DK173643B1 - Freeze drying container under sterile conditions - Google Patents
Freeze drying container under sterile conditions Download PDFInfo
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- DK173643B1 DK173643B1 DK198902525A DK252589A DK173643B1 DK 173643 B1 DK173643 B1 DK 173643B1 DK 198902525 A DK198902525 A DK 198902525A DK 252589 A DK252589 A DK 252589A DK 173643 B1 DK173643 B1 DK 173643B1
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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
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- 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)
Abstract
Description
i DK 173643 B1in DK 173643 B1
Opfindelsen angår en beholder til frysetørring af især biologisk eller farmakologisk materiale under sterile betingelser.The invention relates to a container for freeze-drying of biological or pharmacological material in particular under sterile conditions.
Ved biologisk og farmakologisk materiale er det ofte nødvendigt at opbevare stofferne helt tørt indtil deres anvendelse. Oftest er disse følsomme stoffer kun tilgængelige ved 5 hjælp af frysetørring. Desuden er det som regel en nødvendighed at holde disse stoffer fuldstændigt fri for mikrobiologiske kim, og nærmere bestemt at forhindre såvel den på grund af mikrober forårsagede opløsning af biologiske stoffer, som mulige infektioner ved deres anvendelse.For biological and pharmacological materials it is often necessary to keep the substances completely dry until their use. Most often, these sensitive substances are only available through freeze-drying. Furthermore, it is usually a necessity to keep these substances completely free of microbiological germs, and more specifically to prevent both the dissolution of biological substances caused by microbes as well as possible infections in their use.
Frysetørring af biologiske og farmakologiske stoffer er almindelig kendt (se også Ull-10 manns Enzyklopådieder Technischen Chemie, 3. Aufl., Bd. I, S. 556 ff). I den forbindelse træffes, for at undgå kontamination af det tørrede råstof med kim og andre forureninger, kostbare apparat- og fremgangsmådetekniske forholdsregler.Freeze-drying of biological and pharmacological substances is well known (see also Ull-10 Manns Enzyklopådieder Technischen Chemie, 3rd Aufl., Vol. I, pp. 556 ff). In this connection, in order to avoid contamination of the dried raw material with germs and other contaminants, costly appliance and process technical measures are taken.
Tørringen af farmakologiske præparater i ampuller eller små- flasker foregår eksempelvis således, at småflasken, der indeholder det frosne råstof, udstyres med et bakteriefilter, 15 og råstoffet i flasken tørres så meget i et første tørringstrin, at sublimationen af det frosne opløsningsmiddel er afsluttet.The drying of pharmacological preparations in ampoules or small bottles, for example, takes place so that the small bottle containing the frozen raw material is equipped with a bacterial filter, and the raw material in the bottle is dried so much in a first drying step that the sublimation of the frozen solvent is completed.
Derefter fjernes, i et andet tørringstrin, den såkaldte efter- eller resttørring, den tiloversblevne restfugtighed fra råstoffet. Da dette andet tørringstrin oftest gennemføres i et særskilt apparatur, må ampullerne eller fiolerne, i en yderligere kontaminationsfølsom 20 arbejdsgang, udtages fra det første tørringsapparatur og anbringes i det andet tørringsapparatur. I den forbindelse fjernes bakteriefilteret og erstattes af en aluminiumskappe, der er forsynet med en gummimembran og en kanyle. Efter en, alt efter arten af råstoffet, der skal tørres, flere dages resttørring fyldes tørrerummet med en inert gas ved et lille overtryk, og membranåbningen lukkes så vidt muligt damptæt ved hjælp af et tætningsmiddel.Then, in another drying step, the so-called post-drying or residual drying, the remaining residual moisture is removed from the raw material. Since this second drying step is most often performed in a separate apparatus, the ampoules or violins, in a further contamination-sensitive operation, must be removed from the first drying apparatus and placed in the second drying apparatus. In this connection, the bacterial filter is removed and replaced by an aluminum sheath provided with a rubber membrane and a needle. After one, depending on the nature of the raw material to be dried, several days of residual drying, the drying room is filled with an inert gas at a slight overpressure and the membrane opening is closed as far as possible vapor-tight by means of a sealant.
