scholarly journals Physicochemical and Biological Characterization of a Biosimilar Trastuzumab

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Carlos A. López-Morales ◽  
Mariana P. Miranda-Hernández ◽  
L. Carmina Juárez-Bayardo ◽  
Nancy D. Ramírez-Ibáñez ◽  
Alexis J. Romero-Díaz ◽  
...  
Keyword(s):  
Reference Product ◽  
World Health ◽  
Malignant Neoplasms ◽  
Pharmacological Studies ◽  
Comparability Exercise ◽  
Potential Impact ◽  
Health Organization ◽  
High Degree ◽  
Degree Of Similarity

According to the World Health Organization, the incidence of malignant neoplasms and endocrine, blood, and immune disorders will increase in the upcoming decades along with the demand of affordable treatments. In response to this need, the development of biosimilar drugs is increasing worldwide. The approval of biosimilars relies on the compliance with international guidelines, starting with the demonstration of similarity in their physicochemical and functional properties against the reference product. Subsequent clinical studies are performed to demonstrate similar pharmacological behavior and to diminish the uncertainty related to their safety and efficacy. Herein we present a comparability exercise between a biosimilar trastuzumab and its reference product, by using a hierarchical strategy with an orthogonal approach, to assess the physicochemical and biological attributes with potential impact on its pharmacokinetics, pharmacodynamics, and immunogenicity. Our results showed that the high degree of similarity in the physicochemical attributes of the biosimilar trastuzumab with respect to the reference product resulted in comparable biological activity, demonstrating that a controlled process is able to provide consistently the expected product. These results also constitute the basis for the design of subsequent delimited pharmacological studies, as they diminish the uncertainty of exhibiting different profiles.

scholarly journals Comprehensive Review on Manufacturing Process and Characterization of Biosimilar Drugs

2018 ◽  
Vol 6 (2) ◽  
pp. 53-62
Author(s):  
Yasir Mehmood
Keyword(s):  
Clinical Studies ◽  
Reference Product ◽  
World Health ◽  
Biological Testing ◽  
Immune Disorders ◽  
Comprehensive Review ◽  
The World ◽  
International Regulations ◽  
Health Organization

According to the World Health Organization, the prevalence of deadly neoplasms and endocrine, blood, and immune disorders will observe an incredible rise in coming decades followed by increased demand of affordable treatments. Keeping this incident in mind, the development of similar drugs is increasing globally. The sanction of such drugs depends on the conformity with international regulations, which starts with physical presentation of similarities that lie in their physiochemical and functional properties in contrast to the relating product. Consecutive clinical studies are done to physically present similar pharmacological behaviour and to curtail the distrust in relation to their safety points and effectiveness. Here we are to present a physical and biological testing of biosimilar and its reference product, by making use of different procedures and approaches, to judge the physicochemical and biological peculiarities with every possible impact it can cause on its pharmacokinetics, pharmacodynamics, and immunogenicity.Int. J. Appl. Sci. Biotechnol. Vol 6(2): 53-62 

scholarly journals Regulatory outlook from concept to commercialization of Biosimilars in Brazil market

2020 ◽  
Vol 8 (2) ◽  
pp. 67-74
Author(s):  
Raj Shekhar ◽  
P Muralidharan ◽  
Namrata Hallur ◽  
Sangamesh B Puranik
Keyword(s):  
Reference Product ◽  
Expression System ◽  
Living Organism ◽  
World Health ◽  
Biological Products ◽  
Synthetic Drugs ◽  
Choice Of Treatment ◽  
Comparability Exercise ◽  
Health Organization ◽  
Market Valuations

