EP0278039A1 - Freeze-drying apparatus - Google Patents

Freeze-drying apparatus Download PDF

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Publication number
EP0278039A1
EP0278039A1 EP87102062A EP87102062A EP0278039A1 EP 0278039 A1 EP0278039 A1 EP 0278039A1 EP 87102062 A EP87102062 A EP 87102062A EP 87102062 A EP87102062 A EP 87102062A EP 0278039 A1 EP0278039 A1 EP 0278039A1
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EP
European Patent Office
Prior art keywords
chamber
piston rod
freeze
drying
sterilization
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.)
Granted
Application number
EP87102062A
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German (de)
French (fr)
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EP0278039B1 (en
Inventor
Heinz May
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.)
GEA Lyophil GmbH
Original Assignee
Leybold AG
Finn Aqua Santasalo Sohlberg GmbH
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
Application filed by Leybold AG, Finn Aqua Santasalo Sohlberg GmbH filed Critical Leybold AG
Priority to ES198787102062T priority Critical patent/ES2028804T3/en
Priority to DE8787102062T priority patent/DE3775205D1/en
Priority to EP87102062A priority patent/EP0278039B1/en
Priority to JP63024118A priority patent/JP2652185B2/en
Priority to DK071988A priority patent/DK71988A/en
Priority to US07/156,002 priority patent/US4881326A/en
Publication of EP0278039A1 publication Critical patent/EP0278039A1/en
Application granted granted Critical
Publication of EP0278039B1 publication Critical patent/EP0278039B1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F26—DRYING
    • F26B—DRYING SOLID MATERIALS OR OBJECTS BY REMOVING LIQUID THEREFROM
    • F26B5/00—Drying solid materials or objects by processes not involving the application of heat
    • F26B5/04—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum
    • F26B5/06—Drying solid materials or objects by processes not involving the application of heat by evaporation or sublimation of moisture under reduced pressure, e.g. in a vacuum the process involving freezing

Definitions

  • the invention relates to a device for freeze-drying products located in containers (bottles, vials) with a chamber, a plurality of adjusting plates arranged vertically displaceably in the chamber and with at least one piston rod serving to displace the adjusting plates, the actuating device of which is arranged outside the chamber.
  • Freeze drying is primarily used to preserve temperature-sensitive products, the properties of which should be retained. Freeze drying is mainly used in the fields of pharmacy, biology and medicine.
  • the usual freeze-drying process proceeds approximately as follows: During a first phase, the water-containing product is frozen (for example at a shelf temperature of -40 ° C). Then the sublimation of the water in ice form takes place, under vacuum (about 10 ⁇ 1 mbar). After this main drying, the post-drying takes place in order to achieve extremely low residual moisture. The product is heated as much as possible during the final drying. The pressure at which post-drying takes place is around 10 ⁇ 3 mbar.
  • the piston rod is retracted during the loading process or following the freeze-drying process in order to change the height of the setting plates or to close the containers, a non-sterile section of the piston rod then enters the Chamber that can still be under a pressure of 10 von3 mbar after a freeze-drying process, for example. During this time, there is a risk that undesirable contamination, particularly of the product, will take place.
  • the present invention has for its object to eliminate this risk of contamination in freeze-drying devices of the type mentioned.
  • this object is achieved in that the piston rod is assigned a chamber for sterilizing the piston rod section entering the freeze-drying chamber. If this sterilization chamber and thus the piston rod section therein is also sterilized in the manner described before the actual freeze-drying process or at another time, for example during the "freezing" process phase, then the piston rod section entering the freeze-drying chamber after the end of the freeze-drying process is sterile. There is no longer any risk of undesirable contamination during the adjustment of the shelf.
  • FIG. 1 the freeze drying chamber 1 and the height-adjustable shelves 2 located therein are shown only schematically.
  • the capacitor which is usually still present, has not been shown.
  • a cylinder-piston device (closure device) 4 which is only shown in part, is supported on the freeze-drying chamber 1 via a steel frame 3.
  • the not visible piston of this device 4 is connected to a piston rod 5, the free end of which projects from above into the freeze-drying chamber 1 and carries a pressure plate 6.
  • a lowering of the piston and thus the piston rod 5 causes the setting plates 2 to move together.
  • This process concludes a freeze-drying process for products which are located in containers (bottles, vials) with special stoppers placed on the setting plates 2.
  • the moving together of the setting plates 2 causes the plugs to be pressed into the containers and thus to close the containers. This enables the containers to be sealed under vacuum or an inert gas atmosphere.
  • the piston rod 5 is assigned a separate sterilization chamber 7.
  • This consists of the cylindrical tube 8, which surrounds the piston rod 5 to form the annular space 9.
  • the end of the annular chamber 9 is formed by flanges 11 and 12, which are each sealed off from the piston rod by means of a double seal 13, 14.
  • the distance from the seal 11, 13 located in the area of the closure device 4 to the chamber-side seal 12, 14 is selected so that the section of the piston rod 5 which maximally enters the chamber 1 is accommodated therein.
  • the chamber-side seal 12, 14 is shown enlarged again in FIG. 2.
  • the cylindrical wall of the chamber 9 is equipped with two connections 15 and 16 to which the devices used to carry out the sterilization are connected.
  • the connection of steam (valve 17), the removal of steam (valve 18) and the supply of sterile air or sterile inert gas (valve 19) take place via the connection 15.
  • a water ring pump 21 (via the valve 22) and a rotary vane pump 23 (via the valve 24) are connected to the connection 16.
  • the control 25, shown schematically as a block, is provided. This is connected to a temperature sensor 26 and to a pressure sensor 27, which are connected to the cylindrical wall 8 of the chamber 9 and supply electrical signals corresponding to the temperature or pressure within the chamber 9. Depending on these signals and the desired steam exposure time, the sterilization process described above takes place automatically. This can be done at any time, regardless of or simultaneously with the sterilization of the other parts of the system. However, all facilities that are suitable for Sterilization of the piston rod 5 and the freeze drying system itself are required only once and are used in a targeted manner via control means.
  • the tubular section 31 of the flange 12 is surrounded by two annular fittings 36 and 37 with radial bores 38 and 39.
  • the adapter 36 is welded to the wall of the chamber 1 and sealed both to the flange 12 and to the adapter 37 with sealing rings 41, 42.
  • the radial bore 38 is concentric with a radial bore 43 in the flange 12. This creates a channel through which the piston rod section located between the sealing rings 32 and 33 is accessible.
  • the bore 42 opens into an annular channel 45 which surrounds the piston rod 5. This makes it possible to supply superheated steam to this area of the seal during the course of the sterilization process, so that effective sterilization also takes place in the area of the double seal 14. This effort could be dispensed with if the piston rod 5 were to travel the distance, for example back and forth, during the sterilization, which corresponds to the height of the chamber-side seal 12, 14.
  • the fitting 37 is welded to the cylindrical wall 8 of the chamber 9 and forms with the tubular portion 31 of the flange 12 an annular space 44 which the Radial bore 39 connects to the sterilization chamber 9. Condensate is drawn off via the annular space 44 and the channel 39 during the course of the sterilization process.
  • the piston rod is arranged above the freeze-drying chamber 1. It is therefore expedient for the chamber-side seal 12, 14 to be carefully sterilized by the measures shown in FIG. 2 and for the condensate which is formed to be drawn off in this area too. If the piston rod is pushed into the freeze-drying chamber 1 from below in a manner known per se, then the measures for removing the condensate must be provided in the area of the lower seal, that is to say in the area of the seal adjacent to the cylinder-piston device.

