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114-404: Since 2008, the choir has been conducted by Cecilia Rydinger, in close cooperation with deputy conductor Folke Alin. Orphei Drängar was founded on October 30, 1853, while the city of Uppsala was isolated in an attempt to stop the spread of the cholera epidemic that was then tormenting Sweden. The blockade was successful in that the city more or less came to be spared from the disease, but also had

228-720: A medical practitioner 's supervision like ibuprofen . In 2014, the FDA added an Ebola treatment being developed by Canadian pharmaceutical company Tekmira to the Fast Track program , but halted the phase 1 trials in July pending the receipt of more information about how the drug works. This was widely viewed as increasingly important in the face of a major outbreak of the disease in West Africa that began in late March 2014 and ended in June 2016. During

342-806: A reservoir of infection, and seafood shipped long distances can spread the disease. US Food and Drug Administration The United States Food and Drug Administration ( FDA or US FDA ) is a federal agency of the Department of Health and Human Services . The FDA is responsible for protecting and promoting public health through the control and supervision of food safety , tobacco products, caffeine products, dietary supplements , prescription and over-the-counter pharmaceutical drugs (medications), vaccines , biopharmaceuticals , blood transfusions , medical devices , electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products . The FDA's primary focus

456-436: A temperate bacteriophage called CTXφ . Microbiologists have studied the genetic mechanisms by which the V. cholerae bacteria turn off the production of some proteins and turn on the production of other proteins as they respond to the series of chemical environments they encounter, passing through the stomach, through the mucous layer of the small intestine, and on to the intestinal wall. Of particular interest have been

570-460: A "FDA Compliant" or "FDA Acceptable". Medical countermeasures (MCMs) are products such as biologics and pharmaceutical drugs that can protect from or treat the health effects of a chemical, biological, radiological, or nuclear (CBRN) attack. MCMs can also be used for prevention and diagnosis of symptoms associated with CBRN attacks or threats. The FDA runs a program called the "FDA Medical Countermeasures Initiative" (MCMi), with programs funded by

684-425: A REMS program called iPLEDGE . Generic drugs are chemical and therapeutic equivalents of name-brand drugs, normally whose patents have expired. Approved generic drugs should have the same dosage, safety, effectiveness, strength, stability, and quality, as well as route of administration. In general, they are less expensive than their name brand counterparts, are manufactured and marketed by rival companies and, in

798-745: A case. The FDA has a number of field offices across the United States, in addition to international locations in China, India, Europe, the Middle East, and Latin America. As of 2021, the FDA had responsibility for overseeing $ 2.7 trillion in food, medical, and tobacco products. Some 54% of its budget derives from the federal government, and 46% is covered by industry user fees for FDA services. For example, pharmaceutical firms pay fees to expedite drug reviews. According to Forbes, pharmaceutical firms provide 75% of

912-513: A company may advertise or promote a drug only for the specific indication or medical use for which it was approved by FDA. Also, an advertisement must contain a "fair balance" between the benefits and the risks (side effects) of a drug. The regulation of drug advertising in the U.S. is divided between the Food and Drug Administration (FDA) and the Federal Trade Commission (FTC), based on whether

1026-426: A complaint brought against the FDA by Mylan Laboratories Inc. of Pittsburgh . When its application to manufacture generics were subjected to repeated delays by the FDA, Mylan, convinced that it was being discriminated against, soon began its own private investigation of the agency in 1987. Mylan eventually filed suit against two former FDA employees and four drug-manufacturing companies, charging that corruption within

1140-428: A day. Severe cholera, without treatment, kills about half of affected individuals. If the severe diarrhea is not treated, it can result in life-threatening dehydration and electrolyte imbalances. Estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100. Cholera has been nicknamed the "blue death" because a person's skin may turn bluish-gray from extreme loss of fluids. Fever

1254-428: A greatly reduced pathogen count—though it will not necessarily be perfectly safe, it is an improvement for poor people with limited options. In Bangladesh this practice was found to decrease rates of cholera by nearly half. It involves folding a sari four to eight times. Between uses the cloth should be rinsed in clean water and dried in the sun to kill any bacteria on it. A nylon cloth appears to work as well but

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1368-432: A long period of time. The studies are progressively longer, gradually adding more individuals as they progress from stage I to stage III, normally over a period of years, and normally involve drug companies, the government and its laboratories, and often medical schools and hospitals and clinics. However, any exceptions to the aforementioned process are subject to strict review and scrutiny and conditions, and are only given if

1482-527: A massive inoculation program in British India . Persons who survive an episode of cholera have long-lasting immunity for at least 3 years (the period tested.) A number of safe and effective oral vaccines for cholera are available. The World Health Organization (WHO) has three prequalified oral cholera vaccines (OCVs): Dukoral, Sanchol, and Euvichol. Dukoral , an orally administered, inactivated whole-cell vaccine , has an overall efficacy of about 52% during

1596-555: A new master plan for this expansion in December 2018, and construction is expected to be completed by 2035, dependent on GSA appropriations. The Office of Regulatory Affairs is considered the agency's "eyes and ears", conducting the vast majority of the FDA's work in the field. Its employees, known as Consumer Safety Officers, or more commonly known simply as investigators, inspect production, warehousing facilities, investigate complaints, illnesses, or outbreaks, and review documentation in

