Regulatory Framework and Challenges in Developing Biosimilar Monoclonal Antibodies and Related Biological Products

1970 ◽  
Vol 5 (3) ◽  
pp. 1765-1774
Author(s):  
Bobby George
Keyword(s):  
Monoclonal Antibodies ◽  
Anticancer Agents ◽  
Repeated Administration ◽  
European Medicines Agency ◽  
Dominant Component ◽  
Regulatory Strategy ◽  
The Us ◽  
Us Fda ◽  
New Guidelines ◽  
The Right

Monoclonal antibodies (mAbs) were initially used as laboratory reagents, later they were adopted as clinical diagnostic reagents, and eventually as therapeutic agents. The develop-ment of therapeutic mAbs commenced in the early 1980s and by 1986 the first mAb for human use “Orthoclone OKT3®” was approved by the US Food and Drug Administration (FDA). The next wave of antibody products were mostly anticancer agents which were approved in the US and Europe in the 1990s. The technological evolution from murine-based therapeutic mAbs to chimeric (part murine part human protein), humanized, and fully human antibodies has led to a reduction in immune-mediated clearance and hypersensitivity, improved the safety and feasibility of repeated administration making them therapeuti-cally viable.Since the commercialization of the first therapeutic mAb, these products have become a dominant component of the biopharmaceutical marketgenerating revenues of several billion dollars.The area of biosimilar antibody development is positioned for substantial growth with regulatory agencies like the European Medicines Agency (EMA) coming up with new guidelines on similar biological medicinal products followed by Health Canada, the US FDA and others, addressing biosimilar product development. With few of the blockbuster mAbs going off-patent in the next decade, companies with expertise in manufacturing biosimilar mAbs with the right kind of business and regulatory strategy are likely to have good value proposition.

Elotuzumab in the treatment of relapsed and refractory multiple myeloma

2021 ◽  
Author(s):  
Sebastian Grosicki ◽  
Martyna Bednarczyk ◽  
Agnieszka Barchnicka ◽  
Olga Grosicka
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibodies ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Clinical Studies ◽  
Mechanisms Of Action ◽  
Incurable Disease ◽  
The Us ◽  
Us Fda ◽  
Humanized Monoclonal Antibodies

Multiple myeloma (MM) is still considered an incurable disease. However, drugs with different mechanisms of action that can improve the efficiency of treatment offer hope. Still, there are concerns about an unacceptable increase in toxicity with such regimens. The results of recently published clinical studies of elotuzumab in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone confirm previous hopes to improve the effect of that treatment. Humanized monoclonal antibodies aimed at SLAMF7 stimulate natural killer cells to fight against MM cells. Elotuzumab used in combination with lenalidomide/dexamethasone or with pomalidomide/dexamethasone is approved by the US FDA to treat patients with relapsed and/or refractory MM. The article is a summary of the recent knowledge about the possibility of using elotuzumab in the treatment of relapsed and/or refractory MM and shows its potential uses in the future.

scholarly journals UHPLC–MS/MS method for iohexol determination in human EDTA and lithium-heparin plasma, human urine and in goat- and pig EDTA plasma

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 981-990
Author(s):  
Jasper Stevens ◽  
Mireille A Wessels ◽  
Jan Roggeveld ◽  
Remco A Koster ◽  
Claire CJ Dekkers ◽  
...  
Keyword(s):  
Human Urine ◽  
Pharmacokinetic Profile ◽  
European Medicines Agency ◽  
Simple Method ◽  
The Us ◽  
Heparin Plasma ◽  
Thermo Fisher Scientific ◽  
Tandem Quadrupole Mass Spectrometer ◽  
Edta Plasma ◽  
Us Fda

Aim: Iohexol plasma clearance is used as an indicator of kidney function in clinical and preclinical settings. To investigate the pharmacokinetic profile of iohexol, a rapid, simple method for measurement of iohexol in different matrices and species was needed. Materials & methods: Iohexol was separated on an Accucore C18 column (Thermo Fisher Scientific, CA, USA). Detection was performed on a Thermo Scientific Quantiva tandem quadrupole mass spectrometer. The method was validated according to the requirements for bioanalytical methods issued by the US FDA and European Medicines Agency. Conclusion: We developed and validated a fast and efficient analytical method, suitable for analyzing iohexol in human EDTA plasma, human lithium-heparin plasma, human urine and goat- and pig EDTA plasma, using only one calibration line prepared in human EDTA plasma.

scholarly journals Structural and Functional Characterization of Low-molecular-weight Heparins: Impact on the Development of Guidelines for Generic Products

2009 ◽  
Vol 15 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Cafer Adiguzel ◽  
Walter P. Jeske ◽  
Debra Hoppensteadt ◽  
Jeanine M. Walenga ◽  
Vinod Bansal ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Functional Characterization ◽  
Current Data ◽  
European Medicines Agency ◽  
Low Molecular Weight ◽  
Low Molecular Weight Heparins ◽  
Biological Drugs ◽  
Biologic Drugs ◽  
The Us ◽  
Us Fda

Low-molecular-weight heparins (LMWHs) are poly-pharmacologic drugs used to treat thrombotic and cardiovascular disorders. Recently, several generic versions of branded LMWHs have been introduced. Although generic versions of LMWHs exhibit similar profiles, marked differences in their biological and pharmacologic properties have been demonstrated. Several studies have demonstrated differences in terms of anti-Xa activity and tissue factor pathway inhibitor release. The current data emphasize the need to consider multiple functional parameters when defining bioequivalence of biologic drugs and also underscore the importance of further pharmacologic studies involving animal and human clinical trials. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) are currently developing guidelines for the acceptance of complex biological drugs including LMWHs. The US FDA considers these drugs as follow-on agents whereas the EMEA classifies these drugs as biosimilar agents. Until clear guidelines are developed, generic interchange of LMWHs may not be feasible.

