CA1337974C - Process and container for freeze drying under sterile conditions - Google Patents
Process and container for freeze drying under sterile conditionsInfo
- Publication number
- CA1337974C CA1337974C CA000600212A CA600212A CA1337974C CA 1337974 C CA1337974 C CA 1337974C CA 000600212 A CA000600212 A CA 000600212A CA 600212 A CA600212 A CA 600212A CA 1337974 C CA1337974 C CA 1337974C
- Authority
- CA
- Canada
- Prior art keywords
- container
- process according
- membrane
- biological
- pharmaceutical
- 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
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
Abstract
The present invention provides a process for freeze drying of especially biologically or pharma-ceutical material under sterile conditions, wherein the material to be dried is introduced into a con-tainer the sides of which consist at least partly of a hydrophobic, porous, micro-organism-impermeable, water vapour-permeable membrane, the container is tightly closed and the material is subsequently freeze dried in the closed container under the usual conditions.
The present invention also provides a container for freeze drying materials under sterile conditions, wherein the sides of the container consist at least partly of a hydrophobic, porous, germ-impermeable, water vapour-permeable membrane.
The present invention also provides a container for freeze drying materials under sterile conditions, wherein the sides of the container consist at least partly of a hydrophobic, porous, germ-impermeable, water vapour-permeable membrane.
Description
The present invention is concerned with a process for freeze drying under sterile conditions, as well as with a container for the carrying out of the process.
The present invention is especially concerned with the drying of biological and/or pharmaceutical material-In the case of biological and pharmaceutical.naterials, it is frequently ~ecessary to store the rnaterials completely dry until they are used. Thes~
sensitive substances are mostly only obtainable by freeze drying. Furthermore, as a rule, it is necessary to keep these substances completely free from micro-organisms not only because OL the deco,nposition of biological substances brought about by micro-organisms but also in order to prevent possible infections in the case of their use.
The freeze drying of biological and pharmaceutical -.naterials is generally known (see also Ullmanns Enzyklopadie der Technischen Che-,nie, 3rd edition, Vol. I, p. 556 et seq.). In order to avoid a contamin-ation of the dried material with micro-organisms and other contaminants, laborious apparatus and process-technical measures have to be made.
In the case of drying phari~aceutical preparations in ampoules or small bottles, the procedure is, for example, to provide small bottles which contain the frozen material with a bacterial filter and to dry the material in the small bottles in a first drying step to such an extent that the sublimation of the frozen solvent is concluded.
Subsequently, in a second drying stage, i.e. the so-called ?ost or residual drying, the still remaining residual moisture is removed from the material. 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 working step which is prone to contamination and introduced into the second drying apparatus. For this purpose, the bacterial filter is removed and re?laced by an aluminium cap provided with a rubber diaphragm and a hollow needle. After a residual drying for several days depending upon the nature of the -,naterial to be dried, the drying chamber is filled with an inert gas and with slight overpressure and the diaphrag opening closed as vapour-tightly as ?ossible by a grouting mass.
Since the speed of sublimation in the case of this type of freeze drying is only about half as great as that of openly spread out material, the freeze drying of biological and pharmaceutical material is also carried out on plates under sterile conditions.
A solution of the ~aterial to be dried is thereby first sterilised, for e~alnple by filtration over a sterile filter, subsequently poured under sterile conditions on to plates and fr~eze dried by means of known methods.
1~3797~
However, a prerequisite of this process is that the whole of the freeze drying plant can be sterilised.
~urthermore, it is also necessary to keep the surround-ings of the drying plant free from micro-organisms.
After drying has taken place, it is necessary to remove the material in the drying plant itself or in its surroundings with mechanical processes from the plates under sterile conditions and to fill it into also sterile storage containers. This process requires laborious plant and sterile charnbers, as well as an especially careful working with the material to be dried or already dried until it is confectioned ready for use.
The present invention seeks to overcome the above-mentioned disadvantages and to provide a simple process with the help of which freeze dried material can be obtained without the above-mentioned laborious sterility requirements for the drying plant, as well as for the space surrounding this.
Thus, according to the present invention, there is provided a process for freeze drying of especially biological or pharmaceutical ,naterial under sterile conditions, wherein the ~aterial to be dried is intro-duced under sterile conditions into a container, thesides of which consist at least partly of a hydrophobic germ-impermeable, porous, micro-organisrn-imper~eable B~
~ 5 ~ 133797~
membrane which is permeable to water in vapour form, the container is closed micro-organism-impermeably and tightly, especially cemented or welded, and the material is subsequently freeze dried directly in the closed container under the usual conditions, and more especially the freeze drying of the material is carried out under sterile conditions inside the closed container in a non-sterile ambient environment.
