EP0343596B1 - Récipient pour lyophilisation sous conditions stériles - Google Patents

Récipient pour lyophilisation sous conditions stériles Download PDF

Info

Publication number
EP0343596B1
EP0343596B1 EP89109246A EP89109246A EP0343596B1 EP 0343596 B1 EP0343596 B1 EP 0343596B1 EP 89109246 A EP89109246 A EP 89109246A EP 89109246 A EP89109246 A EP 89109246A EP 0343596 B1 EP0343596 B1 EP 0343596B1
Authority
EP
European Patent Office
Prior art keywords
membrane
container according
container
drying
freeze
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.)
Expired - Lifetime
Application number
EP89109246A
Other languages
German (de)
English (en)
Other versions
EP0343596A2 (fr
EP0343596A3 (en
Inventor
Thomas Dr. Rer. Nat. Bergmann
Herbert Brustmann
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.)
Roche Diagnostics GmbH
Original Assignee
Roche Diagnostics GmbH
Boehringer Mannheim 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 Roche Diagnostics GmbH, Boehringer Mannheim GmbH filed Critical Roche Diagnostics GmbH
Priority to AT89109246T priority Critical patent/ATE73226T1/de
Publication of EP0343596A2 publication Critical patent/EP0343596A2/fr
Publication of EP0343596A3 publication Critical patent/EP0343596A3/de
Application granted granted Critical
Publication of EP0343596B1 publication Critical patent/EP0343596B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • 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 container for freeze-drying under sterile conditions, in particular for drying biological and / or pharmaceutical material.
  • Freeze-drying of biological and pharmaceutical substances is generally known (see also Ullman's Encyclopedia of Industrial Chemistry, 3rd edition, Vol. I, p. 556 ff.), In order to avoid contamination of the dried goods with germs and other impurities , elaborate equipment and process engineering measures taken.
  • the procedure is such that vials containing the frozen good are provided with a bacterial filter and the good in the vial is dried in a first drying step until sublimation of the frozen solvent is complete is.
  • the so-called post-drying or residual drying the goods remaining moisture removed. Since this second drying step is usually carried out in a special apparatus, the ampoules or vials must be removed from the first drying apparatus in a further contamination-sensitive operation and introduced into the second drying apparatus.
  • the bacterial filter is removed and replaced by an aluminum cap with a rubber diaphragm and a hollow needle.
  • the drying room is filled with an inert gas and with a slight overpressure and the diaphragm opening is sealed as vapor-tight as possible by a sealing compound.
  • freeze-drying of biological and pharmaceutical material is also carried out on plates under sterile conditions.
  • a solution of the material to be dried is first sterilized, for example by filtration through a sterile filter, then poured onto plates under sterile conditions and freeze-dried using known methods.
  • this method presupposes that the entire freeze dryer can be sterilized. It is also necessary to keep the area around the drying plant germ-free.
  • the aim of the invention is now to overcome the disadvantages indicated above and to provide a simple container, with the aid of which a sterile, freeze-dried material can be obtained without the above-mentioned complex sterility requirements for the drying system and for the space surrounding it.
  • a container for freeze-drying in particular biological or pharmaceutical material under sterile conditions which is characterized in that the sides thereof at least partially consist of two walls which are tightly and pressure-tightly connected at their edges, one of which consists of a wall liquid-tight material and the other wall of a hydrophobic, porous, germ-tight, water vapor permeable membrane is formed.
  • the invention is based on the knowledge that the steam flow resulting from the sublimation of solvent molecules, in particular water molecules, which flows from the material to be dried to the condenser, is only hindered to a small extent by the membrane used in the container according to the invention. Freeze-drying of material enclosed by the membrane is therefore almost the same quickly like freeze-drying the same open, unpackaged material.
  • the membranes used according to the invention are hydrophobic membranes which contain pores which on the one hand are permeable to water vapor, but on the other hand are so small that they can no longer be passed through by microorganisms. Such pores preferably have a size of ⁇ 0.5 ⁇ m, in particular of ⁇ 0.2 ⁇ m.
  • Preferably membranes are used which are tear-resistant even under the respective process conditions even when wet.
  • the container according to the invention can also be used with less stable membranes, provided that these are reinforced with a carrier material or are not subjected to excessive mechanical stress.
  • the proportion of the membrane on the wall surface selected in the container according to the invention depends on the respectively selected conditions and the drying time and can easily be found out by a person skilled in the art by simply trying it out.
  • the entire wall surface consists of the membrane film, in a further preferred embodiment approximately half.
  • the container according to the invention can also be used advantageously if the wall surface consists of only 10% of the membrane film.