Biological products or biopharmaceuticals are medicinal products derived from living organism systems and manufactured by using modern biotechnology that differ widely from the conventional synthetic drugs. They are much larger and more complex molecules with inherent diversity; hence, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilars endeavor to copy the original technology leading to the production of innovative biotechnological medicines to obtain a product which is similar to the reference product. These products reported to improve the treatment landscape for multiple diseases, particularly in the areas of oncology, blood disorders, rheumatology, endocrinology and are becoming choice of treatment regimen due to policy push by governments for it’s affordability without comprising on quality, safety and efficacy. Pharmaceutical exports from Brazil increased by around 41% between 2009 and 2013, touching a high of U.S. $1.516 billion. The valuation of Brazilian pharma markets has shown double digit growth in the past decade. Between 2012 and 2015, market valuations have increased from U.S. $25.2 billion to U.S. $35.3 billion. Biosimilarity is based on a comprehensive comparability exercise wherein unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency shadows the key principles established by the World Health Organization for the assessment of biosimilarity. However, the regulations also widen the gap by having standalone application pathway that does not require the usual comparability exercise with the reference product, originating non-biosimilar copies. Interchangeability and the use of nonproprietary names are not regulated. The objective of this manuscript is to explore the Brazilian Regulatory outlook from concept to commercialization of Biosimilars.  

Mixed Adenocarcinomas of the Lung: Place in New Proposals in Classification, Mandatory for Target Therapy

2010 ◽  
Vol 134 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Marco Chilosi ◽  
Bruno Murer
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
World Health Organization ◽  
Cell Biology ◽  
Small Cell ◽  
World Health ◽  
Malignant Neoplasms ◽  
New Classification ◽  
Therapeutic Decisions ◽  
Health Organization

Abstract Context.—Lung cancer is one of the most frequent and lethal malignant neoplasms, but knowledge regarding the molecular basis of its pathogenesis is far from complete due to the striking diversity of different forms. The current lung cancer classification (World Health Organization 2004) can efficiently distinguish clinically relevant major subtypes (small cell and non–small cell carcinomas), but its results are partly inadequate when facing prognostic and therapeutic decisions for non–small cell carcinomas, especially for the group of tumors classified as adenocarcinoma. Lung adenocarcinoma comprises a heterogeneous group of tumors characterized by diverse morphologic features and molecular pathogenesis. The category of mixed adenocarcinomas includes most adenocarcinomas (approximately 80%) and, according to World Health Organization criteria, is defined by the occurrence of a mixed array of different patterns (acinar, papillary, bronchioloalveolar, solid with mucin). The histologic recognition of mixed adenocarcinoma is subjective and cannot consistently discriminate between responders and nonresponders to new targeted therapies (eg, tyrosine kinase inhibitors). Diagnostic problems are mainly related to the poor reproducibility of histologic criteria, especially when applied in small biopsies and cytology, and to the difficulty in assigning each form to a precisely defined entity, as needed by updated therapeutic approaches. In this evolving scenario, pathologists face new challenging diagnostic roles that include not only the precise morphologic definition of carcinoma subtypes but also their molecular characterization. Objective.—To use a comprehensive critical analysis reconciling the overwhelming variety of biologic, morphologic, molecular, and clinical data to define new classification schemes for lung adenocarcinoma. Data Sources.—Scientific literature and personal data were used. Conclusions.—A new classification approach should redefine lung adenocarcinoma heterogeneity reconciling classic morphology, immunophenotypic and molecular features of neoplastic cells, and also relevant information provided by stem cell biology. This approach, which has been already successfully applied in World Health Organization classification of other tumors, could improve the recognition of new reproducible profiles for adenocarcinomas, more closely and reproducibly related to clinical features and response to specific therapies, limiting the use of “wastebasket” categories such as mixed adenocarcinoma.

scholarly journals Strengths and weaknesses of the Brazilian regulation on biosimilars: A critical view of the regulatory requirements for biosimilars in Brazil

2018 ◽  
Vol 10 (12) ◽  
pp. 253-259 ◽  
Author(s):  
Marcos Renato de Assis ◽  
Valdair Pinto
Keyword(s):  
Conflicts Of Interest ◽  
Expression System ◽  
World Health ◽  
Regulatory Requirements ◽  
Biological Products ◽  
Synthetic Drugs ◽  
Comparability Exercise ◽  
The Face ◽  
The Usa ◽  
Health Organization

