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WO2011038008A2 - Procédé et appareil d'échantillonnage stérile destinés à des applications de réacteurs bpf - Google Patents

Procédé et appareil d'échantillonnage stérile destinés à des applications de réacteurs bpf Download PDF

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Publication number
WO2011038008A2
WO2011038008A2 PCT/US2010/049835 US2010049835W WO2011038008A2 WO 2011038008 A2 WO2011038008 A2 WO 2011038008A2 US 2010049835 W US2010049835 W US 2010049835W WO 2011038008 A2 WO2011038008 A2 WO 2011038008A2
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WO
WIPO (PCT)
Prior art keywords
valve
sampling
vessel
sterile
sample
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.)
Ceased
Application number
PCT/US2010/049835
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English (en)
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WO2011038008A3 (fr
Inventor
Jr. George E. Barringer
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Groton Biosystems LLC
Original Assignee
Groton Biosystems LLC
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Filing date
Publication date
Application filed by Groton Biosystems LLC filed Critical Groton Biosystems LLC
Publication of WO2011038008A2 publication Critical patent/WO2011038008A2/fr
Publication of WO2011038008A3 publication Critical patent/WO2011038008A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M37/00—Means for sterilizing, maintaining sterile conditions or avoiding chemical or biological contamination
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1095—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers
    • G01N35/1097—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices for supplying the samples to flow-through analysers characterised by the valves

