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US-20260126424-A1 - MODULAR PROCESS ANALYTICAL TECHNOLOGY TESTING APPARATUS

US20260126424A1US 20260126424 A1US20260126424 A1US 20260126424A1US-20260126424-A1

Abstract

The invention provides a modular apparatus comprising at least one process analytical instrument and a controller adapted for fluid communication with a unit operation of a pharmaceutical or biopharmaceutical manufacturing system, systems comprising the modular apparatus, and related compositions and methods. The modular apparatuses described here and associated digital architecture provide a universal solution to fully integrate any pharmaceutical or biopharmaceutical manufacturing process using a wide range of process analytic tools.

Inventors

  • Aaron Cowley
  • Edita Botonjic-Sehic
  • Syed Kaschif Ahmed
  • Mark Jandreski

Assignees

  • ARRANTA BIO HOLDINGS, LLC

Dates

Publication Date
20260507
Application Date
20251219

Claims (17)

  1. 1 . A mobile, modular apparatus for deploying process analytical technology in a pharmaceutical or biopharmaceutical manufacturing process, the apparatus comprising a mobile platform with a weighted base, a control cabinet and an instrument stack disposed within a housing comprising inlet and outlet ports, wherein the control cabinet comprises a human machine interface, a controller, and a data acquisition and analysis software layer and the instrument stack comprises two or more process analytical instruments and associated flow cells, a tubing assembly and valves; wherein each of the process analytical instruments is adapted to measure an indication of at least one product attribute from a process fluid flowing through its associated flow cell; wherein the inlet and outlet ports of the housing connect the flow cells via the tubing assembly in a recirculation loop to a flow path of at least one unit operation of the manufacturing process for in-line data acquisition and analysis; and wherein the controller and data acquisition and analysis software operate to (i) compare the indication of the at least one product attribute against a predetermined range for the attribute, (ii) determine whether the indication is within the range, and (iii) initiate a first action if the received indication is within the range or a second action if the indication is outside the range.
  2. 2 . The apparatus of claim 1 , wherein the instrument stack comprises two or more spectroscopic instruments, optionally wherein the two or more spectroscopic instruments are selected from a Raman spectrophotometer, a mid-infrared (IR) spectrophotometer, a near-IR spectrophotometer, and an ultraviolet-visible (UV-VIS) spectrophotometer.
  3. 3 . The apparatus of claim 1 , wherein the instrument stack comprises a multiangle light scattering (MALS) detector.
  4. 4 . The apparatus of claim 1 , wherein the instrument stack comprises a Raman spectrophotometer, a UV-VIS spectrophotometer, a mid-infrared (IR) spectrophotometer, a near-IR spectrophotometer and a multiangle light scattering (MALS) detector.
  5. 5 . The apparatus of claim 1 , wherein the apparatus comprises an internal vessel in the form of a flexible or a rigid container defining an interior space suitable for holding a fluid, wherein the vessel includes inlet and outlet ports, an optional impeller for fluid recirculation, and an optional probe or sensor.
  6. 6 . The apparatus of claim 1 , wherein the apparatus comprises one or more environmental protections selected from electromagnetic frequency (EMF) shielding, vibrational dampening, shock absorption, and temperature control, optionally in the form of insulation.
  7. 7 . The apparatus of claim 1 , wherein the apparatus comprises at least one sample port or cuvette adapted to be connected to the recirculation loop of the flow path for at-line data acquisition and analysis.
  8. 8 . The apparatus of claim 1 , wherein the recirculation loop connecting the flow cells to the flow path of the at least one unit operation includes an external vessel.
  9. 9 . The apparatus of claim 8 , wherein the external vessel comprises a body in the form of a flexible or a rigid container defining an interior space, inlet and outlet ports, an optional impeller for fluid recirculation, and an optional probe or sensor.
  10. 10 . The apparatus of claim 9 , wherein the external vessel is a hold vessel, a release tank, a dilution tank, a mixing tank, or a stirred tank reactor.
  11. 11 . The apparatus of claim 1 , wherein the recirculation loop is connected via one or more valves to one or more of a material recycle flow path, a waste flow path, and a forward processing flow path.
  12. 12 . The apparatus of claim 11 , wherein the one or more valves is controlled by operation of the controller in accordance with one or more predetermined criteria.
  13. 13 . The apparatus of claim 1 , wherein the controller comprises an advanced process controller (APC).
  14. 14 . The apparatus of claim 13 , wherein the data acquisition and analysis layer includes multivariate data analysis, chemometric modeling and/or other advanced process modeling software.
  15. 15 . A pharmaceutical or biopharmaceutical processing system comprising an apparatus as defined by claim 1 fluidly coupled to a unit operation of a pharmaceutical or biopharmaceutical manufacturing process in a recirculation loop.
  16. 16 . The system of claim 15 , wherein the apparatus is fluidly coupled in-line between the unit operation and a second unit operation in the process and the recirculation loop is connected via one or more valves to one or more of a material recycle flow path, a waste flow path, and a forward processing flow path.
  17. 17 . The system of claim 15 , wherein the apparatus is fluidly coupled in-line between the unit operations and a second unit operation in the process via an external vessel.

