Cleanroom facilities

Abstract

A cleanroom facility 10 is disclosed, which includes a processing area 110 for processing biopharmaceutical products, a service area 120 for supplying processing material 20 to the processing area 110, the service area 120 being separated from the processing area 110 by a wall 130, and a passage 300 located in the wall 130, configured to allow the supply of material 20 to the processing area 110. The passage 300 includes a latch 310 facing the processing area 110 and a docking port 320 facing the service area 120. Furthermore, the docking port 320 is configured to allow a sealed container 400 containing material 20 to be docked to the passage 300 and accessed through the latch 310.

Description

Technical Field

[0001] The present disclosure relates to the manufacture of biopharmaceutical products, and more particularly, to cleanroom facilities and techniques for such manufacture.

Background Art

[0002] As the development of new biopharmaceutical products progresses, there is a corresponding need to build special cleanroom facilities to accommodate the manufacture of such biopharmaceutical products. The manufacture of biopharmaceuticals places high requirements on biosafety and cleanliness to prevent, for example, the loss of biological integrity through the release of harmful chemicals into the environment and product contamination by particulate matter and microorganisms. Therefore, the manufacture of biopharmaceuticals requires relatively complex and expensive cleanroom facilities.

[0003] The reality of developing and manufacturing biopharmaceutical products typically involves having permanent cleanroom facilities that are designed to provide an appropriate level of cleanroom technology and verified to ensure compliance with applicable standards. However, strict standards and regulations can be both time-consuming and costly, and there is a risk of making it difficult to modify and expand cleanroom facilities to meet changing demands. Companies that do not routinely develop or manufacture biopharmaceutical products and therefore do not have appropriate dedicated cleanroom facilities are also experiencing similar difficulties in the design, construction, and verification of new facilities.

Summary of the Invention

Problems to be Solved by the Invention

[0004] Therefore, there is a need for improvement in cleanroom facilities that are more flexible, efficient, and expandable without compromising cleanliness.

Means for Solving the Problems

[0005] The object of the present disclosure is to provide a solution to address one or more of the identified deficiencies in the art.

[0006] According to the first embodiment, a cleanroom facility for the manufacture of a biopharmaceutical product is provided. The cleanroom facility includes a processing area for processing the biopharmaceutical product, a service area for supplying materials for processing the biopharmaceutical product to the processing area, the service area being separated from the processing area by a wall, and a passage located in the wall. The passage is configured to allow the supply of materials to the processing area. The passage includes a latch facing the processing area and a docking port facing the service area. The docking port is configured to allow a sealed container containing materials to be docked to the passage and accessed through the latch.

[0007] According to a second embodiment, a passageway is provided for a cleanroom facility for the manufacture of biopharmaceutical products. The passageway is located in a wall separating a processing area and a service area for the processing of biopharmaceutical products and is configured to allow the supply of materials for the processing of biopharmaceutical products from the service area to the processing area. The passageway includes a docking port located facing the service area and configured to allow sealed containers to be docked into the passageway. Furthermore, the passageway includes a latch located facing the processing area and configured to allow access from the processing area to the materials in the docked containers.

[0008] According to a third embodiment, a sealed container is provided for supplying materials for processing biopharmaceutical products in a cleanroom facility. The container includes a body configured to contain the material, a sealing for maintaining a predetermined degree of cleanliness of the material, and a docking interface configured to dock to a docking port in a passageway. The passageway is located in a wall separating a processing area from a service area for processing biopharmaceutical products, with the docking port facing the service area. Furthermore, the passageway includes a latch facing the processing area, configured to allow access from the processing area to the material in the docked container.

[0009] According to a fourth embodiment, a cleanroom facility for the manufacture of biopharmaceutical products is provided. The cleanroom facility includes a processing area comprising first and second cleanrooms for processing biopharmaceutical products, and a service area for supplying materials for processing biopharmaceutical products to the processing area, with at least a portion of the service area adjacent to the first and second cleanrooms. Furthermore, the processing area is accessible via a processing area corridor, and the service area is accessible via a service area corridor, and the processing area corridor and the service area corridor are separated from each other to prevent the ingress of contaminants from the service area corridor into the processing area corridor.

[0010] According to the fifth embodiment, a cleanroom facility for the manufacture of a biopharmaceutical product is provided, which includes a processing area for processing the biopharmaceutical product, a service area for supplying materials for processing the biopharmaceutical product to the processing area, the service area being separated from the processing area by a wall, and one processing apparatus for processing the biopharmaceutical product. Furthermore, the one processing apparatus is located partly in the processing area and partly in the service area, and has a user interface accessible from the processing area.

[0011] According to the sixth embodiment, a modular cleanroom facility for the manufacture of biopharmaceutical products is provided, the cleanroom facility being formed of a plurality of transportable modules assembled into a processing area for processing biopharmaceutical products and a service area for supplying materials for processing biopharmaceutical products to the processing area. Each module includes side walls, a modular roof, and a modular floor. Furthermore, each module is configured to be in a first state in which the side walls, modular roof, and modular floor form a self-supporting transportable structure, and a second state in which at least one of the side walls is rearranged to form a ceiling portion of the processing area or service area of ​​the assembled cleanroom facility.

[0012] According to a seventh embodiment, an indicator system for a cleanroom facility for the manufacture of biopharmaceutical products is provided. The cleanroom facility includes a processing area comprising a plurality of processing devices for processing biopharmaceutical products, and passages located in the walls of the processing area and configured to allow the supply of materials for processing biopharmaceutical products to the processing area. The indicator system includes passage indicators associated with the passages, processing device indicators associated with the processing devices, and a control device operationally connected to the passage indicators and processing device indicators. The control device is configured to activate the passage indicators and processing devices based on workflow instructions that govern the manufacture of biopharmaceutical products.

[0013] According to some embodiments, processing areas, such as first and second cleanrooms, are configured to maintain a first degree of cleanliness, while service areas, such as service rooms, are configured to maintain a second degree of cleanliness, the second degree being lower than the first degree.