DK 173643 B1 2DK 173643 B1 2
Da sublimationshastigheden ved denne frysetørringsmåde kun er ca. halvt så stor som sublimationshastigheden for frit udspredt materiale, gennemføres frysetørringen af biologisk og farmakologisk materiale også på plader under sterile betingelser. I den forbindelse steriliseres først en opløsning indeholdende råstoffet der skal tørres, eksempelvis ved 5 filtrering gennem et sterilfilter, og hældes umiddelbart derefter under sterile betingelser på plader og frysetørres ved hjælp af kendte metoder. Denne fremgangsmåde forudsætter imidlertid, at hele frysetørringsanlægget er steriliserbart. Desuden er det nødvendigt også at holde tørringsanlæggets omgivelser kimfri.Since the sublimation rate of this freeze-drying method is only approx. half the sublimation rate of freely dispersed material, the freeze-drying of biological and pharmacological material is also carried out on plates under sterile conditions. To this end, a solution containing the raw material to be dried is first sterilized, for example, by filtration through a sterile filter, and immediately poured under sterile conditions onto plates and freeze-dried by known methods. However, this approach assumes that the entire freeze-drying system is sterilizable. Furthermore, it is also necessary to keep the environment of the drying plant germ-free.
Efter endt tørring er det nødvendigt i selve tørringsanlægget eller i dets omgivelser at 10 fjerne råstoffet fra pladerne under sterile betingelser med mekaniske fremgangsmåder og at fylde det på ligeledes sterile opbevaringsbeholdere. Denne fremgangsmåde kræver kostbare anlæg og sterile rum samt et særligt omhyggeligt arbejde med råstoffet der skal tørres henholdsvis det allerede tørrede råstof, indtil den brugsfærdige konfektionering.After drying, it is necessary in the drying plant itself or in its surroundings to remove the feedstock from the plates under sterile conditions by mechanical methods and to fill it on similarly sterile storage containers. This process requires costly plants and sterile spaces, as well as a particularly careful work on the raw material to be dried or the already dried raw material, respectively, until the ready-to-wear clothing.
Fra GB patentskrift 995.930 er det kendt, at frysetørre radioaktive, vandige opløsninger 15 i dampgennemtrængelige poser, for derved at opnå en større overflade til sublimationen end ved tørring i flasker. Problemet med mikrobiel forurening af det tørrede materiale var ikke til stede.From GB patent specification 995,930, it is known to freeze-dry radioactive aqueous solutions 15 in vapor-permeable bags, thereby obtaining a greater surface area for sublimation than for bottle drying. The problem of microbial contamination of the dried material was not present.
Den foreliggende opfindelse har således til formål at overvinde de ovennævnte ulemper ved at tilvejebringe en beholder med hvis hjælp et sterilt frysetørret materiale kan udvin-20 des uden de ovenfor anførte kostbare sterilitetskrav til tørringsanlægget samt til dettes omgivende rum.Thus, the present invention aims to overcome the aforementioned disadvantages of providing a container with the aid of which a sterile freeze-dried material can be recovered without the above-mentioned costly sterility requirements for the drying plant and its surrounding space.
Dette formål opnås ifølge opfindelsen ved at indrette den indledningsvis nævnte beholder som angivet i krav l's kendetegnende del.This object is achieved according to the invention by arranging the container mentioned in the preamble as set forth in the characterizing part of claim 1.
