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The data in Table 1 reflect exposure of patients to Basaglar with a mean exposure duration of 49 weeks. The type 2 diabetes population had the following characteristics: Mean age was 59 years and mean duration of diabetes was 11 years. HbA 1c at baseline was 8.
The data in Table 2 reflect exposure of patients to Basaglar with a mean exposure duration of 22 weeks. Common adverse reactions during clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus other than hypoglycemia are listed in Table 1 and Table 2 , respectively. Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Basaglar [see Warnings and Precautions 5.
The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for Basaglar with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.
Some patients taking insulin therapy, including Basaglar have experienced erythema, local edema, and pruritus at the site of injection. These conditions were usually self-limiting. Severe cases of generalized allergy anaphylaxis have been reported [see Warnings and Precautions 5. Some patients taking Basaglar have experienced sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
Administration of insulin subcutaneously, including Basaglar, has resulted in lipoatrophy depression in the skin or lipohypertrophy enlargement or thickening of tissue in some patients [see Dosage and Administration 2. Weight gain has occurred with some insulin therapies including Basaglar and has been attributed to the anabolic effects of insulin and the decrease in glycosuria.
The percent binding of patients positive at baseline on Basaglar did not increase significantly during the study. There was no evidence that these antibodies had an impact on efficacy and safety outcomes. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: For these reasons, comparison of the incidence of antibodies to Basaglar with the incidence of antibodies in other studies or to other products may be misleading.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Medication errors have been reported in which other insulin products, particularly rapid-acting insulins, have been accidentally administered instead of an insulin glargine product.
To avoid medication errors between insulin glargine products and other insulin products, patients should be instructed to always verify the insulin label before each injection. Table 6 includes clinically significant drug interactions with Basaglar. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control.
It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes, insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters, and rapidly decline after delivery.
Careful monitoring of glucose control is essential in these patients. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Basaglar.
There are no well-controlled clinical studies of the use of insulin glargine in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Subcutaneous reproduction and teratology studies have been performed with another insulin glargine product and with regular human insulin in rats and Himalayan rabbits.
This other insulin glargine product was given to female rats before mating, during mating, and throughout pregnancy at dose up to 0. In rabbits, doses of 0. The effects of this other insulin glargine product did not generally differ from those observed with regular human insulin in rats and rabbits.
However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal. Endogenous insulin is present in human milk; it is unknown whether insulin glargine is excreted in human milk.
Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when Basaglar is administered to a nursing woman. Use of Basaglar is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.
The safety and effectiveness of Basaglar in pediatric patients younger than 6 years of age with type 1 diabetes and pediatric patients with type 2 diabetes has not been established. The dosage recommendation when changing to Basaglar in pediatric patients age 6 to 15 years with type 1 diabetes is the same as that described for adults [see Dosage and Administration 2.
As in adults, the dosage of Basaglar must be individualized in pediatric patients age 6 to 15 years with type 1 diabetes based on metabolic needs and frequent monitoring of blood glucose. In the pediatric clinical trial, pediatric patients age 6 to 15 years with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in trials with type 1 diabetes [see Adverse Reactions 6. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Nevertheless, caution should be exercised when Basaglar is administered to geriatric patients. In elderly patients with diabetes, the initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions.
Hypoglycemia may be difficult to recognize in the elderly. The effect of renal impairment on the pharmacokinetics of Basaglar has not been studied.
Some studies with human insulin have shown increased circulating levels of insulin in patients with renal failure. Frequent glucose monitoring and dose adjustment may be necessary for Basaglar in patients with renal impairment [see Warnings and Precautions 5. The effect of hepatic impairment on the pharmacokinetics of Basaglar has not been studied.
However, as with all insulin products, more frequent glucose monitoring and dose adjustment may be necessary for Basaglar in patients with hepatic impairment [see Warnings and Precautions 5. Excess insulin administration relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia [see Warnings and Precautions 5.
Mild episodes of hypoglycemia can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or physical activity level may be needed. Sustained carbohydrate intake and observation may be necessary because hypoglycemia may recur after apparent clinical recovery.
Hypokalemia must be corrected appropriately. Basaglar insulin glargine injection is a long-acting insulin for subcutaneous use. Insulin glargine is a recombinant human insulin analog [see Clinical Pharmacology 12 ]. Basaglar is produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli K12 as the production organism.
