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75-531: Terminology surrounding biopharmaceuticals varies between groups and entities, with different terms referring to different subsets of therapeutics within the general biopharmaceutical category. Some regulatory agencies use the terms biological medicinal products or therapeutic biological product to refer specifically to engineered macromolecular products like protein- and nucleic acid -based drugs , distinguishing them from products like blood, blood components, or vaccines, which are usually extracted directly from

150-442: A medication , insulin is any pharmaceutical preparation of the protein hormone insulin that is used to treat high blood glucose . Such conditions include type 1 diabetes , type 2 diabetes , gestational diabetes , and complications of diabetes such as diabetic ketoacidosis and hyperosmolar hyperglycemic states . Insulin is also used along with glucose to treat hyperkalemia (high blood potassium levels). Typically it

225-506: A virus to include a desirable piece of genetic material. Viral gene therapies using engineered plant viruses have been proposed to enhance crop performance and promote sustainable production. With the expiration of many patents for blockbuster biologics between 2012 and 2019, the interest in biosimilar production, i.e., follow-on biologics, has increased. Compared to small molecules that consist of chemically identical active ingredients , biologics are vastly more complex and consist of

300-530: A 'peak' followed by a more or less rapid decline in insulin action (as with insulin detemir and insulin glargine ), all while retaining insulin's glucose-lowering action in the human body. However, a number of meta-analyses , including those done by the Cochrane Collaboration in 2005, Germany's Institute for Quality and Cost Effectiveness in the Health Care Sector [IQWiG] released in 2007, and

375-418: A bedtime dose to balance the tendency of glucose to rise with the dawn , along with a smaller morning dose to balance the lower afternoon basal need and possibly an afternoon dose to cover evening need. A disadvantage of bedtime NPH is that if not taken late enough (near midnight) to place its peak shortly before dawn, it has the potential of causing hypoglycemia. One theoretical advantage of glargine and detemir

450-651: A biological source. Biopharmaceutics is pharmaceutics that works with biopharmaceuticals. Biopharmacology is the branch of pharmacology that studies biopharmaceuticals. Specialty drugs , a recent classification of pharmaceuticals, are high-cost drugs that are often biologics. The European Medicines Agency uses the term advanced therapy medicinal products (ATMPs) for medicines for human use that are "based on genes, cells, or tissue engineering", including gene therapy medicines, somatic-cell therapy medicines, tissue-engineered medicines, and combinations thereof. Within EMA contexts,

525-492: A coma through hypoglycemia , convulsions, memory lapse and loss of concentration. However, the International Diabetes Federation's position statement from 2005 is very clear in stating that "there is NO overwhelming evidence to prefer one species of insulin over another" and "[modern, highly purified] animal insulins remain a perfectly acceptable alternative." Since January 2006, all insulins distributed in

600-516: A combination of either fast-acting or short-acting insulin with a longer-acting insulin, typically an NPH insulin . The combination products begin to work with the shorter-acting insulin (5–15 minutes for fast-acting, and 30 minutes for short-acting), and remain active for 16–24 hours. There are several variations with different proportions of the mixed insulins (e.g. Novolog Mix 70/30 contains 70% aspart protamine [akin to NPH], and 30% aspart.) Unlike many medicines, insulin cannot be taken orally at

675-612: A diabetic must be based on experience and training (i.e., at the direction of a physician, PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the person. But it is not straightforward and should never be done by habit or routine. With some care however, it can be done reasonably well in clinical practice. For example, some people with diabetes require more insulin after drinking skim milk than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form. Their particular reaction to skimmed milk

750-578: A frequent pregnancy complication . With a prevalence of 6-20% among pregnant women globally, gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance developing or initially recognized during pregnancy. Neutral protamine Hagedorn (NPH) insulin has been the cornerstone of insulin therapy during pregnancy, administered two to four times per day. Women with GDM and pregnant women with type I diabetes mellitus who frequently check their blood glucose levels and utilize glucose monitoring equipment for doing so, use continuous insulin infusion of

