Customizable facility

Abstract

A campus for making at least one pharmaceutical product has one or more customizable facilities each configured to manufacture at least one pharmaceutical product, a media / buffer plant, and a utility building connected by a utility line to the media / buffer plant and / or the one or more customizable facilities to provide at least one first utility to the media / buffer plant and / or the one or more customizable facilities via the utility line.

Description

[0001] This application is a divisional application of Chinese invention patent application filed on July 25, 2017, with application number 201780057898.8 and invention title "Customizable Facility". Technical Field

[0002] This disclosure relates to customizable facilities that enable users to manufacture multiple products within the facility. In particular, this disclosure relates to customizable facilities for manufacturing products in a cleanroom environment. Background Technology

[0003] Traditional structures used for manufacturing products, such as monoclonal antibodies and microbial products, do not allow for efficient use of structural space. The layout of traditional structures often limits their ease of configuration or expansion to manufacture new product lines. Therefore, manufacturing facilities are needed that allow users to efficiently utilize shared resources across product lines and easily modify facilities to accommodate new manufacturing processes or new production lines with reduced facility downtime. Summary of the Invention

[0004] This disclosure provides a customizable facility for manufacturing at least one product, utilizing at least one production process (e.g., a production process using a fermentation unit and a purification unit). According to one aspect of this disclosure, the customizable facility includes a shell, at least one central unit located within the shell, and at least one modular unit, each modular unit located within the shell. The shell, central unit, and modular units are configured and arranged to maximize the speed and ease of modifying different ranges of manufacturing capacity.

[0005] According to another aspect of this disclosure, a customizable facility for manufacturing at least one pharmaceutical product includes at least one central unit. At least one modular unit communicates with at least one central unit, such that the at least one central unit provides utility to the at least one modular unit.

[0006] In some implementations, the customizable facility includes a housing, wherein at least one central unit is at least partially located within the housing, and at least one modular unit is at least partially located within the housing.

[0007] In some implementations, at least one module unit includes at least one of the following: a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a media buffer facility, an office, a personnel unit, a production unit, a fill-finish unit, a dosage preparation unit, and a packaging unit.

[0008] In some implementations, at least one of the at least one module unit is directly adjacent to at least one central unit.

[0009] In some implementations, at least one module unit comprises a plurality of module units arranged to maximize the number of module units within the housing while minimizing the housing footprint.

[0010] In some implementations, each of the plurality of module units is directly adjacent to at least one of the at least one central unit and another of the plurality of module units.

[0011] In some implementations, at least one central unit and multiple module units form a hub and spoke formation.

[0012] In some implementations, at least one central unit and multiple module units are arranged in an H-shaped layout.

[0013] In some implementations, customizable facilities include bioreactors supported on the ground surface within the shell.

[0014] In some implementations, the customizable facility includes a bioreactor supported within at least one of the modular units.

[0015] In some implementations, the outer wall of the customizable facility is one of the following: formed by the housing, which completely seals the at least one central unit and the at least one module unit; and formed by at least one of the outer walls of the housing and the at least one central unit and the at least one module unit.

[0016] In some embodiments, the housing includes at least one sidewall surrounding the at least one central unit and the at least one module unit, and a roof fixed to the upper edge of the at least one sidewall, the roof extending over the at least one central unit and the at least one module unit.

[0017] In some implementations, at least one of the module units is a clean room.

[0018] In some implementations, at least one module unit is configured for cell therapy operations.

[0019] According to another aspect of this disclosure, a method of assembling a facility for manufacturing at least one pharmaceutical product includes: providing at least one central unit; and providing at least one modular unit that communicates with the at least one central unit, such that the at least one central unit provides utility to the at least one modular unit.

[0020] In some embodiments, the method includes providing a housing; positioning the at least one central unit at least partially within the housing; and positioning the at least one module unit at least partially within the housing.

[0021] In some implementations, at least one module unit includes at least one of the following: a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a culture medium buffer facility, an office, a personnel unit, a production unit, a filling-finished product unit, a dosage preparation unit, and a packaging unit.

[0022] In some implementations, the at least one module unit comprises a plurality of module units arranged to maximize the number of module units within the housing while minimizing the housing's footprint.

[0023] In some implementations, each of the plurality of module units is directly adjacent to at least one of the at least one central unit and another of the at least one module unit.

[0024] In some implementations, at least one central unit and multiple module units form a spoke-shaped structure.

[0025] In some implementations, at least one central unit and multiple module units are arranged in an H-shaped layout.

[0026] In some embodiments, the method includes one of the following: supporting the bioreactor on the ground within the shell and supporting the bioreactor within one of the at least one modular unit.

[0027] In some implementations, the outer wall of the customizable facility is one of the following: formed by the housing, which completely seals the at least one central unit and the at least one module unit; and formed by at least one of the outer walls of the housing and the at least one central unit and the at least one module unit.

[0028] In some embodiments, the housing includes at least one sidewall surrounding the at least one central unit and the at least one module unit, and a top cover fixed to the upper edge of the at least one sidewall, the top cover extending over the at least one central unit and the at least one module unit.

[0029] In some implementation schemes, at least one pharmaceutical product is a biosimilar product.

[0030] According to another aspect of this disclosure, a campus for manufacturing at least one pharmaceutical product includes a customizable facility configured to manufacture at least one pharmaceutical product; a culture medium / buffer plant configured to supply at least one processing material to the customizable facility; and a utility building connected by a utility line to at least one of the culture medium / buffer plant and the customizable facility to provide at least one first utility via the utility line.

[0031] In some implementations, the warehouse is located near customizable facilities.

[0032] In some implementations, at least one primary utility includes steam supply and / or air supply.

[0033] In some implementations, the customizable facility includes at least one central unit and at least one module unit, the at least one module unit communicating with the at least one central unit such that the at least one central unit provides at least one second utility to the at least one module unit.

[0034] In some implementations, the customizable facility also includes a housing. At least one central unit is at least partially located within the housing, and at least one modular unit is at least partially located within the housing.

[0035] In some implementations, at least one module unit includes at least one of the following: a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a culture medium buffer facility, an office, a personnel unit, a production unit, a filling-finished product unit, a dosage preparation unit, and a packaging unit.

[0036] In some implementations, the first utility in at least one first utility is the same as the second utility in at least one second utility.

[0037] In some implementations, the first utility in at least one first utility is different from the second utility in at least one second utility.

[0038] In some implementations, at least one module unit comprises multiple module units arranged to maximize the number of module units within the housing while minimizing the housing's footprint.

[0039] In some implementations, the culture medium / buffer facility is located near a customizable facility, and the utility building is also located near a customizable facility.

[0040] In some implementations, the outer wall of the customizable facility is formed by a shell, which completely seals at least one central unit and at least one modular unit, or

[0041] In some implementations, the outer wall of the customizable facility is formed by at least one of a shell and the outer wall of at least one central unit and the outer wall of at least one modular unit.

[0042] In some embodiments, the housing includes at least one sidewall and a top cover, the at least one sidewall surrounding at least one central unit and at least one module unit, the top cover being fixed to the upper edge of at least one sidewall and extending over at least one central unit and at least one module unit.

[0043] In some implementations, the first floor of a customizable facility includes a utility area.

[0044] In some implementations, at least one pharmaceutical product is multiple pharmaceutical products, and the customizable facility includes multiple manufacturing wings, each configured to manufacture a corresponding pharmaceutical product among the multiple pharmaceutical products.

[0045] In some implementation schemes, the park includes multiple customizable facilities.

[0046] In some implementations, the park includes at least one corridor connecting the culture medium / buffer workshop to the customizable facility, and the at least one corridor is configured to allow users to transport at least one type of processing material from the culture medium / buffer workshop to the customizable facility.

[0047] According to another aspect of this disclosure, a method of assembling a park for manufacturing at least one pharmaceutical product includes providing at least one customizable facility configured to manufacture at least one pharmaceutical product; providing a culture medium / buffer workshop configured to supply processing materials to the customizable facility; and operatively coupling a utility building to at least one of the culture medium / buffer workshop and the customizable facility to provide at least one first utility to the culture medium / buffer workshop via a utility line.

[0048] In some implementations, the method includes providing warehouses near customizable facilities.

[0049] In some implementations, at least one primary utility includes steam supply and / or air supply.

[0050] In some embodiments, the method includes providing at least one central unit and at least one module unit, the at least one module unit communicating with the at least one central unit such that the at least one central unit provides at least one second utility to the at least one module unit.

[0051] In some embodiments, the method includes providing a housing, positioning at least one central unit at least partially within the housing, and positioning at least one module unit at least partially within the housing.

[0052] In some implementations, at least one module unit includes at least one of the following: a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a culture medium buffer facility, an office, a personnel unit, a production unit, a filling-finished product unit, a dosage preparation unit, and a packaging unit.

[0053] In some implementations, the first utility in at least one first utility is the same as the second utility in at least one second utility.

[0054] In some implementations, the first utility in at least one first utility is different from the second utility in at least one second utility.

[0055] In some implementations, the method includes providing at least one module unit, or providing a plurality of module units arranged to maximize the number of module units within the housing while minimizing the footprint of the housing.

[0056] In some implementations, the method includes locating the culture medium / buffer workshop near the customizable facility and locating the utility building near the customizable facility.

[0057] In some implementations, the outer wall of the customizable facility is formed by a shell that completely seals at least one of the central unit and at least one modular unit.

[0058] In some implementations, the outer wall of the customizable facility is formed by at least one of a shell and the outer wall of at least one central unit and the outer wall of at least one modular unit.

[0059] In some embodiments, the housing includes at least one sidewall and a top cover, the at least one sidewall surrounding at least one central unit and at least one module unit, the top cover being fixed to the upper edge of at least one sidewall and extending over at least one central unit and at least one module unit.

[0060] According to another aspect of this disclosure, a method of managing a pharmaceutical facility includes providing a park for manufacturing at least one pharmaceutical product, the park including at least one customizable facility configured for manufacturing at least one pharmaceutical product, a culture medium / buffer workshop, and utility buildings connected by utility lines to at least one of the culture medium / buffer workshop and at least one customizable facility to provide at least one first utility via the utility lines; and providing at least a portion of the park to a customer who wishes to manufacture the pharmaceutical product.

[0061] In some implementations, at least a portion of the park includes a manufacturing wing within at least one customizable facility.

[0062] In some implementations, the step of providing at least a portion of the park includes offering the option to purchase at least a portion of the park.

[0063] In some implementations, the step of providing at least a portion of the park includes the option of providing at least a leased portion of the park.

[0064] According to another aspect of this disclosure, a method for adjusting the capacity of a pharmaceutical facility includes providing a park for manufacturing at least one pharmaceutical product, the park including at least one customizable facility configured for manufacturing at least one pharmaceutical product, a culture medium / buffer workshop, and a utility building connected by a utility line to the culture medium / buffer workshop to provide at least one first utility via the utility line; providing a first portion of the park to a first customer who wishes to manufacture the first pharmaceutical product; and constructing a second portion of the park for manufacturing a second pharmaceutical product, the second portion of the park being technology agnostic.

[0065] In some implementations, the second pharmaceutical product is one of the following: different from the first pharmaceutical product, or the same as the first pharmaceutical product.

[0066] In some implementations, the first part of the park is the manufacturing module within a customizable facility.

[0067] In some implementations, the method includes providing a second portion of the park to a second customer; and constructing a third portion of the park for manufacturing a third pharmaceutical product, said third portion being technology agnostic.

[0068] In some implementations, the first portion is accessible only via a first dedicated access route, which is accessible to a first client but not to a second client; and the second portion is accessible only via a second dedicated access route, which is accessible to a second client but not to the first client.

[0069] In some implementations, the method includes a technology-agnostic component of the campus that continuously maintains the readiness of the campus to begin manufacturing drugs for new customers.

[0070] The present invention also relates to the following embodiments:

[0071] 1. A campus for manufacturing at least one pharmaceutical product, said campus comprising:

[0072] A customizable facility configured to manufacture the at least one pharmaceutical product;

[0073] A culture medium / buffer workshop configured to supply at least one processing material to the customizable facility;

[0074] A utility building, the utility building being connected by a utility line to at least one of the culture medium / buffer workshop and the customizable facility to provide at least one first utility via the utility line.

[0075] 2. The park as described in Implementation Scheme 1 further includes a warehouse located near the customizable facility.

[0076] 3. The park as described in any of the foregoing embodiments, wherein the at least one first utility includes at least one of the following: steam supply and air supply.

[0077] 4. The park as described in any of the foregoing implementation schemes, wherein the customizable facilities include:

[0078] At least one central unit, and

[0079] At least one module unit, which communicates with the at least one central unit, such that the at least one central unit provides at least one second utility to the at least one module unit.

[0080] 5. The park as described in embodiment 4, wherein the customizable facility further comprises a housing, and wherein the at least one central unit is at least partially located within the housing, and the at least one modular unit is at least partially located within the housing.

[0081] 6. The park as described in embodiment 4 or 5, wherein the at least one modular unit comprises at least one of the following: fermentation unit, pre-viral unit, post-viral unit, utility space, warehouse, culture medium buffer facility, office, personnel unit, production unit, filling-finished product unit, dosage preparation unit, and packaging unit.

[0082] 7. The park as described in any one of embodiments 4-6, wherein the first utility in the at least one first utility is the same as the second utility in the at least one second utility.

[0083] 8. The park as described in any one of embodiments 4-6, wherein the first utility in the at least one first utility is different from the second utility in the at least one second utility.

[0084] 9. The park as described in embodiment 5, wherein the at least one module unit comprises a plurality of module units, the plurality of module units being arranged to maximize the number of module units within the housing while minimizing the floor area of ​​the housing.

[0085] 10. The park as described in any of the preceding embodiments, wherein the culture medium / buffer workshop is located near the customizable facility, and wherein the utility building is located near the customizable facility.

[0086] 11. The park as described in Implementation Scheme 5, wherein the exterior wall of the customizable facility is one of the following:

[0087] Formed by the housing, the housing completely seals the at least one central unit and the at least one module unit, and

[0088] The housing is formed by at least one of the following: the outer wall of the at least one central unit and the outer wall of the at least one module unit.