[0014] According to some embodiments, the first and second cleanrooms are accessible from the first side, while the service area is accessible from the second side, opposite to the first side. Therefore, cleanroom operators and service personnel can enter their respective areas from opposite sides, preferably via separate corridors. Beneficially, separating cleanroom operators from service personnel reduces the risk of people entering the wrong room. Furthermore, it reduces the risk of contamination spreading from the service area to the treatment area.

[0015] In some embodiments, the service area may include first and second service rooms, which may be located on either side of the cleanroom of the processing area. In other words, the cleanroom may be adjacent to the first service room on one side and to the second service room on the other. Beneficially, this makes it possible to separate the processing equipment from the material supply flow, with materials supplied through the first service room and the processing equipment located in the second service room. Because there is no passage of personnel or flow of materials between the second service room and the cleanroom, the second service room, i.e., the processing equipment room, can be kept to an even lower degree of cleanliness than the first service room. Furthermore, access to the second service room can be restricted to unauthorized personnel, so that only authorized service technicians can access the equipment. As described above, the equipment may be located partly in the second service room and partly in the cleanroom. Preferably, the user interface portion of the equipment may be located in the cleanroom, or at least accessible from the cleanroom, while the rest of the equipment, such as pumps, conduits, filters, etc., is located in the second service room.

[0016] As mentioned above, the first service room may include a corridor. Therefore, the first service room can be considered a "material supply only" room, while the second service room can be considered a "machine service only" room. Access to these two types of rooms can be restricted as appropriate, so that material supply personnel cannot access the machine service room, and machine service personnel cannot access the material supply room.

[0017] According to several embodiments, the processing equipment can be a chromatography system, the user interface of the processing equipment is located in the processing area, or at least accessible by an operator within the processing area, and the rest of the processing equipment, such as columns, filters, pumps, and conduits, is located in the service area. The invention according to the fifth embodiment specified above is based on the insight that by conveniently placing as much of the equipment as possible in the service area, the space required in the processing area to accommodate the equipment can be reduced. Furthermore, by placing the majority of the equipment in the service area, service engineers may be able to access the equipment without having to enter the processing area. Ideally, the user interface (i.e., the part of the equipment used for interaction with the operator) is the only part of the equipment located in the processing area.

[0018] According to one embodiment, the indicator system includes a plurality of passage indicators, each associated with a respective passage, and a plurality of processing unit indicators, each of which is associated with a respective processing unit. The control unit is configured to selectively activate a first of the plurality of passage indicators and a first of the plurality of processing unit indicators to associate a particular passage with a particular processing unit. The passage indicators and processing unit indicators can be visible indicators, such as indicator lights.

[0019] Biopharmaceutical products, also known as biological pharmaceutical products, typically include any medicinal substance manufactured from biological sources. Examples of such products include, but are not limited to, proteins.

[0020] In the context of this disclosure, the term “processing area” typically refers to an area within a cleanroom facility that includes one or more cleanrooms.

[0021] A "cleanroom" is generally understood as a room designed, maintained, and controlled to prevent contamination of biopharmaceutical products by particulate matter and microorganisms. Preferably, such a room is designated to and reproducibly conform to an appropriate level of air cleanliness, such as ISO Class 7.

[0022] Therefore, a cleanroom area can form an area where cleanliness standards for particulate matter and / or microorganisms are defined. This area may also be called a classification area or a control area.

[0023] A service area can include one or more service rooms and typically refers to an area of ​​a cleanroom facility maintained at a lower level of particulate matter and / or microbiological cleanliness than the cleanroom area. Service areas can be used for the maintenance and servicing of processing equipment, as well as for material supply. Therefore, a service area / room can also be called a maintenance area / room.

[0024] It is understood that contamination, typically during manufacturing, sampling, packaging or repackaging, storage or transportation, can introduce microbiological impurities or foreign particulate matter into materials, intermediates, active ingredients, or products in an undesirable manner, potentially adversely affecting product quality.

[0025] The terms “processing equipment” and “processing equipment” are interchangeable throughout this disclosure and refer to machinery used in the processing and manufacture of biopharmaceutical products. Specific examples include bioreactors, cell culture systems, separation and purification systems such as chromatography and filtration systems, and configurations and systems for fluid storage, fluid transfer, and fluid processing.

[0026] Further features and advantages of the present invention will become apparent from the following description of preferred embodiments of the invention, which are given merely as examples with reference to the attached drawings. The drawings should not be considered limiting, but rather are used for illustrative and understanding purposes. [Brief explanation of the drawing]

[0027] [Figure 1] It is a diagram showing the layout of a cleanroom facility. [Figure 2] It is a diagram showing a cleanroom and a service room separated by a wall. [Figure 3a] It is a diagram showing a passage for supplying materials to a processing area. [Figure 3b] It is a diagram showing a passage for supplying materials to a processing area. [Figure 3c] It is a diagram showing an example of a sealed container for materials used in biopharmaceutical processing. [Figure 3d] It is a diagram showing an example of a sealed container for materials used in biopharmaceutical processing. [Figure 3e] It is a diagram showing the use of a passage for supplying materials to a processing area. [Figure 3f] It is a diagram showing the use of a passage for supplying materials to a processing area. [Figure 4] It is a perspective view of a modular cleanroom facility. [Figure 5] It is a perspective view of a module for a modular cleanroom facility, and the module is arranged in a first state suitable for transportation. [Figure 6] It is a diagram showing the module when arranged in a second state, and the module is being assembled into a cleanroom facility. [Figure 7] It is a diagram showing a part of the assembled modular cleanroom facility. [Figure 8] It is a diagram showing a part of the assembled modular cleanroom facility. [Figure 9] It is a diagram schematically showing an indicator system for a cleanroom facility.