The present invention is based on the surprising finding that, contrary to expectations, the vapour flow resulting by the sublimation of solvent molecules, which flows from the material to be dried to a condenser, is hindered only to a small extent by the membrane used in the process according to the present invention. Thus, surprisingly, the freeze drying of material which is enclosed by the membrane proceeds almost equally quickly as the freeze drying of the same material when open and non-packed.
The membranes used according to the present invention are hydrophobic membranes which contain pores which, on the one hand, are permeable for water vapour but, on the other hand, are so small that micro-organisms can no longer pass through. Such pores preferably have a size of < 0.5 ~m. and especially of <
0.2 ~m. According to the present invention, membranes are preferably used which, under the particular process conditions, are also tearproof even in a wet state.
However, the process according to the present invention can also be carried out with less stable membranes provided that these are strengthened with a carrier C
material or are not excessively mechanically stressed.
~ he particularly selected proportion of the membrane on the wall surface of the container used in the process according to the present invention depends upon the particular selected conditions and the drying period and can easily be ascertained by means of si-nple experiments. In one e~,nbodiment preferred according to the present invention, the whole wall surface consists of the membrane film and in a further preferred embodi-ment about one half of the wall surface consists of themembrarle film. Surprisingly, the process according to the present invention can also be advantageously carried out when the wall surface also only consists of up to 10% of the me.nbrane film.
In particular, there can be used semi-permeable papers of cellulose and usual cellulose derivatives, sucn as cellulose acetate. According to the present invention, rneinbranes of films of polymer co,npounds, for example ?olytetrafluoroethylene or polypropylene, can also be advantageously used. Films of sterilis-ation paper according to German In dustrial Standard DI`L~ 5~ 953 are also quite especially useful as water vapour-per-lleable rnernbranes which standard thus counts as a part of the present description. In further preferred embodiments of the present invention, Gorete,~*and sir,.ilar merllbranes or also co-.nmercially available film tubes can be used, such as are marketed Trade Mark IB
by the firm Vihuri OY, Wipack, Finland, under the designation "`~ediplast". In principle, all film membrane can be used, regardless of their components, provided that they fulfil the requirements with re~ard to raicro-organism impermeability, air pen~eability and especially strength given in German Industrial Standard DIN 5~ 953-In a preferred embodiment, the process accordingto the present invention is carried out with the use of a bag or tube which preferably consists of two walls hennetically and tightly connected with on~ another on their edges, one wall of which consists of a liquid-tight material and the other wall of the me.tlbrane.
The membrane is preferably welded or glued with the vessel. Accordin~ to the present invention, trou~hs are especially pre~erred as the vessels.
In a further preferred embodi~nent, the trough consists of liquid-impermeable synthetic resin and preferably has a wall thickness of 0.5 to 1 mm.
The most favourable drying conditions, such as pressure, temperature and amount, depend upon the particular material to be dried and the thickness of the .nembrane, as well as upon the size and number of the pores thereof and must be determined by usual and simple experimentation for the particular material and the packing.
The following Examples are given for the purpose of illustrating the present invention:
* Trade Mark Example 1.
The testing of the micro-organism impermeability of a membrane was so carried out according to German Industrial Standard DIN 58 953 that micro-organisms in water drops were applied to test pieces and, after drying the water drops, it was ascertained whether micro-organisms have passed through to the under side of the test pieces.
The membrane film to be tested was cut up into lG squares of about 50 rnm. edge length and the test pieces were sterilised and dried. Each test piece of the sterilised mernbrane was placed on a sterilised substrate with the side which can be contaminated in the case of use upwardly and inoculated with 5 drops each of 0.1 ml. (corresponding to 106 to 107 micro-organisms).
The test pieces were stored at a temperature of 20 to 25C. under a relative atmospheric humidity of 40 to 60%. The drops must be completely dried within 6 hours.
Each test piece was placed with the inoculated surface upwardly on the surface of a blood agar plate (1.5%
agar) so that the whole film surface came into contact with the agar. ~fter 5 to 6 seconds, the paper was removed and the plates were incubated for 16 to 25 hours at 37C. If the agar plates treated with such film samples s"how no growth, the film is regarded as being sufficiently impermeable to micro-organisms. Further statements regarding the testing of the impermeability 133797~
of membranes to micro-organisms and especially the preparation of test micro-organism suspensions, can be taken from part 6 of German Industrial Standard DI~
53 953.
Example 2.