[0089] 12. The campus as described in embodiment 5, wherein the housing includes at least one sidewall and a top cover, the at least one sidewall surrounding the at least one central unit and the at least one module unit, the top cover being fixed to the upper edge of the at least one sidewall and extending over the at least one central unit and the at least one module unit.

[0090] 13. The park as described in any of the foregoing embodiments, wherein the first layer of the customizable facility includes a utility area.

[0091] 14. The park as described in any of the preceding embodiments, wherein the at least one pharmaceutical product is multiple pharmaceutical products, and wherein the customizable facility comprises multiple manufacturing wings, each manufacturing wing being configured to manufacture a corresponding pharmaceutical product among the multiple pharmaceutical products.

[0092] 15. The park as described in any of the aforementioned implementation schemes also includes several customizable facilities.

[0093] 16. The park as described in any of the foregoing embodiments further includes at least one corridor connecting the culture medium / buffer workshop to the customizable facility, the at least one corridor being configured to allow a user to transport the at least one processed material from the culture medium / buffer workshop to the customizable facility.

[0094] 17. A method for assembling a site for manufacturing at least one pharmaceutical product, the method comprising:

[0095] Provide at least one customizable facility configured to manufacture the at least one pharmaceutical product;

[0096] Provide a culture medium / buffer facility configured to supply processing materials to the customizable facility; and

[0097] The utility building is operatively coupled to at least one of the culture medium / buffer workshop and the customizable facility to provide at least one first utility to the culture medium / buffer workshop via a utility line.

[0098] 18. The method of embodiment 17, further comprising providing a warehouse near the customizable facility.

[0099] 19. The method as described in embodiment 17 or 18, wherein the at least one first utility comprises at least one of the following: steam supply and air supply.

[0100] 20. The method according to any one of embodiments 17-19, further comprising:

[0101] Provide at least one central unit, and

[0102] At least one module unit is provided, which communicates with the at least one central unit, such that the at least one central unit provides at least one second utility to the at least one module unit.

[0103] 21. The method as described in embodiment 20, wherein providing customizable facilities includes:

[0104] Provide housing,

[0105] The at least one central unit is positioned at least partially within the housing, and

[0106] The at least one module unit is positioned at least partially within the housing.

[0107] 22. The method as described in embodiment 20 or 21, wherein the at least one module unit comprises at least one of the following: a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a culture medium buffer facility, an office, a personnel unit, a production unit, a filling-finished product unit, a dosage preparation unit, and a packaging unit.

[0108] 23. The method according to any one of embodiments 20-22, wherein the first utility in the at least one first utility is the same as the second utility in the at least one second utility.

[0109] 24. The method as described in any one of embodiments 20-22, wherein the first utility in the at least one first utility is different from the second utility in the at least one second utility.

[0110] 25. The method of embodiment 21, wherein providing the at least one module unit comprises providing a plurality of module units arranged to maximize the number of module units within the housing while minimizing the floor area of ​​the housing.

[0111] 26. The park as described in any one of embodiments 17-25 further includes locating the culture medium / buffer workshop near the customizable facility and locating the utility building near the customizable facility.

[0112] 27. The method of embodiment 21, wherein the outer wall of the customizable facility is one of the following:

[0113] Formed by the housing, the housing completely seals the at least one central unit and the at least one module unit, and

[0114] The housing is formed by at least one of the following: the outer wall of the at least one central unit and the outer wall of the at least one module unit.

[0115] 28. The method of embodiment 21, wherein the housing includes at least one sidewall and a top cover, the at least one sidewall surrounding the at least one central unit and the at least one module unit, the top cover being fixed to the upper edge of the at least one sidewall and extending over the at least one central unit and the at least one module unit.

[0116] 29. A method for managing a pharmaceutical facility, the method comprising:

[0117] A park is provided for manufacturing at least one pharmaceutical product, the park comprising at least one customizable facility configured for manufacturing the at least one pharmaceutical product, a culture medium / buffer workshop, and a utility building, the utility building being connected by a utility line to at least one of the culture medium / buffer workshop and the at least one customizable facility to provide at least one first utility via the utility line; and

[0118] At least a portion of the park will be provided to customers who wish to manufacture pharmaceutical products.

[0119] 30. The method of embodiment 29, wherein at least a portion of the park includes a manufacturing wing in the at least one customizable facility.

[0120] 31. The method as described in embodiment 29 or 30, wherein the step of providing at least a portion of the park includes providing the option to purchase at least a portion of the park.

[0121] 32. The method as described in embodiment 29 or 30, wherein the step of providing at least a portion of the park includes the option of providing a lease of at least a portion of the park.

[0122] 33. A method for adjusting the capacity of a drug facility, the method comprising:

[0123] A park is provided for manufacturing at least one pharmaceutical product, the park comprising at least one customizable facility configured for manufacturing the at least one pharmaceutical product, a culture medium / buffer workshop, and a utility building connected by a utility line to the culture medium / buffer workshop to provide at least one first utility via the utility line;

[0124] The first portion of the park will be provided to the first customer who wishes to manufacture the first pharmaceutical product; and

[0125] The second part of the park is constructed for manufacturing a second pharmaceutical product, and the second part of the park is technologically agnostic.

[0126] 34. The method of embodiment 33, wherein the second pharmaceutical product is one of the following: different from the first pharmaceutical product, and the same as the first pharmaceutical product.

[0127] 35. The method as described in embodiment 33 or 34, wherein the first part of the park is a manufacturing module within the customizable facility.

[0128] 36. The method as described in any one of embodiments 33-35, further comprising providing a second portion of the park to a second customer; and

[0129] The third part of the park is constructed for manufacturing a third pharmaceutical product, and the third part is technology agnostic.

[0130] 37. The method of embodiment 36, wherein the first portion is accessible only via a first dedicated access route, which is accessible by the first client but inaccessible by the second client; and

[0131] The second part is accessible only via a second dedicated access route, which is accessible to the second client but not to the first client.

[0132] 38. The method as described in any one of embodiments 33-37, further comprising continuously maintaining the technology agnostic portion of the park to a state of readiness for starting drug manufacturing for new customers. Attached Figure Description

[0133] The accompanying drawings are not intended to be drawn to scale. For clarity, not every component can be labeled in every drawing. In the drawings:

[0134] Figure 1 This is a top view of an implementation scheme of a customizable facility based on this disclosure;

[0135] Figure 2A yes Figure 1 Perspective view of the implementation plan;

[0136] Figure 2B yes Figure 1 A perspective view of the implementation plan, showing the location of components within the customizable facility;

[0137] Figure 2C yes Figure 1 A perspective view of the implementation scheme, showing the location of another component within the customizable facility;

[0138] Figure 2D yes Figure 1 A perspective view of the implementation scheme, showing the location of another component within the customizable facility;

[0139] Figure 2E yes Figure 1 A perspective view of the implementation scheme, showing the location of another component within the customizable facility;

[0140] Figure 3A This is an exploded view of an embodiment of the module unit according to the present invention.

[0141] Figure 3B This is an exploded view of another embodiment of the module unit according to the present invention.

[0142] Figure 3C This is an exploded view of another embodiment of the module unit according to the present invention.

[0143] Figure 3D This is an exploded diagram of another embodiment of the module unit according to this disclosure.

[0144] Figure 3E This is an exploded view of another embodiment of the module unit according to the present invention.

[0145] Figure 4 This is a front perspective sectional view of an implementation of a customizable facility according to this disclosure.

[0146] Figure 5 It is a perspective view of a group of modular units and a central unit arranged in an H-shape;

[0147] Figure 6 It is a top view of a group of modular units and a central unit arranged in an H-shape;

[0148] Figure 7 It is its perspective view;

[0149] Figure 8 It is a top view of the modular units and the central unit arranged in a different configuration within the housing;

[0150] Figure 9 This is a top view of another arrangement of the modular units and the central unit within the housing;

[0151] Figure 10 This is a top view showing another arrangement of the modular units and the central unit;

[0152] Figure 11 This is a schematic diagram of a group of modular units arranged with a spine and a central unit;

[0153] Figure 12 This is a perspective view based on the implementation plan of the park disclosed herein;

[0154] Figure 13 yes Figure 12 An enlarged perspective view of a portion of the park shown;

[0155] Figure 14 yes Figure 12 Another perspective on the implementation plan of the park; and

[0156] Figure 15 This is a perspective sectional view of another embodiment of the customizable facility according to this disclosure. Detailed Implementation

[0157] The structures disclosed herein for customizable facilities can be used to manufacture at least one product at a given time. The structures disclosed herein are particularly suitable for manufacturing a variety of products that utilize common resources.

[0158] This disclosure provides systems and methods that allow one or more scalable product lines to be at least partially enclosed within a housing of a customizable facility. Because the structure is adaptable, it eliminates the need for users to fixate on a structure for a single product line over extended periods. The structure can be reconfigured to meet the size requirements of the product line.

[0159] This disclosed customizable facility enables users to reduce build timelines, reduce capital expenditures, increase global design standardization, and comply with various global standards.

[0160] Customizable structures allow for shorter turnaround times from concept to construction, reduce on-site congestion, and require fewer fixed assets when implementing new product lines.

[0161] Typically, a customizable facility includes a housing, at least one central unit located within the housing, and at least one modular unit, each of which is located within the housing.

[0162] Figure 1 This is a top view of an exemplary implementation of a customizable facility, typically indicated by 10. Figure 1 Customizable facilities can be built in a series of phases, such as Phase 12, Phase 24 and subsequent phases.

[0163] Installed Figure 1 The features of the first phase 12 of the construction of the customizable facility 10 include an air-controlled entryway 16, a changing area 18, a utility area 20, a first manufacturing wing 22A, a first office space 24A, and at least one corridor 28 that allows the occupant of the customizable facility 10 to move from one area to another within the customizable facility 10.

[0164] Outside the customizable facility 10, there exists a yard 30, which contains a processing area 32 for handling equipment and materials. The yard area 30 is adjacent to a roadway 34. Typically, the customizable facility 10 can expand in any direction. Furthermore, the customizable facility 10 is constructed such that it can expand within a series of construction phases and / or sub-phases within the physical constraints of surrounding features, such as the yard area 30 and the roadway 34.

[0165] Figure 1Additional features that can be added during the second phase 14 of construction are shown, such as the second manufacturing wing 22B and the second office space 24B.

[0166] The layout of the customizable facility 10 can be configured for fabrication within a cleanroom setting. The customizable facility 10 utilizes hybrid sticks or frame-build buildings and modular buildings with utility units (or utility hubs).

[0167] Now for reference Figures 2A-2E This shows the relative positions of the various components of the customizable facility.

[0168] Figure 2A A perspective view of the outer wall of the housing 36 of the customizable facility 10 is shown. The housing 36 at least partially seals the central unit (which may be the central utility unit) 38 and at least partially seals the plurality of module units 40, as discussed further below. In some embodiments, the housing 36 completely seals the utility unit (which may be the central utility unit) 38 and completely seals the plurality of module units 40.

[0169] The outer shell 36 can be constructed according to conventional rod-type buildings or another method (such as, but not limited to, prefabricated modules). For example, the outer shell 36 can be made of steel using conventional construction methods. The outer shell 36 can be supported on a fixed footing on the ground. The outer shell 36 is weatherproof.

[0170] The outer shell 36 forms the superstructure. In some embodiments, the outer shell 36 may be a "Butler" type building, which is known in the field of building construction.

[0171] The housing 36 includes sidewalls 42, which are sized and configured to surround one or more central units 38 and one or more modular units 40 contained in the customizable facility 10, and are described in more detail below.

[0172] A top cover 44 is fixed to the upper edge of the sidewall 42 and extends over the central unit 38 and the modular unit 40. Thus, the sidewall 42 and the top cover 44 seal the central unit 38 and the modular unit 40 located within the housing 36. The central unit 38 and the modular unit 40 can be supported on the bottom or top surface of the housing 36, which is fixed to another supporting surface of the housing. Customizable facility 10 provides a partial modular (referred to as modular bar construction) method, which comprises a basic superstructure and then fills the superstructure with modular type elements.

[0173] In one implementation scheme Figure 2AThe customizable facility 10 has an external height of 30 meters. In one embodiment, each manufacturing wing has a length of 100 meters and a width of 30 meters.

[0174] Figure 2B The exterior of the customizable facility 10 is shown in dashed lines, while the utility area is shown in solid lines. The utility area 20 may contain a central unit (which may be referred to as a Central Utility Bay (CUB) or utility building or central utility module) 38, which is oriented toward the center of the customizable facility 10.

[0175] Figure 1 The casing 36 also seals the future utility area 46, which is Figure 1 The future utility module is completely occupied. Future utility region 46 is adjacent to utility module 38 and is within... Figure 1 As shown in the image, the future utility area 46 can be used as a warehouse area adjacent to the utility module 38. This future utility area 46 within the customizable facility 10 can also be used in conjunction with a high bay application, such as a 40-foot-high warehouse with an Automated Search and Retrieval System (ASARS).

[0176] In some implementations, utility module 38 and future utility region 46 are a single utility module, which is divided into a utility portion and a future utility portion.

[0177] The central utility module 38 does not need to be located at the center of the customizable facility 10. In some embodiments, the central utility module 38 may be positioned along the outer edge of the customizable facility 10.

[0178] Figure 2C The exterior of the customizable facility 10 is shown in dashed lines, while manufacturing wings 22A and 22B are shown in solid lines.

[0179] Manufacturing wings 22A and 22B are configured to contain modular units 40 for product lines, such as fermentation or purification modules. The customizable facility 10 is easily expandable and scalable, and different modular units 40 within manufacturing wings 22A and 22B can be used to produce completely different products within the same customizable facility 10.

[0180] For example, in module unit 40 configured as a first fermentation module, a user can manufacture one type of product, such as a monoclonal antibody product derived from a mammalian cell line. In module unit 40, a user can manufacture entirely different products, such as microbial products. The customizable facility 10 of this disclosure can simultaneously support multiple product lines and multiple customers from a single scalable superstructure. The customizable facility 10 of this disclosure can be expanded to add additional product lines.

