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.  

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 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.

Phytoconstituents in the Management of Covid-19: Demystifying the Fact

Drug Research ◽  
2022 ◽  
Author(s):  
Md. Abul Barkat ◽  
Pawan Kaushik ◽  
Harshita Abul Barkat ◽  
Mohammad Idreesh Khan ◽  
Hazrina Ab Hadi
Keyword(s):  
Therapeutic Agent ◽  
Clinical Development ◽  
World Health ◽  
Therapeutic Drug ◽  
Scientific Communities ◽  
Synthetic Drugs ◽  
Naturally Occurring ◽  
Deadly Disease ◽  
Novel Coronavirus ◽  
Health Organization

AbstractThe 2019-nCoV (COVID-19; novel coronavirus disease-2019) outbreak is caused by the coronavirus, and its continued spread is responsible for increasing deaths, social and economic burden. COVID-19 created a chaotic situation worldwide and claimed the lives of over 5,027,183 and 248,467,363 confirmed cases have been reported so far as per the data published by WHO (World Health Organization) till 5th November 2021. Scientific communities all over the world are toiling to find a suitable therapeutic drug for this deadly disease. Although till date no promising drug has been discovered for this COVID-19. However, as per the WHO, over 102 COVID-19 vaccines are in clinical development and 185 in pre-clinical development. Naturally occurring phytoconstituents possess considerable chemical richness in the form of anti-viral and anti-parasitic potential and have been extensively exploited for the same globally. Still, phytomedicine-based therapies are considered as the best available treatment option to minimize and treat the symptoms of COVID-19 because of the least possible side effects compared to synthetic drugs recommended by the physicians/clinicians. In this review, the use of plant chemicals as a possible therapeutic agent for severe acute respiratory syndrome coronavirus 2 (SARS CoV2) is highlighted with their proposed mechanism of action, which will prove fruitful and effective in finding a cure for this deadly disease.

Overview of non-innovator biological products in India

2020 ◽  
Vol 9 (1) ◽  
pp. 30-36 ◽  
Author(s):  
G R Soni
Keyword(s):  
Patent Protection ◽  
Recombinant Dna ◽  
Regulatory System ◽  
Poor Quality ◽  
New Drugs ◽  
World Health ◽  
Clinical Tests ◽  
Regulatory Requirements ◽  
Biological Products ◽  
Health Organization

As per regulatory requirements, biosimilar drugs must show high similarity to their reference product in quality, preclinical and clinical tests. It is by these means that biosimilars are considered to be safe and efficacious. In India, any major deviation(s) from science-based principles in the manufacturing of a recombinant DNA-derived therapeutic biological product leads to its classification as a ‘non-innovator’ biological, which are approved as ‘New Drugs’. According to the World Health Organization (WHO), these biological products have uncertain safety and efficacy when compared to the reference biological and are therefore not recommended for use. However, these so-called non-innovator biological products continue to be developed in India, for reasons including brief and poorly implemented guidelines on biologicals, a lack of expertise on biosimilars amongst drug regulatory committees, lack of coordination among government departments working on biosimilars, poor quality accreditation in testing laboratories, and a lack of patent protection for innovator drugs. There is an urgent need to identify deficiencies in the ministries responsible for biosimilars in India, which could be through a scientific audit. Compliance with such an audit could strengthen the Indian regulatory system and thus increase the provision of affordable, high quality biosimilars in India.

scholarly journals The Smart Solution for DNA Removal in Biopharmaceutical Production by Benzonase Endonuclease

2013 ◽  
Vol 2 (1) ◽  
Author(s):  
Zhu Yang ◽  
Mingxin Li ◽  
Wen Chen ◽  
Alexander Peters
Keyword(s):  
Mammalian Cells ◽  
Rna World ◽  
Rapid Development ◽  
World Health ◽  
Base Pairs ◽  
Biological Products ◽  
Continuous Cell Lines ◽  
Dna And Rna ◽  
Biomedical Technologies ◽  
Health Organization

<p>More and more mammalian cells especially continuous cell lines were used to produce vaccines and therapeutic biological products with the rapid development of biomedical technologies. Therefore, more attention should be paid from drug regulatory authorities to the safety of biological products especially quality control of residual DNA and RNA. World Health Organization has evaluated the methods commonly used in vaccine manufacture for their ability to reduce the biological activity of DNA. Benzonase endonuclease is frequently used during the production of vaccines and can degrade all nucleic acid sequences down to oligonucleotides of approximately 3 to 5 base pairs.</p>

scholarly journals Molecular Docking Studies on the Anti-viral Effects of Compounds From Kabasura Kudineer on SARS-CoV-2 3CLpro