Definitions

  • bioreactor processes maintaining a contamination-free environment is key. Whenever a bioprocess system is exposed to the external environment, it faces the risk of contamination by viruses, micro-organisms, and chemicals.
  • Typical bioprocesses involve batch bioreactors where cells are cultured and harvested over a period of time ranging from hours to days. After a batch is harvested, the reactor vessel is sterilized in preparation for the next batch process.
  • the entire reactor system can be placed in an autoclave and completely sterilized.
  • reactors that are about 5 liters or less typically are made of glass and are sterilized in an autoclave.
  • CIP and SIP are methods used in the pharmaceutical and food industries for the in-line sterilization of processing equipment, including vessels, valves, process lines, and filter assemblies. These methods are used to achieve sterility or a certain level of sanitation required by regulation for a particular process.
  • bioreactor processes do not lend themselves easily to in-situ analysis of the batch. Instead, samples must be physically extracted from the process and examined and manipulated outside the vessel, thereby exposing the
  • GMP Good Manufacturing Practice
  • US Food and Drug Administration require a greater degree of sterility within the system. That is, certain manufacturing systems are required to be "closed.”
  • the term “closed” refers to a system having a sterile environment that, during operation, does not come into direct communication with a non-sterile environment. In such processes, a sampling system that communicates directly with the sterile reactor or vessel containing the material of interest must also be sterile.
  • Sampling within a closed system has conventionally been carried out manually by connecting a pre-sterilized sample container to the outlet of the reactor/vessel containing the sample of interest.
  • a pre-sterilized container sealed by a one-time use septa is placed in communication with the vessel by puncturing the septa with a needle in fluid communication with the vessel. The needle then injects the sample into the pre-sterilized container. The container is then removed from the system and the sample is analyzed.
  • What is needed is a device and method for automatically obtaining a sample from a sterile system without exposing said system directly to a non-sterile environment.
  • the present invention is directed to a method of sampling from a manufacturing system.
  • the method includes coupling a sampling valve and a sampling vessel in series to a fluid sample source, sterilizing the sampling valve and the sampling vessel, supplying a sample from the fluid sample source through the sterile sampling valve to the sterile sampling vessel, closing the sampling valve to close fluid communication between the fluid sample source and the sampling vessel, and directing the sample from the sterile sample vessel to a processing system.
  • the method may further include the step of equalizing pressure between the sampling vessel and a headspace of the fluid sample source through a sterile headspace valve prior to supplying the sample to the sterile sampling vessel.
  • the method may still further include the step of cooling the sterile sampling vessel prior to supplying the sample to the sterile sampling vessel.
  • the step of cooling may include passing sterile water through the sterile sampling vessel.
  • the step of cooling can include circulating cooling fluid through a cooling jacket in thermal
  • the step of sterilizing can include passing steam through the sampling valve and the sampling vessel for a duration sufficient to sterilize the sampling valve, the sampling vessel, and the fluid path therebetween.
  • the method may further include controlling a sterile air valve to allow sterile air to enter the sampling vessel and displace the sample to a location downstream of the sampling vessel.
  • the method may still further include the step of flushing the sterile sampling vessel with sterile water after directing the sample from the sterile sampling vessel to the processing system.
  • the method further includes the step of monitoring the volume of the sample supplied to the sterile sampling vessel.
  • the present invention is directed to an automatic sterile sampling system for obtaining a sample within a manufacturing process.
  • the system includes a steam valve configured to receive steam from a steam source.
  • the system further includes a sampling valve configured to receive fluid from a fluid sample source and connected to receive the steam from the steam source.
  • the system still further includes a sampling vessel connected to receive fluid samples
  • the sampling vessel is in fluid communication with a processing system.
  • the system also includes a controller coupled to the steam valve to control the flow of the steam to sterilize the sampling valve and the sampling vessel prior to sampling and coupled to the sampling valve to control the flow of the fluid sample through the sampling valve to the sampling vessel.
  • the system may further include a steam source to which the steam valve is coupled.
  • the system may include a closed system fluid sampling source to which the sampling valve is coupled.
  • the system may further include a headspace valve configured to couple a headspace of the fluid sample source with the sampling vessel.
  • the controller may be further coupled to the headspace valve to control equalization of pressure between the sampling vessel and the headspace of the fluid sample source.
  • the system includes a sterile air valve connected to receive sterile air from a sterile air source, the sterile air valve being in fluid communication with the sampling vessel. Further, the controller may be coupled to the sterile air valve to control the flow of sterile air into the sampling vessel to equilibrate pressure in the sampling vessel with components located downstream of the sampling vessel.
  • the controller may also be coupled to the sterile air valve to control the flow of sterile air into the sampling vessel to displace the fluid sample to a location downstream of the sampling vessel.
  • the system may further include a sterile water valve connected to receive sterile water from a sterile water source, the sterile water valve being in fluid communication with the sampling vessel. . Further, the controller may be coupled to the sterile water valve to control the flow of the sterile water.
