Regulation of therapeutic goods
The regulation of therapeutic goods, drugs and therapeutic devices, varies by jurisdiction. In some countries, such as the United States, they are regulated at the national level by a single agency. In other jurisdictions they are regulated at the state level, or at both state and national levels by various bodies, as is the case in Australia; the role of therapeutic goods regulation is designed to protect the health and safety of the population. Regulation is aimed at ensuring the safety and efficacy of the therapeutic goods which are covered under the scope of the regulation. In most jurisdictions, therapeutic goods must be registered. There is some degree of restriction of the availability of certain therapeutic goods depending on their risk to consumers. Modern drug regulation has historical roots in the response to the proliferation of universal antidotes which appeared in the wake of Mithridates' death. Mithridates had brought together physicians and shamans to concoct a potion that would make him immune to poisons.
Following his death, the Romans became keen on further developing the Mithridates potion's recipe. Mithridatium re-entered western society through multiple means; the first was through the Leechbook of the Bald, written somewhere between 900 and 950, which contained a formula for various remedies, including for a theriac. Additionally, theriac became a commercial good traded throughout Europe based on the works of Greek and Roman physicians; the resulting proliferation of various recipes needed to be curtailed in order to ensure that people were not passing off fake antidotes, which led to the development of government involvement and regulation. Additionally, the creation of these concoctions took on ritualistic form and were created in public and the process was observed and recorded, it was believed that if the concoction proved unsuccessful, it was due to the apothecaries’ process of making them and they could be held accountable because of the public nature of the creation. In the 9th century, many Muslim countries established an office of the hisba, which in addition to regulating compliance to Islamic principles and values took on the role of regulating other aspects of social and economic life, including the regulation of medicines.
Inspectors were appointed to employ oversight on those who were involved in the process of medicine creation and were given a lot of leigh weigh to ensure compliance and punishments were stringent. The first official'act', the'Apothecary Wares and Stuffs' Act was passed in 1540 by Henry VIII and set the foundation for others. Through this act, he encouraged physicians in his College of Physicians to appoint four people dedicated to inspecting what was being sold in apothecary shops. In conjunction with this first piece of legislation, there was an emergence of standard formulas for the creation of certain ‘drugs’ and ‘antidotes’ through Pharmacopoeias which first appeared in the form of a decree from Frederick II of Sicily in 1240 to use consistent and standard formulas; the first modern pharmacopoeias were the Florence Pharmacopoeia published in 1498, the Spanish Pharmacopoeia published in 1581 and the London Pharmacopoeia published in 1618. In the United States, regulation of drugs was a state right, as opposed to federal right.
But with the increase in fraudulent practices due to private incentives to maximize profits and poor enforcement of state laws, increased the need for stronger federal regulation. President Roosevelt signed the Federal Food and Drug Act in 1906 which established stricter standards. A 1911 Supreme Court decision, United States vs. Johnson, established that misleading statements were not covered under the FFDA; this directly led to Congress passing the Sherley Amendment which established a clearer definition of ‘misbranded’. Another key catalyst for advances in drug regulation were certain catastrophes that served as calls to the government to step in and impose regulations that would prevent repeats of those instances. One such instance occurred in 1937 when more than a hundred people died from using sulfanilamide elixir which had not gone through any safety testing; this directly led to the passing of the Federal, Food and Cosmetic Act in 1938. One other major catastrophe occurred in the late 1950s when Thalidomide, sold in Germany and sold around the world, led to 100,000 babies being born with various deformities.
The UK's Chief Medical Officer had established a group to look into safety of drugs on the market in 1959 prior to the crisis and was moving in the direction of address the problem of unregulated drugs entering the market. The crisis created a greater sense of emergency to establish safety and efficacy standards around the world; the UK started a temporary Committee on Safety of Drugs while they attempted to pass more comprehensive legislation. Though compliance and submission of drugs to the Committee on Safety of Drugs was not mandatory after, the pharmaceutical industry larger complied due to the thalidomide situation; the European Economic Commission passed a directive in 1965 in order to impose greater efficacy standards before marketing a drug. The United States congress passed the Drug Amendments Act of 1962 The Drug Amendments Act required the FDA to ensure that new drugs being introduced to the market had passed certain tests and standards. Both the EU and US acts introduced the requirements to ensure efficacy.
Of note, increased regulations and standards for testing led to greater innovation in pharm
Janssen Pharmaceutica is a pharmaceutical company headquartered in Beerse, Belgium. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceutica was purchased by New Jersey-based American corporation Johnson & Johnson, became part of Johnson & Johnson Pharmaceutical Research and Development, now renamed to Janssen Research and Development, which conducts research and development activities related to a wide range of human medical disorders, including mental illness, neurological disorders and analgesia, gastrointestinal disorders, fungal infection, HIV/AIDS, allergies and cancer. Janssen and Ortho-McNeil Pharmaceutical have been placed in the Ortho-McNeil-Janssen group within Johnson & Johnson; the early roots of what would become Janssen Pharmaceutica date back to 1933. In 1933, Constant Janssen, the father of Paul Janssen, acquired the right to distribute the pharmaceutical products of Richter, a Hungarian pharmaceutical company, for Belgium, the Netherlands and Belgian Congo. On 23 October 1934, he founded the N.
V. Produkten Richter in Turnhout. In 1937, Constant Janssen acquired an old factory building in the Statiestraat 78 in Turnhout for his growing company, which he expanded during World War II into a four-storey building. Still a student, Paul Janssen assisted in the development of paracetamol under the name Perdolan, which would become well-known. After the war, the name for the company products was changed to Eupharma, although the company name Richter would remain until 1956. Paul Janssen founded his own research laboratory in 1953 on the third floor of the building in the Statiestraat, still within the Richter-Eurpharma company of his father. In 1955, he and his team developed their first drug: Neomeritine, an antispasmodic found to be effective for the relief of menstrual pain. On 5 April 1956, the name of the company was changed to NV Laboratoria Pharmaceutica C. Janssen. On 27 April 1957, the company opened a new research facility in Beerse, but the move to Beerse would not be completed until 1971-1972.
On 2 May 1958, the research department in Beerse became a separate legal entity, the N. V. Research Laboratorium C. Janssen. On 24 October 1961, the company was acquired by the American corporation Johnson; the negotiations with Johnson & Johnson were led by Frans Van den Bergh, head of the Board of Directors. On 10 February 1964, the name was changed to Janssen Pharmaceutica N. V. and the seat of the company in Turnhout was transferred to Beerse. The company was led by Bob Stouthuysen and Frans Van Den Bergh. When, in 1971-1972 the pharmaceutical production moved to Beerse, the move from Turnhout was completed. Between 1990 and 2004, Janssen Pharmaceutica expanded worldwide, the company grew in size to about 28000 employees worldwide. From the beginning, Janssen Pharmaceutica emphasized as its core activity research for the development of new drugs; the research department, established in Beerse in 1957, developed into a large research campus. In 1987, the Janssen Research Foundation was founded which performs research into new drugs at Beerse and in other laboratories around the globe.
Janssen Pharmaceutica became the Flemish company with the largest budget for research and development. Beside the headquarters in Beerse with its research departments, pharmaceutical production and the administrative departments, Janssen Pharmaceutica in Belgium still has offices in Berchem, a chemical factory in Geel, Janssen Biotech in Olen; the Chemical Production plant in Geel makes the active ingredients for the company’s medicines. In 1975, the first plant of a new chemical factory Plant I was established in Geel, Plant II was opened in 1977, Plant III' in 1984, Plant IV in 1995. In 1999 the remaining chemical production in Beerse was transferred to Geel. About 80% of its active components are manufactured here; the site in Geel manufactures about two-thirds of the worldwide chemical production of the pharmaceutical sector of Johnson & Johnson. In 1995, the Center for Molecular Design was founded by Paul Lewi. In 1999, clinical research and non-clinical development become a global organization within Johnson & Johnson.
In 2001, part of the research activities was transferred to the United States with the reorganization of research activities in the Johnson & Johnson Pharmaceutical Research Development organization. The research activities of the Janssen Research Foundation and the R. W. Johnson Pharmaceutical Research Institute were merged into the new global research organization. A new building for pharmaceutical development was completed in Beerse in 2001. In 2002, a new logistics and informatics centre was opened at a new site, Beerse 2. In 2003 two new research buildings were constructed, the Discovery Research Center, the Drug Safety Evaluation Center. On 27 October 2004, the Paul Janssen Research Center, for discovery research, was inaugurated. In March 2015, Janssen licensed tipifarnib to Kura Oncology who will assume sole responsibility for developing and commercialising the anti-cancer drug. In the same month the company announced that Galapagos Pharma and regained the rights to the anti-inflammatory drug candidate GLPG1690 as well as two other compounds including GLPG1205.
