In Fig. Stage 1. Solid-Liquid Separation: The first step in product recovery is the separation of whole cells cell biomass and other insoluble ingredients from the culture broth Note: If the desired product is an intracellular metabolite, it must be released from the cells before subjecting to solid-liquid separation. Some authors use the term harvesting of microbial cells for the separation of cells from the culture medium.
|Published (Last):||28 April 2004|
|PDF File Size:||4.21 Mb|
|ePub File Size:||14.56 Mb|
|Price:||Free* [*Free Regsitration Required]|
Cell bioprocessing[ edit ] Cell therapy bioprocessing is a discipline that bridges the fields of cell therapy and bioprocessing i. The goals of cell therapy bioprocessing are to establish reproducible and robust manufacturing processes for the production of therapeutic cells. 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[ edit ] 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[ when? 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[ edit ] 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. The purified product is mixed with several inert ingredients called excipients.
The formulated product is packed and sent to the market for the consumers.
Stages in Downstream Processing: 5 Stages
Cell bioprocessing[ edit ] Cell therapy bioprocessing is a discipline that bridges the fields of cell therapy and bioprocessing i. The goals of cell therapy bioprocessing are to establish reproducible and robust manufacturing processes for the production of therapeutic cells. 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.
This article includes a list of references , but its sources remain unclear because it has insufficient inline citations. Please help to improve this article by introducing more precise citations. April Learn how and when to remove this template message Downstream processing refers to the recovery and the purification of biosynthetic products, particularly pharmaceuticals, from natural sources such as animal or plant tissue or fermentation broth, including the recycling of salvageable components and the proper treatment and disposal of waste. It is an essential step in the manufacture of pharmaceuticals such as antibiotics, hormones e. Downstream processing is usually considered a specialized field in biochemical engineering , itself a specialization within chemical engineering , though many of the key technologies were developed by chemists and biologists for laboratory-scale separation of biological products.