Our intensive work in the field of mammalian cell culture processes makes us an excellent partner for solving your process challenges.
With our flexible and customer focused approach we provide efficient concepts and supply capacities to realize your research projects. To optimize and streamline your process, we apply our broad technology and knowledge platform. Please contact us for any project challenges you wish to discuss.
With our broad range of analytical methods, we offer detailed characterization of your cell lines. Selection pressure and cell line stability are possible issues to be addressed. Depending on the culture medium, the concentration of selection reagents may need to be adapted to guarantee stable production while maintaining high process performance. Furthermore, we recommend the evaluation of long-term stability, which can be critical when extended seed-train periods are necessary.
Fig. 1: Comparison of process values for a monoclonal antibody (mAb)-producing CHO cell line at three time points of a high passage experiment. Peak viable cell density was measured in bioreactor batch cultivations. mAb titer was determined by HPLC and relative gene levels were measured by quantitative real-time PCR. Loss of productivity was detected in long-term culture and was attributed to product gene loss.
Fig. 2: Flow cytometric analysis of a CHO cell line cultivated in a high passage experiment. Heavy and light antibody chains were measured after intracellular staining with fluorescently labeled antibodies. A subpopulation with no HC expression was already detected in the mid-term culture. The long-term culture exhibited no HC expression and reduced LC expression. These results are reflected by the HPLC measurements of mAb titers (see FIG. 1).
In general, raw materials and medium manufacturer are crucial factors influencing the quality of the final medium product. On the one hand, raw materials can vary due to production and origin. On the other hand, manufacturers differ in their production technology and raw material supply chain. As a result, the same medium formulation can lead to deviating process performances (see FIG. 3 and 4).
It is therefore recommended to test several raw material sources and to compare different suppliers. We offer respective biological testing of potential raw materials and evaluation of products from different suppliers with regard to process performance and production. Powder and liquid media characterization as well as solubility studies of your products are also part of our portfolio.
Fig. 3: Comparison of growth performance of a HEK cell line in pre-culture passaging and batch cultivation with one medium formulation containing different variants (1-5) of one raw material for each culture.
Fig. 4: Peak viable cell densities achieved in batch shaker cultivations with the same medium formulation produced by two different suppliers for three CHO cell lines.
Lot-to-lot variation is a well-known effect in media production and can occur even in chemically defined media. It can be caused e.g. by minor changes in the powder production process or the solubilization procedure. Furthermore, lot-to-lot variation can occur due to impurities in raw materials.
For example, components such as amino acids in USP/pharma grade with ≥ 98-99% purity may still contain foreign amino acids and trace metals. To evaluate variation in your media lots, we highly recommend biological performance tests. For that, we can establish and perform respective lot testing (see FIG. 5).
Fig. 4: In-house testing of different medium lots of a chemically defined medium formulation developed by Xell. The test was performed with a CHO cell line to define thresholds for biological performance testing of the powder lots.
Our broad range of commonly used bioreactor systems from different suppliers (e.g. Sartorius, DasGip, Applikon) ensures highest flexibility within technology transfer and comparability. With more than 40 lab-scale bioreactors, we are able to provide a high throughput of parallel experimental settings.
We use bioreactor systems ranging from 0.7 to 10 L. Upscaling to 100 L (stainless steel reactor) or 200 L (disposable system) is also available in collaboration with contracted partners.
Our process development services include:
Fig. 6: Optimization of a perfusion process from initial to final process.
At Xell, we offer a complete range of customized analytical services in cell culture, biotechnology, and beyond.
With a highly capable analytics team, we generate comprehensive data sets for our customers’ cultures or samples, which enable them to better understand their processes and complex cell behavior.
The evaluation of substrate concentrations and consumption rates helps us to develop medium and feed solutions tailored to specific cell lines. We have established methods for quantitation of various analytes, which we also make available to our customers.
Our spent media analysis services cover:
The analysis of product quantity and quality is the most important benchmark for a biological production process. Monitoring and maintaining the stability and consistency of these factors is essential when designing new media or processes.
We can provide you with a broad range of product analytics:
We offer physico-chemial analysis of cell culture media and feeds: