Methods and systems for manufacturing biopharmaceutical products

Abstract

The present disclosure relates to an adjustable-volume manufacturing system for quality-assured production of biosafety-level classified biopharmaceutical products and a method for adjusting the production capacity of the manufacturing system. The adjustable-volume manufacturing system includes one or more multi-product suits and a control facility configured to control unidirectional flow within a circulation system of the one or more multi-product suits. The circulation system is configured to interconnect the one or more multi-product suits and includes a separate supply system and a return system. The supply system includes at least one inlet, and the return system includes at least one outlet paired with the inlet and provided at a spatially predetermined position from the inlet, and each inlet / outlet pair includes a seal when not connected to an adjacent multi-product suit.

Description

[Technical Field]

[0001] The present disclosure relates to scalable volume manufacturing systems and methods for quality assured manufacturing of biopharmaceutical products associated with biosafety level classifications. [Background technology]

[0002] As the development of novel biopharmaceuticals continues to increase, there is a corresponding need to build specialized manufacturing facilities to accommodate the production of such biopharmaceuticals. Biopharmaceutical production imposes high demands on biosafety to prevent loss of biological integrity, for example, through the release of hazardous chemicals and / or organisms into the environment.

[0003] Biosafety is a term used to describe the prevention mechanisms and measures required for handling biohazardous materials, such as biopharmaceuticals. Biosafety is used to protect against adverse events. Many laboratories that handle biohazardous materials employ a continuous risk management assessment and implementation process for biosafety, which is classified by biosafety levels, which refer to biocontainment precautions for laboratory work with infectious materials. Thus, a biosafety level is a set of biocontainment precautions required to isolate hazardous biological agents within a sealed laboratory facility. Containment levels range from the lowest, Biosafety Level 0 (BSL-0), to the highest, Biosafety Level 4 (BSL-4).

[0004] At the lowest levels of biosafety, precautions may consist of regular hand washing and minimal protective equipment. At higher biosafety levels, precautions may include airflow systems, multiple containment rooms, sealed containers, positive-pressure personnel suits, established protocols for all procedures, extensive personnel training, and high levels of security to control access to the facility. As a result, higher biosafety levels result in higher production costs and higher costs to provide the production facilities that can enable such production.

[0005] The development of new biopharmaceuticals typically requires significant investments of time and capital to translate scientific discoveries into new medicines and to build specialized manufacturing facilities and equipment. Advanced technologies drive biopharmaceutical manufacturing in conjunction with research and development, requiring significant scientific know-how and infrastructure. In addition, new medicines drive the need for more complex manufacturing processes, more advanced equipment, and higher biosafety levels.

[0006] Biopharmaceutical production at higher biosafety levels requires custom-built production facilities and extensive and continuous personnel training, which places geographic limitations on production expansion. It is usually more cost-effective to increase production in locations where production facilities are already established than to establish production in new geographic locations. While geographic clustering has previously allowed for more efficient handling of staffing and supply issues, the time and cost required to adjust production volume, such as by expanding production infrastructure, i.e., production plants, presents a major obstacle to increasing production. Overall, current production trends demonstrate the need for increased manufacturing flexibility without compromising quality, while achieving operational efficiencies that can help reduce costs. Summary of the Invention [Problem to be solved by the invention]

[0007] It is an object of the present disclosure to provide a solution that seeks to mitigate, alleviate, or eliminate one or more of the above-mentioned deficiencies in the art, and to provide a solution for flexible and cost-effective manufacturing of biopharmaceutical products, more specifically a scalable volume manufacturing system for manufacturing according to a predetermined biosafety level classification.

[0008] According to a first aspect, this object is achieved by a volume-adjustable manufacturing system for quality-assured production of biosafety-level classified biopharmaceutical products, the volume-adjustable manufacturing system comprising one or more multi-product suits and a control facility configured to control unidirectional flow within a circulation system of the one or more multi-product suits. The circulation system is configured to interconnect the one or more multi-product suits and comprises separate supply and return systems. The supply system comprises at least one inlet, and the return system comprises at least one outlet paired with the inlet and provided at a spatially predetermined position from the inlet, each inlet / outlet pair comprising a seal when not connected to an adjacent multi-product suit.