  • Semi-permeable papers made of cellulose and conventional cellulose derivatives, such as cellulose acetate, are particularly suitable.
  • Membranes made of films of polymer compounds, such as polytetrafluoroethylene or polypropylene, are also preferably used.
  • Films made of sterilization paper according to DIN 58 953 are also particularly suitable as water-vapor-permeable membranes.
  • any film membrane can be used regardless of its components, provided that it meets the requirements specified in DIN standard 58 953 with regard to germ density, air permeability and, in particular, strength.
  • the container according to the invention consists of a bag or hose, which consists of the two walls which are tightly and pressure-tightly connected at their edges, one wall of which consists of liquid-tight material and the other wall is formed by the membrane.
  • the membrane is preferably welded or glued to the vessel.
  • Troughs are particularly suitable as vessels according to the invention.
  • the trough is made of liquid-tight plastic and preferably has a wall thickness of 0.5 to 1 mm.
  • drying conditions such as pressure, temperature and quantity, depend on the material to be dried, the thickness of the membrane as well as the size and number of its pores and must be determined for the respective material and the packaging by simple and customary testing.
  • the germ density of a membrane was tested in accordance with DIN 58 953 in such a way that microorganisms in water drops were placed on the test pieces and after the water drops had dried on, it was examined whether microorganisms had passed through on the underside of the test pieces.
  • the membrane film to be tested was cut into squares with an edge length of approximately 50 mm.
  • the test pieces were sterilized and dried. Each test piece of the sterilized membrane was placed with the side that can be contaminated during use upwards on a sterilized surface and inoculated with 5 drops of 0.1 ml (corresponding to 107 to 107 germs).
  • the test pieces were stored at room temperature from 20 to 25 ° C under a relative humidity of 40 to 60%. The drops must be completely dry within 6 hours.
  • Each specimen was placed with the inoculated area up on the surface of a blood agar plate (1.5% agar) so that the entire film area came into contact with the agar. After 5 to 6 seconds the paper was removed.
  • the plates were incubated at 37 ° C for 16 to 25 h. If the agar plates treated with such film samples show no growth, the film is considered to be sufficiently germ-tight. Further information on the testing of the germ tightness of membranes, in particular the production of test germ suspensions, can be found in part 6 of DIN standard 58 953.
  • a nutrient solution was prepared which consisted of 10 g peptone, 5 g glucose, 5 g NaCl, 0.084 g KH2PO4, 0.187 g Na2-HPO4x2H2O and pyrogen-free water ad 1.0 l existed and which was adjusted to pH 7.0. It was then sterilized in a closed vial.
  • a transparent sterile bag consisting of a transparent film and a suitable paper was prepared to hold the sterile nutrient solution to be lyophilized.
  • the commercially available transparent sterilization pouch film from Wipak Medical, type Steri-King R 47, which is tubular, i.e. welded on both sides, otherwise open, located on a roll (width of the roll 400 mm), cut off a piece with a length of 800 mm. This tube was welded to a bag on the two open sides with a commercially available film device.
  • This bag was then sterilized in an autoclave with a filter program at 123 ° C and 2 bar steam pressure, the sterile bag with the transparent film facing downwards for better handling in an unsterile sheet metal tray (VA sheet, dimensions: length 800 mm, width 400 mm, height 30 mm) and opened in a laminar flow box under sterile conditions with disinfected scissors by cutting off a corner.
  • VA sheet unsterile sheet metal tray
  • 1.5 l of the sterile nutrient solution were introduced via a sterile tube pushed into the opening.
  • the bag filled in this way was sealed in the laminar flow box under sterile conditions by means of a commercially available film sealing device by corner sealing.
  • the entire arrangement (sheet tray, bag and sterile proximity solution) was placed on a plate of a commercially available, non-sterilizable freeze drying system from Edwards + Kniese pre-cooled to -45 ° C a total floor space of 1.5 m2 and the solution frozen. After completely freezing the solution under non-sterile conditions, freeze-drying was carried out at a pressure of 10 ⁇ 1 torr and a plate temperature of 22 ° C and the product was dried at 10 ⁇ 3 torr, also under non-sterile conditions. The total drying time was approx. 72 h.
  • the freeze-dried material thus obtained which was present as a light brown powder in the transparent sterilization bag, was placed in a laminar flow box including the bag and dissolved in 1.5 l of sterile water.
  • the intended puncture site on the paper side was disinfected with alcohol, a total of 1.5 l of sterile water was added to the bag using a sterile cannula and a suitable sterile syringe, the dried material was dissolved and the solution was transferred to a sterile bottle. This solution was incubated for 4 days at 37 ° C. and the germ count of the incubated solution was then determined using the membrane filter method.