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  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Drying Of Solid Materials (AREA)

Abstract

The invention relates to an apparatus for freeze-drying products situated in containers, with a chamber (1), with a number of adjustable plates (2) arranged vertically displaceably in the chamber, and with at least one piston rod (5) which serves to displace the adjustable plates and the operating device (4) of which is arranged outside the chamber (1); in order to avoid the danger of product contaminations which can originate from piston-rod sections which extend into the chamber and are not sterile, it is proposed to assign to the piston rod (5) a chamber (8) for sterilising the piston-rod section which extends into the freeze-drying chamber (1). <IMAGE>

Description

Die Erfindung bezieht sich auf eine Einrichtung zur Gefriertrocknung von in Behältern (Flaschen, Vials) befindlichen Produkten
mit einer Kammer, mehreren in der Kammer vertikal verschiebbar angeordneten Stellplatten und mit mindestens einer der Verschiebung der Stellplatten dienenden Kolben­stange, deren Betätigungseinrichtung außerhalb der Kammer angeordnet ist.The invention relates to a device for freeze-drying products located in containers (bottles, vials)
with a chamber, a plurality of adjusting plates arranged vertically displaceably in the chamber and with at least one piston rod serving to displace the adjusting plates, the actuating device of which is arranged outside the chamber.

Die Gefriertrocknung wird in erster Linie zur Konservierug temperaturempfindlicher Produkte eingesetzt, deren Eigen­schaften erhalten bleiben sollen. In den Bereichen Pharmazie, Biologie und Medizin findet die Gefriertrocknung ihr Haupt- anwendungsgebiet.Freeze drying is primarily used to preserve temperature-sensitive products, the properties of which should be retained. Freeze drying is mainly used in the fields of pharmacy, biology and medicine.

Der übliche Gefriertrocknungs-Prozeß läuft etwa folgender­maßen ab: Während einer ersten Phase wird das Wasser enthaltende Produkt gefroren (zum Beispiel bei einer Stellplatten-Temperatur von -40° C). Danach findet die Sublimation des in Eisform vorliegenden Wassers statt, und zwar unter Vakuum (etwa 10⁻¹ mbar). Nach dieser Haupttrock­nung findet die Nachtrocknung statt, um extrem niedrige Restfeuchten zu erzielen. Während der Nachtrocknung wird das Produkt so weit wie möglich erwärmt. Der Druck, bei dem die Nachtrocknung stattfindet, liegt bei etwa 10⁻³ mbar.The usual freeze-drying process proceeds approximately as follows: During a first phase, the water-containing product is frozen (for example at a shelf temperature of -40 ° C). Then the sublimation of the water in ice form takes place, under vacuum (about 10⁻¹ mbar). After this main drying, the post-drying takes place in order to achieve extremely low residual moisture. The product is heated as much as possible during the final drying. The pressure at which post-drying takes place is around 10⁻³ mbar.