[0009] Scalable volume manufacturing systems offer the advantage of allowing unprecedented flexibility in scale, both in terms of flexibility in production volume and in terms of time to production start.

[0010] In some embodiments, each inlet / outlet pair is prepared for connection to additional inlet / outlet pairs of additional multi-product suits, and the seals of the inlet / outlet pairs are configured to be broken to expand the adjustable volume manufacturing system with additional multi-product suits. In alternative embodiments, each inlet / outlet pair is prepared for connection to additional inlet / outlet pairs of additional multi-product suits, and the inlet / outlet pairs are configured to be sealed when the connection to the additional inlet / outlet pair is broken. Thus, the disclosed adjustable volume manufacturing system allows for easy production expansion or production limiting by adding or removing additional multi-product suits.

[0011] In some embodiments, the adjustable volume manufacturing system includes a first multi-product suit and a second multi-product suit, an inlet / outlet pair of the first multi-product suit connected to an inlet / outlet pair of the second multi-product suit, and a control facility configured to control unidirectional flow within a circulation system interconnecting the first multi-product suit and the second multi-product suit.

[0012] In some embodiments, the supply system is configured as a spine within a central portion of the adjustable volume manufacturing system and is at least partially surrounded by one or more multi-product suits, and the return system of each multi-product suit is configured as a passageway along the periphery of the adjustable volume manufacturing system.

[0013] In some embodiments, each multi-product suite comprises a first communication interface to a supply system and a second communication interface to a return system.

[0014] In some embodiments, the biosafety level classification is Biosafety Level 2 (BSL2).

[0015] In some embodiments, each multi-product suite is interoperably separate from other multi-product suites.

[0016] In some embodiments, one or more multi-product suites are micro-modules configured for biopharmaceutical manufacturing, with separate supply and return systems connected to a macro-structure comprising hydration and storage facilities.

[0017] According to a second aspect, the above object is also achieved by a method for expanding the production capacity of a manufacturing system for quality-assured production of biopharmaceutical products associated with biosafety level classifications. The manufacturing system comprises a first multi-product suit and a control facility configured to control unidirectional flow within a circulation system of the first multi-product suit. The circulation system includes separated supply and return systems. The supply system has an inlet, and the return system has an outlet paired with the inlet and provided at a spatially predetermined position from the inlet, the inlet / outlet pair comprising a seal. The method includes positioning a second multi-product suit adjacent to the first multi-product suit such that the spatially predetermined positions of the inlet / outlet pairs of the second multi-product suit are arranged to mirror the spatially predetermined positions of the inlet / outlet pairs of the first multi-product suit. The method further includes interconnecting the inlet / outlet pairs of the first multi-product suit with the inlet / outlet pairs of the second multi-product suit and breaking the seal of each inlet / outlet pair.

[0018] In some embodiments, the biosafety level classification is Biosafety Level 2 (BSL2).

[0019] In some embodiments, the interconnecting step comprises verifying that the connection formed between the inlet / outlet pair of the first multi-product suit and the inlet / outlet pair of the second multi-product suit complies with requirements for quality assured manufacturing of biosafety level 2 (BSL2) classified biopharmaceutical products, and breaking the seal following such verification.

[0020] In some embodiments, quality assured manufacturing of biopharmaceutical products associated with a biosafety level classification is verified for each of a first multi-product suit and a second multi-product suit, including verification of each inlet / outlet pair, wherein the verification of the second multi-product suit is uncorrelated with the verification of the first multi-product suit, and wherein the verification of each inlet / outlet pair includes pre-verifying the connections to be made.

[0021] According to a third aspect, the above object is also achieved by a method for reducing the throughput capacity of a manufacturing system for quality-assured production of biopharmaceutical products associated with a biosafety level classification. The manufacturing system comprises at least two multi-product suits and a control equipment configured to control unidirectional flow within a circulation system of one or more of the multi-product suits. The circulation system is configured to interconnect the one or more multi-product suits and comprises a separate supply system and a return system. Each multi-product suit comprises at least one inlet to the supply system and at least one outlet from the return system, the outlet being paired with the inlet and provided at a spatially predetermined location from the inlet. The two multi-product suits are positioned adjacent to each other with the inlet / outlet pair of the first multi-product suit interconnected with the inlet / outlet pair of the second multi-product suit. The method includes the steps of disconnecting the first and second multi-product suits by sealing the inlet / outlet pairs of the first and / or second multi-product suits, and adapting the control equipment to control unidirectional flow within the circulation system of the first multi-product suit.

