Biosimilars Regulation in the United States and FDA Approved Biosimilars from 2015-2018

2020 ◽  
Vol 7 (1) ◽  
pp. 12-29
Author(s):  
Vikram ◽  
Aakash Deep ◽  
Manita ◽  
Avtar C. Rana ◽  
Monu Yadav ◽  
...  
Keyword(s):  
Price Competition ◽  
Clinical Performance ◽  
Treatment Options ◽  
The United States ◽  
Living Cells ◽  
Human Beings ◽  
Biological Products ◽  
Technical Requirements ◽  
Manufacturing Techniques ◽  
High Level

Background: Biological products are the chemicals in the form of medicines that are prepared from the living cells through highly intricate manufacturing techniques that should be handled and managed under favorable conditions. The regulation of the biosimilar products consists of significant challenges, since they are part of the growing sector of the pharmaceutical industry and normally used by human beings. The regulatory framework and the technical requirements of the US biosimilars program involve a stepwise approach that relies heavily on analytical methods to demonstrate through a “totality of the evidence” that a proposed product is biosimilar to its reference product. By integrating analytical, pharmacological, and clinical data, each of which has limitations, a high level of confidence can be reached regarding clinical performance. The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the health reform (Affordable Care Act). Objective: The current manuscript will provide the information regarding the regulation of Biosimilars products with the detail of biosimilar USER fees structure and the list of approved biosimilar by FDA from 2015- 2018. Conclusion: Research is continually developing more biological products that will help treat medical conditions or add some innovation to the existing treatment options. Biosimilars and reference products are generated in the living cells and require trained expertise as well as technology for biologics being usually highly effective compared to small molecule drugs. These are usually specific against the respective target, which generally produces lesser side effects and low toxicity. FDA’s regulatory authority for the approval of biologics is under PHS (Public Health Service Act) which are also suggested to regulate under the Federal Food, Drug and Cosmetics Act (FD&C). Biosimilars can help expand access to high-quality treatment options for doctors and patients, as well as reduce costs for the healthcare system.

scholarly journals Regulatory Prototype for Biological Products in the United States

2021 ◽  
pp. 60-72
Author(s):  
G. M. Pavithra ◽  
N. Venugopal
Keyword(s):  
Price Competition ◽  
Generic Drugs ◽  
The United States ◽  
Biological Application ◽  
Biological Products ◽  
License Application ◽  
The Us ◽  
High Degree ◽  
Degree Of Similarity ◽  
Improve Access

Biological products are used for the treatment of many disease, so the biological application submitted for the approval of products are also increasing. The progress of a biosimilarproduct is more difficult and expensive than a small molecule generic product. Biosimilars are not true generic drugs, but demonstrate a high degree of similarity to the reference biological product. In order to improve access to costly biological treatments, a biosimilar pathway in the US was established under the Biologics Price Competition and Innovation Act of 2009. The study highlighted the “Regulatory prospective for the registration of Biological products in US” and a brief description about the development, Manufacturing and approval process of biosimilar products. This article is also focused on the regulatory framework, Biological License Application, Purple book, and Pharmacovigilance of biological products.

scholarly journals 1227. Plazomicin Susceptibility Testing using ETEST® MIC for Enterobacterales

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S634-S634
Author(s):  
Yun Ying ◽  
Tom Armstrong ◽  
Laurine Blanchard ◽  
Michael Kresken ◽  
Gilles Zambardi ◽  
...  
Keyword(s):  
Error Rate ◽  
Clinical Performance ◽  
Treatment Options ◽  
Klebsiella Oxytoca ◽  
Reference Method ◽  
Ambient Air ◽  
Performance Criteria ◽  
Major Error ◽  
High Level ◽  
Tract Infections