  • the system may further include a drain valve connected to a drain to pass the steam from the sampling vessel to the drain and to pass the fluid sample from the sampling vessel to the drain. In addition, the controller may be coupled to the drain valve to control the passing of the steam to the drain and the passing of the fluid sample to the drain. Further still, the system may include an isolation valve connected to receive the fluid sample form the sampling vessel and to pass the fluid sample to the processing system. In addition, the controller may be coupled to the isolation valve to control the passing of the
  • the system includes a manual sampling valve connected to receive the fluid sample from the sampling vessel and pass the fluid sample to a manual sampling output port.
  • the system includes a cooling jacket connected to receive cooling fluid from a cooling fluid source, the cooling jacked being in thermal communication with the sampling vessel.
  • FIG. 1 is a drawing of an embodiment of an automated system at rest according to the present invention
  • FIG. 2 is a drawing of an alternative embodiment of the automated system at rest
  • FIG. 3 is a drawing for the control valve system for the isolation valve
  • FIG. 4 is a drawing of the automated system during a sterilization operation
  • FIG. 5 is a drawing of the automated system during a cooling operation
  • FIG. 6 is a drawing of the automated system during a cooling operation
  • FIG. 7 is a drawing of the automated system during a sample extraction operation
  • FIG. 8 is a drawing of the automated system during a sample transfer operation
  • FIG. 9 is a drawing of the automated system during a sample transfer operation
  • FIG. 10 is a drawing of a sampling valve during a sterilization operation
  • FIG. 11 is a drawing of a sampling valve during a sampling operation.
  • the embodiments provide an automated sampling system within a closed manufacturing system and method for sampling from a closed manufacturing system while ensuring that the manufacturing system, during operation, does not come into direct communication with a non-sterile environment.
  • the sampling system may be configured to obtain samples from a component in a closed system, such as a bioreactor.
  • the invention is not limited to sampling from a bioreactor, but rather can be applied to the sterile sampling of any vessel or other sample source containing a fluid.
  • the system employs a series of pneumatically or electrically actuated valves to control the flow of steam, fluid sample, and optionally air and/or cooling fluid through the system at specified times and includes a sample vessel through which fluid samples are routed from the bioreactor vessel to a downstream processing system.
  • valve refers to a single valve or system of valving that achieves a particular flow configuration.
  • fluid communication refers to a relationship between two components by which fluid can be permitted to flow from one component to the other.
  • a sample source such as reactor vessel 1 is fluidly connected to sampling valve 3. Samples from sample source 1 are dispensed through sampling valve 3 and directed into sample vessel 61. Sample vessel 61 is approximately the same form factor (ratio of height and diameter) as the reactor vessel. It is believed that using a sampling vessel that has the same form factor as the reactor vessel achieves a constant surface area to volume ratio and headspace to liquid volume ratio. It is further believed that keeping these ratios constant helps to achieve equivalent gas saturation in the fluid of both the reactor vessel and sample vessel. For reasons described further below, such equivalent gas saturation is desirable. Temperature sensor 65 and level sensor 67 at sample vessel 61 provide for monitoring of the sample in the sample vessel. Sample vessel 61 is in thermal communication with cooling jacket 63, which circulates cooling fluid from cooling fluid source 75.
  • fluid channel 4 establishes fluid communication between sampling vessel 61 and manual sample sampling valve 15, isolation valve
  • manual sampling valve 15 may be opened and sample fluid may pass through manual sampling output port 21 if the user wishes to obtain samples manually.
  • isolation valve 17 can be controlled to allow fluid samples to pass from fluid channel 4 to sample transfer channel 6. These samples are directed into sampling processing system 11 for automated processing and analysis of the sample.
  • Processing system 11 can include cleaning, processing, and analytical
  • the sample may also be discarded by opening drain valve 19 to route the sample through drain channel 8 to drain 10.
  • sample vessel 61 is connected to the headspace 71 of reactor vessel 1 by way of headspace pipe 73.
  • Headspace pipe 73 may be fitted optionally with sterile filters, fluid traps, or other accessories.
  • Headspace pipe 73 is fitted with an automatic valve 81, which controls the flow of headspace gas and provides for pressure equilibrium between reactor vessel 1 and sample vessel 61. Equilibrating or equalizing the pressure between reactor vessel headspace 71 and sample vessel 61 prevents outgassing of dissolved gas
  • the concentration of components in the sample does not change as a result of introduction into sample vessel 61, and the sample in sampling vessel 61 is representative of the fluid in the reactor vessel 1.
  • Headspace pipe 73 is connected to steam source 5, optional sterile air source 77, and optional sterile water source 117.
  • Steam source 5 is provided for sterilization of the system, particularly sampling valve 3 and sampling vessel 61. Steam is allowed to pass through steam valve 13 into headspace pipe 73.
  • Headspace valve 81 is a three-port valve that includes one valved leg, which can be open or closed, and two common legs, which are in fluid communication.
  • headspace valve 81 The valved leg of headspace valve 81 is in fluid communication with headspace 71.
  • headspace valve 81 When headspace valve 81 is open, headspace 71 is in fluid communication with sampling vessel 61, steam valve 13, and steam channel 2.
  • steam valve 13 and sampling valve 3 are located in close proximity to headspace valve 81, because these valves will be in contact with the sample.
  • Steam valve 13 preferably is in close proximity to head space valve 81, in order to minimize "dead legs," i.e., tubing not directly contacted by steam.
  • sample refers to the contents of the reactor vessel 1 , whether in liquid phase (bottom of reactor) or gas phase (top of reactor).
