Biopharmaceutical
Encyclopedia
Biopharmaceuticals are medical drugs (see pharmacology
) produced using biotechnology
. They include proteins (including antibodies
), nucleic acids (DNA
, RNA
or antisense oligonucleotide
s) and living microorganisms like virus
and bacteria
where the virulence of viruses and bacteria is reduced by the process of attenuation, they can be used for therapeutic or in vivo
diagnostic purposes, and are produced by means other than direct extraction from a native (non-engineered) biological
source.
The first such substance approved for therapeutic use was biosynthetic 'human' insulin
made via recombinant DNA
technology. Sometimes referred to as rHI, under the trade name Humulin, was developed by Genentech
, but licensed to Eli Lilly and Company
, who manufactured and marketed the product starting in 1982.
The large majority of biopharmaceutical products are pharmaceuticals that are derived from life forms. Small molecule drugs are not typically regarded as biopharmaceutical in nature by the industry. However members of the press and the business and financial community often extend the definition to include pharmaceuticals not created through biotechnology. That is, the term has become an oft-used buzzword
for a variety of different companies producing new, apparently high-tech pharmaceutical products. Research and development investment in new medicines by the biopharmaceutical industry stood at $65.2bn in 2008.
When a biopharmaceutical is developed, the company will typically apply for a patent, which is a grant for exclusive manufacturing rights. This is the primary means by which the developer of the drug can recover the investment cost for development of the biopharmaceutical. The patent laws in the United States
and Europe
differ somewhat on the requirements for a patent, with the European requirements are perceived as more difficult to satisfy. The total number of patents granted for biopharmaceuticals has risen significantly since the 1970s. In 1978 the total patents granted was 30. This had climbed to 15,600 in 1995, and by 2001 there were 34,527 patent applications.
Within the United States
, the Food and Drug Administration
(FDA) exerts strict control over the commercial distribution of a pharmaceutical product, including biopharmaceuticals. Approval can require several years of clinical trials, including trials with human volunteers. Even after the drug is released, it will still be monitored for performance and safety risks.
The manufacture of the drug must satisfy the "current Good Manufacturing Practices" regulations of the FDA. They are typically manufactured in a clean room environment with set standards for the amount of airborne particles.
or yeast cultures), mammalian cell lines (see cell culture
) and plant cell cultures (see plant tissue culture
) and moss
plants in bioreactor
s of various configurations, including photo-bioreactors.
Important issues of concern are cost of production (a low volume, high purity product is desirable) and microbial contamination (by bacteria
, virus
es, mycoplasma
, etc.). Alternative platforms of production which are being tested include whole plants (plant-made pharmaceuticals).
One potential approach to this technology is the creation of a transgenic mammal that can produce the biopharmaceutical in its milk (or blood or urine). Once an animal is produced, typically using the pronuclear microinjection method, it becomes efficacious to use cloning technology to create additional offspring that carry the favorable modified genome. The first such drug manufactured from the milk of a genetically-modified goat
was ATryn
, but marketing permission was blocked by the European Medicines Agency
in February 2006.
This decision was reversed in June 2006 and approval was given August 2006.
Pharmacology
Pharmacology is the branch of medicine and biology concerned with the study of drug action. More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function...
) produced using biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...
. They include proteins (including antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
), nucleic acids (DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
or antisense oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
s) and living microorganisms like virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
where the virulence of viruses and bacteria is reduced by the process of attenuation, they can be used for therapeutic or in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...
diagnostic purposes, and are produced by means other than direct extraction from a native (non-engineered) biological
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
source.
The first such substance approved for therapeutic use was biosynthetic 'human' insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
made via recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
technology. Sometimes referred to as rHI, under the trade name Humulin, was developed by Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...
, but licensed to Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
, who manufactured and marketed the product starting in 1982.
The large majority of biopharmaceutical products are pharmaceuticals that are derived from life forms. Small molecule drugs are not typically regarded as biopharmaceutical in nature by the industry. However members of the press and the business and financial community often extend the definition to include pharmaceuticals not created through biotechnology. That is, the term has become an oft-used buzzword
Buzzword
A buzzword is a term of art, salesmanship, politics, or technical jargon that is used in the media and wider society outside of its originally narrow technical context....
for a variety of different companies producing new, apparently high-tech pharmaceutical products. Research and development investment in new medicines by the biopharmaceutical industry stood at $65.2bn in 2008.
When a biopharmaceutical is developed, the company will typically apply for a patent, which is a grant for exclusive manufacturing rights. This is the primary means by which the developer of the drug can recover the investment cost for development of the biopharmaceutical. The patent laws in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
and Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
differ somewhat on the requirements for a patent, with the European requirements are perceived as more difficult to satisfy. The total number of patents granted for biopharmaceuticals has risen significantly since the 1970s. In 1978 the total patents granted was 30. This had climbed to 15,600 in 1995, and by 2001 there were 34,527 patent applications.
Within the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA) exerts strict control over the commercial distribution of a pharmaceutical product, including biopharmaceuticals. Approval can require several years of clinical trials, including trials with human volunteers. Even after the drug is released, it will still be monitored for performance and safety risks.
The manufacture of the drug must satisfy the "current Good Manufacturing Practices" regulations of the FDA. They are typically manufactured in a clean room environment with set standards for the amount of airborne particles.
Classification of biopharmaceuticals
- Blood factors (Factor VIIIFactor VIIIFactor VIII is an essential blood clotting factor also known as anti-hemophilic factor . In humans, Factor VIII is encoded by the F8 gene...
and Factor IXFactor IXFactor IX is one of the serine proteases of the coagulation system; it belongs to peptidase family S1. Deficiency of this protein causes hemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to...