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name ‘biosimilar’. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

scholarly journals Molecular Characterization of S Locus Genes, SLG and SRK, in a Pollen-Recessive Self-Incompatibility Haplotype of Brassica rapa L

Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1587-1597 ◽  
Author(s):  
Katsunori Hatakeyama ◽  
Takeshi Takasaki ◽  
Masao Watanabe ◽  
Kokichi Hinata
Keyword(s):  
Brassica Rapa ◽  
Genomic Dna ◽  
Transmembrane Domain ◽  
Brassica Species ◽  
Self Incompatibility ◽  
S Locus ◽  
Intron Sequence ◽  
High Degree ◽  
Degree Of Similarity

Abstract In Brassica species that exhibit self-incompatibility, two genes, SLG and SRK, at the S locus are involved in the recognition reaction with self and non-self pollen. From a pollen-recessive S29 haplotype of Brassica rapa, both cDNA and genomic DNA clones for these two genes were isolated and characterized. The nucleotide sequence for the S domain of SRK29 showed a high degree of similarity with that of SLG29, and they belong to Class II type. RNA gel blot analysis showed that the transcript of SLG29 consisted of the first and second exons, and no other transcript containing any part of the intron sequence was detected. Because no transmembrane domain was encoded by the second exon of SLG29, SLG29 was designated a secreted type glycoprotein. SLGs of two other pollen-recessive haplotypes, S40 and S44, of B. rapa also had a similar structure to that of SLG29. Previously, SLG2 from a pollen-recessive haplotype, S2, of Brassica oleracea was found to produce two different transcripts, one for the secreted type glycoprotein and the other for a putative membrane-anchored form of SLG. Therefore, the nature of these SLGs from pollen-recessive haplotypes of B. rapa is different from that of SLG2 of B. oleracea.

Emergence of a High-Grade Sarcoma in a Recurrent Meningioma: Malignant Progression or Collision Tumor?

2011 ◽  
Vol 135 (7) ◽  
pp. 935-940
Author(s):  
Buge Oz ◽  
Melike Pekmezci ◽  
Reza Dashti ◽  
Kutlay Karaman ◽  
Cengiz Kuday ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Neurofibromatosis Type ◽  
Collision Tumor ◽  
World Health ◽  
Malignant Neoplasms ◽  
High Grade ◽  
Multiple Meningiomas ◽  
Short Period ◽  
High Grade Sarcoma ◽  
Health Organization

Abstract Anaplastic meningiomas that resemble sarcomas often reveal clues to their meningothelial differentiation or develop in a plausible setting that confirms their meningothelial origin. Malignant mesenchymal neoplasms without obvious evidence of meningothelial differentiation or origin are more likely to be true primary or metastatic sarcomas. Because of their clinical and biological differences, it is important to distinguish anaplastic meningioma from a sarcoma. We present a 67-year-old woman with multiple meningiomas, who developed a high-grade spindle cell tumor 6 months after the resection of a World Health Organization grade I meningioma. It was not clear whether this tumor represented a malignant transformation of meningioma or a primary sarcoma. Malignant transformation of a meningioma is exceptional within this short period and a coexisting sarcoma and meningioma are equally uncommon. Even though these malignant neoplasms are rare in general, they appear to be more prevalent in patients with multiple meningiomas including those with neurofibromatosis type 2.

scholarly journals Characterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood-Stage Antigen 332

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Sandra Nilsson ◽  
Kirsten Moll ◽  
Davide Angeletti ◽  
Letusa Albrecht ◽  
Inari Kursula ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Immunofluorescence Microscopy ◽  
Homology Model ◽  
Cross Reactivity ◽  
Blood Stage ◽  
Conserved Domain ◽  
Erythrocyte Binding ◽  
High Degree ◽  
Degree Of Similarity