In May 2016, the company launched a collaboration MacroGenics and their preclinical cancer treatment, MGD015. The deal could net MacroGenics more than $740 million. In September 2017 it was announced that Janssen teamed up with the Biomedical Advanced Research and Development Authority (BARD
Simplified molecular-input line-entry system
The simplified molecular-input line-entry system is a specification in the form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules; the original SMILES specification was initiated in the 1980s. It has since been extended. In 2007, an open standard called. Other linear notations include the Wiswesser line notation, ROSDAL, SYBYL Line Notation; the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. Acknowledged for their parts in the early development were "Gilman Veith and Rose Russo and Albert Leo and Corwin Hansch for supporting the work, Arthur Weininger and Jeremy Scofield for assistance in programming the system." The Environmental Protection Agency funded the initial project to develop SMILES. It has since been modified and extended by others, most notably by Daylight Chemical Information Systems.
In 2007, an open standard called "OpenSMILES" was developed by the Blue Obelisk open-source chemistry community. Other'linear' notations include the Wiswesser Line Notation, ROSDAL and SLN. In July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is considered to have the advantage of being more human-readable than InChI; the term SMILES refers to a line notation for encoding molecular structures and specific instances should be called SMILES strings. However, the term SMILES is commonly used to refer to both a single SMILES string and a number of SMILES strings; the terms "canonical" and "isomeric" can lead to some confusion when applied to SMILES. The terms are not mutually exclusive. A number of valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol. Algorithms have been developed to generate the same SMILES string for a given molecule; this SMILES is unique for each structure, although dependent on the canonicalization algorithm used to generate it, is termed the canonical SMILES.
These algorithms first convert the SMILES to an internal representation of the molecular structure. Various algorithms for generating canonical SMILES have been developed and include those by Daylight Chemical Information Systems, OpenEye Scientific Software, MEDIT, Chemical Computing Group, MolSoft LLC, the Chemistry Development Kit. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database; the original paper that described the CANGEN algorithm claimed to generate unique SMILES strings for graphs representing molecules, but the algorithm fails for a number of simple cases and cannot be considered a correct method for representing a graph canonically. There is no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, double bond geometry; these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES.
A notable feature of these rules is. The term isomeric SMILES is applied to SMILES in which isotopes are specified. In terms of a graph-based computational procedure, SMILES is a string obtained by printing the symbol nodes encountered in a depth-first tree traversal of a chemical graph; the chemical graph is first trimmed to remove hydrogen atoms and cycles are broken to turn it into a spanning tree. Where cycles have been broken, numeric suffix labels are included to indicate the connected nodes. Parentheses are used to indicate points of branching on the tree; the resultant SMILES form depends on the choices: of the bonds chosen to break cycles, of the starting atom used for the depth-first traversal, of the order in which branches are listed when encountered. Atoms are represented by the standard abbreviation of the chemical elements, in square brackets, such as for gold. Brackets may be omitted in the common case of atoms which: are in the "organic subset" of B, C, N, O, P, S, F, Cl, Br, or I, have no formal charge, have the number of hydrogens attached implied by the SMILES valence model, are the normal isotopes, are not chiral centers.
All other elements must be enclosed in brackets, have charges and hydrogens shown explicitly. For instance, the SMILES for water may be written as either O or. Hydrogen may be written as a separate atom; when brackets are used, the symbol H is added if the atom in brackets is bonded to one or more hydrogen, followed by the number of hydrogen atoms if greater than 1 by the sign + for a positive charge or by - for a negative charge. For example, for ammonium. If there is more than one charge, it is written as digit.