  • sample here refers to the contents of the reactor vessel 1 , whether in liquid phase (bottom of reactor) or gas phase (top of reactor).
  • the following tubing connections or fluid paths may be minimized: from headspace pipe 73 to headspace valve 81, from headspace valve 81 to sampling vessel 61, from headspace 71 to sampling valve 3, from sampling valve 3 to headspace pipe 73, from steam valve 13 to headspace valve 81, from sterile air valve 121 to headspace pipe 73, from sterile water valve 119 to headspace pipe 73, from fluid channel 4 to manual sampling valve 15, from fluid channel 4 to isolation valve 17, from fluid channel 4 to drain valve 19, and fluid channel 4.
  • Steam source 5 is also fluidly connected to sampling valve 3 and sample vessel 61, and is therefore capable of sterilizing both components. Steam passes through sampling valve 3 and sampling vessel 61 and exits to drain 10.
  • Sample vessel 61 may be connected to sterile air source 77 to equilibrate pressure in sample vessel 61 with components downstream of sample vessel 61.
  • the connection is automatically controlled by manipulating an optional sterile air valve 121 between sample vessel 61 and sterile air source 77.
  • sterile air valve allows sterile air to enter sample vessel 61 and displace the fluid sample downstream.
  • the sterile air source 77 may also be used to cool the sample vessel or may be used to blow down steam condensate into steam drain 10 after the sample vessel 61 has cooled and before the sample is admitted from the reactor vessel 1 to the sample vessel, thereby eliminating liquid that could potentially dilute the next sample to enter sample vessel 61.
  • Sample vessel 61 may be also connected to sterile water source 117.
  • Sterile water valve 119 is controlled to allow sterile water to pass through sampling vessel 61 to reduce the temperature of sampling vessel 61 after steam sterilization of sampling vessel 61.
  • sterile water from sterile water valve 119 can be used to flush residual fluid from the sampling vessel prior to sterilization in preparation for a new sample.
  • Steam valve 13 controls the flow of steam through a steam channel 2.
  • Steam valve 13 is typically a diaphragm valve, such as GEMU ® Type 650/015/D80415 A0- 1537, which is a 1/2 inch two-port pneumatically actuated sanitary valve. When steam valve 13 is open, steam is allowed to pass through steam channel 2 to sampling valve 3.
  • Sampling valve 3 is typically a three-port plunger valve specifically adapted for sterile sampling of a liquid sample from a container, such as the KEOFITT ®
  • FIGS. 10 and 11 An example of a suitable KEOFITT ® sampling valve is shown in FIGS. 10 and 11.
  • Sampling valve 3 is connected to three components of the system: the steam channel 2, a fluid sample source 1, such as a reactor vessel, and a steam/sample channel 4. Steam and fluid samples can flow from the sampling valve 3 to sampling vessel 61 through steam/sample channel 4. Steam/sample channel 4 typically has an inner diameter of about 9 mm.
  • the sampling valve 3 is closed as shown in FIG. 10
  • steam is able to flow from steam channel 2 to steam/sample channel 4.
  • fluid sample flows from port 33 toward steam/sample channel 4, the flow path toward steam channel 2 being blocked by steam valve 13.
  • Isolation valve 17 is typically a two-port diaphragm valve, such as a GEMU ®
  • Type 650 TC TFE 15RaEP Conl having two 3/8 inch (9 mm nominal) ports, which is a pneumatically actuated sanitary valve.
  • Drain valve 19 is typically similar to isolation valve 17.
  • An example of a suitable drain valve is a GEMTj ® Type 650 TC TFE 15RaEP Conl having two 3/8 inch (9 mm nominal) ports, which is a pneumatically actuated sanitary valve.
  • Manual sampling valve 15 is typically a two-port valve, such as GEMU ® Type 650 TC TFE 15RaEP Conl with manual actuator. Manual sampling valve 15 is connected to manual sampling output port 21, which can be used by a human operator to draw fluid samples from the sampling vessel 61. The manual valve operates in a similar manner as the isolation valve 17. However, during normal automatic operation, the valve shuts the fluid pathway to manual output port 21.
  • Headspace valve 81 is typically a three-port diaphragm valve, such as a GEMU ® Type 650 TC TFE 15RaEP Con A-B, which is a 3/8 inch three-port pneumatically actuated sanitary valve.
  • Sterile water valve 119 and sterile air valve 121 are typically two-port valves, such as GEMU ® Type 650 TC TFE 15RaEP Conl with pneumatic actuator or equivalent.
  • the steam valve 13, sampling valve 3, isolation valve 17, drain valve 19, headspace valve 81, manual sampling valve 15, optional sterile water valve 119, and optional sterile air valve 121 are controlled in sequence to perform various system operations, which will be described in detail below.
  • Each of the valves may be pneumatically actuated by one of two control valves in parallel: a solenoid control valve and a manual control valve.
  • FIG. 3 shows isolation valve 17, which is pneumatically actuated by either manual control valve 36 or solenoid control valve 35.
  • the user can select between automatic and manual control by toggling auto/manual solenoid switch valve 34, which is connected to compressed air source 33. The valve switches compressed air from source 33 to either the solenoid valve 35 for automatic control or manual control valve 36 for manual control.
  • a controller 27 such as a programmable logic controller (PLC) controls the solenoid valves and solenoid switch valves. As shown in FIG. 1, the controller typically resides in processing system 1 1 and controls the control valves to actuate the pneumatic valves, thereby automatically performing the various operations of the system in sequential order periodically throughout the bioreactor process.
  • PLC programmable logic controller
  • the downstream set-up as shown in FIG. 1 can be alternatively achieved by using three-port or three-way valves, such as shown in FIG. 2 and as described in U.S. Application No. 12/490,960, which is incorporated herein by reference.
  • manual sampling valve 15 and isolation valve 17 are three-port valves.
  • Fluid channel 4' establishes fluid communication between sampling vessel 61 and manual sampling valve 15.
  • Sampling vessel 61 is connected to isolation valve 17 through manual sampling valve 15 and further connected to drain valve 19 through isolation valve 17.
  • isolation valve 17 may be a three-port diaphragm valve.
