Biologics
Encyclopedia
A biologic is a medicinal product such as a vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

, blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 or blood component, allergenic, somatic cell
Somatic cell
A somatic cell is any biological cell forming the body of an organism; that is, in a multicellular organism, any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell...

, gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...

, tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...

, recombinant therapeutic protein, or living cells that are used as therapeutics to treat diseases. Biologics are created by biologic
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

 processes, rather than being chemically
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

 synthesized.

Biologics can be composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources — human, animal, or microorganism — and may be produced by biotechnology methods and other technologies. Gene-based and cellular biologics, for example, often are at the forefront of biomedical research, and may be used to treat a variety of medical conditions for which no other treatments are available.

In some jurisdictions, biologics are regulated through varied regulatory pathway other than small molecule drugs and medical devices.

Extracted from living systems

Some of the oldest forms of biologics are extracted from the bodies of animals, and other humans especially. Important biologics include:
  • Whole blood
    Whole blood
    Whole blood is a term used in transfusion medicine for human blood from a standard blood donation. The blood is typically combined with an anticoagulant during the collection process, but is generally otherwise unprocessed...

     and other blood components.
  • Organs and tissue transplants.
  • Stem cell therapy.
  • Antibodies for passive immunization, e.g., to treat a virus infection.


Some biologics that were previously extracted from animals, such as insulin, are now more commonly produced by recombinant DNA.

Produced by recombinant DNA

As indicated the term "biologics" can be used to refer to a wide range of biological products in medicine. However, in most cases, the term "biologics" is used more restrictively for a class of therapeutics (either approved or in development) that are produced by means of biological processes involving 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. These medications are usually one of three types:
  1. Substances that are (nearly) identical to the body's own key signalling proteins. Examples are the blood-production stimulating protein erythropoetin, or the growth-stimulating hormone named (simply) "growth hormone
    Growth hormone
    Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...

    " or 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....

     and its analogues.
  2. Monoclonal antibodies
    Monoclonal antibodies
    Monoclonal 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....

    . These are similar to the antibodies that the human immune system uses to fight off bacteria and viruses, but they are "custom-designed" (using hybridoma
    Hybridoma
    Hybridoma technology is a technology of forming hybrid cell lines by fusing a specific antibody-producing B cell with a myeloma cell that is selected for its ability to grow in tissue culture and for an absence of antibody chain synthesis...

     technology or other methods) and can therefore be made specifically to counteract or block any given substance in the body, or to target any specific cell type; examples of such monoclonal antibodies for use in various diseases are given in the table below.
  3. Receptor constructs (fusion protein
    Fusion protein
    Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...

    s), usually based on a naturally-occurring receptor linked to the immunoglobulin frame. In this case, the receptor provides the construct with detailed specificity, whereas the immunoglobulin-structure imparts stability and other useful features in terms of pharmacology
    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...

    . Some examples are listed in the table below.


Biologics as a class of medications in this narrower sense have had a profound impact on many medical fields, primarily rheumatology
Rheumatology
Rheumatology is a sub-specialty in internal medicine and pediatrics, devoted to diagnosis and therapy of rheumatic diseases. Clinicians who specialize in rheumatology are called rheumatologists...

 and oncology
Oncology
Oncology is a branch of medicine that deals with cancer...

, but also cardiology
Cardiology
Cardiology is a medical specialty dealing with disorders of the heart . The field includes diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology...

, dermatology
Dermatology
Dermatology is the branch of medicine dealing with the skin and its diseases, a unique specialty with both medical and surgical aspects. A dermatologist takes care of diseases, in the widest sense, and some cosmetic problems of the skin, scalp, hair, and nails....

, gastroenterology
Gastroenterology
Gastroenterology is the branch of medicine whereby the digestive system and its disorders are studied. The name is a combination of three Ancient Greek words gaster , enteron , and logos...

, neurology
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...

, and others. In most of these disciplines, biologics have added major therapeutic options for the treatment of many diseases, including some for which no effective therapies were available, and others where previously existing therapies were clearly inadequate. However, the advent of biologic therapeutics has also raised complex regulatory issues (see below), and significant pharmacoeconomic concerns, because the cost for biologic therapies has been dramatically higher than for conventional (pharmacological) medications. This factor has been particularly relevant since many biological medications are used for the treatment of chronic diseases, such as rheumatoid arthritis or inflammatory bowel disease, or for the treatment of otherwise untreatable cancer during the remainder of life. The cost of treatment with a typical monoclonal antibody therapy for relatively common indications is generally in the range of € 7,000-14,000 per patient per year.