1710-535: A non-toxic B-subunit of cholera toxin and providing protection against V. cholerae O1; and two vaccines developed using the same transfer of technology—ShanChol (Shantha Biotec) and Euvichol (EuBiologics Co.), which have bivalent O1 and O139 oral killed cholera vaccines. Oral cholera vaccination could be deployed in a diverse range of situations from cholera-endemic areas and locations of humanitarian crises, but no clear consensus exists. Developed for use in Bangladesh ,

1824-647: A number of Resident Posts, which are FDA remote offices that serve a particular geographic area. ORA also includes the Agency's network of regulatory laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, and radiation-emitting devices. The Office of Criminal Investigations was established in 1991 to investigate criminal cases. To do so, OCI employs approximately 200 Special Agents nationwide who, unlike ORA Investigators, are armed, have badges, and do not focus on technical aspects of

1938-408: A one-million fold increase in numbers of V. cholerae in the environment. The source of the contamination is typically other people with cholera when their untreated diarrheal discharge is allowed to get into waterways, groundwater or drinking water supplies. Drinking any contaminated water and eating any foods washed in the water, as well as shellfish living in the affected waterway , can cause

2052-430: A person to contract an infection. Cholera is rarely spread directly from person to person . V. cholerae also exists outside the human body in natural water sources, either by itself or through interacting with phytoplankton , zooplankton , or biotic and abiotic detritus. Drinking such water can also result in the disease, even without prior contamination through fecal matter. Selective pressures exist however in

2166-530: A result of transmission by food, while in developing countries it is more often water. Food transmission can occur when people harvest seafood such as oysters in waters infected with sewage , as Vibrio cholerae accumulates in planktonic crustaceans and the oysters eat the zooplankton . People infected with cholera often have diarrhea, and disease transmission may occur if this highly liquid stool, colloquially referred to as "rice-water", contaminates water used by others. A single diarrheal event can cause

2280-494: A role in monitoring safety through influence on ingredients, but they lack legal authority. According to the ACSH, it has reviewed about 1,200 ingredients and has suggested that several hundred be restricted—but there is no standard or systemic method for reviewing chemicals for safety, or a clear definition of what 'safety' even means so that all chemicals get tested on the same basis. However, on December 29, 2022, President Biden signed

2394-523: A satisfied requirement. The FDA does not approve applied coatings used in the food processing industry . There is no review process to approve the composition of nonstick coatings; nor does the FDA inspect or test these materials. Through their governing of processes, however, the FDA does have a set of regulations that cover the formulation, manufacturing, and use of nonstick coatings. Hence, materials like Polytetrafluoroethylene (Teflon) are not and cannot be considered as FDA Approved, but rather, they are

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2508-421: A severe case if they become infected. Any individual, even a healthy adult in middle age, can undergo a severe case, and each person's case should be measured by the loss of fluids, preferably in consultation with a professional health care provider . The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage : heterozygous carriers of

2622-440: A substantial amount of research and at least some preliminary human testing has shown that they are believed to be somewhat safe and possibly effective. (See FDA Special Protocol Assessment about Phase III trials.) The FDA's Office of Prescription Drug Promotion (OPDP) has responsibilities that revolve around the review and regulation of prescription drug advertising and promotion. This is achieved through surveillance activities and

2736-553: A warning to that effect. According to the industry advocacy group, the American Council on Science and Health , though the cosmetic industry is primarily responsible for its own product safety, the FDA can intervene when necessary to protect the public. In general, though, cosmetics do not require pre-market approval or testing. The ACSH says that companies must place a warning note on their products if they have not been tested, and that experts in cosmetic ingredient review also play

2850-442: A year (uncertainty range: 21,000–143,000) as of 2015 . This occurs mainly in the developing world. In the early 1980s, death rates are believed to have still been higher than three million a year. It is difficult to calculate exact numbers of cases, as many go unreported due to concerns that an outbreak may have a negative impact on the tourism of a country. As of 2004, cholera remained both epidemic and endemic in many areas of

2964-555: A year. To date, seven cholera pandemics have occurred, with the most recent beginning in 1961, and continuing today. The illness is rare in high-income countries , and affects children most severely. Cholera occurs as both outbreaks and chronically in certain areas . Areas with an ongoing risk of disease include Africa and Southeast Asia . The risk of death among those affected is usually less than 5%, given improved treatment, but may be as high as 50% without such access to treatment. Descriptions of cholera are found as early as

3078-596: Is endemic . If people are immunized broadly, herd immunity results, with a decrease in the amount of contamination in the environment. WHO recommends that oral cholera vaccination be considered in areas where the disease is endemic (with seasonal peaks), as part of the response to outbreaks, or in a humanitarian crisis during which the risk of cholera is high. Oral Cholera Vaccine (OCV) has been recognized as an adjunct tool for prevention and control of cholera. The World Health Organization (WHO) has prequalified three bivalent cholera vaccines—Dukoral (SBL Vaccines), containing

3192-547: Is oral rehydration salts (ORS), the replacement of fluids and electrolytes by using slightly sweet and salty solutions. Rice-based solutions are preferred. In children, zinc supplementation has also been found to improve outcomes. In severe cases, intravenous fluids , such as Ringer's lactate , may be required, and antibiotics may be beneficial. The choice of antibiotic is aided by antibiotic sensitivity testing . Cholera continues to affect an estimated 3–5 million people worldwide and causes 28,800–130,000 deaths

