JP2005058415A - Carry-in method of medical instrument and production method of prefilled syringe - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a carry-in method of the medical instruments aseptically into the aseptic areas and a production method of a prefilled syringe which enables the production of the prefilled syringe in a shorter time. <P>SOLUTION: In the production method of the prefilled syringe, the radiation-sterilization is applied to an outer cylinder 71 sealed in a packing material 14 outside an isolator 2 together with the packing material 14. Then, the outer cylinder 71 is put together with the packing material 14 from outside the isolator 2 into a small chamber 3 which is provided on the wall part of the isolator 2 and made sealable and communicable with the inside or outside thereof. While the small chamber 3 is kept hermetically closed, the packing material 14 is exposed to the hydrogen peroxide gas to apply the gas sterilization onto the outer surface thereof and thereafter, the outer cylinder 71 is carried into the isolator 2 together with the packing material 14 from the small chamber 3 released from the closed state thereof. The packing material 14 is unsealed and the outer cylinder 71 is taken out of the packing material 14. Then, the outer cylinder 71 is filled with a liquid preparation and the individual members are mounted to complete the prefilled syringe. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a method for carrying in a medical instrument and a method for producing a prefilled syringe.

  For example, pharmaceutical products such as protein preparations and hormonal agents are denatured by heating, and thus cannot be heat sterilized after filling in a medical container. Therefore, the filling operation of such a medicine into a medical container is performed in an aseptic environment.

  As this sterile environment, the use of an isolator is recommended for the purpose of completely eliminating contamination caused by the entry and exit of “people” (see, for example, Patent Document 1).

  The isolator is an isolation device that accommodates production equipment such as a filling device, and the operation of the equipment by a “person” is usually performed from the outside through a glove or a half suit attached to the wall of the isolator. For this reason, there is no contamination due to the entry and exit of “people” during the operation of the facility, and once the inside of the isolator is sterilized, it is theoretically possible to maintain aseptic conditions for a long period of time.

  Here, when it is going to fill a chemical | medical solution in such an isolator, the medical container with which a chemical | medical solution is filled will be carried in in an isolator after performing a sterilization process outside. This medical container is conventionally sterilized by autoclave sterilization.

  However, in autoclave sterilization, it is necessary to dry the water droplets adhering to the surface after sterilization of the medical container. Including this drying step, it takes about 2 hours.

  Therefore, when mass-producing pharmaceuticals, a large-capacity sterilization tank is required so that a large number of medical containers can be sterilized at one time. However, it is difficult to directly connect a large-capacity sterilization tank to an isolator. There is a problem that there is.

  In addition, in autoclave sterilization, there is a problem that the medical container is deformed by heating during the sterilization process.

JP 2002-301138 A

  The objective of this invention is providing the carrying-in method of the medical device which can carry in a medical device aseptically in an aseptic area | region, and the manufacturing method of the prefilled syringe which can manufacture a prefilled syringe in a shorter time.

Such an object is achieved by the present inventions (1) to (14) below.
(1) A method for carrying in a medical device for aseptically carrying a medical device into a sterile field,
With respect to the medical device enclosed in the packaging material, radiation sterilization is performed together with the packaging material,
Next, the medical device is put together with the packaging material in a sealable chamber, the packaging material is exposed to sterilization gas, and the outer surface thereof is gas sterilized,
Thereafter, while maintaining the sterilized state inside and outside the packaging material, the medical device is transported together with the packaging material to the aseptic region, the packaging material is opened, and the medical device is taken out from the packaging material. How to carry in medical equipment.

  (2) The method for carrying in a medical instrument according to (1) above, wherein the medical instrument is carried into the aseptic area from a non-sterile area.

  (3) The delivery method of the medical instrument according to (2), wherein the small chamber is provided at a boundary portion between the aseptic region and the non-sterile region.