Older patients who receive biologic therapy for diseases such as rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis are at increased risk for life-threatening infection, adverse cardiovascular events, and malignancy. However, because other therapies are often ineffective, biologic therapy should be considered for some of these patients.

A few examples of biologics made with 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 include:
USAN
United States Adopted Name
United States Adopted Names are unique nonproprietary names assigned to pharmaceuticals marketed in the United States. Each name is assigned by the USAN Council, which is co-sponsored by the American Medical Association , the United States Pharmacopeial Convention , and the American Pharmacists...

/INN
International Nonproprietary Name
An International Nonproprietary Name is the official nonproprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization...

Trade Name Indication Technology Mechanism of Action
abatacept
Abatacept
Abatacept is a fusion protein composed of an immunoglobulin fused to the extracellular domain of CTLA-4, a molecule capable of binding B7. Abatacept is a selective costimulation modulator as it inhibits the costimulation of T cells...

Orencia rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid 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...

immunoglobin CTLA-4
CTLA-4
CTLA4 also known as CD152 is a protein that plays an important regulatory role in the immune system...

 fusion protein
Fusion protein
Fusion proteins or chimeric proteins are proteins created through the joining of two or more genes which originally coded for separate proteins. Translation of this fusion gene results in a single polypeptide with functional properties derived from each of the original proteins...

T-cell deactivation
adalimumab
Adalimumab
Adalimumab is the third TNF inhibitor, after infliximab and etanercept, to be approved in the United States. Like infliximab and etanercept, adalimumab binds to TNFα, preventing it from activating TNF receptors; adalimumab was constructed from a fully human monoclonal antibody, while infliximab...

Humira rheumatoid arthritis, ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...

, psoriatic arthritis
Psoriatic arthritis
Psoriatic arthritis is a type of inflammatory arthritis that, according to the National Psoriasis Foundation, will develop in up to 30 percent of people who have the chronic skin condition psoriasis...

, psoriasis, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

monoclonal antibody TNF antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

alefacept
Alefacept
Alefacept is a genetically engineered immunosuppressive drug sold under the brand name Amevive in Canada, the United States, Israel, Switzerland and Australia. It is used to control inflammation in moderate to severe psoriasis with plaque formation, where it interferes with lymphocyte activation...

Amevive chronic plaque psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

immunoglobin G1 fusion protein incompletely characterized
erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...

Epogen anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

 arising from cancer chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

, chronic renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...

, etc.
recombinant protein stimulation of red blood cell production
etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...

Enbrel rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis recombinant human TNF-receptor fusion protein TNF antagonist
infliximab
Infliximab
Infliximab is a monoclonal antibody against tumour necrosis factor alpha . It is used to treat autoimmune diseases. Remicade is marketed by Janssen Biotech, Inc...

Remicade rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...

monoclonal antibody TNF antagonist
trastuzumab
Trastuzumab
Trastuzumab is a monoclonal antibody that interferes with the HER2/neu receptor.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell to inside the cell, and turn genes on and off...

Herceptin breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

humanized monoclonal antibody HER2/neu
HER2/neu
HER-2 also known as proto-oncogene Neu, receptor tyrosine-protein kinase erbB-2, CD340 or p185 is an enzyme that in humans is encoded by the ERBB2 gene. Over expression of this gene is correlated with higher aggressiveness in breast cancers...

 (erbB2) antagonist
ustekinumab Stelara psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...

humanized monoclonal antibody
denileukin diftitox
Denileukin diftitox
Denileukin diftitox is an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. This can bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells...

Ontak cutaneous T-cell lymphoma (CTCL) Diphtheria toxin engineered protein combining Interleukin-2 and Diphtheria toxin Interleukin-2 receptor binder

Gene therapy

Viral gene therapy involves artificially manipulating a 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...

 to include a desirable piece of genetic material.