  • An example of a suitable isolation valve is a GEMlj ® Type 650 TC TFE 15RaEP Con A-B, which is a 3/8 inch three-port pneumatically actuated sanitary valve.
  • a first port of isolation valve 17 is connected to the steam/fluid channel 4', while a second port of isolation valve 17 is connected to drain channel 8 and a third port of the isolation valve 17 is connected to sample transfer channel 6.
  • manual sampling valve 15 is typically a three-port diaphragm valve, such as GEMIJ ® Type 601 TC TFE 15RaEP Con A-B, which is a 3/8 inch three-port manually actuated sanitary valve.
  • controller 27 automatically manipulates the system. As shown in the FIG. 1, controller 27 is connected to headspace valve 81, steam valve 13, sterile air valve 121, sterile water valve 119, sampling valve 3, isolation valve 17, manual sampling valve 15, and drain valve 19. The controller may be also connected to temperature sensor 65, level sensor 67, and cooling fluid source 75.
  • the controller operates the sampling system in the following sequence.
  • FIG. 4 is a drawing of the automated reactor sampling system during a sterilization operation for the sampling system when the reactor is in operation.
  • the sampling process begins by first sterilizing sampling valve 3 and sampling vessel 61.
  • steam valve 13 and drain valve 19 are opened, allowing steam source 5 to provide steam through sampling valve 3 and sampling vessel 61 to
  • reactor sampling valve 3 manual sampling valve 15, and isolation valve 17 are closed, so that steam cannot pass to reactor vessel 1, manual sampling output port 21, or sample transfer channel 6.
  • headspace valve 81 and optional sterile air and sterile water valves 121, 119 are also closed. The steam also sterilizes headspace valve 81. After sterilization, steam valve 13 is closed.
  • a preliminary sterilization For preparation of a reactor to be put in use, a preliminary sterilization must be performed.
  • the entire reactor system including headspace pipe 73 and headspace 71, is steam sterilized in addition to the steam path shown in FIG. 4.
  • headspace valve 81 is open and steam can pass through headspace pipe 73, headspace 71, and the fluid path from headspace 71 to sampling valve 3.
  • FIG. 10 shows the sterilizing of a sampling valve, such as sampling valve 3, in detail.
  • Valve head 31 is seated over an aperture 33, thereby obstructing the flow of fluid from a fluid sample source, such as reactor vessel 1.
  • Steam enters sampling valve 3 from the steam source (not shown) through steam channel 2 and exits through steam/sample channel 4.
  • Headspace valve 81 and headspace pipe 73 are not shown in FIG. 10.
  • sampling vessel 61 may be cooled by sterile water from sterile water source 117.
  • sterile water valve 119 is opened and sterile water is allowed to pass through sampling vessel 61 until the vessel reaches a desired temperature.
  • the temperature of sample vessel 61 may be monitored by temperature sensor 65.
  • Drain valve 19 remains open from the sterilization operation, and the sterile water exits the system by way of drain 10. At the end of the cooling operation, sterile water valve 119 and drain valve 19 are closed. Alternatively, as shown in FIG. 6, drain valve 19 may be closed prior to the
  • sample vessel 61 is cooled by circulating cooling fluid from cooling fluid source 75 through cooling jacket 63, which is in thermal
  • FIG. 7 is a drawing of the automated system during a sampling operation.
  • headspace valve 81 is opened, followed by reactor sample valve 3 after a brief delay. Fluid from reactor vessel 1 is allowed to enter sampling vessel 61 through sampling valve 3 until the desired volume of sample is obtained in sampling vessel 61. Because headspace valve 81 remains open during sample extraction, any dissolved gas components in the sample remain saturated in the fluid. Thus, the concentration of the fluid sample after extraction from reactor vessel 1 is unchanged with respect to the concentration of the same fluid sample prior to extraction from reactor vessel 1.
  • the volume of sample entering sampling vessel 61 may be monitored by level sensor 67. Once the desired amount of sample is obtained, sampling valve 3 and headspace valve 81 are closed.
  • FIG. 11 shows as ample valve, such as sampling valve 3, during the sampling operation in detail.
  • Valve head 31 is removed from port 33 by pneumatic control and fluid is allowed to flow from a fluid sample source, such as fluid sample source I, through steam/sample channel 4.
  • the steam valve 13 along the steam channel 2 prevents fluid samples from flowing to the steam source.
  • Headspace valve 81 and headspace pipe 73 are not shown in FIG. 11.
  • sample vessel 61 The sample is now contained in sample vessel 61 and fluid communication to reactor vessel is closed. Now, the sample may be transferred downstream without danger of exposing reactor vessel 1 to a non-sterile environment.
  • the sample is allowed to exit sample vessel 61 and can be directed to one of several parts of the system, as described above. For example, isolation valve 17 can be opened to allow the sample to pass through sample transfer channel 6 into automated processing
  • the sample can be obtained manually by opening manual samplmg valve 15 to allow the sample to pass through manual sampling output port 21 as shown in FIG. 9.
  • drain valve 19 can be opened. After transfer of the sample from sample vessel 61 to the desired downstream system component, the respective valve leading thereto is closed.
  • Sterile air valve 121 may be controlled to allow sterile air to enter sample vessel 61 and displace the fluid sample downstream.
  • sterile water valve 119 is opened and sterile water is allowed to pass through sample vessel 61 to flush the system of any residual sample fluid.
  • Drain valve 19 is opened, and the sterile water exits the system by way of drain 10. This operation is similar to cooling the sampling vessel with sterile water as described with reference to FIG. 5.
  • sterile water valve 119 and drain valve 19 are closed.
  • Steam valve 13 and drain valve 19 are opened, allowing steam source 5 to provide steam through sampling valve 3 and sampling vessel 61 to drain 10. This operation is similar to steam sterilization described with reference to FIG. 4.
  • steam valve 13 is closed.
  • Sample vessel 61 may be cooled by sterile water from sterile water source 117 or by circulating cooling fluid from cooling fluid source 75 through cooling jacket 63.

