JP6455664B2 - Lyophilized preparation system - Google Patents

Lyophilized preparation system Download PDF

Info

Publication number
JP6455664B2
JP6455664B2 JP2015036920A JP2015036920A JP6455664B2 JP 6455664 B2 JP6455664 B2 JP 6455664B2 JP 2015036920 A JP2015036920 A JP 2015036920A JP 2015036920 A JP2015036920 A JP 2015036920A JP 6455664 B2 JP6455664 B2 JP 6455664B2
Authority
JP
Japan
Prior art keywords
container
freeze
isolator
pressure
positive pressure
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
JP2015036920A
Other languages
Japanese (ja)
Other versions
JP2016158635A (en
Inventor
太田　正人
正人 太田
和仁 谷本
和仁 谷本
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shibuya Corp
Original Assignee
Shibuya Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=56845766&utm_source=***_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP6455664(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Shibuya Corp filed Critical Shibuya Corp
Priority to JP2015036920A priority Critical patent/JP6455664B2/en
Publication of JP2016158635A publication Critical patent/JP2016158635A/en
Application granted granted Critical
Publication of JP6455664B2 publication Critical patent/JP6455664B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Filling Of Jars Or Cans And Processes For Cleaning And Sealing Jars (AREA)
  • Sealing Of Jars (AREA)
  • Drying Of Solid Materials (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)

Description

本発明は、容器に充填した薬液を凍結乾燥して粉末化する凍結乾燥製剤製造システムに関し、より詳しくは、製造システムを設置した周辺環境に薬剤成分が飛散することを阻止するようにした凍結乾燥製剤製造システムに関する。   The present invention relates to a freeze-dried preparation manufacturing system that freezes and pulverizes a drug solution filled in a container. The present invention relates to a pharmaceutical manufacturing system.

従来、容器に充填した薬液を凍結乾燥して粉末化する凍結乾燥製剤製造システムが公知である(例えば特許文献１)。
この製造システムでは、製造中の凍結乾燥製剤の汚染を防ぐために、容器の搬送路を無菌チャンバとしてのアイソレータで囲むことにより外部の雰囲気と遮断している。そして、アイソレータ内部を定期的に滅菌ガスによって滅菌し、製造運転時は内部を陽圧に制御することにより無菌を維持している。 2. Description of the Related Art Conventionally, a freeze-dried preparation manufacturing system that freezes and pulverizes a drug solution filled in a container is known (for example, Patent Document 1).
In this production system, in order to prevent contamination of a freeze-dried preparation during production, the container transportation path is surrounded by an isolator as a sterilization chamber so as to be isolated from the external atmosphere. And the inside of an isolator is sterilized regularly with sterilization gas, and sterility is maintained by controlling the inside to a positive pressure during manufacturing operation.

特開２００３−１６４５０９号公報JP 2003-164509 A

凍結乾燥製剤としては、抗ガン剤など少量で強い薬効を与える高薬理活性のものがある。このような高薬理活性の製剤を製造する際は、作業者が誤って薬剤成分を吸引して健康被害が生じることがないよう細心の注意が払われている。
これに対して、従来の製造システムでは、製造運転時はアイソレータ内部を陽圧に維持しているため、薬剤成分が外部に漏れ出す危険性があり、システムの周辺環境に飛散して周囲で作業をしている作業者に健康被害を及ぼす危険性があった。 As freeze-dried preparations, there are those with high pharmacological activity that give strong drug efficacy in a small amount such as anticancer agents. When producing such highly pharmacologically active preparations, great care is taken to ensure that workers do not accidentally inhale the pharmaceutical ingredients and cause health hazards.
On the other hand, in the conventional manufacturing system, since the inside of the isolator is maintained at a positive pressure during the manufacturing operation, there is a risk of the drug component leaking to the outside. There was a risk of damaging health to the workers who were working.

上述した事情に鑑み、本発明は、容器に薬液を充填する充填装置と、容器内の薬液を凍結乾燥する凍結乾燥庫と、凍結乾燥処理された容器を凍結乾燥庫内で密封する密封手段と、充填装置から凍結乾燥庫に容器を搬送する容器搬送装置とを備え、容器に充填した薬液を凍結乾燥して粉末化する凍結乾燥製剤製造システムにおいて、
充填装置を収容し内部が陽圧に維持される陽圧アイソレータと、容器搬送装置を収容する圧力可変アイソレータと、圧力可変アイソレータの内部を陽圧または陰圧に維持する圧力調整手段と、陽圧アイソレータと圧力可変アイソレータを連通または遮断させる開閉手段を備え、液体を充填した容器を充填装置から凍結乾燥庫に搬送する際は、陽圧アイソレータと圧力可変アイソレータを連通させるとともに、圧力可変アイソレータの内部を陽圧に維持し、凍結乾燥処理された容器を凍結乾燥庫から容器搬送装置に搬出する際は、陽圧アイソレ一夕と圧力可変アイソレータの連通を遮断するとともに、圧力可変アイソレータの内部を陰圧に維持するようにしたものである。 In view of the circumstances described above, the present invention provides a filling device for filling a chemical solution in a container, a freeze-drying cabinet for freeze-drying the chemical solution in the container, and a sealing means for sealing the freeze-dried container in the freeze-drying cabinet. In a freeze-dried preparation manufacturing system comprising a container transport device that transports a container from a filling device to a freeze-drying warehouse, and freeze-drying the drug solution filled in the container into a powder,
A positive pressure isolator that accommodates the filling device and is maintained at a positive pressure; a pressure variable isolator that accommodates the container transport device; a pressure adjusting means that maintains the pressure variable isolator at a positive pressure or a negative pressure; and a positive pressure When the container filled with liquid is transported from the filling device to the freeze-drying chamber, the positive pressure isolator and the pressure variable isolator are communicated with each other and the inside of the pressure variable isolator is provided. When the lyophilized container is transported from the lyophilizer to the container transport device, the positive pressure isolator and the pressure variable isolator are disconnected and the inside of the pressure variable isolator is hidden. The pressure is maintained.

上述した構成によれば、製造中の凍結乾燥製剤の汚染を防止しつつ、薬剤成分が周辺環境に飛散することを確実に阻止して、作業者に健康被害が及ぶことを防止することができる。 According to the above-described configuration, it is possible to prevent the pharmaceutical component from being scattered to the surrounding environment while preventing the contamination of the freeze-dried preparation being manufactured, and to prevent the health damage to the worker. .

本発明の一実施例を示す凍結乾燥製剤製造システム１の概略平面図。1 is a schematic plan view of a freeze-dried preparation manufacturing system 1 showing an embodiment of the present invention. 本発明の容器の状態を示す断面図であり、（ａ）は凍結乾燥製剤製品２としての状態を示し、（ｂ）は栓２Ｂが半打栓された状態の容器２Ａを示している。It is sectional drawing which shows the state of the container of this invention, (a) shows the state as the freeze-dried pharmaceutical product 2, (b) has shown the container 2A of the state by which the stopper 2B was half plugged. 凍結乾燥庫６に設けられた密封手段１６を示す断面図。Sectional drawing which shows the sealing means 16 provided in the freeze-drying store | warehouse | chamber 6. FIG.