Aus den US-Patentschriften 3,448,556 und 3,451,189 sind Einrichtungen zur Gefriertrocknung der eingangs erwähnten Art bekannt. Bei den offenbarten Einrichtungen handelt es sich um größere Gefriertrocknungsanlagen, bei denen sich das zu lyophilisierende Produkt (Impfstoffe, Enzyme, Vitamine, Hormone, Viren oder dergleichen) in einer Viel­zahl von kleinen Behältern befindet. Zur Durchführung der Gefriertrocknung werden diese Behälter auf die in der Höhe verschiebbaren Stellplatten abgesetzt. Auf den Behältern befindet sich jeweils ein Spezialstopfen, der während des Ablaufs des Gefriertrocknungsprozesses das Abströmen des Wasserdampfes nur wenig behindert. Ist der Gefriertrock­nungsprozeß abgeschlossen, werden die Stellplatten mit Hilfe einer in die Kammer einfahrenden Kolbenstange zusammengeschoben. Dadurch werden die Stopfen in die Behälteröffnungen gedrückt. Der wesentliche Vorteil dieser Maßnahmen liegt darin, daß die Behälter unter Vakuum oder Inertgasatmosphäre verschlossen werden können. Erst nach dem Verschluß der Behälter wird die Kammer zum Zwecke des Herausnehmens der gefriergetrockneten Produkte geöffnet.Devices for freeze-drying of the type mentioned at the outset are known from US Pat. Nos. 3,448,556 and 3,451,189. The disclosed facilities are are larger freeze drying systems in which the product to be lyophilized (vaccines, enzymes, vitamins, hormones, viruses or the like) is in a large number of small containers. To carry out freeze drying, these containers are placed on the height-adjustable shelves. There is a special stopper on each of the containers, which only slightly impedes the outflow of water vapor during the freeze-drying process. When the freeze-drying process is complete, the shelves are pushed together using a piston rod that moves into the chamber. This pushes the plugs into the container openings. The main advantage of these measures is that the container can be closed under vacuum or an inert gas atmosphere. Only after the containers have been closed is the chamber opened for the purpose of removing the freeze-dried products.

Bei der Durchführung von Gefriertrocknungsprozessen der beschriebenen Art werden besonders hohe Anforderungen an die Sterilität der Umgebung gestellt. Es ist deshalb bekannt, die gesamte Anlage (Gefriertrocknungskammer, Kondensator und dergleichen) entweder vor jedem Einbringen einer neuen Charge des zu lyophilisierenden Produktes oder in gewünschten Zeitabständen zu sterilisieren. Dazu wird beispielsweise in die vorab evakuierte Anlage Sattdampf mit einem bestimmten Überdruck eingelassen. Die Sterilisations­temperatur beträgt üblicherweise ca. 125° C, was einem Druck von etwa 2,3 bar entspricht. Nach einer Einwirkzeit von ca. 25 min wird der Dampf bis auf einen geringen Restüber­druck abgelassen. Anschließend erfolgt die Trocknung von Kammer und Kondensator durch Evakuierung mittels einer Wasserringpumpe bei einem Druck von etwa 50 mbar sowie die Rückkühlung des Stellplattensystems auf Beladetemperatur. Erst nach einem Sterilisationsprozeß dieser Art erfolgt die Beladung der Gefriertrocknungskammer mit den Behältern, in denen sich das zu lyophilisierende Produkt befindet. Diese sind ebenfalls steril vorbereit worden. Auch die Beladung erfolgt von einem Steril-Raum her.When carrying out freeze drying processes of the type described, particularly high demands are placed on the sterility of the environment. It is therefore known to sterilize the entire system (freeze-drying chamber, condenser and the like) either before each introduction of a new batch of the product to be lyophilized or at desired intervals. For this purpose, saturated steam with a certain excess pressure is admitted into the previously evacuated system. The sterilization temperature is usually about 125 ° C, which corresponds to a pressure of about 2.3 bar. After an exposure time of approx. 25 min, the steam is released to a slight residual overpressure. The chamber and condenser are then dried by evacuation using a water ring pump at a pressure of approximately 50 mbar and the rack system is recooled to the loading temperature. Only after a sterilization process of this type is the freeze-drying chamber loaded with the containers in which the product to be lyophilized is located. These have also been prepared sterile. Loading is also carried out from a sterile room.