(4) A method for carrying in a medical device for aseptically carrying a medical device from a non-sterile region to a sterile region,
On the non-sterile region side, radiation sterilization is performed together with the packaging material for the medical instrument enclosed in the packaging material,
Next, the medical device is placed together with the packaging material in a small chamber that is provided at a boundary portion between the aseptic region and the non-sterile region, can be sealed, and can communicate with the aseptic region and the non-sterile region. Putting from the non-sterile area side, with the chamber sealed, exposing the packaging material to sterilizing gas, sterilizing its outer surface,
Thereafter, the medical device is transported together with the packaging material to the aseptic region from the small chamber where the sealed state is released, the packaging material is opened, and the medical device is taken out from the packaging material. How to carry in medical equipment.

  (5) The radiation sterilization is performed for each of the packaging material and the second packaging material with respect to the medical device in a state where the packaging material in which the medical device is enclosed is enclosed in a second packaging material. The medical device carrying-in method according to any one of (1) to (4) above.

  (6) The method for carrying in a medical instrument according to any one of (1) to (5), wherein the sterilizing gas is a gas containing hydrogen peroxide.

  (7) The method for carrying in the medical instrument according to (6), wherein the gas containing hydrogen peroxide is supplied into the small chamber in a reduced pressure state.

  (8) The method for carrying in the medical device according to (7), wherein the pressure in the small chamber in the decompressed state is 50 kPa or less.

  (9) The method for carrying in a medical instrument according to (7) or (8), wherein a gas containing hydrogen peroxide is supplied into the small chamber, and after a predetermined time has elapsed, the pressure in the small chamber is reduced again.

  (10) The method for carrying in the medical device according to (9), wherein the predetermined time is 10 minutes or less.

(11) The medical device carrying-in method according to any one of (1) to (10), wherein a capacity of the small chamber is 1 L to 1 m ³ .

  (12) The method for loading a medical instrument according to any one of (1) to (11), wherein the aseptic region is an internal space of an isolator.

  (13) The medical device loading method according to any one of (1) to (12), wherein the medical device is filled with a liquid preparation and stored.

(14) A step of bringing the outer cylinder of the prefilled syringe into the aseptic region by the method for transporting a medical instrument according to any one of (1) to (13) above,
And a step of filling the outer cylinder with a liquid preparation in the aseptic region.

  According to the present invention, it is possible to sterilize a medical instrument to be carried into the aseptic region in a short time, and it is possible to carry in this sterilized medical device into the aseptic region while reliably maintaining the aseptic state. .

  In the present invention, since high-temperature and high-pressure steam sterilization is not used, it is not necessary to consider thermal deformation of the medical device, and the range of selection of the constituent material of the medical device is widened.

  Moreover, according to this invention, a prefilled syringe can be manufactured in a shorter time.

  Hereinafter, a method for carrying in a medical device and a method for producing a prefilled syringe according to the present invention will be described in detail based on preferred embodiments shown in the accompanying drawings.

  In this specification, the “sterile area” refers to an area having a relatively high sterilization level (degree of sterilization) relative to the “non-sterile area”. It includes both areas that are not applied and areas that are sterilized.

  In the following description, the medical device loading method of the present invention is applied to a prefilled syringe manufacturing method in which the outer cylinder of a prefilled syringe is loaded into an isolator and the outer cylinder is filled with a chemical solution (liquid preparation). To do.

<Configuration of chemical filling system>
First, the chemical solution filling system used in the method for producing a prefilled syringe of the present invention will be described.

  FIG. 1 is a schematic diagram showing a configuration of a chemical solution filling system used in the method for producing a prefilled syringe of the present invention. In FIG. 1, some members are omitted in order to avoid complication of the drawing.

  A chemical solution filling system 1 shown in FIG. 1 includes an isolator 2, a small chamber 3 provided at the boundary between the isolator 2 and the outside, and a hydrogen peroxide gas supply device 40 (sterilization means 4) provided outside the isolator 2. And a chemical filling device 6 disposed in the isolator 2.

  In this chemical solution filling system 1, the internal space of the isolator 2 constitutes a sterile area, and the external space of the isolator 2 constitutes a non-sterile area.