[0022] The foregoing will be apparent from the following more particular description of exemplary embodiments, as illustrated in the accompanying drawings, in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon depicting exemplary embodiments. [Brief explanation of the drawings]

[0023] [Figure 1] FIG. 1 depicts an exemplary schematic layout of an adjustable volume manufacturing system of the present disclosure. [Figure 2a] FIG. 1 depicts an exemplary configuration of an adjustable volume manufacturing system with a first multi-product suit. [Figure 2b]FIG. 1 depicts an exemplary configuration of an adjustable volume manufacturing system comprising interconnected first and second multi-product suites. [Figure 2c] FIG. 1 depicts an exemplary configuration of a volume adjustable manufacturing system comprising first to third interconnected multi-product suits. [Figure 3] 1 is a flowchart depicting exemplary method steps according to some embodiments. [Figure 4] 1 is a flowchart depicting exemplary method steps according to some embodiments. [Figure 5] FIG. 1 discloses an exemplary configuration of a multi-product suite and flow for producing biohazardous compounds. [Figure 6] FIG. 1 illustrates a schematic diagram of an exemplary control facility. DETAILED DESCRIPTION OF THE INVENTION

[0024] Various embodiments of a volume-adjustable manufacturing system and a method for adjusting the production capacity of a manufacturing system are described more fully hereinafter with reference to the accompanying drawings, although some, but not all, embodiments of the manufacturing system and related methods are disclosed. Advantages and features of the present disclosure and methods for achieving them will become apparent from the following description of exemplary embodiments. However, the present disclosure is not limited to the exemplary embodiments disclosed herein and may be embodied in a variety of different ways. The exemplary embodiments are provided so that the disclosure will be thorough and complete, and so that the scope of the disclosure will be fully conveyed to those skilled in the art. It should be noted that the scope of the present disclosure is defined only by the claims.

[0025] The terminology used herein is for the purpose of describing particular aspects of the disclosure only and is not intended to limit the scope of the disclosure. As used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise.

[0026] It should be noted that the term "comprise" does not necessarily exclude the presence of other elements or steps than those listed. Moreover, it should be noted that any reference signs do not limit the scope of the claims.

[0027] Detailed descriptions of well-known functions and structures incorporated in the present application are omitted to avoid obscuring the subject matter of the present disclosure. Furthermore, the terms or words used in the present specification and claims should not be interpreted only in the conventional dictionary definition, but should be interpreted in the meaning and concept corresponding to the technical idea of ​​the present invention.

[0028] FIG. 1 depicts an exemplary configuration of a scalable volume manufacturing system that may be used with various embodiments of the present invention for quality-assured, scalable manufacturing of biopharmaceutical products associated with biosafety level classifications. The scalable volume manufacturing system 100 disclosed in FIG. 1 includes a first multi-product suite 110 for manufacturing, for example, a first compound, and optionally includes second and third multi-product suites 111, 112, where the second multi-product suite 111 may be implemented to enable scale-up of production of Compound A. The third multi-product suite 112 is disclosed as enabling greater production variability within the manufacturing system, for example, by producing Compound B in an expanded production facility. The third multi-product suite 112 may, of course, be used for Compound A if there is a need for a significant increase in production of Compound A. Additionally, while the first and second multi-product suits 110, 111 are shown as being dedicated to the production of Compound A, they may actually be used for the production of multiple compounds, and the first and second multi-product suits 110, 111 may include multiple biopharmaceutical production environments separated from one another but connected to the multi-product suit's unidirectional circulation system. Control equipment located within one or more multi-product suits is configured to control unidirectional flow within the circulation system of the one or more multi-product suits. The circulation system is configured to interconnect one or more multi-product suits, providing a circulation system within each multi-product suit. As discussed further below, with reference to FIGS. 2a-2c, the circulation system includes separate supply and return systems, the supply system including at least one inlet, the return system including at least one outlet paired with the inlet and provided at a spatially predetermined location from the inlet, and each inlet / outlet pair including a seal when not connected to an adjacent multi-product suit. According to some embodiments, the inlet and outlet are located at the same floor level of the building block.

