The most frequent type of biological therapy is monoclonal antibodies (mAbs). The number of mAb therapies on the market and in development continues to rise, putting more pressure on platforms to be dependable and scalable. Multiple cell culture phases are used to maximize cell density, then various downstream unit operations are used to safely purify the chemical to high purity. Although the type and order of these unit activities may vary, there are some common processes that must be followed.
Alfa Chemistry has a qualified technical team with several years of expertise designing and optimizing mAb processes with customers. We'll help you identify the optimum solution based on data and testing, from process development services and end-to-end platforms to on-site testing and application support for specific process steps.
Upstream
Cell Culture (n-2) / (n-1) / Production
Blockbuster medications based on mAbs are often manufactured in stainless steel stirred tank bioreactors. Higher growth titers and improved processes, on the other hand, mean that many bioreactors can create an increasing number of products. These numbers are within disposable substitutes' capabilities and can provide benefits.
- Single-use bioreactors are also more adaptable, allowing for faster turnaround between batches, and the easy setup of new facilities after the process has been verified in each single-use bioreactor.
- The STR disposable stirred tank bioreactor has been meticulously engineered to maximize availability and process assurance while delivering consistent and scalable cell culture performance over a wide range of sizes.
Clarification (Primary / Secondary)
Deep filtration is the simplest and most cost-effective method for clearing cell cultures. Different membranes are often employed for two clarifying phases in a manufacturing-scale mAb process. Our expert technical staff can help you achieve high throughput and yield by optimizing the program and parameters of this stage, in addition to selecting the optimal filter material and size. When cell density and viability fluctuate, the filtering step is tuned to sustain performance, resulting in good yields for varied cell cultures.
Downstream
Bioburden Filtration
Alfa Chemistry minimizes bioburden by using appropriate filters. The sort of filter utilized here depends on the material's titer and volume, the fluid's fouling properties, and the processing time requirements. Our revolutionary bioburden control filter successfully protects the process from microbial and particle contamination by reducing the bacterial load in the process feed to an acceptable low level.
Virus Inactivation
Inactivation of the virus is a critical step in ensuring the safety of mAb therapy. The most frequent methods for viral reduction are those based on a low pH. The robustness of this process is influenced by several parameters, including exposure period, pH range, protein content, and temperature.
- The virus inactivation (VI) system is a completely automated device that can execute low pH virus inactivation on the incoming elution stream continuously.
- The MVP disposable system can deliver a series of batch-volume automated acid and alkali dosing solutions to ensure that the virus is inactivated while avoiding denaturing conditions.
Anion Exchange (Optional)
To remove host cell proteins (HCP), DNA endotoxins, and viruses, you can combine anion exchange with membrane chromatography. We've created a line of scalable membrane chromatography capsules with exceptional performance. These capsules are dependable and simple to use, allowing users to enhance process economics by reducing buffer usage, improving production, and lowering capital costs.
Virus Filtration
To assure product safety, multiple filtration steps are required. The downstream process normally includes steps that include a filter specifically built for virus filtration.
- The Prime filter is a one-of-a-kind viral elimination filter that combines high flow and powerful capacity to ease process development and production around virus safety, resulting in sustainable economics in all sizes of mAb manufacturing.
- The Protect pre-filter is meant to give subsequent Prime virus filters the best protection possible, while also extending the filter's life and lowering the cost of goods.
- The SV4 filter is designed to extract viruses from more viscous feeds, such as those with greater mAb concentrations. They deliver stable, continuous flow rates as well as high throughput.
Concentration and Diafiltration
To further concentrate target molecules and exchange buffers, TFF membrane concentration, and diafiltration can be used. The Single-Pass TFF module and system allow for direct enrichment circulation without the requirement for recirculation of the product. High concentrations of shear-sensitive proteins and antibodies >160 g/L can be achieved thanks to the cassette's unique flow path design and staging.
The PES membrane T series cassettes are excellent for development, pilot, and production-scale TFF applications in a variety of biological and biopharmaceutical processes. They're very good in purifying and recovering monoclonal antibodies (mAb) or recombinant proteins, as well as separating and purifying plasma.
Bulk Drug Substance Filtration
Optimizing sterilization-grade liquid filtration in the pharmaceutical manufacturing process can boost efficiency while ensuring important medication quality features are met. We can provide filtration solutions for all applications and medication kinds with our comprehensive selection of sterile grade liquid filters and formats.