825-652: A genetically engineered insulin independently using a yeast process. According to a survey that the International Diabetes Federation conducted in 2002 on the access to and availability of insulin in its member countries, approximately 70% of the insulin that is currently sold in the world is recombinant, biosynthetic 'human' insulin. A majority of insulin used clinically today is produced this way, although clinical experience has provided conflicting evidence on whether these insulins are any less likely to produce an allergic reaction. Adverse reactions have been reported; these include loss of warning signs that patients may slip into

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900-470: A multitude of subspecies. Due to their heterogeneity and the high process sensitivity, originators and follow-on biosimilars will exhibit variability in specific variants over time. The safety and clinical performance of both originator and biosimilar biopharmaceuticals must remain equivalent throughout their lifecycle. Process variations are monitored by modern analytical tools (e.g., liquid chromatography , immunoassays , mass spectrometry , etc.) and describe

975-417: A preparation that does not contain the specific agent they are reacting to or undergo desensitization . Cutaneous adverse effects Other side effects may include pain or skin changes at the sites of injection. Repeated subcutaneous injection without site rotation can lead to lipohypertrophy and amyloidomas, which manifest as firm palpable nodules under the skin. Early initiation of insulin therapy for

1050-477: A pump. Insulin regiments that consist of doses calculated in this manner are considered intensive insulin regimens . Prandial insulin is usually administered no more than 15–30 minutes prior to a meal using a rapid-acting insulin or a regular insulin. In some patients, a combination insulin may be used that contains both NPH (long acting) insulin and a rapid/regular insulin to provide both a basal insulin and prandial insulin. There are several challenges involved in

1125-429: A rapid-acting insulin analogue, such as lispro and aspart. However, a number of considerations go into choosing a regimen for administering insulin to patients. When managing GDM in pregnant women, these guidelines are crucial and can vary depending on certain physiological and interestingly the sociocultural environment as well. The current perinatal guidelines recommend a low daily dose of insulin and take into account

1200-705: A safe target range. In 1916, Nicolae C. Paulescu (1869–1931) succeeded in developing an aqueous pancreatic extract that normalized a diabetic dog. In 1921, he published 4 papers in the Society of Biology in Paris centering on the successful effects of the pancreatic extract in diabetic dogs. Research on the Role of the Pancreas in Food Assimilation by Paulescu was published in August 1921 in

1275-1121: A supply shortage for these products. Institutions housing these biologics, designated as 'banks', often cannot distribute their product to customers effectively. Conversely, banks for reproductive cells are much more widespread and available due to the ease with which spermatozoa and egg cells can be used for fertility treatment. Biopharmaceuticals may be produced from microbial cells (e.g., recombinant E. coli or yeast cultures), mammalian cell lines (see Cell culture ) and plant cell cultures (see Plant tissue culture ) and moss plants in bioreactors of various configurations, including photo-bioreactors . Important issues of concern are cost of production (low-volume, high-purity products are desirable) and microbial contamination (by bacteria , viruses , mycoplasma ). Alternative platforms of production which are being tested include whole plants ( plant-made pharmaceuticals ). A potentially controversial method of producing biopharmaceuticals involves transgenic organisms, particularly plants and animals that have been genetically modified to produce drugs. This production

1350-490: A temporarily implanted catheter or cannula . Some who cannot achieve adequate glucose control by conventional (or jet) injection are able to do so with the appropriate pump. Indwelling catheters pose the risk of infection and ulceration, and some peoples may also develop lipodystrophy due to the infusion sets. These risks can often be minimized by keeping infusion sites clean. Insulin pumps require care and effort to use correctly. One international unit of insulin (1 IU)

1425-402: A unique design space for each biologic. Biosimilars require a different regulatory framework compared to small-molecule generics. Legislation in the 21st century has addressed this by recognizing an intermediate ground of testing for biosimilars. The filing pathway requires more testing than for small-molecule generics, but less testing than for registering completely new therapeutics. In 2003,