Wird bei den aus den genannten US-Schriften bekannten Gefriertrocknungs-Einrichtungen während des Beladungs­prozesses oder im Anschluß an den Gefriertrocknungsprozeß die Kolbenstange eingefahren, um die Höhe der Stellplatten zu verändern oder zum Verschluß der Behälter zusammenzu­schieben, dann gelangt ein nicht steriler Abschnitt der Kolbenstange in die Kammer, die nach einem Gefriertrock­nungsprozeß zum Beispiel noch unter einem Druck von 10⁻³ mbar stehen kann. In dieser Zeit besteht die Gefahr, daß unerwünschte Kontaminationen insbesondere des Produktes stattfinden.In the case of the freeze-drying devices known from the above-mentioned US documents, the piston rod is retracted during the loading process or following the freeze-drying process in order to change the height of the setting plates or to close the containers, a non-sterile section of the piston rod then enters the Chamber that can still be under a pressure of 10 zum³ mbar after a freeze-drying process, for example. During this time, there is a risk that undesirable contamination, particularly of the product, will take place.

Der vorliegenden Erfindung liegt die Aufgabe zugrunde, bei Gefriertrocknungseinrichtungen der eingangs genannten Art diese Kontaminationsgefahr zu beseitigen.The present invention has for its object to eliminate this risk of contamination in freeze-drying devices of the type mentioned.

Erfindungsgemäß wird diese Aufgabe dadurch gelöst, daß der Kolbenstange eine Kammer zur Sterilisierung des in die Gefriertrocknungskammer einfahrenden Kolbenstangenabschnittes zugeordnet ist. Wird diese Sterilisationskammer und damit der darin befindliche Kolbenstangenabschnitt in der beschriebenen Weise vor dem eigentlichen Gefriertrocknungs­prozeß oder zu einem anderen Zeitpunkt, zum Beispiel während der Prozeßphase "Gefrieren", ebenfalls sterilisiert, dann ist der nach dem Abschluß des Gefriertrocknungspro­zesses in die Gefriertrocknungskammer einfahrende Kolben­stangenabschnitt steril. Die Gefahr unerwünschter Kontami­nationen während der Stellplattenverstellung besteht nicht mehr.According to the invention, this object is achieved in that the piston rod is assigned a chamber for sterilizing the piston rod section entering the freeze-drying chamber. If this sterilization chamber and thus the piston rod section therein is also sterilized in the manner described before the actual freeze-drying process or at another time, for example during the "freezing" process phase, then the piston rod section entering the freeze-drying chamber after the end of the freeze-drying process is sterile. There is no longer any risk of undesirable contamination during the adjustment of the shelf.

Weitere Vorteile und Einzelheiten der Erfindung sollen anhand eines in den Figuren 1 und 2 dargestellten Ausfüh­rungsbeispieles erläutert werden. Es zeigen:

  • Fig. 1 eine Einrichtung zur Gefriertrocknung mit einer sterilisierbaren Kolbenstange zur Verstellung der Stellplatten,
  • Fig. 2 die Abdichtung zwischen der Gefriertrock­nungskammer und einer Sterilisationskammer für die Kolbenstange.
Further advantages and details of the invention will be explained with reference to an embodiment shown in Figures 1 and 2. Show it:
  • 1 is a device for freeze-drying with a sterilizable piston rod for adjusting the setting plates,
  • Fig. 2 shows the seal between the freeze-drying chamber and a sterilization chamber for the piston rod.

In der Figur 1 sind die Gefriertrocknungsakmmer 1 und die darin befindlichen, in der Höhe verstellbaren Stell­platten 2 nur schematisch dargestellt. Auf die Darstellung des üblicherweise noch vorhandenen Kondensators wurde verzichtet. Auf der Gefriertrocknungskammer 1 stützt sich über ein Stahlgerüst 3 eine Zylinder-Kolben-Einrichtung (Verschlußeinrichtung) 4 ab, die nur zum Teil dargestellt ist. Der nicht sichtbare Kolben dieser Einrichtung 4 ist mit einer Kolbenstange 5 verbunden, deren freies Ende von oben in die Gefriertrocknungskammer 1 hineinragt und eine Druckplatte 6 trägt. Ein Absenken des Kolbens und damit der Kolbenstange 5 bewirkt ein Zusammenfahren der Stell­platten 2. Dieser Vorgang bildet zum Beispiel den Abschluß eines Gefriertrocknungsprozesses von Produkten, die sich in auf den Stellplatten 2 abgestellten Behältern (Flaschen, Vials) mit aufgesetzten Spezialstopfen befinden. Das Zusammenfahren der Stellplatten 2 bewirkt das Einpressen der Stopfen in die Behälter und damit ein Verschließen der Behälter. Ein Verschluß der Behälter unter Vakuum oder Inert­gasatmosphäre ist dadurch möglich.In FIG. 1, the freeze drying chamber 1 and the height-adjustable shelves 2 located therein are shown only schematically. The capacitor, which is usually still present, has not been shown. A cylinder-piston device (closure device) 4, which is only shown in part, is supported on the freeze-drying chamber 1 via a steel frame 3. The not visible piston of this device 4 is connected to a piston rod 5, the free end of which projects from above into the freeze-drying chamber 1 and carries a pressure plate 6. A lowering of the piston and thus the piston rod 5 causes the setting plates 2 to move together. This process, for example, concludes a freeze-drying process for products which are located in containers (bottles, vials) with special stoppers placed on the setting plates 2. The moving together of the setting plates 2 causes the plugs to be pressed into the containers and thus to close the containers. This enables the containers to be sealed under vacuum or an inert gas atmosphere.