Mode for Carrying Out the Invention

[0028] Various embodiments of the concept of the present invention will be described more fully hereafter with reference to the attached drawings, although the drawings disclose only some, but not all, embodiments and features. It will be understood that the drawings are not necessarily to scale, and that the scope of the present invention is defined solely by the attached claims.

[0029] Figure 1 is a schematic diagram of the layout of a cleanroom facility 10 for the manufacture of biopharmaceutical products. The cleanroom facility 10 includes a processing area 110 comprising a first cleanroom 111 and a second cleanroom 112 for processing biopharmaceutical products, and a service area 120 comprising a service room 121 for supplying materials to the processing area 110. The service room 121 is located between the first and second cleanrooms 111 and 112 and is positioned adjacent to both cleanrooms 111 and 112. In other words, the service room 121 can be considered to share walls 130 with the first and second cleanrooms 111 and 112, respectively. It should be noted that Figure 1 shows an example of a layout with a one-dimensional arrangement of rooms, where three cleanrooms 111, 112, and 113 are arranged alternately with two service rooms 121 and 122. However, the number of rooms and specific layouts may vary between different embodiments.

[0030] The treatment area 110 and the service area 120 are accessible via corridors, indicated in this figure by treatment area corridor 115 and service area corridor 125, through which operators and service personnel can enter their respective rooms. The treatment area corridor 115 and the service area corridor 125 are separated from each other to generally reduce the risk of contamination, more specifically to prevent the entry of contaminants from the service area corridor 125 into the treatment area corridor 115. Each of the corridors 115 and 125 can be formed as a corridor with rooms along one of its sides. In Figure 1, the treatment area corridor 115 extends along the first side (right side in the figure) of the row of adjacent rooms and has entrances to clean rooms 111, 112, and 113, respectively, while the service area corridor 125 extends along the second side (left side in the figure) of the row of adjacent rooms and has entrances to service rooms 121 and 122, respectively. This makes it possible to access cleanrooms 111, 112, and 113 and service rooms 121 and 122 from the opposite side.

[0031] Access to the processing area 110 and the service area 120 can be controlled by an access control system that uses identification means associated with personnel working in those areas. The identification means can be read by readers located at the entrance points of each area 110 and 120. The identification means may include, for example, radio frequency tags worn by personnel and read upon entry requests. This allows access to authorized individuals, such as service personnel entering the service area 120 and process operators entering the processing area 110. The identification means can also be used to improve traceability and quality control.

[0032] The processing area 110 can be accessed from an anteroom 141, where the operator can put on cleanroom clothing and then enter the processing area corridor 115 via an airlock 143. Similarly, the service area 120 can be accessed from an anteroom 142, where the operator can put on cleanroom clothing and then enter the service area corridor 125 via another airlock 144. In the example shown in Figure 1, each corridor 115 and 125 is accessed via separate anterooms 141 and 142. However, other layouts are possible in which the processing area corridor 115 and the service area corridor 125 are accessed from a common anteroom 141 and 142.

[0033] The layout of the cleanroom facility 10, as shown by the dashed arrows in Figure 1, beneficially allows personnel to enter the processing area 110 and the service area 120 via two separate access routes. The separate routes are understood to be unconnected, preventing personnel in one route from entering the other. In other words, this layout prevents service personnel in the service area 120 from accessing the processing area 110, and prevents operators in the processing area 110 from accessing the service area 120. Therefore, the service area 120 is a less controlled area, meaning it can be maintained at a lower level of cleanliness than the processing area 110 without the risk of contaminating the processing area 110. Furthermore, this layout facilitates access and security control by reducing the number of people accessing each area 110 and 120.

[0034] Generally, the processing area 110, or at least the cleanrooms 111, 112, and 113 within the processing area 110, can be configured as clean areas with particulate and microbiological cleanliness standards defined as those set forth by the relevant authorities. Thus, the processing area 110 can be referred to as a classification area. The service area 120, including service rooms 121 and 122 for maintenance, service, or material supply, may have the same level of cleanliness as the processing area 110, but with less control. Cleanroom standards and classifications are considered well known to those skilled in the art and are therefore not discussed in detail in this disclosure.

[0035] The cleanroom facility 10 in Figure 1 can be a modular cleanroom facility 10 formed of multiple modules, as will be discussed in relation to Figures 4 to 8.

[0036] The processing of biopharmaceutical products can be carried out by processing equipment or processing device 200 using raw materials supplied to clean rooms 111, 112, and 113 via passages 300 in wall 130.

[0037] Figure 1 shows service rooms 121 and 122 (i.e., rooms containing both passages 300 for material supply and processing equipment) that combine maintenance, service, and material supply capabilities, but it will be understood that other configurations are also possible. In one example, the processing equipment 200 and material supply can be separated into different service rooms. For example, the first service room 121 could be dedicated to the supply of materials through passage 300, while the second service room 122 is dedicated to the processing equipment 200. By dedicating the second service room 122 to the processing equipment 200, the second service room 122 can be maintained at an even lower level of cleanliness than the rest of the service area 120, as there is no direct access to the cleanroom 112 or material transfer. Furthermore, access to each service room 121 and 122 can be restricted so that only authorized personnel can access the processing equipment 200.

[0038] Next, with reference to Figure 2, we will discuss embodiments of the processing equipment 200.

[0039] Figure 2 schematically shows the cleanroom 111 and service room 121, which can be configured similarly to those shown in Figure 1. Therefore, the cleanroom 111 and service room 121 are adjacent rooms separated by a wall 130. As shown in the figure, processing equipment 200 can be provided for processing biopharmaceutical products. The processing equipment 200 is located partly in the processing area 110 and partly in the service area 120. Preferably, as much of the housing of the processing equipment 200 as possible can be placed in the service area 120 to save space in the processing area 110. In this example, the user interface of the processing equipment 200 is located in the cleanroom 111, while the rest of the processing equipment 200 is located in the service room 121. Therefore, the processing equipment 200 is accessible to operators via its user interface located in the cleanroom 111, and simultaneously accessible for service and maintenance via the service room 121. By moving the majority of the processing equipment to the less controlled service area 120, the volume of the more controlled processing area 110 can be reduced, saving energy and costs. The processing equipment 200 can be properly sealed at its interface leading to the cleanroom in order to maintain the integrity and airtightness of the cleanroom.