  The isolator 2 is provided with a globe 21 and an air supply blower 22 with a built-in HEPA (High Efficiency Paticulate Air) filter.

  The glove 21 is provided on the wall or bottom of the isolator 2, and the operator attaches the glove 21 to enter the chemical solution filling device 6 or the like from the outside of the isolator 2 without entering the isolator 2. The equipment stored in the isolator 2 can be operated.

  The air supply blower 22 ejects a sterilizing gas such as hydrogen peroxide introduced through the valve 221 into the isolator 2. The inside of the isolator 2 is sterilized periodically by the sterilizing gas ejected from the air supply blower 22. This regular sterilization operation is performed at a frequency of about once a week, for example.

In the isolator 2, a chemical solution filling device 6 is accommodated.
The chemical solution filling device 6 is a device that injects a predetermined amount of a chemical solution (liquid preparation) into the outer cylinder 71 of the prefilled syringe 7, for example, and has a chemical solution introduction unit 61 and a chemical solution injection unit 62.

  One end of a chemical solution introduction tube 8 is connected to the chemical solution introduction unit 61, and the chemical solution is introduced through the chemical solution introduction tube 8. The chemical solution introduced into the chemical solution introducing unit 61 is supplied to the chemical solution injecting unit 62 through the chemical solution channel pipe 63.

  The chemical liquid injection unit 62 discharges a chemical liquid in a predetermined amount and injects it into an outer cylinder (medical instrument) 71, a pressurizing mechanism (not shown) for discharging the chemical liquid, a chemical liquid discharge nozzle 621, and the like. And have.

  For example, the chemical liquid injector 62 sequentially injects a predetermined amount of chemical liquid into the outer cylinder 71 that is conveyed immediately below.

  Further, a chemical liquid adjustment tank (not shown) is connected to the other end of the chemical liquid introduction pipe 8 so that the chemical liquid stored in the chemical liquid adjustment tank is introduced into the chemical liquid introduction part 61 via the chemical liquid introduction pipe 8. It has become.

A small chamber 3 is provided in the wall portion of the isolator 2.
The small chamber 3 has a cylindrical small chamber body 30 whose both ends are open. The small chamber body 30 is provided through the wall portion of the isolator 2, and has a first opening 36 that opens to the inside of the isolator 2 at one end and a second opening 37 that opens to the outside of the isolator 2 at the other end. And have. Thereby, the small chamber 3 can communicate with the inside of the isolator 2 and the outside.

  The small chamber body 30 is detachably mounted with a first lid 33 that hermetically seals the first opening 36 and a second lid 34 that hermetically seals the second opening 37. Is possible.

  The inside of the small chamber 3 is hermetically sealed by attaching a first lid 33 and a second lid 34 to both ends of the small chamber main body 30, respectively.

  A first valve 31 and a second valve 32 are provided on the side wall of the small chamber main body 30 so as to communicate with the inside of the small chamber main body 30. One end of a steam supply pipe 41 connected to the hydrogen peroxide gas supply device 40 is connected to the first valve 31, and a pump connection pipe 111 connected to the pump 11 is connected to the second valve 32. One end is connected.

  The pump 11 exhausts air in the small chamber 3 or supplies air into the small chamber 3, and the pressure in the small chamber 3 can be adjusted by adjusting the exhaust amount and the air supply amount.

The capacity of the small chamber 3 is appropriately set according to the size of the packaging material 14 to be accommodated in the sterilization process in the small chamber 3 described later, and is not particularly limited, but is preferably about 1 L to 1 m ³ (1000 L). More preferably, it is about 5-20L. If the capacity of the small chamber 3 is too small, the size of the packaging material 14 that can be accommodated is limited. On the other hand, if the capacity of the small chamber 3 is too large, a large amount of sterilization gas or the like is required for sterilizing the small chamber 3 and the cost increases. There is a risk.

  The small chamber 3 may be configured to be detachable with respect to the wall portion of the isolator 2.

  Outside the isolator 2, a hydrogen peroxide gas supply device 40 is installed as the sterilization means 4.

