JP7474222B2 - Method for drying a liquid supply system - Google Patents

Description

The present invention relates to a method for drying a liquid supply system that includes a liquid tank that stores liquid and a filter disposed on the outlet side of the tank.

Liquid supply systems equipped with a liquid tank for storing liquid and a filter for filtering the liquid in the liquid tank when supplying the liquid to another device are used, for example, to supply injection liquid to a filling machine that fills injection liquid into containers such as vials. In such liquid supply systems, when changing the medicinal liquid to another medicinal liquid, it is necessary to clean and dry the liquid tank for storing the medicinal liquid in the system, the filter and other devices disposed on the outlet side of the liquid tank, and the pipelines connecting each device.

With conventional technology, when piping equipment is reused, it must first be disassembled and cleaned into individual parts. After that, each unit must be reassembled, steam sterilized, and then reassembled after drying to create a series of piping equipment, which is a very time-consuming and labor-intensive process. Furthermore, steam sterilizing each unit, drying, and then reassembling the piping equipment increases the risk of bacterial infection, making it difficult to maintain the strict manufacturing guidelines for injectables.

In addition, because the liquid tank has a relatively large volume and low pressure resistance, the pressure of the drying gas circulating through the liquid tank during the drying process cannot be increased. In contrast, the filter material arranged on the outlet side of the liquid tank has high pressure resistance when gas is circulated, especially when wet, and it takes a very long time to dry the filter material with low-pressure drying gas.

The present invention aims to solve these problems of the conventional technology and provide a method for more efficiently drying a liquid supply system that includes a liquid tank for storing liquid and a filter for filtering the liquid in the liquid tank when the liquid is supplied to another device.

To achieve the above-mentioned object, the present invention provides a drying method for a liquid supply system having a liquid tank for storing liquid and a filter disposed on the outlet side of the tank, which includes separating the liquid tank from the filter, circulating a drying gas at a predetermined first pressure through the liquid tank to dry the liquid tank, and circulating a drying gas at a predetermined second pressure through the filter to dry the filter, the second pressure being higher than the first pressure.

According to the present invention, the filter can be dried with drying gas at a higher pressure than before, so it is possible to complete the drying process of the entire liquid supply system in a significantly shorter time. It is possible to completely dry the piping equipment of a liquid supply device, for example an automated injection production line, in a short time without disassembling it. It is possible to dry the entire line in a short time without disassembling the present invention.

In addition, an automated production line for injections requires a sealed space that maintains sterility through stationary cleaning and stationary sterilization, but the present invention is particularly advantageous when applied to a production line for preparations that must not contain moisture, such as oil-based preparations. In the case of aqueous injections, sterilization usually leaves residual sterile water in the line, but in terms of the manufacturing process, even if there is residual water, the quality level of the residual water is equivalent to that of water for injection, so it is possible to deal with this by initially disposing of the water that is slightly diluted in mixture with the initial liquid of the drug. However, in the case of oil-based preparations, etc., since water contamination is strictly prohibited, the entire line needs to be dried after sterilization, and in reality, the line structure is complex and multiple sterilization filters, etc. are tangled on the line, making it extremely difficult to completely dry the line. In addition to ordinary oil-based preparations, this system can also be applied to the production of adjuvants used in vaccine preparations, for example.

1 is a schematic diagram showing an example of a liquid supply system to which the present invention is applied.

Hereinafter, preferred embodiments of the present invention will be described with reference to the accompanying drawings.
In Fig. 1, the sterile liquid supply system 100 can be used to supply a liquid drug solution to a filling machine that fills a container such as a vial with a liquid drug solution containing a surfactant such as natural oils (e.g., olive oil, floral oil, sesame oil, camellia oil, etc.), mineral oils (e.g., paraffin oil), and surfactants (e.g., non-ionic surfactants such as fatty acid substituted sorbitan surfactants, fatty acid esters of polyethoxylated sorbitol (TWEEN (registered trademark)), fatty acid polyethylene glycol esters, polyethoxylated fatty acids, polyethoxylated isooctylphenol/formaldehyde polymers, polyoxyethylene fatty acid alcohol ethers, polyoxyethylene nonylphenyl ether, and polyoxyethylene isooctylphenyl ether). The sterile liquid supply system 100 includes a liquid tank 118 that stores liquid supplied from an upstream fluid supply system (not shown) via a supply line 102. The upper fluid supply system may include a general-purpose fluid supply system that supplies fluids such as nitrogen, clean air, pure steam, water for injection, and cooled water for injection, in addition to a supply system (not shown) for the medicinal liquid to be filled.