An updated review of infliximab biosimilar, CT-P13, in the treatment of immune-mediated inflammatory diseases

Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 609-623
Author(s):  
Seung Wook Hong ◽  
Yong-Gil Kim ◽  
Byong Duk Ye
Keyword(s):  
Clinical Trials ◽  
Clinical Outcomes ◽  
Real World ◽  
Inflammatory Diseases ◽  
European Medicines Agency ◽  
Immune Mediated ◽  
The Us ◽  
Us Fda ◽  
The Cost

The introduction of anti-TNFs, such as infliximab (IFX), has revolutionized the treatment of immune-mediated inflammatory diseases. Anti-TNF agents have shown outstanding efficacy and long-term improvement of clinical outcomes, but the cost has been relatively high. Out of this concern, several ‘biosimilar’ drugs of anti-TNF agents have been developed. CT-P13, the first biosimilar of reference IFX, was approved by the European Medicines Agency and licensed by the US FDA for use in all indications of IFX. This updated review summarizes all aspects of CT-P13, including pharmacology and pharmacokinetics, and evaluates its efficacy, safety and immunogenicity for all indications based on the results of the latest clinical trials as well as on real-world experiences.

Compatibility of immunogenicity guidance by the EMA and the US FDA

Bioanalysis ◽  
2019 ◽  
Vol 11 (17) ◽  
pp. 1619-1629 ◽  
Author(s):  
Pekka Kurki
Keyword(s):  
Multidisciplinary Approach ◽  
Reference Product ◽  
Therapeutic Protein ◽  
European Medicines Agency ◽  
Fda Guidance ◽  
Antidrug Antibody ◽  
The Us ◽  
Antibody Assays ◽  
Us Fda

The guidelines for immunogenicity studies by the European Medicines Agency and the US FDA are based on different legislations and regulatory philosophies. In spite of the different background, the main guidelines are compatible on the scientific level, especially for new innovative therapeutic protein products. The importance of sensitive and drug-tolerant antidrug antibody assays and multidisciplinary approach to development and assessment are highlighted by both agencies. The main differences are in the field of biosimilars. The nonclinical in vivo immunogenicity studies are seen more useful by the FDA than by the European Medicines Agency. The draft FDA guidance on interchangeability will complicate global biosimilar development by requiring clinical switch studies with US sourced reference product.

Histone Deacetylase Inhibitors: A Review on Class-I Specific Inhibition

2015 ◽  
Vol 15 (9) ◽  
pp. 731-750 ◽  
Author(s):  
Jagannath Behera ◽  
Venkatesan Jayaprakash ◽  
Barij Nayan Sinha
Keyword(s):  
Clinical Trial ◽  
Histone Deacetylase ◽  
Anticancer Agents ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Class I ◽  
Specific Inhibition ◽  
Comprehensive Review ◽  
The Us ◽  
Us Fda

Histone Deacetylase (HDAC) is an established and validated target for the treatment of cancer. It has been attempted to present a comprehensive review on the inhibitors for Class-I Histone Deacetylase enzyme family, reported during the period from 2002 to 2012. This review has summarized the inhibitors, based on their specificity towards different isoforms within this class. Further various recent United State (US) patents and the HDAC inhibitors, used singly or in combination undergoing clinical trial as anticancer agents have been reviewed. Three such inhibitors SAHA, Romidepsin and Belinostat have already been approved by the US-FDA for the treatment of cancer.

scholarly journals Roles and Rules of Some Regulatory Agencies around the World during COVID-19 Pandemic

2021 ◽  
pp. 178-187
Author(s):  
Aseel Bin Sawad ◽  
Fatema Turkistani
Keyword(s):  
Drug Administration ◽  
Medical Devices ◽  
Regulatory Agencies ◽  
European Medicines Agency ◽  
Cure Models ◽  
The Us ◽  
The World ◽  
Us Fda ◽  
Health Canada ◽  
Official Sources

Objective: Collecting and synthesizing relevant data on COVID-19 from official sources of some different regulatory agencies around the world. Methods: The information and actions related to responding to the COVID-19 situation were collected from the websites of some regulatory agencies, including the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), Health Canada (HC), Swiss Agency for Therapeutic Products (Swissmedic), and the Australian Therapeutic Goods Administration (TGA). Results: All the regulatory agencies help in expediting the development of COVID-19 treatments and medical devices. These agencies also developed an international regulatory collaboration to develop cure models for the pandemic. While some of the agencies conduct the COVID-19 testing, like the US FDA, the others do not. The agencies also differ in their approaches towards resolving the pandemic. FDA and EMA are more aggressive in a way that they prioritize more testing and hospitalization coverage. However, as of the 22nd of June 2021, the FDA authorized the highest number (388) of diagnostic COVID-19 test kits followed by TGA (128), and EMA (88). Conclusions: Although the regulatory agencies differ in their approaches towards resolving pandemic COVID-19, all regulatory agencies help in expediting the development of COVID-19 treatments and medical devices.

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