  The hydrogen peroxide gas supply device 40 heats the hydrogen peroxide to form vaporized vapor, and supplies the vaporized vapor of hydrogen peroxide (hydrogen peroxide gas) into the small chamber 3 to sterilize the small chamber 3. To do. The sterilization method using hydrogen peroxide gas can be sterilized relatively easily and does not require heating, and thus is suitable for application to a chemical solution filling system 1 that is filled with a chemical solution that is easily altered or deteriorated by heat. Further, since the hydrogen peroxide gas is used for sterilization in the small chamber 3 and then disappears by exhaust or the gas that remains attached disappears with time, the problem of residual toxicity due to sterilization can be avoided. There is also.

  For such sterilization, for example, sterilization gas such as ethylene oxide gas can be used in addition to hydrogen peroxide gas. These gases can be used alone or as a mixed gas.

One end of a steam supply pipe 41 is connected to the hydrogen peroxide gas supply device 40, and the other end is connected to the first valve 31. Hydrogen peroxide gas is supplied into the small chamber 3 from the hydrogen peroxide gas supply device 40 via the vapor supply pipe 41.
A prefilled syringe 7 as shown in FIG. 9 is manufactured using such a chemical solution filling system 1.

<First Embodiment>
Next, 1st Embodiment of the manufacturing method of the prefilled syringe of this invention is described.

2 to 9 are diagrams for explaining the first embodiment of the method for producing a prefilled syringe of the present invention, and FIG. 10 is a graph schematically showing a pressure change in the small chamber during sterilization.
[A1] Preparation of outer cylinder First, as shown in FIG. 2, a plurality of outer cylinders 71 of the prefilled syringe 7 are prepared.

  The outer cylinder 71 is composed mainly of, for example, polypropylene (PP), cyclic polyolefin, or the like. These materials are resistant to radiation, are readily available and are relatively inexpensive. Therefore, by configuring the outer cylinder 71 using these as main materials, the manufacturing cost can be reduced, and the preparation can be stably and inexpensively provided to the market.

Next, a cap (sealing member) 72 is attached to the tip (mouth) of each outer cylinder 71.
Then, a plurality of (for example, 10 to 20) outer cylinders 71 are placed side by side on the tray 12.

[A2] Enclosing the outer cylinder in the packaging material Next, as shown in FIG. 3, the tray 12 on which the outer cylinder 71 is arranged is accommodated in the packaging material 14 through the opening 143.

  Here, as the packaging material 14, for example, a material obtained by sealing the outer peripheral portion of the stacked sheet material 141 with a seal portion 142 is used. In the present embodiment, two sheet materials 141 are overlapped, their three sides are sealed with a seal portion 142, and an unsealed portion of one side is an opening 143.

  The seal portion 142 can be formed by, for example, fusion such as heat fusion, high frequency fusion, or ultrasonic fusion, or adhesion with an adhesive or a solvent.

  The sheet material 141 preferably has a gas barrier property that the air does not substantially enter the packaging material 14. As for this gas barrier property, for example, the oxygen permeation amount at 20 ° C. (as defined in JIS K 7126) is preferably 10 cc / m 2 · 24 hrs · atm or less, and more preferably 1 cc / m 2 · 24 hrs · atm or less. . Thereby, for example, after sealing the packaging material 14, intrusion of air (oxygen) into the packaging material 14 is prevented, and the amount of air in the packaging material 14 can be reduced. For this reason, at the time of pressure reduction in the post-process [A4-1], damage due to expansion of the packaging material 14 can be prevented.

  Examples of the constituent material of the sheet material 141 include polyolefins such as polyethylene (PE), polypropylene (PP), and ethylene-vinyl acetate copolymer (EVA), and other materials such as polyamide, polyester, and ethylene vinyl alcohol. Examples thereof include a resin and the like, or a multilayer laminate thereof.

  Further, an inorganic layer such as a metal layer or an oxide layer may be deposited on the sheet material 141 by lamination or vapor deposition.