以下、図示実施例について本発明を説明すると、図１において、１は本発明にかかる凍結乾燥製剤製造システムであり、図２（ａ）に示す凍結乾燥製剤製品２を製造する。
この製造システム１は、供給位置Ａから供給されるバイアル等の空の容器２Ａの内外面を洗浄する洗浄装置３と、洗浄された容器２Ａを滅菌する滅菌装置４と、滅菌された容器２Ａに薬液Ｌ（図２（ｂ）参照）を充填するとともに栓２Ｂを打栓する充填装置５と、充填された容器２Ａ内の薬液Ｌを凍結乾燥して粉末化する凍結乾燥庫６と、充填装置５と凍結乾燥庫６の前方の処理位置Ｂの間で容器２Ａを搬送する容器搬送装置７と、容器搬送装置７から容器２Ａを排出させる容器排出手段８と、容器排出手段８で排出される凍結乾燥後の容器２Ａにアルミ製のリング２Ｃを施す巻締め手段９と、リング２Ｃが施された容器２Ａの外表面を洗い流す外洗手段１０を備えて構成されている。これらシステムを構成する装置および手段の作動は、システム制御装置１１によって制御されるようになっている。
製造システム１の供給位置Ａには、作業者が供給した空の容器２Ａを洗浄装置３に一列に整列させて供給する供給手段１２が設けられ、排出位置Ｃには、排出された凍結乾燥製剤製品２を作業者が回収するための回収手段１３が設けられている。また、処理位置Ｂには、容器搬送装置７上から凍結乾燥庫６内に一列ずつ容器２Ａを押し込む搬入機構１４が設けられている。 Hereinafter, the present invention will be described with reference to the illustrated embodiment. In FIG. 1, reference numeral 1 denotes a freeze-dried preparation manufacturing system according to the present invention, which manufactures a freeze-dried preparation product 2 shown in FIG.
The manufacturing system 1 includes a cleaning device 3 for cleaning the inner and outer surfaces of an empty container 2A such as a vial supplied from a supply position A, a sterilization device 4 for sterilizing the cleaned container 2A, and a sterilized container 2A. A filling device 5 for filling the chemical liquid L (see FIG. 2B) and punching the stopper 2B, a freeze-drying chamber 6 for freeze-drying the chemical liquid L in the filled container 2A and pulverizing, and a filling device 5 and a container transporting device 7 for transporting the container 2A between the processing position B in front of the freeze-drying cabinet 6, a container discharging device 8 for discharging the container 2A from the container transporting device 7, and a container discharging device 8 A winding means 9 for applying an aluminum ring 2C to the container 2A after lyophilization and an outer washing means 10 for washing the outer surface of the container 2A provided with the ring 2C are provided. The operations of the devices and means constituting these systems are controlled by the system control device 11.
The supply position A of the manufacturing system 1 is provided with supply means 12 for supplying empty containers 2A supplied by an operator in a line to the cleaning device 3, and at the discharge position C, the discharged freeze-dried preparation is supplied. A collection means 13 is provided for the operator to collect the product 2. Further, at the processing position B, a carry-in mechanism 14 that pushes the containers 2A one by one into the freeze-drying cabinet 6 from the container transfer device 7 is provided.

洗浄装置３では、容器２Ａを搬送しながら洗浄水を噴射し、空の容器２Ａの内部と外表面を洗い流すようになっている。滅菌装置４では、容器２Ａを多列で搬送しながら加熱エアを吹き付けて加熱滅菌するとともに、冷却エアを吹き付けて温度を下げて排出する。多列で排出される容器２Ａは、整列機構１５によって一列に整列されて充填装置５に送られる。
充填装置５では、充填手段５Ａにより容器２Ａに薬液Ｌが充填され、打栓手段５Ｂによりゴムや樹脂製の栓２Ｂが半打栓されるようになっている。半打栓とは、図２（ｂ）に示すように、栓２Ｂを容器２Ａの口部に完全に押し込まず、栓２Ｂに設けた切り欠き２Ｂａを介して、容器２Ａの内部と外部を連通可能とした状態である。
凍結乾燥庫６の搬出入口６ａは容器２Ａ複数本分の幅を有しており、シャッタ等の閉鎖手段６Ａにより閉鎖可能となっている。凍結乾燥庫６内では、栓２Ｂが半打栓状態の容器２Ａに収容されている薬液Ｌを凍結させ、減圧して昇華させ乾燥させて粉末化している。この凍結乾燥処理は１日から数日かけて行われる。凍結乾燥後、図３に示すように、凍結乾燥庫６内に設けた密封手段１６により容器２Ａを密封する。この密封手段１６は、板状の押下部材１６ａと、これを上下に進退動させる駆動シリンダや電動アクチュエータ等の駆動手段１６ｂを備え、押下部材１６ａを下降させて、栓２Ｂを容器２Ａに完全に押し込んで複数の容器２Ａを一斉に密封する。密封された容器２Ａは凍結乾燥庫６内に設けたコンベヤ等の移送手段６Ｂにより、容器搬送装置７上に搬出される。 In the cleaning device 3, cleaning water is jetted while the container 2 </ b> A is conveyed, and the inside and the outer surface of the empty container 2 </ b> A are washed away. In the sterilization apparatus 4, the container 2A is heated and sterilized by blowing heated air while transporting the containers 2A in multiple rows, and cooling air is blown to lower the temperature and discharge. The containers 2 </ b> A discharged in multiple rows are aligned in a row by the alignment mechanism 15 and sent to the filling device 5.
In the filling device 5, the chemical solution L is filled into the container 2A by the filling means 5A, and the stopper 2B made of rubber or resin is half-plugged by the plugging means 5B. As shown in FIG. 2 (b), the half stopper plug does not completely push the stopper 2B into the mouth of the container 2A, but communicates the inside and outside of the container 2A through the notch 2Ba provided in the stopper 2B. This is a possible state.
The carry-in / out opening 6a of the freeze-drying cabinet 6 has a width corresponding to a plurality of containers 2A, and can be closed by closing means 6A such as a shutter. In the freeze-drying chamber 6, the chemical liquid L accommodated in the container 2 </ b> A in which the stopper 2 </ b> B is half-plugged is frozen, sublimed under reduced pressure, dried and powdered. This freeze-drying process is performed over 1 to several days. After freeze-drying, as shown in FIG. 3, the container 2A is sealed by a sealing means 16 provided in the freeze-drying cabinet 6. The sealing means 16 includes a plate-like pressing member 16a and a driving means 16b such as a drive cylinder and an electric actuator for moving the pressing member 16 up and down, and the pressing member 16a is lowered so that the stopper 2B is completely attached to the container 2A. The plurality of containers 2A are sealed at the same time. The sealed container 2 </ b> A is carried out onto the container transport device 7 by transfer means 6 </ b> B such as a conveyor provided in the freeze-drying warehouse 6.

