Movers and SHAKERS
Biologic drugs or “biologics” are therapeutic agents extracted or partially synthesized from biological sources, and the demand for them is growing.
This year alone 37% of the drugs the U.S. Food & Drug Administration approved have been biologics and they make up an estimated 70% of the top selling drugs in the marketplace.
Now, the manufacturers are facing a critical decision. Do they keep sailing the current course when it comes to production? Or do they seek out new ways to improve?
Divergent approach to improve bio-production
Despite the relative success of CHO system, there is room and need for a novel “cost/time efficient” expression system. There are clear limitations to what could be accomplished using the CHO platform. Among the main challenges associated with the use of CHO system, experts emphasize the following:
- Time consuming and labor-intensive selection process to screen
- Growing CHO cells in cell culture carry an expiration date
These challenges clearly indicate the requirement for the emerging technologies, which have the potential to offer a solution to some of the mentioned challenges. The novel technologies can expand bio-production of main biologics, having a significant impact on the industry’s profit margins lowering the cost of manufacturing. The need for new bio-production technologies will drive valuation of biotechnology companies in this segment of the sector.
Alternative technologies can provide cost and time efficiency in bioproduction
C1 gene expression platform is employed to improve manufacturing of biologics. C1 technology is part of a fungi expression system and was isolated from soil. The expression system is characterized by low viscosity morphology, allowing easy, large-scale, high-cell-density growth in fermenters. The technology utilizes inexpensive substrates, diminishing cost while keeping yields and product quality intact. The C1 system support growth in broad ranges of pH (4.5–7.0) and temperature (25–44°C). The advantages of this system include:
- Low cost
- High yields
The current research and development work are focused to optimize generations of human-like proteins using C1 expressions systems. High production of proteases destroying and limiting recombinant protein manufacturing was a critical step in streamlining production of target protein. This step has been optimized with deletions of protease strains.
Another expression platform, called SoluPro, is designed to lower cost and time used to manufacture biologic products. SoluPro is an Escherichia coli (E-coli) based expression system, that has been able to overcome limitations of traditional E. coli systems while taking advantage of the simplicity and lower costs of this expression system.
Does the industry need to change status quo?
At present, Chinese Hamster Ovary (CHO) cells, a mammalian expression system, is the standard platform to manufacture biologics in the biotechnology industry. Nowadays, over 70% of biologics are manufactured using this expression system. Among the top ten bestselling biologics, seven of them are manufactured using CHO cells. Over two decades of utilization of CHO cells in bio-production have led to significant fine tuning of this platform, with more than 100-fold yield improvement using established cell lines.
Some advantages of CHO expression systems include:
- Capacity for efficient post-translational modification of biologics (capability to make biologics as similar as possible to human natural proteins)
- Familiarity and improvement in production (improved expression efficiency and higher tolerance to pH temperature) after years of research in this expression system
- Works well for certain types of proteins such as membrane proteins (proteins that interact with, or are part of biological membranes)
This system is widely used and well accepted by pharmaceutical companies and regulatory agencies. Utilization of emerging technologies in this field might be challenging until strong advantages are demonstrated. However, industry efforts continue to discover and develop new processes.
Most industry experts believe the manufacturing of biologics will continue to evolve, as more efficient methods are developed by emerging biotechnology companies. The consensus among scientists and entrepreneurs is that choosing an appropriate protein expression system is the key to the success of biologics manufacturing, especially given the considerable degree of variability, limited understanding of the sources of variations, and laborious and extensive screening requirements in mammalian cell culture processes.
The expression efficiency of various modalities (monoclonal antibodies, vaccines, oncolytic viruses) are distinct in various expression systems. A novel technology, such as C1 technology, could potentially provide a cost and time efficient processing in certain types of biologic manufacturing. Further investigations will provide improvement and light on the capabilities of this system in bio-production.
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