The general-purpose fluid supply system includes, among other things, a drying gas supply device that supplies drying gas to the sterile liquid supply system 100. The drying gas supply device may include a blower (not shown) or a compressor (not shown) as a gas supply source that supplies drying gas, such as air, to the supply line 102, a filter (not shown) that filters the gas supplied from the gas supply source to the supply line 102, a pressure regulating valve (not shown) that adjusts the pressure of the gas supplied from the gas supply source to the supply line 102, a pressure sensor (not shown) or a pressure gauge (not shown) that measures the pressure of the gas supplied to the supply line 102, a heater (not shown) that heats the temperature of the gas supplied to the supply line 102, and a temperature sensor (not shown) or a thermometer (not shown) that measures the temperature of the gas supplied to the supply line 102.

The liquid tank 118 receives and prepares medicinal solutions and injections supplied from the fluid supply system, such as natural oils (e.g., olive oil, sesame oil, camellia oil, etc.) that are often used as solvents or additives in injections, mineral oils (e.g., paraffin oil), and surfactants (e.g., nonionic surfactants, such as fatty acid substituted sorbitan surfactants, fatty acid esters of polyethoxylated sorbitol (TWEEN (registered trademark)), fatty acid polyethylene glycol esters, polyethoxylated fatty acids, polyethoxylated isooctylphenol/formaldehyde polymers, polyoxyethylene fatty acid alcohol ethers, polyoxyethylene nonylphenyl ethers, and polyoxyethylene isooctylphenyl ethers). A first shutoff valve 124 is provided in the supply line 102.

The thus prepared liquid medicine is supplied to the filling machine through the process line 104 connected to the bottom of the liquid tank 118. At least one filter is provided in the process line 104 to remove impurities from the liquid medicine supplied to the filling machine. In this embodiment, the filter includes a pre-filter or first filter 120 and a post-filter or second filter 122. The first and second filters 120 and 122 include housings for accommodating filter media. Second and third cutoff valves 125 and 126 are provided in the process line 104a upstream of the first filter 120, fourth and fifth cutoff valves 128 and 129 are provided in the process line 104b between the first and second filters 120 and 122, and a fifth cutoff valve 129 is provided downstream of the second filter 122 in the process line 104.

In the process line 104, a main drain line 106 is connected between the second and third cutoff valves 125, 126. A seventh cutoff valve 132 is disposed in the main drain line 106. In the main drain line 106, downstream of the seventh cutoff valve 132, filter drain lines (first and second filter drain lines) 114, 116 of the first and second filters 120, 122 are connected. Eighth and ninth cutoff valves 134, 136 are disposed in the first and second filter drain lines 114, 116.

The process line 104 and the main drain line 106 are further connected by the first and second residual water drain lines 146, 148. More specifically, the first residual water drain line 146 is connected at one end between the fourth and fifth shutoff valves 128, 129 provided in the portion 104b between the first and second filters 120, 122 in the process line 104, and at the other end between the portion where the first and second filter drain lines 114, 116 are connected in the main drain line 106. The second residual water drain line 148 is connected at one end between the second filter 122 and the sixth shutoff valve 130 in the main drain line 106, and at the other end to the downstream side of the second filter drain line 116 in the main drain line 106. The first and second residual water drain lines 146, 148 are provided with tenth and eleventh shutoff valves 138, 140, respectively.