Um die von der Oberfläche des in die Kammer einfahrenden Abschnittes der Kolbenstange 5 ausgehende Kontaminations­gefahr zu verhindern, ist der Kolbenstange 5 eine separate Sterilisationskammer 7 zugeordnet. Diese besteht aus dem zylindrischen Rohr 8, das die Kolbenstange 5 unter Bildung des Ringraumes 9 umgibt. Den stirnseitigen Abschluß der Ringkammer 9 bilden Flansche 11 und 12, die zur Kolbenstange hin jeweils mittels einer Doppeldichtung 13, 14 abgedichtet sind. Der Abstand von der im Bereich der Verschlußeinrich­tung 4 liegenden Abdichtung 11, 13 zur kammerseitigen Abdichtung 12, 14 ist so gewählt, daß der maximal in die Kammer 1 einfahrende Abschnitt der Kolbenstange 5 darin Platz findet. Die kammerseitige Abdichtung 12, 14 ist in Figur 2 nochmals vergrößert dargestellt.In order to prevent the risk of contamination from the surface of the section of the piston rod 5 entering the chamber, the piston rod 5 is assigned a separate sterilization chamber 7. This consists of the cylindrical tube 8, which surrounds the piston rod 5 to form the annular space 9. The end of the annular chamber 9 is formed by flanges 11 and 12, which are each sealed off from the piston rod by means of a double seal 13, 14. The distance from the seal 11, 13 located in the area of the closure device 4 to the chamber-side seal 12, 14 is selected so that the section of the piston rod 5 which maximally enters the chamber 1 is accommodated therein. The chamber-side seal 12, 14 is shown enlarged again in FIG. 2.

Die zylindrische Wandung der Kammer 9 ist mit zwei Anschlüssen 15 und 16 ausgerüstet, an die die der Durch­führung der Sterilisation dienenden Einrichtungen ange­schlossen sind. Über den Anschluß 15 erfolgt die Zufuhr von Dampf (Ventil 17), die Abfuhr von Dampf (Ventil 18) und die Zufuhr von steriler Luft oder sterilem Inertgas (Ventil 19). An den Anschluß 16 sind eine Wasserring­pumpe 21 (über das Ventil 22) sowie eine Drehschieber­pumpe 23 (über das Ventil 24) angeschlossen.The cylindrical wall of the chamber 9 is equipped with two connections 15 and 16 to which the devices used to carry out the sterilization are connected. The connection of steam (valve 17), the removal of steam (valve 18) and the supply of sterile air or sterile inert gas (valve 19) take place via the connection 15. A water ring pump 21 (via the valve 22) and a rotary vane pump 23 (via the valve 24) are connected to the connection 16.

Um den Sterilisationsprozeß automatisch ablaufen lassen zu können, ist die schematisch als Block dargestellte Steuerung 25 vorgesehen. Diese steht mit einem Temperatur­sensor 26 und mit einem Drucksensor 27 in Verbindung, welche an die zylindrische Wandung 8 der Kammer 9 ange­schlossen sind und der Temperatur beziehungsweise dem Druck innerhalb der Kammer 9 entsprechende elektrische Signale liefern. In Abhängigkeit von diesen Signalen und von der gewünschten Dampfeinwirkzeit erfolgt der weiter vorn geschilderte Ablauf des Sterilisationsvorganges automatisch. Dieses kann zu jedem gewünschten Zeitpunkt geschehen, also unabhängig von oder auch gleichzeitig mit der Sterilisation der übrigen Teile der Anlage. Zweck­mäßigerweise sind jedoch alle Einrichtungen, die zur Sterilisierung der Kolbenstange 5 und der Gefriertrock­nungsanlage selbst erforderlich sind, nur einmal vorgesehen und werden über Steuermittel gezielt eingesetzt.In order to allow the sterilization process to run automatically, the control 25, shown schematically as a block, is provided. This is connected to a temperature sensor 26 and to a pressure sensor 27, which are connected to the cylindrical wall 8 of the chamber 9 and supply electrical signals corresponding to the temperature or pressure within the chamber 9. Depending on these signals and the desired steam exposure time, the sterilization process described above takes place automatically. This can be done at any time, regardless of or simultaneously with the sterilization of the other parts of the system. However, all facilities that are suitable for Sterilization of the piston rod 5 and the freeze drying system itself are required only once and are used in a targeted manner via control means.