Opfindelsen beror på den overraskende erkendelse, at den ved sublimationen af opløs-25 ningsmiddelmolekyler, især af vandmolekyler, opståede dampstrøm, der strømmer fra DK 173643 B1 3 det tørrende råstof til kondensatoren, gennem den til fremgangsmåden ifølge opfindelsen anvendte membran imod forventningerne kun hindres i ringe omfang. Altså forløber frysetørringen af materiale, der er indesluttet af membranen, overraskende næsten lige så hurtigt som ved frysetørringen af de samme åbne, ikke pakkede materialer. Ved de 5 ifølge opfindelsen anvendte membraner handler det om hydrofobe membraner, indeholdende porer, som på den ene side er gennemtrængelige for vanddamp, men som på den anden side er så små, at de ikke kan passeres af mikroorganismer. Sådanne porer har fortrinsvis en størrelse på 0,5 μπι, især på 0,2 μνη. Der anvendes fortrinsvis membraner, der også er ridsefaste i fugtig tilstand under firemgangsmådebetingelserne. Imidlertid 10 er fremgangsmåden ifølge opfindelsen også gennemførlig med mindre stabile membraner, såfremt disse forstærkes med et bæremateriale eller ikke bliver overdrevent mekanisk belastet.The invention is based on the surprising realization that the vapor stream generated by the sublimation of solvent molecules, especially of water molecules, flows from the drying raw material to the condenser through the membrane used for the process according to the invention is only prevented in the little scope. Thus, the freeze drying of material enclosed by the membrane surprisingly proceeds almost as quickly as the freeze drying of the same open, unpacked materials. In the membranes used according to the invention, these are hydrophobic membranes containing pores which, on the one hand, are permeable to water vapor but on the other hand are so small that they cannot be passed by microorganisms. Such pores preferably have a size of 0.5 μπι, in particular 0.2 μνη. Preferably, membranes which are also scratch-resistant in a moist state are used under the four-way conditions. However, the process according to the invention is also feasible with less stable membranes if they are reinforced with a support material or are not overly mechanically loaded.
Den til beholderen ifølge opfindelsen valgte membrandel af beholderens vægflade afhænger af de valgte betingelser og tørretiden, og kan let fastslås af fagmanden ved hjælp af 15 simple afprøvninger. I en foretrukken udførelsesform ifølge opfindelsen består hele vægfladen af membranfoliet, og i en yderligere foretrukken udførelsesform omtrent halvdelen. Det har overraskende vist sig, at beholderen ifølge opfindelsen også med fordel kan anvendes, hvis vægfladen kun består af indtil 10% af membranfolie.The membrane portion of the container chosen for the container according to the invention depends on the conditions of the container and the drying time, and can be readily ascertained by one skilled in the art by means of 15 simple tests. In a preferred embodiment of the invention, the entire wall surface consists of the membrane foil and in a further preferred embodiment about half. Surprisingly, it has been found that the container according to the invention can also be used advantageously if the wall surface consists only of up to 10% of membrane film.
Især egner sig halvgennemtrængelige papirer af cellulose og sædvanlige cellulosederiva-20 ter, såsom celluloseacetat. Fortrinsvis finder også foliemembraner af polymerforbindelser, såsom polytetrafluorethylen eller polypropylen, anvendelse ifølge udførelsesformer for opfindelsen. Helt specielt egner sig som vanddampgennemtrængelige membraner også sterilisationspapirsfolier ifølge DIN 58 953, der følgelig anses som en del af beskrivelsen.In particular, semi-permeable papers of cellulose and conventional cellulose derivatives such as cellulose acetate are suitable. Preferably, film membranes of polymeric compounds, such as polytetrafluoroethylene or polypropylene, also find use according to embodiments of the invention. Particularly suitable as water vapor-permeable membranes are also suitable for sterilization paper sheets according to DIN 58 953, which is therefore considered part of the specification.
I en yderligere foretrukken udførelsesform af opfindelsen anvendes "Goretex"- og lignen-25 de membraner eller også i handelen værende slangeformede folier, såsom dem fra firmaet Vihuri OY, Wipack, Finland, der sælges under betegnelsen "Mediplast". I princippet er enhver foliemembran anvendelig uafhængig af dens bestanddele, såfremt de opfylder de DK 173643 B1 4 i DIN-normen 58 953 angivne krav med hensyn til kimtæthed, luftgennemtrængelighed og især styrke.In a further preferred embodiment of the invention, "Goretex" and similar membranes or also commercially available tubular films, such as those of Vihuri OY, Wipack, Finland, sold under the designation "Mediplast" are used. In principle, any film membrane is usable independently of its constituents if they meet the requirements of germ density, air permeability and especially strength, specified in DIN standard 58 953.
I en foretrukken udførelsesform udformes beholderen ifølge opfindelsen som en pose eller slange, der fortrinsvis består af to ved deres kanter med hinanden tæt og trykfast 5 forbundne vægge, hvoraf den ene væg består af væsketæt materiale og den anden væg dannes af membranen.In a preferred embodiment, the container according to the invention is formed as a bag or hose, which preferably consists of two walls which are tightly and pressure-tightly connected to one another, one wall of which is liquid-tight material and the other wall formed by the membrane.