充填装置５は、外部雰囲気から隔離するために陽圧アイソレータ１７に収容されている。陽圧アイソレータ１７の入口側と出口側には、容器２Ａが通過できる程度の開口からなる導入口１７ａ、排出口１７ｂが形成されており、それぞれシャッタや閉鎖部材等からなる開閉手段１７Ａ、１７Ｂにより連通または遮断可能となっている。
陽圧アイソレータ１７は給排気手段からなる圧力調整手段１７Ｃを備えており、内部空間に清浄化したエアを給排して、製造運転中は内部空間を加圧して外部より陽圧に維持している。
陽圧アイソレータ１７の導入口１７ａの外側の滅菌装置４との間には、陽圧チャンバ１８が整列機構１５を取り囲んで設けられている。陽圧チャンバ１８は給気手段１８Ａを備えており、内部空間に清浄化したエアを給気して、製造運転中は内部空間を加圧して陽圧アイソレータ１７より高い圧力に維持している。これにより、陽圧アイソレータ１７の導入口１７ａを閧放した状態では、陽圧チャンバ１８から陽圧アイソレータ１７に向けて気流が生じ、蒸気やミストとなって漂う薬剤成分を含む陽圧アイソレータ１７内の雰囲気が、陽圧チャンバ１８や陽圧チャンバ１８を通過して滅菌装置４に流出することはない。
陽圧アイソレータ１７には、除染ガス供給手段１９から供給管１９Ａを介して過酸化水素蒸気等の除染ガスが供給されるようになっている。これにより、開閉手段１７Ａ、１７Ｂで導入口１７ａおよび排出口１７ｂを閉鎖した状態で除染ガスを供給することで、陽圧アイソレータ１７の内部を除染することができる。除染後、内部を陽圧に制御することで無菌状態を維持するようになっている。また、排出口１７ｂは閉鎖し導入口１７ａを開放して、滅菌装置４の搬出口４ａを閉鎖手段４Ａで閉鎖した状態で、陽圧アイソレータ１７に除染ガスを供給することで、陽圧チャンバ１８の内部を含めて除染することもできる。 The filling device 5 is accommodated in a positive pressure isolator 17 in order to isolate it from the external atmosphere. The inlet side and the outlet side of the positive pressure isolator 17 are formed with an inlet port 17a and an outlet port 17b each having an opening that allows the container 2A to pass therethrough, and opening / closing means 17A and 17B each including a shutter, a closing member, and the like. Communication or disconnection is possible.
The positive pressure isolator 17 is provided with pressure adjusting means 17C composed of air supply / exhaust means, and supplies and exhausts purified air to and from the internal space, and pressurizes the internal space and maintains a positive pressure from the outside during the manufacturing operation. Yes.
A positive pressure chamber 18 is provided so as to surround the alignment mechanism 15 between the sterilization apparatus 4 outside the inlet 17 a of the positive pressure isolator 17. The positive pressure chamber 18 is provided with an air supply means 18 </ b> A, which supplies purified air to the internal space and pressurizes the internal space to maintain a higher pressure than the positive pressure isolator 17 during the manufacturing operation. Thereby, in the state where the introduction port 17a of the positive pressure isolator 17 is released, an air flow is generated from the positive pressure chamber 18 toward the positive pressure isolator 17, and the inside of the positive pressure isolator 17 containing the chemical component drifting as vapor or mist is generated. Does not flow through the positive pressure chamber 18 or the positive pressure chamber 18 to the sterilizer 4.
The positive pressure isolator 17 is supplied with a decontamination gas such as hydrogen peroxide vapor from a decontamination gas supply means 19 via a supply pipe 19A. Thereby, the inside of the positive pressure isolator 17 can be decontaminated by supplying the decontamination gas in a state in which the inlet 17a and the outlet 17b are closed by the opening / closing means 17A and 17B. After decontamination, the inside is maintained at a positive pressure to maintain aseptic conditions. In addition, the discharge port 17b is closed, the introduction port 17a is opened, and the decontamination gas is supplied to the positive pressure isolator 17 in a state where the outlet 4a of the sterilization apparatus 4 is closed by the closing means 4A. It is also possible to decontaminate including the interior of 18.

陽圧アイソレータ１７の排出口１７ｂから凍結乾燥庫６の前方の処理位置Ｂにかけて、単列コンベヤからなる容器搬送装置７が設けられている。また、その途中の容器搬送装置７の搬送経路には、同じく単列コンベヤからなる容器排出手段８が接続されている。容器搬送装置７は容器排出手段８が接続された分岐位置Ｄから処理位置Ｂまでの間において、上流側搬送手段７Ａと下流側搬送手段７Ｂに分割されており、容器排出手段８は上流側搬送手段７Ａに接続されている。
上流側搬送手段７Ａと下流側搬送手段７Ｂは、ともに搬送方向を正逆に切り換えることが可能で、陽圧アイソレータ１７の排出口１７ｂから処理位置Ｂに向けた正方向と、処理位置Ｂから分岐位置Ｄおよび陽圧アイソレータ１７の排出口１７ｂに向けた逆方向とに、容器２Ａを搬送することができるようになっている。
分岐位置Ｄには容器２Ａの搬送方向を転換させるガイド部材からなる転換手段２０が配置されており、容器搬送装置７の上流側搬送手段７Ａを正方向または逆方向に搬送されている容器２Ａを、必要に応じて容器排出手段８に案内することができるようになっている。
容器排出手段８によって容器搬送装置７（上流側搬送手段７Ａ）から排出された容器２Ａは、巻締め手段９に供給される。巻締め手段９では、容器２Ａに完全に打栓された栓２Ｂの上にキャップ状をしたリング２Ｃを被せ、裾を内側に折り曲げるように巻き締めることで、栓２Ｂが抜け出ることがないよう固定している。また、外洗手段１０では、容器２Ａの外表面に洗浄水を流して、粉末状の凍結乾燥製剤Ｐ等の表面に付着している薬剤成分を洗い流すようにしている。 A container transport device 7 composed of a single-row conveyor is provided from the discharge port 17b of the positive pressure isolator 17 to the processing position B in front of the freeze-drying cabinet 6. Further, a container discharge means 8 composed of a single-row conveyor is connected to the transfer path of the container transfer device 7 in the middle. The container conveying device 7 is divided into an upstream conveying means 7A and a downstream conveying means 7B from the branch position D to which the container discharging means 8 is connected to the processing position B. The container discharging means 8 is divided into the upstream conveying means. Connected to means 7A.
Both the upstream conveying means 7A and the downstream conveying means 7B can switch the conveying direction between forward and reverse, and branch from the processing position B in the forward direction from the discharge port 17b of the positive pressure isolator 17 to the processing position B. The container 2 </ b> A can be transported in the position D and in the reverse direction toward the discharge port 17 b of the positive pressure isolator 17.
At the branch position D, a conversion means 20 comprising a guide member for changing the conveyance direction of the container 2A is arranged, and the container 2A conveyed in the forward or reverse direction by the upstream conveyance means 7A of the container conveyance device 7 is arranged. The container discharge means 8 can be guided as required.
The container 2A discharged from the container transfer device 7 (upstream transfer means 7A) by the container discharge means 8 is supplied to the winding means 9. In the tightening means 9, the cap 2 </ b> B that is completely plugged into the container 2 </ b> A is covered with a cap-shaped ring 2 </ b> C, and tightened so that the hem is bent inward so that the stopper 2 </ b> B is not pulled out. doing. In the outer washing means 10, washing water is poured on the outer surface of the container 2 </ b> A to wash away the drug components adhering to the surface of the powdered lyophilized preparation P or the like.