Studies on Pf332, a major Plasmodium falciparum blood-stage antigen, have largely been hampered by the cross-reactive nature of antibodies generated against the molecule due to its high content of repeats, which are present in other malaria antigens. We previously reported the identification of a conserved domain in Pf332 with a high degree of similarity to the Duffy-binding-like (DBL) domains of the erythrocyte-binding-like (EBL) family. We here describe that antibodies towards Pf332-DBL are induced after repeated exposure to P. falciparum and that they are acquired early in life in areas of intense malaria transmission. Furthermore, a homology model of Pf332-DBL was found to be similar to the structure of the EBL-DBLs. Despite their similarities, antibodies towards Pf332-DBL did not display any cross-reactivity with EBL-proteins as demonstrated by immunofluorescence microscopy, Western blotting, and peptide microarray. Thus the DBL domain is an attractive region to use in further studies on the giant Pf332 molecule.

scholarly journals Microbiological and Physicochemical Characterization of Hospital Effluents before and after Treatment with Two Types of Sawdust

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Rabea Elmountassir ◽  
Bahia Bennani ◽  
Youssef Miyah ◽  
Ahlam Fegousse ◽  
Ghita El Mouhri ◽  
...  
Keyword(s):  
Physicochemical Characterization ◽  
Oxygen Demand ◽  
Fecal Coliforms ◽  
World Health ◽  
Hospital Effluents ◽  
Before And After ◽  
Health Organization ◽  
Filter Bed ◽  
Microbiological Analyses

Physicochemical and microbiological analyses of liquid hospital effluents have demonstrated that they are loaded with organic and inorganic pollutants then discharged into the sewerage networks without treatment. The aim of this study is to suggest an effective solution for their treatment. Column filtration is an adequate method to reduce the pollutant load which makes it possible to have a rate of abatement of 97% and 79% by filtering the pollutant material using sawdust of catia and red sawdust, respectively, with a filter bed height equal to 13 cm. Physicochemical parameters such as chemical oxygen demand, biological oxygen demand, nitrate, ammonia, phosphorus, electrical conductivity and the bacteriological parameters like fecal coliforms, Streptococci, and Staphylococci have been measured. The analysis of heavy metals displays compliance with the World Health Organization standards. The red sawdust and catia sawdust have been characterized by scanning electron microscopy and Fourier-transform infrared spectroscopy.

scholarly journals Time is of the essence: exploring a measles outbreak response vaccination in Niamey, Niger

2007 ◽  
Vol 5 (18) ◽  
pp. 67-74 ◽  
Author(s):  
R.F Grais ◽  
A.J.K Conlan ◽  
M.J Ferrari ◽  
A Djibo ◽  
A Le Menach ◽  
...  
Keyword(s):  
Urban Setting ◽  
World Health ◽  
Outbreak Response ◽  
High Coverage ◽  
Measles Outbreak ◽  
Potential Impact ◽  
Individual Based Simulation ◽  
Health Organization ◽  
Age Range ◽  
The Impact

The current World Health Organization recommendations for response during measles epidemics focus on case management rather than outbreak response vaccination (ORV) campaigns, which may occur too late to impact morbidity and mortality and have a high cost per case prevented. Here, we explore the potential impact of an ORV campaign conducted during the 2003–2004 measles epidemic in Niamey, Niger. We measured the impact of this intervention and also the potential impact of alternative strategies. Using a unique geographical, epidemiologic and demographic dataset collected during the epidemic, we developed an individual-based simulation model. We estimate that a median of 7.6% [4.9–8.9] of cases were potentially averted as a result of the outbreak response, which vaccinated approximately 57% (84 563 of an estimated 148 600) of children in the target age range (6–59 months), 23 weeks after the epidemic started. We found that intervening early (up to 60 days after the start of the epidemic) and expanding the age range to all children aged 6 months to 15 years may lead to a much larger (up to 90%) reduction in the number of cases in a West African urban setting like Niamey. Our results suggest that intervening earlier even with lower target coverage (approx. 60%), but a wider age range, may be more effective than intervening later with high coverage (more than 90%) in similar settings. This has important implications for the implementation of reactive vaccination interventions as they can be highly effective if the response is fast with respect to the spread of the epidemic.

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