[0029] FIG. 2a depicts an exemplary embodiment of an adjustable-volume manufacturing system configuration that can be used with various embodiments of the present disclosure for quality-assured, adjustable-volume manufacturing of biopharmaceutical products associated with a biosafety level classification. Initially, the adjustable-volume manufacturing system 200 of the present disclosure includes a first multi-product suit 210 and a control facility, e.g., a processing device located within the manufacturing system area, in a separate control center, or as a cloud solution. The control facility is configured to control unidirectional flow within a circulation system of the multi-product suit 210. The circulation system is configured to interconnect one or more multi-product suits. The circulation system is also configured to enable the circulation of personnel, raw materials, products, and waste required to comply with the biosafety level classification of the production facility, i.e., the multi-product suit. According to some aspects of the present disclosure, the biosafety level classification is Biosafety Level 2 (BSL2), implying unidirectional flow of personnel, raw materials, products, and waste. Any type of biopharmaceutical production requiring BSL1 or BSL2 can be produced within the multi-product suite of manufacturing facilities, conforming to BSL2 requirements. Such biomolecules include mAbs, Rec proteins, vaccines, viral vectors, insulin, etc.

[0030] As shown in FIG. 2a, the circulation system includes separate supply and return systems, where supply system 220 includes at least one inlet 220a, and return system 230 includes at least one outlet 230a paired with inlet 220a and provided at a predetermined spatial location from the inlet, e.g., with each inlet 220a and outlet 230a arranged at a predetermined respective width and a predetermined distance d from each other. Each inlet / outlet pair 220a / 230a may include a seal 240 when not connected to an adjacent multi-product suite, e.g., a first portion of seal 240 sealing inlet 220a and a second portion of seal 240 sealing outlet 230a, whereby the first and second portions of seal 240 may be physically separated from each other. According to some embodiments, the inlet and outlet are located at the same floor level of the building block.

[0031] Manufacturing system 200 further comprises a cleanroom area 260, i.e., an area within which biocontainment precautions dictated by a given biosafety level classification must be met. In addition to the return system, examples of areas within which such biocontainment precautions must be observed include seed areas, USP areas, DSP areas, and laboratory areas. Manufacturing system 200 also includes a prep area 250, which provides an important contribution to biopharmaceutical manufacturing without the need for strict biocontainment precautions. Such areas include an entrance, office, storage, utility areas, support areas, media preparation areas, and buffer preparation areas. Some further details related to production flow between these areas are provided below with reference to FIG. 5.

[0032] In some embodiments, each inlet / outlet pair 220a, 230a is provided for connection to additional inlet / outlet pairs of additional multi-product suits, and the seal 240 of the inlet / outlet pair is configured to be broken to expand the adjustable volume manufacturing system with additional multi-product suits. In some embodiments, each inlet / outlet pair 220a, 230a is provided for connection to additional inlet / outlet pairs of additional multi-product suits, and the inlet / outlet pair is configured to be sealed with seal 240 when the connection to the additional inlet / outlet pair is broken. The disclosure of FIG. 2a also depicts seal 240' at the edge of reserve region 250. Because biosafety level classification does not apply to this region, interconnection of this region with a corresponding reserve region of an adjacent multi-product suit does not require safety level verification. The ability to achieve quick connection of these regions may also provide a user benefit. Accordingly, the multi-product suit may also be configured with a breakable seal here.

[0033] FIG. 2b depicts an exemplary embodiment of a manufacturing system configuration that can be used with embodiments in which the manufacturing volume is adjustable for increased production. For the embodiment of FIG. 2a, the production is associated with quality-assured manufacturing of biopharmaceutical products associated with a biosafety level classification. In the disclosure of FIG. 2b, first and second multi-product suits are connected, where the adjustable-volume manufacturing system 200 comprises first and second multi-product suits 210, 215. An inlet / outlet pair providing access to the separate supply and return systems of the first multi-product suit is connected to an inlet / outlet pair providing access to the separate supply and return systems of the second multi-product suit. The control equipment is configured to control unidirectional flow within the circulation system formed by the supply and return systems interconnecting the first and second multi-product suits. If the first and second multi-product suits are validated for the same biosafety level classification, e.g., BSL2, pre-validation of each portion of the manufacturing system allows for rapid validation of the connection region 225 formed when the two multi-product suits are connected and the seal is broken for the corresponding biosafety level classification. As a result, a major benefit of the present disclosure is the ability to offer scalable production conforming to stringent biocontainment precautions, requiring only validation of the connection structure prior to use.

