Efficient Lab Separation Technologies Boost Biotherapeutic Development and Quality Control
Lab Essentials for Research and Development
The Must-Haves for Every Lab – Instruments, Consumables, and Services
Clarification, filtration, and purification are critical processes for successful research and development. By effectively removing cell debris, impurities, and other contaminants, these methods enable accurate analysis of samples and reliable results during molecule development, cell line development (CLD) and quality control (QC). Here’s a closer look.
What is the role of lab separation in biotherapeutics development?
Biotherapeutics R&D kicks off with molecule development, followed by CLD to generate high-titer, stable cell lines. This stage includes gene cloning and rapid screening to thoroughly analyze multiple expression constructs and make sure they meet the required quality attributes and specificities. Next, researchers identify optimal culture conditions to maximize cell growth and productivity.
At this point, filtration and purification processes become critical, as they significantly influence the yield and quality of the final therapeutic product, such as a monoclonal antibody (mAb).
When are clarification and purification used in the mAb workflow?
Clarification and purification are crucial in the downstream processing of mAbs. After cell culture, clarification separates the mAb-containing supernatant from cells and cell debris. This step uses centrifugation, filtration, or both to produce a clear supernatant.
One or more purification steps are then used to remove host cell proteins, DNA, and other contaminants, progressively purifying the mAb product.
How do researchers concentrate or buffer exchange their mAb sample?
In mAb development, sample concentration and buffer exchange are used for increasing antibody concentration and optimizing conditions for downstream processing or final formulation.
Tangential flow filtration (TFF), also known as crossflow filtration, is commonly used for this purpose. TFF has a membrane with a specific molecular weight cut-off to retain the mAbs while allowing smaller impurities and the starting buffer to pass through.
At what stage is sample sterilization important?
Sample sterilization happens after the purification stage, where the mAb solution is passed through a sterile filter, typically with a pore size of 0.2 microns, to eliminate any remaining bacteria or microorganisms. This allows the final biologic product to be used in cell-based assays without affecting cell viability and, once the separation process has been transferred to commercial production, to meet the stringent quality and safety standards for clinical use.
What are the common challenges with clarification and filtration?
Sample variability is a key factor. For example, high-density cell cultures can cause filter clogging, reducing efficiency and throughput. This, in turn, slows the process and increases costs. Managing this means balancing contaminant removal with yield. As production scales up from research to clinical trials and commercial production, ensuring product quality and process efficiency becomes increasingly challenging.
How are new separation technologies addressing these pain points?
Many filtration technologies aim to improve efficiency. Complete kits like Sartoclear Dynamics? Lab streamline workflows and reduce contamination risks by combining clarification and sterile filtration. They simplify the process by eliminating the centrifugation step, improving both efficiency and safety.
For ultrafiltration, Vivaflow? TFF cassettes offer high process speeds with no need for optimization, making them ideal for easy concentration and buffer exchange of larger (0.1 to 5 L) feed volumes. Next-generation cassettes promise even greater ease of use and enhanced efficiency while improving sustainability.
How do you choose the best membrane for QC assays?
In QC of biotherapeutics, filtration devices play an important role in removing insoluble particles like cell debris and protein aggregates from samples. If not removed, these particles can damage analytical instruments and consumables, such as HPLC columns.
Choosing the right filter membrane is critical because it can adsorb proteins and distort analytical results. To minimize analyte loss, it's essential to select membranes with minimal protein adsorption and consider factors like sample pH, surface charge, and handling steps.
We have so many resources to address common challenges around lab filtration and purification. Check out the page and find expert advice now!
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