Landscapes

  • Engineering & Computer Science (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Medical Preparation Storing Or Oral Administration Devices (AREA)
  • Drying Of Solid Materials (AREA)
  • Freezing, Cooling And Drying Of Foods (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Claims (10)

1. Récipient pour la lyophilisation en particulier d'un produit biologique ou pharmaceutique dans des conditions stériles, caractérisé en ce que ses côtés consistent au moins en partie en deux parois reliées entre-elles de manière étanche et résistante à la pression, l'une des parois consistant en un matériau étanche aux liquides et l'autre paroi consistant en une membrane hydrophobe, poreuse, imperméable aux germes, perméable à la vapeur d'eau.
2. Récipient selon la revendication 1, caractérisé en ce que les pores de la membrane ont une taille ≦ 0,5 µm.
3. Récipient selon la revendication 1 ou 2, caractérisé en ce que les pores de la membrane ont une taille ≦ 0,2 µm.
4. Récipient selon l'une des revendications 1 à 3, caractérisé en ce que la membrane est une feuille présentant les caractéristiques selon DIN 58 953.
5. Récipient selon l'une des revendications 1 à 4, caractérisé en ce que la membrane consiste en papier semi-perméable, de préférence en cellulose et en dérivés cellulosiques.
6. Récipient selon la revendication 5, caractérisé en ce que la membrane consiste en acétate de cellulose.
7. Récipient selon les revendications 1 à 4, caractérisé en ce que la membrane est une feuille d'un composé polymérique, de préférence de polytétrafluoroéthylène ou de polypropylène.
8. Récipient selon les revendications 1 à 7, caractérisé en ce qu'il est sous forme de tuyau souple ou de poche.
9. Récipient selon les revendications 1 à 7, caractérisé en ce qu'il est sous forme de bouteille, d'ampoule ou de fiole fermée par la membrane.
10. Récipient selon les revendications 1 à 7, caractérisé en ce qu'il est sous forme de cuve qui est reliée de manière résistante à la pression à la membrane formant couvercle.
EP89109246A 1988-05-26 1989-05-23 Récipient pour lyophilisation sous conditions stériles Expired - Lifetime EP0343596B1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AT89109246T ATE73226T1 (de) 1988-05-26 1989-05-23 Behaelter zum gefriertrocknen unter sterilen bedingungen.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE3817906 1988-05-26
DE3817906A DE3817906A1 (de) 1988-05-26 1988-05-26 Verfahren und behaeltnis zum gefriertrocknen unter sterilen bedingungen

Publications (3)

Publication Number Publication Date
EP0343596A2 EP0343596A2 (fr) 1989-11-29
EP0343596A3 EP0343596A3 (en) 1990-02-28
EP0343596B1 true EP0343596B1 (fr) 1992-03-04

Family

ID=6355171

Family Applications (1)

Application Number Title Priority Date Filing Date
EP89109246A Expired - Lifetime EP0343596B1 (fr) 1988-05-26 1989-05-23 Récipient pour lyophilisation sous conditions stériles

Country Status (13)

Country Link
EP (1) EP0343596B1 (fr)
JP (1) JPH0229256A (fr)
AT (1) ATE73226T1 (fr)
CA (1) CA1337974C (fr)
DD (1) DD283864A5 (fr)
DE (2) DE3817906A1 (fr)
DK (1) DK173643B1 (fr)
ES (1) ES2030556T3 (fr)
FI (1) FI91442C (fr)
GR (1) GR3004584T3 (fr)
HU (1) HU204126B (fr)
IE (1) IE61012B1 (fr)
PL (1) PL159938B1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5958778A (en) * 1995-09-22 1999-09-28 The United States Of America As Represented By The Department Of Health And Human Services Container for drying biological samples, method of making such container, and method of using same
US6312648B1 (en) 1998-01-12 2001-11-06 The United States Of America As Represented By The Department Of Health And Human Services Applicator system
US10793327B2 (en) 2017-10-09 2020-10-06 Terumo Bct Biotechnologies, Llc Lyophilization container and method of using same
US11604026B2 (en) 2019-03-14 2023-03-14 Terumo Bct Biotechnologies, Llc Lyophilization loading tray assembly and system

