Since only a small proportion of biotherapeutics that enter clinical trials make it to reach the market, companies tend to have a large pipeline of candidates, like monoclonal antibodies (mAbs) or gene therapy. This implies that there are many processes that need to be developed at the same time. In addition, pressure from healthcare providers is driving the need to reduce the manufacturing costs. Therefore, upstream and downstream optimization is necessary.
The Bioprocessing of Biologics like monoclonal antibodies, gene therapy vectors, and other innovative treatments
Bioprocessing involves utilizing cultured cell lines to procure biological products. However, due to the natural difficulties of handling biological materials, bioprocesses frequently fall victim to inefficiency and large expenses.
Fortunately, the careful analysis and engineering of upstream and downstream processes can help reduce these inefficiencies and costs.
When beginning to consider where improvements can be made in the bioprocessing pipeline, the CDMO must consider upstream and downstream processes individually.
Improving upstream bioprocessing systems
The production of biologics begins with a series of upstream procedures. It may involve choosing cell lines or expression vectors as well as completing transfection, isolation and culturing. Errors in early decisions or inefficient technique can lead to diminished product availability at collection time.
Improving decision-making and application of the technique can help solve problems such as ammonium or lactate buildup or biostability issues that negatively impact cell division and protein production.
With regard to culture media, the use of serum-free media or media without ingredients of animal origin, can improve cell growth and protein generation. In addition, it avoids contamination, a frequent cause of upstream product loss.
Another option is to tailor media components to specific cell lineages that can result in enhancement to scalability. The problem here is that it can be a significant investment of time and resources, as the most optimal ingredients need to be found.
Bioreactor and harvest system upgrades can also increase pipeline adaptability and reduces upfront costs. The use of single-use bioreactors can be an excellent option.
If a CDMO is producing a large number of therapeutic agents which utilize similar processes, use of a generic harvesting system can be helpful. This strategy could reduce time and resources.
Careful design and planning of protocols for upstream processes can be just as important as tailoring media or selecting a scalable bioreactor setup for optimizing output.
53Biologics scientific team will lead you through the best lean strategy to diagnose the room for improvement and industrialize your upstream process
Upgrading downstream bioprocessing
The downstream improvements aim to increase batch output and purity. There are several ways to promote downstream scalability, including filtering and refining techniques, high-throughput protocols and reworking current procedures for optimal efficiency from end to end.
The use of devices for filtration -and acceleration- based cell retention like cell settlers or vortex-flow filters enable CMOs to ramp up production on an as-needed basis, ensuring product purity while reducing expenses
To enhance the purification of therapeutic agents after harvesting, the chromatographic separation is an excellent choice. Chromatography boosts flow-rates and impurity removal due to its strict selectivity compared to other means of filtering fermentation media.
Moreover, new chromatographic separation techniques eliminate the need to change the buffer before and after separation. This is made possible by the possibility of adjusting the elution conditions. In this sense, CDMOs can make internal adjustments to ligands and chromatographic matrices to improve elution flow rates, thus minimising retention time.
Besides using chromatographic separations, CDMOs can also use the non-chromatographic filtration. These new types of membranes are able to filter out unwanted components by molecular weight even before chromatography. Not only that, they also have the ability to screen particular molecules based on certain chemical characteristics.
During the Downstream process development and optimization, 53Biologics would be also your analytical partner for the establishment and validation of the most suitable In-Process Control (IPC) methodologies
Incorporating individual methods for downstream bioprocess improvement is an important step for CDMOs. To truly see the benefits of these optimizations, these procedures must be combined to build a purification protocol customized and scalable.
In this sense, each production line will require tailor-made optimizations for speed-limiting steps. The most common of these are the transfer of biomaterials between pieces of equipment or buffer exchanges. Further opportunities for cutting development cycle length and expense will arise when these solutions can be repurposed as new therapeutics are added to production.
To summarize, the application of these techniques, techonologies and strategies would promote upstream and downstream optimization, thus achieving time savings, higher yields, and lower costs.
By partnering with 53Biologics, experienced in upstream and downstream optimization bioprocesses clients can meet their manufacturing goals using the most cutting-edge techniques available.
At 53Biologics we know that securing the manufacturing process facilitates success through clinical development and commercialization of our customers’ products.