A nutrient solution was produced whicn consisted of 10 g. peptone, 5 g. glucose, 5 g. sodium chlori~, Q.OS4 g. monopotassiu~ dihydrogen phosphate, 0.187 g.
disodium hydrogen phosphate dihydrate and pyrogen-free water ad 1.0 litre and which had been adjusted to pH
7Ø Subsequently, it was end-sterilised in a closed, piercable bottle.
For the reception of the sterile nutrient solution to be lyophilised, there was prepared a trans-parent sterile bag consisting of a transparent filmand an appropriate paper. For this purpose, a piece with a length of 800 mm. was cut off from a commercially available roll of transparent sterilisation bag film of the firm Wipak Medical, type Steri-King*R 47 which is available in the form of a tube, i.e. is welded on both sides but is otherwise open, the roll having a width of 400 mm. This tube was welded on both of the open sides with a commercially available film-welding apparatus to form a bag. Subsequently, this bag was sterilised in an autoclave with filter programme at 123C. and 2 bar vapour pressure, the sterile bag was placed with the transparent film downwardly for better i B * Trade Mark 1337~7~
handling in a non-sterile sheet metal trough (VA sheet metal, dimensions: length 800 mm., breadth 400 mm., height 30 mm.) and opened in a laminar flowbox under sterile conditions with disinfected scissors by cutting off of a corner. Through this opening of about 30 mm.
between the film and the paper was introduced 1.5 litres of sterile nutrient solution via a sterile tube pushed into the opening. The so filled bag was again closed in the laminar flowbox under sterile conditions by means of a commercially available film welding device by welding over the corner.
The whole assembly (sheet metal trough, bag and sterile nutrient solution) was applied to a plate pre-cooled to -45C. of a commercially available, non-sterilisable freeze drying apparatus of the firmEdwards + Kniese with a total positioning surface of 1.5 m and the solution frozen in. After complete freezing in of the solution under non-sterile conditions, it was freeze dried at a pressure of 10 1 mm.Hg and a plate temperature of 22C. and the product post-dried at 10 3 mm.Hg, again under non-sterile conditions. The total drying time was about 72 hours.
The so obtained freeze-dried material, present as a pale brown powder in the transparent sterilisation bag, was subsequently introduced into a laminar flowbox and dissolved in 1.5 litres of sterile water. For this purpose, the intended puncturing point was disinfected with alcohol on the paper side, by means of a sterile canula and appropriate sterile syringe a total of 1.5 litres of sterile water was introduced into the bag, the dried material dissolved and the solution transferred into a sterile bottle. This solution was incubated for 4 days at 37C. and subsequently the micro-organism count of the incubated solution deter-mined by the membrane filter method.
It was shown that no micro-organisms had been entrained by the freeze drying.
The present invention is especially concerned with the drying of biological and/or pharmaceutical material-In the case of biological and pharmaceutical.naterials, it is frequently ~ecessary to store the rnaterials completely dry until they are used. Thes~
sensitive substances are mostly only obtainable by freeze drying. Furthermore, as a rule, it is necessary to keep these substances completely free from micro-organisms not only because OL the deco,nposition of biological substances brought about by micro-organisms but also in order to prevent possible infections in the case of their use.
The freeze drying of biological and pharmaceutical -.naterials is generally known (see also Ullmanns Enzyklopadie der Technischen Che-,nie, 3rd edition, Vol. I, p. 556 et seq.). In order to avoid a contamin-ation of the dried material with micro-organisms and other contaminants, laborious apparatus and process-technical measures have to be made.
In the case of drying phari~aceutical preparations in ampoules or small bottles, the procedure is, for example, to provide small bottles which contain the frozen material with a bacterial filter and to dry the material in the small bottles in a first drying step to such an extent that the sublimation of the frozen solvent is concluded.
Subsequently, in a second drying stage, i.e. the so-called ?ost or residual drying, the still remaining residual moisture is removed from the material. 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 working step which is prone to contamination and introduced into the second drying apparatus. For this purpose, the bacterial filter is removed and re?laced by an aluminium cap provided with a rubber diaphragm and a hollow needle. After a residual drying for several days depending upon the nature of the -,naterial to be dried, the drying chamber is filled with an inert gas and with slight overpressure and the diaphrag opening closed as vapour-tightly as ?ossible by a grouting mass.
Since the speed of sublimation in the case of this type of freeze drying is only about half as great as that of openly spread out material, the freeze drying of biological and pharmaceutical material is also carried out on plates under sterile conditions.
A solution of the ~aterial to be dried is thereby first sterilised, for e~alnple by filtration over a sterile filter, subsequently poured under sterile conditions on to plates and fr~eze dried by means of known methods.
1~3797~
However, a prerequisite of this process is that the whole of the freeze drying plant can be sterilised.
~urthermore, it is also necessary to keep the surround-ings of the drying plant free from micro-organisms.
After drying has taken place, it is necessary to remove the material in the drying plant itself or in its surroundings with mechanical processes from the plates under sterile conditions and to fill it into also sterile storage containers. This process requires laborious plant and sterile charnbers, as well as an especially careful working with the material to be dried or already dried until it is confectioned ready for use.
The present invention seeks to overcome the above-mentioned disadvantages and to provide a simple process with the help of which freeze dried material can be obtained without the above-mentioned laborious sterility requirements for the drying plant, as well as for the space surrounding this.
Thus, according to the present invention, there is provided a process for freeze drying of especially biological or pharmaceutical ,naterial under sterile conditions, wherein the ~aterial to be dried is intro-duced under sterile conditions into a container, thesides of which consist at least partly of a hydrophobic germ-impermeable, porous, micro-organisrn-imper~eable B~
~ 5 ~ 133797~
membrane which is permeable to water in vapour form, the container is closed micro-organism-impermeably and tightly, especially cemented or welded, and the material is subsequently freeze dried directly in the closed container under the usual conditions, and more especially the freeze drying of the material is carried out under sterile conditions inside the closed container in a non-sterile ambient environment.
The present invention is based on the surprising finding that, contrary to expectations, the vapour flow resulting by the sublimation of solvent molecules, which flows from the material to be dried to a condenser, is hindered only to a small extent by the membrane used in the process according to the present invention. Thus, surprisingly, the freeze drying of material which is enclosed by the membrane proceeds almost equally quickly as the freeze drying of the same material when open and non-packed.
The membranes used according to the present invention are hydrophobic membranes which contain pores which, on the one hand, are permeable for water vapour but, on the other hand, are so small that micro-organisms can no longer pass through. Such pores preferably have a size of < 0.5 ~m. and especially of <
0.2 ~m. According to the present invention, membranes are preferably used which, under the particular process conditions, are also tearproof even in a wet state.
However, the process according to the present invention can also be carried out with less stable membranes provided that these are strengthened with a carrier C
material or are not excessively mechanically stressed.
~ he particularly selected proportion of the membrane on the wall surface of the container used in the process according to the present invention depends upon the particular selected conditions and the drying period and can easily be ascertained by means of si-nple experiments. In one e~,nbodiment preferred according to the present invention, the whole wall surface consists of the membrane film and in a further preferred embodi-ment about one half of the wall surface consists of themembrarle film. Surprisingly, the process according to the present invention can also be advantageously carried out when the wall surface also only consists of up to 10% of the me.nbrane film.
In particular, there can be used semi-permeable papers of cellulose and usual cellulose derivatives, sucn as cellulose acetate. According to the present invention, rneinbranes of films of polymer co,npounds, for example ?olytetrafluoroethylene or polypropylene, can also be advantageously used. Films of sterilis-ation paper according to German In dustrial Standard DI`L~ 5~ 953 are also quite especially useful as water vapour-per-lleable rnernbranes which standard thus counts as a part of the present description. In further preferred embodiments of the present invention, Gorete,~*and sir,.ilar merllbranes or also co-.nmercially available film tubes can be used, such as are marketed Trade Mark IB
by the firm Vihuri OY, Wipack, Finland, under the designation "`~ediplast". In principle, all film membrane can be used, regardless of their components, provided that they fulfil the requirements with re~ard to raicro-organism impermeability, air pen~eability and especially strength given in German Industrial Standard DIN 5~ 953-In a preferred embodiment, the process accordingto the present invention is carried out with the use of a bag or tube which preferably consists of two walls hennetically and tightly connected with on~ another on their edges, one wall of which consists of a liquid-tight material and the other wall of the me.tlbrane.
The membrane is preferably welded or glued with the vessel. Accordin~ to the present invention, trou~hs are especially pre~erred as the vessels.
In a further preferred embodi~nent, the trough consists of liquid-impermeable synthetic resin and preferably has a wall thickness of 0.5 to 1 mm.
The most favourable drying conditions, such as pressure, temperature and amount, depend upon the particular material to be dried and the thickness of the .nembrane, as well as upon the size and number of the pores thereof and must be determined by usual and simple experimentation for the particular material and the packing.
The following Examples are given for the purpose of illustrating the present invention:
* Trade Mark Example 1.
The testing of the micro-organism impermeability of a membrane was so carried out according to German Industrial Standard DIN 58 953 that micro-organisms in water drops were applied to test pieces and, after drying the water drops, it was ascertained whether micro-organisms have passed through to the under side of the test pieces.
