck (not shown).

The discharge cylinder 15 raises the mounting table 13 from the base table only when the empty container of the test sample 7 is discharged from the mounting table 13. The height to be raised is designed so that the test sample 7 is removed from the holder 8 in which the sandwiching piece 8A is opened, that is, the mounting table 13 is higher than the upper end of the sandwiching piece 8A of the holder 8. The discharge cylinder 15 usually arranges the mounting table 13 in a lowered position.

The base 12 of the sample table 2 is connected to a frame 17 via a rotary shaft 16 so that the test sample 7 can be inverted. The rotating shaft 16 is horizontally extended and fixed to both sides of the lower end of the base in an upright posture, and both ends thereof are rotatably connected to the frame 17.

The base 12 is connected to the reversing means 10 so that the sample table 2 can be tilted. The reversing means 10 is
A reversing cylinder connects the upper end of the rod to the base, as shown in FIG. When the rod is extended, the reversing cylinder brings the sample table 2 into an upright posture, and when the rod is contracted, the sample table 2 is brought into an upright posture. As shown in FIG. 1, the reversing unit 10 inclines the cap portion 7A of the test sample 7 at a downward slope with the cap portion 7A facing downward. The inclination angle at which the test sample 7 is inverted is 20 to 70 degrees with respect to the horizontal plane, preferably, so that the test sample 7 on the mounting table 13 can be stably held by the holder 8 and the injectable drug to be stored can be completely sucked out. , 30
It is designed in the range of -60 degrees.

The suction means 3 sucks the injectable solution as a sample from the inverted test sample 7 and transfers it to the filtration container 5. The suction unit 3 includes a sample suction needle 3A that moves in the axial direction toward the cap portion 7A of the test sample 7. The sample suction needle 3A can be provided with an air filter, and can accommodate a test sample whose container is not flexible.
The sample suction needle 3A is connected to the tube 9 for transferring the injection agent, and is also fixed to the tip of the piercing cylinder so as to pierce the cap portion 7A. As shown in FIG. 2, the sample suction needle 3A is used as an inverted test sample 7
It is arranged at a position where it can be pierced toward the cap portion 7A. The piercing cylinder 18 pushes out the rod to suck the injection from the test sample 7 and the sample suction needle 3
Insert A into the cap portion 7A. The rod is contracted when the sample table 2 is tilted and when the test sample 7 is discharged from the mounting table 13.

Tube 9 connected to sample suction needle 3A
Is connected to the suction side of the pump 4 via a flow path sensor, and the discharge side of the pump 4 is connected to the filtration container 5.
The most suitable pump 4 is a pump 4 of the type that presses an annular tube 9 in the transfer direction for transfer. This type of pump 4 has the feature that it can be easily washed.

The filter container 5 is shown in FIG. The filtration container 5 has a cylindrical shape, and a membrane filter (not shown) for filtering the sample transferred from the test sample 7 is built in the bottom portion. The membrane filter filters the injection to separate and capture bacteria. In order to capture bacteria with the membrane filter, the tube 9 connected to the pump 4 and the air tube 20 connected to the joint 19 are connected to the upper end of the filtration container 5, and the discharge tube 21 is connected to the lower end.
Are connected. In the device shown in the figure, the discharge side of the pump 4 is bifurcated and the bifurcation path is connected to the two filtration containers 5.

The joint 19 opens and closes the air tube 20 'communicating with the filtration container 5, and its enlarged view is shown in FIG. The elbow union 27 is connected to both sides of the joint 19 shown in this figure. The elbow union 27 is connected with the air tube 20 (having an air filter in the middle) of the filtration container 5 with one touch and communicates with the air tube 20 ′. The air tube 20 'is
It is opened and closed by the on-off valve 22. Further, the pressure gauge 28 and the pressure sensor 2 are connected to the elbow union 27.
And 9 are connected. The pressure gauge 28 indicates the air pressure of the air tube 20 connected to the elbow union 27.

Immediately after the start of the filtration, the joint 19 closes the air tube 20 'with the opening / closing valve 22 and filters the filtration container 5 under a pressurized condition for filtration. At this time, the pressure sensor 29 controls the operation of the pump 4 to maintain the pressure in the filtration container 5 and thus the liquid level within a predetermined range. The sample is evenly transferred and filtered in both filtration containers 5. When the transfer / filtration is completed, the air tube 20 'is opened and the inside of the filtration container 5 is returned to the normal pressure.

In order to fill the medium into the filtration container 5 after the washing liquid is transferred and filtered, the suction side tube of the pump 4 is replaced by 3 tubes.
There are branches at some places. A cleaning liquid container 23 is provided at each branch.
And the two culture medium containers 24 are connected. One of the medium containers 24 is filled with a glucose / peptone medium for sterility test, and another container is filled with a thioglycolic acid medium for sterility test. The filtration container 5 is provided with a liquid level sensor that detects the liquid level.