Abstract Background Plazomicin (PLZ) approved by FDA in June of 2018, is an aminoglycoside class antibacterial indicated for the treatment of adults with complicated urinary tract infections (cUTI) including pyelonephritis caused by Enterobacterales. It is used in patients who have limited or no alternative treatment options, e.g. CRE and MDRO patients. The drug has bactericidal activity, it is active against organisms producing ESBL, Carbapenemase and aminoglycoside-modifying enzymes. The purpose of this study was to compare ETEST® PLZ bioMérieux to the broth microdilution reference method (BMD) for Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and pneumoniae, Morganella morganii, Providencia stuartii, Proteus mirabilis and vulgaris and Serratia marcescens isolates. Methods A total of 598 isolates were tested by ETEST® (PLZ) and BMD at four clinical trial sites. Isolates were subcultured on tryptic soy or Columbia agar plates supplemented with 5% sheep blood. Suspensions of the isolates were prepared in 0.85% saline, which were used to inoculate BMD and Mueller Hinton agar for ETEST®. Results were read after 16-20 hours incubation at 35°C +2°C in ambient air. QC organisms were tested with each run following CLSI QC guidelines. Results were analyzed using FDA breakpoints for PLZ (Susceptible <2 µg/mL, Intermediate 4 µg/mL, Resistant >8 µg/mL). Performance was evaluated using FDA performance criteria, EA and CA (≥ 90%), major error rate (≤3.0%) and very major error rate (≤2.0%). Results Conclusion ETEST® PLZ clinical performance met the FDA acceptance criteria and was found useful for determining Plazomicin MIC of Enterobacterales, including ESBL, CRE (MBL, KPC, Oxa-48), high level AmpC and aminoglycoside resistant strains. Percent susceptibility of Plazomicin is at 80% among the 598 isolates tested, the mode MIC is 0.5 ug/ml as Susceptible. Disclosures Tom Armstrong, BS, bioMérieux (Employee) Laurine Blanchard, PhD, bioMérieux (Employee) Michael Kresken, PhD, bioMérieux (Scientific Research Study Investigator, Research Grant or Support) Gilles Zambardi, biomerieux (Employee) Marion Pompilio, BioMérieux (Employee)

scholarly journals 803. Overcoming β-Lactam Resistance in Mycobacterium abscessus

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S288-S288 ◽  
Author(s):  
Elizabeth Story-Roller ◽  
Gyanu Lamichhane
Keyword(s):  
Inhibitory Concentration ◽  
Treatment Options ◽  
The United States ◽  
Mycobacterium Abscessus ◽  
Nontuberculous Mycobacterium ◽  
Synergistic Activity ◽  
Drug Resistant ◽  
High Level ◽  
Enzyme Class

Abstract Background Mycobacterium abscessus (Mab) is an environmentally acquired nontuberculous mycobacterium (NTM) that causes severe pulmonary infections in patients with chronic lung disease, such as cystic fibrosis (CF). The incidence of drug-resistant Mab infections in CF patients in the United States is steadily rising, making it increasingly difficult to manage these often chronic and incurable infections. Mab requires two enzyme classes, l,d- and d,d-transpeptidases, to synthesize peptidoglycan (PG); an integral component of the bacterial cell wall. Each enzyme class is uniquely susceptible to different classes of β-lactam antibiotics. We hypothesize that a combination of two β-lactams, each specific for an enzyme class, will optimally inhibit PG synthesis and swiftly kill Mab, with potential to overcome drug-resistance. Methods Paired antibiotic combinations were tested in vitro for synergy against the Mab reference strain ATCC 19977 at 106 CFU/mL, per CLSI guidelines. Combinations included two β-lactams, a β-lactam and a β-lactamase inhibitor, or a β-lactam and a rifamycin. The minimum inhibitory concentration (MIC) of each drug was initially confirmed via broth microdilution assay. A validated checkerboard assay was used to determine the fractional inhibitory concentration index (FICI) for each combination to identify pairs that exhibit synergistic activity against Mab. Results Of the initial 227 combinations screened, 18 pairs exhibited a high level of synergy (FICI ≤ 0.5). Half of these were combinations of two β-lactams. The average reduction in MIC for each drug in combination was at least fourfold, with 8/18 combinations exhibiting reductions greater than eightfold. Although MIC breakpoints against Mab have not been established for all of the antibiotics tested in this study, the MICs of at least seven combinations were within the therapeutic range. Conclusion Comprehensive inhibition of essential enzymes involved in PG synthesis requires more than one β-lactam antibiotic, and this phenomenon is hypothesized to be the basis for observed synergy between β-lactams. Some of the combinations reduced MICs to within therapeutically achievable levels, potentially leading to vital new treatment options against drug-resistant Mab. Disclosures All authors: No reported disclosures.

Some Materials Concerns in Nuclear Waste Management

MRS Bulletin ◽  
1992 ◽  
Vol 17 (3) ◽  
pp. 43-45
Author(s):  
Regina L. Hunter
Keyword(s):  
Power Plants ◽  
The United States ◽  
Department Of Energy ◽  
Radioactive Material ◽  
High Level Waste ◽  
Human Beings ◽  
Spent Fuel ◽  
Waste Container ◽  
High Level ◽  
The U.S