3306-401: Is a center of the FDA that regulates food additives and drugs that are given to animals. CVM regulates animal drugs, animal food including pet animal, and animal medical devices. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers. CVM does not regulate vaccines for animals; these are handled by

3420-422: Is a common problem. Stool and swab samples collected in the acute stage of the disease, before antibiotics have been administered, are the most useful specimens for laboratory diagnosis. If an epidemic of cholera is suspected, the most common causative agent is V. cholerae O1. If V. cholerae serogroup O1 is not isolated, the laboratory should test for V. cholerae O139. However, if neither of these organisms

3534-503: Is a common source. Humans are the only known host for the bacteria . Risk factors for the disease include poor sanitation , insufficient clean drinking water , and poverty . Cholera can be diagnosed by a stool test , or a rapid dipstick test , although the dipstick test is less accurate. Prevention methods against cholera include improved sanitation and access to clean water . Cholera vaccines that are given by mouth provide reasonable protection for about six months, and confer

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3648-651: Is a separate process, and the drug must be approved through an NDA first. A drug that is approved is said to be "safe and effective when used as directed". Very rare, limited exceptions to this multi-step process involving animal testing and controlled clinical trials can be granted out of compassionate use protocols. This was the case during the 2015 Ebola epidemic with the use, by prescription and authorization, of ZMapp and other experimental treatments, and for new drugs that can be used to treat debilitating and/or very rare conditions for which no existing remedies or drugs are satisfactory, or where there has not been an advance in

3762-442: Is available to determine the presence of V. cholerae . In those samples that test positive, further testing should be done to determine antibiotic resistance. In epidemic situations, a clinical diagnosis may be made by taking a patient history and doing a brief examination. Treatment via hydration and over-the-counter hydration solutions can be started without or before confirmation by laboratory analysis, especially where cholera

3876-446: Is effective for adults aged 18–64 as a single dose. One injectable vaccine was found to be effective for two to three years. The protective efficacy was 28% lower in children less than five years old. However, as of 2010 , it has limited availability. Work is under way to investigate the role of mass vaccination. The WHO recommends immunization of high-risk groups, such as children and people with HIV , in countries where this disease

3990-547: Is enforcement of the Federal Food, Drug, and Cosmetic Act (FD&C). However, the agency also enforces other laws, notably Section 361 of the Public Health Service Act as well as associated regulations. Much of this regulatory-enforcement work is not directly related to food or drugs but involves other factors like regulating lasers , cellular phones , and condoms . In addition, the FDA takes control of diseases in

4104-416: Is increasing within cholera bacteria. In Bangladesh , for example, most cases are resistant to tetracycline , trimethoprim-sulfamethoxazole , and erythromycin . Rapid diagnostic assay methods are available for the identification of multi-drug resistant cases. New generation antimicrobials have been discovered which are effective against cholera bacteria in in vitro studies. A rapid dipstick test

4218-424: Is isolated, it is necessary to send stool specimens to a reference laboratory. Infection with V. cholerae O139 should be reported and handled in the same manner as that caused by V. cholerae O1. The associated diarrheal illness should be referred to as cholera and must be reported in the United States. The World Health Organization (WHO) recommends focusing on prevention, preparedness, and response to combat

4332-460: Is less in those with lowered gastric acidity (for instance those using proton pump inhibitors ). Children are also more susceptible, with two- to four-year-olds having the highest rates of infection. Individuals' susceptibility to cholera is also affected by their blood type , with those with type O blood being the most susceptible. Persons with lowered immunity , such as persons with AIDS or malnourished children, are more likely to develop

4446-713: Is located in the White Oak area of Silver Spring, Maryland . The agency has 223 field offices and 13 laboratories located across the 50 states, the United States Virgin Islands , and Puerto Rico . In 2008, the FDA began to post employees to foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom. FDA headquarters facilities are currently located in Montgomery County and Prince George's County , Maryland. Since 1990,

4560-754: Is maintained. The WHO only recommends antibiotics in those with severe dehydration. Doxycycline is typically used first line, although some strains of V. cholerae have shown resistance . Testing for resistance during an outbreak can help determine appropriate future choices. Other antibiotics proven to be effective include cotrimoxazole , erythromycin , tetracycline , chloramphenicol , and furazolidone . Fluoroquinolones , such as ciprofloxacin , also may be used, but resistance has been reported. Antibiotics improve outcomes in those who are both severely and not severely dehydrated. Azithromycin and tetracycline may work better than doxycycline or ciprofloxacin . In Bangladesh zinc supplementation reduced

4674-469: Is not as affordable. Continued eating speeds the recovery of normal intestinal function. The WHO recommends this generally for cases of diarrhea no matter what the underlying cause. A CDC training manual specifically for cholera states: "Continue to breastfeed your baby if the baby has watery diarrhea, even when traveling to get treatment. Adults and older children should continue to eat frequently." The most common error in caring for patients with cholera

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4788-442: Is rapid and thready, and urine output decreases with time. Muscle cramping and weakness, altered consciousness, seizures , or even coma due to electrolyte imbalances are common, especially in children. Cholera bacteria have been found in shellfish and plankton . Transmission is usually through the fecal-oral route of contaminated food or water caused by poor sanitation . Most cholera cases in developed countries are

