Abstract: The monitoring and control of bioprocesses is provided. More particularly, the present disclosure is directed to formulating buffer products from multiple buffer solutions for feeding the different operations occurring within a bioprocess line. As the buffer product is being formulated, the buffer product is tested for conductivity, refractive index, and optionally pH. The conductivity measurements are used in conjunction with refractive index measurements to ensure that the buffer product not only has the correct concentration of ions but also has the correct concentration of components. A controller can be used to make automatic adjustments to the buffer product should any of the measured parameters fall outside a preset range.

Abstract: A method for delivering a processing solution includes providing a concentrated processing solution in a bioprocess container, the concentrated processing solution being produced at a first site. The method also includes combining the concentrated processing solution with a biopolymer containing solution produced in a bioreactor at a second site different from the first site. In some embodiments, the processing solution is a buffer for processing products of cells cultured in a bioreactor. A system and a pharmaceutical production facility for carrying out the method is also provided.

Abstract: The present disclosure is directed to a big-bag transfer station for API seed crystals. The transfer station may permit the filling of smaller containers, such as bags or pouches, from a large container, such as a big bag. The transfer station may permit the transfer without contaminating the atmosphere of the room in which the station is housed. Additionally, the transfer station may limit cross-contamination between filling cycles by employing single-use liners.

Abstract: A campus for fabricating at least one pharmaceutical product has one or more customizable facilities each configured to manufacture the 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.

Abstract: Antibodies having modified constant regions so as to permit conjugation of the antibody to a payload such as a therapeutic agent are described. Preferred antibodies include a mutation at light chain position 180 (positional numbering), most preferably the mutation is to a residue selected from C, K, Q, or a non-natural amino acid. Additional mutations may also be combined with a mutation at position 180; including one or more of light chain (LC) S208, LC S171, LC S182, LC A184, LC V191, LC S202, LC S203, LC T206, heavy chain (HC) S160, HC T190, HC S443, HC S447, HC S139, HC S168, HC V170, HC V176, HC T200, HC S445 according to a positional numbering convention.

Abstract: A mammalian cell comprising at least four distinct recombination target sites (RTS), an adenovirus (Ad) gene comprising E1A, E1B or a combination thereof, and a promoter operatively linked to the Ad gene, wherein the RTS, the Ad gene, and the promoter are chromosomally-integrated; methods for using the cell for generating a recombinant adeno-associated virus (rAAV) producer host cell; and methods for using the AAV producer host cell to produce, package and purify rAAV.

Abstract: A recombinant host cell comprising an endogenous gene encoding a FLO8 protein comprising the amino acid sequence identified as SEQ ID NO:1 or a homologue thereof, which host cell is engineered by one or more genetic modifications to reduce expression of said gene compared to the host cell prior to said one or more genetic modifications, and which host cell comprises a heterologous expression cassette comprising a gene of interest (GO!) under the control of an expression cassette promoter (ECP) which ECP is repressible by a non-methanol carbon source, and a method of producing a protein of interest using said recombinant host cell.

Abstract: An impeller is usable in a variable diameter bioreactor having multiple vessel sections of successively increasing or decreasing volume. The impeller includes an impeller blade extending along an impeller blade axis between first and second axial ends and having opposed impeller blade faces, an impeller blade leading edge, and an impeller blade trailing edge. Each of the leading and trailing edges defines a helix or spiral between the axial ends of the impeller blade. In certain arrangements, the impeller blade is one of at least two impeller blades joined together along an impeller shaft extending axially along the impeller blade axis mentioned, and the helix or spiral has a pitch approximately equal to one half of a length between the first and second axial ends.

Abstract: The present invention is in the field of recombinant biotechnology, in particular in the field of protein expression. The invention generally relates to a method of expressing a protein of interest (POI) from a host cell. The invention relates particularly to improving a host cell's capacity to express and/or secrete a protein of interest and use of the host cell for protein expression. The invention also relates to cell culture technology, and more specifically to culturing cells to produce desired molecules for medical purposes or food products.

Abstract: A predictive model is described that can predict parameter concentrations in the future based on initial, measured concentrations and historical data. A plurality of multivariate techniques can be used to construct the predictive model capable of forecasting concentrations over multiple and diverse cell lines. The predictive model is also scalable. In one embodiment, a future lactate concentration trajectory is determined and at least one condition within a bioreactor is changed or modified to maintain lactate concentration within desired ranges.