The membrane film to be tested was cut up into lG squares of about 50 rnm. edge length and the test pieces were sterilised and dried. Each test piece of the sterilised mernbrane was placed on a sterilised substrate with the side which can be contaminated in the case of use upwardly and inoculated with 5 drops each of 0.1 ml. (corresponding to 106 to 107 micro-organisms).
The test pieces were stored at a temperature of 20 to 25C. under a relative atmospheric humidity of 40 to 60%. The drops must be completely dried within 6 hours.
Each test piece was placed with the inoculated surface upwardly on the surface of a blood agar plate (1.5%
agar) so that the whole film surface came into contact with the agar. ~fter 5 to 6 seconds, the paper was removed and the plates were incubated for 16 to 25 hours at 37C. If the agar plates treated with such film samples s"how no growth, the film is regarded as being sufficiently impermeable to micro-organisms. Further statements regarding the testing of the impermeability 133797~
of membranes to micro-organisms and especially the preparation of test micro-organism suspensions, can be taken from part 6 of German Industrial Standard DI~
53 953.
Example 2.
A nutrient solution was produced whicn consisted of 10 g. peptone, 5 g. glucose, 5 g. sodium chlori~, Q.OS4 g. monopotassiu~ dihydrogen phosphate, 0.187 g.
disodium hydrogen phosphate dihydrate and pyrogen-free water ad 1.0 litre and which had been adjusted to pH
7Ø Subsequently, it was end-sterilised in a closed, piercable bottle.
For the reception of the sterile nutrient solution to be lyophilised, there was prepared a trans-parent sterile bag consisting of a transparent filmand an appropriate paper. For this purpose, a piece with a length of 800 mm. was cut off from a commercially available roll of transparent sterilisation bag film of the firm Wipak Medical, type Steri-King*R 47 which is available in the form of a tube, i.e. is welded on both sides but is otherwise open, the roll having a width of 400 mm. This tube was welded on both of the open sides with a commercially available film-welding apparatus to form a bag. Subsequently, this bag was sterilised in an autoclave with filter programme at 123C. and 2 bar vapour pressure, the sterile bag was placed with the transparent film downwardly for better i B * Trade Mark 1337~7~
handling in a non-sterile sheet metal trough (VA sheet metal, dimensions: length 800 mm., breadth 400 mm., height 30 mm.) and opened in a laminar flowbox under sterile conditions with disinfected scissors by cutting off of a corner. Through this opening of about 30 mm.
between the film and the paper was introduced 1.5 litres of sterile nutrient solution via a sterile tube pushed into the opening. The so filled bag was again closed in the laminar flowbox under sterile conditions by means of a commercially available film welding device by welding over the corner.
The whole assembly (sheet metal trough, bag and sterile nutrient solution) was applied to a plate pre-cooled to -45C. of a commercially available, non-sterilisable freeze drying apparatus of the firmEdwards + Kniese with a total positioning surface of 1.5 m and the solution frozen in. After complete freezing in of the solution under non-sterile conditions, it was freeze dried at a pressure of 10 1 mm.Hg and a plate temperature of 22C. and the product post-dried at 10 3 mm.Hg, again under non-sterile conditions. The total drying time was about 72 hours.
The so obtained freeze-dried material, present as a pale brown powder in the transparent sterilisation bag, was subsequently introduced into a laminar flowbox and dissolved in 1.5 litres of sterile water. For this purpose, the intended puncturing point was disinfected with alcohol on the paper side, by means of a sterile canula and appropriate sterile syringe a total of 1.5 litres of sterile water was introduced into the bag, the dried material dissolved and the solution transferred into a sterile bottle. This solution was incubated for 4 days at 37C. and subsequently the micro-organism count of the incubated solution deter-mined by the membrane filter method.
It was shown that no micro-organisms had been entrained by the freeze drying.
Claims (64)
1. A process for freeze drying of material under sterile conditions, wherein the material to be dried is introduced into a container the container having sides which consist at least partly of two walls connected hermetically and pressure-proof with one another on their edges, one wall of which is made from liquid-tight material and the other wall of a hydrophobic, porous, germ-tight water vapour-permeable material, the container is tightly closed and the material is subsequently freeze dried in the closed container.
2. A process according to claim 1, wherein said membrane has pores with a size of < 0.5 µm.
3. A process according to claim 2, wherein said membrane has pores with a size of < 0.2 µm.
4. A process according to claim 1, 2 or 3, wherein said membrane is a film having properties according to German Industrial Standard DIN 58 953.