4902-412: Is rare and should raise suspicion for secondary infection. Patients can be lethargic and might have sunken eyes, dry mouth, cold clammy skin, or wrinkled hands and feet. Kussmaul breathing , a deep and labored breathing pattern, can occur because of acidosis from stool bicarbonate losses and lactic acidosis associated with poor perfusion . Blood pressure drops due to dehydration, peripheral pulse

5016-406: Is rare. For example, the last major outbreak of cholera in the United States occurred in 1910–1911. Cholera is mainly a risk in developing countries in those areas where access to WASH (water, sanitation and hygiene) infrastructure is still inadequate. Effective sanitation practices, if instituted and adhered to in time, are usually sufficient to stop an epidemic. There are several points along

5130-449: Is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. These include blood and blood products, vaccines, allergenics, cell and tissue-based products, and gene therapy products. New biologics are required to go through a premarket approval process called a Biologics License Application (BLA), similar to that for drugs. The original authority for government regulation of biological products

5244-737: Is the branch of the FDA responsible for the premarket approval of all medical devices , as well as overseeing the manufacturing, performance and safety of these devices. The definition of a medical device is given in the FD&;C Act, and it includes products from the simple toothbrush to complex devices such as implantable neurostimulators . CDRH also oversees the safety performance of non-medical devices that emit certain types of electromagnetic radiation . Examples of CDRH-regulated devices include cellular phones , airport baggage screening equipment , television receivers , microwave ovens , tanning booths , and laser products . CDRH regulatory powers include

5358-575: Is the preferred solution, often with added potassium. Large volumes and continued replacement until diarrhea has subsided may be needed. Ten percent of a person's body weight in fluid may need to be given in the first two to four hours. This method was first tried on a mass scale during the Bangladesh Liberation War , and was found to have much success. Despite widespread beliefs, fruit juices and commercial fizzy drinks like cola are not ideal for rehydration of people with serious infections of

5472-404: Is to underestimate the speed and volume of fluids required. In most cases, cholera can be successfully treated with oral rehydration therapy (ORT), which is highly effective, safe, and simple to administer. Rice-based solutions are preferred to glucose-based ones due to greater efficiency. In severe cases with significant dehydration, intravenous rehydration may be necessary. Ringer's lactate

5586-696: Is used for a different purpose, or undergoes any substantial change. The most rigorous requirements apply to new molecular entities : drugs that are not based on existing medications. New drugs receive extensive scrutiny before FDA approval in a process called a new drug application (NDA). Under the Presidency of Donald Trump , the agency has worked to make the drug-approval process go faster. Critics, however, argue that FDA standards are not sufficiently rigorous to prevent unsafe or ineffective drugs from getting approval. New drugs are available only by prescription by default. A change to over-the-counter (OTC) status

5700-451: Is voluntary. While this remains the primary tool of post-market safety surveillance , FDA requirements for post-marketing risk management are increasing. As a condition of approval, a sponsor may be required to conduct additional clinical trials , called Phase IV trials. In some cases, the FDA requires risk management plans called Risk Evaluation and Mitigation Strategies (REMS) for some drugs that require actions to be taken to ensure that

5814-671: The Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), the Center for Biologics Evaluation and Research (CBER) and offices for the Center for Veterinary Medicine (CVM). With the passing of the FDA Reauthorization Act of 2017, the FDA projects a 64% increase in employees to 18,000 over the next 15 years and wants to add approximately 1,600,000 square feet (150,000 square metres) of office and special use space to their existing facilities. The National Capital Planning Commission approved

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5928-446: The Gs alpha subunit of the heterotrimeric G protein . This results in constitutive cAMP production, which in turn leads to the secretion of water, sodium, potassium, and bicarbonate into the lumen of the small intestine and rapid dehydration. The gene encoding the cholera toxin was introduced into V. cholerae by horizontal gene transfer . Virulent strains of V. cholerae carry a variant of

6042-639: The coronavirus pandemic , FDA granted emergency use authorization for personal protective equipment (PPE), in vitro diagnostic equipment, ventilators and other medical devices. On March 18, 2020, FDA inspectors postponed most foreign facility inspections and all domestic routine surveillance facility inspections. In contrast, the USDA's Food Safety and Inspection Service (FSIS) continued inspections of meatpacking plants, which resulted in 145 FSIS field employees who tested positive for COVID-19, and three who died. The Center for Biologics Evaluation and Research

6156-406: The human stomach . The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down protein production. When the surviving bacteria exit the stomach and reach the small intestine , they must propel themselves through the thick mucus that lines the small intestine to reach the intestinal walls where they can attach and thrive. Once

6270-479: The potassium level may be normal, even though large losses have occurred. As the dehydration is corrected, potassium levels may decrease rapidly, and thus need to be replaced. This is best done by Oral Rehydration Solution (ORS). Antibiotic treatments for one to three days shorten the course of the disease and reduce the severity of the symptoms. Use of antibiotics also reduces fluid requirements. People will recover without them, however, if sufficient hydration

6384-455: The small intestine by some strains of the bacterium Vibrio cholerae . Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea lasting a few days. Vomiting and muscle cramps may also occur. Diarrhea can be so severe that it leads within hours to severe dehydration and electrolyte imbalance . This may result in sunken eyes , cold skin, decreased skin elasticity, and wrinkling of

6498-411: The "sari filter" is a simple and cost-effective appropriate technology method for reducing the contamination of drinking water. Used sari cloth is preferable but other types of used cloth can be used with some effect, though the effectiveness will vary significantly. Used cloth is more effective than new cloth, as the repeated washing reduces the space between the fibers. Water collected in this way has