  The average thickness of the sheet material 141 (single layer or multilayer laminate) is not particularly limited, but is usually preferably about 30 to 300 μm, and more preferably about 50 to 150 μm.

  Such a sheet material 141 is formed by various methods such as an inflation method, a T-die method, a blow molding method, a dry lamination method, a hot melt lamination method, a coextrusion inflation method, a coextrusion T die method, and a hot press method. Can be manufactured.

  Next, as shown in FIG. 4, the opening 143 of the packaging material 14 is sealed and sealed. Thereby, the outer cylinder 71 is enclosed in the packaging material 14.

  This sealing is preferably performed by degassing the air in the packaging material 14. Before introducing the sterilizing gas into the small chamber 3, the pressure in the small chamber 3 is reduced in the post-process [A4-1], but the packaging material 14 is sealed in a degassed state, so that the packaging material 14 is damaged due to expansion. Can be prevented.

  At this time, for example, the oxygen absorber 13 is enclosed together with the outer cylinder 71 in the packaging material 14, and oxygen is absorbed (adsorbed) by the oxygen absorber 13 so that the packaging material 14 is degassed. It may be.

Examples of the oxygen scavenger 13 include iron-based oxygen scavengers and organic oxygen scavengers. By using these oxygen scavengers 13, the inside of the packaging material 14 can be relatively easily deaerated.
Such an oxygen scavenger 13 is housed in a container (packaging material) 131 having air permeability. Examples of the constituent material of the container 131 include a polyethylene nonwoven fabric and a polytetrafluoroethylene porous body.

[A3] Radiation Sterilization for Outer Cylinder Next, the packaging material 14 in which the outer cylinder 71 is enclosed is placed in a radiation sterilization apparatus. Then, as shown in FIG. 5, radiation is sterilized together with the packaging material 14 by irradiating the plurality of outer cylinders 71 with radiation from the outside of the packaging material 14.

  As radiation to be irradiated, radiation usually used for radiation sterilization can be used, and examples thereof include γ rays and electron radiation.

The radiation dose is also the dose used in normal radiation sterilization, and is not particularly limited, but is preferably about 10 to 30 K gray, more preferably about 16 to 25 K gray.
Moreover, the irradiation time of a radiation is not specifically limited, It is about 2 to 7 hours.

  After the radiation sterilization is performed on the outer cylinder 71 as described above, the outer cylinder 71 is taken out from the radiation sterilization apparatus while being enclosed in the packaging material 14.

The outer cylinder 71 is carried into the isolator 2 in a state of being enclosed in the packaging material 14, but the outer surface of the packaging material 14 is exposed to an external environment that is a non-sterile region, and thus is in a non-sterile state. It becomes. Note that the inside of the packaging material 14 is maintained in a sterile state by radiation sterilization.
Therefore, when carrying into the isolator 2, the outer surface of the non-sterile packaging material 14 is sterilized in the small chamber 3 provided in the isolator 2.

[A4] Gas sterilization of packaging material First, as shown in FIG. 6, the first lid 33 is attached to the small chamber body 30 so as to seal the first opening 36 of the small chamber 3, and the second opening 37. Is in an open state.

  Next, as shown in FIG. 7, the outer cylinder 71 is sealed together with the packaging material 14 in the packaging material 14 from the outside of the isolator 2 through the second opening 37 in the small chamber body 30. The outer cylinder 71 is inserted.

  Then, the second lid 34 is attached to the small chamber main body 30 so as to seal the second opening 37, and the small chamber 3 is sealed.

  In this state, hydrogen peroxide gas is supplied into the small chamber 3, and the packaging material 14 is exposed to hydrogen peroxide gas (sterilization gas) to sterilize the outer surface thereof.

Hereinafter, this gas sterilization process will be described with reference to FIG.
[A4-1] First, the inside of the small chamber 3 is decompressed by operating the pump 11 (section a in FIG. 10). At this time, the pressure P in the small chamber 3 is preferably 50 kPa or less, and more preferably about 1 to 30 kPa. By setting the pressure P in the small chamber 3 within the above range, hydrogen peroxide gas can be efficiently introduced into the small chamber 3 in the next step.
[A4-2] Next, the hydrogen peroxide gas supply device 40 is operated to supply, for example, hydrogen peroxide gas in a heated state of about 100 to 150 ° C. into the small chamber 3.