Biosimilars

With the more common small-molecule drugs, an exactly identical generic drug
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...

 can be reliably produced and marketed. Because biologics are vastly more complex, other manufacturers cannot guarantee that their version is exactly identical to the original manufacturer's version, although it is similar to the original biologic. The subsequent manufacturer may use a slightly different manufacturing process, which can occasionally produce significantly different effects. The follow-on manufacturer does not have access to the originator's molecular clone bank and original cell bank. Finally, nearly undetectable differences in impurities and/or breakdown products are known to have serious health implications.

Because different manufacturers may produce slightly different products, they consequently cannot guarantee that their version is exactly as safe and effective as the original manufacturer's version. So, unlike most drugs, generic versions of biologics were not authorized in the United States or the European Union through the simplified procedures allowed for small-molecule generics. As a result, nearly all biologics have been brand-name therapeutics and required very extensive testing. Notable exceptions to this rule include several of the earliest biopharmaceuticals made via recombinant DNA technology, including 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....

 and human growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...

.

Legislation in the 21st century has attempted to address this by recognizing an intermediate ground of testing, which is more testing than for small-molecule drugs proven to be identical to each other, but less testing than for completely new therapeutics.

In the European Union a specially adapted approval procedure has been authorized for certain protein drugs, termed similar biological medicinal products
Biosimilar
Biosimilars or follow-on biologics are terms used to describe officially-approved subsequent versions of innovator biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the innovator product. Biosimilars are also referred to as subsequent entry biologics ...

. This procedure is based on a thorough demonstration of "comparability" of the "similar" product to an existing approved product.

Within the U.S., the Patient Protection and Affordable Care Act
Patient Protection and Affordable Care Act
The Patient Protection and Affordable Care Act is a United States federal statute signed into law by President Barack Obama on March 23, 2010. The law is the principal health care reform legislation of the 111th United States Congress...

 of 2010 created an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA licensed reference biological product.

The acceptance of biosimilars may reduce the profitability of biologics and the cost to the patients and healthcare systems.

European Union

In the European Union, a biological medicinal product is one the active substance(s) produced from or extracted from a biological (living) system, and requires, in addition to physico-chemical testing, biological testing for full characterisation. The characterisation of a biological medicinal product is a combination of testing the active substance and the final medicinal product together with the production process and its control.

For example,
  • With regard to the production process, a biological medicinal product can be derived from biotechnology or derived from other new technologies. It may be prepared using more conventional techniques, as well, as is the case for blood or plasma-derived products and a number of vaccines.
  • With regard to the nature of its active substance, a biological medicinal product can consist of entire microorganisms or mammalian cells or of nucleic acids or proteinaceous or polysaccharide component(s) originating from a microbial, animal, human or plant source.
  • With regard to its mode of action, a biological medicinal product can be a therapeutic medicinal product, an immunological medicinal product, gene transfer materials, or cell therapy materials.

United States

Within the United States, biologics are regulated by the FDA's Center for Biologics Evaluation and Research
Center for Biologics Evaluation and Research
The Center for Biologics Evaluation and Research is one of six main centers for the U.S. Food and Drug Administration , which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Dr. Karen Midthun, M.D...

 (CBER). Drugs, by contrast, are regulated by the Center for Drug Evaluation and Research
Center for Drug Evaluation and Research
The Center for Drug Evaluation and Research is a division of the U.S. Food and Drug Administration that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also legally considered drugs, but they are covered by the Center for Biologics Evaluation and...

 (CDER).

See also

  • Biopharmaceutical
    Biopharmaceutical
    Biopharmaceuticals are medical drugs produced using biotechnology. They include proteins , nucleic acids 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...

    s
  • Biosimilar
    Biosimilar
    Biosimilars or follow-on biologics are terms used to describe officially-approved subsequent versions of innovator biopharmaceutical products made by a different sponsor following patent and exclusivity expiry on the innovator product. Biosimilars are also referred to as subsequent entry biologics ...

    s
  • antibody-drug conjugate
    Antibody-drug conjugate
    Antibody-drug conjugates are a new type of targeted therapy, used for example for cancer. They consist of an antibody linked to a payload drug . Hence, they are a type of immunoconjugate and often an immunotoxin.The antibody causes the ADC to bind to the target cancer cells...

  • Center for Biologics Evaluation and Research
    Center for Biologics Evaluation and Research
    The Center for Biologics Evaluation and Research is one of six main centers for the U.S. Food and Drug Administration , which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Dr. Karen Midthun, M.D...

    (CBER)
The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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