[0181] The reactor can be supported within the modular unit 40 of the manufacturing wings 22A, 22B of the customizable facility 10. The customizable facility 10 can support any desired and suitable container volume. For example, in... Figure 1 In some aspects shown, the customizable facility 10 can be configured to contain production containers of up to 20,000 liters and storage containers (e.g., harvesting containers) exceeding 20,000 liters (e.g., 23,000-24,000 liters). For example, the size and construction of the customizable facility 10 can support containers with volumes of approximately 20,000 liters, 15,000 liters, 10,000 liters, 5,000 liters, 2,000 liters, and / or 1,000 liters. Containers with other volumes can also be supported.

[0182] Any typical manufacturing and cleanroom equipment can be included in the customizable facility 10, and the customizable facility 10 can be fully adapted to cGMP (current good manufacturing practice) processes.

[0183] Examples of equipment that can be adapted to the customizable facility 10 include, but are not limited to: bioreactors, disc stack centrifuges, tangential flow filtration (TFF) skids, depth filtration skids, in-line dilution skids, chromatography columns and associated control equipment, culture tanks, harvest tanks, purification containers, depth filter holders, water softening and dechlorination systems, clean steam generators, water for injection (WFI) tanks, WFI break tanks, WFI stills, cooling towers, switchboards, emergency generators, coolers, hydronic pumps, autoclaves, air handling units, process waste neutralization (e.g., fiberglass reinforced plastic (FRP)), biological waste collection and inactivation systems, clean-in-place systems, glass washers, and / or other equipment.

[0184] The bioreactor in the customizable facility 10 disclosed herein can be a ground-based reactor. Alternatively, the bioreactor can be suspended from the structure itself. For example, the bioreactor can be suspended from one or more modular units 40.

[0185] Customizable facility 10 may include one or more central units 38 and one or more modular units 40. In some embodiments, each modular unit 40 is selected from the group consisting of: fermentation or cell culture units, previral units, postviral units, utility rooms, warehouses, culture medium buffer facilities, offices, personnel units, production units, fill-to-finish units, dosage preparation units, and packaging units. Production units are used to manufacture products. Fill-to-finish units are used to fill containers such as vials. Dosage preparation units dispense pre-dosed products. Packaging units package products for distribution or sale.

[0186] The space allocated to each module unit can be further divided as needed to suit specific processing requirements. Each manufacturing wing 22A, 22B can be configured to allow more than one module unit 40 to be located within the corresponding manufacturing wing 22A, 22B.

[0187] exist Figure 1 and Figure 2C In this configuration, the first manufacturing wing 22A comprises three module units 40. The second manufacturing wing 22B comprises two module units 40. The central utility region 20 has a length of 50 meters and a width of 20 meters, and has three internal levels. The central utility block is expandable.

[0188] In some embodiments, at least one of the module units 40 is a cleanroom. In some embodiments, at least one of the module units 40 includes a cleanroom portion within the respective module unit 40.

[0189] The building shell 36 is designed to accommodate different production modules. In some embodiments, the shell can accommodate four 20,000-liter containers for mammalian cell lines. In some embodiments, the shell can accommodate four 2,000-liter containers for single-use technical operations.

[0190] In some implementations, the manufacturing wing may include a modular unit containing four 20,000-liter containers and downstream processing equipment and configured for manufacturing monoclonal antibody products derived from mammalian cell lines; a modular unit containing disposable equipment for manufacturing monoclonal antibody products derived from mammalian cell lines and having four 20,000-liter containers; a modular unit configured for manufacturing microbial products; and / or a modular unit containing disposable equipment for manufacturing microbial products.

[0191] In one embodiment, the modular unit is configured for mammalian manufacturing and includes four 20,000-liter containers and downstream processing equipment. In another embodiment, the modular unit includes four 20,000-liter containers for commercial and clinical manufacturing. In another embodiment, the modular unit includes one 1,000-liter container for clinical manufacturing. In another embodiment, the modular unit is configured for manufacturing microbial products and includes one 15,000-liter container. In another embodiment, the modular unit includes three 5,000-liter containers. In another embodiment, the modular unit includes one or more process development laboratories. In another embodiment, the modular unit includes filling and finished clinical development vial filling equipment, one or more sets of lyophilization equipment, equipment for manufacturing pre-filled syringes, and / or equipment for manufacturing high-potency products for commercial applications. In some embodiments, the modular unit includes cell therapy equipment. In some embodiments, the modular unit includes viral therapy equipment.

[0192] Figure 2D The exterior of the customizable facility 10 is shown in dashed lines, with the first office space 24A and the second office space 24B shown in solid lines. The first office space 24A includes an office, cabinets for personal storage, and a support area. The second office space 24B includes an office, cabinets for personal storage, and a support area. The front wall 48A of the first office space 24A forms part of the front outer surface of the customizable facility 10, as shown in Figure 2. The front wall 48B of the first office space 24B forms part of the front outer surface of the customizable facility 10. Therefore, each office space 24A, 24B is only partially sealed by the housing 36 of the customizable facility 10.

[0193] Similarly, in some embodiments, the outer wall of the central unit and / or the outer wall of at least one of the module units forms at least a portion of the outer wall of the customizable facility. In some embodiments, the upper surface of the central utility module and / or the upper surface of the module unit forms a portion of the upper surface of the customizable facility.

[0194] Figure 2E The exterior of the customizable facility 10 is shown in dashed lines, while the changing area 18 is shown in solid lines. The changing area 18 allows users to enter the customizable facility 10 and change from casual clothes to work clothes. Figure 2E The changing area 18 is further subdivided into a male changing area 18A and a female changing area 18B. In some embodiments, the changing area 18 is subdivided into two or more changing areas. In some embodiments, the changing area 18 is not subdivided.

[0195] In other embodiments, the relative positions of the first manufacturing wing 22A and the second manufacturing wing 22B, the first office space 24A, the second office space 24B, the changing area 18, and the utility area 20 may be located differently within the customizable facility 10 and / or oriented differently relative to the customizable facility 10.

[0196] The scaffolding and corridor 28 allow users of the customizable facility 10 to access the utility units 38 and module units (such as fermentation modules) 40 of the utility area 20.

[0197] After adding the second construction phase 14 to the customizable facility 10, the user may wish to further expand the customizable facility 10 over time. For example, consumers in the global economy may have increased demand for products manufactured by the user, or consumers in the global economy may have increased demand for products that the user can produce. In response to such an increase in demand for products, the user can expand the customizable facility 10 in subsequent construction phases, which add additional features. Figure 1 Customizable facilities. In some embodiments, such additional features (such as additional module units, additional manufacturing wings, or another component of the customizable facility) are horizontally positioned near the first manufacturing wing 22A or the second manufacturing wing 22B. In some embodiments, such additional features are vertically positioned near the first manufacturing wing 22A and / or the second manufacturing wing 22B.

[0198] Now for reference Figures 3A-3E Users can expand the manufacturing of wings in different sub-stages, such as Figure 1 The first manufacturing wing 22A or the second manufacturing wing 22B. Users can... Figures 3A-3E One of the configurations shown is converted to Figures 3A-3E Another configuration is shown. Alternatively, the user can change the manufacturing wing layout to another configuration.

[0199] Figure 3A A partial exploded view of an embodiment of module unit 40A is shown, which is configured to fill finished modules. Figure 3A The filled finished product module 40A comprises a single-layer structure with a footprint of 1500 square meters. The filled finished product module includes a mezzanine layer for HVAC workshop rooms and some localized uses. The free field 50A, adjacent to the filled finished product module and shown in dashed lines, also has a footprint of 1500 square meters. The free field 50A can be used for various purposes, such as product storage. Together with the filled finished product module 40A and the free field 50A, they extend over the second manufacturing wing 22B with a footprint of 3000 square meters.

[0200] Figure 3BA partial exploded view of an implementation of module unit 40B configured as a "2k module" is shown. Figure 3B The 2K module has a single layer 60B with a footprint of 1500 square meters. The 2K module can seal containers up to 2,000 liters. The 2K module includes a middle layer for HVAC workshop rooms and some localized uses. Free space 50B is adjacent to the 2K module and shown in dashed lines, also with a footprint of 1500 square meters. Free space 50B can be used for various purposes, such as product storage. Together with 2K module 40B and free space 50B, they extend over the second manufacturing wing 22B with a footprint of 3,000 square meters.

[0201] Figure 3C A partial exploded view of an implementation of module unit 40C configured as a "5k module" is shown. Figure 3C The 5K module features a single-layer 60C design and occupies a 3,000 square meter footprint. The 5K module can seal a 5,000-liter container. It includes a middle layer for HVAC workshop rooms and some localized utilities. The 5K module extends across the 3,000 square meter footprint of the manufacturing wing.

[0202] Figure 3D A partial exploded view of an implementation of module unit 40D configured as "15k module" is shown. Figure 3D The 15k module has a first layer of 60D and a second layer of 62. Figure 3D The 15k module has a footprint of 3,000 square meters. The 15k module can seal a 15,000-liter container. The 15k module includes a local HVAC unit, a Clean in Place (CIP) unit, and a Temperature Control Unit (TCU). In some embodiments, the temperature control unit includes a water jacket with a heat exchanger on the tank to control the temperature of the tanks used in the production line. The CIP unit is typically a module skid and has multiple tanks to hold cleaning solutions (e.g., caustic soda solutions and bleach), pumps, and sensors to deliver the cleaning solution to the appropriate tank to be cleaned.

[0203] The first layer 60D of the 15k module extends over a 3,000 square meter footprint of the manufacturing wing. The second layer 62 of the 15k module extends vertically above the first layer of the 15k module and also over a 3,000 square meter footprint of the manufacturing wing. Together, the first layer 60D and the second layer 62 of the 15k module have a combined area of ​​6,000 square meters.

[0204] Figure 3E A partial exploded view of an implementation of module unit 40E configured as "20k module" is shown. Figure 3EThe 20k module has a footprint of 3,000 square meters. The 20k module can seal a 20,000-liter container. The 20k module includes a local HVAC unit, a CIP unit, and a TCU. The 20k module comprises a first layer, a second layer, and a third layer. The first layer 60E of the 20k module extends over the 3,000 square meter footprint of the manufacturing wing. The second layer 64 of the 20k module extends vertically above the first layer 60E of the 20k module and also extends over the 3,000 square meter footprint of the manufacturing wing. The third layer 66 of the 20k module extends vertically above the first layer 60E and the second layer 64 of the 20k module and also extends over the 3,000 square meter footprint of the manufacturing wing. Together, the first layer 60E, the second layer 64, and the third layer 66 of the 20k module have a combined area of ​​9,000 square meters.

[0205] Figure 4 This is a front perspective sectional view of an exemplary embodiment of a customizable facility generally indicated by 110 according to this disclosure. The layout of the customizable facility 110 can be configured for fabrication in a cleanroom setting. The customizable facility 110 utilizes a hybrid bar or frame building and a modular building having a central utility hub (or central unit) 114 located at the center.

[0206] The outer shell (or enclosure) 112 seals the central unit 114 and a plurality of modular units 116 adjacent to the central unit 114. The outer shell 112 can be constructed according to conventional rod-type construction methods or another method (such as, but not limited to, prefabricated modules). For example, the outer shell 112 can be made from a steel structure using conventional construction methods. The outer shell 112 can be supported on a fixed footing on the ground. The outer shell 112 is weatherproof.

[0207] The outer shell 112 forms the superstructure. In some embodiments, the outer shell 112 may be a "butler" type building, which is known in the field of building construction.

[0208] The housing 112 includes sidewalls 118, 42 sized and configured to surround one or more central units 114 and one or more modular units 116 contained within the customizable facility 110, as described in more detail below. A top cover 120 is attached to the upper edge of the sidewalls 118 and extends over the central units 114 and modular units 116. Thus, the sidewalls 118 and the top cover 120 seal the central units 114 and modular units 116 located within the housing 112. The central units 114 and modular units 116 may be supported on the bottom surface 122 of the housing 112 or on another supporting surface of the housing 112. The customizable facility 110 provides a partially modular (maybe referred to as modular bar construction) method, which includes a substantially superstructure and then fills the superstructure with modular type elements.

[0209] Inside the housing 112, Figure 4 The customizable facility 110 includes at least one central unit 114, each of which may be referred to as a Central Utility Chamber (CUB). The central unit 114 provides... Figure 4 The central utility within. As shown, CUB 114 is located in the middle of a structure with modular unit 116, which may be referred to as a manufacturing pod, derived from CUB 114 (or multiple CUBs). Figure 4 In this context, module unit 116 is a fermentation module. Customizable facility 110 is easily expandable and scalable, and the pod / module approach (i.e., spoke-wheel approach) allows different modules to produce completely different products in the same customizable facility 110.

[0210] For example, in the first fermentation module, such as Figure 4 The fermentation module on the left allows users to manufacture one type of product, such as a monoclonal antibody product derived from a mammalian cell line. In the second module, for example... Figure 4 The fermentation module on the right allows users to manufacture entirely different products, such as microbial products. This disclosed customizable facility 110 can simultaneously support multiple product lines and multiple customers from a single scalable superstructure.

[0211] Figure 4 The reactor 124 supported within the customizable facility 110 is shown. The customizable facility 110 can support any desired and suitable container volume. For example, in... Figure 4 In some aspects shown, facility 110 can be configured to contain production containers of up to 20,000 liters and storage containers (e.g., harvesting containers) exceeding 20,000 liters (e.g., 23,000-24,000 liters). For example, customizable facility 110 can be sized and configured to support containers 124 having volumes of approximately 20,000 liters, 15,000 liters, 10,000 liters, 5,000 liters, 2,000 liters, and / or 1,000 liters. Containers 124 with other volumes can also be supported.

[0212] Scaffolding 126 and corridor 128 allow users of facility 110 to access central unit (central utility) 114 and modular units (fermentation modules, etc.) 116. For example... Figure 4 As shown, scaffolding 126 is positioned inside housing 112.

[0213] In some implementations, one or more central units (CUB) 114 and one or more module units 116 are arranged in a spoke-like configuration.