2020 ◽  
Vol 7 ◽  
Author(s):  
Savariar Vincent ◽  
Selvaraj Arokiyaraj ◽  
Muthupandian Saravanan ◽  
Manoj Dhanraj
Keyword(s):  
Molecular Docking ◽  
Critical Role ◽  
Drug Repurposing ◽  
Docking Studies ◽  
World Health ◽  
Synthetic Drugs ◽  
Energy Score ◽  
Main Protease ◽  
Novel Coronavirus ◽  
Health Organization

The COVID-19 has now been declared a global pandemic by the World Health Organization. No approved drug is currently available; therefore, an urgent need has been developed for any antiviral therapy for COVID-19. Main protease 3CLpro of this novel Coronavirus (SARS-CoV-2) play a critical role in the disease propagation, and hence represent a crucial target for the drug discovery. Herein, we have applied a bioinformatics approach for drug repurposing to identify the possible potent inhibitors of SARS-CoV-2 main proteases 3CLpro (6LU7). In search of the anti-COVID-19 compound, we selected 145 phyto-compounds from Kabasura kudineer (KK), a poly-herbal formulation recommended by AYUSH for COVID-19 which are effective against fever, cough, sore throat, shortness of breath (similar to SARS-CoV2-like symptoms). The present study aims to identify molecules from natural products which may inhibit COVID-19 by acting on the main protease (3CLpro). Obtained results by molecular docking showed that Acetoside (−153.06), Luteolin 7 -rutinoside (−134.6) rutin (−133.06), Chebulagic acid (−124.3), Syrigaresinol (−120.03), Acanthoside (−122.21), Violanthin (−114.9), Andrographidine C (−101.8), myricetin (−99.96), Gingerenone -A (−93.9), Tinosporinone (−83.42), Geraniol (−62.87), Nootkatone (−62.4), Asarianin (−79.94), and Gamma sitosterol (−81.94) are main compounds from KK plants which may inhibit COVID-19 giving the better energy score compared to synthetic drugs. Based on the binding energy score, we suggest that these compounds can be tested against Coronavirus and used to develop effective antiviral drugs.

scholarly journals Blueberry Extracts as a Novel Approach to Prevent Ozone-Induced Cutaneous Inflammasome Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Erika Pambianchi ◽  
Francesca Ferrara ◽  
Alessandra Pecorelli ◽  
Brittany Woodby ◽  
Mary Grace ◽  
...  
Keyword(s):  
New Technology ◽  
Skin Toxicity ◽  
Living Organism ◽  
Skin Inflammation ◽  
Outdoor Environment ◽  
World Health ◽  
Inflammasome Activation ◽  
Novel Approach ◽  
And Migration ◽  
Health Organization

The World Health Organization estimates that 7 million people die every year due to pollution exposure. Among the different pollutants to which living organism are exposed, ozone (O3) represents one of the most toxic, because its location which is the skin is one of the direct tissues exposed to the outdoor environment. Chronic exposure to outdoor stressors can alter cutaneous redox state resulting in the activation of inflammatory pathways. Recently, a new player in the inflammation mechanism was discovered: the multiprotein complex NLRP1 inflammasome, which has been shown to be also expressed in the skin. The topical application of natural compounds has been studied for the last 40 years as a possible approach to prevent and eventually cure skin conditions. Recently, the possibility to use blueberry (BB) extract to prevent pollution-induced skin toxicity has been of great interest in the cosmeceutical industry. In the present study, we analyzed the cutaneous protective effect of BB extract in several skin models (2D, 3D, and human skin explants). Specifically, we observed that in the different skin models used, BB extracts were able to enhance keratinocyte wound closure and normalize proliferation and migration responses previously altered by O3. In addition, pretreatment with BB extracts was able to prevent ozone-induced ROS production and inflammasome activation measured as NRLP1-ASC scaffold formation and also prevent the transcripts of key inflammasome players such as CASP1 and IL-18, suggesting that this approach as a possible new technology to prevent cutaneous pollution damage. Our data support the hypothesis that BB extracts can effectively reduce skin inflammation and be a possible new technology against cutaneous pollution-induced damage.