6612-606: The '2023 Consolidated Budget Act', which includes the 'Cosmetics Regulatory Modernization Act of 2022 (MoCRA)', which is a stricter regulation that is different from the previous regulations. MoCRA requires compliance with matters such as serious adverse event reporting, safety substantiation, additional labeling, record keeping, and Good Manufacturing Practices (GMP). MoCRA also calls on the FDA to grant Mandatory Recall Authority and establish regulations for GMP rules, flavor allergen labeling rules, and testing methods for cosmetics containing talc. The Center for Veterinary Medicine (CVM)

6726-406: The 1990s, accounted for about a third of all prescriptions written in the United States. For a pharmaceutical company to gain approval to produce a generic drug, the FDA requires scientific evidence that the generic drug is interchangeable with or therapeutically equivalent to the originally approved drug. This is called an Abbreviated New Drug Application (ANDA). 80% of prescription drugs sold in

6840-502: The 5th century BC in Sanskrit . In Europe, cholera was a term initially used to describe any kind of gastroenteritis, and was not used for this disease until the early 19th century. The study of cholera in England by John Snow between 1849 and 1854 led to significant advances in the field of epidemiology because of his insights about transmission via contaminated water, and a map of the same

6954-501: The FD&C Act. OCI Special Agents often come from other criminal investigations backgrounds, and frequently work closely with the Federal Bureau of Investigation , Assistant Attorney General , and even Interpol . OCI receives cases from a variety of sources—including ORA, local agencies, and the FBI, and works with ORA Investigators to help develop the technical and science-based aspects of

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7068-622: The FDA exercises differ from one category to the next. Furthermore, legislation had granted the FDA a variety of means to address violations of standards for a given substance category. Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), the FDA is responsible for ensuring that manufacturers and distributors of dietary supplements and dietary ingredients meet the current requirements. These manufacturers and distributors are not allowed to advertise their products in an adulterated way, and they are responsible for evaluating

7182-687: The FDA has had employees and facilities on 130 acres (53 hectares) of the White Oak Federal Research Center in the White Oak area of Silver Spring, Maryland . In 2001, the General Services Administration (GSA) began new construction on the campus to consolidate the FDA's 25 existing operations in the Washington metropolitan area , its headquarters in Rockville , and several fragmented office buildings. The first building,

7296-703: The FDA released a statement regarding new guidelines to help food and drug manufacturers "implement protections against potential attacks on the U.S. food supply". One of the guidelines includes the Intentional Adulteration (IA) rule, which requires strategies and procedures by the food industry to reduce the risk of compromise in facilities and processes that are significantly vulnerable. The FDA also uses tactics of regulatory shaming, mainly through online publication of non-compliance, warning letters, and "shaming lists." Regulation by shaming harnesses firms' sensitivity to reputational damage. For example, in 2018,

7410-581: The FDA's drug review budget Emergency Use Authorization (EUA) is a mechanism that was created to facilitate the availability and use of medical countermeasures, including vaccines and personal protective equipment, during public health emergencies such as the Zika virus epidemic, the Ebola virus epidemic and the COVID-19 pandemic. The programs for safety regulation vary widely by the type of product, its potential risks, and

7524-871: The Food and Drug Administration is governed by various statutes enacted by the United States Congress and interpreted by the FDA. Pursuant to the Federal Food, Drug, and Cosmetic Act and accompanying legislation, the FDA has authority to oversee the quality of substances sold as food in the United States, and to monitor claims made in the labeling of both the composition and the health benefits of foods. The FDA subdivides substances that it regulates as food into various categories—including foods, food additives , added substances (human-made substances that are not intentionally introduced into food, but nevertheless end up in it), and dietary supplements . Dietary supplements or dietary ingredients include vitamins, minerals, herbs, amino acids , and enzymes . Specific standards

7638-623: The Life Sciences Laboratory, was dedicated and opened with 104 employees in December 2003. As of December 2018, the FDA campus has a population of 10,987 employees housed in approximately 3,800,000 square feet (350,000 square metres) of space, divided into ten offices and four laboratory buildings. The campus houses the Office of the Commissioner (OC), the Office of Regulatory Affairs (ORA), 

7752-620: The Olympic Games in Paris 1924. In the 21st century, Orphei Drängar consists of approximately 80 singers. Admission tests are usually carried out in the beginning of September each year. Yearly recurring concerts are the spring concert in April, the traditional spring song on April 30, with the Caprice concerts in December. Cholera Cholera ( / ˈ k ɒ l ər ə / ) is an infection of

7866-477: The United States are generic brands. In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. Charges of corruption in generic drug approval first emerged in 1988 during the course of an extensive congressional investigation into the FDA. The oversight subcommittee of the United States House Energy and Commerce Committee resulted from

7980-561: The added benefit of protecting against another type of diarrhea caused by E. coli . In 2017, the US Food and Drug Administration (FDA) approved a single-dose, live, oral cholera vaccine called Vaxchora for adults aged 18–64 who are travelling to an area of active cholera transmission. It offers limited protection to young children. People who survive an episode of cholera have long-lasting immunity for at least three years (the period tested). The primary treatment for affected individuals