Insulin glargine differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Insulin glargine has the following structural formula:. Basaglar is a clear, colorless, sterile aqueous solution of insulin glargine. The pH is adjusted by addition of aqueous solutions of hydrochloric acid and sodium hydroxide.
Basaglar has a pH of approximately 4. The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analog lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.
The pharmacodynamic profile for Basaglar was determined after subcutaneous administration of a single 0. The median time to maximum effect of Basaglar measured by the peak rate of glucose infusion was approximately The pharmacodynamic profile of Basaglar following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. A euglycemic clamp study in 20 patients with type 1 diabetes showed a similar pharmacodynamic profile with a sustained glucose lowering activity over 24 hours following a single 0.
After subcutaneous injection of 0. The time course of action of insulins, including insulin glargine, may vary between individuals and within the same individual. The pharmacokinetic profile for Basaglar was determined after subcutaneous administration of a single 0.
The median time to maximum serum insulin concentration was 12 hours after injection. On average, serum insulin concentrations declined to baseline by approximately 24 hours.
The in vitro activity of M1 and M2 were similar to that of insulin. Age, Race, and Gender: Effect of age, race, and gender on the pharmacokinetics of Basaglar has not been evaluated. Effect of BMI on the pharmacokinetics of Basaglar has not been evaluated.
In mice and rats, standard two-year carcinogenicity studies with another insulin glargine product were performed at doses up to 0. The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats statistically significant and male mice not statistically significant in acid vehicle containing groups.
These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown. Another insulin glargine product was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells Ames- and HGPRT-test and in tests for detection of chromosomal aberrations cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters.
In a combined fertility and prenatal and postnatal study of another insulin glargine product in male and female rats at subcutaneous doses up to 0. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH insulin. In general, the reduction in glycated hemoglobin HbA 1c with this other insulin glargine product was similar to that with NPH insulin.
Randomized were adults with type 1 diabetes. Mean age was The mean BMI was approximately Observed HbA 1c data at 24 weeks were available from Regular human insulin was administered before each meal. This other insulin glargine product was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily.
In Study A, the average age was The mean duration of diabetes was In Study B, the average age was The majority of patients were Caucasian Insulin lispro was used before each meal. This other insulin glargine product was administered once daily at bedtime and NPH insulin was administered once or twice daily. The average age was Type 1 Diabetes — Pediatric see Table 9. Patients were randomized to either this other insulin glargine product administered once daily at bedtime or NPH insulin administered once or twice daily.
The mean duration of diabetes was 4. Similar effects on HbA 1c see Table 9 were observed in both treatment groups. A total of patients were randomized. Three patients randomized to Basaglar did not receive study drug and were not included in efficacy analysis. The average age was approximately 59 years. This other insulin glargine product administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA 1c and fasting glucose see Table The rate of hypoglycemia was similar in this other insulin glargine product and NPH insulin treated patients [see Adverse Reactions 6.
Regular human insulin was used before meals, as needed. This other insulin glargine product had similar effectiveness as either once- or twice daily NPH insulin in reducing HbA 1c and fasting glucose see Table 11 with a similar incidence of hypoglycemia [see Adverse Reactions 6. While most of the Centers are located in the Washington, D. The Office of Regulatory Affairs is considered the "eyes and ears" of the agency, conducting the vast majority of the FDA's work in the field.
Consumer Safety Officers, more commonly called Investigators, are the individuals who inspect production and warehousing facilities, investigate complaints, illnesses, or outbreaks, and review documentation in 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.
Districts are based roughly on the geographic divisions of the federal court system. Each district comprises a main district office and 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 to investigate criminal cases. OCI agents pursue and develop cases where individuals and companies have committed criminal actions, such as fraudulent claims, or knowingly and willfully shipping known adulterated goods in interstate commerce.
In many cases, OCI pursues cases involving Title 18 violations e. OCI is a smaller branch, comprising about agents nationwide. Often local and state government agencies also work with the FDA to provide regulatory inspections and enforcement action. Much of these expenditures are for goods imported into the United States; the FDA is responsible for monitoring imports.
Pharmaceutical firms pay the majority of these fees,  which are used to expedite drug reviews. In many cases these responsibilities are shared with other federal agencies. The programs for safety regulation vary widely by the type of product, its potential risks, and 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 In June , the FDA released a statement regarding new guidelines to help food and drug manufacturers "implement protections against potential attacks on the U.