Abstract: A customizable facility for manufacturing at least one product has at least one modular unit in communication with at least one central unit configured to provide utilities to the at least one modular unit. In some embodiments, the central unit(s) and modular unit(s) are positioned at least partially within a shell. Each modular unit can be 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, or another unit. The modular units can be arranged to maximize a number of modular units within the shell while minimizing a footprint of the shell. A method of assembling a facility for manufacturing at least one product includes providing at least one central unit and providing at least one modular unit in communication with the central unit(s) such that utilities are provided by the central unit(s) to the modular unit(s).

Abstract: The monitoring and control of bioprocesses is provided. The present disclosure provides the ability to generate generic calibration models, independent of cell line, using inline Raman probes to monitor changes in glucose, lactate, glutamate, ammonium, viable cell concentration (VCC), total cell concentration (TCC) and product concentration. Calibration models were developed from cell culture using two different CHOK1SV GS-KO™ cell lines producing different monoclonal antibodies (mAbs). Developed predictive models, qualified using an independent CHOK1SV GS-KO™ cell line not used in calibration, measured changes in glucose, lactate, ammonium, VCC, and TCC with minor prediction errors over the course of cell culture with minimal cell line dependence. The development of these generic models allows the application of spectroscopic PAT techniques in a clinical manufacturing environment, where processes are typically run once or twice in GMP manufacturing based on a common platform process.

Abstract: A variable diameter bioreactor vessel is provided that includes a first vessel section having a first diameter configured to hold a liquid media and biologic material, and a second vessel section having a second diameter that is greater than the first diameter such that the liquid media can be increased from a first volume to a second volume within the vessel.

Abstract: A process and system for efficiently producing reference data that can be fed into a predictive model for predicting quality attribute concentrations in cell culture processes. A perfusion bioreactor is operated at pseudo-steady-state conditions and one or more attribute influencing parameters are manipulated and changed over time. As the one or more attribute influencing parameters are manipulated, one or more quality attributes are monitored and measured. In one embodiment, multiple quality attributes are monitored and measured in parallel. The quality attribute information is recorded in conjunction with the changes in the attribute influencing parameters. This information is then fed to the predictive model for propagating cell cultures in commercial processes and maintaining the cell cultures within desired preset limits.

Abstract: The invention relates to methods of reducing the immunogenicity of CRISPR-associated (Cas) proteins and the modified Cas proteins produced therefrom. In addition, the invention relates to methods for cell and gene therapy, including any and all genetic modifications and alterations of gene expression (and/or genetic elements) made in-vivo or ex-vivo using Cas proteins with reduced immunogenicity.

Abstract: A bioprocess system and a method for incubating, growing and harvesting cell cultures is described. Also disclosed is a bioprocess container that can be used with the system. In one aspect of the present disclosure, the bioprocess system includes bioprocess tubes and cell culture tubes having particular dimensions and being made from specific materials that allow the tubes to be welded together while preventing open connections and/or ruptures. In this manner, bioprocess containers can be connected and disconnected from a cell culture apparatus without having to perform the manipulation within a closed environment and without associated monitoring.

Abstract: A rupture disk includes a body including an internal wall extending from a first end of the body to a second end of the body. The internal wall defines an opening extending through the body. In some embodiments, the body further includes an internal flange formed on the internal wall, and the internal flange has a stepped surface. A rupture membrane is positioned within the body, and secured, for example, by cold welding. The rupture membrane may be secured to the stepped surface. The rupture membrane is positioned within the body such that the rupture membrane does not extend beyond the first end of the body. A process system including the rupture disk is also provided. A method of maintaining a process system that includes the rupture disk is also provided.

Abstract: The present invention is in the field of recombinant biotechnology, in particular in the field of protein expression. The invention generally relates to a method of expressing a protein of interest (POI) from a host cell. The invention relates particularly to improving a host cell's capacity to express and/or secrete a protein of interest and use of the host cell for protein expression. The invention also relates to cell culture technology, and more specifically to culturing cells to produce desired molecules for medical purposes or food products.

Abstract: The present disclosure features methods and compositions for modulating lipid metabolism to achieve improved production and quality of recombinant products, such as next generation biologics. Modulation of lipid metabolism as described herein includes, for example, introducing a lipid metabolism modulator described herein to a cell or a cell-free system. Also encompassed by the present disclosure are engineered cells with improved production capacity and improved product quality, methods for engineering such cells, and preparations and mixtures comprising the products from such cells.

Abstract: Disclosed herein are, inter alia, methods and compositions useful for detecting and/or quantifying host cell proteins during the production of a product, e.g., a recombinant protein, e.g., an antibody.