8094-757: The agency published an online "black list", in which it named dozens of branded drug companies that are supposedly using unlawful or unethical means to attempt to impede competition from generic drug companies. The FDA frequently works with other federal agencies, including the Department of Agriculture , the Drug Enforcement Administration , Customs and Border Protection , and the Consumer Product Safety Commission . They also often work with local and state government agencies in performing regulatory inspections and enforcement actions. The regulation of food and dietary supplements by

8208-474: The aquatic environment that may reduce the virulence of V. cholerae . Specifically, animal models indicate that the transcriptional profile of the pathogen changes as it prepares to enter an aquatic environment. This transcriptional change results in a loss of ability of V. cholerae to be cultured on standard media, a phenotype referred to as ' viable but non-culturable ' (VBNC) or more conservatively ' active but non-culturable ' (ABNC). One study indicates that

8322-468: The authority to require certain technical reports from the manufacturers or importers of regulated products, to require that radiation-emitting products meet mandatory safety performance standards, to declare regulated products defective, and to order the recall of defective or noncompliant products. CDRH also conducts limited amounts of direct product testing. Clearance requests are required for medical devices that prove they are "substantially equivalent" to

8436-473: The case of medical devices, drugs, biological products, and other items where it may be difficult to conduct a physical examination or take a physical sample of the product. The Office of Regulatory Affairs is divided into five regions, which are further divided into 20 districts. The districts are based roughly on the geographic divisions of the Federal court system . Each district comprises a main district office and

8550-422: The cholera bacteria reach the intestinal wall, they no longer need the flagella to move. The bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins that they express in response to the changed chemical surroundings. On reaching the intestinal wall, V. cholerae start producing the toxic proteins that give the infected person a watery diarrhea. This carries

8664-612: The cholera transmission path at which its spread may be halted: Handwashing with soap or ash after using a toilet and before handling food or eating is also recommended for cholera prevention by WHO Africa. Surveillance and prompt reporting allow for containing cholera epidemics rapidly. Cholera exists as a seasonal disease in many endemic countries, occurring annually mostly during rainy seasons . Surveillance systems can provide early alerts to outbreaks, therefore leading to coordinated response and assist in preparation of preparedness plans. Efficient surveillance systems can also improve

8778-502: The contexts varying from household pets to human sperm donated for use in assisted reproduction . The FDA is led by the commissioner of Food and Drugs , appointed by the President with the advice and consent of the Senate . The commissioner reports to the secretary of health and human services . Robert Califf is the current commissioner as of February 17, 2022. The FDA's headquarters

8892-424: The culturability of V. cholerae drops 90% within 24 hours of entering the water, and furthermore that this loss in culturability is associated with a loss in virulence. Both toxic and non-toxic strains exist. Non-toxic strains can acquire toxicity through a temperate bacteriophage . About 100   million bacteria must typically be ingested to cause cholera in a normal healthy adult. This dose, however,

9006-466: The drug in question is a prescription drug or an over-the-counter (OTC) drug. The FDA oversees the advertising of prescription drugs, while the FTC regulates the advertising of OTC drugs. The term off-label refers to the practice of prescribing a drug for a different purpose than what the FDA approved. Due to this approval requirement, manufacturers were prohibited from advertising COVID-19 vaccines during

9120-416: The drug is used safely. For example, thalidomide can cause birth defects, but has uses that outweigh the risks if men and women taking the drugs do not conceive a child; a REMS program for thalidomide mandates an auditable process to ensure that people taking the drug take action to avoid pregnancy; many opioid drugs have REMS programs to avoid addiction and diversion of drugs. The drug isotretinoin has

9234-433: The duration and severity of diarrhea in children with cholera when given with antibiotics and rehydration therapy as needed. It reduced the length of disease by eight hours and the amount of diarrhea stool by 10%. Supplementation appears to be also effective in both treating and preventing infectious diarrhea due to other causes among children in the developing world. If people with cholera are treated quickly and properly,

9348-678: The early 1990s, the U.S. Securities and Exchange Commission filed securities fraud charges against the Bolar Pharmaceutical Company, a major generic manufacturer based in Long Island, New York. Over-the-counter (OTC) are drugs like aspirin that do not require a doctor's prescription. The FDA has a list of approximately 800 such approved ingredients that are combined in various ways to create more than 100,000 OTC drug products. Many OTC drug ingredients had been previously approved prescription drugs now deemed safe enough for use without

9462-461: The effect that the students instead felt that they were about to die of boredom. In an attempt to remedy this, first tenor Jonas Widén gathered twelve students (ten singers, a pianist and a spectator) and the conductor Oscar Arpi in a local Banquet Hall, where they passed the time singing together. One of the songs that was performed was Fredman's Epistle No. 14, "Hör, I Orphei Drängar" ("Hear, ye sons of Orpheus") by Carl Michael Bellman , and before

9576-529: The evening was over the singing friends (including the spectator) had formed the Orphei Drängar singing society. The ambitions rose, as composer Jacob Axel Josephson , since 1849 director musices at the Uppsala university, was recruited as the director of the choir in 1854. The first public performance under the choir's own name took place in 1864, and a yearly tradition with spring concerts started in 1870. OD