1500-785: A wide range of biological products in medicine. However, in most cases, the term is used more restrictively for a class of therapeutics (either approved or in development) that are produced using biological processes involving recombinant DNA technology. These medications are usually one of three types: 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 treating many diseases, including some for which no effective therapies were available, and others where previously existing therapies were inadequate. However,

1575-453: Is a significant risk for its investor due to production failure or scrutiny from regulatory bodies based on perceived risks and 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, blood, or urine. Once an animal

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1650-440: Is active for 16 to 24 hours. Includes the analogues glargine U100 and detemir , each of which begins working within 1 to 2 hours and continues to be active, without major peaks or dips, for about 24 hours, although this varies in many individuals. Includes the analogues insulin glargine U300 and degludec , which begin working within 30 to 90 minutes and continues to be active for greater than 24 hours. Includes

1725-491: Is defined as the "biological equivalent" of 34.7 μg pure crystalline insulin. The first definition of a unit of insulin was the amount required to induce hypoglycemia in a rabbit. This was set by James Collip at the University of Toronto in 1922. Of course, this was dependent on the size and diet of the rabbits. The unit of insulin was set by the insulin committee at the University of Toronto. The unit evolved eventually to

1800-497: Is designed to mimic the natural physiological cycle of insulin secretion, while taking into account the various properties of the formulations used such as half-life, onset of action, and duration of action. In many people, both a rapid- or short-acting insulin product as well as an intermediate- or long-acting product are used to decrease the amount of injections per day. In some, insulin injections may be combined with other injection therapy such as GLP-1 receptor agonists . Cleansing of

1875-533: Is different from other people with diabetes, but the same amount of whole milk is likely to cause a still different reaction even in that person. Whole milk contains considerable fat while skimmed milk has much less. It is a continual balancing act for all people with diabetes, especially for those taking insulin. People with insulin-dependent diabetes typically require some base level of insulin (basal insulin), as well as short-acting insulin to cover meals (bolus also known as mealtime or prandial insulin). Maintaining

1950-704: Is effective in humans as it is highly similar to human insulin (three amino acid difference in bovine insulin, one amino acid difference in porcine). Initially, lower preparation purity resulted in allergic reactions to the presence of non-insulin substances. Purity has improved steadily since the 1920s ultimately reaching purity of 99% by the mid-1970s thanks to high-pressure liquid chromatography (HPLC) methods. Minor allergic reactions still occur occasionally, even to synthetic "human" insulin varieties. Beginning in 1982, biosynthetic "human" insulin has been manufactured for clinical use through genetic engineering techniques using recombinant DNA technology. Genentech developed

2025-459: Is generally achieved via the use of an intermediate-acting insulin (such as NPH) or a long-acting insulin analog. In type 1 diabetics, it may also be achieved via continuous infusion of rapid-acting insulin using an insulin pump . Approximately half of a person's daily insulin requirement is administered as a basal insulin, usually administered once per day at night. When a person eats food containing carbohydrates and glucose, insulin helps regulate

2100-440: Is given by injection under the skin , but some forms may also be used by injection into a vein or muscle . There are various types of insulin, suitable for various time spans. The types are often all called insulin in the broad sense , although in a more precise sense, insulin is identical to the naturally occurring molecule whereas insulin analogues have slightly different molecules that allow for modified time of action. It

2175-538: Is not part of the International System of Units (abbreviated SI) which is the modern form of the metric system . Instead the pharmacological international unit (IU) is defined by the WHO Expert Committee on Biological Standardization . The central problem for those requiring external insulin is picking the right dose of insulin and the right timing. Physiological regulation of blood glucose, as in

2250-741: Is on the World Health Organization's List of Essential Medicines . In 2022, it was the 192nd most commonly prescribed medication in the United States, with more than 2   million prescriptions. Insulin can be made from the pancreas of pigs or cows. Human versions can be made either by modifying pig versions, or recombinant technology using mainly E. coli or Saccharomyces cerevisiae . It comes in three main types: short–acting (such as regular insulin ), intermediate-acting (such as neutral protamine Hagedorn (NPH) insulin), and longer-acting (such as insulin glargine ). Insulin