Here, since the inside of the small chamber 3 is in a decompressed state, the hydrogen peroxide gas is quickly introduced into the small chamber 3. Further, the hydrogen peroxide gas introduced into the small chamber 3 is condensed and condensed on the surface of the packaging material 14 when the temperature is suddenly lowered, so that a high-concentration hydrogen peroxide film is formed. Thereby, it becomes possible to sterilize the outer surface of the packaging material 14 more reliably and in a short time. At this time, the pressure in the small chamber 3 slightly increases (section b in FIG. 10).
At this time, since the outer cylinder 71 is sealed in the packaging material 14, it is possible to prevent the hydrogen peroxide droplets from directly attaching to the surface of the outer cylinder 71.

[A4-3] Next, after a predetermined time (section b + c in FIG. 10) has elapsed, the inside of the small chamber 3 is decompressed again by operating the pump 11 (section d in FIG. 10). Thereby, the hydrogen peroxide which has aggregated on the outer surface of the packaging material 14 is vaporized.
The pressure in the small chamber 3 at this time is preferably equal to or less than that in the step [A4-1].
The predetermined time (leaving time) is preferably 10 minutes or less, more preferably about 0.1 second to 10 minutes, and further preferably about 1 to 3 minutes. If the standing time is too short, the outer surface of the packaging material 14 may not be sufficiently sterilized depending on the supply amount (introduction amount) of the hydrogen peroxide gas, while the leaving time exceeds the above range. Even if the length is longer, no further improvement in the sterilization effect can be expected, which is not preferable because it results in time loss.

[A4-4] Next, the filter-equipped clean air introduction valve 331 is opened. Thereby, the sealed state of the small chamber 3 is released, and the pressure in the small chamber 3 returns to atmospheric pressure (section e in FIG. 10).
[A5] Loading the outer cylinder into the isolator Next, as shown in FIG. 8, the first lid 33 is opened, and the outer cylinder 71 enclosed in the packaging material 14 is transferred into the isolator 2. . At this time, since the sterility of the small chamber 3 and the isolator 2 is maintained, not only the inside of the packaging material 14 but also the sterility of the outer surface (inside and outside of the packaging material 14) is maintained.
Then, in the isolator 2, the packaging material 14 is opened, the outer cylinder 71 is taken out from the packaging material 14, and is set in the chemical solution filling device 6.

[A6] Completion of Prefilled Syringe Next, the chemical solution stored in the chemical solution adjustment tank is introduced into the chemical solution introduction unit 61 via the chemical solution introduction pipe 8, and this chemical solution is injected into the outer cylinder 71 from the chemical solution injection unit 62.

  Then, the gasket 73 is attached and carried out of the isolator 2. Thereafter, other members such as a plunger (presser) 74 are mounted and packaging is performed. Alternatively, after these are mounted and packaged in the isolator 2, they can be taken out of the isolator 2.

  In such a prefilled syringe manufacturing method, the outer cylinder 71 enclosed in the packaging material 14 is subjected to radiation sterilization together with the packaging material 14 and then the packaging material in the small chamber 3 provided in the wall portion of the isolator 2. 14 is sterilized and carried into the isolator 2.

  Here, the radiation sterilization apparatus is large-scale, and the sterilization passage is open to the external environment, and the radiation sterilization apparatus cannot be directly connected to the isolator 2. The outer cylinder 71 can be aseptically carried into the isolator 2 without requiring the direct connection of the sterilizer to the isolator 2, which is highly convenient.

  Further, as a sterilization method in the small chamber 3, by using a method in which hydrogen peroxide is condensed and condensed on the outer surface of the packaging material 14, the sterilization efficiency is remarkably higher than the sterilization with gaseous hydrogen peroxide. To improve. Thereby, the sterilization time of the outer cylinder 71 can be further shortened.

