Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products

Kwon, Oh-Seok; Joung, Jeewon; Park, Younjoo; Kim, Chan Wha; Hong, Seung Hwa

doi:10.1016/j.biologicals.2017.04.005

Cited by 31 publications

(32 citation statements)

References 43 publications

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“…However, the observed differences are due to the modifications, not mutations or other structural deficiencies. Kwon et al have listed the critical attributes of etanercept and deamidation was not considered to have a big impact on the functionality of etanercept and might not decrease the functionality of this molecule [27]. Therefore, the differences in levels of amidation or deamidation observed in this study between the proposed biosimilar and the originator peptides may not affect the functionality of etanercept.…”

Section: Discussionmentioning

confidence: 88%

Structural and In Vitro Functional Comparability Analysis of Altebrel™, a Proposed Etanercept Biosimilar: Focus on Primary Sequence and Glycosylation

et al. 2019

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The demand for reliable comparability studies of biosimilars grows with their increased market share. These studies focus on physicochemical, structural, functional and clinical properties to ensure that a biosimilar has no significant differences to the originator product and can be released into the market without extensive clinical trials. In the current study, Enbrel® (etanercept, the originator) and Altebrel™ (the proposed biosimilar) underwent direct comparison. “Bottom-up” mass spectrometric analysis was used for primary sequence analysis, evaluation of N/O-glycosylation sites and quantification of methionine oxidation. N/O-glycans were analyzed after permethylation derivatization and the effect of N-glycans on in-vitro functionality of etanercept was assayed. Three enzyme peptide mapping resulted in complete identification of the primary structure. It was confirmed that total ion chromatograms are valuable datasets for the analysis of the primary structure of biodrugs. New N/O-glycan structures were identified and all the N-glycans were quantified. Finally, investigation of the functional properties of N-deglycosylated and non-modified etanercept samples using surface plasmon resonance analysis and in-vitro bioassay showed that N-glycosylation has no significant effect on its in-vitro functionality. Analysis of etanercept and its biosimilar, revealed a high similarity in terms of glycosylation, primary structure and in-vitro functionality.

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Section: Discussionmentioning

confidence: 88%

Structural and In Vitro Functional Comparability Analysis of Altebrel™, a Proposed Etanercept Biosimilar: Focus on Primary Sequence and Glycosylation

et al. 2019

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“…It has contributed to lowering the occurrence of adverse events to ensure the quality, safety, and efficacy of biotherapeutics. Figure 1 shows that the risk for issuing a regulatory decision was lowered as the cumulative scientific knowledge was raised and the evaluation criteria became more stringent from the 1970s to 2018 ( 27 ).…”

Section: Regulatory Strategymentioning

confidence: 99%

“…DS and DP characterization: This section includes the use of orthogonal analytical methodologies and bioassays to assess the physicochemical and functional properties of the product (composition, shape, size, mass and charge, affinities, and mechanism of action). The characterization determines such properties that might impact its functionality and helps to establish its CQAs that should be considered in the quality specifications ( 27 , 31 ).…”

Section: Regulatory Strategymentioning

confidence: 99%

“…Under this rationale a highly similar molecule in terms of physicochemical and functional properties, will result in highly similar safety and efficacy profiles (Figure 3 ). The information required to register biosimilars has to be structured following the same scheme mentioned above as for the “reference product” ( 27 , 37 ). It should be noticed that a Biocomparability section must be included in the submission.…”

Section: Regulatory Strategymentioning

confidence: 99%

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Regulatory Pathway for Licensing Biotherapeutics in Mexico