2325-612: Is present in both mammals and invertebrates . The insulin/ insulin-like growth factor signalling pathway (IIS) has been extensively studied in species including nematode worms (e.g. C. elegans ), flies ( Drosophila melanogaster ) and mice ( Mus musculus ). Its mechanisms of action are highly similar across species. Both type 1 diabetes and type 2 diabetes are marked by a loss of pancreatic function, though to differing degrees. People who are affected with diabetes are referred to as diabetics. Many diabetics require an exogenous source of insulin to keep their blood sugar levels within

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2400-591: 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

2475-417: Is that they only need to be administered once a day, although in practice many people find that neither lasts a full 24 hours. They can be administered at any time during the day as well, provided that they are given at the same time every day. Another advantage of long-acting insulins is that the basal component of an insulin regimen (providing a minimum level of insulin throughout the day) can be decoupled from

2550-449: Is used to approximate the basal secretion of insulin by the pancreas, which varies in the course of the day. NPH/isophane, lente, ultralente, glargine, and detemir may be used for this purpose. The advantage of NPH is its low cost, the fact that you can mix it with short-acting forms of insulin, thereby minimizing the number of injections that must be administered, and that the activity of NPH will peak 4–6 hours after administration, allowing

2625-588: Is used to treat a number of diseases including diabetes and its acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic states . It is also used along with glucose to treat high blood potassium levels . Use during pregnancy is relatively safe for the baby. Insulin was formerly used in a psychiatric treatment called insulin shock therapy . Some side effects are hypoglycemia (low blood sugar), hypokalemia (low blood potassium), and allergic reactions . Allergy to insulin affected about 2% of people, of which most reactions are not due to

2700-515: Is why managing the side effects associated with long-term early routine use of insulin for type 2 diabetes mellitus can prove to be a therapeutic and behavioral challenge.     A-Chain Position ;  B-Chain Position Insulin is an endogenous hormone , which is produced by the pancreas . The insulin protein has been highly conserved across evolutionary time, and

2775-439: Is widely taught, although it has been heavily criticized. Sliding scale insulin (SSI) is not an effective way of managing long-term diabetes in individuals residing in nursing homes. Sliding scale insulin leads to greater discomfort and increased nursing time. Sample regimen using insulin glargine and insulin lispro: During pregnancy, spontaneous hyperglycemia can develop and lead to gestational diabetes mellitus (GDM) ,

2850-578: The European Medicines Agency introduced an adapted pathway for biosimilars, termed similar biological medicinal products . This pathway is based on a thorough demonstration of comparability of the product to an existing approved product. Within the United States, the Patient Protection and Affordable Care Act of 2010 created an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed reference biological product. Researchers are optimistic that

2925-558: The Archives Internationales de Physiologie, Liège, Belgium. Initially, the only way to obtain insulin for clinical use was to extract it from the pancreas of another creature. Animal glands were obtainable as a waste product of the meatpacking industry. Insulin was derived primarily from cows ( Eli Lilly and Company ) and pigs ( Nordisk Insulinlaboratorium ). The making of eight ounces of purified insulin could require as much as two tons of pig parts. Insulin from these sources

3000-634: The Biologics and Genetic Therapies Directorate within Health Canada . Regulatory agency Too Many Requests If you report this error to the Wikimedia System Administrators, please include the details below. Request from 172.68.168.151 via cp1112 cp1112, Varnish XID 368929659 Upstream caches: cp1112 int Error: 429, Too Many Requests at Fri, 29 Nov 2024 05:43:16 GMT Humulin As

3075-566: The Canadian Agency for Drugs and Technology in Health (CADTH) also released in 2007 have shown no unequivocal advantages in clinical use of insulin analogues over more conventional insulin types. The commonly used types of insulin are as follows. Includes the insulin analogues aspart , lispro , and glulisine . These begin to work within 5 to 15 minutes and are active for 3 to 4 hours. Most insulins form hexamers , which delay entry into

