Barrier system with a manipulation device for automatic sampling and method for automatic sampling

Abstract

The present invention relates to a barrier system for a production facility, in particular a pharmaceutical production facility, having an enclosed or separated area in which a sterile environment is provided, wherein a handling device for automatically sampling a contact sample is arranged in the enclosed or separated area. Also disclosed is a method for automatic sampling.

Description

Technical Field

[0001] When performing microbial monitoring in, for example, pharmaceutical production equipment, petri dishes and contact samples are often used. These are plastic dishes filled with a nutrient medium (such as agar) and equipped with lids. Petri dishes are used to monitor the air, while contact samples are used to monitor surfaces. Background Art

[0002] To be able to sample on a surface, the contact sample is designed such that the nutrient medium protrudes slightly beyond the edge of the plastic dish (hereinafter referred to as the bottom). The two microbial samples (petri dishes and contact samples) differ in size and shape, but both are usually provided in stacks of ten, triple-sterilized, and packaged in tubular aluminum foil bags.

[0003] The bags containing the microbial samples are brought into the pharmaceutical production equipment for use, where they are unpacked through a glove port or automatically. Finally, they are ready for monitoring, for example, in a silo.

[0004] As part of the "Good Manufacturing Practice" for pharmaceutical production equipment, contact samples are usually collected after production to pick up any microorganisms (such as fungi or bacteria) that may be present on the surface, and then incubated in an incubator.

[0005] In currently known pharmaceutical production equipment, this process is carried out manually by an operator after production. In production equipment with a barrier system, such as an isolator that can be designed, this is done by an operator who enters the equipment through a glove port. The operator takes out unused contact samples from, for example, a silo. The operator removes the lid from the sample and performs sample collection by pressing the tray against the surface to be tested. After that, the operator puts the lid back on the tray and labels the contact sample (for example, when the sample was collected and at which location in the factory). Usually, the sample is finally put back into the silo.

[0006] Recording the sampling location is very important because contact samples are also used to prove the effectiveness of disinfection and purification measures, such as a purification cycle with hydrogen peroxide (H2O2) in a critical production area. Only when the location where the sample was collected is recorded without loopholes and errors can batches be released or blocked targeted when microorganisms are detected during incubation, or the purification and disinfection measures be improved.

[0007] After contact sampling at all designated locations, the production equipment can be opened, the silo containing the microbial samples can be taken out, and the microbial samples can be cultured in a laboratory.

[0008] A microbial sample can be taken out of the production equipment through, for example, an RTP transfer system with double doors (the so-called rapid transfer port, consisting of an α port and a β container), so that it is not necessary to transport it through a possible non-sterile room. However, since the samples are sealed by lids, in practice, they are usually taken out of the factory with the doors open and brought to the laboratory.

[0009] Previous solutions had the disadvantage that surface sampling required the operator to intervene in the production equipment through gloves. However, the glove port is a possible contamination risk for the machine and thus also for the product to be processed. In addition, due to wearing gloves during sampling, there is a risk of contamination, so it is wrongly considered that the equipment was contaminated during the previous production process. For this reason, in modern pharmaceutical production equipment, it is preferably to dispense with the glove port in the barrier system. This is called a glove-free barrier system or a "glove-free isolator". However, without a glove port, it is impossible for the operator to perform surface sampling. It is also impossible to open the door before surface sampling, because this may cause the equipment to be contaminated from the outside, and such contamination has not occurred during the production process.

[0010] In addition, the previous solution (contact sampling through the operator and the glove port) had the disadvantage that it was not repeatable, because sampling of the critical surface was carried out by the operator, who did not always sample at exactly the same position and did not always press the contact disk against the surface with exactly the same force within the same time. Therefore, the sampling conditions for each sample were different.

[0011] In addition, there is a possibility that the operator may make mistakes when recording the sampling position, and it may not be possible to assign the individual samples to the sampling position later. Summary of the Invention

[0012] The task of the present invention is to improve the reliability of surface sampling of pharmaceutical production equipment.

[0013] The present invention enables fully automated and repeatable sampling on the surface of pharmaceutical equipment without any intervention by the operator. In traditional equipment with a barrier system having a glove port, the use of the present invention can minimize the handling steps of the operator, and contact sampling can be carried out repeatedly and without incorrect recording.