et al. 2018

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Biotherapeutic products which are derived from living organisms using recombinant DNA technology significantly contribute to the progress in the treatment of life-threatening and chronic diseases. The worldwide sale of biological drugs in 2016 was near US $263,700 million. In Latin America, where monoclonal antibodies market was worth US $7000 million, being Mexico the second largest market. Approval is one of the key aspects which influences the market of medicinal products, thus it is responsibility of the regulatory authority to establish a regulatory framework that ensure safety and efficacy of the products, and it is responsibility of the applicants to provide a high quality dossier in accordance with the registration requirements of the country. The applicants submitting registration requests in Mexico need to be aware of the requirements. Similar to many other countries, Mexico has adopted the Common Technical Document (CTD) structure for organizing dossier of the medicinal product for submission into main modules (i.e., quality, non-clinical, and clinical). This facilitates the submission process of medicinal products following a logical sequence aligned to the International Council on Harmonisation (ICH) guidelines. Moreover, this structure improves the transparency and clarity of the dossier in process of evaluation of medicinal products. In Mexico, the Ministry of Health has published a regulation, NOM-257-SSA1-2014, which established the general requirements to be followed by applicants to complete the registration of biotherapeutics. This regulation stipulates that the evaluation process is supported by a regulatory framework involving Good Manufacturing Practices, labeling, stability, clinical trials, biocomparability studies, pharmacovigilance, and a technical evaluation performed by a multidisciplinary team of experts in biotherapeutics development. Additionally, the Mexican regulatory agency, COFEPRIS, has published specific guidelines to facilitate the application process. Despite the availability of this information, the scope is limited to regulatory and administrative purposes, rather than technical-scientific supporting knowledge. The aim of this article is to provide concise information to improve and promote communication between industry and regulatory agencies. Herein, we describe the current process of COFEPRIS in regulating biotherapeutics in Mexico. This process explains the basis for the organization and structure of the technical-scientific information of biotherapeutics required for registration application.

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“…Biosimilar drugs are biological products with an active ingredient that is highly similar, but not identical, to a reference biological product that has been authorized for use by a regulatory agency. These are new versions of reference products that have been developed independently after the patent of the original product has expired, driven by the high costs of reference biological drugs, which affect patients and the whole healthcare system [1]. Biologic therapies were introduced over a decade ago for the management and treatment of chronic inflammatory diseases [2] and their regulation remains a worldwide discussion.…”

Section: Introductionmentioning

confidence: 99%

Practical Issues Concerning the Approval and Use of Biosimilar Drugs for the Treatment of Multiple Sclerosis in Latin America

et al. 2019

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The use of biosimilar drugs for multiple sclerosis (MS) has become widespread in Latin America, with the goal of reducing costs of treatments, promoting the sustainability of healthcare systems, and improving patient access to these therapies. There is currently a need to define and comply with requirements to guarantee the efficacy, safety, and quality of these drugs. Thus, the objective of the present study was to compile up-to-date information from each Latin American country assessed on (a) approval of biosimilar drugs by regulatory agencies; (b) use of biosimilar drugs, pharmacovigilance plans, risk management; and (c) update in the knowledge on different molecules. To do so, a group of experts from Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Panama, Peru, Uruguay, and Venezuela met to discuss the current situation regarding good practices and risks associated with the use of biosimilar drugs in their respective countries. Regulation, risk management plans, and pharmacovigilance in the whole continent must guide the strategies on the commercialization and access of biosimilar drugs and copies of complex molecules. Current regulations must be implemented for the registration of biosimilar drug products and complex molecules. It is paramount to ensure that new products follow the best quality standards at all stages beyond being safe and efficient. Uncontrolled interchangeability between original biological and biosimilar should be avoided. Latin America requires the implementation and full use of strong pharmacovigilance programs. National and multinational clinical studies are required to demonstrate the similarity in safety, efficacy, and immunogenicity profiles of complex molecules, as well as biological and biosimilar products.Plain Language SummaryPlain language summary available for this article.

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Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products

Cited by 31 publications

References 43 publications

Structural and In Vitro Functional Comparability Analysis of Altebrel™, a Proposed Etanercept Biosimilar: Focus on Primary Sequence and Glycosylation

Structural and In Vitro Functional Comparability Analysis of Altebrel™, a Proposed Etanercept Biosimilar: Focus on Primary Sequence and Glycosylation

Regulatory Pathway for Licensing Biotherapeutics in Mexico

Practical Issues Concerning the Approval and Use of Biosimilar Drugs for the Treatment of Multiple Sclerosis in Latin America

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