The Jmol applet, among other abilities, offers an alternative to the Chime plug-in, no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, the Sculpt mode. Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS 9. Jmol operates on a wide variety of platforms. For example, Jmol is functional in Mozilla Firefox, Internet Explorer, Google Chrome, Safari. Chemistry Development Kit Comparison of software for molecular mechanics modeling Jmol extension for MediaWiki List of molecular graphics systems Molecular graphics Molecule editor Proteopedia PyMOL SAMSON Official website Wiki with listings of websites and moodles Willighagen, Egon. "Fast and Scriptable Molecular Graphics in Web Browsers without Java3D". Doi:10.1038/npre.2007.50.1
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, poison, or other substance is taken into the body. Routes of administration are classified by the location at which the substance is applied. Common examples include intravenous administration. Routes can be classified based on where the target of action is. Action may be enteral, or parenteral. Route of administration and dosage form are aspects of drug delivery. Routes of administration are classified by application location; the route or course the active substance takes from application location to the location where it has its target effect is rather a matter of pharmacokinetics. Exceptions include the transdermal or transmucosal routes, which are still referred to as routes of administration; the location of the target effect of active substances are rather a matter of pharmacodynamics. An exception is topical administration, which means that both the application location and the effect thereof is local. Topical administration is sometimes defined as both a local application location and local pharmacodynamic effect, sometimes as a local application location regardless of location of the effects.
Administration through the gastrointestinal tract is sometimes termed enteral or enteric administration. Enteral/enteric administration includes oral and rectal administration, in the sense that these are taken up by the intestines. However, uptake of drugs administered orally may occur in the stomach, as such gastrointestinal may be a more fitting term for this route of administration. Furthermore, some application locations classified as enteral, such as sublingual and sublabial or buccal, are taken up in the proximal part of the gastrointestinal tract without reaching the intestines. Enteral administration can be used for systemic administration, as well as local, such as in a contrast enema, whereby contrast media is infused into the intestines for imaging. However, for the purposes of classification based on location of effects, the term enteral is reserved for substances with systemic effects. Many drugs as tablets, capsules, or drops are taken orally. Administration methods directly into the stomach include those by gastric feeding tube or gastrostomy.
Substances may be placed into the small intestines, as with a duodenal feeding tube and enteral nutrition. Enteric coated tablets are designed to dissolve in the intestine, not the stomach, because the drug present in the tablet causes irritation in the stomach; the rectal route is an effective route of administration for many medications those used at the end of life. The walls of the rectum absorb many medications and effectively. Medications delivered to the distal one-third of the rectum at least avoid the "first pass effect" through the liver, which allows for greater bio-availability of many medications than that of the oral route. Rectal mucosa is vascularized tissue that allows for rapid and effective absorption of medications. A suppository is a solid dosage form. In hospice care, a specialized rectal catheter, designed to provide comfortable and discreet administration of ongoing medications provides a practical way to deliver and retain liquid formulations in the distal rectum, giving health practitioners a way to leverage the established benefits of rectal administration.
The parenteral route is any route, not enteral. Parenteral administration can be performed by injection, that is, using a needle and a syringe, or by the insertion of an indwelling catheter. Locations of application of parenteral administration include: central nervous systemepidural, e.g. epidural anesthesia intracerebral direct injection into the brain. Used in experimental research of chemicals and as a treatment for malignancies of the brain; the intracerebral route can interrupt the blood brain barrier from holding up against subsequent routes. Intracerebroventricular administration into the ventricular system of the brain. One use is as a last line of opioid treatment for terminal cancer patients with intractable cancer pain. Epicutaneous, it can be used both for local effect as in allergy testing and typical local anesthesia, as well as systemic effects when the active substance diffuses through skin in a transdermal route. Sublingual and buccal medication administration is a way of giving someone medicine orally.
Sublingual administration is. The word "sublingual" means "under the tongue." Buccal administration involves placement of the drug between the cheek. These medications can come in the form of films, or sprays. Many drugs are designed for sublingual administration, including cardiovascular drugs, barbiturates, opioid analgesics with poor gastrointestinal bioavailability and vitamins and minerals. Extra-amniotic administration, between the endometrium and fetal membranes nasal administration (th
Benzalkonium chloride known as BZK, BKC, BAC, alkyldimethylbenzylammonium chloride and ADBAC, is a type of cationic surfactant. It is an organic salt classified as a quaternary ammonium compound, it has three main categories of use: as a biocide, a cationic surfactant, as a phase transfer agent. ADBACs are a mixture of alkylbenzyldimethylammonium chlorides, in which the alkyl group has various even-numbered alkyl chain lengths. Depending on purity, benzalkonium chloride ranges from colourless to a pale yellow. Benzalkonium chloride is soluble in ethanol and acetone. Dissolution in water is slow. Aqueous solutions should be neutral to alkaline. Solutions foam. Concentrated solutions have a faint almond-like odour. Standard concentrates are manufactured as 50% and 80% w/w solutions, sold under trade names such as BC50, BC80, BAC50, BAC80, etc; the 50% solution is purely aqueous, while more concentrated solutions require incorporation of rheology modifiers to prevent increases in viscosity or gel formation under low temperature conditions.
