A bioprocess is a specific process that uses complete living

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

or their components (e.g.,

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

chloroplast A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it in ...

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 includes many forms of processing foods, from grinding grain to make raw flour to home cooking to complex industr ...

(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 cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

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

and

global warming In common usage, climate change describes global warming—the ongoing increase in global average temperature—and its effects on Earth's climate system. Climate change in a broader sense also includes previous long-term changes to E ...

, 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-c ...

and

bioprocessing Bioprocess engineering, also biochemical engineering, is a specialization of chemical engineering or biological engineering. It deals with the design and development of equipment and processes for the manufacturing of products such as agriculture, ...

(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 GMP may refer to: Finance and economics * Gross metropolitan product * Guaranteed maximum price * Guaranteed Minimum Pension Science and technology * GNU Multiple Precision Arithmetic Library, a software library * Granulocyte-macrophage progenito ...

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 cells are grown under controlled conditions, generally outside of their natural environment. The term "tissue culture" was coined by American pathologist Montrose Thomas Burrows. This te ...

), in

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

. 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, included for the purpose of long-term stabilization, bulking up solid formulations that contain potent active ingredients in small amounts (thus often referred ...

. 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