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cGMP Yeast Fermentation

cGMP Yeast Fermentation

Microbial fermentation is the basis for the production of a wide range of pharmaceutical products, such as anticancer atatoxic drugs and vaccines, anti-infectious disease antibiotics and vaccines, etc. Many complex protein macromolecules, like human monoclonal antibodies require extensive post-translational modification. They can be produced in phylogenetically higher eukaryotic organisms such as yeast. Recombinant technology enables the expression of foreign gene encoding for therapeutic proteins in microbial systems, including those from human source. Using microbial fermentation is advantageous for expression of proteins. The recovery and selective purification of the specific desired product out of the completely molecular repertoire-makes fermentation technology a multi-disciplinary methodology encompassing microbiology, organic chemistry, biochemistry and molecular biology. Under cGMP fermentation procedures, quality is built into the entire process ensuring that regulatory agencies requirements are met in terms of safety, product identity, quality and purity.

Production System Advantages Limitations
Saccharomyces cerevisiae Production System Saccharomyces cerevisiae (S. cerevisiae) has been widely used in the manufacture of biologics. S. cerevisiae benefits from its eukaryotic model system, which enables the production and proper folding of many human proteins. The biopharmaceutical proteins can be secreted to the extracellular medium, which facilitates subsequent purification. S. cerevisiae can also perform post-translational modifications of the protein, including proteolytic processing of signal peptides, disulphide bond formation, subunit assembly, acylation and glycosylation. S. cerevisiae performs high-mannose type N-glycosylation and confers a short half-life of the modified protein in vivo, which produces a reduced efficacy for some therapeutic uses.
Pichia pastoris Production System Pichia pastoris (P. pastoris) is a robust, durable and cost-effective yeast expression system. P. pastoris grows on simple media and secretes low amounts of endogenous protein, making it easier to recover and purify the desired recombinant protein from the cell supernatant. Pichia is a methylotroph and can grow with the simple alcohol methanol as its only source of energy, and can grow in media containing only one carbon source and one nitrogen source. Besides, Pichia can grow to very high cell densities, and under ideal conditions can multiply to the point where the cell suspension is practically a paste. Pichia is unable to produce proteins (appropriate chaperones) for proper folding which the host lacks. Additionally, Pichia has been reported to produce hyperglycosylations of several proteins, which makes it unsuitable for the production of molecules for applications in structural biology.

Table 1 Comparison between the Saccharomyces cerevisiae and Pichia pastoris Production System

cGMP Yeast Fermentation

Types of Products

Small Molecules Proteins

Enzymes

Antibody Fragments

Peptides

Downstream Processing

cGMP Yeast Fermentation

Centrifugation

Lysis

Purification

UF/DF

Synthetic Chemistry

Our Capacity

  • Yields/Titres

Good experience in increasing yields and reducing of unwanted by-products.

  • Scale

Variety of scales with high throughput systems from plates, tubes and flasks through to bench- and small pilot-scale bioreactors.

  • Process Control

Advanced control capabilities for optimized aeration and feeding strategies.

  • GMP

Experience with preparing and migrating fermentation and DSP processes through various regulatory phases - IND/NDA and preparation of CMC documentation.

  • Scale-up/scale-down

Ability of troubleshoot challenging processes and deliver a robust´╝îreproducible and scaleable batch recipe with validated in-process controls.

Creative Biogene has extensive experience and considerable expertise in the use of S. cerevisiae and P. pastoris in the manufacture of recombinant proteins, whole-cell vaccines, viral vaccines, and live biotherapeutics. We utilizes licensed processes and technologies operating to international Current Good Manufacturing Practices (cGMP) standards that provide comprehensive solutions for both biological and small molecule drugs.

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