Description

FIELD OF THE INVENTION The present invention relates to improvements process analytic technology (PAT) for use in a continuous pharmaceutical and biopharmaceutical manufacturing system. CROSS REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No. 63/566,133 filed Mar. 15, 2024, and U.S. Provisional Application No. 63/708,332 filed Oct. 17, 2024, the contents of which are hereby incorporated by reference in their entirety. BACKGROUND Most biopharmaceuticals are manufactured using batch production methods in which human intervention is required to process a set quantity of material to be produced at the same time. Batch operations may require as long as 1-2 months or more from bioreactor to final formulated product. An alternative approach is continuous manufacturing which is attractive due to its potential to reduce costs while increasing productivity and improving product consistency. Continuous manufacturing processes have been developed in the chemical, petrochemical, food, and mechanical industries. In these contexts, continuous processes have demonstrated less reliance on human labor and fewer gaps in transitioning between unit operations in the process resulting in increased productivity, while the smaller facility footprint required by a continuous process reduces facility costs. There is a need for continuous manufacturing systems in the biopharmaceutical sector, as an alternative to the more time consuming, resource intensive, and expensive batch processes that represent the current standard of practice, as acknowledged by regulatory agencies which have urged the adoption of continuous biomanufacturing in this sector. See National Academies of Sciences, Engineering and Medicine. Continuous manufacturing for the modernization of pharmaceutical production. 2019. While continuous bioprocessing has yet to be fully realized, several innovations in unit operations have made its implementation more feasible in biopharmaceutical manufacturing. In upstream processing these include developments in perfusion cell culture systems and continuous clarification systems such as continuous centrifugation, alternating tangential flow filtration, and acoustic wave separation. Developments in downstream operations include continuous chromatography and single-pass ultrafiltration and diafiltration capable of achieving high concentration factors and buffer exchange in a single pass of the process material through the module, e.g., in a continuous formulation process. Despite these and other advances in adapting various unit operations to continuous processing, significant challenges remain in process integration, real-time monitoring and control systems. The present invention addresses the need for improved process analytic technology (PAT) and universal integration to address the needs of a continuous pharmaceutical and biopharmaceutical manufacturing system. BRIEF SUMMARY Provided is a customizable, automated, mobile, modular apparatus adapted for performing analytical testing, analysis, and monitoring of a bioprocess in-line or at-line in a biomanufacturing process, and related methods and compositions. In one aspect, provided is a mobile, modular apparatus for deploying process analytical technology in a pharmaceutical or biopharmaceutical manufacturing process, the apparatus comprising a mobile platform with a weighted base, a control cabinet and an instrument stack disposed within a housing comprising inlet and outlet ports, where the control cabinet includes a human machine interface, a controller, and a data acquisition and analysis software layer and the instrument stack includes two or more process analytical instruments and associated flow cells, tubing and valves, where each of the process analytical instruments is adapted to measure an indication of at least one product attribute from a process fluid flowing through its associated flow cell, where the inlet and outlet ports of the housing connect the flow cells via the tubing in a recirculation loop to a flow path of at least one unit operation of the manufacturing process for in-line data acquisition and analysis, and where the controller and data acquisition and analysis software operate to (i) compare the indication of the at least one product attribute against a predetermined range for the attribute, (ii) determine whether the indication is within the range, and (iii) initiate a first action if the received indication is within the range or a second action if the indication is outside the range. The apparatus may also include where the instrument stack comprises two or more spectroscopic instruments, optionally where the two or more spectroscopic instruments are selected from a Raman spectrophotometer, a mid-infrared (IR) spectrophotometer, a near-IR spectrophotometer, and an ultraviolet-visible (UV-VIS) spectrophotometer. The apparatus may also include where the instrument stack comprises a multiangle ligh