5. A process according to claim 1, 2 or 3, wherein said membrane is of semi-permeable paper.
6. A process according to claim 5, wherein the semi-permeable paper is made of cellulose or a cellu-lose derivative.
7. A process according to claim 6, wherein said membrane is of cellulose acetate.
8. A process according to claim 4, wherein said membrane is of semi-permeable paper.
9. A process according to claim 8, wherein the semi-permeable paper is made of cellulose or a cellu-lose derivative.
10. A process according to claim 9, wherein said membrane is of cellulose acetate.
11. A process according to claim 1, 2 or 3, wherein the membrane used is a film of a polymer com-pound.
12. A process according to claim 8, wherein the polymer compound is polytetrafluoroethylene or polypropylene.
13. A process according to claim 4, wherein the membrane used is a film of a polymer compound.
14. A process according to claim 13, wherein the polymer compound is polytetrafluoroethylene or polypropylene.
15. A process according to claim 1, 2, 3, 6, 7, 8, 9, 10, 12, 13 or 14, wherein said container is in the form of a tube or bag.
16. A process according to claim 4, wherein said container is in the form of a tube or bag.
17. A process according to claim 5, wherein said container is in the form of a tube or bag.
18. A process according to claim 11, wherein said container is in the form of a tube or bag.
19. A process according to claim 15, wherein the tube or bag has a water-impermeable wall which is tightly connected with a further wall formed by the membrane.
20. A process according to claim 16, 17 or 18, wherein the tube or bag has a water-impermeable wall which is tightly connected with a further wall formed by the membrane.
21. A process according to claim 1, 2, 3, 6, 7, 8, 9, 10, 12, 13 or 14, wherein said container is a flask, ampoule or vial which is closed with the mem-brane.
22. A process according to claim 4, wherein said container is a flask, ampoule or vial which is closed with the membrane.
23. A process according to claim 1, 2, 3, 6, 7, 8, 9, 10, 12, 13 or 14, wherein the container is a trough which is tightly connected with the membrane as covering.
24. A process according to claim 4, wherein the container is a trough which is tightly connected with the membrane as covering.
25. A process according to claim 1, 2, 3, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 18 or 19, wherein said material is a biological or pharmaceutical material.
26. A process according to claim 4, wherein said material is a biological or pharmaceutical material.
27. A process according to claim 5, wherein said material is a biological or pharmaceutical material,
28. A process according to claim 11, wherein said material is a biological or pharmaceutical mate-rial.
29. A process according to claim 15, wherein said material is a biological or pharmaceutical mate-rial.
30. A process according to claim 20, wherein said material is a biological or pharmaceutical mate-rial.
31. A process according to claim 21, wherein said material is a biological or pharmaceutical mate-rial.
32. A process according to claim 22, wherein said material is a biological or pharmaceutical mate-rial.
33. A process according to claim 23, wherein said material is a biological or pharmaceutical mate-rial.
34. A process according to claim 24, wherein said material is a biological or pharmaceutical mate-rial.
35. A process according to claim 1, 2, 3, 6, 7, 8, 9, 10, 12, 13, 14, 16, 17, 18, 19, 27, 28, 29, 30, 31, 32, 33 or 34, wherein said container is in a non-sterile environment and introduction of the material into the container, closing of the container and freeze drying of the material in the closed container is conducted in said non-sterile environment.
36. A container for freeze drying materials under sterile conditions, the container having sides which consist at least partly of two walls connected hermetically and pressure-proof with one another on their edges, one wall of which is made from liquid-tight material and the other wall of a hydrophobic, porous, germ-tight water vapour-permeable material.
37. A container according to claim 36, in the form of a bag.
38. A container according to claim 36, in the form of a tube.
39. A container according to claim 36, in the form of a trough which is tightly connected with said membrane as a covering.
40. A container according to claim 36, in the form of a flask, ampoule or vial closed with the mem-brane.
41. A container according to claim 36, 37, 38, 39 or 40, wherein pores of the membrane have a size of ?0.5 µm.
42. A container according to claim 41, wherein said size is ?0.2 µm.
43. A container according to claim 36, 37, 38, 39, 40 or 42, wherein said membrane is a film with properties according to DIN 58953.
44. A container according to claim 36, 37, 38, 39, 40 or 42, wherein said membrane is of semi-permeable paper.
45. A container according to claim 44, wherein said membrane is of cellulose or a cellulose derivative.
46. A container according to claim 45, wherein said membrane is of cellulose acetate.
47. A container according to claim 36, 37, 38, 39, 40 or 42, wherein said membrane is a film of a polymer compound.
48. A container according to claim 47, wherein said polymer compound is polytetrafluoroethylene or polypropylene.
49. The method of freeze drying biological or pharmaceutical material under sterile conditions, which comprises introducing said material into a container the sides of which consist at least partly of a hydrophobic, porous, micro-organism-impermeable and water vapour-permeable membrane, tightly closing the container and freeze drying said material under sterile conditions inside the closed container in a non-sterile ambient environment.