9690-648: The federal agency resulted in racketeering and in violations of antitrust law . "The order in which new generic drugs were approved was set by the FDA employees even before drug manufacturers submitted applications" and, according to Mylan, this illegal procedure was followed to give preferential treatment to certain companies. During the summer of 1989, three FDA officials (Charles Y. Chang, David J. Brancato, Walter Kletch) pleaded guilty to criminal charges of accepting bribes from generic drugs makers, and two companies ( Par Pharmaceutical and its subsidiary Quad Pharmaceuticals) pleaded guilty to giving bribes. Furthermore, it

9804-436: The federal government. It helps support "partner" agencies and organisations prepare for public health emergencies that could require MCMs. The Center for Drug Evaluation and Research uses different requirements for the three main drug product types: new drugs, generic drugs, and over-the-counter drugs. A drug is considered "new" if it is made by a different manufacturer, uses different excipients or inactive ingredients,

9918-438: The first to immunize humans against a bacterial disease. His vaccine and inoculation was rather controversial and was rejected by his peers and several investigation commissions but it ended up demonstrating its effectiveness and being recognized for it: out of the 30 thousand people he vaccinated only 54 died. Russian-Jewish bacteriologist Waldemar Haffkine also developed a human cholera vaccine in July 1892. He conducted

10032-475: The first year after being given and 62% in the second year, with minimal side effects. It is available in over 60 countries. However, it is not currently recommended by the Centers for Disease Control and Prevention (CDC) for most people traveling from the United States to endemic countries. The vaccine that the US Food and Drug Administration (FDA) recommends, Vaxchora , is an oral attenuated live vaccine , that

10146-420: The genetic mechanisms by which cholera bacteria turn on the protein production of the toxins that interact with host cell mechanisms to pump chloride ions into the small intestine, creating an ionic pressure which prevents sodium ions from entering the cell. The chloride and sodium ions create a salt-water environment in the small intestines, which through osmosis can pull up to six liters of water per day through

10260-457: The genetic structure. Two clusters have been identified: Cluster I and Cluster II. For the most part, Cluster I consists of strains from the 1960s and 1970s, while Cluster II largely contains strains from the 1980s and 1990s, based on the change in the clone structure. This grouping of strains is best seen in the strains from the African continent. In many areas of the world, antibiotic resistance

10374-401: The hands and feet. Dehydration can cause the skin to turn bluish . Symptoms start two hours to five days after exposure. Cholera is caused by a number of types of Vibrio cholerae , with some types producing more severe disease than others. It is spread mostly by unsafe water and unsafe food that has been contaminated with human feces containing the bacteria. Undercooked shellfish

10488-463: The intestinal cells, creating the massive amounts of diarrhea. The host can become rapidly dehydrated unless treated properly. By inserting separate, successive sections of V. cholerae DNA into the DNA of other bacteria, such as E. coli that would not naturally produce the protein toxins, researchers have investigated the mechanisms by which V. cholerae responds to the changing chemical environments of

10602-400: The intestines, and their excessive sugar content may even harm water uptake. If commercially produced oral rehydration solutions are too expensive or difficult to obtain, solutions can be made. One such recipe calls for 1 liter of boiled water, 1/2 teaspoon of salt, 6 teaspoons of sugar, and added mashed banana for potassium and to improve taste. As there frequently is initially acidosis ,

10716-545: The issuance of enforcement letters to pharmaceutical manufacturers. Advertising and promotion for over-the-counter drugs is regulated by the Federal Trade Commission . The FDA also implements regulatory oversight through engagement with third-party enforcer-firms. It expects pharmaceutical companies to ensure that third-party suppliers and labs comply with the agency's health and safety guidelines . The drug advertising regulation contains two broad requirements: (1)

10830-497: The mortality rate is less than 1%; however, with untreated cholera, the mortality rate rises to 50–60%. For certain genetic strains of cholera, such as the one present during the 2010 epidemic in Haiti and the 2004 outbreak in India, death can occur within two hours of becoming ill. Cholera affects an estimated 2.8 million people worldwide, and causes approximately 95,000 deaths

10944-448: The multiplying new generations of V. cholerae bacteria out into the drinking water of the next host if proper sanitation measures are not in place. The cholera toxin (CTX or CT) is an oligomeric complex made up of six protein subunits : a single copy of the A subunit (part A), and five copies of the B subunit (part B), connected by a disulfide bond . The five B subunits form a five-membered ring that binds to GM1 gangliosides on

11058-400: The mutation (who are not affected by cystic fibrosis) are more resistant to V. cholerae infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the intestinal epithelium , thus reducing the effects of an infection. When consumed, most bacteria do not survive the acidic conditions of

11172-533: The period in which they had only been approved under Emergency Use Authorization . After NDA approval, the sponsor must then review and report to the FDA every single patient adverse drug experience it learns of. They must report unexpected serious and fatal adverse drug events within 15 days, and other events on a quarterly basis. The FDA also receives directly adverse drug event reports through its MedWatch program. These reports are called "spontaneous reports" because reporting by consumers and health professionals

11286-422: The predicate devices already on the market. Approved requests are for items that are new or substantially different and need to demonstrate "safety and efficacy", for example they may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed. Cosmetics are regulated by the Center for Food Safety and Applied Nutrition ,

11400-566: The regulated industries. Rather, OCI agents pursue and develop cases when individuals and companies commit criminal actions, such as fraudulent claims or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI pursues cases involving violations of Title 18 of the United States Code (e.g., conspiracy, false statements, wire fraud, mail fraud), in addition to prohibited acts as defined in Chapter III of