容器搬送装置７と容器排出手段８は、圧力可変アイソレータ２１に収容されて外部雰囲気から隔離されている。圧力可変アイソレータ２１は、上流側搬送手段７Ａと下流側搬送手段７Ｂの接続位置で上流側部２１Ａと下流側部２１Ｂに分割されており、その間に区画壁２１Ｃが設けられている。上流側部２１Ａに上流側搬送手段７Ａと容器排出手段８と巻締め手段９を収容し、下流側部２１Ｂに下流側搬送手段７Ｂを収容している。
上流側部２１Ａの内部と陽圧アイソレータ１７の内部は排出口１７ｂを介して連通しており、開閉手段１７Ｂにより遮断できるようになっている。区画壁２１Ｃには容器２Ａが通過できる程度の開口からなる連通口２１Ｃａが形成されているとともに、シャッタや閉鎖部材等からなる開閉手段２１Ｄにより連通または遮断可能となっている。下流側部２１Ｂには、下流側搬送手段７Ｂの搬送方向側方の面に凍結乾燥庫６が連結され、搬出入口６ａを介して連通している。
上流側部２１Ａは、陽圧アイソレータ１７と同様の給排気手段からなる圧力調整手段２１Ａａを備えており、内部空間に対して清浄化したエアを給排気して、製造運転中は内部空間を加圧して陽圧アイソレータ１７と同程度の陽圧に維持する場合と、減圧して外部より陰圧に維持する場合とで切換可能になっている。
下流側部２１Ｂは、陽圧アイソレータ１７と同様の給排気手段からなる圧力調整手段２１Ｂａを備えており、凍結乾燥庫６の閉鎖手段６Ａを開放した状態では、下流側部２１Ｂおよび凍結乾燥庫６の内部空間に対して清浄化したエアを給排気して、製造運転中は内部空間を加圧して陽圧アイソレータ１７と同程度の陽圧に維持する場合と、減圧して外部より陰圧に維持する場合とで切換可能になっている。 The container transfer device 7 and the container discharge means 8 are housed in a pressure variable isolator 21 and are isolated from the external atmosphere. The variable pressure isolator 21 is divided into an upstream portion 21A and a downstream portion 21B at a connection position between the upstream conveying means 7A and the downstream conveying means 7B, and a partition wall 21C is provided therebetween. The upstream side conveying means 7A, the container discharging means 8 and the winding means 9 are accommodated in the upstream side portion 21A, and the downstream side conveying means 7B is accommodated in the downstream side portion 21B.
The inside of the upstream side portion 21A and the inside of the positive pressure isolator 17 communicate with each other via the discharge port 17b and can be shut off by the opening / closing means 17B. The partition wall 21 </ b> C is formed with a communication port 21 </ b> Ca having an opening through which the container 2 </ b> A can pass, and can be communicated or blocked by an opening / closing means 21 </ b> D made of a shutter or a closing member. The lyophilization store 6 is connected to the downstream side portion 21B on the surface in the transport direction side of the downstream transport means 7B, and is communicated with the transport port 6a.
The upstream side portion 21A is provided with pressure adjusting means 21Aa composed of air supply / exhaust means similar to the positive pressure isolator 17, and supplies and exhausts purified air to and from the internal space to add the internal space during the manufacturing operation. The pressure can be switched between a case where the pressure is maintained at a positive pressure similar to that of the positive pressure isolator 17 and a case where the pressure is reduced and maintained at a negative pressure from the outside.
The downstream side portion 21B is provided with pressure adjusting means 21Ba composed of the same air supply / exhaust means as the positive pressure isolator 17, and the downstream side portion 21B and the freeze drying chamber 6 are in a state where the closing means 6A of the freeze drying chamber 6 is opened. Supplying / exhausting purified air to / from the internal space and pressurizing the internal space during manufacturing operation to maintain a positive pressure similar to that of the positive pressure isolator 17, reducing the pressure to a negative pressure from the outside It is possible to switch between the cases of maintaining.

上流側部２１Ａの容器排出手段８の搬送方向前方側の端部壁２１Ｅには、容器２Ａが通過できる程度の開口からなる排出口２１Ｅａが形成されるとともに、シャッタや閉鎖部材等からなる開閉手段２１Ｆにより連通または遮断可能となっている。この排出口２１Ｅａの外側に外洗手段１０を収容する陰圧チャンバ２２が設けられている。陰圧チャンバ２２の出口側には、容器２Ａが通過できる程度の開口２２ａが形成され外部と連通している。陰圧チャンバ２２は排気手段２２Ａを備えており、内部空間からエアを排気して、製造運転中は内部空間を減圧して圧力可変アイソレータ２１における陰圧と同程度の圧力に維持している。これにより、外部から陰圧チャンバ２２内部に向けて気流が生じ、圧力可変アイソレータ２１内の雰囲気が外部に流出することを阻止している。
下流側部２１Ｂには、供給管１９Ｂが接続され、除染ガス供給手段１９から過酸化水素蒸気等の除染ガスが供給されるようになっている。これにより、陽圧アイソレータ１７の開閉手段１７Ｂおよび圧力可変アイソレータ２１の開閉手段２１Ｆを閉鎖し、開閉手段２１Ｄおよび凍結乾燥庫６の閉鎖手段６Ａを開放した状態で除染ガスを供給することで、上流側部２１Ａ、下流側部２１Ｂおよび凍結乾燥庫６の内部を除染することができる。除染後、これらの内部を陽圧に制御することで無菌状態を維持するようになっている。 The end wall 21E on the front side in the transport direction of the container discharge means 8 on the upstream side 21A is formed with a discharge port 21Ea having an opening through which the container 2A can pass, and an opening / closing means including a shutter, a closing member, and the like. It can be communicated or blocked by 21F. A negative pressure chamber 22 that houses the washing means 10 is provided outside the discharge port 21Ea. On the outlet side of the negative pressure chamber 22, an opening 22a that allows the container 2A to pass therethrough is formed and communicated with the outside. The negative pressure chamber 22 includes exhaust means 22A, and exhausts air from the internal space, and the internal space is decompressed and maintained at a pressure comparable to the negative pressure in the pressure variable isolator 21 during the manufacturing operation. As a result, an air flow is generated from the outside toward the inside of the negative pressure chamber 22 to prevent the atmosphere in the pressure variable isolator 21 from flowing out to the outside.
A supply pipe 19B is connected to the downstream side portion 21B, and a decontamination gas such as hydrogen peroxide vapor is supplied from the decontamination gas supply means 19. Thereby, the decontamination gas is supplied in a state where the opening / closing means 17B of the positive pressure isolator 17 and the opening / closing means 21F of the pressure variable isolator 21 are closed and the opening / closing means 21D and the closing means 6A of the freeze-drying cabinet 6 are opened. The inside of the upstream side portion 21A, the downstream side portion 21B, and the freeze-drying cabinet 6 can be decontaminated. After decontamination, the inside of these components is controlled to a positive pressure to maintain sterility.