[0014] The present invention provides a barrier system for this purpose. This barrier system can in particular be an isolator. The barrier system is part of or provided for a production device, in particular a pharmaceutical production device. The barrier system can also be a restricted access barrier system (RABS). RABS physically separates the product and the process from the production environment and the user, thus ensuring a high degree of protection for the product and the operator. This is usually a protective cover with glass plates, and there is a directional air flow prevailing in the separated area, but the separated area is not completely enclosed; air can flow downward (e.g., just above the tabletop) to the outside.

[0015] The barrier system can be closed and have a closed area in which a sterile environment is provided. The barrier system can also be open (RABS), having a separated area that is not completely enclosed but provides a sterile environment (the degree of sterility here is usually lower than that of a system with a closed area, but we will refer to a sterile environment in both cases hereinafter).

[0016] According to the present invention, it can be arranged such that the manipulation device and the contact sample holder are arranged in the closed or separated area. The contact sample holder is designed to provide at least one sample. The manipulation device is designed to automatically remove and open the provided contact sample from the contact sample holder and repeatedly sample a surface section in the closed or separated area. Repeatability means that the manipulation device can repeat the sampling process with the same sampling parameters, such as the same pressure duration and the same sample pressure. The sampling parameters are in particular stored and / or can be read out. The manipulation device is designed to perform these steps automatically, i.e., without human intervention, such as through a glove port intervention, or it can also be arranged to not require direct control during sampling but to be carried out within a predetermined sequence framework. For example, a robotic arm can be used. In particular, the manipulation device can sample from multiple sampling positions.

[0017] The contact sample in the sense of the present invention includes a bottom on which a nutrient medium, in particular agar, is placed. In the initial state, the contact sample is closed with a lid.

[0018] The method of opening the contact sample is to remove the lid from the bottom of the contact sample.

[0019] Sampling is accomplished by bringing the position to be sampled into contact with the nutrient medium of the contact sample. In particular, it is envisaged that before sampling, the contact sample is arranged with the nutrient medium downward and the bottom upward (by the manipulation device), and then moved onto the surface to be sampled, in particular in a movement mode perpendicular to the surface of the nutrient medium. In particular, the surface to be sampled is brought into contact with the nutrient medium under a predetermined pressure and / or for a predetermined time.

[0020] Thus, any bacteria present on the sampled surface will be applied to the nutrient medium and can be detected without the need for the operator to intervene within an enclosed or isolated area. Thus, contamination of the sterile environment can be detected.

[0021] In particular, the present invention makes it possible to control the sampling (precise pressure and precise pressing time).

[0022] It can also be arranged such that the manipulation device is designed to directly grasp and contact the sample during sampling. This represents a particularly simple sampling method and minimizes the design effort.

[0023] Additionally, it can be arranged such that the manipulation device is designed to send the contact sample to the sample carrier after removing it from the contact sample holder (which can be designed, for example, as a magazine) and move the sample carrier during sampling. In particular, the sample carrier can be designed to be autoclaveable. Compared to the glove port required for manual sampling, which can only be purified with hydrogen peroxide (H2O2), autoclaving of the device reduces the risk of contamination of the device, product, or sample forgery.

[0024] The task of the sample carrier is to safely hold and retain the contact sample and simplify the pressing of the contact sample against the surface. In particular, the bottom of the contact sample can be placed flat on the sample carrier, or the sample carrier can have a corresponding contact surface. In this way, it is possible to effectively prevent the contact sample or its bottom from being damaged when pressed against the surface to be sampled.

[0025] The holding of the contact sample on the contact sample holder can be achieved by force fit or form fit or by a combination of force fit and form fit. The force fit between the device and the contact sample can be achieved, for example, by a microstructured polymer film or a vacuum chuck. The form fit can be achieved, for example, by gripping fingers on the sample carrier. The gripping fingers can expand and be formed with recesses into which the contact sample can engage.

[0026] The fingers can be circumferentially distributed around the contact surface. The contact surface can be covered with the aforementioned microstructured polymer film. The contact surface can include the suction ports of the vacuum chuck. The connection of the vacuum line can be arranged on the side of the sample carrier opposite to the contact surface.

[0027] The device can also include a lid manipulation device. The lid manipulation device can be arranged to remove and / or place the lid of the sample held by the manipulation device or the lid arranged on the sample carrier. The lid manipulation device can be designed as a cylinder.

