Biologics include a wide range of medicinal products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. A vaccine is a biological preparation which is used to establish or improve immunity to a particular disease Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products Somatic cells are any cells forming the body of an organism as opposed to Germline cells Gene therapy is the insertion of Genes into an individual's cells and tissues to treat a Disease, and Hereditary diseases in which a Tissue is a cellular organizational level intermediate between cells and a complete organism Recombinant DNA is a form of synthetic DNA that is engineered through the combination or insertion of one or more DNA strands thereby combining DNA sequences 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. ^[1]

Contents 1 Biologics 2 Biosimilars 3 Examples 4 See also 5 References 6 External links

Biologics

As indicated above, 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 medications (either approved or in development) that are produced by means of biological processes involving recombinant DNA 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". Erythropoietin (ɨˌɹɪθɹoʊˈpɔɪɨtɨn /ɨˌɹɪθɹoʊˈpɔɪtən/ or /ɨˌɹiːθɹoʊ-/ or EPO is a Glycoprotein Hormone that controls Growth hormone ( GH) is a Peptide hormone that stimulates growth and cell reproduction in humans and other animals
• 2) Monoclonal antibodies. Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune 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 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. Hybridoma are cells that have been engineered to produce a desired Antibody in large amounts
• 3) Receptor constructs (fusion proteins), usually based on a naturally-occurring receptor linked to the immunoglobulin frame. Fusion proteins, also known as chimeric proteins, are proteins created through the joining of two or more Genes which originally coded for separate proteins Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily 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. 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 and oncology, but also cardiology, dermatology, gastroenterology, neurology, 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.

Biosimilars

See also biosimilars

Unlike the more common "small-molecule" drugs, biologics generally exhibit high molecular complexity, and may be quite sensitive to manufacturing process changes. Biosimilars or Follow-on Biologics are terms used to describe officially approved new versions of innovator Biopharmaceutical products following patent In Pharmacology, a small molecule is a small Organic compound that is biologically active ( Biomolecule) but is not a Polymer. The follow-on manufacturer does not have access to the originator's molecular clone and original cell bank, nor to the exact fermention and purification process. Finally, nearly undetectable differences in impurities and/or breakdown products are known to have serious health implications. This has created a concern that generic versions of biologics might perform differently than the original branded version of the drug. A generic drug (generic drugs short generics is a drug which is produced and distributed without Patent protection ^[2] So, unlike most drugs, generic versions of biologics are not authorized in the US or the European Union through the simplified procedures allowed for small molecule generics. Notable exceptions include several of the earliest biopharmaceuticals made via recombinant DNA technology, including biosynthetic 'human' insulin and human growth hormone, which are grandfathered under the U. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance Growth hormone ( GH) is a Peptide hormone that stimulates growth and cell reproduction in humans and other animals S. Federal Food, Drug & Cosmetic Act which addresses mainly small-molecule chemical drugs. By comparison, vaccines and most other biotech drugs are governed under the Public Health Services Act, which would need to be amended by U. S. Congress and signed into law by the President to allow for generics.

In the EU a specially-adapted approval procedure has been authorized for certain protein drugs, termed "similar biological medicinal products". Biosimilars or Follow-on Biologics are terms used to describe officially approved new versions of innovator Biopharmaceutical products following patent This procedure is based on a thorough demonstration of "comparability" of the "similar" product to an existing approved product. ^[3] In the US the FDA has taken the position that new legislation will be required to address these concerns. ^[4] Additional Congressional hearings have been held,^[5] but no legislation had been approved as of December 2007. Due to a lack of FDA manufacturing guidelines for generic versions of insulin and human growth hormone, generics manufacturers are caught in a bind.

The FDA announced in 2001 that it was working on guidelines for pharmaceutical companies to produce generic versions of insulin and human growth hormone. The Agency had long had suggested the guidelines were forthcoming, but in April 2006, the FDA suddenly announced it would not be releasing the long-delayed guidelines for the production of generic versions of insulin and human growth hormone as anticipated[1]. In a March 17, 2006 letter obtained by the Associated Press, which was written in response to a Feb. 10, 2006 letter from Sen. Orrin Hatch (R-UT), and Rep. Henry Waxman (D-CA), the FDA associate commissioner for legislation Patrick Ronan said that the FDA instead intended to publish broader guidelines that applied to ALL generic versions of protein-based drugs, also known as follow-on protein products, therefore the FDA would not be outlining specific guidelines for insulin or human growth hormone.

In response, Rep. Waxman said in a statement that the Agency's action was "a misguided step that will only result in further delay" of rules for low-cost generics. The regulatory hiatus regarding generic versions has effectively extended the patents for the past few years at the expense of consumers and their healthcare providers.

In August 2006, four state governors, looking to ease drug costs under state programs, petitioned the FDA to provide guidelines for generic versions of insulin and human growth hormone. In their petition, the governors joined other critics in accusing the Agency of dragging its feet[2].