  Furthermore, since the prefilled syringe manufacturing method of the present invention does not use high-temperature and high-pressure steam sterilization, there is no need to consider the thermal deformation of the outer cylinder 71 and the range of selection of the constituent material of the outer cylinder 71 is widened.

Second Embodiment
Next, 2nd Embodiment of the manufacturing method of the prefilled syringe of this invention is described.

FIG. 11 is a diagram for explaining a second embodiment of the method for producing a prefilled syringe of the present invention.
Hereinafter, although the manufacturing method of the prefilled syringe of 2nd Embodiment is demonstrated, it demonstrates centering on difference with the manufacturing method of the prefilled syringe of the said 1st Embodiment, and the description is abbreviate | omitted about the same matter.

[B1] Preparation of outer cylinder The same process as [A1] is performed.
[B2] Enclosing the outer cylinder in the packaging material Next, as shown in FIG. 3, the tray 12 on which the outer cylinder 71 is arranged is accommodated in the packaging material 14 through the opening 143.

  As the constituent material of the sheet material constituting the packaging material 14, the same materials as those mentioned in the first embodiment can be used.

  Also in the present embodiment, the inside of the packaging material 14 may be deaerated as necessary.

Next, as shown in FIG. 11, the packaging material 14 enclosing the outer cylinder 71 is encapsulated in the second packaging material 15. Thus, by enclosing the packaging material 14 enclosing the outer cylinder 71 in the second packaging material 15, the number of dusts and the like adhering to the outer surface of the packaging material 14 can be more reliably reduced. Thereby, it is possible to more reliably prevent dust and the like from being brought into the isolator 2.
As the constituent material of the sheet material constituting the second packaging material 15, for example, the same materials as those mentioned for the packaging material 14 can be used.

[B3] Radiation sterilization of the outer cylinder Next, in the same manner as in the step [A3], the outer casing 71 is irradiated with radiation from the outside of the second packaging material 15, and the packaging material 14 and The second packaging material 15 is subjected to radiation sterilization.
[B4] Gas sterilization of packaging material Next, the second packaging material 15 is opened outside the isolator 2 (non-sterile region), and the packaging material 14 in which the outer cylinder 71 is enclosed is taken out from the inside. .

  And like the said process [A4], after putting the outer cylinder 71 of the state enclosed with the packaging material 14 in the small chamber 3, the small chamber 3 is made into a sealing state.

Here, by packaging with the second packaging material 15 until immediately before the packaging material 14 is carried into the small chamber 3, adhesion of dust or the like to the outer surface of the packaging material 14 can be more reliably prevented. . Thereby, the carrying of garbage etc. into the small chamber 3 accompanying the carrying-in of the packaging material 14 is prevented more reliably.
Thereafter, gas sterilization is performed on the outer surface of the packaging material 14 in the same manner as in the step [A4].

[B5] Carrying outer cylinder into isolator The same process as the process [A5] is performed.
[B6] Completion of prefilled syringe The same process as the process [A6] is performed.

  Also by the manufacturing method of the prefilled syringe of such 2nd Embodiment, the effect | action and effect similar to the said 1st Embodiment are obtained.

  Further, by further wrapping the packaging material 14 with the second packaging material 15 as in the present embodiment, adhesion of dust or the like to the outer surface of the packaging material 14 is further prevented. Thereby, it is possible to more reliably prevent dust and the like from being brought into the isolator 2 through the small chamber 3.

  As mentioned above, although embodiment of illustration was described about the carrying-in method of the medical device of this invention, and the manufacturing method of a prefilled syringe, this invention is not limited to this.

  For example, in each of the above embodiments, the method for carrying in a medical device of the present invention has been described as a representative case where the method for producing a prefilled syringe is applied to the aseptic region of a prefilled syringe outer cylinder. The medical device can be brought into the aseptic area of various medical devices (medical containers) such as bottles, bags, bags, and injection medical cartridges used for vials, ampoules, infusions, nutrition therapy, etc. It can also be applied to conveyance.