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Abstract

L'invention concerne un procédé consistant à effectuer un échantillonnage à partir d'un système de fabrication. Ce procédé consiste à accoupler une vanne d'échantillonnage et un contenant d'échantillonnage en série à une source d'échantillon fluidique, à stériliser la vanne d'échantillonnage et le contenant d'échantillonnage, à acheminer un échantillon provenant de la source de l'échantillon fluidique dans le contenant d'échantillonnage stérile, par la vanne d'échantillonnage stérile, à fermer la vanne d'échantillonnage pour fermer la communication fluidique entre la source d'échantillon fluidique et le contenant d'échantillonnage, et à diriger l'échantillon provenant du contenant d'échantillon stérile vers le système de traitement
PCT/US2010/049835 2009-09-23 2010-09-22 Procédé et appareil d'échantillonnage stérile destinés à des applications de réacteurs bpf Ceased WO2011038008A2 (fr)

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US24506609P 2009-09-23 2009-09-23
US61/245,066 2009-09-23

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Cited By (8)

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Publication number Priority date Publication date Assignee Title
WO2012154603A1 (fr) * 2011-05-06 2012-11-15 Bend Research, Inc. Vanne d'échantillonnage aseptique automatique pour échantillonnage à partir de récipients fermés
WO2013063128A1 (fr) * 2011-10-24 2013-05-02 Bend Research, Inc. Systèmes et procédés de production de bioproduits
US9322749B2 (en) 2012-11-05 2016-04-26 Bend Research, Inc. Automatic sampling system for sampling from enclosed containers
WO2016064846A1 (fr) * 2014-10-24 2016-04-28 Genzyme Corporation Isolement continu intégré de flux de fluides provenant de cuves de traitement stérile
US9389151B2 (en) 2012-11-05 2016-07-12 Bend Research, Inc. Fixed volume aseptic sampling valve for sampling from enclosed containers
US9568449B2 (en) 2012-01-06 2017-02-14 Bend Research, Inc. Dielectric spectroscopy methods and apparatus
WO2017025641A1 (fr) * 2015-08-13 2017-02-16 General Electric Company Échantillonnage de thermoscellage
RU2790876C2 (ru) * 2014-10-24 2023-02-28 Джензим Корпорейшн Способ производства рекомбинантного терапевтического белка

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US20070074761A1 (en) 2003-10-28 2007-04-05 Keofitt A/S Valve for sterile sampling of a liquid sample from a container

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