本発明に係る凍結乾燥製剤製造システム１の凍結乾燥製剤製造運転における、容器２Ａに薬液を充填して凍結乾燥庫６に収容させる凍結乾燥前運転について説明する。
この運転では、充填装置５で容器２Ａに所定量の薬液を充填して栓２Ｂを半打栓し、容器搬送装置７の上流側搬送手段７Ａと下流側搬送手段７Ｂにより処理位置Ｂに容器２Ａを搬送する。処理位置Ｂでは搬入機構１４により、下流側搬送手段７Ｂ上の容器２Ａを所定数ずつ凍結乾燥庫６に搬入する。凍結乾燥する所定数の容器２Ａが全て凍結乾燥庫６に収容されたら、搬出入口６ａを閉鎖手段６Ａにより閉鎖し、凍結乾燥庫６内を密閉して凍結乾燥処理を実行する。
この運転に際して、事前に陽圧チャンバ１８、陽圧アイソレータ１７、圧力可変アイソレータ２１の上流側部２１Ａおよび下流側部２１Ｂ、凍結乾燥庫６の内部に、供給管１９Ａ、１９Ｂを介して除染ガス供給手段１９から除染ガスを供給して除染する。その後の製造運転中は、開閉手段１７Ａ、１７Ｂ、２１Ｄ、２１Ｆおよび閉鎖手段４Ａ、６Ａの全てを開放した状態で、陽圧アイソレータ１７、上流側部２１Ａ、下流側部２１Ｂ、凍結乾燥庫６については外部より高い陽圧に維持し、陽圧チャンバ１８についてはさらに高い陽圧に維持するとともに、陰圧チャンバ２２については外部より低い陰圧に維持する。
これにより、陽圧アイソレータ１７、上流側部２１Ａ、下流側部２１Ｂ、凍結乾燥庫６の内部に外気が流人することはなく無菌性を維持することが可能であり、容器２Ａに充填された薬液の汚染を防止することができる。また、陽圧チャンバ１８を設けて陽圧アイソレータ１７の内部よりも高い圧力に維持することで、充填される薬液の成分を含む雰囲気が導入口１７ａから滅菌装置４側に流出することは阻止されており、また、陰圧チャンバ２２を設けて外部より低い陰圧に維持することで、排出口２１Ｅａから陰圧チャンバ２２に流出する薬液の成分を含む雰囲気が開口２２ａから外部に流出することも阻止され、薬剤成分を製造システム１内に封じ込めて、薬剤成分が周辺環境に飛散することを確実に阻止して、作業者に健康被害が及ぶことを防止している。 In the freeze-dried preparation manufacturing operation of the freeze-dried preparation manufacturing system 1 according to the present invention, the operation before freeze-drying in which the container 2A is filled with the chemical solution and stored in the freeze-drying cabinet 6 will be described.
In this operation, the filling device 5 fills the container 2A with a predetermined amount of chemical liquid and the stopper 2B is half-plugged, and the container 2A is moved to the processing position B by the upstream conveying means 7A and the downstream conveying means 7B of the container conveying device 7. Transport. At the processing position B, the carry-in mechanism 14 carries a predetermined number of containers 2A on the downstream transport means 7B into the freeze-drying cabinet 6. When all the predetermined number of containers 2A to be freeze-dried are accommodated in the freeze-drying cabinet 6, the carry-in / out opening 6a is closed by the closing means 6A, the inside of the freeze-drying cabinet 6 is sealed, and the freeze-drying process is executed.
In this operation, the decontamination gas is supplied into the upstream portion 21A and downstream portion 21B of the positive pressure chamber 18, the positive pressure isolator 17, the pressure variable isolator 21 and the freeze-drying chamber 6 in advance through supply pipes 19A and 19B. Decontamination gas is supplied from the supply means 19 for decontamination. During the subsequent manufacturing operation, the positive pressure isolator 17, the upstream side portion 21A, the downstream side portion 21B, and the lyophilizer 6 are opened with all of the opening / closing means 17A, 17B, 21D, 21F and the closing means 4A, 6A open. Is maintained at a higher positive pressure than the outside, the positive pressure chamber 18 is maintained at a higher positive pressure, and the negative pressure chamber 22 is maintained at a lower negative pressure than the outside.
As a result, the positive pressure isolator 17, the upstream side portion 21A, the downstream side portion 21B, and the freeze-drying chamber 6 can maintain sterility without flowing outside air and filled into the container 2A. It is possible to prevent chemical contamination. Further, by providing the positive pressure chamber 18 and maintaining a pressure higher than the inside of the positive pressure isolator 17, the atmosphere containing the chemical solution to be filled is prevented from flowing out from the inlet 17a to the sterilizer 4 side. In addition, by providing the negative pressure chamber 22 and maintaining the negative pressure lower than the outside, the atmosphere containing the chemical solution flowing out from the discharge port 21Ea into the negative pressure chamber 22 may flow out from the opening 22a. It is blocked and the drug component is contained in the manufacturing system 1 to reliably prevent the drug component from being scattered into the surrounding environment, thereby preventing health damage to the worker.