Health Canada and the United States Food and Drug Administration FDA under the RCC mandate, undertook the "first of its kind" initiative by selecting "as its first area of alignment common cold indications for certain over-the-counter antihistamine ingredients GC The regulation of food and dietary supplements by the U.
Pursuant to the Federal Food, Drug, and Cosmetic Act "the 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 about 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 man-made substances that are not intentionally introduced into food, but nevertheless end up in it , and dietary supplements. Specific standards 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. The FDA does not approve applied coatings used in the food processing industry.
Through their governing of processes, however, the FDA does have a set of regulations that cover the formulation, manufacturing, and use of nonstick coatings. The Center for Drug Evaluation and Research uses different requirements for the three main drug product types: A drug is considered "new" if it is made by a different manufacturer, uses different excipients or inactive ingredients, is used for a different purpose, or undergoes any substantial change.
The most rigorous requirements apply to new molecular entities: A drug that is approved is said to be "safe and effective when used as directed". 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 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.
The FDA's Office of Prescription Drug Promotion reviews and regulates prescription drug advertising and promotion through surveillance activities and issuance of enforcement letters to pharmaceutical manufacturers.
Advertising and promotion for over-the-counter drugs is regulated by the Federal Trade Commission. The drug advertising regulation  contains two broad requirements: Also, an advertisement must contain a "fair balance" between the benefits and the risks side effects of a drug.
The term off-label refers to drug usage for indications other than those approved by the FDA. They must report unexpected serious and fatal adverse drug events within 15 days, and other events on a quarterly basis.
While this remains the primary tool of postmarket safety surveillance , FDA requirements for postmarketing risk management are increasing. As a condition of approval, a sponsor may be required to conduct additional clinical trials , called Phase IV trials.
Generic drugs are chemical equivalents of name-brand drugs whose patents have expired. Food and Drug Administration FDA requires scientific evidence that the generic drug is interchangeable with or therapeutically equivalent to the originally approved drug.
In , a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. 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 Mylan eventually filed suit against two former FDA employees and four drug-manufacturing companies, charging that corruption within the federal agency resulted in racketeering and in violations of antitrust law.
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 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 , the FDA investigated 11 manufacturers for irregularities; and later brought that number up to Dozens of drugs were eventually suspended or recalled by manufacturers. In the early s, the U.
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 drugs like aspirin are drugs and combinations that do not require a doctor's prescription. Many OTC drug ingredients had been previously approved prescription drugs now deemed safe enough for use without a medical practitioner 's supervision like ibuprofen.
In , 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. The Center for Biologics Evaluation and Research is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. 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 was established by the Biologics Control Act , with additional authority established by the Public Health Service Act. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health ; this authority was transferred to the FDA in The Center for Devices and Radiological Health CDRH 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.
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 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 for medical devices that prove they are "substantially equivalent" to 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 it 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. 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.
The FDA regulates cosmetics labeling, and cosmetics that have not been safety tested must bear a warning to that effect. Though the cosmetic industry is predominantly responsible in ensuring the safety of its products, the FDA also has the power to intervene when necessary to protect the public but in general does not require pre-market approval or testing.
Companies are required to place a warning note on their products if they have not been tested. Experts in cosmetic ingredient reviews also play a role in monitoring safety through influence on the use of ingredients, but also lack legal authority. Overall the organization has reviewed about 1, ingredients and has suggested that several hundred be restricted, but there is no standard or systemic method for reviewing chemicals for safety and a clear definition of what is meant by 'safety' so that all chemicals are tested on the same basis.
CVM's primary focus is on medications that are used in food animals and ensuring that they do not affect the human food supply. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers. In , Congress passed a law requiring color warnings on cigarette packages and on printed advertising, in addition to text warnings from the U.
The nine new graphic warning labels were announced by the FDA in June and were scheduled to be required to appear on packaging by September The implementation date is uncertain, due to ongoing proceedings in the case of R.
Food and Drug Administration. Reynolds , Lorillard , Commonwealth Brands Inc. A First Amendment lawyer, Floyd Abrams , is representing the tobacco companies in the case, contending requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny.
District Court for the District of Columbia temporarily halted the new labels, likely delaying the requirement that tobacco companies display the labels.