End-to-end process support, from development to industrialization
Monoclonal antibodies (mAbs) are the most common type of biological therapeutics. The number of mAbs therapies on the market and under development continues to grow, increasing the need for reliable, scalable manufacturing platforms.
mAb production includes multiple cell culture steps to maximize cell density followed by several downstream unit operations to safely purify the molecule to a high level of purity. While the type and order of these unit operations can vary, there are some fundamental steps required. We have over 30 years of experience in developing and optimizing mAb processes with customers, and a knowledgeable technical team that is ready to partner with you. From process development services and end-to-end platforms, to on-site testing and applications support for specific process steps, we will help you find the best solution based on data and testing.
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Upstream & Downstream
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Cell Culture (n-2) / (n-1) / Production
Historically, blockbuster drugs based on mAbs have been produced in multiple, multi-thousand-liter stainless steel stirred tank production bioreactors. But higher culture titers and intensified processes mean that an increasing number of products can be produced in multiple 2000 L bioreactors. These volumes are within the capability of single-use alternatives and the benefits that this can deliver.
Single-use based facilities are also more agile, allowing for fast turnaround between multiple batches, production of different products in the same facility, and quick set up of new facilities once a process is validated in each single-use bioreactor. Even for very large-scale processes, the benefits of single-use may still be achieved when applied within the seed train and can deliver productivity improvements as part of a hybrid, single-use and stainless-steel upstream process.
Allegro™ STR Bioreactors
Allegro STR single-use stirred tank bioreactors were thoughtfully designed to maximize usability and process assurance while delivering consistent and scalable cell culture performance across a full range of sizes from 50 – 2000 L.
Clarification (Primary / Secondary)
The first process step after cell culture is the removal of cells, cell debris, and other impurities to reduce biological burden as much as possible. The easiest and most economical technology to clarify the cell culture is depth filtration. Low yields are a common challenge in this step, especially as cell densities increase upstream. In a manufacturing-scale mAbs process, two clarification steps are usually needed, using different membranes. Our experienced technical team can help you achieve high throughput and yield by optimizing protocols and parameters for this step, in addition to selecting the best filter materials and size.
Stax™ mAx Platform
The Stax™ mAx Clarification Platform is a robust, high-performance depth filtration solution that scales directly with a range of formats and sizes suitable for bench-top testing up to large-scale clinical production. The filtration stages are optimized to maintain performance as cell density and viability change, providing high yields across a wide range of cell cultures.
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Reducing bioburden through a suitable grade 0.2 µm or 0.45 µm filter is usually the next step in this process. The type of filter used here can vary based on the titer and volume of material, fouling properties of the fluid, and processing time requirements.
Bioburden Reduction Filters
Our technologically innovative bioburden control filters reduce bacterial loads in process feeds to acceptably low levels for successful and cost-effective protection of processes from microbial and particulate contamination. Membranes are inert and have low protein and excipient binding properties suitable for all types of drug products. Available in a wide range of formats: cartridges for stainless steel installations and capsules for single-use systems.
All process development-scale filter formats are designed to scale directly to larger cGMP filter configurations for fast and easy production scale-up.
A concentration step may be helpful to optimize other downstream processing steps and reduce in-process pool tank volumes, especially in continuous processing facilities.
Cadence™ Inline Concentrator
The Cadence Inline Concentrator (ILC) allows direct flow through in-process volume reduction and can be implemented into a process system or operated as a standalone unit. It is designed for easy integration, and does not require a holder. The single-pass technology reduces shear exposure, making it well-suited for highly shear-sensitive products.
Virus inactivation is a critical step to ensure the safety of mAb therapeutics. Low pH-based methods are most commonly used for viral reduction. There are several factors that can impact the robustness of this step, including exposure time, pH range, protein concentration and temperature.
Cadence™ Virus Inactivation System
The Cadence Virus Inactivation (VI) system is a fully automated system that provides the ability to perform low pH virus inactivation to an incoming elution stream continuously, with minimal operator involvement. It may be operated in batch or continuous mode for flexible facility fit.
Allegro™ MVP Single-Use System
The Allegro™ MVP single-use system can be used in combination with our single-use mixing technology over a range of batch volumes to provide an automated solution for acid and base dosing, ensuring pH control that will inactivate viruses whilst avoiding denaturing conditions for the mAb. It uses fully disposable flowpaths and incorporates single-use sensors for control and monitoring of key parameters. This enables processing to be conducted at optimum conditions, using fully automated process sequences. We also offer a broad range of mixers and will help you find the best option for your process needs.