[0214] Any typical manufacturing and cleanroom equipment can be included in the customizable facility 110, and the customizable facility 110 can be fully adapted to cGMP processes.

[0215] Examples of equipment that may be installed in facility 110 include, but are not limited to: bioreactors, tray-stacking centrifuges, tangential flow filtration (TFF) skids, depth filtration skids, in-line dilution skids, chromatography columns and associated control equipment, culture tanks, harvest tanks, purification vessels, depth filter supports, water softening and dechlorination systems, clean steam generators, water for injection (WFI) storage tanks, WFI shut-off tanks, WFI distillers, cooling towers, switchboards, emergency generators, coolers, liquid circulation heating pumps, autoclaves, air handling units, process waste neutralization (e.g., glass fiber reinforced plastic (FRP)), biological waste collection and inactivation systems, in-situ cleaning systems, glass washers and / or other equipment.

[0216] like Figure 4 As shown, the bioreactor in the customizable facility 110 of this disclosure can be a ground-based reactor. Alternatively, the bioreactor 124 can be suspended from the structure itself. For example, the bioreactor 124 can be suspended from one or more modular units 116.

[0217] Figure 4 The enclosure 112 surrounds the warehouse area 130 to the right rear of facility 110. The warehouse area 130 within facility 110 can also be used in conjunction with high-partition applications, such as a 40-foot-high warehouse with an Automated Search and Retrieval System (ASARS).

[0218] Customizable facility 110 may include one or more central units 114 and one or more modular units 116. In some embodiments, each modular unit 116 is selected from the group consisting of: fermentation or cell culture units, previral units, postviral units, utility rooms, warehouses, culture medium buffer facilities, offices, personnel units, production units, fill-to-finish units, dosage preparation units, and packaging units. The space allocated to each modular unit can be further subdivided as needed to suit specific processing requirements.

[0219] In some implementations, at least one of the module units 116 is a cleanroom.

[0220] Figure 5 A perspective view shows a group of central units 114 and module units 116 arranged in an H-shaped layout 132. The position of each module unit 116 can be adjusted to best suit processing requirements.

[0221] Figure 6 and 7An implementation of a customizable facility is shown, in which, when viewed from above, a central unit 114 and a group of eight modular units configured as purification unit 116A and fermentation unit 116B are arranged in an H-shaped layout 133. The housing 112 is not shown in these views. Figure 6 The plan view shows a central unit (labeled as the central utility building) 114, which has a first row of modular units and a second row of modular units. The first row of modular units is configured as purification units 116A and fermentation units 116B, arranged in a linear array 134 adjacent to a first side 136 of the central unit 114. The second row of modular units is configured as purification units 116A and fermentation units 116B, arranged in a linear array 138 adjacent to a second side 140 of the central unit 114. The array 134 of modular units contains four modular units: a first purification unit 116A at the first end of the array 134, two fermentation units 116B in the middle of the array 134, and a second purification unit 116A at the second end of the array 134. Similarly, the array 138 of modular units contains four modular units: a first purification unit 116A at the first end of the array 138, two fermentation units 116B in the middle of the array 138, and a second purification unit 116A at the second end of the array 138.

[0222] Each of the two fermentation units 116B in the first array 134 of the modular units includes a sidewall that directly faces and engages with the first sidewall 136 of the central unit 114. Similarly, each of the two fermentation units 116B in the second array 138 of the modular units includes a sidewall that directly faces and engages with the second sidewall 140 of the central unit 114. Purification units 116A are in a direct-facing relationship with their respective adjacent fermentation units 116B. Due to the direct-facing engagement of the central unit 114 and the fermentation units 116B, the number of central units 114 and modular units that can be assembled within a housing 112 of a given size increases. Likewise, the footprint of the housing 112 required to seal a given set of central units 114 and modular units decreases. Alternatively, in some aspects, the sidewalls of the fermentation units 116B (or other modular units) do not need to be directly facing and engaged, but can be spaced out to provide any desired footprint.

[0223] Module unit 116 and central unit 114 can be arranged to facilitate the simultaneous manufacture of multiple products. Module unit 116 and central unit 114 are arranged to effectively share resources between production lines for corresponding products. For example, in some embodiments, central unit 114 includes at least one of the following: a generator, a plumbing line, a power line, and other resources that can be shared by module unit 116. Furthermore, module unit 116 and central unit 114 can be arranged to facilitate future expansion of manufacturing capacity. For example, a single module unit 116 can be initially utilized, and additional module units 116 can be added later with minimal impact on existing operations.

[0224] In some implementations, each module unit 116 includes its own corresponding heating, ventilation, and air conditioning (HVAC) system, as required for operation and isolation.

[0225] In some implementations, the spoke arrangement can resemble the letter H, such as in... Figure 6 In the plan view. In other embodiments, the spoke arrangement does not resemble the letter H. Other shapes are possible, including but not limited to: squares, rectangles, pentagons, and other geometric shapes, as long as it has a central unit (central utility compartment) with at least one modular unit extending from there. Other shapes are also possible, for example, such as Figure 10 As shown. In some implementations, for example, a linear "ridge" shape or an "E" shape can be used, such that the spoke arrangement resembles the letter E.

[0226] In some implementations, the central unit 114 is not located at the center of the arrangement of the central unit 114 and the module units 116. The arrangement of the module units 116 and the central unit 114 is preferably configured to reduce the number of module units 116 required for a given set of production lines.

[0227] Module units 116 can be separated from each other to reduce cross-contamination of products or kits.

[0228] Figure 8 A floor plan of another preferred embodiment of the customizable facility 1000 of this disclosure is shown. Two central units 114 face... Figure 8 The bottom center of the plan view of the structure shown is located between common corridors 128, which extend along the wall of the central unit 114. To the left of the central unit 114 is a group of six modular units. This group includes two pre-viral units 116C, two post-viral units 116D, and two fermentation units 116B. Figure 8To the right of the central unit 114 shown is a group of six modular units, comprising two pre-viral units 116C, two post-viral units 116D, and two fermentation units 116B. This configuration is designed to accommodate additional capabilities as needed (e.g., see [link to documentation]). Figure 10 (As an example of an implementation of display extended options). Along such Figure 8 At the top of facility 1000 shown, there are other modular units, including a utility unit 116E, two storage units 116F, two culture medium / buffer facility units 116G, an office unit 116H, and two personnel access units 116J. The ability to add independent buffer retention modular units directly above each purification unit is not shown in the figure. A shared corridor 128 extends along the walls of the units, allowing users to access them from the common corridor 128. Figure 8 Each module unit and the central unit 114.

[0229] Depending on the rating criteria, different units can have different classification levels. For example, according to the grading criteria established by the US Food and Drug Administration or EudraLex, the EU Guidelines to Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use (Supplemented by Annex 1, Manufacture of Sterile Medicinal Products in the European Union), different units can have different classification levels. For example, according to EU standards, Figure 8 The pre-viral unit 116C, post-viral unit 116D, and culture medium / buffer facility unit 116G are classified as "Grade C," while the fermentation unit 116B is classified as "Grade D," and the remaining units are unclassified. Other unit classifications are possible and can be selected according to user needs.

[0230] Figure 9 Another implementation of the customizable facility 1200 disclosed herein is shown. Figure 9 It includes a central unit (central utility building) 114, which has a corridor 128 on either side for cleaning materials and personnel. Corridor 128 leads from... Figure 9The warehouse 116F at the upper end of the facility 1200 shown extends beyond the central unit 114 at the bottom of the facility. Outside the corresponding corridor 128 are the locker room unit 116K, the pre-virus unit 116C, the post-virus unit 116D, and the fermentation unit 116B.

[0231] In one implementation scheme, such as Figure 9 In the embodiment shown, each fermentation unit 116B has dimensions of 63 feet by 65 feet and a height of 35 feet. In one embodiment, in such... Figure 9 In the embodiment shown, the pre-viral unit 116C can have dimensions of 62 feet by 50 feet and a height of 17 feet. In one embodiment, such as... Figure 9 In the illustrated embodiment, each of the post-viral units 116D has dimensions of 62 feet by 65 feet and a height of 35 feet. In other embodiments, the units may have other dimensions.

[0232] Figure 10 Another embodiment of the customizable facility 1300 of this disclosure is shown, in which housing 112 is not shown. Figure 10 It includes the Five Elements region. In Figure 10 The first row (top row) 142 in the plan view contains the purification zone 117A. The second row 144 contains the fermentation zone 117B. The third row 150 contains the central utility zone 114. The fourth row 146 contains the fermentation zone 117B. The fifth row 148 contains the purification zone 117A.

[0233] In some aspects, a customizable facility for manufacturing at least one pharmaceutical product may include at least one central unit and at least one modular unit, but the customizable facility does not include a housing. Each modular unit communicates with at least one central unit, such that the at least one central unit provides utility to each modular unit.

[0234] The solid lines indicate a set of regions provided in the initial configuration. In this initial configuration 160, there are three purification regions (PURE 1, PURE 3, PURE 5) 117A in the first row 142, three fermentation regions (FERM 1, FERM 3, FERM 5) 117B in the second row 144, a central utility region (central utility 1) 115 in the third row 150, three fermentation regions (FERM 2, FERM 4, FERM 6) 117B in the fourth row 146, and three purification regions (PURE 2, PURE 4, PURE 6) 117A in the fifth row 148.

[0235] A set of regions 162 can be added by expanding the region array to the right. For example, two additional purification regions (PURE 7, PURE 9) 117A can be added to the first row 142, two additional fermentation regions (FERM 7, FERM 9) 117B can be added to the second row 144; an additional central utility region 114 can be added to the third row 150, two additional fermentation regions (FERM 8, FERM 10) 117B can be added to the fourth row 146, and two additional purification regions (PURE 8, PURE 10) 117A can be added to the fifth row 148. The arrows on the right, such as arrow A between fermentation regions 117B labeled FERM 9 and FERM N+1, indicate the potential direction of expansion of the region arrangement. Additional regions can be added to the corresponding rows as needed, and Figure 10 The diagram shows the purification unit (PURE N + 1) 117 at the end of the first row 142, the fermentation zone (FERM N + 1) 117B at the end of the second row 144, the fermentation zone (FERM N) 117B at the end of the fourth row 146 along the direction of arrow B, and the purification zone (PURE N) 117A at the end of the fifth row 148. The value of N can be an integer value selected by the user as needed and is limited only by the internal dimensions of the housing 112, within which the module unit 116 and the central unit 114 are located.

[0236] The third row can be expanded by adding the central utility area 114 to the third row 150 along arrow C.

[0237] Figure 10 Each area can be a central unit or a modular unit (e.g., a fermentation unit, a purification unit, etc.), or an area that can support equipment for the unit. Figure 10 In the case of a region (e.g., region FERM 1), this region can be subdivided into fermentation units FERM 1 within the region and one or more corridors. In at least some regions, a unit may occupy the entire region.

[0238] The module unit 116 disclosed herein can be further subdivided into sub-units. For example, a unit can have a pre-virus sub-unit and a post-virus sub-unit. The post-virus sub-unit is virus-free.

[0239] At once Figure 4-9 In this regard, although the figure shows a view divided into regions described as units, the regions of the view can be specified as individual regions (such as purification zones, fermentation zones, etc.), each containing units and one or more corridors connecting the units.

[0240] Figure 11Another exemplary embodiment of facility 1400 is shown, in which the central unit 114 is shaped like a linear “ridge” from which multiple modules 116 emanate. In this embodiment, modules 116 can be subsequently added in multiple construction phases, allowing the facility to expand over time.

[0241] According to one aspect of this disclosure, a method of assembling a facility for manufacturing at least one pharmaceutical product may include providing a housing, positioning at least one central unit at least partially within the housing, and positioning at least one modular unit at least partially within the housing.

[0242] According to aspects of this disclosure, a park for manufacturing at least one pharmaceutical product is provided. Figure 12 and Figure 13 The image shows one implementation of a campus 1500. Campus 1500 comprises five customizable facilities, each indicated at 1510. Each customizable facility 1510 is configured to manufacture at least one pharmaceutical product. The five customizable facilities 1510 rely on existing infrastructure and support networks provided by the campus. For example, culture media can be supplied to customizable facility 1510 from a culture medium / buffer facility (culture medium / buffer facility) 1520 located near customizable facility 1510. Figure 12 In the middle, culture medium / buffer workshop 1520 is adjacent to four of the customizable facilities 1510.

[0243] In some aspects, the culture medium / buffer workshop 1520 is operatively coupled to at least one customizable facility 1510 and / or configured to provide or supply processing materials, such as, but not limited to, culture media or buffers, to at least one customizable facility 1510. In some aspects, the culture medium / buffer workshop 1520 may be configured to provide processing materials in transportable containers, such as bags, and to transport the processing materials to the customizable facility 1510 via trucks, rail, or other ground transportation systems on the campus. In some aspects, the campus may include a supply line 1530, and a corresponding supply line 1530 connects the culture medium / buffer workshop 1520 to each respective customizable facility 1510 to supply culture media to each customizable facility 1510 for the manufacture of (multiple) pharmaceutical products.

[0244] In some embodiments, supply line 1530 is a connecting corridor that connects culture medium / buffer room 1520 to each customizable facility 1510. In some embodiments, the connecting corridor is a 6-meter-high covered walkway. Personnel or automated vehicles can transport processing materials such as buffers or culture media through the connecting corridor to deliver the processing materials to each customizable facility 1510.

[0245] In some aspects, utility building 1540 is connected to culture medium / buffer facility 1520 by utility line 1550 to provide at least one first utility to culture medium / buffer facility 1520 via utility line 1550. For example, utility building 1540 can provide at least one first utility to... Figure 12 The culture medium / buffer room 1520 provides air and steam supply. Utility building 1540 may be configured to deliver or otherwise provide utility to the culture medium / buffer room 1520 and / or the customizable facility 1510. Utility building 1540 is located near one of the customizable facilities 1510. In some respects, utility building 1540 is optional.

[0246] In some embodiments, utility building 1540 further includes one or more utility lines connected to each customizable facility 1510, such that utility building 1540 supplies utility to culture medium / buffer workshop 1520 and to each customizable facility 1510. In some embodiments, utility building 1540 can be used to supply utility to culture medium / buffer workshop 1520, customizable facility 1510, warehouse 1560, and any other building on the campus.