[0028] It can also be arranged such that the manipulation device includes a gripper having two jaws that can move towards or away from each other. In this case, the gripper can be arranged on the gripping member of the manipulation device, and the gripping member can pivot at least 90°, particularly 180°, particularly 360°. This enables the gripper to be used in a particularly flexible manner. The jaws of the gripper can in particular be designed to be complementary to the contact samples (curved, since these samples are usually circular).

[0029] The jaws of the manipulation device can in particular be designed to include sections complementary to the round shape of the contact samples and / or to include sections complementary to the shape of the grippable sections of the sample carrier. The sample carrier and the manipulation device can also have coupling means by which the sample carrier can be releasably connected to the manipulation device in a defined position and orientation. For example, this can be achieved by a form-fitting rear grip. The sample carrier can include a trough-shaped recess, and the complementary coupling means of the manipulation device can be introduced into the trough-shaped recess, whereby the coupling means of the manipulation device can engage behind the trough-shaped recess in the coupled state.

[0030] It can also be arranged such that the contact sample holder includes a holder for the sample carrier. In this way, the sample carrier is arranged close to the contact sample holder and in a defined position. The manipulation device can remove the contact sample from the contact sample holder and place it on the sample carrier, particularly on its contact surface. In particular, the contact sample can be held on the contact surface in a force-fitting and / or form-fitting manner (as described above, for example, by vacuum, a microstructured polymer film, and / or gripping fingers or other form-fitting elements that can grip the contact sample in a form-fitting manner). Then, the manipulation device can remove the lid of the contact sample. Then, the manipulation device can pick up the sample carrier or the contact sample and perform surface sampling.

[0031] It can also be arranged such that the contact sample holder is designed to accommodate a plurality of contact samples, and the contact samples can be arranged horizontally in the contact sample holder. In this way, the contact samples can be easily accessed and can be used for sampling in chronological order.

[0032] It can be arranged such that the barrier system includes a detection device which is designed to detect the identification features of the contact sample, in particular to associate the identified contact sample with the time and / or location of sampling. In this case, it can also be arranged such that the detection device includes a barcode reader, an RFID reader or a Data Matrix Code reader, which is suitable for reading the corresponding code on, in or at the contact sample. Thus, the identification feature can be a barcode or a Data Matrix Code or an RFID feature readably attached to, in or at the contact sample, and the detection device can include or be the corresponding reader. In this way, a specific sampling process (the time and location of sampling) can be assigned to an accurately identifiable contact sample through its identification feature. This enables a very high degree of traceability and recordability of sampling.

[0033] As mentioned above, the contact sample can include an RFID chip. On the RFID chip, an identification function can be provided. However, the RFID chip can alternatively or additionally include other information and / or information can be stored on the RFID chip.

[0034] It can be arranged such that the detection device is designed to detect the location and / or time of sample collection. It can also be arranged such that the barrier system includes a data processing system which is configured to assign the location and / or time of sampling in the data record of the contact sample or its identification feature and, if necessary, store and save it in a database.

[0035] It can be arranged such that the barrier system is configured to be glove - mouthless. The present invention makes the glove - mouth redundant. The glove - mouth is a weak link in the barrier system. Not using them can improve the reliability of the barrier system.

[0036] As mentioned above, the present invention also relates to a method for automatically sampling in a closed or separated area of a barrier system. The barrier system is in particular an isolator of a production facility, and the production facility is in particular a pharmaceutical production facility. A sterile environment is provided in the closed or separated area. The method can be used to reliably monitor, record and ensure the quality of the sterile environment.

[0037] At least one manipulation device is arranged in the closed or separated area. In addition, a contact sample is provided in the closed or separated area.

[0038] Within the scope of the method according to the invention, the handling device grasps the provided contact sample. The handling device opens the contact sample. The handling device thus performs such a working step in which the lid of the contact sample is removed so that the nutrient medium of the contact sample can be accessed. The handling device automatically samples a surface section in an enclosed or separated area using the opened contact sample. During the sampling process, the contact sample or its nutrient medium is brought into contact with the surface to be sampled. The sampling is carried out in a reproducible manner. Thus, the sampling parameters are reproducible. The second sampling can be carried out with the same parameters.

