The Experts below are selected from a list of 241794 Experts worldwide ranked by ideXlab platform
Huub Schellekens - One of the best experts on this subject based on the ideXlab platform.
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Immunogenicity of Innovative and Biosimilar Monoclonal Antibodies
Antibodies, 2019Co-Authors: Erik Doevendans, Huub SchellekensAbstract:The development of hybridoma technology for producing monoclonal antibodies (mAbs) by Kohler and Milstein (1975) counts as one of the major medical breakthroughs, opening up endless possibilities for research, diagnosis and for treatment of a whole variety of diseases. Therapeutic mAbs were introduced three decades ago. The first generation of therapeutic mAbs of murine origin showed high Immunogenicity, which limited efficacy and was associated with severe infusion reactions. Subsequently chimeric, humanized, and fully human antibodies were introduced as therapeutics, these mAbs were considerably less immunogenic. Unexpectedly humanized mAbs generally show similar Immunogenicity as chimeric antibodies; based on sequence homology chimeric mAbs are sometimes more "human" than humanized mAbs. With the introduction of the regulatory concept of similar biological medicines (biosimilars) a key concern is the similarity in terms of Immunogenicity of these biosimilars with their originators. This review focuses briefly on the mechanisms of induction of Immunogenicity by biopharmaceuticals, mAbs in particular, in relation to the target of the immune system.
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Immunogenicity of Therapeutic Proteins: The Use of Animal Models
Pharmaceutical Research, 2011Co-Authors: Vera Brinks, Wim Jiskoot, Huub SchellekensAbstract:Immunogenicity of therapeutic proteins lowers patient well-being and drastically increases therapeutic costs. Preventing Immunogenicity is an important issue to consider when developing novel therapeutic proteins and applying them in the clinic. Animal models are increasingly used to study Immunogenicity of therapeutic proteins. They are employed as predictive tools to assess different aspects of Immunogenicity during drug development and have become vital in studying the mechanisms underlying Immunogenicity of therapeutic proteins. However, the use of animal models needs critical evaluation. Because of species differences, predictive value of such models is limited, and mechanistic studies can be restricted. This review addresses the suitability of animal models for Immunogenicity prediction and summarizes the insights in Immunogenicity that they have given so far.
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The Immunogenicity of therapeutic proteins.
Discovery Medicine, 2010Co-Authors: Huub SchellekensAbstract:Nearly all therapeutic proteins induce antibodies in patients. However this Immunogenicity has been neglected in the use of these products, even though the antibodies may have severe consequences. During the last few years, progress has been made in understanding why patients do not tolerate these protein therapeutic products and also how to manage the problem of Immunogenicity.
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Immunogenicity of Therapeutic Proteins
Pharmaceutical Sciences Encyclopedia, 2010Co-Authors: Suzanne Hermeling, Huub Schellekens, Daan J. A. Crommelin, Wim JiskootAbstract:The introduction of recombinant DNA techniques has made possible to produce proteins on a large scale. These protein therapeutics are potentially immunogenic, inducing antibodies in patients after a certain period of treatment. This article gives an overview of the current knowledge about the Immunogenicity of therapeutic proteins. Keywords: recombinant DNA techniques; protein therapeutics; antibodies; Immunogenicity
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Immunogenicity of bone morphogenetic proteins: A review
Journal of Neurosurgery, 2009Co-Authors: Chang Ju Hwang, Huub Schellekens, Alexander R. Vaccaro, James P. Lawrence, Joseph Hong, Moulay Hicham Alaoui-ismaili, Dean FalbAbstract:Object The object of this paper is to review the Immunogenicity of bone morphogenetic proteins (BMPs) and to compare the results of the Immunogenicity characterization and clinical consequences between recombinant human (rh)BMP-2 and recombinant human osteogenic protein-1 (rhOP-1/BMP-7). Methods The Immunogenicity of therapeutic proteins and its clinical effects were reviewed. The characteristics of BMPs were also described in terms of Immunogenicity. The methods and results of antibody detection in various clinical trials of rhBMP-2 and rhOP-1 were compared, including the most recent studies using a systematic characterization strategy with both a binding assay and bioassay. Results Similar to all recombinant human proteins, rhBMPs induce immune responses in a select subgroup of patients. Adverse effects from this response in these patients, however, have not been reported with antibody formation to either rhBMP-2 or rhOP-1. Overall, the incidence of antibody formation was slightly higher in rhOP-1 trial...
Robin Thorpe - One of the best experts on this subject based on the ideXlab platform.