[0034] In the disclosure of FIG. 2b, the connection between the inlet / outlet pairs of two adjacent multi-product suits is formed by aligning these inlet / outlet pairs. However, in some embodiments, the interconnection may be achieved by using an intermediate connector between each inlet / outlet pair. Such a solution offers the advantage that two multi-product suits may be coupled together even when environmental obstacles exist to placing the multi-product suits immediately adjacent to one another. When one or more intermediate connectors are used, each connector may be sealed prior to installation, and for each connection formed between a multi-product suit and an intermediate connector, the procedure disclosed below may be used to establish the connection between the two multi-product suits.

[0035] In some embodiments, the supply system 220 is configured as a backbone within a central portion of the adjustable volume manufacturing system and is at least partially surrounded by one or more multi-product suits, such as by a clean room area 260. According to various embodiments, the return system 230 for each multi-product suit may be configured as a passageway along the periphery of the adjustable volume manufacturing system that at least partially surrounds the clean room area.

[0036] FIG. 2c depicts an exemplary embodiment of a manufacturing system configuration that can be used with various embodiments of the present invention for quality-assured, scalable manufacturing of biopharmaceutical products associated with biosafety level classifications. In the disclosure of FIG. 2c, an expanded manufacturing system 200 is achieved using multi-product suits 211, 212 configured to connect with additional multi-product suits. As a result, the second and third multi-product suits 211, 212 each include two inlet / outlet pairs with respective outlets provided at spatially predetermined locations from the corresponding inlets, and each inlet / outlet pair includes a seal 240 when not connected to an adjacent multi-product suit. In some embodiments, each multi-product suit is interoperably separate from the other multi-product suits, implying that compound A may be manufactured in a first multi-product suit while compound B is manufactured in a second multi-product suit that shares a circulation system with the first multi-product suit. When manufacturing under BSL2 requirements, a fresh air supply may be provided to the first and second multi-product suits from a common air conditioning unit. However, to meet BSL2 requirements, each suit would have its own air circulation system, independent of the circulation systems of the other suits. Of course, it is also possible to use separate air conditioning units for each multi-product suit. While this would mean a slight increase in the cost of the infrastructure required for production, the advantage of also having such a separation of supply systems is shorter interruptions that occur during the phase of expanding the production system with one or more additional multi-product suits.

[0037] Turning to FIG. 3, a method for expanding the production capacity of a manufacturing system for quality-assured production of biopharmaceutical products associated with biosafety level classifications is disclosed. The manufacturing system includes one or more multi-product suits, e.g., as disclosed in FIGS. 2a-2c, and a control facility configured to control unidirectional flow of the one or more multi-product suits within a circulation system. The circulation system is configured to interconnect the one or more multi-product suits and includes separate supply and return systems. The supply system includes an inlet, and the return system includes an outlet paired with the inlet and provided at a spatially predetermined location from the inlet, the inlet / outlet pair including a seal. The method includes a step S31 of positioning a second multi-product suit adjacent to a first multi-product suit such that the spatially predetermined location of the inlet / outlet pair of the second multi-product suit is positioned to mirror the spatially predetermined location of the inlet / outlet pair of the first multi-product suit. In a subsequent step, the inlet / outlet pairs of the first multi-product suit are interconnected with the inlet / outlet pairs of the second multi-product suit (S32) and the seal of each inlet / outlet pair is broken (S34).