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3150-456: The US and some other countries are synthetic "human" insulins or their analogues. A special FDA importation process is required to obtain bovine or porcine derived insulin for use in the US, although there may be some remaining stocks of porcine insulin made by Lilly in 2005 or earlier, and porcine lente insulin is also sold and marketed under the brand name Vetsulin(SM) in the US for veterinary usage in

3225-436: 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 to treat chronic diseases , such as rheumatoid arthritis or inflammatory bowel disease, or for

3300-410: The basal rate and the bolus rate is a continuous balancing act that people with insulin-dependent diabetes must manage each day. This is normally achieved through regular blood tests, although continuous blood sugar testing equipment ( Continuous Glucose Monitors or CGMs) are now becoming available which could help to refine this balancing act once widespread usage becomes common. A long-acting insulin

3375-514: The biopharmaceutical industry, generating 37 percent of the total number of granted patents worldwide; however, there is still a large margin for growth and innovation within the industry. Revisions to the current IP system to ensure greater reliability for R&D (research and development) investments is a prominent topic of debate in the US as well. Blood products and other human-derived biologics such as breast milk have highly regulated or very hard-to-access markets; therefore, customers generally face

3450-430: The blood in active form; these analog insulins do not but have normal insulin activity. Newer varieties are now pending regulatory approval in the US which are designed to work rapidly, but retain the same genetic structure as regular human insulin . Includes regular insulin , which begins working within 30 minutes and is active about 5 to 8 hours. Includes NPH insulin , which begins working in 1 to 3 hours and

3525-451: The body's metabolism of the food. Prandial insulin, also called mealtime or bolus insulin, is designed as a bolus dose of insulin prior to a meal to regulate the spike in blood glucose that occurs following a meal. The dose of prandial insulin may be static, or may be calculated by the patient using either their current blood sugar, planned carbohydrate intake, or both. This calculation may also be performed by an insulin pump in patients using

3600-471: The drug is released, it will still be monitored for performance and safety risks. The manufacture process must satisfy the FDA's "Good Manufacturing Practices", which are typically manufactured in a cleanroom environment with strict limits on the amount of airborne particles and other microbial contaminants that may alter the efficacy of the drug. In Canada , biologics (and radiopharmaceuticals) are reviewed through

3675-436: The endogenous insulin surge produced in anticipation of eating. Regular insulin, lispro, aspart and glulisine can be used for this purpose. Regular insulin should be given with about a 30-minute lead-time prior to the meal to be maximally effective and to minimize the possibility of hypoglycemia. Lispro, aspart and glulisine are approved for dosage with the first bite of the meal, and may even be effective if given after completing

3750-562: The human insulin molecule are called insulin analogues , (technically "insulin receptor ligands ") so named because they are not technically insulin, rather they are analogues which retain the hormone's glucose management functionality. They have absorption and activity characteristics not currently possible with subcutaneously injected insulin proper. They are either absorbed rapidly in an attempt to mimic real beta cell insulin (as with insulin lispro , insulin aspart , and insulin glulisine ), or steadily absorbed after injection instead of having

3825-632: The injection site and injection technique are required to ensure effective insulin therapy. Insulin pumps are a reasonable solution for some. Advantages to the person are better control over background or basal insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that may help with determining bolus infusion dosages. The limitations are cost, the potential for hypoglycemic and hyperglycemic episodes, catheter problems, and no "closed loop" means of controlling insulin delivery based on current blood glucose levels. Insulin pumps may be like 'electrical injectors' attached to

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3900-416: The inserted human DNA, they produce a synthetic version of human insulin. Manufacturers claim this reduces the presence of many impurities. However, the clinical preparations prepared from such insulins differ from endogenous human insulin in several important respects; an example is the absence of C-peptide which has in recent years been shown to have systemic effects itself. Novo Nordisk has also developed