A filter supply line 108 is also connected to the supply line 102 upstream of the first shutoff valve 124. The filter supply line 108 branches into first and second filter supply lines 110, 112. The first filter supply line 110 is connected to a first filter 120, and the second filter supply line 112 is connected to a second filter 122. A twelfth shutoff valve 150 is provided in the first filter supply line 110, and a thirteenth shutoff valve 152 is provided in the second filter supply line 112.

A method for drying the sterile liquid supply system 100 will now be described.
After sterilization of delivery system 100 is completed, fluid tank 118, first filter 120, and second filter 122 are sequentially dried as described below.

In this specification, "separation" does not mean that the liquid tank 118 and the first and second filters 120, 122 are physically removed from the supply line 102, the process line 104, the drain line 106, and the filter supply line 108, but rather that the liquid tank 118 and the first and second filters 120, 122 are not fluidly connected or in communication with each other.

Drying gas, for example air heated to 100°C, is supplied to the supply pipe 102. At this time, the drying gas is supplied at a first supply pressure. The first supply pressure can be appropriately determined to be equal to or lower than the allowable pressure of the liquid tank 118. The first supply pressure can be determined, for example, in advance by experiment. As an example, the first supply pressure can be 0.17 MPa. The supply time of the drying gas to the liquid tank 118 can be a time sufficient to dry the liquid tank 118, and can be determined, for example, in advance through experiment.

(1) With the first through thirteenth shutoff valves all closed, the first shutoff valve 124, the second shutoff valve 125, and the seventh shutoff valve 132 are opened. This connects the liquid tank 118 to the supply line 102 and the drain line 106. At this time, the liquid tank 118 is separated from the first and second filters 120, 122. After a predetermined time has elapsed, the first shutoff valve 124, the second shutoff valve 125, and the seventh shutoff valve 132 are closed.

(2) Next, the drying gas is supplied at a second supply pressure. The second supply pressure can be appropriately determined to be a pressure that is equal to or lower than the allowable pressure of the first and second filters 120, 122 and allows aeration through the filter media of the first and second filters 120, 122. The second supply pressure can be determined, for example, by experiments in advance. As an example, the second supply pressure can be 0.45 MPa. The supply time of the drying gas to the first and second filters 120, 122 can be a time sufficient to dry the first filter 120, and can be determined, for example, by experiments in advance.

(3) The third shutoff valve 126, the seventh shutoff valve 132, the eighth shutoff valve 134, and the twelfth shutoff valve 150 are opened. This allows the first filter 120 (primary side) to communicate with the supply line 102 and the main drain line 106. At this time, the first filter 120 is separated from the liquid tank 118 and the second filter 122.

(4) After a predetermined time has elapsed, the third shutoff valve 126, the seventh shutoff valve 132, and the eighth shutoff valve 134 are closed, and the fourth shutoff valve 128 and the tenth shutoff valve 138 are opened. This allows the first filter 120 (secondary side (the side to which the filtrate is supplied)) to communicate with the supply line 102 and the main drain line 106. At this time, the first filter 120 is separated from the liquid tank 118 and the second filter 122. After a predetermined time has elapsed, the fourth shutoff valve 128, the tenth shutoff valve 138, and the twelfth shutoff valve 150 are closed.

Next, the cutoff valve is operated as follows so that only the second filter 122 communicates with the supply line 102 and the main drain line 106. During this time, the second supply pressure of the drying gas is maintained as it is.
(5) The fifth cutoff valve 129, the tenth cutoff valve 138, the ninth cutoff valve 136, and the thirteenth cutoff valve 152 are opened. This allows the second filter 122 (primary side) to communicate with the supply line 102 and the main drain line 106. At this time, the second filter 122 is separated from the liquid tank 118 and the second filter 122.

(6) After a predetermined time has elapsed, the fifth shutoff valve 129, the tenth shutoff valve 138, and the ninth shutoff valve 136 are closed, and the eleventh shutoff valve 140 is opened. This causes the second filter 122 (secondary side (the side to which the filtrate is supplied)) to communicate with the supply line 102 and the main drain line 106. At this time, the second filter 122 is separated from the liquid tank 118 and the first filter 120. After a predetermined time has elapsed, the eleventh shutoff valve 140 and the thirteenth shutoff valve 152 are closed.