次に、本発明に係る凍結乾燥製剤製造システム１の凍結乾燥製剤製造運転における、凍結乾燥後の容器２Ａにリング２Ｃを施し、凍結乾燥製剤製品２として外部に排出する凍結乾燥後運転について説明する。
この運転では凍結乾燥庫６の内部で凍結乾燥処理が終了し、容器２Ａには粉末状の製剤Ｐが収容されている。この状態において、凍結乾燥庫６の内部で密封手段１６により栓２Ｂを一斉に押し込んで完全に打栓し、容器２Ａを密封する。その後、閉鎖手段６Ａを開放して移送手段６Ｂを作動させて、容器２Ａを一列ずつ下流側搬送手段７Ｂ上に搬出する。下流側搬送手段７Ｂおよび上流側搬送手段７Ａは搬送方向を逆方向に運転されており、転換手段２０に向けて容器２Ａを搬送する。転換手段２０は、逆方向に搬送されてくる容器２Ａを上流側搬送手段７Ａから容器排出手段８に移載するよう制御されており、容器排出手段８は、容器２Ａを容器搬送装置７（上流側搬送手段７Ａ）から排出させて、巻締め手段９に供給する。巻締め手段９では、完全に打栓されている栓２Ｂにリング２Ｃを被せて巻き締めを行う。その後、外洗手段１０に容器２Ａを送って外表面を洗い流し、凍結乾燥製剤製品２として回収手段１３に排出する。
凍結乾燥処理により粉末化されることで、薬剤成分が浮遊して外部に流出するリスクは高まっている。一方で栓２Ｂが完全に打栓された後では、容器２Ａは密封されているため、容器２Ａ内の凍結乾燥製剤Ｐに外気が触れることはなく汚染の心配はない。そこでこの運転中は、開閉手段１７Ｂを閉鎖するとともに、開閉手段２１Ｄ、２１Ｆは開放した状態で、上流側部２１Ａ、下流側部２１Ｂ、凍結乾燥庫６を、陰圧チャンバ２２と同程度の圧力に減圧して外部より低い陰圧に維持する。これにより、圧力可変アイソレータ２１に外気が流入するため内部空間の無菌状態は解除されるが、粉末化された薬剤成分が浮遊している凍結乾燥庫６や圧力可変アイソレータ２１内の雰囲気が外部に流出することは阻止され、薬剤成分を確実に製造システム１内に封じ込めることができる。
また、この運転中には、陽圧アイソレータ１７において、供給管１９Ａを介して除染ガス供給手段１９から除染ガスを供給して内部を除染したり清掃するなど、次回の作業の準備を行うことができる。 Next, in the freeze-dried preparation manufacturing operation of the freeze-dried preparation manufacturing system 1 according to the present invention, the operation after freeze-drying in which the ring 2C is applied to the container 2A after freeze-drying and discharged to the outside as the freeze-dried preparation product 2 will be described. .
In this operation, the freeze-drying process is completed inside the freeze-drying chamber 6, and the powdery preparation P is accommodated in the container 2A. In this state, the stoppers 2B are pushed all at once by the sealing means 16 inside the freeze-drying chamber 6 and completely plugged to seal the container 2A. Thereafter, the closing means 6A is opened, the transfer means 6B is operated, and the containers 2A are carried out one line at a time onto the downstream conveying means 7B. The downstream side conveyance means 7B and the upstream side conveyance means 7A are operated in the opposite conveyance directions, and convey the container 2A toward the conversion means 20. The conversion means 20 is controlled to transfer the container 2A conveyed in the reverse direction from the upstream conveying means 7A to the container discharging means 8, and the container discharging means 8 transfers the container 2A to the container conveying device 7 (upstream). The sheet is discharged from the side conveying means 7A) and supplied to the winding means 9. In the tightening means 9, the ring 2 </ b> B is put on the stopper 2 </ b> B that has been completely stoppered to perform tightening. Thereafter, the container 2 </ b> A is sent to the outer washing means 10 to wash out the outer surface, and the lyophilized preparation product 2 is discharged to the collecting means 13.
By pulverizing by freeze-drying, the risk that the drug component floats and flows out is increasing. On the other hand, after the stopper 2B is completely plugged, the container 2A is sealed, so that the outside air does not touch the lyophilized preparation P in the container 2A and there is no fear of contamination. Therefore, during this operation, the opening / closing means 17B is closed and the opening / closing means 21D, 21F are opened, and the upstream side portion 21A, the downstream side portion 21B, and the freeze-drying chamber 6 are set to the same pressure as the negative pressure chamber 22. To a negative pressure lower than the outside. As a result, since the outside air flows into the pressure variable isolator 21, the aseptic state of the internal space is released, but the atmosphere in the freeze-drying cabinet 6 and the pressure variable isolator 21 in which the powdered drug component is floating is exposed to the outside. Outflow is prevented and the drug component can be reliably contained in the manufacturing system 1.
During this operation, the positive pressure isolator 17 prepares for the next operation such as supplying the decontamination gas from the decontamination gas supply means 19 via the supply pipe 19A to decontaminate or clean the inside. It can be carried out.

さらに、本発明に係る凍結乾燥製剤製造システム１において、容器２Ａに薬液を充填した後、凍結乾燥処理を行わず液状製剤製品として排出する場合について説明する。
この運転では、充填装置５において、充填手段５Ａで容器２Ａに所定量の薬液を充填した後、打栓手段５Ｂでは栓２Ｂを完全に打栓して容器２Ａを密封する。容器搬送手段７は上流側搬送手段７Ａだけを作動させて、容器２Ａは分岐位置Ｄで転換手段２０により容器排出手段８に案内されて排出され巻締め手段９に送られる。巻締め手段９では、完全に打栓されている栓２Ｂにリング２Ｃを被せて巻き締めを行う。その後、容器２Ａは外洗手段１０に送られて、外表面が洗い流されて液状製剤製品として回収手段１３に排出される。
この運転に際して、開閉手段２１Ｄを閉鎖して圧力可変アイソレータ２１の内部を上流側部２１Ａと下流側部２１Ｂの間で遮断した状態で、陽圧チャンバ１８、陽圧アイソレータ１７、上流側部２１Ａの内部を、供給管１９Ａを介して除染ガス供給手段１９から供給される除染ガスにより除染する。その後の運転中は、閉鎖手段４Ａおよび開閉手段１７Ａ、１７Ｂ、２１Ｆを開放するとともに、開閉手段２１Ｄは閉鎖した状態で、陽圧アイソレータ１７、上流側部２１Ａを外部より高い陽圧に維持し、陽圧チャンバ１８についてはさらに高い陽圧に維持するとともに、陰圧チャンバ２２については外部より低い陰圧に維持する。これにより、陽圧アイソレータ１７、上流側部２１Ａの内部に外部雰囲気が流入することはなく無菌性を維持することが可能である。また、容器２Ａに充填される薬液の成分を含む雰囲気が、導入口１７ａから滅菌装置４側に流出することは阻止されるとともに、排出口２１Ｅａから陰圧アイソレータ２２に流出する雰囲気が外部に流出することも阻止され、薬剤成分を確実に製造システム１内に封じ込めることができる。
この運転中には、下流側部２１Ｂおよび凍結乾燥庫６において、供給管１９Ｂを介して除染ガス供給手段１９から除染ガスを供給して内部を除染したり清掃するなど、次回の作業の準備を行うことができる。 Furthermore, in the freeze-dried preparation manufacturing system 1 according to the present invention, a case where the container 2A is filled with a chemical solution and then discharged as a liquid preparation product without performing freeze-drying processing will be described.
In this operation, in the filling device 5, after a predetermined amount of chemical solution is filled in the container 2A by the filling means 5A, the stopper 2B is completely stoppered by the stopper means 5B to seal the container 2A. The container conveying means 7 operates only the upstream conveying means 7A, and the container 2A is guided to the container discharging means 8 by the converting means 20 at the branch position D and discharged, and sent to the winding means 9. In the tightening means 9, the ring 2 </ b> B is put on the stopper 2 </ b> B that has been completely stoppered to perform tightening. Thereafter, the container 2A is sent to the outer washing means 10, the outer surface is washed away, and the liquid preparation product is discharged to the collecting means 13.
In this operation, the open / close means 21D is closed and the inside of the variable pressure isolator 21 is blocked between the upstream side portion 21A and the downstream side portion 21B, and the positive pressure chamber 18, the positive pressure isolator 17, and the upstream side portion 21A are closed. The inside is decontaminated with the decontamination gas supplied from the decontamination gas supply means 19 via the supply pipe 19A. During the subsequent operation, the closing means 4A and the opening / closing means 17A, 17B, 21F are opened, and the positive pressure isolator 17, the upstream side portion 21A is maintained at a higher positive pressure than the outside while the opening / closing means 21D is closed, The positive pressure chamber 18 is maintained at a higher positive pressure, and the negative pressure chamber 22 is maintained at a negative pressure lower than the outside. Thereby, the external atmosphere does not flow into the positive pressure isolator 17 and the upstream side portion 21A, and sterility can be maintained. In addition, the atmosphere containing the chemical component filled in the container 2A is prevented from flowing out from the introduction port 17a to the sterilizer 4 side, and the atmosphere flowing out from the discharge port 21Ea to the negative pressure isolator 22 flows out to the outside. This prevents the drug component from being contained in the manufacturing system 1.
During this operation, in the downstream side portion 21B and the freeze-drying cabinet 6, the next operation such as decontamination or cleaning is performed by supplying decontamination gas from the decontamination gas supply means 19 via the supply pipe 19B. Can be prepared.