Benzalkonium chloride possesses surfactant properties, dissolving the lipid phase of the tear film and increasing drug penetration, making it a useful excipient, but at the risk of causing damage to the surface of the eye°. Laundry detergents and treatments Softeners for textiles<°TFOS DEWS II Report July 2017> Benzalkonium chloride is a mainstay of phase-transfer catalysis, an important technology in the synthesis of organic compounds, including drugs. For their antimicrobial activity, benzalkonium chloride is an active ingredient in many consumer products: Pharmaceutical products such as eye and nasal drops or sprays, as a preservative Personal care products such as hand sanitizers, wet wipes, shampoos and cosmetics Skin antiseptics, such as Bactine and Dettol. Throat lozenges and mouthwashes, as a biocide Spermicidal creams Over-the-counter single-application treatments for herpes, cold-sores, fever blisters, such as RELEEV and Viroxyn Burn and ulcer treatment Spray disinfectants for hard surface sanitization Cleaners for floor and hard surfaces as a disinfectant, such as Lysol Algaecides for clearing of algae, lichens from paths, roof tiles, swimming pools, etc.
Benzalkonium chloride is used in many non-consumer processes and products, including as an active ingredient in surgical disinfection. A comprehensive list of uses includes industrial applications. An advantage of benzalkonium chloride, not shared by ethanol-based antiseptics or hydrogen peroxide antiseptic, is that it does not cause a burning sensation when applied to broken skin.. However, prolonged or repeated skin contact may cause dermatitis. Benzalkonium chloride is a used preservative in eye drops. Stronger concentrations can be caustic and cause irreversible damage to the corneal endothelium. Avoiding the use of benzalkonium chloride solutions while contact lenses are in place is discussed in the literature. Although benzalkonium chloride has been ubiquitous as a preservative in ophthalmic preparations, its ocular toxicity and irritant properties, in conjunction with consumer demand, have led pharmaceutical companies to increase production of preservative-free preparations, or to replace benzalkonium chloride with preservatives which are less harmful.
Many mass-marketed inhaler and nasal spray formulations contain benzalkonium chloride as a preservative, despite substantial evidence that it can adversely affect ciliary motion, mucociliary transport, nasal mucosal histology, human neutrophil function, leukocyte response to local inflammation. Although some studies have found no correlation between use of benzalkonium chloride in concentrations at or below 0.1% in nasal sprays and drug-induced rhinitis, others have recommended that benzalkonium chloride in nasal sprays be avoided. In the United States, nasal steroid preparations that are free of benzalkonium chloride include budesonide, triamcinolone acetonide and Beconase and Vancenase aerosol inhalers. Benzalkonium chloride is irritant to middle ear tissues at used concentrations. Inner ear toxicity has been demonstrated. Occupational exposure to benzalkonium chloride has been linked to the development of asthma. In 2011, a large clinical trial designed to evaluate the efficacy of hand sanitizers based on different active ingredients in preventing virus transmission amongst schoolchildren was re-designed to exclude sanitizers based on benzalkonium chloride due to safety concerns.
Benzalkonium chloride has been in common use as a pharmaceutical preservative and antimicrobial since the 1940s. While early studies confirmed the corrosive and irritant properties of benzalkonium chloride, investigations into the adverse effects of, disease states linked to, benzalkonium chloride have only surfaced during the past 30 years. Benzalkonium chloride is classed as a Category III antiseptic active ingredient by the United States Food and Drug Administration. Ingredients are categorised as Category III when "available data are insufficient to classify as safe and effective, further testing is required”. Benzalkonium chloride is excluded from the current United States Food and Drug Administration review of the safety and effectiveness of consumer antiseptics and topical antimicrobial over-the-counter drug products, meaning it will remain a Category III ingredient. There is acknowledgement that more data are required on its safety and effectiveness with relation to: Human pharmacokinetic studies, including information on its metabolites Studies on animal absorption, distribution and excretion Data to help define the effect of formulation on