  In each of the above embodiments, the chemical liquid adjustment tank is installed in the isolator. However, the chemical liquid adjustment tank is installed outside the isolator, and the first connection pipe connected to the chemical liquid filling device and the chemical liquid adjustment tank are provided. You may make it supply the chemical | medical solution stored in the chemical | medical solution adjustment tank to a chemical | medical solution filling apparatus by connecting the connected 2nd connecting pipe. Thereby, it is possible to replace the chemical adjustment tank without opening the isolator. In this case, after the second connecting pipe is sterilized in a sealed small chamber, the first opening is opened and the first connecting pipe is connected to the first connecting pipe. The tube can be connected aseptically.

  Moreover, in each said embodiment, although the chemical | medical solution filling apparatus is installed in the aseptic area | region, the equipment arrange | positioned in an aseptic area | region is not limited to this, It can change into the various facilities normally handled in an aseptic area | region.

  In the present invention, one or two or more steps for an arbitrary purpose can be added as necessary.

It is a schematic diagram which shows the structure of the chemical | medical solution filling system used in the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a figure for demonstrating 1st Embodiment of the manufacturing method of the prefilled syringe of this invention. It is a graph which shows typically the pressure change in the small room at the time of sterilization. It is a figure for demonstrating 2nd Embodiment of the manufacturing method of the prefilled syringe of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Chemical liquid filling system 2 Isolator 21 Globe 22 Supply air blower 221 Valve 3 Small chamber 30 Small chamber main body 31 First valve 32 Second valve 33 First lid 331 Clean air introduction valve 34 Second lid 36 First opening 37 Second opening 4 Sterilization means 40 Hydrogen peroxide gas supply device 41 Steam supply pipe 6 Chemical liquid filling device 61 Chemical liquid introduction part 62 Chemical liquid injection part 621 Discharge nozzle 63 Chemical liquid flow path pipe 7 Prefilled syringe 71 Outer cylinder (medical instrument)
72 Cap 73 Gasket 74 Plunger 8 Chemical solution introduction pipe 11 Pump 111 Pump connection pipe 12 Tray 13 Oxygen scavenger 131 Container 14 Packaging material 141 Sheet material 142 Seal portion 143 Opening portion 15 Second packaging material

Claims (8)

A method for carrying in a medical device for aseptically carrying a medical device into a sterile field,
With respect to the medical device enclosed in the packaging material, radiation sterilization is performed together with the packaging material,
Next, the medical device is put together with the packaging material in a sealable chamber, the packaging material is exposed to sterilization gas, and the outer surface thereof is gas sterilized,
Thereafter, while maintaining the sterilized state inside and outside the packaging material, the medical device is transported together with the packaging material to the aseptic region, the packaging material is opened, and the medical device is taken out from the packaging material. How to carry in medical equipment.   The method for carrying in a medical instrument according to claim 1, wherein the medical instrument is carried into the aseptic area from a non-sterile area.   The method for carrying in a medical instrument according to claim 2, wherein the small chamber is provided at a boundary portion between the aseptic region and the non-sterile region.   The said radiation sterilization is performed with respect to the said medical device with the said packaging material and the said 2nd packaging material in the state which enclosed the said packaging material which enclosed the said medical device in the 2nd packaging material. A method for carrying in the medical device according to any one of 1 to 3.   The method for carrying in a medical instrument according to any one of claims 1 to 4, wherein the sterilizing gas is a gas containing hydrogen peroxide.   The method according to claim 5, wherein the gas containing hydrogen peroxide is supplied into the small chamber in a reduced pressure state.   The method for carrying in a medical instrument according to claim 6, wherein a gas containing hydrogen peroxide is supplied into the small chamber, and after a predetermined time has elapsed, the small chamber is decompressed again. The step of carrying the outer cylinder of the prefilled syringe into the aseptic region by the method for transporting a medical instrument according to any one of claims 1 to 7,
And a step of filling the outer cylinder with a liquid preparation in the aseptic region.

Images