[0247] The culture medium / buffer workshop area is separated from the downstream processing areas in the manufacturing wings of each customizable facility 1510. Although the culture medium / buffer workshop and the customizable facility 1510 are located on the same campus 1500, contiguity is not required as long as concentrated solutions can be delivered from the culture medium / buffer workshop 1520 to the downstream processing areas within each customizable facility 1510 without adversely affecting the stability or activity of the solutions. Solutions are scheduled, formulated, and delivered to prepare solutions at or just before their intended use. This arrangement reduces storage space on the bioreactor site and allows multiple manufacturers to share the costs associated with the culture medium / buffer workshop 1520.

[0248] In some implementations, the first layer of one of the customizable facilities 1510 includes a utility area.

[0249] Warehouse 1560 is located at Figure 12 One of the customizable facilities 1510 is located nearby. Users can store materials in warehouse 1560 and then transport the materials from warehouse 1560 to another building on campus 1500, such as one of the customizable facilities 1510 on campus. In some respects, the warehouse is optional.

[0250] Each customizable facility 1510 can be configured to manufacture pharmaceutical products different from those of other customizable facilities 1510 on campus 1500. Furthermore, as described herein, each customizable facility 1510 can be configured to produce multiple pharmaceutical products using modules, wings, or suites within the customizable facility.

[0251] Figure 13 A magnified view of a portion of the 1500-square-meter area of ​​the park is shown, revealing more details. Figure 12 One of the 1510 customizable facilities. Figure 13 The customizable facility 1510 includes different modules. Specifically, Figure 13 The customizable facility 1510 includes an office module 1570, a gown module 1580, a utility module 1590, and two manufacturing wings 1600A and 1600B.

[0252] Manufacturing wing 1600A can be configured to have three manufacturing modules 1610, each usable by a different manufacturer to produce different pharmaceutical products. Each manufacturing module 1610 has its own dedicated access within the customizable facility 1510, with independent routes from the robe module 1580 to the corresponding manufacturing module 1610. Manufacturing wing 1600B can be configured to have multiple manufacturing modules in a similar manner to manufacturing wing 1600A.

[0253] In some implementations of Park 1500, at least one of the customizable facilities 1510 has a pre-built first manufacturing wing 1600A, which is used to manufacture at least one pharmaceutical product. While the first manufacturing wing 1600A is being fully utilized for manufacturing operations, the user can construct a second manufacturing wing 1600B, which is technology-agnostic to the first manufacturing wing 1600A. This means that the second manufacturing wing 1600B is generally configured for a wide range of manufacturing operations to produce a wide range of manufactured products, which may differ from the pharmaceutical products produced by the first manufacturing wing 1600A. Because manufacturing wings 1600A and 1600B are technology-agnostic, Park 1500 provides users with flexible manufacturing options. In some implementations, the second manufacturing wing 1600B can be configured to be built within the corresponding customizable facility 1510 before the user requests additional manufacturing space. In this way, additional manufacturing wings are constructed in the five customizable facilities 1510 on Park 1500. For example, when five manufacturing wings are being used to manufacture pharmaceutical products, the user constructs a sixth manufacturing wing. By constructing additional manufacturing wings beyond the required manufacturing space, users ensure that the customizable facility does not have 100% utilization of the manufacturing wings until all ten manufacturing wings are in place. Figure 12 Each of the five customizable facilities (1510) has two manufacturing wings for manufacturing pharmaceutical products.

[0254] Utility module 1590 can also be identified as a central unit and provides at least one second utility to the modular units of customizable facility 1510, said modular units being Figure 12 The implementation scheme includes office module 1570, robe module 1580, utility module 1590, and two manufacturing wings 1600A and 1600B.

[0255] In some embodiments of the park 1500, utility building 1540 is connected to each of the customizable facilities 1510, and the first utility is the same as the second utility. In such embodiments, utility module 1590 supplements the utility provided by the utility building 1540 to the modular unit of the corresponding customizable facility 1510. In some embodiments, the first utility is different from the second utility.

[0256] In some implementation schemes of Park 1500, each customizable facility 1510 can be a customizable facility, as mentioned above. Figure 1-11 As described. For example, in some embodiments, the customizable facility 1510 includes at least one central unit and at least one module unit, the at least one module unit communicating with the at least one central unit such that the at least one central unit provides at least one second utility to the at least one module unit.

[0257] In some implementations, one or more modular units include a fermentation unit, a pre-viral unit, a post-viral unit, a utility space, a warehouse, a culture medium / buffer workshop, an office, a personnel unit, a production unit, a filling-finished product unit, a dosage preparation unit, and / or a packaging unit.

[0258] although Figure 12 and Figure 13 The housing is not shown, but each customizable facility 1510 includes a housing, similar to the one described above. Figure 1-2E or Figure 4 The housing in the described implementation of the customizable facility or another implementation of the customizable facility disclosed herein.

[0259] In some implementations, one or more central units are at least partially located within the housing, and one or more module units are at least partially located within the housing.

[0260] In some implementations, the customizable facility comprises multiple modular units arranged to maximize the number of modular units within the housing while minimizing the housing's footprint.

[0261] In some embodiments of the park 1500, the outer wall of at least one of the customizable facilities 1510 is formed by a shell of the customizable facility 1510, and the corresponding shell completely seals one or more central units and at least one modular unit of the customizable facility 1510. In some embodiments of the park 1500, the outer wall of at least one of the customizable facilities 1510 is formed by the shell of the customizable facility 1510 and at least one of the outer walls of the one or more central units and the one or more modular units of the customizable facility 1510. In some embodiments, the shell includes at least one sidewall surrounding one or more central units and one or more modular units. A top cover is fixed to the upper edge of at least one sidewall and extends over one or more central units and one or more modular units.

[0262] Building manufacturing wings within the park's customizable facilities is rapid and cost-effective. The park offers a faster production line development timeline. Because at least one manufacturing wing is pre-built and ready for use, manufacturers can reduce pre-market time by 12 months in some implementations and by 16 months in others. In some implementations, the park allows users to shorten pre-market time from four and a half years to two years. In still others, the park allows users to further reduce pre-market time, for example, from three years to two years. Drug manufacturers can easily scale up or down their manufacturing lines as needed.

[0263] The industrial park reduces financial and operational risks for manufacturers. It allows manufacturers to more easily cope with the uncertainty of drug demand over time. This disclosed industrial park allows manufacturers to respond rapidly as their demand evolves.

[0264] By providing buildings (such as utility building 1540, warehouse 1560, and culture medium / buffer workshop 1520) that can be shared by each of the customizable facilities 1510, the campus provides utility and supports technology in one location. The campus contains dedicated facilities with state-of-the-art technology. For example, each manufacturer can benefit from the state-of-the-art culture medium / buffer workshop, utility buildings, and other facilities on the campus.

[0265] In some implementations, the campus 1500 may contain more or fewer than five customizable facilities 1510. In some aspects, the campus may be built iteratively over time, such that a first customizable facility is built, and then, once the first facility reaches capacity, a second customizable facility is brought online, and so on.

[0266] According to aspects of this disclosure, a method for assembling a facility for manufacturing at least one pharmaceutical product is provided. A customizable facility configured for manufacturing at least one pharmaceutical product is provided. The customizable facility is as described above regarding... Figure 1-13 The described implementation of the customizable facility is configured to provide a culture medium / buffer workshop, which can be used to produce culture media / buffers that can be delivered to manufacturing modules within the park. In some aspects, the culture medium / buffer workshop is operatively coupled to at least one customizable facility and / or configured to supply or feed processing materials, such as, but not limited to, culture media or buffers, to at least one customizable facility. In some aspects, the culture medium / buffer workshop may be configured to supply processing materials in transportable containers, such as bags, and to transport the processing materials to the customizable facility via trucks, rail, or other ground transportation systems within the park. In some aspects, the park may include supply lines, and corresponding supply lines connect the culture medium / buffer workshop to each respective customizable facility to supply each customizable facility with culture media for the manufacture of (multiple) pharmaceutical products.

[0267] A first end of the utility line is connected to a utility building, and a second end of the utility line is connected to a culture medium / buffer workshop, to provide at least one first utility to the culture medium / buffer workshop via the utility line. For example, the first utility could be a steam supply and / or an air supply. A warehouse is located near the customizable facility and can be used to supply materials to the customizable facility. The culture medium / buffer workshop is located near the customizable facility, and the utility building is located near the customizable facility.

[0268] When the first manufacturing wing 1600A in one of the customizable facilities is being used entirely for manufacturing operations, the method involves constructing a second manufacturing wing 1600B in the corresponding customizable facility.

[0269] Figure 14 Showing according to Figure 12 The diagram shows a perspective view of the five customizable facilities 1510, culture medium / buffer workshop 1520, and utility building 1540 constructed as shown.

[0270] Figure 15A customizable facility 1710 is shown, comprising a first manufacturing wing 1800A and a second manufacturing wing 1800B. The first manufacturing wing 1800A contains a first manufacturing module 1810A and a second manufacturing module 1810B. The second manufacturing wing 1800B contains a third manufacturing module 1810C. Each manufacturing module 1810A, 1810B, and 1810C is a module unit within its respective manufacturing wing 1800A or 1800B. Each manufacturing module 1810A, 1810B, and 1810C may be operated, owned, or leased by different manufacturers. In embodiments where one of manufacturing modules 1810A, 1810B, and 1810C is leased, the module may be leased from the owner of the respective manufacturing module 1810A, 1810B, or 1810C. In some embodiments, the owner of the manufacturing module may be the owner of the park or the owner of the customizable facility 1710.

[0271] Each manufacturer may use a different robe area. In one embodiment, the first manufacturer has its own dedicated access to the first manufacturing module 1810A and dedicated access to the first robe area 1820A. Only personnel associated with the first manufacturer can enter the first robe area 1820A. Only personnel associated with the first manufacturer can enter the first manufacturing module 1810A, which is accessible via a first dedicated access route 1880A from the first robe area 1820A to the first manufacturing module 1810A.

[0272] In this implementation, the second manufacturer has dedicated access to the second manufacturing module 1810B and dedicated access to the second robe area 1820B. Only personnel associated with the second manufacturer can enter the second robe area 1820B. Personnel associated with the second manufacturer can also enter the second manufacturing module 1810B, which is accessible via a second dedicated access route 1880B from the second robe area 1820B to the second manufacturing module 1810B.

[0273] Continuing with this implementation, the third manufacturer has its own dedicated access to the third manufacturing module 1810C and dedicated access to the third robe area 1820C. Only personnel associated with the third manufacturer can enter the third robe area 1820C. Only personnel associated with the third manufacturer can enter the third manufacturing module 1810C, which is accessible from the third robe area 1820C to the third manufacturing module 1810C via the third dedicated access route 1880C.

[0274] Customizable facility 1710 includes utility module 1890, which provides utility to other modules in customizable facility 1710, such as first manufacturing module 1810A, second manufacturing module 1810B, and third manufacturing module 1810C.

[0275] Figure 15 Customizable facilities can be included in this publicly disclosed campus, such as Figure 12 The park is 1500.

[0276] Because the customizable facility 1710 contains manufacturing modules 1810A, 1810B, and 1810C, each with its own dedicated access routes 1880A, 1880B, and 1880C, these modules are isolated from each other. This avoids cross-contamination among employees of the respective manufacturers. The isolation of the three manufacturing modules 1810A, 1810B, and 1810C also prevents cross-contamination of products manufactured by the respective manufacturers. For example, this prevents pathogens from one manufacturing module within the customizable facility 1710 from spreading to another within the same manufacturing module.

[0277] Utility module 1890 provides shared utility to three manufacturing modules 1810A, 1810B, and 1810C. Similarly, when customizable facilities 1710 are integrated into a campus (such as...), Figure 12 or Figure 14 When in the park shown, utility building 1540 can be connected to three manufacturing modules 1810A, 1810B, and 1810C to deliver utility to the three manufacturing modules 1810A, 1810B, and 1810C.

[0278] In this way, the customizable facility 1710 provides shared utility while offering a safe and isolated manufacturing environment for manufacturers within the manufacturing module.

[0279] According to aspects of this disclosure, methods for managing pharmaceutical facilities are provided. The methods include providing a park for manufacturing one or more pharmaceutical products. In some embodiments, the park may be the park described herein, such as… Figure 12The campus is 1500. For example, in some embodiments, the campus includes at least one customizable facility configured to manufacture one or more pharmaceutical products. In some embodiments, the campus also includes a culture medium / buffer workshop. In some embodiments, the campus also includes a bagging unit in the culture medium / buffer workshop, where culture media / buffers are bagged so that they can be moved by ground transport to the customizable facility. In some aspects, the culture medium / buffer workshop is operatively coupled to at least one customizable facility and / or configured to provide or supply processing materials, such as, but not limited to, culture media or buffers, to at least one customizable facility. In some aspects, the culture medium / buffer workshop may be configured to provide processing materials in transportable containers such as bags, and to transport the processing materials to the customizable facility via truck, rail, or other ground transport system on the campus. In some aspects, the campus may include supply lines, and corresponding supply lines connect the culture medium / buffer workshop to each respective customizable facility to supply each customizable facility with culture media for manufacturing (multiple) pharmaceutical products.

[0280] In some implementations, the park also includes utility buildings connected by utility lines to the culture medium / buffer workshop to provide at least one primary utility to the culture medium / buffer workshop via the utility lines. Methods of managing pharmaceutical facilities also include providing at least a portion of the park to customers who wish to manufacture pharmaceutical products (e.g., through sale, lease, or another contract).

[0281] In some implementations, a portion of what is offered to customers within the park includes a manufacturing wing within one of the park's customizable facilities.

[0282] In some implementations, a portion of the facilities offered to customers within the park includes manufacturing modules within one of the manufacturing wings of one of the park's customizable facilities.