[0040] The wall 130 may include one or more openings or passages through which the processing equipment 200 can be introduced into the cleanroom 111. This makes it possible to install and replace the processing equipment 200 from the service side of the wall 130, thereby reducing contamination of the cleanroom 111. When not in use, the wall openings can be sealed with covers that can be removed when installing or inserting the processing equipment 200.

[0041] In one example, the processing equipment 200 may also be called a processing device and may be a chromatography system. A chromatography system can be understood as a system that supplies a fluid flow across a chromatography separation unit, such as a chromatography column or membrane adsorbent, to achieve the separation and purification of the active pharmaceutical ingredient. It includes fluid transfer components such as valves, at least one pump, and sensors for process monitoring and control. Typical examples of sensors include sensors for pressure, fluid flow rate, fluid conductivity, absorbance, or pH. The process is usually automatically controlled and monitored by a control system. Starting / stopping the system, and / or inputting required process and batch data, may require some operator intervention.

[0042] The processing equipment can be configured as a single-use system with a single-use channel, which is installed before fluid processing and removed after processing is complete. By providing a clean, preferably pre-sterilized, channel for processing the active pharmaceutical ingredient, the need for washing and washing validation, as well as the need for washing solutions and related equipment in the first place, is eliminated. Single-use processing can enhance process flexibility and efficiency, as well as process and product safety, for example, by avoiding the risk of cross-contamination when processing different active pharmaceutical ingredients and batches.

[0043] A single-use chromatography system typically consists of reusable fixtures that enable the installation and operation of replaceable and disposable single-use channels. Single-use channels can include all wetted components that come into contact with the process fluid, such as tubing conduits, connectors, sensors, and pump heads. Single-use containers, typically including flexible bags, are usually connected to the channels of the single-use system to supply and receive the relevant process fluid and / or portions thereof.

[0044] A typical example of a single-use chromatography system is the AKTA ready 450 system (available to the applicant at the time of filing). This system is offered as a benchtop system, but can be further adapted and modified to be provided and integrated into a cleanroom-to-service area interface as described in this invention.

[0045] As shown in Figure 2, the wall 130 may further include one or more passages 300 for transporting goods and materials between the service area 120 and the processing area 110. The passages 300 may be located adjacent to one processing machine 200 and configured to supply goods and raw materials, i.e., raw materials intended for use in the manufacture of products using that particular machine, to that processing machine 200. The passages 300 may include interlock doors configured to maintain pneumatic control between adjacent rooms and to prevent the entry of particulate matter and microbial contamination from the less controlled service room 121. In one example, the supply of materials is separated from the processing machine 200, with the processing machine 200 located in the first service room 121 and the materials supplied from a second service room (not shown in Figure 2).

[0046] As described above, one processing unit 200 can be installed in the passageway 300 or a modified passageway. The configuration of the passageway 300 makes it easy to add and remove processing units as needed, which can improve the flexibility of the cleanroom facility 10. By using an existing passageway to install the processing unit, there is no need to create additional holes in the wall.

[0047] Figures 3a and 3b show an example of such a passage 300 located in a wall 130 separating the processing area 110 and the service area 120. The processing area 110 and the service area 120 can be configured in the same manner as discussed above with reference to Figures 1 and 2.

[0048] The illustrated passage 300 is configured to allow the supply of articles and raw materials 20, including but not limited to bioprocess bags and single-use assemblies (such as ReadyCircuit 2-D and 3-D bag assemblies, which were made available by the applicant at the time of filing), flow path assemblies for chromatography systems (e.g., flow kits for AKTA ready 450 systems), and / or chromatography columns, from the service area 120 to the processing area 110. Furthermore, pre-filled fluid bags or containers providing raw materials, buffers, or other process fluids can be supplied to the cleanroom area for processing. Similarly, materials can be removed from the cleanroom area during and after processing, including samples for offline analysis outside the cleanroom area, products as a result of processing, waste containing processed fluids, and used flow path assemblies. Furthermore, the passage can be arranged to allow parallel processing of multiple similar batches of active pharmaceutical ingredients, for example, for personalized treatment. This can be achieved by a parallel arrangement of multiple processing stations of the same or similar types that generate batches, and products for individual patients. Each processing device, or processing station, can have an adjacent, dedicated passage in this configuration, which allows for the separation of product and process. By providing a dedicated passage paired with each processing station, the need to transport materials back and forth between a central passage or transfer airlock and each processing station is eliminated, as in the prior art. This, in turn, reduces the risk of material errors and confusion. Furthermore, it reduces the extra installation space required in the prior art system for transporting materials to and from the central airlock across the cleanroom. In the concept of the present invention, it is sufficient to move materials to and from passages located adjacent to the processing stations. Material movement can be performed manually by an operator or, in other examples, by a robot.

[0049] By utilizing different passages, products and samples can be separated from waste, or incoming materials can be separated from outgoing materials. The material 20 is supplied in a sealed container 400, which docks into the passage 300 from the service area 120 side and can be accessed by an operator from the processing area 110 side of the passage 300. The transfer of material between the processing area 110 and the service area 120 is made possible by the design of the passage 300, which includes a docking port 320 facing the service area 120 and a latch 310 accessible from the processing area 110. The docking port includes a docking interface 321 for receiving the corresponding docking interface of the container 400, as well as a docking door or latch 322 for sealing the passage 300 when the container 400 is not docked. The docking door 322 can be opened or removed from the passage either before the container 400 is docked into the passage 300 or after the container 400 is docked. Figure 3a shows the docking door 322 in a closed position, which is positioned to prevent contaminants from entering the passage 300, while Figure 3b shows the docking port 320 with the docking door 322 open. Once the container 400 is docked in the passage 300, an operator in the processing area 110 can open the latch 310 to access the container 400 and retrieve the material 20.