3975-463: The insulin itself but to preservatives added to insulin such as zinc, protamine , and meta-cresol . Most reactions are Type I hypersensitivity reactions and rarely cause anaphylaxis . A suspected allergy to insulin can be confirmed by skin prick testing , patch testing and occasionally skin biopsy . First line therapy against insulin hypersensitivity reactions include symptomatic therapy with antihistamines. The affected persons are then switched to

4050-501: The introduction of biosimilars will reduce medical expenses to patients and the healthcare system. When a new biopharmaceutical is developed, the company will typically apply for a patent , which is a grant to exclusive manufacturing rights. This is the primary means by which the drug developer can recover the investment cost for development of the biopharmaceutical. The patent laws in the United States and Europe differ somewhat on

4125-786: The long-term management of conditions such as type 2 diabetes would suggest that the use of insulin has unique benefits, however, with insulin therapy, there is a need to gradually raise the dose and the complexity of the regimen, as well as the likelihood of developing severe hypoglycemia which is why many people and their doctors are hesitant to begin insulin therapy in the early stage of disease management. Many obstacles associated with health behaviors also prevent people with type 2 diabetes mellitus from starting or intensifying their insulin treatment, including lack of motivation, lack of familiarity with or experience with treatments, and time restraints causing people to have high glycemic loads for extended periods of time prior to starting insulin therapy. This

4200-403: The meal. The short-acting insulin is also used to correct hyperglycemia. First described in 1934, what physicians typically refer to as sliding-scale insulin (SSI) is fast- or rapid-acting insulin only, given subcutaneously, typically at meal times and sometimes bedtime, but only when blood glucose is above a threshold (e.g. 10 mmol/L, 180 mg/dL). The so-called "sliding-scale" method

4275-538: The next. Therefore, it is realistic to expect higher needs for glucose control with subsequent pregnancies in multiparous women. The possibility of using insulin in an attempt to improve athletic performance was suggested as early as the 1998 Winter Olympics in Nagano, Japan , as reported by Peter Sönksen in the July 2001 issue of Journal of Endocrinology . The question of whether non-diabetic athletes could legally use insulin

4350-428: The non-diabetic, would be best. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. The increased insulin level causes glucose absorption and storage in cells, reduces glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. The result is that the blood glucose level rises somewhat after eating, and within an hour or so, returns to

4425-531: The normal 'fasting' level. Even the best diabetic treatment with synthetic human insulin or even insulin analogs, however administered, falls far short of normal glucose control in the non-diabetic. Complicating matters is that the composition of the food eaten (see glycemic index ) affects intestinal absorption rates. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. In addition, fats and proteins cause delays in absorption of glucose from carbohydrates eaten at

4500-482: The old USP insulin unit, where one unit (U) of insulin was set equal to the amount of insulin required to reduce the concentration of blood glucose in a fasting rabbit to 45 m g / d L (2.5 m mol / L ). Once the chemical structure and mass of insulin was known, the unit of insulin was defined by the mass of pure crystalline insulin required to obtain the USP unit. The unit of measurement used in insulin therapy

4575-414: The prandial or bolus component (providing mealtime coverage via ultra-short-acting insulins), while regimens using NPH and regular insulin have the disadvantage that any dose adjustment affects both basal and prandial coverage. Glargine and detemir are significantly more expensive than NPH, lente and ultralente, and they cannot be mixed with other forms of insulin. A short-acting insulin is used to simulate

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4650-694: The present time. Like nearly all other proteins introduced into the gastrointestinal tract , it is reduced to fragments (single amino acid components), whereupon all activity is lost. There has been some research into ways to protect insulin from the digestive tract, so that it can be administered in a pill. So far this is entirely experimental. Insulin is usually taken as subcutaneous injections by single-use syringes with needles , an insulin pump , or by repeated-use insulin pens with needles. People who wish to reduce repeated skin puncture of insulin injections often use an injection port in conjunction with syringes. The use of subcutaneous injections of insulin