In Figur 2 ist der kammerseitige Abschluß 12, 14 der Ringkammer 9 vergrößert dargestellt. In die Innenwandung des Flansches 12, der mit einer rohrabschnittförmigen Führung 31 für die Kolbenstange 5 ausgerüstet ist, sind die Ringnuten 32 und 33 vorgesehen, in denen sich die die Doppeldichtung 14 bildenden Dichtringe 34 und 35 befinden. Eine sichere Abdichtung der Kammer 9 von der Gefriertrocknungskammer 1 ist dadurch gewährleistet.In Figure 2, the chamber end 12, 14 of the annular chamber 9 is shown enlarged. In the inner wall of the flange 12, which is equipped with a tubular section-shaped guide 31 for the piston rod 5, the annular grooves 32 and 33 are provided, in which the sealing rings 34 and 35 forming the double seal 14 are located. This ensures a secure seal of the chamber 9 from the freeze-drying chamber 1.

Der rohrabschnittförmige Teil 31 des Flansches 12 ist von zwei ringförmigen Paßstücken 36 und 37 mit Radialboh­rungen 38 und 39 umfaßt. Das Paßstück 36 ist mit der Wandung der Kammer 1 verschweißt und sowohl zum Flansch 12 als auch zum Paßstück 37 mit Dichtringen 41, 42 abge­dichtet. Die Radialbohrung 38 liegt konzentrisch mit einer Radialbohrung 43 im Flansch 12. Dadurch wird ein Kanal geschaffen, über den der sich zwischen den Dichtringen 32 und 33 befindliche Kolbenstangenabschnitt zugänglich ist. Die Bohrung 42 mündet in einen Ringkanal 45, der die Kolbenstange 5 umgibt. Dadurch ist es möglich, während des Ablaufs des Sterilisationsprozesses auch diesem Bereich der Abdichtung Heißdampf zuzuführen, so daß auch im Bereich der Doppeldichtung 14 eine wirksame Sterilisation stattfindet. Auf diesen Aufwand könnte verzichtet werden, wenn die Kolbenstange 5 während der Sterilisation um die Strecke verfahren, zum Beispiel hin- und herbewegt, würde, die der Höhe der kammerseitigen Abdichtung 12, 14 entspricht.The tubular section 31 of the flange 12 is surrounded by two annular fittings 36 and 37 with radial bores 38 and 39. The adapter 36 is welded to the wall of the chamber 1 and sealed both to the flange 12 and to the adapter 37 with sealing rings 41, 42. The radial bore 38 is concentric with a radial bore 43 in the flange 12. This creates a channel through which the piston rod section located between the sealing rings 32 and 33 is accessible. The bore 42 opens into an annular channel 45 which surrounds the piston rod 5. This makes it possible to supply superheated steam to this area of the seal during the course of the sterilization process, so that effective sterilization also takes place in the area of the double seal 14. This effort could be dispensed with if the piston rod 5 were to travel the distance, for example back and forth, during the sterilization, which corresponds to the height of the chamber-side seal 12, 14.

Das Paßstück 37 ist mit der zylindrischen Wandung 8 der Kammer 9 verschweißt und bildet mit dem rohrabschnittför­migen Teil 31 des Flansches 12 einen Ringraum 44, der die Radialbohrung 39 mit der Sterilisationskammer 9 verbindet. Über den Ringraum 44 und den Kanal 39 erfolgt während des Ablaufs des Sterilisationsvorganges der Abzug von Kondensat.The fitting 37 is welded to the cylindrical wall 8 of the chamber 9 and forms with the tubular portion 31 of the flange 12 an annular space 44 which the Radial bore 39 connects to the sterilization chamber 9. Condensate is drawn off via the annular space 44 and the channel 39 during the course of the sterilization process.

Bei dem in den Figuren 1 und 2 dargestellten Ausführungs­beispiel ist die Kolbenstange oberhalb der Gefrier­trocknungskammer 1 angeordnet. Es ist deshalb zweckmäßig, für eine sorgfältige Sterilisierung der kammerseitigen Abdichtung 12, 14 durch die in Figur 2 dargestellten Maßnahmen zu sorgen und auch in diesem Bereich das sich bildende Kondensat abzuziehen. Wird die Kolbenstange in an sich bekannter Weise von unten in die Gefrier­trocknungskammer 1 eingeschoben, dann müssen die Maßnahmen zur Abführung des Kondensats im Bereich der unteren Abdichtung, also im Bereich der der Zylinder-Kolben-­Einrichtung benachbarten Abdichtung, vorgesehen sein.In the embodiment shown in FIGS. 1 and 2, the piston rod is arranged above the freeze-drying chamber 1. It is therefore expedient for the chamber-side seal 12, 14 to be carefully sterilized by the measures shown in FIG. 2 and for the condensate which is formed to be drawn off in this area too. If the piston rod is pushed into the freeze-drying chamber 1 from below in a manner known per se, then the measures for removing the condensate must be provided in the area of the lower seal, that is to say in the area of the seal adjacent to the cylinder-piston device.