[0050] The material 20 to be supplied to the processing area 110 can be pre-cleaned, i.e., washed before being placed in the container 400. By sealing the container 400, the cleanliness of the material 20 can be preserved during storage, transport, and handling, reducing the need for additional washing of the material 20 before it is brought into the processing area 110. Thus, the material 20 for processing biopharmaceutical products can be provided to the processing area 110 by service personnel docking the container 400 into a passageway, making the material 20 accessible to operators operating the processing equipment in the processing area 110.

[0051] The cleanroom facility 10 can be used for so-called closed-system processing, where sterilized products are not exposed to the surrounding environment. This can be achieved by using bulk product holders, such as tanks or bags, that are connected to each other as a system, and the system is sterilized after the connection is made. The closed system can be extended outside the cleanroom facility 10 by providing pre-washed materials 20 to sealed containers 400. In other words, the clean environment can be extended beyond the cleanroom facility 10 by washing and sealing the materials in the containers outside the facility.

[0052] The container 400 includes a body 410 configured to contain the material 20, a sealing 420 for maintaining a predetermined degree of cleanliness of the material 20 during storage and handling, and a docking interface 421 for docking the container 400 to a docking port 320 of the passage 300. The body 410 can form a box having a size and shape adapted to contain the desired material, such as single-use bags of various sizes. The docking interface 421 of the container 400 may include a structure located at an opening or edge of the body 410 and adapted to engage with a corresponding structure on the docking interface 321 of the passage. Examples of such structures include threaded and snap-lock interconnects that engage with each other.

[0053] The container seal 420 can be formed by a lid or single-use seal that can be opened or perforated by an operator from the processing area side of the wall 130. In one example, the seal 420 includes a plastic film that is airtightly sealed to the edge of the container body 410 and is removable after the container 400 has been docked into the passage.

[0054] Container 400 can be sealed before being removed from the passage. This allows the material removed from the cleanroom to be transported to a different location for further processing under closed, sealed, and controlled conditions. This may involve connecting the container to another cleanroom. If the material is to be disposed of, the container can ensure the safety of the operator and the environment during transport, and / or the container can be disposed of along with its contents.

[0055] The passage 300 may include a cleaning system to remove contaminants present in the passage 300 before the latch 310 is opened. The cleaning system may be, for example, an air replacement system or an air flushing system that replaces the air in the passage 300 after the container 400 is docked. In another embodiment, the cleaning system may further include a bioburden reduction system such as an ultraviolet treatment device or an automated spraying system.

[0056] As shown in Figures 1 and 2, the passageway can be positioned adjacent to the processing equipment to which the material is to be supplied. This reduces the risk of material transport within the cleanroom 111 and of material being supplied to the wrong processing equipment. Furthermore, by supplying pre-cleaned material to the cleanroom 111, operators do not need to spend time on additional material cleaning.

[0057] Access to the aisle can be controlled so that only authorized or properly trained personnel can open the latch 310 and retrieve the material. In some examples, access can be restricted to the operator's identification card or an identification means carried by the operator. The identification means may include, for example, a radio frequency tag worn by the operator and read by a reader operationally coupled to the aisle. Examples of possible identification means include active and passive RFID tags, which can be integrated into wearable items such as armbands. To open the aisle, the operator can scan the tag with a reader associated with the aisle. This makes it possible to restrict access to the aisle to authorized personnel and improve traceability and quality assurance.

[0058] Figure 3c shows a container 400 according to one embodiment, comprising a main body 410 and a sealing 420 that defines a clean environment conforming to cleanliness standards in the processing area. The container 400 can be provided in transport packaging material 430 such as a cardboard box, from which it can be removed and then docked to the passage 300. In this example, the container 400 is a transparent polypropylene plastic box with a lid 420 that snaps onto the box.

[0059] The container 400 can be handled and transported within the service area by trolley or cart 440. Figure 3d shows an example of a cart 440 configured to transport two containers 400, the first of which has a single compartment and the second of which has three compartments. It will be understood that the body 410 of the container 400 may have a shape and number of compartments that vary depending on the type of material being handled, and that the illustrated container 400 is a non-limiting example.

[0060] The cart 440 is configured to orient the container 400 so that the sealing 420 faces forward in order to facilitate docking into the aisle.

[0061] In Figure 3e, the container 400 is docked to the passage 300, and the sealing 420 is removed, allowing access to the material from the cleanroom 111. Figure 3f shows the passage 300 from the cleanroom side, where the latch 310 is opened by the operator, allowing the material stored in the compartment of the container 400 to be removed and transported to the processing equipment.

[0062] The cleanroom facility 10 described above can be formed from multiple modules, as shown in the example in Figure 4. Figure 4 shows a facility 10 formed from multiple transportable modules 500 assembled into processing and service areas similar to those discussed above in relation to Figures 1, 2, and 3a-3b. Thus, the cleanroom facility 10 can be called a modular cleanroom facility 10. The modular configuration makes it possible to change the layout, size, or shape of the facility to meet changing requirements and to relocate the cleanroom. Thus, a more flexible cleanroom facility is provided, which is easier to expand to an optimized capacity.

[0063] Module 500 can be a pre-fabricated, self-supporting structure equipped with independent heating, ventilation, and air conditioning (HVAC) and electrical systems. Module 500 can have a shape and size that accommodates conventional intermodal shipping containers, enabling easy and efficient transport. The module can be transported, for example, by road or rail to locations where new or additional production capacity is needed. In this example, Module 500 is sized as a 20-foot high-cube (HC) container, conforming to the global containerized intermodal freight transport system.