A review of the two major regulatory pathways for non-proprietary low-molecular-weight heparins

2012 ◽  
Vol 107 (02) ◽  
pp. 201-214 ◽  
Author(s):  
Frederick Ofosu
Keyword(s):  
Molecular Weight ◽  
Drug Application ◽  
World Health ◽  
European Medicines Agency ◽  
Low Molecular Weight ◽  
Regulatory Pathways ◽  
Synthetic Drugs ◽  
Chemical Structures ◽  
Asian Society ◽  
Health Organization

SummaryWith the expiry or pending expiry of originator low-molecular-weight heparin (LMWH) patents, pharmaceutical companies have invested in developing non-proprietary versions of LMWHs. LMWHs are manufactured by depolymerising highly purified unfractionated heparin. In contrast to traditional synthetic drugs with well-defined chemical structures, LMWHs contain complex oligosaccharide mixtures and the different manufacturing processes for LMWHs add to the heterogeneity in their physicochemical properties such that the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) consider existing originator LMWHs to be distinct medicinal entities that are not clinically interchangeable. The FDA views LMWHs as drugs and has approved two non-proprietary (generic) LMWHs, using the Abbreviated New Drug Application pathway. In contrast, the World Health Organization and the EMA view LMWHs as biological medicines. Therefore, the EMA and also the Scientific and Standardization Subcommittee on Anticoagulation of the International Society on Thrombosis and Haemostasis and the South Asian Society of Atherosclerosis and Thrombosis have all published specific guidelines for assessing non-proprietary (biosimilar) LMWHs. This manuscript reviews why there are two distinct pathways for approving non-proprietary LMWHs. Available literature on non-proprietary LMWHs approved in some jurisdictions is also reviewed in order to assess whether they satisfy the requirements for LMWHs in the three guidance documents. The review also highlights some of the significant difficulties the two pathways pose for manufacturers and an urgent need to develop a consensus governing the manufacture and regulation of non-proprietary LMWHs to make them more widely available.

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 The Challenges to be a Regulatory Affair Associate: Day-To-Day Questions on How to Reach Consensus between Manufacturers of Pharmaceutical Products and Government Regulatory Authorities

2020 ◽  
pp. 37-40
Author(s):  
Elene Chikobava ◽  
Irma Beridze
Keyword(s):  
Living Organism ◽  
Pharmaceutical Products ◽  
World Health ◽  
Main Task ◽  
Professional Career ◽  
Regulatory Authorities ◽  
Regulatory Affairs ◽  
Authorization Holder ◽  
Health Organization ◽  
Registration Dossier

The modern pharmaceutical industry is one of the main branches in the healthcare segment and is considered to be the most highly regulated industries worldwide. The regulation is provided by a specialist, named Regulatory Affairs Manager (syn.: Regulatory Affairs Executive or Regulatory Affairs Associate), involved in authorization process of pharmaceutical products. When person graduates from University with medical, pharmaceutical or even chemical diploma, he/she never thinks about professional career as a Regulatory Affairs Manager, because this specialty is new, about 40 years old. What is a Regulatory Affairs Associate’s duty? One category-Regulatory Affairs Associate inside the manufacturing office, whose duty is to prepare registration dossier based on the process of artworks and Patient Information Leaflet preparation, prior to completing Common Technical Document (CTD) format dossier; other category (national regulatory affairs Associate)-are those who are ensuring mediation between Manufacturer and Government Regulatory Authorities. Regardless of differences of each Government requirement for dossier registration, the main task of each Regulatory Affairs Associate is to prepare Dossier for submission which will pass successful registration. For this purpose, the National Regulatory Affairs Associate should ensure that manufacturer/Marketing Authorization Holder (MAH)’s dossier is complete and in line with different documentation requirements, following the national requirements and in case such requirement don’t exist-with the guidelines of the World Health Organization (WHO) and International Council for Harmonization (ICH). On the other hand, National Regulatory Affairs Associate is working with National Regulatory Affairs officers to correct and align deficiencies in documentation in accordance with the National requirements. Each drug as a living organism (innovative drugs even have birthdays), which is subject to many changes reflected in the registration dossier: whether in its pharmaceutical part (composition, production process, stability etc.,) or pharmacological (therapeutic indications, side effects and others), as a consequence the Regulatory Affairs Manager is constantly involved in registration of an infinite number of Variations. The main goal of Regulatory structures-both governmental and private-is to ensure the safety, quality and efficacy of medicines.

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