A bioprocess is a specific process that uses complete living cells or their components (e.g.,

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

chloroplast A chloroplast () is a type of membrane-bound organelle, organelle known as a plastid that conducts photosynthesis mostly in plant cell, plant and algae, algal cells. Chloroplasts have a high concentration of chlorophyll pigments which captur ...

s) to obtain desired products. Transport of energy and mass is fundamental to many biological and environmental processes. Areas, from

food processing Food processing is the transformation of agricultural products into food, or of one form of food into other forms. Food processing takes many forms, from grinding grain into raw flour, home cooking, and complex industrial methods used in the mak ...

(including

brewing Brewing is the production of beer by steeping a starch source (commonly cereal grains, the most popular of which is barley) in water and #Fermenting, fermenting the resulting sweet liquid with Yeast#Beer, yeast. It may be done in a brewery ...

beer) to thermal design of buildings to biomedical devices, manufacture of

monoclonal antibodies A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a Lineage (evolution), cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Mon ...

pollution control Pollution is the introduction of contaminants into the natural environment that cause harm. Pollution can take the form of any substance (solid, liquid, or gas) or energy (such as radioactivity, heat, sound, or light). Pollutants, the component ...

, require knowledge of how energy and mass can be transported through materials (momentum, heat transfer, etc.).

Cell bioprocessing

Cell therapy bioprocessing is a discipline that bridges the fields of

cell therapy Cell therapy (also called cellular therapy, cell transplantation, or cytotherapy) is a therapy in which viable cells are injected, grafted or implanted into a patient in order to effectuate a medicinal effect, for example, by transplanting T- ...

and bioprocessing (i.e., biopharmaceutical manufacturing), and is a sub-field of bioprocess engineering. The goals of cell therapy bioprocessing are to establish reproducible and robust manufacturing processes for the production of therapeutic cells.Rowley, J.A. Developing Cell Therapy Biomanufacturing Processes, Chem Eng Progress, SBE Stem Cell Engineering Nov Supplement, 50-55, 2010. Commercially relevant bioprocesses will: # Produce products that maintain all of the quality standards of biopharmaceutical drugs # Supply both clinical and commercial quantities of therapeutic cells throughout the various stages of development. The processes and production technologies must be scalable, and # Control the cost of goods (CoGs) of the final drug product. This aspect is critical to building the foundation for a commercially viable industry.

Upstream bioprocessing

Therapeutic cell manufacturing processes can be separated into upstream processes and downstream processes. The upstream process is defined as the entire process from early cell isolation and cultivation, to cell banking and culture expansion of the cells until final harvest (termination of the culture and collection of the live cell batch). Aside from technology challenges, concerning the scalability of culture apparatus, a number of raw material supply risks have emerged in recent years, including the availability of GMP grade fetal bovine serum. The upstream part of a bioprocess refers to the first step in which microbes/cells are grown, e.g. bacterial or mammalian cell lines (see

cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...

), in

bioreactors A bioreactor is any manufactured device or system that supports a biologically active environment. In one case, a bioreactor is a vessel in which a chemical process is carried out which involves organisms or biochemically active substances derive ...

. Upstream processing involves all the steps related to inoculum development, media development, improvement of inoculum by genetic engineering process, optimization of growth kinetics so that product development can improve tremendously. Fermentation has two parts: upstream and downstream. After product development, the next step is the purification of product for desired quality. When they reach the desired density (for batch and fed-batch cultures) they are harvested and moved to the downstream section of the bioprocess.

Downstream bioprocessing

The downstream part of a bioprocess refers to the part where the cell mass from the upstream are processed to meet purity and quality requirements. Downstream processing is usually divided into three main sections: cell disruption, a purification section and a polishing section. The volatile products can be separated by distillation of the harvested culture without pre-treatment. Distillation is done at reduced pressure at continuous stills. At reduced pressure, distillation of product directly from fermentor may be possible. The steps of downstream processing are: # Separation of biomass: separating the biomass (microbial cells) generally carried out by centrifugation or ultra-centrifugation. If the product is biomass, then it is recovered for processing and spent medium is discarded. If the product is extra cellular the biomass will be discarded. Ultra filtration is an alternative to the centrifugation. # Cell disruption: If the desired product is intra cellular the cell biomass can be disrupted so that the product should be released. The solid-liquid is separated by centrifugation or filtration and cell debris is discarded. # Concentration of broth: The spent medium is concentrated if the product is extracellular. # Initial purification of metabolites: According to the physico-chemical nature of the product molecule several methods for recovery of product from the clarified fermented broth were used (precipitation, etc.) # De-watering: If low amount of product is found in very large volume of spent medium, the volume is reduced by removing water to concentrate the product. It is done by vacuum drying or reverse osmosis. # Polishing of metabolites: this is the final step of making the product 98 to 100% pure. The purified product is mixed with several inert ingredients called

excipients An excipient is a substance formulated alongside the active ingredient of a medication. They may be used to enhance the active ingredient’s therapeutic properties; to facilitate drug absorption; to reduce viscosity; to enhance solubility; to i ...

. The formulated product is packed and sent to the market for the consumers.

References

{{Reflist Biotechnology

Cell bioprocessing

Upstream bioprocessing

Downstream bioprocessing

See also

References