A robust single-use mixing system ideal for solid to liquid applications requiring efficient mixing. It is a mobile, flexible mixing system that provides reproducible single-use mixing of a wide range of volumes in a broad range of applications.
Anion Exchange (Optional)
Anion exchange using membrane chromatography may be incorporated to help remove host cell protein (HCP), DNA endotoxin and assist with virus clearance.
Mustang® Q Membrane Chromatography Capsules
We have combined our competencies in membrane device design and chromatography to develop a range of high-performance, scalable Mustang Q XT membrane chromatography capsules. These capsules are reliable, easy to use and enable users to significantly improve their process economics through reduced buffer consumption, increased throughput and reduced capital expenditure.
Mustang Q XT Acrodisc
Disposable membrane chromatography units for scale-down process development. Mustang XT Acrodisc units, available in Q and S chemistries, are ideal for scale-down process development work in a variety of downstream process applications. A membrane volume of < 1 mL reduces the amount of sample required for evaluation, and the female luer lock inlet and outlet simplifies connection to typical low pressure chromatography systems.
Multiple filtration steps are required to ensure product safety. Including a step with filters specifically designed for virus filtration is usually incorporated into the downstream process.
Pegasus™ Prime and Pegasus Protect Filters
Pegasus Prime filters are unique virus removal filters which combine high flow and robust capacity. These filters can simplify process development and manufacturing processes around virus safety, and will deliver sustainable economy at all scales of mAb manufacturing.
Pegasus Protect pre-filters are designed to provide optimal protection for the subsequent Pegasus Prime virus filter, extending filter life and improving cost of goods.
Pegasus SV4 Filters
Pegasus SV4 filters are specially designed for viral clearance from more viscous feeds like intravenous IgG, and higher concentration mAbs. They offer consistent, constant flow rates and outstanding throughput performance, allowing a very high degree of process control.
Concentration and Diafiltration
Concentration and Diafiltration using Tangential Flow Filtration (TFF) membranes further concentrates the target molecule and exchanges buffers. Achieving high yield is a common challenge with TFF, but our technical experts can work with you to optimize this unit operation based on experience and thorough testing.
Cadence Single-Pass TFF Modules and Systems
Cadence Single-Pass TFF (SPTFF) is a patented breakthrough technology that allows direct flow-through concentration with no recirculation of product. The unique flow path design and staging of the cassettes enables high concentration of shear sensitive proteins and antibodies >160 grams/liter.
T-Series TFF Cassettes with Omega Membrane
T-Series cassettes with Omega membrane are ideal for development, pilot, and production-scale TFF applications in diverse biological and biopharmaceutical processes. They are especially useful in vaccine and conjugate concentration and diafiltration, purification and recovery of monoclonal antibodies (mAb) or recombinant proteins, and blood plasma fractionation and purification.
T-Series TFF Cassettes with Delta Membrane
Delta regenerated cellulose membrane offers high flux and selectivity. The membrane has been specifically developed to minimize protein binding to the surface and interstitial structure of the membrane. Inherently hydrophilic, this membrane shows low protein adsorption properties and is optimal for processes involving very hydrophilic proteins.
T-Series TFF Cassette Holders
Designed for optimum performance and product recovery, our TFF cassette holders are available in a variety of sizes to meet every application requirement. This way applications that are developed on a small system using a Centramate or Maximate cassette can be easily scaled up, either by adding additional cassettes to the holder or by scaling into a larger cassette format and holder configuration with identical flow path like the Centrasette/Centrastak™ or Maxisette holders.
Bulk Drug Substance Filtration
Manufacturing for clinical purposes requires the production of highly pure and biologically active vectors that meet regulatory requirements. A last sterilizing grade (0.2 µm) filtration step is usually needed before product is sent for final filling.
Sterile Liquid Filtration
Optimized sterilizing-grade liquid filtration in your drug manufacturing process drives efficiencies while providing confidence in achieving drug critical quality attributes. Selecting the right sterile filter media and format, for your specific process helps to maximize yield and recovery of valuable drug product and ensure production efficiency. Our extensive range of sterilizing-grade liquid filters and formats enable us to offer filtration solutions for all applications and drug types, from mAbs, recombinant proteins, vaccines and gene therapies to small molecule drugs, and plasma derivatives.
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Connect With An Expert
Pall has a global team of over 300 experienced technical professionals to support your molecule from pre-clinical to commercial manufacturing. From process development services and end-to-end platforms, to on-site testing and applications support for specific process steps, we will help you find the best solution based on data and testing.