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Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility.
Biologicals, 2015Co-Authors: Meenu Wadhwa, Ivana Knezevic, Hye-na Kang, Robin ThorpeAbstract:Biotherapeutic products (BTPs) are the fastest growing medicines in the pharmaceutical market. Despite their clinical success, the Immunogenicity of BTPs continues to be a major concern. Assessment of Immunogenicity as well as appropriate interpretation of Immunogenicity data is therefore, of critical importance for defining safety profile of these products for the purpose of their licensure and use. In the past decade, much progress has been made towards how Immunogenicity should be studied. This article reflects the content of the brief presentation on principles of methods used for Immunogenicity assessment and their merits and limitations given at the first World Health Organization (WHO) implementation workshop on rDNA derived biotherapeutic products held in the Republic of Korea in May 2014 to support the case studies on Immunogenicity presented and discussed during the workshop. The purpose of this article is to provide an overview of the methods used for assessing Immunogenicity of biotherapeutic products (BTPs) and the most important considerations in interpreting results in the context of regulatory overview of these products.
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The challenges of Immunogenicity in developing biosimilar products.
IDrugs : the investigational drugs journal, 2009Co-Authors: Meenu Wadhwa, Robin ThorpeAbstract:Unwanted Immunogenicity is a significant issue affecting most biotherapeutic products, including subsequent entry biological (SEB) medicines. Such Immunogenicity can be associated with adverse reactions and can cause impaired clinical responses to the biotherapeutic. This feature article provides an overview of the challenges facing the biotechnology industry with regard to the prediction and assessment of Immunogenicity of SEBs and, in particular, biosimilar products. In addition, the available guidance on assessing the Immunogenicity of biotherapeutic products is discussed.
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Unwanted Immunogenicity: Implications for Follow-on Biologicals
Drug information journal : DIJ Drug Information Association, 2007Co-Authors: Meenu Wadhwa, Robin ThorpeAbstract:The unexpected and unpredictable development of unwanted Immunogenicity is a significant issue affecting therapeutic proteins, including follow-on biologicals. The development of antibodies against the therapeutic biological can cause allergic or anaphylactic reactions, reduction in efficacy, and, in some cases, severe adverse effects. The risk of inducing immune responses is largely dependent on the recipient as well as a number of product-related factors (eg, production process, formulation, and number of doses administered during the course of treatment). Consideration should be given to the evaluation of unwanted Immunogenicity of follow-on biologicals from preclinical development, through clinical trials, and into the postregistration period to minimize the risks associated with Immunogenicity in recipients of therapeutic products. Properly planned Immunogenicity studies during phase I/II clinical trials using a range of carefully validated procedures are needed to assess unwanted Immunogenicity of therapeutic products.
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Strategies and assays for the assessment of unwanted Immunogenicity
Journal of Immunotoxicology, 2006Co-Authors: Meenu Wadhwa, Robin ThorpeAbstract:The assessment of unwanted Immunogenicity associated with biological products continues to be a major issue for the biotechnology industry. Monitoring of unwanted Immunogenicity during the development of the product from pre-clinical stage through clinical trials is now a regulatory expectation with extended post-marketing commitments required for at least some of these products. Prospective planning of Immunogenicity studies incorporating appropriately devised strategies is critical if valid conclusions concerning the Immunogenicity profile of a product are to be derived. An important consideration of such studies is the selection of optimized, rigorously validated and standardized methodologies for detection and characterization of antibodies with emphasis on desired assay design, assay controls, and performance criteria. Binding assays with different formats and detection systems, radioimmuno-precipitation assays or surface plasmon resonance procedures are often used as the basis for a screening assay. For assessing the neutralizing capacity of the antibodies, however, a neutralization assay is an absolute requirement. Therefore, a panel of methods is usually necessary for a detailed understanding of the type(s) of antibodies induced against a therapeutic product. This manuscript considers briefly the benefits and limitations of the different techniques available for antibody detection and characterization. A strategy that can be adopted for the assessment of unwanted Immunogenicity of therapeutic products is also suggested.
Yanchen Zhou - One of the best experts on this subject based on the ideXlab platform.