[0038] In some embodiments, the method includes verifying a first multi-product suit for manufacturing according to a biosafety level classification and / or verifying a second multi-product suit for manufacturing according to a biosafety level classification prior to installation of the multi-product suits, where the verification of each multi-product suit is performed independently of the verification of the other multi-product suits, i.e., representing a pre-verification process for each production facility. Thus, in some embodiments, quality-assured manufacturing of biopharmaceutical products associated with a biosafety level classification is verified for each of the first multi-product suit and the second multi-product suit, including verification of each inlet / outlet pair, where the verification of the second multi-product suit is uncorrelated with the verification of the first multi-product suit, and where the verification of each inlet / outlet pair includes pre-verifying the connections to be made. In some embodiments, verification is performed for a biosafety level classification of Biosafety Level 2 (BSL2).

[0039] In some embodiments, the interconnecting step comprises a step S33 of verifying that the connection formed between the inlet / outlet pair of the first multi-product suit and the inlet / outlet pair of the second multi-product suit complies with the requirements for quality assured manufacturing of biosafety level 2 (BSL2) classified biopharmaceutical products, and a step S34 of breaking the seal only following such verification.

[0040] Turning to FIG. 4, a method for reducing the throughput capacity of a manufacturing system for quality-assured production of biopharmaceutical products associated with biosafety level classifications is disclosed. The manufacturing system includes two or more multi-product suits, such as those disclosed in FIG. 2b or 2c, and a control equipment configured to control unidirectional flow within a circulation system of one or more multi-product suits. The circulation system is configured to interconnect the one or more multi-product suits and includes a separate supply system and a return system. Each multi-product suit includes at least one inlet to the supply system and at least one outlet from the return system, the outlet paired with the inlet and provided at a spatially predetermined location from the inlet. Two multi-product suits are positioned adjacent to each other, with the inlet / outlet pair of the first multi-product suit interconnected with the inlet / outlet pair of the second multi-product suit. The method includes step S41 of disconnecting the first multi-product suit and the second multi-product suit by sealing the inlet / outlet bearings of the first multi-product suit and / or the second multi-product suit, and step S42 of adapting the control equipment to control unidirectional flow within the circulation system of the first multi-product suit.

[0041] Turning to Figure 5, details are provided schematically for the above-discussed adjustable-volume manufacturing system, including a multi-product suit configured for BSL2. In the disclosure of Figure 5, areas subject to corresponding biosafety level requirements are indicated by corresponding patterns. Arrows are used to indicate the various flows of raw materials, products, and waste that may occur within the manufacturing system. The manufacturing system includes a utility area 510 and an entrance / office / storage area 520, which are not subject to specific biocontainment precaution requirements. The manufacturing system also includes an entrance corridor 560, a support area 570, a media preparation area 580, and a buffer preparation area 590, which require several safety precautions, but these precautions do not meet BSL2 requirements. Areas where specific BSL2 requirements must be observed include an exit corridor 530 (i.e., return system) and the cleanroom facility (i.e., multi-product suit 540, including the seed area, USP area, and DSP area). While the disclosure of FIG. 5 indicates that the seed area and USP area should be subject to BSL2 requirements, embodiments in which different safety requirements apply to different areas within the biosafety environment are also within the scope of this disclosure. There is a supply of personnel and raw materials from the entrance corridor 560 to the biosafety area, i.e., a supply system. As depicted by the arrows in FIG. 5, raw materials may be received into the supply system from the media preparation area 580 or the buffer preparation area 590. A support area / laboratory 550 may also be present, and BSL2 requirements must be observed. The entrance and exit corridors, i.e., the supply system and return system, are located a distance d from each other. If the manufacturing system is to be expanded, corresponding mirrored production equipment may be located adjacent to and connected to the multi-product suit of FIG. 5. As depicted in FIG. 5, there may be different safety requirements associated with the supply system and return system, which may affect the requirements for each connection between two adjacent multi-product suits.

[0042] According to some embodiments, each multi-product suit comprises a first communication interface to a supply system and a second communication interface to a return system. The first communication interface may comprise a material delivery interface, for example, for delivering raw materials as depicted in FIG. 5. The second communication interface may comprise a product delivery interface. In some embodiments, the material delivery interface and the product delivery interface are provided by an airlock. In some embodiments, the material delivery comprises feed materials delivered to a designated multi-product suit within a disposable device, the feed materials comprising custom media and / or buffers. In some embodiments, the multi-product suit is configured to receive material delivery of disposable product-contact components.