"The FDA's delay in informing manufacturers of the requirements for obtaining approval of therapeutically equivalent versions of insulin and human growth hormone has cost the states and other health-care providers hundreds of millions of dollars," the petition said. Democratic Governors Kathleen Sebelius of Kansas and Jim Doyle of Wisconsin joined Republicans Tim Pawlenty of Minnesota and James Douglas of Vermont in signing the petition. Since then, the governors of New Mexico, Virginia and West Virginia have also signed the petition.

"We have been informed that there are no scientific reasons for delaying the issuance of the guidance documents FDA already has drafted," the bipartisan group of governors wrote the FDA. "There is no legal or regulatory obstacle to the immediate issuance of these guidance documents," they added.

The governors said that insulin and human growth hormone are a breed apart from other biotech medicines and should therefore be considered distinct from other biotech drugs. Insulin and human growth hormone both have relatively simple structures and a long history of safe use, they said.

Examples

A few examples of biologics made with recombinant DNA technology include:

USAN/INN	Trade Name	Indication	Technology	Mechanism of Action
abatacept	Orencia	rheumatoid arthritis	immunoglobin CTLA-4 fusion protein	T-cell deactivation
adalimumab	Humira	rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis	monoclonal antibody	TNF antagonist
alefacept	Amevive	chronic plaque psoriasis	immunoglobin G1 fusion protein	incompletely characterized
erythropoietin	Epogen	anemia arising from cancer chemotherapy, chronic renal failure, etc. Recombinant DNA is a form of synthetic DNA that is engineered through the combination or insertion of one or more DNA strands thereby combining DNA sequences __FORCETOC__The Union of South American Nations (Unión de Naciones Suramericanas - UNASUR, União de Nações Sul-Americanas - UNASUL, Unie van Zuid-Amerikaanse Naties An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed Abatacept (marketed as Orencia) is a Fusion protein composed of an Immunoglobulin fused to the extracellular domain of CTLA-4, a molecule capable Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily CTLA4 ( C ytotoxic T - L ymphocyte A ntigen 4) is a CD28-family receptor expressed on mainly CD4+ T cells. Fusion proteins, also known as chimeric proteins, are proteins created through the joining of two or more Genes which originally coded for separate proteins T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Adalimumab (brand name HUMIRA) is the third TNF inhibitor, after Infliximab and Etanercept, to be approved in the United States. Ankylosing spondylitis ( AS; previously known as Bechterew's disease, Bechterew syndrome, Marie Strümpell disease and a form of Spondyloarthritis Psoriatic arthritis (also arthritis psoriatica, arthropathic psoriasis or psoriatic arthropathy) is a type of Inflammatory Arthritis Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell Tumor necrosis factor ( TNF, cachexin or cachectin and formally known as Tumor necrosis factor-alpha) is a Cytokine involved in systemic 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 Alefacept is a genetically engineered Immunosuppressive drug sold under the brand name Amevive in Canada, the United States, and Psoriasis (səˈraɪəsɪs ( suh-RI-uh-sus) is a non-contagious disorder which affects the Skin and Joints It commonly causes red scaly Erythropoietin (ɨˌɹɪθɹoʊˈpɔɪɨtɨn /ɨˌɹɪθɹoʊˈpɔɪtən/ or /ɨˌɹiːθɹoʊ-/ or EPO is a Glycoprotein Hormone that controls Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Chemotherapy, in its most general sense refers to treatment of disease by chemicals that kill cells specifically those of micro-organisms or Cancer. Chronic kidney disease (CKD also known as chronic renal disease, is a progressive loss of renal function over a period of months or years	recombinant protein	stimulation of red blood cell production
etanercept	Embrel	rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis	recombinant human TNF-receptor fusion protein	TNF antagonist
infliximab	Remicade	rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn's disease	monoclonal antibody	TNF antagonist
trastuzumab	Herceptin	breast cancer	humanized monoclonal antibody	HER2/neu (erbB2) antagonist

See also

• Biopharmaceuticals
• Biosimilars

References

External links

• MeSH Biological+Products
• Yali Friedman (2007). Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books Why are biogenerics so hard to regulate?. BiotechBlog. com. Retrieved on 2007-12-17. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 546 - Gothic War (535–554: The Ostrogoths of King Totila
• Debbie Strickland (2007). Guide to Biotechnology. Biotechnology Industry Organization (BIO). Retrieved on 2007-12-17. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 546 - Gothic War (535–554: The Ostrogoths of King Totila
• Timothy B. Coan and Ron Ellis (2001-06-01). Year 2001 ( MMI) was a Common year starting on Monday according to the Gregorian calendar. Events 193 - Roman Emperor Didius Julianus is Assassinated 987 - Hugh Capet is elected Report for USA Specialty Pharmaceuticals: Generic Biologics: The Next Frontier. Consumer Project on Technology. Retrieved on 2007-12-17. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 546 - Gothic War (535–554: The Ostrogoths of King Totila
• About biologics. National Psoriasis Foundation (2006-11-01). Year 2006 ( MMVI) was a Common year starting on Sunday of the Gregorian calendar. Events 996 - Emperor Otto III issues a deed to Gottschalk Bishop of Freising which is the oldest known document using the name Ostarrîchi Retrieved on 2007-12-17. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 546 - Gothic War (535–554: The Ostrogoths of King Totila

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