11514-470: The regulatory powers granted to the agency. For example, the FDA regulates almost every facet of prescription drugs, including testing, manufacturing, labeling, advertising, marketing, efficacy, and safety—yet FDA regulation of cosmetics focuses primarily on labeling and safety. The FDA regulates most products with a set of published standards enforced by a modest number of facility inspections. Inspection observations are documented on Form 483 . In June 2018,

11628-399: The risk assessment for potential cholera outbreaks. Understanding the seasonality and location of outbreaks provides guidance for improving cholera control activities for the most vulnerable. For prevention to be effective, it is important that cases be reported to national health authorities. Spanish physician Jaume Ferran i Clua developed the first successful cholera inoculation in 1885,

11742-448: The safety and labeling of their product. The FDA has a "Dietary Supplement Ingredient Advisory List" that includes ingredients that sometimes appear on dietary supplements but need further evaluation. An ingredient is added to this list when it is excluded from use in a dietary supplement, does not appear to be an approved food additive or recognized as safe, and/or is subjected to the requirement for pre-market notification without having

11856-458: The same branch of the FDA that regulates food. Cosmetic products are not, in general, subject to premarket approval by the FDA unless they make "structure or function claims" that make them into drugs (see Cosmeceutical ). However, all color additives must be specifically FDA approved before manufacturers can include them in cosmetic products sold in the U.S. The FDA regulates cosmetics labeling, and cosmetics that have not been safety tested must bear

11970-406: The spread of cholera. They also stress the importance of an effective surveillance system. Governments can play a role in all of these areas. Although cholera may be life-threatening, prevention of the disease is normally straightforward if proper sanitation practices are followed. In developed countries , due to their nearly universal advanced water treatment and sanitation practices, cholera

12084-632: The stomach, mucous layers, and intestinal wall. Researchers have discovered a complex cascade of regulatory proteins controls expression of V. cholerae virulence determinants. In responding to the chemical environment at the intestinal wall, the V. cholerae bacteria produce the TcpP/TcpH proteins, which, together with the ToxR/ToxS proteins, activate the expression of the ToxT regulatory protein. ToxT then directly activates expression of virulence genes that produce

12198-607: The surface of the intestinal epithelium cells. The A1 portion of the A subunit is an enzyme that ADP-ribosylates G proteins , while the A2 chain fits into the central pore of the B subunit ring. Upon binding, the complex is taken into the cell via receptor-mediated endocytosis . Once inside the cell, the disulfide bond is reduced, and the A1 subunit is freed to bind with a human partner protein called ADP-ribosylation factor 6 (Arf6). Binding exposes its active site, allowing it to permanently ribosylate

12312-410: The toxins, causing diarrhea in the infected person and allowing the bacteria to colonize the intestine. Current research aims at discovering "the signal that makes the cholera bacteria stop swimming and start to colonize (that is, adhere to the cells of) the small intestine." Amplified fragment length polymorphism fingerprinting of the pandemic isolates of V. cholerae has revealed variation in

12426-451: The world. Recent major outbreaks are the 2010s Haiti cholera outbreak and the 2016–2022 Yemen cholera outbreak . In October 2016, an outbreak of cholera began in war-ravaged Yemen . WHO called it "the worst cholera outbreak in the world". In 2019, 93% of the reported 923,037 cholera cases were from Yemen (with 1911 deaths reported). Between September 2019 and September 2020, a global total of over 450,000 cases and over 900 deaths

12540-504: Was by that time an established elite choir, that also performed in Stockholm and in Gothenburg. During the latter half of the 19th century, the choir went on tours abroad to Paris (1867, 1878, 1900), Berlin (1898) and has over the years been performing to audiences in many different parts of the world. Orphei Drängar made its first recording during a tour to London in 1907 and performed at

12654-533: Was discovered that several manufacturers had falsified data submitted in seeking FDA authorization to market certain generic drugs. Vitarine Pharmaceuticals of New York, which sought approval of a generic version of the drug Dyazide , a medication for high blood pressure, submitted Dyazide, rather than its generic version, for the FDA tests. In April 1989, the FDA investigated 11 manufacturers for irregularities; and later brought that number up to 13. Dozens of drugs were eventually suspended or recalled by manufacturers. In

12768-534: Was established by the 1902 Biologics Control Act , with additional authority established by the 1944 Public Health Service Act . Along with these Acts, the Federal Food, Drug, and Cosmetic Act applies to all biologic products, as well. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health ; this authority was transferred to the FDA in 1972. The Center for Devices and Radiological Health (CDRH)

12882-629: Was reported; however, the accuracy of these numbers suffer from over-reporting from countries that report suspected cases (and not laboratory confirmed cases), as well as under-reporting from countries that do not report official cases (such as Bangladesh, India and Philippines). Although much is known about the mechanisms behind the spread of cholera, researchers still do not have a full understanding of what makes cholera outbreaks happen in some places and not others. Lack of treatment of human feces and lack of treatment of drinking water greatly facilitate its spread. Bodies of water have been found to serve as

12996-440: Was the first recorded incidence of epidemiological tracking. The primary symptoms of cholera are profuse diarrhea and vomiting of clear fluid. These symptoms usually start suddenly, half a day to five days after ingestion of the bacteria. The diarrhea is frequently described as "rice water" in nature and may have a fishy odor. An untreated person with cholera may produce 10 to 20 litres (3 to 5 US gal) of diarrhea

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