An open / close valve 22 is provided in the middle of the tube 9. The on-off valve 22 is an L connected to the tip of the cylinder.
The tube 9 is clamped and closed by the rod 25, and the clamped state is released to open the valve. The on-off valve 22 includes a sample suction needle 3A,
The cleaning liquid container 23, the culture medium container 24, and the suction side and the discharge side of the filtration container 5 are connected.

Further, in the apparatus shown in the figure, a discharge table 26 is arranged on the upper surface of the suction means 3. The discharge table 26 is a table for discharging the empty container of the test sample 7 from which the injection solution has been sucked out. Therefore, it is positioned in front of the elevated mounting table 13 and is arranged to be inclined downward from the mounting table 13.

The discharge mechanism will be described below, for example. The discharge cylinder 15 operates to raise the platform 13 vigorously. The empty container jumps up from the mounting table 13 with a crack. The push-up arm 14 has a mechanism for surely jumping up the neck of the empty container. The empty container jumped up falls by gravity onto the discharge table 26 and slides down on its surface.

The sterility test apparatus shown in the figure is used as follows. [Step of setting up sterility test apparatus] The on-off valve 22 of the tube 9 connected to the washing liquid container 23 and the culture medium container 24 is closed to shut off the flow path of the tube 9 connected to each container. A washing solution 23, a glucose / peptone medium for sterility test (hereinafter referred to as GP medium) 24-A, and a thioglycolic acid medium for sterility test (hereinafter referred to as TGC medium) 24-B are attached. However, the volume of the medium corresponds to the volume of the filtration container 5. The air tube of the filtration container 5 is set in the joint 19. The drainage tube 21 of the filtration container 5 is set in the open / close valve 22. The tube 9 connected to the sample suction needle 3A is set on the flow path sensor, and after connecting to the pump 4, the flow path sensor is made operable. Test specimen 7 with the cap seal removed aseptically,
It is supplied to the conveying means 1 in an upright state.

[Step of Suctioning Injection of Test Specimen 7] The test specimen 7 is transferred from the transport means 1 to the mounting table 13 of the specimen table 2 in an upright posture. At this time, the holding piece 8A of the holder 8 is opened by the air chuck, and after the test sample 7 is supplied to the mounting table 13, the holding piece 8A of the holder 8 is closed and the neck portion of the holder 8 is held. It is sandwiched by the pieces 8A. The mounting table 13 tilts, and the cap portion 7A of the test sample 7
To face downward. At this time, the sample suction needle 3 of the suction means 3
A is arranged in the retracted position. The sample suction needle 3A of the suction means 3 advances and is pierced by the cap portion 7A of the test sample 7. The pump 4 starts operating and starts transferring the injection from the test sample 7 to the filtration container 5. In this state, the air tube 20 'is closed by the opening / closing valve 22 of the joint 19 that connects the air tube 20 connected to the upper end of the filtration container 5. The pressure sensor of the joint 19 controls the operation of the pump 4 to control the internal pressure of the filtration container 5 within a certain range. When the flow rate of the pump 4 exceeds the flow rate of the membrane filter, the internal pressure of the filtration container 5 rises. On the contrary, when the flow rate of the pump 4 becomes smaller than the flow rate of the membrane filter, the internal pressure of the filtration container 5 decreases. Therefore, the flow rate of the pump 4 can be controlled to control the internal pressure of the filtration container 5. When the injection is completely discharged from the test sample 7, the operation of the pump 4 is stopped, the sample suction needle 3A is retracted and withdrawn from the cap portion 7A. The discharge of the injection from the test sample 7 is detected by the flow channel sensor. The sandwiching piece 8A of the holder 8 is opened, the mounting table 13 is raised, and the empty container of the test sample 7 that has completed the ejection of the injection is ejected from the ejection table 26, and thereafter, the steps from to are repeated to make a plurality of steps. The injection is transferred from the test sample 7 to the filtration container 5.