Claims (8)

1. Einrichtung zur Gefriertrocknung von in Behältern befindlichen Produkten mit einer Kammer (1), mit mehreren, in der Kammer vertikal verschiebbar ange­ordneten Stellplatten (2) und mit mindestens einer der Verschiebung der Stellplatten dienenden Kolben­stange (5), deren Betätigungseinrichtung (4) außerhalb der Kammer (1) angeordnet ist, dadurch gekennzeichnet, daß der Kolbenstange (5) eine Kammer (8) zur Sterili­sierung des in die Gefriertrocknungskammer (1) einfah­renden Kolbenstangenabschnittes zugeordnet ist.1. Device for freeze-drying products in containers with a chamber (1), with a plurality of adjusting plates (2) arranged vertically displaceably in the chamber and with at least one piston rod (5) serving to displace the adjusting plates, the actuating device (4) of which is outside the chamber (1) is arranged, characterized in that the piston rod (5) is assigned a chamber (8) for sterilizing the piston rod section entering the freeze-drying chamber (1). Einrichtung nach Anspruch 1, dadurch gekennzeichnet, daß die Sterilisationskammer (8) zylindrisch ausgebildet ist, daß sie den in die Gefriertrocknungskammer (1) einfahrenden Kolbenstangenabschnitt (5) unter Bildung eines Ringraumes (9) umgibt und daß sie mit Anschlüs­sen (15, 16) für eine Vakuumpumpe (21, 23) sowie für die Zuführung von Sterilisations- oder Inertgasen ausgerüstet ist.Device according to claim 1, characterized in that the sterilization chamber (8) is cylindrical, that it surrounds the piston rod section (5) entering the freeze-drying chamber (1) to form an annular space (9) and that it has connections (15, 16). for a vacuum pump (21, 23) and for the supply of sterilization or inert gases. 3. Einrichtung nach Anspruch 1 oder 2, dadurch gekenn­zeichnet, daß der Innenraum (9) der Sterilisations­kammer (8) stirnseitig durch Flansche (11, 12) ver­schlossen ist, die gegenüber der die Flansche durch­setzenden Kolbenstange (5) mittels einer Doppeldich­tung (13, 14) abgedichtet sind.3. Device according to claim 1 or 2, characterized in that the interior (9) of the sterilization chamber (8) is closed on the end face by flanges (11, 12) which are opposite the piston rod passing through the flanges (5) by means of a double seal (13, 14) are sealed. 4. Einrichtung nach Anspruch 3, dadurch gekennzeichnet, daß der zwischen der Gefriertrocknungskammer (1) und der Sterilisationskammer (8) befindliche Flansch (12) mit einer rohrabschnittförmigen Führung (31) für die Kolbenstange (5) ausgerüstet ist.4. Device according to claim 3, characterized in that between the freeze-drying chamber (1) and the sterilization chamber (8) located flange (12) is equipped with a tubular section-shaped guide (31) for the piston rod (5). 5. Einrichtung nach Anspruch 3 oder 4, dadurch gekenn­zeichnet, daß die Innenseite des Flansches (12) mit Ringnuten (32, 33) für Ringdichtungen (34, 35) ausge­rüstet ist und daß zwischen den Nuten (32, 33) eine den Flansch (12) durchsetzende Radialbohrung (43) vorgesehen ist.5. Device according to claim 3 or 4, characterized in that the inside of the flange (12) with annular grooves (32, 33) for ring seals (34, 35) is equipped and that between the grooves (32, 33) a flange ( 12) penetrating radial bore (43) is provided. 6. Einrichtung nach Anspruch 5, dadurch gekennzeichnet, daß die Bohrung (43) in einen die Kolbenstange (5) umgebenden Ringkanal (45) mündet.6. Device according to claim 5, characterized in that the bore (43) opens into an annular channel (45) surrounding the piston rod (5). 7. Einrichtung nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß im Bereich der tiefer gelegenen Abdichtung (12, 14) eine Bohrung (39) zum Abzug von Kondensat vorgesehen ist.7. Device according to one of the preceding claims, characterized in that in the region of the lower-lying seal (12, 14) a bore (39) is provided for the removal of condensate. 8. Einrichtung nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die Sterilisations­kammer (8) mit einem Druckfühler (27) und/oder mit einem Temperaturfühler (26) ausgerüstet ist.8. Device according to one of the preceding claims, characterized in that the sterilization chamber (8) is equipped with a pressure sensor (27) and / or with a temperature sensor (26).
EP87102062A 1987-02-13 1987-02-13 Freeze-drying apparatus Expired - Lifetime EP0278039B1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
ES198787102062T ES2028804T3 (en) 1987-02-13 1987-02-13 LYOPHILIZATION INSTALLATION.
DE8787102062T DE3775205D1 (en) 1987-02-13 1987-02-13 DEVICE FOR FREEZING DRYING.
EP87102062A EP0278039B1 (en) 1987-02-13 1987-02-13 Freeze-drying apparatus
JP63024118A JP2652185B2 (en) 1987-02-13 1988-02-05 Lyophilizer
DK071988A DK71988A (en) 1987-02-13 1988-02-12 FREEZER EQUIPMENT
US07/156,002 US4881326A (en) 1987-02-13 1988-02-16 Sterilizing device for a freeze-drying apparatus