[0039] According to the invention, it can be specifically arranged that, after a first production interval, the first sampling is carried out by the method just described or the embodiments described later or an alternative method with two handling devices. This first sampling is carried out with first sampling parameters. After a second production interval, the second sampling is carried out by the method just described or the embodiments described later or an alternative method with two handling devices. This second sampling is carried out with second sampling parameters. The first and second sampling parameters can include at least one, preferably a plurality of, identical sampling parameters, preferably all the sampling parameters are the same. The sampling parameters can include one or more of the following parameters: sample contact pressure, sample contact time, sampling position.

[0040] According to the invention, for implementing the method, it can be arranged that the handling device places the contact sample on a sample carrier after grasping it. The sample carrier holds the contact sample especially in a force-fitting and / or form-fitting manner. After being placed on the sample carrier, the handling device opens the contact sample. For sampling, the handling device can grasp the sample carrier and move the sample carrier together with the contact sample held thereon to the surface section to be sampled in an enclosed or separated area and perform the sampling. For this purpose, the contact sample or its nutrient medium is brought into contact with the surface to be sampled. The sample carrier on which the contact sample is placed is moved by the handling device.

[0041] During the sampling process, the handling device can also orient the contact sample or the sample carrier on which the contact sample is held so that the sample surface of the contact sample is arranged parallel to the surface of the surface section to be sampled. Then, the contact sample can be pressed against the surface of the surface section to be sampled by a translational movement, especially with a defined pressure and / or for a defined time. The parallel orientation makes the pressing action particularly simple.

[0042] The manipulation device can also reseal the contact with the sample after sampling. To this end, the manipulation device can lower the contact with the sample or hold the sample carrier with the contact with the sample and place it on the lid. If necessary, the manipulation device can pick up the contact with the sample or hold the sample carrier with the contact with the sample and feed it into the next working step. For example, the contact with the sample can be fed into the storage area of the sample or into an air lock in order to remove it from a closed or separated area.

[0043] It can be arranged such that the manipulation device delivers the contact with the sample to a detection device before or after sampling. The detection device detects the identification features of the contact with the sample. Then, the identification features can be associated with the sampling, in particular with its time and / or location. The identification features can be barcodes or data matrix codes (the contact with the sample can also include an RFID chip that provides the identification features in a readable manner). The detection device can be or include a camera and / or a barcode and / or data matrix code reader or an RFID reader. In particular, the identification features can be stored in a data processing system together with data describing the sampling features, in particular its time and / or location (the sampling location in a closed or separated area). For example, the identification features can be stored in a table together with data describing the sampling features. This facilitates the automatic recording of individual samplings.

[0044] It can be arranged such that the manipulation device removes the contact with the sample from the contact sample holder before sampling and / or supplies it to the contact sample holder after sampling. The contact sample holder can be designed similar to a rack and have compartments or holders for a plurality of contacts with the sample. For example, the contact sample holder can be inserted into or removed from a closed or separated area through an air lock, where the sample is held in the contact sample holder. To this end, the contact sample holder can be detachably fixed within the closed or separated area.

[0045] As described above, the invention also relates to a method for automatically sampling in a closed or separated area of a barrier system, wherein at least two manipulation devices are arranged in the closed or separated area. The barrier system can be an isolator. The barrier system is part of a production facility, in particular part of a pharmaceutical production facility. A sterile environment is provided in the closed or separated area. Contact samples are provided in the closed or separated area. What has been mentioned regarding the method with one manipulation device and other embodiments of the barrier system can also be understood as other embodiments of the method with at least two manipulation devices.

[0046] The method comprises the following steps:

[0047] One of the manipulation devices grasps the provided contact with the sample;

[0048] One of the manipulation devices opens the provided contact with the sample;

[0049] One of the handling devices samples by contacting a surface section of the sample in a closed or separated area. The method optionally includes one or more of the following steps: closing the contact sample after sampling; placing the contact sample on a sample carrier after grasping it, and the sample carrier can hold the contact sample, in particular in a force-fitting and / or form-fitting manner; grasping the sample carrier for sampling, and moving the sample carrier together with the contact sample held thereon to a surface section in a closed or separated area, and then sampling. In this regard, the method provides that each handling device performs at least one step of the method. For example, it is conceivable that a first handling device removes the contact sample from a contact sample holder, while a second handling device receives the sample carrier, the first handling device places the contact sample on the sample carrier and removes the lid. Then, the second handling device samples with the sample held by the sample carrier. After sampling, the first handling device can put the lid back in place, remove the contact sample from the sample carrier, and return it to the contact sample holder or the airlock of the barrier system.