[0283] This method of managing pharmaceutical facilities can be implemented by the park owner. In some implementations, the park owner provides customers with a first option to purchase a portion of the park and a second option to lease a portion of the park from the owner. In some implementations, the park owner provides customers with only the option to purchase a portion of the park. For example, the park owner may provide customers with the option to purchase a portion of a customizable facility on the park. Specifically, the park owner may provide customers with the option to purchase manufacturing modules within the customizable facility. In some implementations, the park owner provides customers with only the option to lease a portion of the park. For example, the park owner may provide customers with the option to lease a portion of a customizable facility. Specifically, the park owner may provide customers with the option to lease manufacturing modules within the customizable facility.

[0284] In some implementations, the park owner may offer customers an additional option, such as allowing customers to rent a portion of the park for a first period, and then allowing customers to choose whether to purchase that portion of the park at the end of the first period. Additional ownership and rental options are also within the scope of this disclosure. In some implementations, the park owner proposes assigning its own employees to manufacture pharmaceutical products on behalf of customers within a designated portion of the park.

[0285] According to aspects of this disclosure, a method for adjusting the capacity of a pharmaceutical facility is provided. The method for adjusting capacity includes providing a park for manufacturing at least one pharmaceutical product. In some embodiments, the park may be a park described herein, such as... Figure 12 The campus is 1500. For example, in some embodiments, the campus includes at least one customizable facility configured to manufacture one or more pharmaceutical products. In some embodiments, the campus also includes a culture medium / buffer workshop. In some embodiments, the campus also includes a bagging unit in the culture medium / buffer workshop, where culture media / buffers are bagged so that they can be moved to the customizable facility by ground transport. In some aspects, the culture medium / buffer workshop is operatively coupled to at least one customizable facility and / or configured to provide or supply processing materials, such as, but not limited to, culture media or buffers, to at least one customizable facility. In some aspects, the culture medium / buffer workshop may be configured to provide processing materials in transportable containers such as bags, and to transport the processing materials to the customizable facility via truck, rail, or other ground transport system on the campus. In some aspects, the campus may include supply lines, and corresponding supply lines connect the culture medium / buffer workshop to each respective customizable facility to supply each customizable facility with culture media for manufacturing (multiple) pharmaceutical products.

[0286] In some implementations, the park also includes utility buildings connected by utility lines to the culture medium / buffer facility to provide at least one primary utility to the culture medium / buffer facility via the utility lines. Methods of managing pharmaceutical facilities also include providing at least a portion of the park to customers who wish to manufacture pharmaceutical products.

[0287] The method also includes providing at least a first portion of the park to a first customer who wishes to manufacture a first pharmaceutical product. The method further includes constructing at least a second portion of the park for manufacturing a second pharmaceutical product. This second portion is technology-agnostic. For example, the park owner may provide a first manufacturing module to the first customer who wishes to manufacture the first pharmaceutical product. The park owner constructs the second manufacturing module (or otherwise ensures that the second manufacturing module is usable by a second customer). This second manufacturing module is technology-agnostic.

[0288] In some implementations, the second manufacturing module can then be used by the manufacturer to manufacture a second product, which may be different from or the same as the first product.

[0289] In some implementations, the park owner then provides at least a second portion of the park to a second customer. The park owner constructs a third manufacturing module (or otherwise ensures that the third manufacturing module is usable by a third customer). This third manufacturing module is technology-agnostic.

[0290] By constructing additional sections of the park beyond the required manufacturing space, users ensure that the customizable facility does not have 100% utilization of the manufacturing wings until all manufacturing wings on the park are used to manufacture pharmaceutical products.

[0291] In some implementations, the park owner provides a first portion of the park to a first customer, accessible only via a first dedicated access route, which is accessible to the first customer but not to a second customer. The park owner then provides a second portion of the park to a second customer, accessible only via a second dedicated access route, which is accessible to the second customer but not to the first customer. The first and second portions are not necessarily limited to manufacturing modules.

[0292] In some implementations, the park owner continuously maintains a technology-agnostic portion of the park in a state of readiness for new customers to begin manufacturing drugs. This allows the park owner to respond rapidly to changes in drug demand. The technology-agnostic portion of the park that is ready for new customers to begin manufacturing drugs can be quickly leased, rented, sold, or otherwise used by new or existing customers to meet market demand for the drugs.

[0293] The methods for managing drug facilities and adjusting their capacity can be carried out by the park owner or another party, such as the park operator or a party acting on behalf of the park owner.

[0294] Examples of fermentation units

[0295] Fermentation unit 116B houses equipment suitable for cell culture and / or fermentation. For example, equipment for cell culture and fermentation includes, but is not limited to, bioreactors (e.g., suitable for culturing cells or fermentation), tanks (e.g., suitable for containing cells, culture media, or products produced by cells), decanting devices, centrifuges, pumps, and other equipment that can be used for product recovery. A refold tank and a microfiltration unit will be used in the microbial fermentation process.

[0296] In one embodiment, fermentation unit 116B contains one or more bioreactor units suitable for culturing cells. The bioreactor units can perform one or more of the following: feeding of nutrients and / or carbon sources, injection of suitable gases (e.g., oxygen), flow of fermentation or cell culture medium, separation of gas and liquid phases, maintenance of growth temperature, maintenance of pH levels, stirring (e.g., agitation), and / or cleaning / sterilization. The fermentation unit may contain 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, or 100 or more bioreactors. In various embodiments, the bioreactors are suitable for batch, semi-batch, fed-batch, perfusion, and / or continuous fermentation processes. In one embodiment, the bioreactor is a stirred tank reactor. In one embodiment, the bioreactor is an airlift reactor. In one embodiment, the bioreactor can have a volume of about 100 ml to about 50,000 liters. Non-limiting examples include 100 ml, 250 ml, 500 ml, 750 ml, 1 L, 2 L, 3 L, 4 L, 5 L, 6 L, 7 L, 8 L, 9 L, 10 L, 15 L, 20 L, 25 L, 30 L, 40 L, 50 L, 60 L, 70 L, 80 L, 90 L, 100 L, 150 L, 200 L, 250 L, 300 L, 350 L, 400 L, 450 L, 500 L, and 550 L. Volumes of 600 liters, 650 liters, 700 liters, 750 liters, 800 liters, 850 liters, 900 liters, 950 liters, 1000 liters, 1500 liters, 2000 liters, 2500 liters, 3000 liters, 3500 liters, 4000 liters, 4500 liters, 5000 liters, 6000 liters, 7000 liters, 8000 liters, 9000 liters, 10,000 liters, 15,000 liters, 20,000 liters, or 50,000 liters.

[0297] In one embodiment, the bioreactor is suitable for culturing suspension cells or adherent cells. In one embodiment, the fermentation kit is suitable for cell therapy and / or viral therapy operations. In one embodiment, the bioreactor is suitable for culturing prokaryotic or eukaryotic cells. Examples of cells include, but are not limited to, bacterial cells (e.g., *Escherichia coli*, *Pichia pastoris*), yeast cells (e.g., *Saccharomyces cerevisiae*, *Trichoderma reesei*), plant cells, insect cells (e.g., Sf9), Chinese hamster ovary cells (CHO, and any genetically modified or derived CHO cell lines), mouse cells (e.g., mouse embryonic fibroblasts, cells derived from mouse cancer models), human cells (e.g., cells from any tissue or organ, cells from cancer or other diseased cell lines, stem cells), hybridoma cells, or other genetically modified or hybrid cells. In one embodiment, the cells express or produce products, such as recombinant therapeutic or diagnostic products. Examples of cell-derived products include, but are not limited to, antibody molecules (e.g., monoclonal antibodies, bispecific antibodies), fusion proteins (e.g., Fc fusion proteins, chimeric cytokines), other recombinant proteins (e.g., glycosylated proteins, enzymes, hormones), or lipid-encapsulated particles (e.g., exosomes, virus-like particles). In one embodiment, the fermentation unit also includes equipment for separating, purifying, and isolating such products from cells. In one embodiment, the facility and / or bioreactor can be used to produce biosimilar products.

[0298] In the implementation plan, the fermentation unit conforms to good manufacturing process and biosafety standards. In one implementation plan, the fermentation unit conforms to Biosafety Level 1 (BSL1), Biosafety Level 2 (BSL2), Biosafety Level 3 (BSL3), or Biosafety Level 4 (BSL4).

[0299] A fermentation unit may comprise sub-compartments, each of which may be used for different functions or aspects supporting cell culture, fermentation, and production processes. For example, a fermentation unit may include sub-compartments housing one or more bioreactors, sub-compartments housing product recovery equipment, sub-compartments for inoculation, and sub-compartments for cleaning and purifying the equipment and for operators handling such equipment.

[0300] Examples of downstream processing units

[0301] The purification unit 116A discussed above is an example of a downstream processing unit.

[0302] As an example, a standard downstream processing (DSP) unit comprises pre-viral and post-viral separation subunits. While virulence reduction does occur throughout typical mammalian cell-derived protein purification, the critical virulence reduction step is considered to be the appropriate point of separation from the post-viral separation subunit, which should be considered substantially virus-free. The post-viral separation subunit houses equipment and utilities suitable for any of the following: ultrafiltration (tangential filtration), normal filtration, chromatography, formulation, titration, mixing, concentration, buffer exchange, raw material container filling, and freezing.

[0303] Various embodiments and / or examples of this disclosure have been described for illustrative purposes, but are not intended to be exhaustive or limited to the disclosed embodiments. Many modifications and variations will be apparent to those skilled in the art without departing from the scope and spirit of the described embodiments. The terminology used herein has been chosen to best explain the principles of the embodiments, their practical application, or technical improvements to technologies found in the market, or to enable those skilled in the art to understand the embodiments disclosed herein.

[0304] The various embodiments described in this disclosure can be used to manufacture pharmaceutical and biopharmaceutical products. The apparatuses, facilities, and methods described herein are suitable for culturing any desired cell lines, including prokaryotic and / or eukaryotic cell lines. Furthermore, in embodiments, the apparatuses, facilities, and methods are suitable for culturing suspension cells or adherent cells and are adapted to be configured for the production of pharmaceutical and biopharmaceutical products, such as peptide products, nucleic acid products (e.g., DNA or RNA), or cells and / or viruses, such as cell and / or virus production operations for cell and / or virus therapies.

[0305] In the implementation scheme, cells express or produce products, such as recombinant therapeutic or diagnostic products. Examples of cell-generated products, as described in more detail below, include, but are not limited to, antibody molecules (e.g., monoclonal antibodies, bispecific antibodies), antibody mimics (peptide molecules that specifically bind to antigens but are structurally unrelated to antibodies, such as DARPins, affibodies, adnectin, or IgNARs), fusion proteins (e.g., Fc fusion proteins, chimeric cytokines), other recombinant proteins (e.g., glycosylated proteins, enzymes, hormones), viral therapeutics (e.g., anticancer oncolytic viruses, viral vectors for gene therapy, and viral immunotherapy), cell therapies (e.g., pluripotent stem cells, mesenchymal stem cells, and adult stem cells), vaccine or lipid-encapsulated particles (e.g., exosomes, virus-like particles), RNA (e.g., siRNA) or DNA (e.g., plasmid DNA), antibiotics, or amino acids. In the implementation scheme, the apparatus, facilities, and methods can be used to produce biosimilars.

[0306] As mentioned, in the embodiments, the apparatus, facilities, and methods allow the production of eukaryotic cells, such as mammalian cells or lower eukaryotic cells, such as yeast cells or filamentous fungal cells, or prokaryotic cells, such as Gram-positive cells or Gram-negative cells, and / or eukaryotic or prokaryotic cell products, such as proteins, peptides, antibiotics, amino acids, and nucleic acids (e.g., DNA or RNA), which are synthesized by eukaryotic cells in a large-scale manner. Unless otherwise stated herein, the apparatus, facilities, and methods may include any desired volume or production capacity, including but not limited to laboratory-scale, pilot-scale, and full-scale production capabilities.

[0307] Furthermore, unless otherwise stated herein, apparatus, facilities, and methods may include any suitable reactor, including but not limited to stirred tanks, airlifts, fiber, microfiber, hollow fiber, ceramic matrix, fluidized bed, fixed bed, and / or sputtered bed bioreactors. As used herein, "reactor" may include fermenters or fermentation units, or any other reaction vessel, and the term "reactor" may be used interchangeably with "fermenter." For example, in some aspects, exemplary bioreactor units may perform one or more or all of the following: feeding of nutrients and / or carbon sources, injection of suitable gases (e.g., oxygen), inlet and outlet flow of fermentation or cell culture media, separation of gas and liquid phases, maintenance of temperature, maintenance of oxygen and CO2 levels, maintenance of pH levels, stirring (e.g., agitation), and / or cleaning / sterilization. Exemplary reactor units, such as fermentation units, may contain multiple reactors within a unit. For example, a unit may have 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, or 100 or more bioreactors in each unit, and / or a facility may contain multiple units within a facility having one or more reactors. In various embodiments, the bioreactor may be suitable for batch, semi-feed-batch, fed-batch, perfusion, and / or continuous fermentation processes. Any suitable reactor diameter may be used. In embodiments, the bioreactor may have a volume of from about 100 mL to about 50,000 L. Non-limiting examples include 100 ml, 250 ml, 500 ml, 750 ml, 1 L, 2 L, 3 L, 4 L, 5 L, 6 L, 7 L, 8 L, 9 L, 10 L, 15 L, 20 L, 25 L, 30 L, 40 L, 50 L, 60 L, 70 L, 80 L, 90 L, 100 L, 150 L, 200 L, 250 L, 300 L, 350 L, 400 L, 450 L, 500 L, 550 L, 6 Volumes of 00 liters, 650 liters, 700 liters, 750 liters, 800 liters, 850 liters, 900 liters, 950 liters, 1000 liters, 1500 liters, 2000 liters, 2500 liters, 3000 liters, 3500 liters, 4000 liters, 4500 liters, 5000 liters, 6000 liters, 7000 liters, 8000 liters, 9000 liters, 10,000 liters, 15,000 liters, 20,000 liters, and / or 50,000 liters. Additionally, suitable reactors can be reusable, single-use, disposable, or non-disposable, and can be formed from any suitable material, including metal alloys such as stainless steel (e.g., 316L or any other suitable stainless steel) and Inconel, plastics, and / or glass.