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IL90188A0 (en) * 1988-05-18 1989-12-15 Cryopharm Corp Process and medium for the lyophilization of erythrocytes
US5045446A (en) * 1988-08-26 1991-09-03 Cryopharm Corporation Lyophilization of cells
US5257983A (en) * 1991-04-12 1993-11-02 Cryopharm Corporation Blood bag for lyophilization
WO1995027180A1 (fr) * 1994-04-04 1995-10-12 W.L. Gore & Associates, Inc. Procede ameliore pour minimiser la contamination de produits lyophilises
EP0776297B1 (fr) * 1994-08-19 1998-08-05 W.L. Gore & Associates, Inc. Flacon a event pour lyophilisation et procede permettant de minimiser la contamination de produits lyophilises
FR2738057B1 (fr) * 1995-08-22 1997-11-07 Lab Francais Du Fractionnement Emballage etanche pour sechage, notamment lyophilisation, et procede de sechage, notamment de lyophilisation, a l'aide d'un tel emballage
FR2740108B1 (fr) * 1995-08-22 1998-03-27 Lab Francais Du Fractionnement Emballage etanche pour sechage, notamment lyophilisation, et procede de sechage, notamment de lyophilisation, a l'aide d'un tel emballage
US5596814A (en) * 1995-11-06 1997-01-28 W. L. Gore & Associates, Inc. Vented vial stopper for processing freeze-dried products
AT1399U1 (de) 1995-11-29 1997-04-25 Immuno Ag Verfahren und einrichtung zum lyophilisieren
DE19751031A1 (de) 1997-11-19 1999-06-24 Ingo Dipl Ing Heschel Verfahren zur Herstellung poröser Strukturen
DE19815993C2 (de) * 1998-04-09 2003-03-06 Schott Glas Behälter zur Gefriertrocknung und Aufbewahrung medizinischer Produkte
EP1958618A1 (fr) 2007-02-15 2008-08-20 Octapharma AG Procédé destiné à la lyophilisation par reconstitution optimisée de biopolymères
JP2010124931A (ja) * 2008-11-26 2010-06-10 Kanae Co Ltd 凍結乾燥製剤の包装体の製造方法
EP2386399B8 (fr) * 2010-04-23 2015-08-05 MC Beteiligungs-GmbH Procédé pour faire des trous dans un revêtement étanche et corps de base avec un tel revêtement
WO2015162273A1 (fr) 2014-04-25 2015-10-29 Merck Sharp & Dohme Bv Procédé pour assécher de multiples corps individuels congelés et système permettant d'appliquer ce procédé
JP2019090596A (ja) * 2017-11-10 2019-06-13 エイブル株式会社 凍結乾燥生成物の製造方法、及び、凍結乾燥用袋、並びに、凍結乾燥装置

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE620147A (fr) * 1961-07-17
BE622411A (fr) * 1961-11-28
GB1154320A (en) * 1965-09-24 1969-06-04 Unilever Ltd Freeze Drying
FR2284842A1 (fr) * 1974-09-11 1976-04-09 Nestle Sa Perfectionnement apporte la lyophilisation des produits solides, liquides ou pateux
JPS60168464A (ja) * 1983-11-18 1985-08-31 新技術事業団 血液保存方法及びその保存用容器
JPS6136942A (ja) * 1984-07-28 1986-02-21 Sony Corp 電子部品装置

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5958778A (en) * 1995-09-22 1999-09-28 The United States Of America As Represented By The Department Of Health And Human Services Container for drying biological samples, method of making such container, and method of using same
US6312648B1 (en) 1998-01-12 2001-11-06 The United States Of America As Represented By The Department Of Health And Human Services Applicator system
US10793327B2 (en) 2017-10-09 2020-10-06 Terumo Bct Biotechnologies, Llc Lyophilization container and method of using same
US11604026B2 (en) 2019-03-14 2023-03-14 Terumo Bct Biotechnologies, Llc Lyophilization loading tray assembly and system
US11609042B2 (en) 2019-03-14 2023-03-21 Terumo Bct Biotechnologies, Llc Multi-part lyophilization container and method of use

Also Published As

Publication number Publication date
FI91442C (fi) 1994-06-27
IE61012B1 (en) 1994-09-07
HU204126B (en) 1991-11-28
DK252589D0 (da) 1989-05-24
JPH0229256A (ja) 1990-01-31
ATE73226T1 (de) 1992-03-15
FI892563A0 (fi) 1989-05-25
DE58900902D1 (de) 1992-04-09
PL159938B1 (pl) 1993-01-29
EP0343596A2 (fr) 1989-11-29
EP0343596A3 (en) 1990-02-28
FI892563A (fi) 1989-11-27
GR3004584T3 (fr) 1993-04-28
PL279609A1 (en) 1990-01-22
ES2030556T3 (es) 1992-11-01
CA1337974C (fr) 1996-01-23
FI91442B (fi) 1994-03-15
DD283864A5 (de) 1990-10-24
DE3817906A1 (de) 1989-11-30
HUT52617A (en) 1990-07-28
IE891541L (en) 1989-11-26
JPH0450830B2 (fr) 1992-08-17
DK252589A (da) 1989-11-27
DK173643B1 (da) 2001-05-14

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