[0050] The advantage of using two handling devices with a division of labor is that the operation can be carried out more quickly, and the action radius of the handling device is larger than that of a single handling device.

[0051] In particular, within the scope of the present invention, the detection area of the detection device covers the action radius of the handling device, or the handling device can send the contact sample to the detection area of the detection device. It is advantageous to record the sampling because this can safely and reliably record the state of the closed or separated area.

[0052] The handling device can always press the contact sample against the surface with the same force, for example, by force controlled by a force sensor, or by displacement controlled by an elastic element. Thus, the repeatability of sampling can be further improved.

[0053] The force sensor or the elastic element can be arranged in the handling device or the sample carrier. The scope of the present invention also includes the combination of force and displacement control. The data generated during this process, such as the contact force and time, can also be used for recording.

[0054] Pressing the contact sample with a defined force can help prevent nutrients in the culture medium, such as agar, from falling out of the sample. This occasionally occurs when an operator samples manually and interferes with the production process or sampling, which is usually carried out after production.

[0055] Within the scope of the present invention, it is also particularly contemplated that the handling device can sample multiple sampling points arranged differently within a closed or separated area.

[0056] A detection device or other monitoring device can be provided and designed to check whether the nutrient medium is still present in the contact sample after sampling. For example, the monitoring device can be designed as a camera system. If no nutrient medium is detected in the sample, sampling can be repeated, for example, at a predetermined other location.

[0057] According to the present invention, particularly after the first production interval, the first sampling is carried out by one of the methods described above (the method with one manipulation device or the method with two manipulation devices). This first sampling is carried out with the first sampling parameters. The sampling parameters are the parameters characterizing the sampling. Based on the sampling parameters, the way of sampling can be traced. After the second production interval, the second sampling is carried out by one of the methods described above (the method with one manipulation device or the method with two manipulation devices). This second sampling is carried out with the second sampling parameters. The first and second sampling parameters thus include at least one, preferably a plurality of, the same sampling parameters, preferably all the sampling parameters are the same. The sampling parameters can include one or more of the following parameters: sample contact pressure, sample contact time, sampling location.

[0058] The first production interval and the second production interval can particularly be of equal length. The first and second samplings can particularly be carried out after operations at the same time.

[0059] In particular, the sampling parameters can be stored on the RFID chip of the corresponding contact sample used and read from the chip. Description of the Drawings

[0060] The present invention will be explained in more detail below with reference to the drawings. Among them:

[0061] Figure 1 The production equipment with enclosed or separated areas is schematically shown;

[0062] Figure 2 is a cross-sectional view of the contact sample;

[0063] Figure 3 is a perspective view of the manipulation device;

[0064] Figure 4 is another perspective view of the manipulation device with the sample carrier;

[0065] Figure 5 is another perspective view of the manipulation device with the contact sample holder;

[0066] Figure 6 is another perspective view of the manipulation device;

[0067] Figure 7 is a side view of the manipulation device during sampling;

[0068] Figure 8 is a perspective view of the manipulation device during sampling;

[0069] Figure 9 is the contact sample on the sample carrier;

[0070] Figure 10 is the sample carrier with the contact sample; and

[0071] Figure 11 is a schematic production device having an enclosed or separated area in which two manipulation devices are arranged and which can perform sampling according to a division of labor. Detailed implementation mode

[0072] Figure 1 Shows a pharmaceutical production device 12 having a barrier system 10, which barrier system includes an enclosed or separated area 14. The barrier system 10 is designed as an isolator 10. A sterile environment 16 is provided in the enclosed or separated area 14 of the isolator 10.

[0073] Inside the enclosed or separated area 14, there are a manipulation device 20 and a contact sample holder 22. As Figure 2 shown, the contact sample holder 22 is configured to provide at least one contact sample 24. In this embodiment, the shown contact sample holder 22 is configured to receive a plurality of contact samples 24, and the contact samples 24 can be horizontally arranged in the contact sample holder 22. As Figure 2 shown in detail, the contact sample 24 includes a bottom 26 and a lid 28. A nutrient medium 30, usually agar, is provided on the bottom 26 and is sealed by the lid 28. An identification feature 48 is further provided on the bottom 26. For example, the identification feature can be a QR code (information in a data matrix code, or a bar code, or an RFID chip). The identification feature 48 is usually located on the outer surface of the bottom 26. The lid 28 is detachable to expose the sample surface 31 of the contact sample 24 or the nutrient medium 30.