Membranen sammensvejses eller tilklæbes fortrinsvis med beholderen. Som beholder egner sig ifølge en udførelsesform for opfindelsen især kar.The membrane is preferably welded or adhered to the container. As a container, according to one embodiment of the invention, vessels are particularly suitable.
I en yderligere foretrukken udførelsesform består karret af væsketæt kunststof og har 10 fortrinsvis en vægtykkelse fra 0,5 til 1 mm.In a further preferred embodiment, the vessel is made of liquid-tight plastic and preferably has a wall thickness of 0.5 to 1 mm.
De gunstigste tørringsbetingelser, såsom tryk, temperatur og mængde, er afhængig af materialet der skal tørres, membranens tykkelse samt størrelsen og antallet af dennes porer, og bør bestemmes gennem sædvanlige og simple afprøvninger af materialet og emballeringen.The most favorable drying conditions, such as pressure, temperature and amount, depend on the material to be dried, the thickness of the membrane, and the size and number of its pores, and should be determined through usual and simple tests of the material and packaging.
15 I det følgende belyses opfindelsen nærmere ved hjælp af nogle udførelseseksempler. Eksempel 1In the following, the invention will be further elucidated by means of some exemplary embodiments. Example 1
Afprøvningen af en membrans kimtæthed gennemførtes ifølge DIN 58 953 således, at mikroorganismer i vanddråber anbragtes på prøvestykket og efter vanddråbens indtørring undersøgtes om der var trængt mikroorganismer igennem på undersiden af prøvestykket.Testing of a membrane's germ density was carried out according to DIN 58 953 such that microorganisms in water droplets were placed on the sample and after drying of the water droplet was examined whether microorganisms had penetrated on the underside of the sample.
20 De membranfolier, der skulle afprøves, blev udskåret i kvadrater med en omtrentlig kantlængde på 50 mm. Prøvestykket steriliseredes og tørredes. Hvert steriliseret membranprøvestykke blev med den side opad, der kun kontamineres ved anvendelsen, lagt DK 173643 B1 5 på et steriliseret underlag og podedes med 5 dråber af hver især 0,1 ml (svarende til 106-107 kim). Prøvestykkerne opbevaredes ved stuetemperatur fra 20 til 25°C og ved en relativ luftfugtighed fra 40 til 60%. Dråberne fik lov at tørre fuldstændigt i løbet af 6 timer. Hvert prøvestykke anbragtes med den podede flade vendende opad på en bloda-5 garplades (1,5% agar) overflade, således at hele foliefladen kom i kontakt med agaren.The membrane foils to be tested were cut into squares with an approximate edge length of 50 mm. The specimen was sterilized and dried. Each sterilized membrane specimen, with the upside side contaminated by use only, was placed on a sterilized substrate and seeded with 5 drops of 0.1 ml each (corresponding to 106-107 germs). The specimens were stored at room temperature from 20 to 25 ° C and at a relative humidity of 40 to 60%. The drops were allowed to dry completely within 6 hours. Each sample piece was positioned face-up on a blood (5% agar) surface of the blood so that the entire foil surface came into contact with the agar.
Efter 5 til 6 sekunder fjernedes papiret. Pladerne inkuberedes ved 37°C i 16-25 timer. Udviser de med sådanne folieprøver behandlede agarplader ingen vækst, regnes foliet for tilstrækkeligt kimtæt. Yderligere angivelser vedrørende afprøvningen af membranernes kimtæthed, især til testkimsuspensionsfremstillingen, kan hentes i 6. del af DIN-normen 10 58 953.After 5 to 6 seconds, the paper was removed. The plates were incubated at 37 ° C for 16-25 hours. If the agar plates treated with such foil samples show no growth, the foil is considered sufficiently germ-tight. Further information regarding the testing of the germ density of the membranes, especially for the test germ suspension preparation, can be obtained in part 6 of DIN 10 58 953.