[0064] The modular configuration of cleanroom facilities allows for the expansion of facilities to meet increasing market demand, as well as the beneficial possibility of decommissioning, relocating, and then restarting them if necessary. Therefore, a modular configuration can be seen as a flexible option for addressing future demands.

[0065] Figure 5 is a perspective view of module 500 according to one embodiment, which can be configured similarly to module 500 shown in Figure 4. Module 500 includes side walls 510, a module roof 520, and a module floor (not shown in this figure). In this figure, the side walls 510, the module roof 520, and the module floor are arranged in a first state to form a self-supporting, transportable structure. Module 500 further includes interconnection structures 540 located on the module roof 520 in this example for connecting infrastructure systems such as HVAC and electrical systems to adjacent modules 500 of an assembled cleanroom facility 10.

[0066] Figure 6 shows module 500 in the second state, where at least some of the side walls 510 have been rearranged to form the ceiling or floor portion of the processing area 110 or service area 120 of the assembled cleanroom facility 10. The side walls 510 of the transportable module 500 are thus equipped with the necessary infrastructure, such as HVAC and electrical equipment, before delivery to the site, thereby reducing on-site construction time.

[0067] In this figure, the side wall 510 is moved from its vertical position in the first state shown in Figure 5 to the horizontal position shown in Figure 6. Therefore, the side wall 510 can be considered to have a dual function: a first function of protecting pre-installed processing machinery during transport, and a second function as the ceiling or floor of the assembled cleanroom facility 10. The dual function of the side wall 510 beneficially reduces the need for additional transport packaging materials.

[0068] In Figure 7, multiple modules 500, similar to those shown in Figures 5 and 6, are assembled into a cleanroom facility 10, including a processing area 110 and a service area 120, as discussed above in relation to Figures 1 and 2. Each module 500 is positioned in a second state, with at least some of its side walls 510 repositioned horizontally to form the floor and ceiling portions of the processing and service areas 110 and 120 of the assembled cleanroom facility 10. The ceiling-forming side walls 510 of the first module 500 are connected to the module roof 520 of the second adjacent module 500 to form a continuous ceiling structure of the assembled cleanroom facility 10. Similarly, the floor-forming side walls 510 of the first module 500 are connected to the module floor 530 of the second adjacent module 500 to form a continuous floor of the assembled cleanroom facility 10. Furthermore, the modules 500 are interconnected via their respective interconnection structures 540, and the interconnection points 541 are structurally and functionally connected to each other via bridging members 542. In this example, the interconnection points 541 of each module 500 are accessible from above, outside the module 500, and the bridging members 542 can be attached to the interconnection points 541 from outside the cleanroom facility 10.

[0069] When assembled, the modular cleanroom facility 10 includes a processing area 110 comprising a plurality of cleanrooms and a service area 120 comprising a plurality of service rooms for supplying materials to the processing area 110. In the layout shown in Figure 7, the cleanrooms are separated from each other by the service rooms, where at least some of the processing equipment is located to reduce the volume of the cleanrooms. Thus, the cleanrooms can be considered to form a one-dimensional array of cleanrooms, which interlock with the service rooms. The service rooms and cleanrooms are separated from each other by a wall 130, where a plurality of passages 300 can be located to allow the supply of articles and materials to the cleanrooms. The passages 300 can be configured similarly to the embodiments disclosed above in relation to Figures 3a and 3b. Figure 7 shows a cleanroom, where the separating wall 130 includes a plurality of passage latches 310 that an operator can open to evaluate the materials to be supplied to the cleanroom. On the opposite wall 130 from the service rooms, a trolley is disclosed containing a plurality of containers 400 docked to corresponding passages 300 to adjacent cleanrooms. Therefore, the trolley or cart can be configured to carry one or more containers 400 to facilitate transport within the service area 120 and docking into the aisle 300. The containers 400 can be configured as in the embodiments disclosed in Figures 3a and 3b and can therefore be sealed to maintain a clean environment in which pre-washed materials are contained, such as single-use bags for processing biopharmaceutical products.

[0070] Figure 8 shows a further example of an assembled cleanroom facility 10, which can be configured similarly to those shown in Figures 1 and 7, for example. Figure 8 shows a row of adjacent rooms, with the first cleanroom 111 and the second cleanroom 112 of the processing area 110 separated by the first service room 121 of the service area 120. Each of the cleanrooms 111 and 112 is also adjacent to the second and third service rooms 122 and 123, respectively, located on the opposite side from the first service room 121. In this example, the first service room 121 forms a supply area for supplying materials to the cleanrooms 111 and 112, while the second and third service rooms 122 and 123 form their respective maintenance areas for maintenance of processing equipment and other service and maintenance work related to the operation of the cleanroom facility 10. The cleanroom facility 10 may include separate corridor areas (not shown) between the processing area 110 and the service area 120, preventing personnel working in cleanrooms 111 and 112 from accessing the service area 120, and vice versa. Figure 8 shows the presence of two different personnel categories with different access privileges: operators 30 who handle the processing equipment 200 in the processing area 110, and service or maintenance personnel 40 who perform maintenance on the processing equipment 200 and supply materials to the processing area 110. In this example, operators 30 are authorized to access the processing area 110 but not the service area 120, while service or maintenance personnel 40 are authorized to access the service area 120 but not the processing area 110. By placing entrances to each area in separate corridors (not shown), the risk of unauthorized access and cross-contamination between the processing and service areas can be reduced.

[0071] During operation, the sealed container 400, transported by a trolley, can be supplied to the supply area 121. Personnel 40 working in the service area 120 can use the trolley to transport the sealed container 400 to a passage 300 located in the wall 130 adjacent to the cleanrooms 111 and 112, where the container 300 is docked and the sealing is removed. On the other side of the wall 130 in the adjacent cleanrooms 111 and 112, an operator 30 can open a latch in the passage to access the material inside the container 400 and transport the material to the user interface of the associated processing equipment 200. The operator 30 may be assisted by visual indicators that associate the passage 300 with specific equipment 200, or vice versa.