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP87102062A EP0278039B1 (en) 1987-02-13 1987-02-13 Freeze-drying apparatus

Publications (2)

Publication Number Publication Date
EP0278039A1 true EP0278039A1 (en) 1988-08-17
EP0278039B1 EP0278039B1 (en) 1991-12-11

Family

ID=8196753

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Application Number Title Priority Date Filing Date
EP87102062A Expired - Lifetime EP0278039B1 (en) 1987-02-13 1987-02-13 Freeze-drying apparatus

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US (1) US4881326A (en)
EP (1) EP0278039B1 (en)
JP (1) JP2652185B2 (en)
DE (1) DE3775205D1 (en)
DK (1) DK71988A (en)
ES (1) ES2028804T3 (en)

Cited By (6)

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FR2655020A1 (en) * 1989-11-30 1991-05-31 Usifroid Mechanism for stoppering bottles in a lyophilisation (freeze-drying) vessel
WO1997020181A1 (en) 1995-11-29 1997-06-05 Immuno Aktiengesellschaft Lyophilization method and device, containers and filling systems
EP0848221A1 (en) * 1996-12-16 1998-06-17 Praxair Technology, Inc. Cryogenic cold shelf
WO2004029529A1 (en) 2002-09-18 2004-04-08 Sueverkruep Richard Method for production of a preparation of a pharmaceutical material as a lyophilisate and plant for the same
DE102008017461A1 (en) 2008-04-03 2009-10-08 Süverkrüp, Richard, Prof. Dr. Lyophilized material i.e. spherical lyophilisate, producing device for use in pharmaceutical industry, has deep cooling device connected with freezing pipe such that pipe is supplied with diverted partial flow of gas from cooling device
EP2128547A1 (en) * 2008-05-26 2009-12-02 Paolo Debolini A dryer, in particular for powdered or granular material

Families Citing this family (4)

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Publication number Priority date Publication date Assignee Title
US5288460A (en) * 1989-03-08 1994-02-22 Abtox, Inc. Plasma cycling sterilizing process
CA2146090C (en) * 1994-05-10 1998-11-24 Mark E. Mitchell Apparatus and method of mixing materials in a sterile environment
JP3985241B2 (en) * 1998-09-18 2007-10-03 株式会社アルバック Freeze vacuum dryer
JP6173495B2 (en) 2013-05-29 2017-08-02 ゲア・プロセス・エンジニアリング・アクティーゼルスカブ Method for realizing serial sterilization lyophilization of products in trays contained in a trolley, system for carrying out the method and use of the method

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JPS52142360A (en) * 1976-04-22 1977-11-28 Kiyoshi Shimada Apparatus for changing space between shelves in freeze vacuum drying machine
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GB701888A (en) * 1951-06-26 1954-01-06 Alois Vogt Improvements in or relating to processes and apparatus for freeze-drying
US3280471A (en) * 1964-11-23 1966-10-25 American Sterilizer Co Apparatus and process for freeze drying
US3451189A (en) * 1967-04-14 1969-06-24 Everett R Taggart Desiccator apparatus including improved vacuum bottle capping arrangement
GB1423353A (en) * 1972-06-19 1976-02-04 Boc International Ltd Vacuum lock

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2655020A1 (en) * 1989-11-30 1991-05-31 Usifroid Mechanism for stoppering bottles in a lyophilisation (freeze-drying) vessel
WO1997020181A1 (en) 1995-11-29 1997-06-05 Immuno Aktiengesellschaft Lyophilization method and device, containers and filling systems
EP0848221A1 (en) * 1996-12-16 1998-06-17 Praxair Technology, Inc. Cryogenic cold shelf
WO2004029529A1 (en) 2002-09-18 2004-04-08 Sueverkruep Richard Method for production of a preparation of a pharmaceutical material as a lyophilisate and plant for the same
DE102008017461A1 (en) 2008-04-03 2009-10-08 Süverkrüp, Richard, Prof. Dr. Lyophilized material i.e. spherical lyophilisate, producing device for use in pharmaceutical industry, has deep cooling device connected with freezing pipe such that pipe is supplied with diverted partial flow of gas from cooling device
DE102008017461B4 (en) * 2008-04-03 2010-04-15 Süverkrüp, Richard, Prof. Dr. Apparatus and method for producing a powdery lyophilized material consisting of approximately equal sized spherical particles
EP2128547A1 (en) * 2008-05-26 2009-12-02 Paolo Debolini A dryer, in particular for powdered or granular material

Also Published As

Publication number Publication date
US4881326A (en) 1989-11-21
DK71988D0 (en) 1988-02-12
DE3775205D1 (en) 1992-01-23
EP0278039B1 (en) 1991-12-11
JP2652185B2 (en) 1997-09-10
JPS63207978A (en) 1988-08-29
ES2028804T3 (en) 1992-07-16
DK71988A (en) 1988-08-14

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