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A Proposal to Redefine Clinical Immunogenicity Assessment
The AAPS Journal, 2017Co-Authors: Daniel T. Mytych, M. Benjamin Hock, Mark Kroenke, Vibha Jawa, Arunan Kaliyaperumal, Yanchen ZhouAbstract:With more than 100 therapeutic proteins (TP) approved since the first EMA guidance on Immunogenicity in 2007, a vast amount of clinical experience with a variety of therapeutic proteins has been gained. This has provided data on anti-drug antibodies (ADA) and their observed clinical impact, or lack thereof. It has become evident that not all ADA responses are clinically relevant. The current “standard practice” is to test for ADA in all patients on every study. It is essential that we acknowledge the Immunogenicity data gained from marketed TPs and that options for Immunogenicity testing reflect this information. Improvements in bioanalytical support throughout the drug development process will eliminate extraneous, non-impactful practices. We propose that low-risk therapeutic proteins could be supported with an event-driven (“collect-and-hold”) Immunogenicity testing strategy throughout early phases of the clinical program. In the absence of an event, only pivotal studies (where ADA incidence and impact can be decisively assessed) would include default ADA testing. In keeping with the “standard practice,” Immunogenicity risk assessment must be an on-going and real-time evaluation. This approach has the potential to deliver meaningful, clinically relevant Immunogenicity results while maintaining an emphasis on patient safety.
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A Proposal to Redefine Clinical Immunogenicity Assessment.
Aaps Journal, 2017Co-Authors: Daniel T. Mytych, M. Benjamin Hock, Mark Kroenke, Vibha Jawa, Arunan Kaliyaperumal, Yanchen ZhouAbstract:With more than 100 therapeutic proteins (TP) approved since the first EMA guidance on Immunogenicity in 2007, a vast amount of clinical experience with a variety of therapeutic proteins has been gained. This has provided data on anti-drug antibodies (ADA) and their observed clinical impact, or lack thereof. It has become evident that not all ADA responses are clinically relevant. The current “standard practice” is to test for ADA in all patients on every study. It is essential that we acknowledge the Immunogenicity data gained from marketed TPs and that options for Immunogenicity testing reflect this information. Improvements in bioanalytical support throughout the drug development process will eliminate extraneous, non-impactful practices. We propose that low-risk therapeutic proteins could be supported with an event-driven (“collect-and-hold”) Immunogenicity testing strategy throughout early phases of the clinical program. In the absence of an event, only pivotal studies (where ADA incidence and impact can be decisively assessed) would include default ADA testing. In keeping with the “standard practice,” Immunogenicity risk assessment must be an on-going and real-time evaluation. This approach has the potential to deliver meaningful, clinically relevant Immunogenicity results while maintaining an emphasis on patient safety.
Gopi Shankar - One of the best experts on this subject based on the ideXlab platform.
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assessment and reporting of the clinical Immunogenicity of therapeutic proteins and peptides harmonized terminology and tactical recommendations
Aaps Journal, 2014Co-Authors: Gopi Shankar, Steven Arkin, L Cocea, Viswanath Devanarayan, Susan Kirshner, A Kromminga, Valerie Quarmby, S Richards, C K Schneider, Meena SubramanyamAbstract:Immunogenicity is a significant concern for biologic drugs as it can affect both safety and efficacy. To date, the descriptions of product Immunogenicity have varied not only due to different degrees of understanding of product Immunogenicity at the time of licensing but also due to an evolving lexicon that has generated some confusion in the field. In recent years, there has been growing consensus regarding the data needed to assess product Immunogenicity. Harmonization of the strategy for the elucidation of product Immunogenicity by drug developers, as well as the use of defined common terminology, can benefit medical practitioners, health regulatory agencies, and ultimately the patients. Clearly, understanding the incidence, kinetics and magnitude of anti-drug antibody (ADA), its neutralizing ability, cross-reactivity with endogenous molecules or other marketed biologic drugs, and related clinical impact may enhance clinical management of patients treated with biologic drugs. To that end, the authors present terms and definitions for describing and analyzing clinical Immunogenicity data and suggest approaches to data presentation, emphasizing associations of ADA development with pharmacokinetics, efficacy, and safety that are necessary to assess the clinical relevance of Immunogenicity.
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scientific and regulatory considerations on the Immunogenicity of biologics
Trends in Biotechnology, 2006Co-Authors: Gopi Shankar, Elizabeth Shores, Carrie Wagner, Anthony MiresluisAbstract:Immune responses against non-vaccine biologics can affect their efficacy and safety, resulting in adverse events that could include administration reactions, hypersensitivity, deficiency syndromes and lack of a clinical response in treated patients. With the relatively recent development of numerous biologics, Immunogenicity testing has become a key component in the demonstration of clinical safety and efficacy; in fact, it is highly unlikely that regulatory approval would be granted for a biologic without an assessment of its Immunogenicity. However, recommendations from regulatory agencies regarding the requirements for when and how to carry out Immunogenicity testing are dispersed among numerous guidance documents. To enable the evaluation of the effects of Immunogenicity on safety and efficacy, the authors have consolidated recommendations from the regulatory guidelines, and present current approaches and future directions for the assessment of Immunogenicity.