[0308] In implementations and unless otherwise stated herein, the apparatus, facilities, and methods described herein may also include any suitable unit operations and / or equipment not otherwise mentioned, such as operations and / or equipment for separating, purifying, and isolating such products. Any suitable facility and environment may be used, such as conventional rod-type building facilities, modular, mobile and temporary facilities, or any other suitable structure, facility, and / or layout. For example, in some implementations, a modular cleaning room may be used. Additionally, unless otherwise stated, the apparatus, systems, and methods described herein may be housed and / or carried out in a single location or facility, or alternatively in separate locations and / or facilities or multiple locations and / or facilities.

[0309] By way of non-limiting example and not limitation, U.S. Publications 2013 / 0280797; 2012 / 0077429; 2009 / 0305626; and U.S. Patent Nos. 8,298,054; 7,629,167; and 5,656,491 (which are incorporated herein by reference in their entirety) describe exemplary facilities, devices, and / or systems that may be suitable.

[0310] In this embodiment, the cells are eukaryotic cells, such as mammalian cells. Mammalian cells can be, for example, human, rodent, or bovine cell lines or cell strains. Examples of such cells, cell lines, or cell strains include, for example, mouse myeloma (NSO) cell lines, Chinese hamster ovary (CHO) cell lines, HT1080, H9, HepG2, MCF7, MDBK Jurkat, NIH3T3, PC12, BHK (juvenile hamster kidney cells), VERO, SP2 / 0, YB2 / 0, Y0, C127, L cells, COS (e.g., COS1 and COS7), QC1-3, HEK-293, VERO, PER.C6, HeLA, EB1, EB2, EB3, oncolytic, or hybridoma cell lines. Preferably, the mammalian cells are CHO cell lines. In one embodiment, the cells are CHO cells. In one embodiment, the cells are CHO-K1 cells, CHO-K1 SV cells, DG44 CHO cells, DUXB11 CHO cells, CHOS, CHO GS knockout cells, CHO FUT8 GS knockout cells, CHOZN, or CHO-derived cells. CHO GS knockout cells (e.g., GSKO cells) are, for example, CHO-K1 SV GS knockout cells. CHO FUT8 knockout cells are, for example, Potelligent® CHOK1 SV (Lonza Biologics, Inc.). Eukaryotic cells may also be avian cells, cell lines, or cell strains, such as, for example, EBx® cells, EB14, EB24, EB26, EB66, or EBv13.

[0311] In one implementation, the eukaryotic cell is a stem cell. Stem cells can be, for example, pluripotent stem cells, including embryonic stem cells (ESCs), adult stem cells, induced pluripotent stem cells (iPSCs), tissue-specific stem cells (e.g., hematopoietic stem cells), and mesenchymal stem cells (MSCs).

[0312] In one embodiment, the cell is any differentiated form of cell described herein. In one embodiment, the cell is a cell derived from any primary cell in culture.

[0313] In the implementation scheme, the cells are hepatocytes, such as human hepatocytes, animal hepatocytes, or non-parenchymal cells. For example, the cells may be plateable metabolism-qualified human hepatocytes, plateable induction-qualified human hepatocytes, plateable Qualyst Transporter Certified™ human hepatocytes, suspension-qualified human hepatocytes (containing hepatocytes from 10 donors and 20 donors combined), human hepatic Kupffer cells, human hepatic stellate cells, canine hepatocytes (containing single and combined Beagle hepatocytes), mouse hepatocytes (containing CD-1 and C57BI / 6 hepatocytes), rat hepatocytes (containing Sprague-Dawley, Wistar Han, and Wistar hepatocytes), monkey hepatocytes (containing cynomolgus or rhesus monkey hepatocytes), cat hepatocytes (containing domestic shorthair hepatocytes), and rabbit hepatocytes (containing New Zealand White hepatocytes). Exemplary hepatocytes were available from Triangle Research Labs, LLC, 6 Davis Drive Research Triangle Park, North Carolina, USA 27709.

[0314] In one embodiment, the eukaryotic cell is a lower eukaryotic cell, such as, for example, yeast cells (e.g., Pichia genus (e.g., Pichia pastoris, Pichia ethanolica, Pichia kluyveri, and Pichia angusta)), Komagataella genus (e.g., Komagataella pastoris, Komagata ellapseudopastoris, or Komagataella phaffii), yeast genus (e.g., Saccharomyces cerevisae, Saccharomyces cerevisiae, Saccharomyces kluyveri, Saccharomyces uvarum)), Kluyveromyces genus (e.g., Kluyveromyces lactis, Kluyveromyces marxianus)), and Candida genus (e.g., Candida utilis). *Pichia pastoris* is a preferred yeast. Examples of *Pichia pastoris* strains include *Candida cacaoi*, *Candida boidinii*, *Geotrichum* (e.g., *Geotrichum fermentans*), *Hansenula polymorpha*, *Yarrowialipolytica*, and *Schizosaccharomyces pombe*. *Pichia pastoris* is also preferred. Examples of *Pichia pastoris* strains include X33, GS115, KM71, KM71H, and CBS7435.

[0315] In one embodiment, the eukaryotic cells are fungal cells (e.g., *Aspergillus* (e.g., *Aspergillus niger*, *Aspergillus fumigates*, *Aspergillus orzyae*, *Aspergillus nidula*)), *Acremonium* (e.g., *Acremonium thermophilum*)), *Chaetomium* (e.g., *Chaetomium thermophilum*)), *Chrysosporium* (e.g., *Chrysosporium thermophile*)), *Cordyceps* (e.g., *C. militaris*)), *Corynascus*, *Ctenomyces*, *Fusarium* (e.g., *Fusarium oxysporum*)), and *Glomerella* (e.g., *Glomerella gracilis*). The genera *graminicola*, *Hypocrea* (e.g., *H. jecorina*), *Magnaporthe* (e.g., *M. orzyae*), *Myceliophthora* (e.g., *M. thermophile*), *Nectria* (e.g., *N. heamatococca*), *Neurospora* (e.g., *N. crassa*), *Penicillium*, *Sporotrichum* (e.g., *S. thermophile*), *Thielavia* (e.g., *T. terrestris*, *T. thermoothallica*), *Trichoderma* (e.g., *Trichoderma reesei*), or *Verticillium* (e.g., *V. dahlia*).

[0316] In one embodiment, the eukaryotic cells are insect cells (e.g., Sf9, Mimic™ Sf9, Sf21, HighFive™ (BT1-TN-5B1-4) or BT1-Ea88 cells), algal cells (e.g., cells of the genera *Amphora*, *Bacillariophyceae*, *Dunaliella*, *Chlorella*, *Chlamydomonas*, *Cyanophyta* (cyanobacteria), *Nannochloropsis*, *Spirulina*, or *Ochromonas*), or plant cells (e.g., cells from monocotyledonous plants such as corn, rice, wheat, or *Setaria*), or cells from dicotyledonous plants such as cassava, potato, soybean, tomato, tobacco, alfalfa, *Physcomitrella patens*, or *Arabidopsis*).

[0317] In one implementation, the cell is a bacterium or a prokaryotic cell.

[0318] In this embodiment, the prokaryotic cells are Gram-positive cells, such as Bacillus, Streptomyces, Streptococcus, Staphylococcus, or Lactobacillus. Suitable Bacillus species include, for example, Bacillus subtilis, Bacillus amyloliquefaciens, Bacillus licheniformis, Bacillus natto, or Bacillus megaterium. In this embodiment, the cells are Bacillus subtilis, such as Bacillus subtilis 3NA and Bacillus subtilis 168. The Bacillus can be obtained, for example, from the Bacillus Genetic Stock Center, Biological Sciences 556, 484 West 12th Avenue, Columbus, OH 43210-1214.

[0319] In one implementation, the prokaryotic cells are Gram-negative cells, such as Salmonella species or Escherichia coli, such as TG1, TG2, W3110, DH1, DHB4, DH5a, HMS 174, HMS174 (DE3), NM533, C600, HB101, JM109, MC4100, XL1-Blue and Origami, as well as those derived from Escherichia coli B strains, such as, for example, BL-21 or BL21 (DE3), all of which are commercially available.

[0320] Suitable host cells can be purchased from, for example, culture collections such as DSMZ (German Microbial Culture Collection, Braunschweig, Germany) or the American Type Culture Collection (ATCC).

[0321] In this embodiment, the cultured cells are used to produce proteins for therapeutic purposes, such as antibodies, including monoclonal antibodies and / or recombinant proteins. In this embodiment, the cultured cells produce peptides, amino acids, fatty acids, or other useful biochemical intermediates or metabolites. For example, in this embodiment, molecules with molecular weights ranging from about 4,000 Daltons to greater than about 140,000 Daltons can be prepared. In this embodiment, these molecules can have a range of complexities and may include post-translational modifications, including glycosylation.