[0074] The manipulation device 20 is configured to remove the provided contact sample 24 from the contact sample holder 22, open it and perform sampling on a surface section 42 in the enclosed or separated area 14. The surface section 42 to be sampled is thus arranged at a sampling position 50, which is configured to enable repeatable sampling.

[0075] The manipulation device 20 is designed to be able to directly grasp the contact sample 24 during sampling. For this purpose, the manipulation device 20 includes a gripper 36 having grippers 38, as Figure 3It can be clearly seen in the figure. The gripper 36 is arranged on the 360° pivotable gripping member 34 of the handling device 20. The handling device 20 has a plurality of pivotally interconnected members 32 to enable the gripper to move freely in space.

[0076] As Figure 5 shown, the contact sample holder 22 may include a holder 23 for the sample carrier 40. Although the handling device 20 can directly grasp the contact sample 24 through the gripper 36, it can also use the sample carrier 40 for sampling.

[0077] The handling device 20 is suitably configured to transfer the contact sample to the sample carrier 40 after removing the contact sample 24 from the contact sample holder 22 (see Figure 5 and 6 ), and to move the sample carrier 40 during sampling (see Figure 7 and 8 ). The situation of the sample carrier will be further described in detail below.

[0078] The barrier system 10 includes a detection device 46 configured to detect the identification feature 48 of the contact sample 24. The detection device 46 generally includes or is a barcode reader or a data matrix code reader. Accordingly, the identification feature 48 can be the corresponding code (barcode or data matrix code) on the contact sample 24. The contact sample 24 may also include an RFID chip having the identification feature 48 such that the identification feature 48 is provided in a readable manner as information on the RFID chip.

[0079] The detection device 46 is connected to the data processing system 54 via a data link 56, which can be wired or wireless. The data processing system 54 can associate the identified contact sample 24 (identified by its identification feature 48) with the corresponding sampling time and / or location, for example, storing it as a corresponding data record. The detection area 52 of the detection device 46 may include the movement range of the handling device 20, or the contact sample 24 can move with its identification feature 48 into the detection area 52 of the detection device 46.

[0080] Since the steps required for sampling in the production device 12 are automated, the barrier system 10 can be designed without a glove port.

[0081] According to the present invention, there is also a method for automatically sampling in the enclosed or separated area 14 of the barrier system 10. Here, as with the production device 12 according to the present invention, at least one handling device 20 is arranged in the enclosed or separated area 14. In the enclosed or separated area 14, the method involves providing the contact sample 24, and the handling device 20 grasping ( Figure 6)The provided contact sample 24 is opened by removing its lid 28, and sampling is performed on the surface section 42 in the enclosed or separated area 14.

[0082] As shown in Figure 7 , the contact sample 24 is placed on the sample carrier 40 by means of the manipulation device 20.

[0083] The sample carrier 40 holds the contact sample 24 in a force - fit manner (variant Figures 4 to 8 ) and / or a form - fit manner (variants Figure 9 and 10 ). The form - fit is achieved by a plurality of fastening fingers 44, which is shown in Figure 9 and Figure 10 . The fastening fingers 44 are evenly distributed in the circumferential direction around the contact surface 45. The contact surface 45 is designed such that the contact sample 24 can be placed flat thereon. The contact sample 24 can be held in a force - fit manner by the suction port 58 or the adhesive surface 60, and the adhesive surface 60 can form, for example, a microstructured polymer film. The suction port 58 is connected to the connection 64 for vacuum supply through a pressure line 62 extending in the sample carrier 40.

[0084] The manipulation device 20 opens the contact sample 24 held on the sample carrier 40. For sampling, the manipulation device grasps the sample carrier 40 and moves the sample carrier 40 together with the contact sample 24 held thereon to the surface section 42 in the enclosed or separated area 14, and sampling is performed by pressing the nutrient medium against the surface 43 of the surface section 42 to be sampled.

