Pipeline enhancements increase biologic yields while lowering costs.
Bioprocessing involves utilizing cultured cell lines to procure biological products. Pharmaceutical bioprocessing is often used to produce proteins such as monoclonal antibodies (mAbs), gene therapy vectors, and other innovative treatments.
Due to the natural difficulties of handling biological materials, bioprocesses frequently fall victim to inefficiency and large expenses. Growing massive quantities of cells and collecting or preserving cell products often results in lower-than-optimal yields. However, careful analysis and engineering can help reduce inefficiencies and lower overhead.
When beginning to consider where improvements can be made in the bioprocessing pipeline, analysts consider upstream and downstream processes individually. Upstream processes typically comprise early cell isolation, tissue culture, and storage head of biomaterial collection. Downstream processes include biomass separation, culture agitation, condensing collected materials, and other isolation and concentration procedures.
Competition among pharmaceutical manufacturers is fierce when it comes to trialing and marketing novel biologic therapies. In order to remain competitive, developers must work to control variables in upstream and downstream bioprocessing efforts to maximize yields while minimizing expense.
The most important factors in achieving this goal are increasing production by reducing common disruptions to upstream processes and obtaining larger, purer yields by improving technique in downstream processes.
Improving upstream bioprocessing systems to increase scalability.
Producing therapeutic vectors and monoclonal antibodies begins with a series of upstream procedures. These 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 upstream decision making and technique implementation helps with avoiding pitfalls such as ammonium or lactate buildup or biostability issues that negatively impact cell division and protein production.
Improvements to tissue culture media can improve cell growth and generation of target proteins. Contamination, a frequent cause of upstream product loss, can be ameliorated via the use of serum-free media or media that eschews animal products all together.
Tailoring media components to specific cell lineages can be a significant investment, as it requires additional time and expense to discover and trial the most optimal media ingredients, but the resulting enhancement to scalability can be well worth it.
In addition to media customization, bioreactor and harvest system upgrades provide additional potential areas for biologics developers and contract manufacturing organizations (CMOs) to scale upstream production. To increase pipeline adaptability and lower initial expenses, one-time use bioreactors are an excellent option.
If a manufacturer is producing a large number of therapeutic agents which utilize similar processes, use of a generic harvest system is recommended. These systems comprise multiple tools for applying upstream procedures, including depth filtration and centrifugation capabilities for purification and condensation protocols.
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. CMOs benefit from engineering highly specific procedures custom-fit to their unique bioprocesses.
These protocols might include steps such as extraction of byproducts and addition of growth factors to media at opportune times. 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. Developers who make use of these flow filtration tools can ensure product purity while reducing expenses.
Obtaining more product of higher quality by upgrading downstream bioprocessing.
Unlike optimizing upstream processes for conservation of biomaterials, downstream improvements aim to increase batch output and purity. There are a number of ways to promote downstream scalability, including filtering and refining techniques, high-throughput protocols, and reworking current procedures for optimal efficiency from end to end.
Chromatographic separation is an excellent choice for enhanced processing and isolation of target therapeutics from media post-harvest. This method of separation boosts flow-rates and impurity removal due to its strict selectivity compared to other means of filtering fermentation media.
Normally protocols require buffer to be swapped before and after separation, but new techniques in chromatographic separation do away with this requirement thanks to the ability to tweak elution conditions. Manufacturers may also opt to formulate in-house adjustments to chromatography ligands and matrices to improve flow rates by minimizing the amount of time cells are bound.
In addition to chromatographic separations, manufacturers and developers can make use of innovations in non-chromatographic filtrate media. New types of membranes are able to filter out unwanted components by molecular weight even before chromatography. Cutting edge precision microfilter membrane materials also have the ability to screen particular molecules based on certain chemical characteristics.
Although still in testing phases, crystallization may also be utilized for protein isolation. Soon crystallization technology will reach a point where products are consistent enough for the technique to be widely applied in downstream bioprocess strategies.
Incorporating individual methods for downstream bioprocess improvement is an important step for developers and CMOs. To truly reap the benefits of these optimizations, though, these procedures must be combined to build a uniquely customized, scalable purification protocol.
Each pipeline will of course require tailored optimizations for rate-limiting steps like the hand-off of biomaterials between pieces of equipment or completing buffer exchanges. Further opportunities for cutting development cycle length and expense arise when these solutions can be repurposed as new therapeutics are added to production.
While the past few decades have witnessed significant progress in the fields of upstream and downstream bioprocess optimization, the proliferation of new media and filtration methods demands ongoing attention from developers and CMOs alike.
Meanwhile, as a growing number of biosimilars and newly patented vectors enter the clinical trial phase, process experts must work continually to develop and implement new operations, in order to ensure maximum yield and quality in their final products.
By partnering with CMOs experienced in optimizing upstream and downstream bioprocesses, biologic developers can meet their manufacturing goals while staying ahead of ever-evolving trends and technologies in this highly competitive space.
Recent advancements have lead to marked improvements in upstream and downstream bioprocess optimization. Developers and CMOs must remain abreast of novel filtration materials and methods to continually optimize procedures.
The market of biosimilar and vector therapeutics continues to expand rapidly. With these new products arriving at the clinical trial stage, those tasked with process design face the ongoing challenge of deploying enhanced protocols and procedures designed to facilitate optimal product output and purity.
CMOs with a deep understanding of what goes into building high performance upstream and downstream bioprocesses make excellent partners for ambitious biologic developers looking to achieve production objectives using the most cutting edge techniques available.