[Step of Dispensing Medium into Filter Container 5] After transferring the injection to the filter container 5 and filtering with a membrane filter, the on-off valve 22 of the tube 9 connected to the suction means 3 is closed, The opening / closing valve 22 of the tube 9 connected to the cleaning liquid container 23 is opened. In this state, the opening / closing valve 22 of the tube 9 connected to the medium container 24 remains closed. The pump 4 is operated to transfer the cleaning liquid to the filtration container 5, and when the cleaning liquid reaches a predetermined liquid level, the liquid level sensor is activated to close the air tube 20 '. The operation of the pump 4 is continued, the cleaning liquid is discharged from the filtration container 5 through the membrane filter. In this way, the membrane filter and the filtration container 5 are each washed with a predetermined amount of cleaning liquid.
Clean inside. The tube 9 of the medium container 24 filled with the GP medium is opened, and the tube 9 of the container filled with the TGC medium is kept closed. The tube 9 connected to the left filtration container 5 is opened, and the tube 9 connected to the right filtration container 5 is closed. In this state, the pump 4 is operated to fill the left filtration container 5 with the GP medium. At this time, the discharge tube 21 connected to the lower end of the filtration container 5 is closed. In this way, the left filtration container 5 is filled with a predetermined amount of GP medium. G
The filling level of the P medium is detected by a liquid level sensor provided in the filtration container 5, and the sensor operation causes the tube 9 connected to the left filtration container 5 to be blocked, and at the same time, the right filtration container 5
The tube 9 connected to is opened. The drain tube 21 is opened, the air tube 20 'is closed, and the pump 9 pressurizes the tube 9'.
Transfer the remaining GP medium remaining inside to the filtration container 5 on the right,
Discharge through the membrane filter of the container. After that, the pump 4 is stopped and the tube 9 connected to the GP medium container is closed. The tube 9 connected to the TGC medium container and the tube 9 of the right filtration container 5 are opened and the discharge tube 21 is closed while the tube 9 connected to the left filtration container 5 containing the GP medium is closed. Pump 4 in this state
Is operated to transfer and fill the TGC medium into the right filtration container 5. The filling amount is controlled by the liquid level sensor described in. The tube 9 connected to the TGC medium container and the tube 9 of the right filtration container 5 are closed, and the pump 4 is stopped. The tube 9 connected to the left and right filtration containers 5 is closed with a pinch cock, a double clip or the like, and the end is cut from the closed portion. The outlet of the filtration container 5 filled with the GP medium and the TGC medium was closed with a stopper such as silicon, and
Are cultured in an incubator controlled to a predetermined temperature environment, and the test judgment is performed.

[0041]

The injectable sterilization test apparatus of the present invention simplifies the entire mechanism, simplifies the sterility test of test samples, and removes bacterial contamination due to human factors to accurately test. There is a feature that can be done. That is, the sterility test apparatus of the present invention is a sample in which the test sample supplied to the transport means is inverted by the sample table so that the cap portion faces downward, and the sample suction needle of the suction means is pierced through the cap portion in this posture. This is because the injection can be transferred to the filtration container and filtered. The transport means for transferring the test sample by the parallel guide and the sample table for inverting the test sample on the mounting table can efficiently process the test samples having different shapes and sizes, especially the test sample contained in the plastic container, and further inject it. The container of the test sample that sucked out the agent can be easily discharged because it is inverted and placed on the mounting table, and the transport means, the sample table, and the suction means can efficiently filter the injection from the test sample one after another. Can be transferred to. Therefore, the sterility test apparatus of the present invention has a feature that human injection is eliminated and a test sample filled with an injection can be efficiently and accurately inspected.

[Brief description of drawings]

FIG. 1 is a side view of an injection sterility test apparatus showing an embodiment of the present invention.

FIG. 2 is a side view showing the sample table and suction means shown in FIG.

FIG. 3 is a schematic perspective view of the sterility test apparatus shown in FIG.

FIG. 4 is a plan view of a mounting table.

FIG. 5 is a perspective view showing a mechanism for phase / filtering an injection from a test sample into a filtration container.

6 is a perspective view showing a joint of the apparatus shown in FIG.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Conveying means 2 ... Sample stand 3 ... Suction means 3A ... Sample suction needle 4 ... Pump 5 ... Filtration container 6 ... Parallel guide 7 ... Test specimen 7A ... Cap part 8 ... Holder 8A ... Clamping piece 9 ... Tube 10 ... Inversion Means 11 ... Stopper 12 ... Base 13 ... Platform 14 ... Push-up arm 15 ... Ejection cylinder 16 ... Rotating shaft 17 ... Frame 18 ... Penetration cylinder 19 ... Joint 20 ... Air tube 20 '... Air tube 21 ... Ejection tube 22 ... Open / close valve 23 ... Washing liquid container 24 ... Medium container 25 ... L rod 26 ... Discharge stand 27 ... Elbow union 28 ... Pressure gauge 29 ... Pressure sensor

Claims (1)

[Claims] 1. A sterility test device for injection having the following constitution. The sterility test apparatus comprises a test sample transporting means (1) having two parallel guides (6) for sliding and transporting the neck of the test sample having a collar at the upper end, and a tip of this transporting means (1). It is connected and arranged,
The test sample (7) has a holder (8) for holding the test sample (7) transferred from the transporting means (1) and holding the test sample in an inverted state, and is itself tiltably arranged. ), And the cap part (7A) of the test sample (7) by tilting the sample table (2).
And the suction means (3) for piercing the sample suction needle (3A) into the cap portion (7A) of the test sample (7) held on the inverted sample table (2). And the test sample (7) connected to the sample suction needle (3A) of the suction means (3).
It is equipped with a pump (4) for transferring the injection, and a filter container (5) connected to the pump (4) for transferring the injection from the test sample (7) and filtering the injection. , The test sample (7) sent from the transport means (1) is the sample table (2)
The test sample (7) is inverted by the sample table (2), and the sample suction needle (3A) of the suction means (3) is pierced through the cap part (7A) of the inverted test sample (7) to suck the sample. Test specimen via needle (3A)
An injection sterility test device configured to transfer the injection of (7) to the filtration container (5).