Janifha Evangeline | Saturday, 07 May 2022
The basis for the production of a broad range of pharmaceutical products is Microbial fermentation, targeting practically any medical indication. The examples range from anti-infectious disease antibiotics and vaccines, anti-cancer cytotoxic drugs and vaccines, to hormonal disorder therapy and various other indications.
While some of the endogenous molecules can be manipulated for the biosynthesis of foreign molecules, Natural biosynthesis of endogenous molecules involves specific multi-step complex routes. Micro-organisms can either be metabolically engineered by substantial alteration of their endogenous routes or genetically modified. Strain selection & optimization, media & process development, and finally, scale-up to maximize productivity are the most important elements of fermentation development.
For extracting, concentrating, and purifying the product from a dilute fermentation broth is downstream processing utilizes numerous technologies. What makes the fermentation technology a multi-disciplinary methodology comprising microbiology, organic chemistry, biochemistry & molecular biology is the Fermentation derived product diversity – the recovery & selective purification of the specific desired product out of the whole molecular repertoire. Necessary biosafety measures are taken particularly when fermenting volumes are larger than 10L especially when Risk Group 2 (RG2) pathogens are used.
These include special operational procedures & Biosafety Level 2 Large Scale containment facility design since these products can be hazardous & toxic. Furthermore, the recovery & purification needs adequate chemical/biochemical facilities as well as equipment such as isolators for handling High-Potent APIs. Quality is built into the complete process which ensures the regulatory agencies' requirements are met in terms of safety, product identity, purity & quality, under the cGMP fermentation procedures.Strains handled under strict aseptic procedures will be characterized & identified for homogeneity, and deposited in temperature-controlled bio-storage.
Why should we choose microbial fermentation The only route to chemical APIs is Fermentation. It relies majorly on micro-organisms. It doesn’t have any other equivalent in other biological systems. One example is mammalian cells. Others include antibiotic/secondary metabolites. How these organic molecules can be obtained is via multi-step synthesis from their building blocks.
But organic molecules are highly complex in nature, with encompassing structures that include chiral centers, unique conjugated double bond systems, or large stereospecific rings. Going down the synthetic route not only needs important development however it is time-consuming and entails higher costs than the fermentation option.
While the semi-synthetic approach draws upon the merits of fermentation in the generation of new drugs, Natural molecules are produced using fermentation and then modified synthetically, decreasing toxicity, increasing potency & selectivity, and overcoming bacterial resistance to traditional antibiotics. Fermentation may also be the only source for natural therapeutic proteins solely expressed in microbial systems.
Proteins are complex molecules of high to mid molecular weight and their functionality as well as stability majorly depend on their secondary as well as tertiary structure along with various post-translational modifications, mainly glycosylation. Recombinant technology facilitates the expression of the foreign gene that is coding for therapeutic proteins in microbial systems. These include those from a human source. Using microbial fermentation is advantageous for the expression of proteins which doesn’t need post-translation modifications as microbial systems. Another approach is to reduce the protein expressed to the minimal effective domain.
The major merits of fermentation when compared to the mammalian system, are timed and yield that ultimately translate to cost. Therapeutic proteins that require modification, for instance, glycosylation of antibodies were expressed in mammalian cell cultures, until recently. Driven by factors such as cost considerations, scientists looked to express glycosylated therapeutic proteins in microbial systems, which will lead to a novel approach. The modified route reproduced the human pathway hence allowing the expression of humanized antibody fragments.
Innovation in microbial fermentation New perspectives, as well as new expectations, are being generated from cell therapy to predictive diagnosis technologies. These are appearing for the prevention of many human diseases & for the treatment, while an increasing number of Biopharma & culture media manufacturers are implementing ProCel yeast nutrients in their production. Furthermore, vitamins, Recombinant proteins, antibiotics, antibodies, vaccine productions along with ready-to-use-media & culture media for diagnostic purposes can all benefit from the utilization of the ProCel product range.
The ProCel range is particularly designed for Biopharma & diagnostic culture media producers. It helps in addressing the specific demands of these industries. “Procelys has a separate product line dedicated to the biopharma industry. So, this dedication comes with quality standards and auditability. In addition to that, the product meets the consistency that the biopharma industry should expect and that media manufacturers should expect”, says Shawn Nelson, North American Technical Service Manager, Procelys.
The way ahead Microbial fermentation is not a new technology and it continues to evolve. This is now often one of the most preferred production methods for chemical compounds as well as therapeutic proteins. It provides a maximum economic route that allows pharmaceutical companies to shorten the time to market and production processes.
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