Dataset Information

Correct primary structure assessment and extensive glyco-profiling of cetuximab by a combination of intact, middle-up, middle-down and bottom-up ESI and MALDI mass spectrometry techniques.

ABSTRACT: The European Medicines Agency received recently the first marketing authorization application for a biosimilar monoclonal antibody (mAb) and adopted the final guidelines on biosimilar mAbs and Fc-fusion proteins. The agency requires high similarity between biosimilar and reference products for approval. Specifically, the amino acid sequences must be identical. The glycosylation pattern of the antibody is also often considered to be a very important quality attribute due to its strong effect on quality, safety, immunogenicity, pharmacokinetics and potency. Here, we describe a case study of cetuximab, which has been marketed since 2004. Biosimilar versions of the product are now in the pipelines of numerous therapeutic antibody biosimilar developers. We applied a combination of intact, middle-down, middle-up and bottom-up electrospray ionization and matrix assisted laser desorption ionization mass spectrometry techniques to characterize the amino acid sequence and major post-translational modifications of the marketed cetuximab product, with special emphasis on glycosylation. Our results revealed a sequence error in the reported sequence of the light chain in databases and in publications, thus highlighting the potency of mass spectrometry to establish correct antibody sequences. We were also able to achieve a comprehensive identification of cetuximab's glycoforms and glycosylation profile assessment on both Fab and Fc domains. Taken together, the reported approaches and data form a solid framework for the comparability of antibodies and their biosimilar candidates that could be further applied to routine structural assessments of these and other antibody-based products.

SUBMITTER: Ayoub D

PROVIDER: S-EPMC3851223 | biostudies-literature | 2013 Sep-Oct

REPOSITORIES: biostudies-literature

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Publications

Correct primary structure assessment and extensive glyco-profiling of cetuximab by a combination of intact, middle-up, middle-down and bottom-up ESI and MALDI mass spectrometry techniques.

Ayoub Daniel D Jabs Wolfgang W Resemann Anja A Evers Waltraud W Evans Catherine C Main Laura L Baessmann Carsten C Wagner-Rousset Elsa E Suckau Detlev D Beck Alain A

mAbs 20130620 5

The European Medicines Agency received recently the first marketing authorization application for a biosimilar monoclonal antibody (mAb) and adopted the final guidelines on biosimilar mAbs and Fc-fusion proteins. The agency requires high similarity between biosimilar and reference products for approval. Specifically, the amino acid sequences must be identical. The glycosylation pattern of the antibody is also often considered to be a very important quality attribute due to its strong effect on q ...[more]

PMID: 23924801

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Project description:BACKGROUND:Obstetric guidelines are useful to improve the quality of care. Availability of international guidelines has rapidly increased, however the contextualization to enhance feasibility of implementation in health facilities in low and middle-income settings has only been described in literature in a few instances. This study describes the approach and lessons learned from the 'bottom-up' development process of context-tailored national obstetric guidelines in middle-income country Suriname. METHODS:Local obstetric health care providers initiated the guideline development process in Suriname in August 2016 for two common obstetric conditions: hypertensive disorders of pregnancy (HDP) and post partum haemorrhage (PPH). RESULTS:The process consisted of six steps: (1) determination of how and why women died, (2) interviews and observations of local clinical practice, (3) review of international guidelines, (4) development of a primary set of guidelines, (5) initiation of a national discussion on the guidelines content and (6) establishment of the final guidelines based on consensus. Maternal enquiry of HDP- and PPH-related maternal deaths revealed substandard care in 90 and 95% of cases, respectively. An assessment of the management through interviews and labour observations identified gaps in quality of the provided care and large discrepancies in the management of HDP and PPH between the hospitals. International recommendations were considered unfeasible and were inconsistent when compared to each other. Local health care providers and stakeholders convened to create national context-tailored guidelines based on adapted international recommendations. The guidelines were developed within four months and locally implemented. CONCLUSION:Development of national context-tailored guidelines is achievable in a middle-income country when using a 'bottom-up' approach that involves all obstetric health care providers and stakeholders in the earliest phase. We hope the descriptive process of guideline development is helpful for other countries in need of nationwide guidelines.

Dataset Information

Correct primary structure assessment and extensive glyco-profiling of cetuximab by a combination of intact, middle-up, middle-down and bottom-up ESI and MALDI mass spectrometry techniques.

Publications

Correct primary structure assessment and extensive glyco-profiling of cetuximab by a combination of intact, middle-up, middle-down and bottom-up ESI and MALDI mass spectrometry techniques.

Similar Datasets

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