[0085] During the sampling process, the manipulation device 20 orients the contact sample 24 or the sample carrier 40 holding the contact sample 24 such that the sample surface 31 of the contact sample 24 is arranged parallel to the surface 43 of the sampling surface section 42 and presses against the surface of the sampling surface section 42, especially with a defined pressure and for a defined time.

[0086] After sampling, the manipulation device 20 reseals the contact sample 24 by placing the lid on it.

[0087] Before or after sampling, the manipulation device 20 sends the contact sample 24 to the detection device 46, and the detection device 46 detects the identification feature 48 of the contact sample 24 (see Figure 9 ). After sampling and detecting the identification feature 48, the manipulation device 20 sends the contact sample 24 back to the contact sample holder 22.

[0088] Figure 11A barrier system 10 with two actuating devices 20 is shown. The actuating devices 20 operate alternately and perform different steps required for sampling. The first of the two actuating devices 20 grasps the provided contact sample 24. The second of the two actuating devices 20 opens the provided contact sample 24, i.e., removes its lid 28. The first actuating device 20 places the contact sample 24 on the sample carrier 40. The second actuating device 20 grasps the sample carrier 40 and samples the surface section 42 in the enclosed or separated area 14 with the contact sample 24. After sampling, the first actuating device 20 reseals by loading the lid 28 onto the contact sample 24. Thereafter, the second actuating device 20 places the contact sample 24 back into the contact sample holder 22. Each step can also be performed by the respective other actuating device 20, but each actuating device 20 performs at least one step of the method. This relates to a process variant with two actuating devices according to the invention.

Claims

1. A barrier system (10) for a production device (12), having an enclosed or separated area (14) in which a sterile environment (16) is provided, characterized in that, - a manipulation device (20) and a contact sample holder (22) are arranged in the enclosed or separated area (14), - wherein the contact sample holder (22) is configured to provide at least one contact sample (24), and - wherein the manipulation device (20) is configured to automatically remove, open the contact sample and automatically perform sampling on a surface section (42) in the enclosed or separated area (14) in a repeatable manner. The contact sample holder (22) includes a holder (23) for a sample carrier (40). The manipulation device (20) is configured to send the contact sample (24) to the sample carrier (40) after removing it and to move the sample carrier (40) away from the holder (23) during sampling. The sample carrier is configured to safely hold and retain the contact sample. The bottom of the contact sample can be placed flat on the sample carrier, or the sample carrier can have a corresponding contact surface. The holding of the contact sample on the sample carrier can be achieved by force fit of a microstructured polymer film or a vacuum chuck and / or by form fit of fingers on the sample carrier, such that the contact sample held by the sample carrier can be pressed against the surface to be sampled in parallel for sampling, so as to prevent the contact sample from being damaged when pressed against the surface to be sampled.

2. The barrier system (10) according to claim 1, wherein The manipulation device (20) includes a gripper (36) having two gripper jaws (38) that can move towards or away from each other.

3. The barrier system (10) according to claim 2, characterized in that, The gripper (36) is arranged on a gripping member (34) of the manipulation device (20), and the gripping member can pivot at least 90°.

4. The barrier system (10) according to claim 3, characterized in that, The gripping member can pivot 180°.

5. The barrier system (10) according to claim 3, characterized in that, The gripping member can pivot 360°.

6. The barrier system (10) according to any one of claims 1-5, characterized in that, The contact sample holder (22) is configured to receive a plurality of contact samples (24), and the contact samples (24) can be horizontally arranged in the contact sample holder (22).

7. The barrier system (10) according to any one of claims 1-5, characterized in that, The barrier system includes a detection device (46) configured to detect an identification feature (48) of the contact sample (24).

8. The barrier system (10) according to claim 7, characterized in that, The detection device is configured to associate the identified contact sample (24) with the time and / or location of sampling.

9. The barrier system (10) according to claim 7, characterized in that, The detection device (46) includes a barcode reader, a data matrix code reader, a plain text code reader or an RFID reader, which is configured to read the corresponding code or information of the contact sample (24) or a data carrier on the contact sample (24).

10. The barrier system (10) according to claim 7, characterized in that, The detection device (46) is configured to detect the location and / or time of sample extraction.