) - Thrombolytic agents (tissue plasminogen activatorTissue plasminogen activatorTissue plasminogen activator is a protein involved in the breakdown of blood clots. It is a serine protease found on endothelial cells, the cells that line the blood vessels. As an enzyme, it catalyzes the conversion of plasminogen to plasmin, the major enzyme responsible for clot breakdown...
) - Hormones (insulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, glucagon, growth hormone, gonadotrophins) - Haematopoietic growth factors (ErythropoietinErythropoietinErythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
, colony stimulating factors) - Interferons (Interferons-α, -β, -γ)
- InterleukinInterleukinInterleukins are a group of cytokines that were first seen to be expressed by white blood cells . The term interleukin derives from "as a means of communication", and "deriving from the fact that many of these proteins are produced by leukocytes and act on leukocytes"...
-based products (Interleukin-2) - Vaccines (Hepatitis B surface antigenAntigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
) - Monoclonal antibodiesMonoclonal antibodiesMonoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
(Various) - Additional products (tumour necrosis factor, therapeutic enzymes)
Uses
- ErythropoietinErythropoietinErythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
- Treatment of anaemia - Interferon-α - Treatment of leukaemia
- Interferon-βIFNB1Interferon beta is a protein that in humans is encoded by the IFNB1 gene.-Further reading:...
- Treatment of multiple sclerosisMultiple sclerosisMultiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms... - Monoclonal antibody - Treatment of rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
- Colony stimulating factors - Treatment of neutropeniaNeutropeniaNeutropenia, from Latin prefix neutro- and Greek suffix -πενία , is a granulocyte disorder characterized by an abnormally low number of neutrophils, the most important type of white blood cell...
- GlucocerebrosidaseGlucocerebrosidaseβ-Glucocerebrosidase is an enzyme with glucosylceramidase activity that is needed to cleave, by hydrolysis, the beta-glucosidic linkage of the chemical glucocerebroside, an intermediate in glycolipid metabolism...
- Treatment of Gaucher's diseaseGaucher's diseaseGaucher's disease is a genetic disease in which a fatty substance accumulates in cells and certain organs.Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid...
Large scale production
Biopharmaceuticals may be produced from microbial cells (e.g. recombinant E. coliEscherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
or yeast cultures), mammalian cell lines (see cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
) and plant cell cultures (see plant tissue culture
Plant tissue culture
Plant tissue culture is a collection of techniques used to maintain or grow plant cells, tissues or organs under sterile conditions on a nutrient culture medium of known composition. Plant tissue culture is widely used to produce clones of a plant in a method known as micropropagation...
) and moss
Moss
Mosses are small, soft plants that are typically 1–10 cm tall, though some species are much larger. They commonly grow close together in clumps or mats in damp or shady locations. They do not have flowers or seeds, and their simple leaves cover the thin wiry stems...
plants in bioreactor
Bioreactor
A bioreactor may refer to any manufactured or engineered 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 derived from such organisms. This...
s of various configurations, including photo-bioreactors.
Important issues of concern are cost of production (a low volume, high purity product is desirable) and microbial contamination (by bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es, mycoplasma
Mycoplasma
Mycoplasma refers to a genus of bacteria that lack a cell wall. Without a cell wall, they are unaffected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans,...
, etc.). Alternative platforms of production which are being tested include whole plants (plant-made pharmaceuticals).
Transgenics
A potentially controversial method of producing biopharmaceuticals involves transgenic organisms, particularly plants and animals that have been genetically modified to produce drugs. The production of these organisms represents a significant risk on the part of the investor, both in terms of the risk of failure to produce the required organism, and in the risk of non-acceptance by government bodies due to the perceived risks and from ethical issues. Biopharmaceutical crops also represent a risk of cross-contamination with non-engineered crops, or crops engineered for non-medical purposes.One potential approach to this technology is the creation of a transgenic mammal that can produce the biopharmaceutical in its milk (or blood or urine). Once an animal is produced, typically using the pronuclear microinjection method, it becomes efficacious to use cloning technology to create additional offspring that carry the favorable modified genome. The first such drug manufactured from the milk of a genetically-modified goat
Goat
The domestic goat is a subspecies of goat domesticated from the wild goat of southwest Asia and Eastern Europe. The goat is a member of the Bovidae family and is closely related to the sheep as both are in the goat-antelope subfamily Caprinae. There are over three hundred distinct breeds of...
was ATryn
ATryn
ATryn is the brand name of the anticoagulant antithrombin manufactured by the Massachusetts-based U.S. company GTC Biotherapeutics. It is made from the milk of goats that have been genetically modified to produce human antithrombin, a plasma protein with anticoagulant properties. Microinjection was...
, but marketing permission was blocked by the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
in February 2006.
This decision was reversed in June 2006 and approval was given August 2006.
See also
- BiologicsBiologicsA biologic is a medicinal product such as a vaccine, blood or blood component, allergenic, somatic cell, gene therapy, tissue, recombinant therapeutic protein, or living cells that are used as therapeutics to treat diseases...
- Genetic engineeringGenetic engineeringGenetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
- List of recombinant proteins
- List of pharmaceutical companies
- NanobiopharmaceuticsNanobiopharmaceuticsNanobiopharmaceutics is an inter-disciplinary field involving delivery of biopharmaceutical products through nanobiotechnology applications like nanoparticles, liposomes. It involves knowledge from nanobiotechnology, biotechnology and biopharmaceutics....
- Pharming (genetics)Pharming (genetics)Pharming is a portmanteau of farming and "pharmaceutical" and refers to the use of genetic engineering to insert genes that code for useful pharmaceuticals into host animals or plants that would otherwise not express those genes. As a consequence, the host animals or plants then make the...
- Medical science liaison