Bioprocessing: Cell, Upstream & Downstream Bioprocessing

Bioprocessing is a technology that utilizes living cells or their cellular components, viruses or an entire organism to obtain the products we desire. The entire process can be divided into two main parts- upstream processing and downstream processing. The Upstream processing involves the preparatory phases such as early cell isolation and cultivation, to cell banking and expansion of the cell culture until the final harvest i.e. termination of the culture and collection of the same takes place while the downstream processing incorporates the procedure where the cell mass from the upstream is processed to meet the quality and the purity requirements. 

Also Read: Strategies for Enhancement in Food Production

Key Takeaways: Bioprocessing, Upstream processing, downstream processing, PFD, P&I diagrams, symbology.

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Bioprocessing

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Bioprocess can be defined as a particular process that utilizes living cells or their cellular components to obtain desired products. As the transfer of mass and energy is quite critical for all the biological and environmental processes the areas from pharmaceuticals to biomedical devices to pollution control and global warming require the knowledge of mass and energy transfer. 

Application of Bioprocessing in various fields

Thus Bioprocessing, also known as biotechnology is being widely utilized in the creation of nourishments, flavours, synthetic biocatalysts, hereditary designing for the control of animals, plants or microorganisms.

The whole process is usually divided into three sections: 

• Cell disruption
• Purification 
• Polishing

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Cell Bioprocessing

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Cell Therapy and bioprocessing (pharmaceutical manufacturing) are two of the fascinating areas of study that can be bridged by a discipline called Cell Therapy Bioprocessing which is a sub-field of Bioprocess engineering. The goals of cell therapy bioprocessing are to build up robust and reproducible manufacturing techniques for the production of therapeutic cells. 

Stem cell bioprocessing

A commercially relevant bioprocess will:

1. Create products to maintain the quality standards of the biopharmaceutical drugs.
2. Supply therapeutic cells for both clinical and commercial purposes throughout various stages of development and scalable technologies.
3. Control the cost of goods(CoGs) of the final materials which is a critical aspect to build the foundation for commercially viable industry.

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Upstream Bioprocessing

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Bioprocessing hardware incorporates an extensive range of gear of explicit applications. In terms of procedure stream graph, it might be classified into three parts- upstream processing, downstream processing and support. The upstream process includes the procedures from early cell isolation and cultivation, to cell banking and expansion of the cell culture until the final harvest i.e. termination of the culture and collection of the same takes place.

Upstream Bioprocessing

The upstream processes are the first step in which the microbes or the cells are grown. For example, mammalian or bacterial cell lines, in bioreactors. Thus, it involves all the steps related to inoculum development, improvement of inoculum, media development, genetic engineering, optimization of growth kinetics for improvement of the product. 

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Downstream Bioprocessing

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Downstream process, as important as the upstream process, refers to the part of the process where the cell mass from the upstream is processed to meet the quality and purity requirements. The whole process is usually divided into three sections: cell disruption, purification and polishing. 

Downstream Processing

The volatile products are separated by distillation of the harvested culture without any pre-treatment. Distillation is done through continuous stills at reduced pressure. At such reduced pressure, the distillation of product directly from the fermenter is sometimes possible. The steps involved in the downstream processing are:

1. Separation of biomass: It is generally carried out by centrifugation or ultra-centrifugation. If the product is biomass then it is recovered from further processing and the spent medium is discarded completely. In the case of extracellular, the biomass is discarded. Sometimes ultra-filtration can also be carried out as an alternative to centrifugation.
2. Cell disruption: If the desired product is an intracellular component then the cell biomass is usually disrupted so that the product is released. Then centrifugation of filtration can be done to separate the solid and the liquid; the debris is discarded then.
3. The spent medium is concentrated if the product is extracellular.
4. Initial Purification: According to the physicochemical characteristics of the product molecule various recovery methods are applied for the recovery of the product.

Steps in Downstream Process

5. De-watering: If a low amount of product is found in a very large quantity of spent medium, the volume is usually reduced by removing water to concentrate the product. It is usually done by vacuum drying or reverse osmosis.
6. Polishing of metabolites: This is the final step to make the product of the highest purity (98-100%). The purified product is generally mixed with other inert ingredients named excipients. Then the product is packed and sent to the market for consumption.

Also Read: Artificial Pollination

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P&I Diagrams and Process Flow Diagrams

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In bioprocessing, the equipment and the process from the design phase through the life cycle of the process can be expressed with the help of several types of flow diagrams. This involves different levels of detailing from the stages of the conception to construction, engineering production etc.

Typical P&I diagram

Usually, simplified process flow diagrams are used in the early conceptual phase of a new process where generally they do not contain all details that the final version will have. PFD documents at this phase are only used for discussion until the design is finalized. Process and Instrumentation diagrams (P&I diagrams) are more detailed than that of PFD. Therefore, they are seen as primary documents in the documentation serving as support for the functioning and maintenance throughout the working span.

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Symbology

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A standardized symbology is used in P&I diagrams and Process Flow Diagrams to indicate the components of instrumentations and others. The International Society of Automation (ISA) standard is the standard commonly used for such symbols.

Symbols used in P&I Diagrams

Components such as filters, pumps and all instrument loops which are typically assigned instrument loop numbers serve as unique identities for all elements of a system. Loop numbers are used in other parts of the engineering documentation. These are either made of stainless steel or plastic. Thus, all the components are linked to the right documentation to promote operation, qualification and maintenance of the equipment in future.

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Things to Remember

• Bioprocess is a particular process that utilizes living cells or their cellular components to obtain the products we desire or require.
• Bioprocessing is being widely used in nourishments, flavours, synthetic biocatalysts, hereditary designing for the control of animals, plants or microorganisms.
• Cell Therapy Bioprocessing which is a sub-field of Bioprocess engineering bridges the fields like Cell Therapy and bioprocessing( pharmaceutical manufacturing).
• The upstream process incorporates the processes from early cell isolation and cultivation to cell banking and expansion of the cell culture until the final harvest i.e. termination of the culture and collection of the same takes place.
• The downstream process refers to the part of the process where the cell mass from the upstream is processed to meet the quality and purity requirements. 
• The International Society of Automation (ISA) standard is the standard commonly used for symbols in PFD and P&I documents.

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