11. The barrier system (10) according to claim 10, characterized in that, The barrier system (10) includes a data processing system (54) configured to associate the location and / or time of sample extraction in a data record with the identification feature (48) of the contact sample (24).

12. The barrier system (10) according to any one of claims 1-5, 8-11, characterized in that, The barrier system (10) is designed to be glove-portless.

13. A method for automatically sampling in a closed or separated area (14) of a barrier system (10) of a production device (12), wherein, A sterile environment (16) is provided in the enclosed or separated area (14). It is characterized in that - at least one manipulation device (20) is arranged in the enclosed or separated area (14); - a contact sample (24) is provided in the enclosed or separated area (14); and - after the manipulation device (20) grasps the contact sample: the contact sample (24) is placed on a sample carrier (40), and the sample carrier holds the contact sample (24) by force fit through a microstructured polymer film or a vacuum chuck and / or by form fit of fingers on the sample carrier, the bottom of the contact sample can be placed flat on the sample carrier, or the sample carrier can have a corresponding contact surface; the contact sample (24) is opened; for sampling, the sample carrier (40) is grasped and the sample carrier (40) together with the contact sample (24) held thereon is moved to a surface section (42) in the enclosed or separated area (14) and the contact sample is opened for sampling, and the surface section is arranged on a static or movable element in the enclosed or separated area (14). During sampling, the manipulation device (20) orientates the sample carrier (40) holding the contact sample (24) such that the sample surface (31) of the contact sample (24) is arranged parallel to and pressed against the surface (43) of the sampling surface section (42) to prevent the contact sample from being damaged when pressed against the surface to be sampled.

14. The method according to claim 13, wherein The sample surface (31) of the contact sample (24) is pressed against the surface (43) of the sampling surface section (42) with a defined pressure and for a defined time.

15. The method according to claim 13 or 14, characterized in that, The manipulation device (20) closes the contact sample (24) after sampling.

16. The method according to claim 13 or 14, characterized in that The manipulation device (20) sends the contact sample (24) to a detection device (46) before or after sampling, and the detection device (46) detects the identification features of the contact sample (24).

17. The method according to claim 16, wherein The identification features (48) are assigned to the time and / or location of the sampling operation.

18. The method according to any one of claims 13, 14, and 17, characterized in that, The manipulation device (20) removes the contact sample (24) from the contact sample holder (22) before sampling and / or sends the contact sample to the contact sample holder (22) after sampling.

19. A method for automatically sampling in an enclosed or separated area (14) of a barrier system (10) of a production device (12), wherein, A sterile environment (16) is provided in the enclosed or separated area (14). It is characterized in that - at least two manipulation devices (20) are arranged in the enclosed or separated area (14); - a contact sample (24) is provided in the enclosed or separated area, and - wherein the method comprises the following steps: - one of the manipulation devices (20) grasps the provided contact sample (24); - one of the manipulation devices (20) opens the provided contact sample (24); - One of the manipulation devices (20) samples on a surface section (42) of the contact sample (24) in the closed or separated area (14), wherein the method includes one or more of the following steps: - Closing the contact sample (24) after sampling; - Placing the grabbed contact sample (24) on a sample carrier (40), the sample carrier holding the contact sample (24) by force fit through a microstructured polymer film or a vacuum chuck and / or by form fit of fingers on the sample carrier, the bottom of the contact sample being able to lie flat on the sample carrier, or the sample carrier being able to have a corresponding contact surface; - Grabbing the sample carrier (40) for sampling and moving the sample carrier (40) together with the contact sample (24) held thereon to the surface section (42) in the closed or separated area (14), and then the manipulation device (20) orienting the sample carrier (40) holding the contact sample (24) such that the sample surface (31) of the contact sample (24) is arranged parallel to and pressed against the surface (43) of the sampled surface section (42) for sampling to prevent the contact sample from being damaged when pressed against the surface to be sampled. Wherein each manipulation device (20) performs at least one step of the method.

20. The method according to any one of claims 13, 14, 17 or 19, characterized in that After a first production interval, a first sampling is performed with first sampling parameters, and after a second production interval, a second sampling is performed with second sampling parameters, wherein the first and second sampling parameters include at least one identical sampling parameter.

21. The method according to claim 20, wherein The sampling parameters in the first and second sampling parameters are all the same, and the sampling parameters include one or more of the following parameters: sample contact pressure, sample contact time, sampling position.

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