(7) Next, drying gas is supplied at the first supply pressure, and the first cutoff valve 124, the second cutoff valve 125, the third cutoff valve 126, the fourth cutoff valve 128, the fifth cutoff valve 129 and the eleventh cutoff valve 140 are opened to communicate the liquid tank 118, the first and second filters 120, 122 and the process line 104. Until the start of the next liquid filling process, the sixth cutoff valve 130 is kept closed to maintain the sterile liquid supply system 100 in a state isolated from the filling machine.

According to this embodiment, the first and second filters 120, 122 can be dried with drying gas at a higher pressure than in the past, making it possible to complete the drying process of the entire sterile liquid supply system 100 in a significantly shorter time than in the past.

100 Sterile liquid supply system 102 Supply line 104 Process line 106 Drain line 106
108 filter supply line 110 first filter supply line 112 second filter supply line 114 first filter drain line 116 second filter drain line 118 liquid tank 120 first filter 122 second filter 124 first cut-off valve 125 second cut-off valve 126 third cut-off valve 128 fourth cut-off valve 129 fifth cut-off valve 130 sixth cut-off valve 132 seventh cut-off valve 134 eighth cut-off valve 136 ninth cut-off valve 138 tenth cut-off valve 140 eleventh cut-off valve 150 twelfth cut-off valve 152 thirteenth cut-off valve

Claims (4)

1. A method for drying a liquid supply system, comprising:
The liquid supply system comprises:
a liquid tank connected to a universal fluid supply system via a supply line;
a shutoff valve disposed in the supply line;
a process line connecting the liquid tank to a filling machine;
a filter disposed in the process line;
two shutoff valves disposed in the process line between the liquid tank and the filter;
a main drain line connected to the process line between the two shutoff valves of the process line;
a filter supply line connecting the filter to the supply line upstream of the shutoff valve;
a shutoff valve disposed in the filter supply line;
a filter drain line connecting the filter to a main drain line;
The drying method is
isolating the liquid tank from the filter by opening a shutoff valve in the supply line and closing a shutoff valve in the filter supply line;
opening one of the two cutoff valves in the process line that is closer to the liquid tank and closing the other cutoff valve that is closer to the filter;
a drying gas having a first predetermined pressure is caused to flow from the general-purpose fluid supply system into the liquid tank to dry the liquid tank;
closing a shutoff valve in the supply line and opening a shutoff valve in the filter supply line;
flowing a drying gas from the shutoff valve universal fluid supply system at a second predetermined pressure through the filter to dry the filter;
A drying method, characterized in that the second pressure is higher than the first pressure. the filter includes a first filter and a second filter;
the filter supply line includes a first filter supply line connected to the first filter and a second filter supply line connected to the second filter;
a cutoff valve is disposed in each of the first and second filter supply lines;
After the drying gas is circulated through the liquid tank,
isolating the first filter from the liquid tank and the second filter by opening a shutoff valve in the first filter supply line and closing a shutoff valve in the second filter supply line;
2. The method according to claim 1, further comprising the step of passing a drying gas at said second pressure through said first filter to dry said first filter. After flowing the drying gas through the first filter supply line,
isolating the second filter from the liquid tank and the first filter by closing a shutoff valve in the first filter supply line and opening a shutoff valve in the second filter supply line ;
3. The method according to claim 2, further comprising the step of passing a drying gas at said second pressure through said second filter to dry said second filter. After flowing the drying gas through the second filter supply line,
4. The method of claim 3, further comprising connecting the liquid tank, the first filter and the second filter to the universal fluid supply system by opening respective shutoff valves in the process line, the first filter supply line and the second filter supply line, and flowing a drying gas through the liquid tank, the first filter and the second filter at the first pressure to dry the liquid tank, the first filter and the second filter .

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