[0072] Figure 9 is a schematic diagram of an indicator system 600 for assisting operators in the processing of biopharmaceutical products and the handling of materials supplied to processing equipment 200. The indicator system 600 includes a number of indicators 611, 612, 621, and 622 that can be individually activated to guide personnel working in the processing area. The indicators may be visual indicators, such as indicator lights or light towers. The indicators may operate digitally, i.e., by being switched on or off to communicate information to the operator. Alternatively, the indicators may communicate information by exhibiting different colors, such as green, yellow, or red, and / or by flashing in a predetermined pattern. For the purposes of this disclosure, the indicators are configured or considered to be activated in such a way as to communicate information to the operator in any of the above options. By activating the indicators in this way, the operator can be shown which of the processing equipment to use or from which of the passages to take the material. Thus, each processing equipment can be associated with its own indicator, which may be integrated in the user interface of the processing equipment or placed on or adjacent to the processing equipment. Similarly, each aisle can be associated with its own indicator, which can be integrated at the aisle latch or placed adjacent to the aisle.

[0073] Figure 9 shows an exemplary embodiment of such an indicator system 600 provided in a processing area, the processing area comprising a plurality of processing devices 201, 202 (also called processing equipment) and a plurality of passages 301, 302 located in a wall 130 separating the processing area from an adjacent service area. The processing area and service area can form part of a cleanroom facility configured, for example, similar to the cleanroom facility discussed above in relation to Figures 1 and 2. In this example, the processing area includes a first processing device 201 and a second processing device 202, each having its own user interface 211 through which an operator can supply raw materials taken out from passages 301, 302. The processing devices 201, 202 further include their respective indicators, or processing device indicators, which in this example include indicator lights 621, 622 that can be controlled individually. The processing area further includes a first passage 301 and a second passage 302, each having its own latch 310 through which an operator can access raw materials supplied from an adjacent service area. Each of the passages 301 and 302 includes its own indicator, such as indicator lights 611 and 612, which can be controlled individually, as well as the processing unit indicators 621 and 622.

[0074] The indicator system 600 further includes a control device 630 configured to control the operation of indicators 611, 612, 621, and 622. The control device 630 can be configured, for example, to associate one of the passages 301 and 302 with one of the processing devices 201 and 202 by activating the respective indicators 611, 612, 621, and 622. Thus, the control device 630 can activate the first passage indicator 611 and the second processing device indicator 622 (in this case, by turning on the lights or by generating flashing lights) to indicate to the operator that material should be taken from the first passage 301 and used in the second processing device 202.

[0075] The control device 630 can operate on instructions provided from a predetermined process workflow, which include a set of instructions on how to operate the processing apparatus to produce a desired biopharmaceutical product. In some examples, the control device 630 can be configured to operate indicators in response to queries or triggers provided by an operator. For example, the operator may request instructions related to a specific step in the process workflow, and the indicator system 600 may respond by indicating which processing apparatuses 201, 202 and passages 301, 302 to use.

[0076] In some examples, the control device can operate based on input from an identification means reader. The reader can be configured to read an identification means worn by an operator, as outlined above. The operator can use the identification means to initiate or obtain information about the next steps in the process workflow and to inquire about which aisle to take the material from and which processing unit to transport the material to.

[0077] The identification means can also assist in the generation of digital batch protocols. Operators may be able to have the identification means read when starting a new step in a workflow or when ending a step in a workflow.

[0078] The control device 630 can be configured to maintain a digital inventory of which types of raw materials are accessible through which aisles. In other words, aisles can be pre-loaded with raw materials that will be stored in the aisle until needed. Thus, multiple aisles can be used to store the supply of materials. By keeping track of which types of materials are found in which aisle, the control device 630 can guide the operator on where to retrieve materials from when needed. In this configuration, aisles 301, 302 and the indicator system 600 can be used as a push-type buffer inventory where stored materials are replenished as they are consumed. However, aisles 301, 302 and the indicator system 600 can also be used as a pull-type inventory, where materials are supplied to the aisles when requested, i.e., when materials are needed in processing.

[0079] It will be understood that similar indicators can be used on the service area side of a passageway to guide service area personnel supplying materials into that passageway. Therefore, indicators associated with a particular passageway can be activated to show service area personnel where materials should be inserted.

[0080] The embodiments described above should be understood as illustrating the concept of the present invention. It should be understood that any feature described in relation to any one embodiment may be used alone or in combination with other features described, in combination with one or more features of any other embodiment, or in any combination of any other embodiment. Furthermore, equivalents and modifications not described above may also be used without departing from the scope of the present invention as defined in the appended claims. [Explanation of Symbols]

[0081] 10 Cleanroom facilities 20 materials 110 Processing Area 111 Cleanroom 1 112 Second Cleanroom 113 Cleanroom 115 Processing Area Corridor 120 Service Areas 121 Service Rooms, Supply Areas 122 Second Service Room 123 Third Service Room 125 Service Area Corridor 130 Walls, separation walls 141 Vestibule 142 Vestibule 143 Airlock 144 Airlock 200 Processing equipment or processing device 201 Processing unit, first processing unit 202 Processing Unit, Second Processing Unit 211 User Interface 300 aisles 301 aisle, 1st aisle 302 aisle, second aisle 310 Docking door or latch, latch 320 docking ports 321 Docking Interface 322 Docking Doors 400 Containers, sealed containers 410 Main unit, container body 420 Sealing, container sealing, lids 421 Docking Interface 430 Shipping packaging materials 440 carts 500 modules 510 Side wall, ceiling forming side wall, floor forming side wall 520 Module Roof 530 modular floor 540 Interconnection Structure 542 Bridge Member 600 Indicator System 611 Indicator, Indicator Light, First Aisle Indicator 612 Indicator, Indicator Light 621 Indicator, Indicator Light, Processing Unit Indicator 622 Indicator, Indicator Light, Processing Unit Indicator, Second Processing Unit Indicator 630 Control device

Claims

1. A cleanroom facility (10) for the manufacture of biopharmaceutical products, A processing area (110) for processing the aforementioned biopharmaceutical product, A service area (120) for supplying the material (20) for the processing of the biopharmaceutical product to the processing area, the service area (120) being separated from the processing area by a wall (130), A passage (300) arranged in the wall, configured to allow the material to be supplied to the processing area, Includes, The passage includes a latch (310) facing the processing area (110) and a docking port (320) facing the service area (120). The docking port is configured to allow docking of a sealed container (400) containing the material into the passage and access to it through the latch. Cleanroom facility (10).