50. The method of claim 49, wherein the membrane has pores with a size of 0.5 µm.
51. The method of claim 50, wherein the membrane has pores with a size of 0.2 µm.
52. The method of claim 49, 50 or 51, wherein said membrane is semi-permeable paper.
53. The method of claim 52, wherein the semi-permeable paper is made of cellulose or a cellulose derivative.
54. The method of claim 53, wherein the membrane is of cellulose acetate.
55. The method of claim 49, wherein the membrane is a film of a polymer compound.
56. The method of claim 55, wherein the polymer compound is polytetrafluoroethylene or polypropylene.
57. The method of claim 49, 50, 51, 53, 54, 55 or 56, wherein the container is in the form of a tube or bag.
58. The method of claim 57, wherein the tube or bag comprises a water-impermeable wall which is tightly connected with a further wall formed by the membrane.
59. The method of claim 49, 50, 41, 53, 54, 55 or 56, wherein the container is a flask, ampoule or vial which is closed with the membrane.
60. The method of claim 49, 50, 51, 53, 54, 55 or 56, wherein the container is a trough which is tightly connected with the membrane as covering.
61. A process according to claim 5, wherein said container is a flask, ampoule or vial which is closed with the membrane.
62. A process according to claim 11, wherein said container is a flask, ampoule or vial which is closed with the membrane.
63. A process according to claim 5, wherein the container is a trough which is tightly connected with the membrane as covering.
64. A process according to claim 11, wherein the container is a trough which is tightly connected with the membrane as covering.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3817906A DE3817906A1 (en) | 1988-05-26 | 1988-05-26 | METHOD AND CONTAINER FOR FREEZING DRYING UNDER STERILE CONDITIONS |
| DEP3817906.7 | 1988-05-26 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1337974C true CA1337974C (en) | 1996-01-23 |
Family
ID=6355171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000600212A Expired - Lifetime CA1337974C (en) | 1988-05-26 | 1989-05-19 | Process and container for freeze drying under sterile conditions |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP0343596B1 (en) |
| JP (1) | JPH0229256A (en) |
| AT (1) | ATE73226T1 (en) |
| CA (1) | CA1337974C (en) |
| DD (1) | DD283864A5 (en) |
| DE (2) | DE3817906A1 (en) |
| DK (1) | DK173643B1 (en) |
| ES (1) | ES2030556T3 (en) |
| FI (1) | FI91442C (en) |
| GR (1) | GR3004584T3 (en) |
| HU (1) | HU204126B (en) |
| IE (1) | IE61012B1 (en) |
| PL (1) | PL159938B1 (en) |
Families Citing this family (20)
| 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 |
| AU7356094A (en) * | 1994-04-04 | 1995-10-23 | W.L. Gore & Associates, Inc. | Improved method for minimizing contamination of freeze-dried products |
| CA2178496A1 (en) * | 1994-08-19 | 1996-02-29 | C. Bradford Jones | Vented vial for freeze-drying and method of minimizing contamination of freeze-dried products |
| FR2738057B1 (en) * | 1995-08-22 | 1997-11-07 | Lab Francais Du Fractionnement | WATERPROOF PACKAGING FOR DRYING, ESPECIALLY LYOPHILIZATION, AND DRYING METHOD, ESPECIALLY LYOPHILIZATION, USING SUCH PACKAGING |
| FR2740108B1 (en) * | 1995-08-22 | 1998-03-27 | Lab Francais Du Fractionnement | WATERPROOF PACKAGING FOR DRYING, ESPECIALLY LYOPHILIZATION, AND DRYING METHOD, ESPECIALLY LYOPHILIZATION, USING SUCH PACKAGING |
| EP0854911B1 (en) | 1995-09-22 | 2004-11-24 | GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY OF THE DEPARTMENT OF HEALTH AND HUMAN SERVICES | Container for drying biological samples, method of making such container, and method of using same |
| US5596814A (en) * | 1995-11-06 | 1997-01-28 | W. L. Gore & Associates, Inc. | Vented vial stopper for processing freeze-dried products |
| AT1399U1 (en) | 1995-11-29 | 1997-04-25 | Immuno Ag | METHOD AND DEVICE FOR LYOPHILIZING |