Meenu Wadhwa - One of the best experts on this subject based on the ideXlab platform.
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Immunogenicity assessment of biotherapeutic products: An overview of assays and their utility.
Biologicals, 2015Co-Authors: Meenu Wadhwa, Ivana Knezevic, Hye-na Kang, Robin ThorpeAbstract:Biotherapeutic products (BTPs) are the fastest growing medicines in the pharmaceutical market. Despite their clinical success, the Immunogenicity of BTPs continues to be a major concern. Assessment of Immunogenicity as well as appropriate interpretation of Immunogenicity data is therefore, of critical importance for defining safety profile of these products for the purpose of their licensure and use. In the past decade, much progress has been made towards how Immunogenicity should be studied. This article reflects the content of the brief presentation on principles of methods used for Immunogenicity assessment and their merits and limitations given at the first World Health Organization (WHO) implementation workshop on rDNA derived biotherapeutic products held in the Republic of Korea in May 2014 to support the case studies on Immunogenicity presented and discussed during the workshop. The purpose of this article is to provide an overview of the methods used for assessing Immunogenicity of biotherapeutic products (BTPs) and the most important considerations in interpreting results in the context of regulatory overview of these products.
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The challenges of Immunogenicity in developing biosimilar products.
IDrugs : the investigational drugs journal, 2009Co-Authors: Meenu Wadhwa, Robin ThorpeAbstract:Unwanted Immunogenicity is a significant issue affecting most biotherapeutic products, including subsequent entry biological (SEB) medicines. Such Immunogenicity can be associated with adverse reactions and can cause impaired clinical responses to the biotherapeutic. This feature article provides an overview of the challenges facing the biotechnology industry with regard to the prediction and assessment of Immunogenicity of SEBs and, in particular, biosimilar products. In addition, the available guidance on assessing the Immunogenicity of biotherapeutic products is discussed.
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Unwanted Immunogenicity: Implications for Follow-on Biologicals
Drug information journal : DIJ Drug Information Association, 2007Co-Authors: Meenu Wadhwa, Robin ThorpeAbstract:The unexpected and unpredictable development of unwanted Immunogenicity is a significant issue affecting therapeutic proteins, including follow-on biologicals. The development of antibodies against the therapeutic biological can cause allergic or anaphylactic reactions, reduction in efficacy, and, in some cases, severe adverse effects. The risk of inducing immune responses is largely dependent on the recipient as well as a number of product-related factors (eg, production process, formulation, and number of doses administered during the course of treatment). Consideration should be given to the evaluation of unwanted Immunogenicity of follow-on biologicals from preclinical development, through clinical trials, and into the postregistration period to minimize the risks associated with Immunogenicity in recipients of therapeutic products. Properly planned Immunogenicity studies during phase I/II clinical trials using a range of carefully validated procedures are needed to assess unwanted Immunogenicity of therapeutic products.
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Strategies and assays for the assessment of unwanted Immunogenicity
Journal of Immunotoxicology, 2006Co-Authors: Meenu Wadhwa, Robin ThorpeAbstract:The assessment of unwanted Immunogenicity associated with biological products continues to be a major issue for the biotechnology industry. Monitoring of unwanted Immunogenicity during the development of the product from pre-clinical stage through clinical trials is now a regulatory expectation with extended post-marketing commitments required for at least some of these products. Prospective planning of Immunogenicity studies incorporating appropriately devised strategies is critical if valid conclusions concerning the Immunogenicity profile of a product are to be derived. An important consideration of such studies is the selection of optimized, rigorously validated and standardized methodologies for detection and characterization of antibodies with emphasis on desired assay design, assay controls, and performance criteria. Binding assays with different formats and detection systems, radioimmuno-precipitation assays or surface plasmon resonance procedures are often used as the basis for a screening assay. For assessing the neutralizing capacity of the antibodies, however, a neutralization assay is an absolute requirement. Therefore, a panel of methods is usually necessary for a detailed understanding of the type(s) of antibodies induced against a therapeutic product. This manuscript considers briefly the benefits and limitations of the different techniques available for antibody detection and characterization. A strategy that can be adopted for the assessment of unwanted Immunogenicity of therapeutic products is also suggested.