[0043] In some embodiments, each multi-product suit comprises at least one further communication interface (also referred to as a personnel access interface) controlled by a control unit within the multi-product suit, the at least one further communication interface being arranged to control personnel access to / from the multi-product suit. In some embodiments, one or more multi-product suits are micro-modules configured for biopharmaceutical manufacturing, with separate supply and return systems connected to a macro-structure comprising hydration and storage facilities.

[0044] 6 shows a schematic diagram of an exemplary control facility 600 configured to control unidirectional flow within a circulation system of one or more multi-product suites. The control facility includes a memory 631, a processing circuit 632, and an input device 633. The control facility may also include a data interface that provides data connectivity with the circulation system and the supply and return systems contained within the circulation system.

[0045] In general, the term processing circuitry may refer to, for example, one or more computers, computing entities, distributed systems, processing devices, processing entities, and / or any combination of devices or entities adapted to perform the functions, operations, and / or processes described herein. Such functions, operations, and / or processes may include, for example, transmitting, receiving, operating, processing, storing, creating / generating, and / or similar terms used herein.

[0046] The control facility 600 is configured to execute a computer program product including at least one non-transitory computer-readable storage medium having computer-executable program code instructions stored therein. When the program code instructions are executed by the processing circuitry 632, control of unidirectional flow within the circulatory system of one or more multi-product suits may be achieved. That is, by controlling unidirectional flow, personnel, raw materials, and other types of feed materials are provided to the multi-product suits by a supply system of the circulatory system and removed from the multi-product suits by a return system of the circulatory system. In particular, the control facility is configured to ensure that there is no direct communication between the supply system and the return system.

[0047] In the drawings and specification, illustrative embodiments of the present disclosure have been disclosed. However, many variations and modifications can be made to these embodiments without substantially departing from the principles of the present disclosure. Accordingly, the present disclosure should be regarded as illustrative rather than restrictive, and should not be regarded as limited to the specific embodiments described above. Thus, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation.

[0048] The descriptions of exemplary embodiments provided herein are presented for illustrative purposes. The descriptions are not intended to be exhaustive or to limit the exemplary embodiments to the precise forms disclosed; modifications and variations are possible in light of the above teachings or may result from various alternative implementations of the provided embodiments. The examples discussed herein have been chosen and described to explain the principles and properties of various exemplary embodiments and their practical application, so as to enable those skilled in the art to utilize the exemplary embodiments in various ways and with various modifications suited to the particular uses expected.

[0049] Illustrative embodiments have been disclosed in the drawings and detailed description. However, many variations and modifications to these embodiments are possible. Accordingly, although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation, and the scope of the embodiments is defined by the appended claims.

Claims

1. 1. A scalable volume manufacturing system (200) for quality assured production of biopharmaceutical products associated with a biosafety level classification, such as Biosafety Level 2 (BSL2), comprising: the adjustable volume manufacturing system comprising two or more multi-product suits (210, 215) and a control facility configured to control unidirectional flow of the two or more multi-product suits within a circulation system; the circulation system is configured to interconnect the two or more multi-product suits; the circulation system comprises a separate supply system and a return system; The supply system (220) comprises at least one inlet (220a); the return system (230) comprises at least one outlet (230a) paired with the inlet and provided at a predetermined spatial location from the inlet; the control facility is configured to control unidirectional flow such that feed material is provided to the multi-product suit by the supply system of the circulation system and discharged from the multi-product suit by the return system of the circulation system, and further ensure that there is no direct communication between the supply system and the return system; each inlet / outlet pair (220a, 230a) is provided with a seal (240) when not connected to an adjacent multi-product suite; the scalable volume manufacturing system comprises a reserve area, and the biosafety level classification does not apply to the reserve area; The supply system (220) is surrounded by a clean room area (260); The inlet / outlet pairs of the multi-product suite are connected to the inlet / outlet pairs of adjacent multi-product suites by intermediate connectors; Volumetrically adjustable manufacturing system.