The U.S. Environmental Protection Agency (EPA) has determined that deep geologic disposal is appropriate for three types of radioactive waste generated in the United States: spent fuel, high-level waste, and transuranic waste. Spent fuel is nuclear fuel that has been discharged from a reactor after irradiation. High-level waste (HLW) is the highly radioactive material that remains after the reprocessing of spent fuel to recover uranium or plutonium. Transuranic (TRU) waste is any waste material contaminated with more than 100 nCi/g of elements having atomic numbers greater than 92 and half-lives longer than 20 years. Spent fuel and HLW can result from either commercial or governmental activities, although no commercially generated spent fuel has been reprocessed since 1972. TRU waste results primarily from the design and manufacture of nuclear weapons, not from nuclear power plants.The physical characteristics of TRU waste differ substantially from those of spent fuel and HLW. This imposes different requirements on materials associated with containment and isolation, so TRU waste will be discussed separately from spent fuel and HLW Because all three are judged to be particularly dangerous to human beings and the environment, the EPA standard requires a demonstration of adequate 10,000-year performance of geologic repositories for these radioactive wastes. The U.S. Department of Energy (DOE) is responsible for implementing the standard by designing, siting, and building the repositories.This article briefly describes TRU waste, HLW, and spent fuel and the two repositories currently planned by DOE. It con cludes by offering some observations on materials compatibility among waste, container materials, and host rock.

scholarly journals The United States, the West and the Rest of the World

2001 ◽  
Author(s):  
Johan Galtung
Keyword(s):  
United States ◽  
Deep Level ◽  
The United States ◽  
Human Beings ◽  
The West ◽  
State Terrorism ◽  
The World ◽  
High Level ◽  
The Military ◽  
Very High

The world will never be the same again after the terrible attack on the economic U.S., the military U.S., the foreign policy U.S., and on human beings like all of us. We embrace the victims of the violence, of all violence, in deep grief, and express our hope that perpetrators will be brought to justice. Violence at this level can only be explained by a very high level of dehumanisation of the victims in the minds of the aggressors, often due to a very deep level of unresolved, basic conflict. The word “terrorism” may describe the tactics, but like “state terrorism” only portrays the perpetrator as evil, satanic, and does not go to the roots of the conflict.

Social inequality in the evolution of human societies

2019 ◽  
pp. 98-120
Author(s):  
Georgi Derluguian
Keyword(s):  
Social Inequality ◽  
Large Scale ◽  
Human Beings ◽  
Mass Violence ◽  
Public And Private ◽  
Tangible Assets ◽  
Transition To Agriculture ◽  
New Institutions ◽  
High Level ◽  
Political Economic

The author develops ideas about the origin of social inequality during the evolution of human societies and reflects on the possibilities of its overcoming. What makes human beings different from other primates is a high level of egalitarianism and altruism, which contributed to more successful adaptability of human collectives at early stages of the development of society. The transition to agriculture, coupled with substantially increasing population density, was marked by the emergence and institutionalisation of social inequality based on the inequality of tangible assets and symbolic wealth. Then, new institutions of warfare came into existence, and they were aimed at conquering and enslaving the neighbours engaged in productive labour. While exercising control over nature, people also established and strengthened their power over other people. Chiefdom as a new type of polity came into being. Elementary forms of power (political, economic and ideological) served as a basis for the formation of early states. The societies in those states were characterised by social inequality and cruelties, including slavery, mass violence and numerous victims. Nowadays, the old elementary forms of power that are inherent in personalistic chiefdom are still functioning along with modern institutions of public and private bureaucracy. This constitutes the key contradiction of our time, which is the juxtaposition of individual despotic power and public infrastructural one. However, society is evolving towards an ever more efficient combination of social initiatives with the sustainability and viability of large-scale organisations.

The Hard Sell

2017 ◽  
Author(s):  
Peter Scott
Keyword(s):  
Price Competition ◽  
New Economy ◽  
The United States ◽  
Vacuum Cleaner ◽  
Firm Level ◽  
Direct Sales ◽  
Cost Distribution ◽  
Household Cleaning ◽  
Time Savings ◽  
Cleaning Methods

The vacuum cleaner was an archetypal new economy product of the early twentieth century. It offered both major time savings and qualitative advantages over previous household cleaning methods—the brush, broom, and manual carpet sweeper—and was sold in a novel way (by household demonstration). The direct sales techniques pioneered by vacuum manufacturers in the United States were to have a profound impact on the way vacuums were sold in Britain, and globally. Yet by 1939 their household diffusion was relatively slow compared to refrigerators or washing machines. This chapter explores why the industry evolved a structure based on high prices, high cost distribution methods (door-to-door sales), and a strong emphasis on non-price competition, based on differentiation through features. It also shows how door-to-door selling eventually came to constitute both a key firm-level competitive advantage and a substantial industry-level constraint on product diffusion.