Eksempel 2Example 2
Der fremstilledes et næringssubstrat bestående af 10 g pepton, 5 g glucose, 5 g NaCl, 0,084 g KH2P04,0,187 g Na2HP04x2H20 og pyrogenfrit vand ad 1,01, og det indstilledes til en pH-værdi på 7,0. Derefter steriliseredes det i en lukket gennembrydningsfla-15 ske (tysk: Durchstichflasche).A nutrient substrate consisting of 10 g of peptone, 5 g of glucose, 5 g of NaCl, 0.084 g of KH 2 PO 4,0,187 g of Na 2 HPPO 4 x 2 H 2 O and pyrogen-free water was prepared at 1.01 and adjusted to a pH of 7.0. Then, it was sterilized in a closed breakthrough bottle (German: Durchstich bottle).
Til udtagelse af det sterile næringssubstrat, der skal lyofiliseres, udfærdigedes en steril gennemsigtig pose bestående af en gennemsigtig folie og et egnet papir. Hertil blev afskåret et stykke med en længde på 800 mm af den i handelen værende gennemsigtige steriliseringsposefolie fra firmaet Wipak Medical af typen Steri-King R 47, der er slange-20 formet, dvs. sammensvejset i begge sider, ellers åben, befindende sig på en rulle (bredde af rallen: 400 mm). Denne slange sammensvejsedes ved begge de åbne sider til en pose, ved hjælp af et i handelen værende folieapparat. Derefter steriliseredes denne pose i en autoklave med filterprogram ved 123 °C og 2 bars damptryk, idet den sterile pose anbragtes med dens gennemsigtige folie nedad, for at lette håndteringen, i et usterilt kar af plade 25 (VA-plade), dimensioner: længde 800 mm, bredde 400 mm, højde 30 mm) og åbnedes i en "Laminar-flowbox" under sterile betingelser med en desinficeret saks ved at afklippe et hjørne. Gennem denne åbning på ca. 30 mm mellem folie og papir fyldtes 1,5 liter af DK 173643 B1 6 det sterile næringssubstrat via en i åbningen placeret steril slange. Den således fyldte pose lukkedes i "Laminar-flowboxeiT under sterile betingelser ved hjælp af et i handelen værende foliesvejseapparat ved sammensvejsning over hjørnet.To remove the sterile nutrient substrate to be lyophilized, a sterile transparent bag consisting of a transparent film and a suitable paper was prepared. To this was cut a piece with a length of 800 mm of the commercially available sterilization bag foil from the company Wipak Medical of the type Steri-King R 47, which is hose-shaped, ie. welded on both sides, otherwise open, standing on a roller (width of the roller: 400 mm). This hose was welded to a bag by both open sides using a commercially available foil apparatus. Then, this bag was sterilized in an autoclave with filter program at 123 ° C and 2 bar vapor pressure, placing the sterile bag with its transparent foil down, to facilitate handling, in an unsterile vessel of plate 25 (VA plate), dimensions: length 800 mm, width 400 mm, height 30 mm) and opened in a "Laminar flow box" under sterile conditions with a disinfected scissors by cutting a corner. Through this opening of approx. About 30 mm between foil and paper, 1.5 liters of DK 173643 B1 6 filled the sterile nutrient substrate via a sterile tube located in the opening. The bag thus filled was closed in Laminar flow box under sterile conditions by a commercially available foil welding apparatus by welding over the corner.
Hele anordningen (zinkkar, pose og sterilt næringssubstrat) anbragtes på en til -45°C 5 forkølet plade fra et i handelen værende ikke steriliserbart frysetørringsanlæg fra firmaet Edwards + Kniese, med en total overflade på 1,5 m2, og substratet indfrosset. Efter fuldstændig indfrysning af substratet under ikke sterile betingelser, frysetørredes ved et tryk på 10-1 torr og en pladetemperatur på 22°C, og produktet eftertørredes ved 10-3 torr, ligeledes under ikke sterile betingelser. Den totale tørringstid androg ca. 72 timer.The entire device (zinc vessel, bag and sterile nutrient substrate) was placed on a pre-cooled plate at -45 ° C from a commercially available non-sterilizable freeze-drying plant of Edwards + Kniese, with a total surface area of 1.5 m2, and the substrate frozen. After complete freezing of the substrate under non-sterile conditions, freeze-dried at a pressure of 10-1 torr and a plate temperature of 22 ° C and the product dried at 10-3 torr, also under non-sterile conditions. The total drying time was approx. 72 hours.