なお、本発明に係る凍結乾燥製剤製造システム１においては、予め薬剤が収容されたプレフィルドシリンジを製造することも可能である。その場合は、容器としてトップキャップで先端を塞いだバレル（シリンジの本体部分）を供給し、このバレルに充填装置５において、充填手段５Ａで薬液を充填し、打栓手段５Ｂでガスケットを半打栓する。これを容器搬送装置７で処理位置Ｂまで搬送して凍結乾燥庫６に収納し、凍結乾燥処理を行うとともに、密封手段１６でトップキャップを完全に押し込んで密封する。トップキャップが押し込まれたバレルは、凍結乾燥庫６から搬出されて搬送方向を逆方向とした容器搬送装置７によって分岐位置Ｄまで搬送され、容器排出手段８によって外洗手段１０に送られて外表面を洗い流されて外部へ排出される。シリンジの場合は、リングを施す必要はないため巻締め手段９は通過させる。また、充填した薬液のまま凍結乾燥処理を行わず液状製剤製品として排出することも可能である。このような場合においても、陽圧チャンバ１８、陽圧アイソレータ１７、圧力可変アイソレータ２１、凍結乾燥庫６、陰圧チャンバ２２の圧力の状態を、前述のバイアル等の容器を対象とした製造運転時と同様に制御することにより、本発明と同様の効果を得ることができる。   In the freeze-dried preparation manufacturing system 1 according to the present invention, it is also possible to manufacture a prefilled syringe that contains a medicine in advance. In that case, a barrel (syringe body part) whose tip is closed with a top cap is supplied as a container, and the barrel is filled with a chemical solution by the filling means 5A in the filling device 5, and the gasket is half-stroked by the plugging means 5B. Plug. This is transported to the processing position B by the container transport device 7 and stored in the freeze-drying cabinet 6 to perform freeze-drying processing, and the top cap is completely pushed in by the sealing means 16 and sealed. The barrel into which the top cap has been pushed is unloaded from the freeze-drying chamber 6 and is transported to the branch position D by the container transport device 7 whose transport direction is the reverse direction. The surface is washed away and discharged to the outside. In the case of a syringe, it is not necessary to apply a ring, so that the winding means 9 is allowed to pass. Moreover, it is also possible to discharge as a liquid preparation product without performing freeze-drying treatment as it is in the filled chemical solution. Even in such a case, the pressure states of the positive pressure chamber 18, the positive pressure isolator 17, the pressure variable isolator 21, the freeze-drying chamber 6, and the negative pressure chamber 22 are changed during the manufacturing operation for the container such as the aforementioned vial. By controlling in the same manner as above, the same effect as in the present invention can be obtained.

１‥凍結乾燥製剤製造システム ２‥凍結乾燥製剤製品
２Ａ‥容器 ５‥充填装置
６‥凍結乾燥庫 ７‥容器搬送装置
１６‥密封手段 １７‥陽圧アイソレータ
２１‥圧力可変アイソレータ
２１Ａａ、２１Ｂａ‥圧力調整手段 １７Ｂ‥開閉手段 DESCRIPTION OF SYMBOLS 1 ... Lyophilized preparation manufacturing system 2 ... Lyophilized preparation product 2A ... Container 5 ... Filling device 6 ... Lyophilizer 7 ... Container transport device 16 ... Sealing means 17 ... Positive pressure isolator 21 ... Pressure variable isolator
21Aa, 21Ba ... Pressure adjustment means 17B ... Opening and closing means

Claims (5)

容器に薬液を充填する充填装置と、容器内の薬液を凍結乾燥する凍結乾燥庫と、凍結乾燥処理された容器を凍結乾燥庫内で密封する密封手段と、充填装置から凍結乾燥庫に容器を搬送する容器搬送装置とを備え、容器に充填した薬液を凍結乾燥して粉末化する凍結乾燥製剤製造システムにおいて、
充填装置を収容し内部が陽圧に維持される陽圧アイソレータと、容器搬送装置を収容する圧力可変アイソレータと、圧力可変アイソレータの内部を陽圧または陰圧に維持する圧力調整手段と、陽圧アイソレータと圧力可変アイソレータを連通または遮断させる開閉手段を備え、
液体を充填した容器を充填装置から凍結乾燥庫に搬送する際は、陽圧アイソレータと圧力可変アイソレータを連通させるとともに、圧力可変アイソレータの内部を陽圧に維持し、
凍結乾燥処理された容器を凍結乾燥庫から容器搬送装置に搬出する際は、陽圧アイソレ一夕と圧力可変アイソレータの連通を遮断するとともに、圧力可変アイソレータの内部を陰圧に維持することを特徴とする凍結乾燥製剤製造システム。 A filling device for filling the container with the chemical solution, a freeze-drying chamber for freeze-drying the chemical solution in the container, a sealing means for sealing the freeze-dried container in the freeze-drying chamber, and a container from the filling device to the freeze-drying chamber. In a freeze-dried preparation manufacturing system comprising a container transporting device for transporting, and freeze-drying the drug solution filled in the container into a powder,
A positive pressure isolator that accommodates the filling device and is maintained at a positive pressure; a pressure variable isolator that accommodates the container transport device; a pressure adjusting means that maintains the pressure variable isolator at a positive pressure or a negative pressure; and a positive pressure Opening / closing means for communicating or blocking the isolator and the variable pressure isolator,
When the container filled with liquid is transported from the filling device to the freeze-drying chamber, the positive pressure isolator and the variable pressure isolator are communicated with each other, and the inside of the variable pressure isolator is maintained at a positive pressure.
When the freeze-dried container is transported from the freeze-dryer to the container transport device, the positive pressure isolator and the pressure variable isolator are disconnected from each other and the inside of the pressure variable isolator is maintained at a negative pressure. A freeze-dried preparation manufacturing system. 上記圧力可変アイソレータは、凍結乾燥処理された容器を排出する排出口を備え、この排出口の外側に内部が陰圧に維持される陰圧チャンバを設けたことを特徴とする請求項１に記載の凍結乾燥製剤製造システム。   2. The pressure variable isolator according to claim 1, further comprising a discharge port for discharging the freeze-dried container, and a negative pressure chamber in which the inside is maintained at a negative pressure outside the discharge port. Lyophilized preparation manufacturing system. 上記容器搬送装置は、容器の搬送方向を正逆に切換可能であり、充填装置と凍結乾燥庫の間の搬送経路中に容器排出手段を備え、
液体を充填した容器を充填装置から凍結乾燥庫に搬送する際は、搬送方向を正方向とし、
凍結乾燥処理された容器を凍結乾燥庫から容器排出手段に搬送する際は、搬送方向を逆方向とすることを特徴とする請求項１又は請求項２に記載の凍結乾燥製剤製造システム。 The container transport device can switch the container transport direction forward and reverse, and includes a container discharge means in the transport path between the filling device and the freeze-drying warehouse,
When transporting a container filled with liquid from the filling device to the freeze-drying cabinet, the transport direction is the forward direction,
3. The freeze-dried preparation manufacturing system according to claim 1, wherein when the freeze-dried container is transported from the freeze-drying chamber to the container discharging means, the transport direction is the reverse direction. 上記陽圧アイソレータは、空の容器を導入する導入口を備え、この導入口の外側に内部が陽圧アイソレータよりも高い圧力に維持される陽圧チャンバを設けたことを特徴とする請求項１ないし請求項３のいずれかに記載の凍結乾燥製剤製造システム。   2. The positive pressure isolator includes an inlet for introducing an empty container, and a positive pressure chamber is provided outside the inlet to maintain the inside at a higher pressure than the positive pressure isolator. The freeze-dried preparation manufacturing system according to any one of claims 3 to 4. 上記充填装置は、薬液が充填された容器に半打栓を行う打栓手段を備え、上記容器搬送装置は、液体が充填された半打栓状態の容器を凍結乾燥庫に搬送することを特徴とする請求項１ないし請求項４のいずれかに記載の凍結乾燥製剤製造システム。   The filling device is provided with a stoppering means for half-plugging a container filled with a chemical solution, and the container transporting device transports a half-plugged container filled with a liquid to a freeze-drying warehouse. The freeze-dried preparation manufacturing system according to any one of claims 1 to 4.
JP2015036920A 2015-02-26 2015-02-26 Lyophilized preparation system Active JP6455664B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2015036920A JP6455664B2 (en) 2015-02-26 2015-02-26 Lyophilized preparation system