[0322] In the implementation plan, the proteins are, for example, BOTOX, Myobloc, Neurobloc, Dysport (or other botulinum neurotoxin serotypes), aglucosidase α, daptomycin, YH-16, human chorionic gonadotropin α, filgrastim, cetrorelix, interleukin-2, aldesleukin, teceleulin, denileukin diftitox, interferon α-n3 (injection), interferon α-nl, DL-8234, interferon, Suntory (γ-1a), interferon γ, thymosin α1, tasonermin, DigiFab, ViperaTAb, EchiTAb, CroFab, nesiritide, abatacept, alefacept, Rebif, and etordamine α. (eptoterminalfa), teriparatide (osteoporosis), calcitonin injection (bone disease), calcitonin (nasal, osteoporosis), etanercept, hemoglobin glutamer 250 (bovine), drotrecogin alpha, collagenase, carperitide, recombinant human epidermal growth factor (topical gel, wound healing), DWP401,Erythropoietin alpha (darbepoetin alpha), epoetin omega, epoetin beta, epoetin alpha, desirudin, lepirudin, bivalirudin, nonacog alpha, mononine, eptacog alpha (activated), recombinant factor VIII + VWF, recombinate, recombinant factor VIII, factor VIII (recombinant), Alphnmate, octocog alpha, factor VIII, palifermin, indikinase, tenecteplase, alteplase, pamiteplase, reteplase, nateplase, monteplase, follitropin alpha alpha), rFSH, hpFSH, micafungin, pegfilgrastim, lenograstim, nartograstim, sermorelin, glucagon, exenatide, pramlintide, iniglucerase, galsulfase, leucotropin, molgramostirn, triptorelin acetate Acetate), histrelin (subcutaneous implant, Hydron), deslorelin, histrelin, nafarelin, leuprolide sustained-release reservoir (ATRIGEL), leuprolide implant (DUROS), goserelin, Eutropin, KP-102 program, growth hormone, mecasermin (growth failure), enlfavirtide, Org-33408, insulin glargine, insulin glutares, insulin (inhalation), insulin lispro, insulin deternir, insulin (oral).RapidMist, mecaserminrinfabate, anakinra, celmoleukin, 99 mTc-apcitide injection, myelopid, recombinant interferon β-1b (Betaseron), glatiramer acetate, Gepon, sargramostim, oprelvekin, human leukocyte-derived alpha interferon, Bilive, recombinant insulin, recombinant human insulin, aspart insulin, mecasenin, Roferon-A, interferon-α2, Alfaferone, interferon alfacon-1, interferon α, Avonex recombinant human luteinizing hormone, deoxyribonuclease alpha, trafermin, ziconotide, taltirelin, depotamine α (diboterminalfa), atosiban, becaplermin, eptifibatide, Zemaira, CTC-111, Shanvac-B, quadrivalent HPV vaccine, octreotide, lanreotide, ancestirn, agalsidase β, agalsidase α, laronidase, prezatide copper acetate (topical gel), rasburicase, ranibizumab, interferon γ-1b (Actimmune), PEG-Intron, Tricomin, Recombinant House Dust Mite Allergy Desensitization Injection, Recombinant Human Parathyroid Hormone (PTH) 1-84 (sc, osteoporosis), Epoetin δ, Genetically Modified Antithrombin III, Granditropin, Hyaluronidase (Vitrase), Recombinant Insulin, Interferon-α (oral tablets), GEM-21S, Vapreotide, Idursulfase, Omnapatrilat, Recombinant Serum Albumin, Certolizumab Pegol, Glucarpidase, Recombinant Human C1 Esterase Inhibitor (Angioedema), Lanoteplase, Recombinant Human Growth Hormone, Enfuvirtide (needle-free injection).Biojector 2000), VGV-1, interferon (α), lucinactant, avitadil (inhalation, for lung diseases), icatibant, ecallantide, omeganan, Aurograb, pexiganan acetate Acetate), ADI-PEG-20, LDI-200, degarelix, cintredelinbesudotox, Favld, MDX-1379, ISAtx-247, liraglutide, teriparatide (for osteoporosis), tifacogin, AA4500, T4N5 liposome lotion, catutoxumab, DWP413, ART-123, Chrysalin, desmoteplase, amedipase, chorionic follicle-stimulating hormone (hFS-α) Corifollitropinalpha, TH-9507, teduglutide, Diamyd, DWP-412, growth hormone (continuously released injection), recombinant G-CSF, insulin (inhalation, AIR), insulin (inhalation, Technosphere), insulin (inhalation, AERx), RGN-303, DiaPep277, interferon beta (for hepatitis C virus infection (HCV)), interferon alpha-n3 (oral), belacept, transdermal insulin patch, AMG-531, MBP-8298, Xerecept, opebacan, AIDSVAX, GV-1001, LymphoScan, ranpirnase, lipoxysan, lusupultide, MP52 (β-tricalcium phosphate carrier, bone regeneration), melanoma vaccine, sipuleucel-T, CTP-37, Insegia, vitespen, human thrombin (freezing, surgical bleeding), thrombin, TransMID, snake venom plasminogen lysate (alfimeprase), Puricase, terlipressin (intravenous, hepatorenal syndrome), EUR-1008M, recombinant FGF-I (injectable, vascular disease), BDM-E, rotigaptide, ETC-216, P-113, MBI-594AN, duramycin (inhalation,Cystic fibrosis), SCV-07, OPI-45, Endostatin, Angiostatin, ABT-510, Bowman Birk inhibitor concentrate, XMP-629, 99 mTc-Hynic-annexin V, kahalalide F, CTCE-9908, Teverelix (extended release), Ozarelix, Romidepsin, BAY-504798, Interleukin-4, PRX-321, Pepscan, Iboctadekin, Rh lactoferrin, TRU-015, IL-21, ATN-161, Cilengitide, Albuferon, Biphasix, IRX-2, ω-interferon, PCK-3145, CAP-232, Pasireotide, huN901-DMI, Ovarian cancer immunotherapy vaccine, SB-249553, Oncovax-CL, OncoVax-P, BLP-25, CerVax-16, Multi-epitope peptide melanoma vaccine (MART-1, gp100, tyrosinase), Nemifi Tide), rAAT (inhalation), rAAT (dermatology), CGRP (inhalation, asthma), pegsunercept, thymosin β4, plitidepsin, GTP-200, ramoplanin, GRASPA, OBI-1, AC-100, salmon calcitonin (oral, eligen), calcitonin (oral, osteoporosis), examorelin, capremorelin, Cardeva, velafermin, 131I-TM-601, KK-220, T-10, ularitide, depelestat, hematide, Chrysalin (topical), rNAPc2, recombinant factor V111 (PEGylated liposomes), bFGF, PEGylated recombinant styrokinase variant, V-10153, SonoLysis Prolyse, NeuroVax, CZEN-002, Islet Cell Regeneration Therapy, rGLP-1, BIM-51077, LY-548806, Exenatide (Controlled Release)Medisorb), AVE-0010, GA-GCB, avorelin, ACM-9604, linaclotide eacetate, CETi-1, Hemospan, VAL (for injection), rapid-acting insulin (for injection, Viadel), intranasal insulin, insulin (inhalation), insulin (oral, eligen), recombinant methionine-based human leptin, Pitrakinra (subcutaneous injection, eczema), Pitrakinra (inhaled dry powder, asthma), Multikine, RG-1068, MM-093, NBI-6024, AT-001, PI-0824, Org-39141, Cpn10 (autoimmune diseases / inflammation), talactoferrin (topical), rEV-131 (ophthalmology), rEV-131 (respiratory diseases), oral recombinant human insulin (diabetes), RPI-78M, oprelvekin (oral), CYT-99007 CTLA4-Ig, DTY-001, valategrast, interferon α-n3 (local), IRX-3, RDP-58, Tauferon, bile salt-stimulated lipase, Meripase, alkaline phosphatase, EP-2104R, Melanotan-II, bremelanotide, ATL-104, recombinant human microplasmin, AX-200, SEMAX, ACV-1, Xen-2174, CJC-1008, dynorphin A, SI-6603, LAB GHRH, AER-002, BGC-728, Malaria vaccine (virovirus, PeviPRO), ALTU-135, Parvovirus B19 vaccine, Influenza vaccine (recombinant neuraminidase), Malaria / HBV vaccine, Anthrax vaccine, Vacc-5q, Vacc-4x, HIV vaccine (oral), HPV vaccine, Tat toxoid, YSPSL, CHS-13340, PTH(1-34) liposomal cream (Novasome), Ostabolin-C, PTH analogues (topical, for psoriasis).MBRI-93.02, MTB72F vaccine (tuberculosis), MVA-Ag85A vaccine (tuberculosis), FARA04, BA-210, recombinant virucidal FIV vaccine, AG-702, OxSODrol, rBetV1, Der-p1 / Der-p2 / Der-p7 allergen-targeted vaccine (house dust mite allergy), PR1 peptide antigen (leukemia), mutant ras vaccine, HPV-16 E7 lipopeptide vaccine, labyrinthine vaccine Vaccines (adenocarcinoma), CML vaccine, WT1-peptide vaccine (cancer), IDD-5, CDX-110, Pentrys, Norelin, CytoFab, P-9808, VT-111, icrocaptide, telbermin (dermatitis, diabetic foot ulcer), rupintrivir, reticulose, rGRF, HA, α-galactosidase A, ACE-011, ALTU-140, CGX-1160, angiotensin-based therapeutic vaccine, D- 4F, ETC-642, APP-018, rhMBL, SCV-07 (oral, for tuberculosis), DRF-7295, ABT-828, ErbB2 specific immunotoxin (anti-cancer), DT3SSIL-3, TST-10088, PRO-1762, Combotox, cholecystokinin-β / gastrin receptor-binding peptide, 111In-hEGF, AE-37, trasnizumab-DM1, antagonist G, IL-12 (recombinant), PM-02734, IMP-321, rhIGF-BP3, BLX-883 CUV-1647 (topical), L-19-based radioimmunotherapy (cancer), Re-188-P-2045, AMG-386, DC / 1540 / KLH vaccine (cancer), VX-001, AVE-9633, AC-9301, NY-ESO-1 vaccine (peptide), NA17.A2 peptide, melanoma vaccine (pulse antigen therapy), prostate cancer vaccine, CBP-501, recombinant human lactoferrin (dry eye), FX-06, AP-214, WAP-8294A (injectable), ACP-HIP, SUN-11031, peptide YY [3-36] (obesity, intranasal), FGLL, atacicept, BR3-Fc, BN-003, BA-058, human parathyroid hormone 1-34 (nasal, osteoporosis), F-18-CCR1, AT-1100 (celiac disease / diabetes), JPD-003, PTH (7-34) liposome cream (Novasome), dextrin (ophthalmic,Dry eye), CAB-2, CTCE-0214, GlycoPEGylated erythropoietin, EPO-Fc, CNTO-528, AMG-114, JR-013, Factor XIII, aminocandin, PN-951, 716155, SUN-E7001, TH-0318, BAY-73-7977, teverelix (immediate release), EP-51216, hGH (Controlled release, Biosphere), OGP-I, sifuvirtide, TV4710, ALG-889, Org-41259, rhCC10, F-991, thymopentin (for lung disease), r(m)CRP, liver-selective insulin, subalin, L19-IL-2 fusion protein, elafin, NMK-150, ALTU-139, EN-122004 rhTPO, thrombopoietin receptor agonists (thrombocytopenia), AL-108, AL-208, nerve growth factor antagonists (pain), SLV-317, CGX-1007, INNO-105, oral teriparatide (eligen), GEM-OS1, AC-162352, PRX-302, LFn-p24 fusion vaccine (Therapore), EP-1043, Streptococcus pneumoniae (S... Pediatric vaccines for pneumonia, malaria, Neisseria meningitidis Group B vaccine, neonatal Group B Streptococcus vaccine, anthrax vaccine, HCV vaccine (gpE1 + gpE2 + MF-59), otitis media therapy, HCV vaccine (core antigen + ISCOMATRIX), hPTH (1-34) (transdermal, ViaDerm), 768974, SYN-101, PGN-0052, aviscumnine, BIM-23190, tuberculosis vaccine, multi-epitope tyrosinase peptide, cancer vaccines, enkastim, APC-8024, GI-5005, ACC-001, TTS-CD3, vascular-targeted TNF (solid tumors), desmopressin (oral controlled release), onercept, and TP-9201.

[0323] In some implementations, the peptide is adalimumab (HUMIRA), infliximab (REMICADE™), rituximab (RITUXAN™ / MAB THERA™), etanercept (ENBREL™), bevacizumab (AVASTIN™), trastuzumab (HERCEPTIN™), pegrillastim (NEULASTA™), or any other suitable peptide, including biosimilars and biobetters.

[0324] Other suitable peptides are those listed below and in Table 1 of US2016 / 0097074:

[0325]

[0326] In the implementation plan, the polypeptide is a hormone, coagulation / coagulation factor, cytokine / growth factor, antibody molecule, fusion protein, protein vaccine or peptide, as shown in Table 2.

[0327] Table 2: Exemplary Products

[0328]

[0329] In the implementation scheme, the protein is a multispecific protein, such as the bispecific antibody shown in Table 3.

[0330] Table 3: Bispecific Forms

[0331]

[0332] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. While any methods and materials similar to or equivalent to those described herein may be used in the practice and / or testing of this disclosure, preferred materials and methods are described herein. In describing and claiming protection for this disclosure, the following terms are used where defined.

[0333] It should also be understood that the terminology used herein is for the purpose of describing a particular implementation and is not intended to be restrictive.

[0334] In this article, the articles “a kind” and “one” are used to refer to one or more grammatical objects of the article (i.e., at least one). For example, “module unit” can mean one or more module units.

[0335] Without further description, it is believed that those skilled in the art can use the foregoing description and illustrative examples to create and utilize the customizable facilities of this disclosure.

[0336] While the invention has been disclosed with reference to specific aspects, it will be apparent to those skilled in the art that other aspects and variations of the invention can be devised without departing from the true spirit and scope thereof. The appended claims are intended to be construed as encompassing all such aspects and equivalent variations.

Claims

1. A method for constructing a customizable facility, the method comprising: A housing is provided, the housing comprising at least one sidewall and a top cover, wherein the housing is supported on a fixed footing on the ground; The bioreactor is supported on the ground inside the shell; A first-stage feature is installed in the first stage on the ground. The first-stage feature includes an air-controlled entrance channel, a changing area, a utility area, a first manufacturing wing, a first office space, and a first set of modular units. The first set of modular units has a first modular unit as a fermentation unit, a second modular unit as a pre-virus unit, a third modular unit as a post-virus unit, a fourth modular unit as a filling-finished product unit, a fifth modular unit as a dosage preparation unit, and a sixth modular unit as a packaging unit, and at least one corridor connecting at least two first-stage features to each other. The second stage involves installing second-stage features, including a second manufacturing wing, a second office space, and a second set of modular units. The second set of modular units comprises a seventh modular unit as a fermentation unit, an eighth modular unit as a pre-viral unit, a ninth modular unit as a post-viral unit, a tenth modular unit as a filling-to-finished product unit, an eleventh modular unit as a dosage preparation unit, and a twelfth modular unit as a packaging unit. The second set of modular units is vertically positioned at least one layer above the bioreactor and the first set of modular units. Additional features, including additional modular units and additional manufacturing wings, are installed in at least one subsequent stage. The additional features may be positioned horizontally or vertically near the first manufacturing wing or the second manufacturing wing, and The customizable facility is configured to manufacture at least one pharmaceutical product.

2. The method according to claim 1, wherein the filling-finished unit of the second group of module units has a single layer with a floor area of ​​1,500 square meters.

3. The method of claim 2, wherein the fill-finish unit further comprises an intermediate layer for an HVAC workshop room.

4. The method of claim 2, wherein the fill-finished unit further comprises a free space configured to be directly adjacent to the fill-finished unit, the free space and the fill-finished unit having a combined floor area of ​​3,000 square meters.

5. The method according to claim 1, wherein the first or second group of module units comprises a 2k module having a single layer with a floor area of ​​1,500 square meters, and the 2k module is capable of sealing a 2,000-liter container.

6. The method of claim 5, wherein the 2k module further comprises a middle layer for an HVAC workshop room.

7. The method of claim 5, wherein the 2k module may further include a free space configured to be directly adjacent to the 2k module, the free space and the 2k module having a combined floor area of ​​3,000 square meters.

8. The method of claim 1, wherein the first or second group of module units comprises a 5k module having a single layer with a floor area of ​​3,000 square meters, the 5k module being capable of sealing a 5,000-liter container.

9. The method of claim 8, wherein the 5k module further comprises a middle layer for an HVAC workshop room.

10. The method of claim 1, wherein the first group or the second group of module units comprises 15k modules having a first layer and a second layer.

11. The method of claim 10, wherein the 15k module has a floor area of ​​3,000 square meters and can seal a 15,000 L container.

12. The method of claim 10, wherein the 15k module further comprises a local HVAC unit, a cleaning in place (CIP) unit, and a temperature control unit (TCU).

13. The method of claim 10, wherein the second layer of the 15k module extends vertically above the first layer of the 15k module.

14. The method of claim 10, wherein the first layer of the 15k module and the second layer of the 15k module have a combined area of ​​6,000 square meters.

15. The method of claim 1, wherein the customizable facility comprises a 20k module having a first layer, a second layer, and a third layer.

16. The method of claim 15, wherein the 20k module has a floor area of ​​3,000 square meters and can seal a 20,000 L container.

17. The method of claim 15, wherein the second layer of the 20k module extends vertically over the first layer of the 20k module, and the third layer of the 20k module extends vertically over the first layer and the second layer of the 20k module.

18. The method of claim 15, wherein the first layer of the 20k module, the second layer of the 20k module, and the third layer of the 20k module have a combined area of ​​9,000 square meters.

19. The method of claim 1, wherein the customizable facility further comprises a courtyard directly adjacent to the customizable facility, the courtyard comprising a processing area for processing equipment and materials.

20. The method of claim 1, wherein the customizable facility further comprises a warehouse area sealed within the housing.

21. A customizable facility for manufacturing at least one pharmaceutical product, comprising five rows of areas, said five rows of areas comprising: The first row contains multiple purification zones; The second row contains multiple fermentation zones; The third row contains at least one central utility zone; The fourth row contains multiple fermentation zones; and The fifth row contains multiple purification zones.

22. The customizable facility of claim 21, wherein the facility does not include a housing.

23. The customizable facility of claim 21, wherein the central utility zone provides utility to each of the other zones.

24. The customizable facility of claim 21, wherein the first row comprises three purification zones, the second row comprises three fermentation zones, the fourth row comprises three fermentation zones, and / or the fifth row comprises three purification zones.

25. The customizable facility of claim 24, further comprising an extension that adds two additional purification zones to the first row, two additional fermentation zones to the second row, two additional fermentation zones to the fourth row, and / or two additional purification zones to the fifth row.

26. The customizable facility of claim 25, further comprising an extension that adds an additional utility area to the third row.

27. The customizable facility of claim 21, further comprising a housing that seals all of the first to fifth rows.

28. The customizable facility of claim 21, wherein the second row is adjacent to the first row, the third row is adjacent to the second row, the fourth row is adjacent to the third row, and the fifth row is adjacent to the fourth row.

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