10 Det således opnåede, som lyst brunt pulver i den gennemsigtige steriliseringspose foreliggende frysetørrede råstof, anbragtes med pose i en "Laminar-flowbox" og opløstes i 1,5 1 sterilt vand. Til dette formål steriliseredes det på papirsiden planlagte indstikningssted, i alt 1,5 1 sterilt vand tilsattes ved hjælp af en steril kanyle og egnede sterile sprøjter, det tørrede råstof opløstes, og opløsningen overførtes til en steril flaske. Denne opløsning 15 inkuberedes i 4 dage ved 37°C, og derefter bestemtes den inkuberede opløsnings kimtal efter membranfiltermetoden.The thus obtained, as light brown powder, in the freeze-dried raw material available in the transparent sterilization bag, was placed in a "Laminar flow box" bag and dissolved in 1.5 liters of sterile water. For this purpose, the insertion site planned on the paper side was sterilized, a total of 1.5 liters of sterile water was added by means of a sterile cannula and suitable sterile syringes, the dried raw material was dissolved and the solution transferred to a sterile bottle. This solution was incubated for 4 days at 37 ° C and then the seed count of the incubated solution was determined by the membrane filter method.
Det viste sig, at der under frysetørringen ikke var sluppet nogen kim ind.It turned out that during the freeze-drying, no germs were allowed in.
Claims (10)
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 |
| DE3817906 | 1988-05-26 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DK252589D0 DK252589D0 (en) | 1989-05-24 |
| DK252589A DK252589A (en) | 1989-11-27 |
| DK173643B1 true DK173643B1 (en) | 2001-05-14 |
Family
ID=6355171
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK198902525A DK173643B1 (en) | 1988-05-26 | 1989-05-24 | Freeze drying container 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 |
| WO1996006018A1 (en) * | 1994-08-19 | 1996-02-29 | W. L. Gore & Associates, Inc. | 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 |
| WO1997011155A1 (en) | 1995-09-22 | 1997-03-27 | Government Of The United States Of America, 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 |
| JP7110360B2 (en) | 2017-10-09 | 2022-08-01 | テルモ ビーシーティー バイオテクノロジーズ，エルエルシー | Freeze-drying method |
| 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 |
| US11604026B2 (en) | 2019-03-14 | 2023-03-14 | 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 | |||
| NL283895A (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 ES ES198989109246T patent/ES2030556T3/en not_active Expired - Lifetime
- 1989-05-23 DE DE8989109246T patent/DE58900902D1/en not_active Expired - Lifetime
- 1989-05-23 AT AT89109246T patent/ATE73226T1/en not_active IP Right Cessation
- 1989-05-23 EP EP89109246A patent/EP0343596B1/en not_active Expired - Lifetime
- 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
- 1989-05-24 PL PL1989279609A patent/PL159938B1/en unknown
- 1989-05-25 FI FI892563A patent/FI91442C/en not_active IP Right Cessation
- 1989-05-25 HU HU892683A patent/HU204126B/en unknown
- 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 |
|---|---|
| ATE73226T1 (en) | 1992-03-15 |
| FI91442C (en) | 1994-06-27 |
| DE58900902D1 (en) | 1992-04-09 |
| EP0343596A3 (en) | 1990-02-28 |
| DD283864A5 (en) | 1990-10-24 |
| JPH0450830B2 (en) | 1992-08-17 |
| FI892563A0 (en) | 1989-05-25 |
| DK252589D0 (en) | 1989-05-24 |
| ES2030556T3 (en) | 1992-11-01 |
| HUT52617A (en) | 1990-07-28 |
| EP0343596B1 (en) | 1992-03-04 |
| DE3817906A1 (en) | 1989-11-30 |
| IE891541L (en) | 1989-11-26 |
| GR3004584T3 (en) | 1993-04-28 |
| HU204126B (en) | 1991-11-28 |
| FI892563A (en) | 1989-11-27 |
| PL159938B1 (en) | 1993-01-29 |
| FI91442B (en) | 1994-03-15 |
| CA1337974C (en) | 1996-01-23 |
| JPH0229256A (en) | 1990-01-31 |
| IE61012B1 (en) | 1994-09-07 |
| PL279609A1 (en) | 1990-01-22 |
| EP0343596A2 (en) | 1989-11-29 |
| DK252589A (en) | 1989-11-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| B1 | Patent granted (law 1993) | ||
| PUP | Patent expired |