| DE19751031A1 (en) * | 1997-11-19 | 1999-06-24 | Ingo Dipl Ing Heschel | Process for the production of porous structures |
| 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 |
| DE19815993C2 (en) * | 1998-04-09 | 2003-03-06 | Schott Glas | Freeze-drying containers and storage for medical products |
| EP1958618A1 (en) | 2007-02-15 | 2008-08-20 | Octapharma AG | Method for freeze-drying with optimum reconstitution of biopolymers |
| JP2010124931A (en) * | 2008-11-26 | 2010-06-10 | Kanae Co Ltd | Method for manufacturing package of freeze-dried medicine |
| EP2386399B8 (en) * | 2010-04-23 | 2015-08-05 | MC Beteiligungs-GmbH | Method for making openings in a waterproof coating and base body with such coating |
| WO2015162273A1 (en) | 2014-04-25 | 2015-10-29 | Merck Sharp & Dohme Bv | A method to dry multiple individual frozen bodies and a system for applying this method |
| WO2019074886A1 (en) | 2017-10-09 | 2019-04-18 | Terumo Bct Biotechnologies, Llc | Lyophilization container and method of using same |
| JP2019090596A (en) * | 2017-11-10 | 2019-06-13 | エイブル株式会社 | Method for producing freeze-dried product, freeze-drying bag, and freeze-drying device |
| CA3224729A1 (en) | 2019-03-14 | 2020-09-17 | Terumo Bct Biotechnologies, Llc | Lyophilization loading tray assembly and system |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE620147A (en) * | 1961-07-17 | |||
| BE622411A (en) * | 1961-11-28 | |||
| GB1154320A (en) * | 1965-09-24 | 1969-06-04 | Unilever Ltd | Freeze Drying |
| FR2284842A1 (en) * | 1974-09-11 | 1976-04-09 | Nestle Sa | IMPROVEMENT PROVIDES LYOPHILIZATION OF SOLID, LIQUID OR PASTE PRODUCTS |
| JPS60168464A (en) * | 1983-11-18 | 1985-08-31 | 新技術事業団 | Blood preserving method and container |
| JPS6136942A (en) * | 1984-07-28 | 1986-02-21 | Sony Corp | Apparatus for electronic part |
-
1988
- 1988-05-26 DE DE3817906A patent/DE3817906A1/en not_active Withdrawn
-
1989
- 1989-05-11 IE IE154189A patent/IE61012B1/en not_active IP Right Cessation
- 1989-05-19 CA CA000600212A patent/CA1337974C/en not_active Expired - Lifetime
- 1989-05-23 DE DE8989109246T patent/DE58900902D1/en not_active Expired - Lifetime
- 1989-05-23 EP EP89109246A patent/EP0343596B1/en not_active Expired - Lifetime
- 1989-05-23 AT AT89109246T patent/ATE73226T1/en not_active IP Right Cessation
- 1989-05-23 ES ES198989109246T patent/ES2030556T3/en not_active Expired - Lifetime
- 1989-05-24 PL PL1989279609A patent/PL159938B1/en unknown
- 1989-05-24 DD DD89328870A patent/DD283864A5/en not_active IP Right Cessation
- 1989-05-24 DK DK198902525A patent/DK173643B1/en not_active IP Right Cessation
- 1989-05-25 HU HU892683A patent/HU204126B/en unknown
- 1989-05-25 FI FI892563A patent/FI91442C/en not_active IP Right Cessation
- 1989-05-26 JP JP1131693A patent/JPH0229256A/en active Granted
-
1992
- 1992-05-13 GR GR920400224T patent/GR3004584T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL159938B1 (en) | 1993-01-29 |
| DE58900902D1 (en) | 1992-04-09 |
| ATE73226T1 (en) | 1992-03-15 |
| PL279609A1 (en) | 1990-01-22 |
| FI91442C (en) | 1994-06-27 |
| FI892563A0 (en) | 1989-05-25 |
| EP0343596A2 (en) | 1989-11-29 |
| IE61012B1 (en) | 1994-09-07 |
| ES2030556T3 (en) | 1992-11-01 |
| GR3004584T3 (en) | 1993-04-28 |
| JPH0229256A (en) | 1990-01-31 |
| HU204126B (en) | 1991-11-28 |
| DD283864A5 (en) | 1990-10-24 |
| EP0343596B1 (en) | 1992-03-04 |
| EP0343596A3 (en) | 1990-02-28 |
| DK252589A (en) | 1989-11-27 |
| DK252589D0 (en) | 1989-05-24 |
| JPH0450830B2 (en) | 1992-08-17 |
| HUT52617A (en) | 1990-07-28 |
| FI892563A (en) | 1989-11-27 |
| IE891541L (en) | 1989-11-26 |
| DE3817906A1 (en) | 1989-11-30 |
| FI91442B (en) | 1994-03-15 |
| DK173643B1 (en) | 2001-05-14 |
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| Date | Code | Title | Description |
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| MKEX | Expiry |
Effective date: 20130123 |