Downstream processing refers to the recovery and the purification of

biosynthetic product Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

s, particularly

pharmaceutical Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy ( pharmacotherapy) is an important part of the ...

s, from natural sources such as animal tissue,

plant tissue In biology, tissue is an assembly of similar cells and their extracellular matrix from the same embryonic origin that together carry out a specific function. Tissues occupy a biological organizational level between cells and a complete organ. ...

fermentation Fermentation is a type of anaerobic metabolism which harnesses the redox potential of the reactants to make adenosine triphosphate (ATP) and organic end products. Organic molecules, such as glucose or other sugars, are catabolized and reduce ...

broth Broth, also known as bouillon (), is a savory liquid made of water in which meat, fish, or vegetables have been simmered for a short period of time. It can be eaten alone, but it is most commonly used to prepare other dishes, such as soups ...

, including the recycling of salvageable components as well as the proper treatment and disposal of waste. It is an essential step in the manufacture of pharmaceuticals such as

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...

s (e.g.

insulin Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (''INS)'' gene. It is the main Anabolism, anabolic hormone of the body. It regulates the metabol ...

and

human growth hormone Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in ...

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

(e.g.

infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing ...

and

abciximab Abciximab, a glycoprotein IIb/IIIa receptor antagonist manufactured by Janssen Biologics BV and distributed by Eli Lilly under the trade name ReoPro, is a platelet aggregation inhibitor mainly used during and after coronary artery procedures lik ...

) and

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifi ...

s; antibodies and

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 ...

s used in diagnostics; industrial enzymes; and natural fragrance and flavor compounds. Downstream processing is usually considered a specialized field in biochemical engineering, which is itself a specialization within

chemical engineering Chemical engineering is an engineering field which deals with the study of the operation and design of chemical plants as well as methods of improving production. Chemical engineers develop economical commercial processes to convert raw materials ...

. Many of the key technologies were developed by chemists and biologists for laboratory-scale separation of biological and synthetic products, whilst the role of biochemical and chemical engineers is to develop the technologies towards larger production capacities. Downstream processing and analytical bioseparation both refer to the separation or purification of biological products, but at different scales of operation and for different purposes. Downstream processing implies manufacture of a purified product fit for a specific use, generally in marketable quantities, while analytical bioseparation refers to purification for the sole purpose of measuring a component or components of a mixture, and may deal with sample sizes as small as a single cell.

Stages

A widely recognized heuristic for categorizing downstream processing operations divides them into four groups which are applied in order to bring a product from its natural state as a component of a tissue, cell or fermentation broth through progressive improvements in purity and concentration. ''Removal of insolubles'' is the first step and involves the capture of the product as a solute in a particulate-free liquid, for example the separation of

cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...

, cell debris or other particulate matter from fermentation broth containing an antibiotic. Typical operations to achieve this are

filtration Filtration is a physical separation process that separates solid matter and fluid from a mixture using a ''filter medium'' that has a complex structure through which only the fluid can pass. Solid particles that cannot pass through the filte ...

centrifugation Centrifugation is a mechanical process which involves the use of the centrifugal force to separate particles from a solution according to their size, shape, density, medium viscosity and rotor speed. The denser components of the mixture migrate ...

sedimentation Sedimentation is the deposition of sediments. It takes place when particles in suspension settle out of the fluid in which they are entrained and come to rest against a barrier. This is due to their motion through the fluid in response to th ...

, precipitation,

flocculation In colloidal chemistry, flocculation is a process by which colloidal particles come out of Suspension (chemistry), suspension to sediment in the form of floc or flake, either spontaneously or due to the addition of a clarifying agent. The actio ...

, electro-precipitation, and gravity settling. Additional operations such as grinding, homogenization, or leaching, required to recover products from solid sources such as plant and animal tissues, are usually included in this group. ''Product isolation'' is the removal of those components whose properties vary considerably from that of the desired product. For most products, water is the chief impurity and isolation steps are designed to remove most of it, reducing the volume of material to be handled and concentrating the product.

Solvent A solvent (from the Latin language, Latin ''wikt:solvo#Latin, solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a Solution (chemistry), solution. A solvent is usually a liquid but can also be a solid, a gas ...

extraction,

adsorption Adsorption is the adhesion of atoms, ions or molecules from a gas, liquid or dissolved solid to a surface. This process creates a film of the ''adsorbate'' on the surface of the ''adsorbent''. This process differs from absorption, in which a ...

, ultrafiltration, and

precipitation In meteorology, precipitation is any product of the condensation of atmospheric water vapor that falls from clouds due to gravitational pull. The main forms of precipitation include drizzle, rain, rain and snow mixed ("sleet" in Commonwe ...

are some of the unit operations involved. ''Product purification'' is done to separate those contaminants that resemble the product very closely in physical and chemical properties. Consequently, steps in this stage are expensive to carry out and require sensitive and sophisticated equipment. This stage contributes a significant fraction of the entire downstream processing expenditure. Examples of operations include affinity, size exclusion, reversed phase

chromatography In chemical analysis, chromatography is a laboratory technique for the Separation process, separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it ...

ion-exchange chromatography Ion chromatography (or ion-exchange chromatography) is a form of chromatography that separates ions and ionizable polar molecules based on their affinity to the ion exchanger. It works on almost any kind of Charge (chemistry), charged molecule ...

crystallization Crystallization is a process that leads to solids with highly organized Atom, atoms or Molecule, molecules, i.e. a crystal. The ordered nature of a crystalline solid can be contrasted with amorphous solids in which atoms or molecules lack regu ...

and fractional precipitation. ''Product polishing'' describes the final processing steps which end with packaging of the product in a form that is stable, easily transportable and convenient.

Crystallization Crystallization is a process that leads to solids with highly organized Atom, atoms or Molecule, molecules, i.e. a crystal. The ordered nature of a crystalline solid can be contrasted with amorphous solids in which atoms or molecules lack regu ...

desiccation Desiccation is the state of extreme dryness, or the process of extreme drying. A desiccant is a hygroscopic (attracts and holds water) substance that induces or sustains such a state in its local vicinity in a moderately sealed container. The ...

lyophilization Freeze drying, also known as lyophilization or cryodesiccation, is a low temperature dehydration process that involves freezing the product and lowering pressure, thereby removing the ice by sublimation. This is in contrast to dehydration by m ...

and spray drying are typical unit operations. Depending on the product and its intended use, polishing may also include operations to sterilize the product and remove or deactivate trace contaminants which might compromise product safety. Such operations might include the removal of viruses or depyrogenation. A few product recovery methods may be considered to combine two or more stages. For example, expanded bed adsorption (Vennapusa ''et al.'' 2008) accomplishes removal of insolubles and product isolation in a single step.

Affinity chromatography Affinity chromatography is a method of separating a biomolecule from a mixture, based on a highly specific macromolecular binding interaction between the biomolecule and another substance. The specific type of binding interaction depends on the ...

often isolates and purifies in a single step.

References

* * *{{cite book , first=Nooralabettu , last=Krishna Prasad , title=Downstream Processing-A New Horizone in Biotechnology , publisher=Prentice Hall of India Pvt. Ltd, New Delhi , year=2010 , isbn=978-81-203-4040-4 Chemical processes Drug manufacturing

Stages

See also

References