2. (a) each inlet / outlet pair is prepared for connection to an additional inlet / outlet pair of an additional multi-product suit, the seal of the inlet / outlet pair being configured to be broken to expand the adjustable volume manufacturing system with the additional multi-product suit; or (b) the or each inlet / outlet pair is provided for connection to a further inlet / outlet pair of a further multi-product suit, the inlet / outlet pair being configured to be sealed when the connection to the further inlet / outlet pair is broken; The adjustable volume manufacturing system of claim 1 .

3. 3. The adjustable volume manufacturing system of claim 1 or 2, wherein the adjustable volume manufacturing system includes a first multi-product suit and a second multi-product suit, an inlet / outlet pair of the first multi-product suit connected to an inlet / outlet pair of the second multi-product suit, and the control equipment is configured to control unidirectional flow within a circulation system interconnecting the first multi-product suit and the second multi-product suit.

4. The adjustable volume manufacturing system of any one of claims 1 to 2, wherein the supply system is configured as a spine within a central portion of the adjustable volume manufacturing system and is at least partially surrounded by the two or more multi-product suits, and the return system of each multi-product suit is configured as a passageway along the periphery of the adjustable volume manufacturing system.

5. The adjustable volume manufacturing system of any one of claims 1 to 4, wherein each multi-product suit comprises a first communication interface to the supply system and a second communication interface to the return system.

6. The adjustable volume manufacturing system of any one of claims 4-5, wherein the first communication interface comprises a material delivery interface and the second communication interface comprises a product delivery interface.

7. 10. The scalable volume manufacturing system of claim 6, wherein material delivery comprises supply materials delivered to designated multi-product suites within disposable devices, said supply materials comprising custom media and / or buffers.

8. The adjustable volume manufacturing system of any one of claims 6-7, wherein the multi-product suite is arranged to receive material delivery of disposable product contact parts.

9. (a) each multi-product suite comprises at least one further communications interface controlled by a control unit within said multi-product suite, said at least one further communications interface being arranged to control personnel access to / from said multi-product suite; and / or (b) the two or more multi-product suites are micro-modules configured for biopharmaceutical manufacturing, and the separated supply and return systems are connected to a macro-structure comprising hydration and storage facilities; The volume-adjustable manufacturing system according to any one of claims 1 to 8.

10. 1. A method for expanding the production capacity of a manufacturing system for quality assured production of biopharmaceutical products associated with a biosafety level classification, such as Biosafety Level 2 (BSL2), comprising: the manufacturing system comprises a first multi-product suit and a control facility configured to control unidirectional flow of the first multi-product suit within a circulatory system; the circulation system comprises a separate supply system and a return system; the supply system includes an inlet; the return system includes an outlet paired with the inlet and provided at a predetermined spatial location from the inlet; the inlet / outlet pair comprises a seal; the control facility is configured to control unidirectional flow such that feed material is provided to the multi-product suit by the supply system of the circulation system and discharged from the multi-product suit by the return system of the circulation system, and further ensure that there is no direct communication between the supply system and the return system; the manufacturing system comprises a reserve area, and the biosafety level classification does not apply to the reserve area; The method comprises: (S31) positioning a second multi-product suit adjacent to the first multi-product suit such that the spatially predetermined locations of the inlet / outlet pairs of the second multi-product suit are arranged to mirror the spatially predetermined locations of the inlet / outlet pairs of the first multi-product suit; interconnecting the inlet / outlet pairs of the first multi-product suite with the inlet / outlet pairs of the second multi-product suite using intermediate connectors (S32); and breaking the seal of each inlet / outlet pair (S33), The method, wherein the delivery system (220) is surrounded by a clean room area (260).

11. 11. The method of claim 10, wherein the interconnecting step comprises verifying that the connection formed between the inlet / outlet pair of the first multi-product suit and the inlet / outlet pair of the second multi-product suit complies with requirements for quality-assured manufacturing of biosafety level 2 (BSL2) classified biopharmaceutical products, and breaking the seal following such verification.

12. 12. The method of claim 11, wherein quality assured manufacturing of biopharmaceutical products associated with the biosafety level classification is verified for each of the first multi-product suit and the second multi-product suit, including verification of each inlet / outlet pair, wherein verification of the second multi-product suit is uncorrelated with verification of the first multi-product suit, and wherein verification of each inlet / outlet pair includes pre-verifying the connections to be made.

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