4725-483: The production process and its control. For example: In the United States , biologics are licensed through the biologics license application (BLA), then submitted to and regulated by the FDA's Center for Biologics Evaluation and Research (CBER) whereas drugs are regulated by the Center for Drug Evaluation and Research . Approval may require several years of clinical trials , including trials with human volunteers. Even after

4800-457: The requirements for a patent, with the European requirements 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. In 2012 the US had the highest IP (Intellectual Property) generation within

4875-453: The result of hypoglycemia, especially in patients with type 1 diabetes, because they are frequently more insulin sensitive than persons with type 2 diabetes and more likely to be unaware of their hypoglycemic state. Close glucose monitoring is essential because after 16 weeks of pregnancy, women with preexisting diabetes become more insulin resistant and their insulin demands may fluctuate weekly. The need for insulin may rise from one pregnancy to

4950-595: The same time. As well, exercise reduces the need for insulin even when all other factors remain the same, since working muscle has some ability to take up glucose without the help of insulin. Because of the complex and interacting factors, it is, in principle, impossible to know for certain how much insulin (and which type) is needed to 'cover' a particular meal to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetics' beta cells routinely and automatically manage this by continual glucose level monitoring and insulin release. All such decisions by

5025-401: The technique used to produce the first such insulin, Humulin, but did not commercially market the product themselves. Eli Lilly marketed Humulin in 1982. Humulin was the first medication produced using modern genetic engineering techniques in which actual human DNA is inserted into a host cell ( E. coli in this case). The host cells are then allowed to grow and reproduce normally, and due to

5100-473: The term advanced therapies refers specifically to ATMPs, although that term is rather nonspecific outside those contexts. Gene-based and cellular biologics, for example, often are at the forefront of biomedicine and biomedical research , and may be used to treat a variety of medical conditions for which no other treatments are available. Building on the market approvals and sales of recombinant virus-based biopharmaceuticals for veterinary and human medicine,

5175-538: The treatment of companion animals with diabetes. In type 1 diabetes, insulin production is extremely low, and as such the body requires exogenous insulin. Some people with type 2 diabetes, particularly those with very high hemoglobin A1c values, may also require a baseline rate of insulin, as their body is desensitized to the level of insulin being produced. Basal insulin regulates the body's blood glucose between mealtimes, as well as overnight. This basal rate of insulin action

5250-540: 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 . The first such substance approved for therapeutic use

5325-543: The use of engineered plant viruses has been proposed to enhance crop performance and promote sustainable production. In some jurisdictions, biologics are regulated via different pathways from other small molecule drugs and medical devices . Some of the oldest forms of biologics are extracted from the bodies of animals, and other humans especially. Important biologics include: Some biologics that were previously extracted from animals, such as insulin, are now more commonly produced by recombinant DNA . Biologics can refer to

5400-443: The use of insulin as a clinical treatment for diabetes: Medical preparations of insulin are never just insulin in water (with nothing else). Clinical insulins are mixtures of insulin plus other substances including preservatives. These prevent the protein from spoiling or denaturing too rapidly, delay absorption of the insulin, adjust the pH of the solution to reduce reactions at the injection site, and so on. Slight variations of

5475-513: The woman's physiological features and the frequency of self-monitoring. The importance of using specialized insulin therapy planning based on parameters like those stated above rather than a broad approach is emphasized. Women with pre-existing diabetes have the highest levels of insulin sensitivity early in pregnancy. Close glucose monitoring is required to prevent hypoglycemia, which can potentially result in altered consciousness, seizures, and maternal damage. Low birth weight newborns might also be

5550-594: Was biosynthetic "human" insulin made via recombinant DNA . 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 it starting in 1982. Major kinds of biopharmaceuticals include: Research and development investment in new medicines by the biopharmaceutical industry stood at $ 65.2 billion in 2008. A few examples of biologics made with recombinant DNA technology include: Many vaccines are grown in tissue cultures. Viral gene therapy involves artificially manipulating

5625-482: Was given August 2006. In the European Union , a biological medicinal product is one of the active substance(s) produced from or extracted from a biological (living) system, and requires, in addition to physicochemical 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

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