2. A passageway (300) for a cleanroom facility (10) for the manufacture of biopharmaceutical products, It is positioned in a wall (130) that separates the processing area (110) for processing the biopharmaceutical product from the service area (120), This makes it possible to supply the material (20) for the processing of the biopharmaceutical product from the service area to the processing area, It is configured to do the following: A docking port (320) is positioned facing the service area and configured to allow a sealed container (400) to be docked in the passage, A latch (310) is positioned facing the processing area and configured to allow access from the processing area to the material in the docked container, A passage (300) including this.

3. A sealed container (400) for supplying materials (20) for processing biopharmaceutical products in a cleanroom facility, A main body (410) configured to house the aforementioned material, A seal (420) for maintaining a predetermined degree of cleanliness of the aforementioned material, A docking interface (421) configured to dock with a docking port (320) in the passageway, Includes, The passage is located in a wall (130) that separates a processing area (110) for processing the biopharmaceutical product from a service area (120), and the docking port faces the service area. The passage faces the processing area and includes a latch (310) configured to allow access from the processing area to the material in the docked container, in a sealed container (400).

4. A cleanroom facility (10) for the manufacture of biopharmaceutical products, A processing area (110) including first and second clean rooms (111, 112) for processing the biopharmaceutical product, A service area (120) including a service room (121) for supplying the materials (20) for processing the biopharmaceutical product to the processing area, wherein the service room is adjacent to the first and second clean rooms, and the service area (120) Includes, The aforementioned processing area is accessible via the processing area corridor (115), The aforementioned service area is accessible via the service area corridor (125). A cleanroom facility (10) in which the processing area corridor and the service area corridor are separated from each other to prevent the entry of contaminants from the service area corridor into the processing area corridor.

5. The cleanroom facility (10) according to claim 4, wherein the first and second cleanrooms are configured to maintain a first degree of cleanliness, and the service room is configured to maintain a second degree of cleanliness, the second degree being lower than the first degree.

6. The cleanroom facility (10) according to claim 4 or 5, wherein the first and second cleanrooms are accessible from the first side, and the service room is accessible from the second side opposite to the first side.

7. A cleanroom facility (10) for the manufacture of biopharmaceutical products, A processing area (110) for processing the aforementioned biopharmaceutical product, A service area (120) for supplying the material (20) for the processing of the biopharmaceutical product to the processing area, the service area (120) being separated from the processing area by a wall (130), A processing device (210) for processing the aforementioned biopharmaceutical product, Includes, The cleanroom facility (10) includes a processing device that is partially located in the processing area and partially in the service area, and is equipped with a user interface (211) accessible from the processing area.

8. The service area includes a first service room (121) and a second service room (122), the first service room and the second service room are located on either side of the clean rooms (111, 112) of the processing area. The first service room is arranged for the supply of the material (20), The cleanroom facility (10) according to claim 7, wherein one of the processing devices is partially located in the second service room.

9. The cleanroom facility (10) according to claim 7 or 8, wherein one of the processing devices is a chromatography system.

10. The cleanroom facility (10) according to claim 9, wherein the user interface (211) of the chromatography system is located in the processing area, and the rest of the chromatography system (212) is located in the service area.

11. A modular cleanroom facility (10) for the manufacture of biopharmaceutical products, The modular cleanroom facility is formed of a plurality of transportable modules (500) assembled into a processing area (110) for processing the biopharmaceutical product and a service area (120) for supplying materials (20) for processing the biopharmaceutical product to the processing area. Each of the aforementioned modules includes a side wall (510), a module roof (520), and a module floor (530), Each of the aforementioned modules is A first state in which the side walls, modular roof, and modular floor form a self-supporting, transportable structure, A second state in which at least one of the side walls is rearranged to form the ceiling portion of the processing area or service area of ​​the assembled modular cleanroom facility, A modular cleanroom facility (10) is configured to be located at [location].

12. The modular cleanroom facility (10) according to claim 11, wherein the modules are configured to be manufactured in advance, away from the site.

13. An indicator system (600) for a cleanroom facility (10) for the manufacture of biopharmaceutical products, wherein the cleanroom facility is A processing area (110) including a plurality of processing devices (200) for processing the biopharmaceutical product, A passage (300) is positioned on the wall of the processing area and is configured to allow the supply of materials (20) for the processing of the biopharmaceutical product to the processing area, Includes, The indicator system is, The passage indicators (611, 612) associated with the passage, The processing device indicators (621, 622) associated with the processing device, A control device (630) operationally connected to the passage indicator and the processing device indicator, Includes, The control device is configured to operate the passage indicator and the processing device based on workflow instructions for managing the manufacturing of the biopharmaceutical product, and is an indicator system (600).

14. The indicator system (600) according to claim 13, comprising a plurality of passage indicators, each associated with a respective passage, and a plurality of processing unit indicators, each associated with a respective processing unit, wherein the control unit is configured to selectively operate a first of the plurality of passage indicators and a first of the plurality of processing unit indicators, thereby associating a particular passage with a particular processing unit.

15. The indicator system (600) according to claim 13, wherein the passage indicators (611, 612) and the processing device indicators (621, 622) include indicator lights.

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