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP2015036920A JP6455664B2 (en) 2015-02-26 2015-02-26 Lyophilized preparation system

Publications (2)

Publication Number Publication Date
JP2016158635A JP2016158635A (en) 2016-09-05
JP6455664B2 true JP6455664B2 (en) 2019-01-23

Family

ID=56845766

Family Applications (1)

Application Number Title Priority Date Filing Date
JP2015036920A Active JP6455664B2 (en) 2015-02-26 2015-02-26 Lyophilized preparation system

Country Status (1)

Country Link
JP (1) JP6455664B2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106495078A (en) * 2016-12-09 2017-03-15 广东鸿美达科技有限公司 A kind of full-automatic ice crystal coolant filling apparatus
JP6900510B2 (en) * 2017-02-10 2021-07-07 ウェスト ファーマスーティカル サービシーズ ドイチェラント ゲーエムベーハー ウント カンパニー カーゲー How to clean fixing equipment and containers
JP6741930B2 (en) 2017-02-13 2020-08-19 株式会社エアレックス Cleaning performance evaluation system
CN107940632A (en) * 2017-08-02 2018-04-20 湖南科伦制药有限公司 One kind isolation system of processing
JP7299490B2 (en) * 2019-07-09 2023-06-28 澁谷工業株式会社 Goods transport system
CN112629172A (en) * 2021-01-29 2021-04-09 黑龙江省紫舒生物科技有限公司 Energy-saving freeze dryer
CN117367043B (en) * 2023-12-07 2024-04-02 欣诺泰克(江苏)智造科技有限公司 Vacuum freeze drier

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS63235214A (en) * 1988-03-11 1988-09-30 Yamanouchi Pharmaceut Co Ltd Freeze dryer
JP2001106242A (en) * 1999-10-06 2001-04-17 Shionogi & Co Ltd Freeze-drying container, and freeze-drying method using it
JP4547828B2 (en) * 2001-04-19 2010-09-22 大日本印刷株式会社 Container transfer system
JP4770062B2 (en) * 2001-06-01 2011-09-07 澁谷工業株式会社 Space pressure control system
JP2003164509A (en) * 2001-11-30 2003-06-10 Shibuya Kogyo Co Ltd Medical fluid filling-up system provided with freeze- drying means
DE102007034197B4 (en) * 2007-07-23 2013-06-06 Accurro Gmbh Device for loading and unloading an adjusting plate of a freeze-drying plant and a method therefor
JP5617440B2 (en) * 2010-08-30 2014-11-05 澁谷工業株式会社 Aseptic equipment
JP2012116495A (en) * 2010-11-30 2012-06-21 Kazuto Hanazono Manufacturing device of medicinal product

Also Published As

Publication number Publication date
JP2016158635A (en) 2016-09-05

Similar Documents

Publication Publication Date Title
JP6455664B2 (en) Lyophilized preparation system
CN1968888B (en) Apparatuses and methods for sterilising and filling components of packaging units, particularly bottles and/or caps
US8117803B2 (en) Vessel filling system
US20100043915A1 (en) Aseptic beverage bottle filling plant with a clean room arrangement enclosing the aseptic beverage bottle filling plant and a method of operating same, and an aseptic container filling plant with a clean room arrangement enclosing the aseptic container filling plant, and a method of operating same
KR102316664B1 (en) Sterilized work system
KR101864294B1 (en) Method for protecting and unprotecting the fluid path in a controlled environment enclosure
JP6420662B2 (en) Chemical supply apparatus and method
CN102458484A (en) Method and apparatus for sterilizing footwear
US11607468B2 (en) Decontamination device, isolator system, and operating method
US20220047749A1 (en) Food processing and/or packaging device and method for cleaning such device
JP6604954B2 (en) Device and method for transferring a sterile product between two containers
JP7116053B2 (en) Decontamination system utilizing forced air and method of using same
CN102552952B (en) Steam sterilization device with control valves
CN102348471A (en) Apparatus and method for sterilizing objects
JP4910737B2 (en) Article sterilizer
JP2007209675A (en) Manufacturing method of prefilled syringe
JP6310768B2 (en) Container sterilizer
CN203172916U (en) Vacuumizing nitrogen-charging stoppering assembly
JP7348476B2 (en) Freeze-dried drug manufacturing system
JP6198050B2 (en) Enclosure system for enclosing object and method for enclosing the object
US20180154403A1 (en) Device for sterile treatment
JP6651696B2 (en) Container sterilization method and device
JP6975374B2 (en) Goods processing system
JP6163940B2 (en) Aseptic filling machine
CN105980071A (en) Insulator for processing medical substances and method for decontaminating an insulator

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20180131

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20181121

A977 Report on retrieval

Free format text: JAPANESE INTERMEDIATE CODE: A971007

Effective date: 20181121

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20181204

R150 Certificate of patent or registration of utility model

Ref document number: 6455664

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150