Student Privacy and the Law in the Internet Age

2019 ◽  
Author(s):  
Leah Plunkett ◽  
Urs Gasser ◽  
Sandra Cortesi
Keyword(s):  
Learning Environments ◽  
School Environment ◽  
Privacy Protection ◽  
Data Privacy ◽  
Digital Technologies ◽  
The United States ◽  
Legal Framework ◽  
Privacy Law ◽  
Student Privacy ◽  
High Level

New types of digital technologies and new ways of using them are heavily impacting young people’s learning environments and creating intense pressure points on the “pre-digital” framework of student privacy. This chapter offers a high-level mapping of the federal legal landscape in the United States created by the “big three” federal privacy statutes—the Family Educational Rights and Privacy Act (FERPA), the Children’s Online Privacy Protection Act (COPPA), and the Protection of Pupil Rights Amendment (PPRA)—in the context of student privacy and the ongoing digital transformation of formal learning environments (“schools”). Fissures are emerging around key student privacy issues such as: what are the key data privacy risk factors as digital technologies are adopted in learning environments; which decision makers are best positioned to determine whether, when, why, and with whom students’ data should be shared outside the school environment; what types of data may be unregulated by privacy law and what additional safeguards might be required; and what role privacy law and ethics serve as we seek to bolster related values, such as equity, agency, and autonomy, to support youth and their pathways. These and similar intersections at which the current federal legal framework is ambiguous or inadequate pose challenges for key stakeholders. This chapter proposes that a “blended” governance approach, which draws from technology-based, market-based, and human-centered privacy protection and empowerment mechanisms and seeks to bolster legal safeguards that need to be strengthen in parallel, offers an essential toolkit to find creative, nimble, and effective multistakeholder solutions.

scholarly journals Beyond Religiosity: A Model to Explain Spirituality Among Middle-Aged and Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 413-414
Author(s):  
Carlyn Vogel ◽  
Debra Dobbs ◽  
Brent Small
Keyword(s):  
United States ◽  
Older Adults ◽  
Good Life ◽  
Multinomial Logistic Regression ◽  
College Experience ◽  
The United States ◽  
Strong Connection ◽  
Deep Appreciation ◽  
The World ◽  
High Level

Abstract Spirituality is difficult to define as researchers assign it different meanings and individuals’ perceptions can vary. For example, spirituality may connect to religiosity, while others consider religiosity a less significant part of spirituality. This study investigates factors outside of religiosity that are significantly associated with spirituality to inform the characteristics of the concept. Webster’s (2004) existential framework of spirituality was used to guide variable selection. The National Survey of Midlife in the United States wave three (MIDUS 3; 2013-2014; n = 2,594; Mage = 63.5, SD = 11, range = 39–92) was used to examine individuals’ reported levels of spirituality. Multinomial logistic regression was conducted to examine factors related to low and high levels of spirituality compared to a moderate level. Participants with low spirituality were more likely to be male, less likely to be mindful, mediate/chant, feel a strong connection to all life, to indicate that they cannot make sense of the world, and to be religious. Participants with high spirituality were more likely to be female, have at least some college experience, be mindful, meditate/chant, feel deep inner peace, have a sense of deep appreciation, think that a sense of purpose is important for a good life, and have a high level of religiosity. Framed by Webster’s conceptual model, the current study observed that religiosity is significantly associated with spirituality and that other mindfulness-based aspects are also present within this concept. Incorporating mindfulness with religious efforts will more accurately and holistically address spirituality.

Geographic Variation in Dominance of Spinosad Resistance in Colorado Potato Beetles (Coleoptera: Chrysomelidae)

2020 ◽  
Author(s):  
Coby Klein ◽  
Mitchell Baker ◽  
Andrei Alyokhin ◽  
David Mota-Sanchez
Keyword(s):  
New York ◽  
Long Island ◽  
New York State ◽  
The United States ◽  
Island Population ◽  
Potato Beetle ◽  
Rate Of Increase ◽  
Short Period ◽  
Leptinotarsa Decemlineata Say ◽  
High Level

Abstract Eastern New York State is frequently the site of Colorado potato beetle (Leptinotarsa decemlineata, Say) populations with the highest observed levels of insecticide resistance to a range of active ingredients. The dominance of a resistant phenotype will affect its rate of increase and the potential for management. On organic farms on Long Island, L. decemlineata evolved high levels of resistance to spinosad in a short period of time and that resistance has spread across the eastern part of the Island. Resistance has also emerged in other parts of the country as well. To clarify the level of dominance or recessiveness of spinosad resistance in different parts of the United States and how resistance differs in separate beetle populations, we sampled in 2010 beetle populations from Maine, Michigan, and Long Island. In addition, a highly resistant Long Island population was assessed in 2012. All populations were hybridized with a laboratory-susceptible strain to determine dominance. None of the populations sampled in 2010 were significantly different from additive resistance, but the Long Island population sampled in 2012 was not significantly different from fully recessive. Recessive inheritance of high-level resistance may help manage its increase.

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