Assessment of Structural and Functional Comparability of Biosimilar Products: Trastuzumab as a Case Study

Joshi, Srishti; Rathore, Anurag S.

doi:10.1007/s40259-020-00404-3

Cited by 30 publications

(11 citation statements)

References 36 publications

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“…These variations were potentially within an acceptable range typically generated by culture process. In comparison with the glycosylation of originator and biosimilars reported in two recent publications, Joshi and Rathore (2020) and Dakshinamurthy et al (2017) (see Supporting Information), the present glycan distribution was in a comparable range. Notice however that afucosylated G1 glycan was observed in the present study while it seemed absent in the reference studies.…”

Section: Discussionsupporting

confidence: 70%

“…It is probable that the cultivation process influenced the charge variant distribution due to different conditions such as the cell line and culture medium. Furthermore, deamidation of light chain asparagine 30 in the complementary‐determining region 1 (CDR1) and isomerization of heavy chain aspartate 102 in CDR3 are responsible for increased acidic variants in Trastuzumab (Du et al, 2012; Harris et al, 2001; Joshi & Rathore, 2020). Both modifications have been shown to be the sites most susceptible to degradation in the CDR region of trastuzumab subjected to stress conditions of temperature and pH (Schmid et al, 2018), for which shifts can be introduced by storage and purification conditions.…”

Section: Discussionmentioning

confidence: 99%

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Antibody capture process based on magnetic beads from very high cell density suspension

Brechmann

Schwarz

Eriksson

et al. 2021

Biotech & Bioengineering

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Cell clarification represents a major challenge for the intensification through very high cell density in the production of biopharmaceuticals such as monoclonal antibodies (mAbs). The present report proposes a solution to this challenge in a streamlined process where cell clarification and mAb capture are performed in a single step using magnetic beads coupled with protein A. Capture of mAb from non‐clarified CHO cell suspension showed promising results; however, it has not been demonstrated that it can handle the challenge of very high cell density as observed in intensified fed‐batch cultures. The performances of magnetic bead‐based mAb capture on non‐clarified cell suspension from intensified fed‐batch culture were studied. Capture from a culture at density larger than 100 × 106 cells/ml provided an adsorption efficiency of 99% and an overall yield of 93% with a logarithmic host cell protein (HCP) clearance of ≈2–3 and a resulting HCP concentration ≤≈5 ppm. These results show that direct capture from very high cell density cell suspension is possible without prior processing. This technology, which brings significant benefits in terms of operational cost reduction and performance improvements such as low HCP, can be a powerful tool alleviating the challenge of process intensification.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Antibody capture process based on magnetic beads from very high cell density suspension

Brechmann

Schwarz

Eriksson

et al. 2021

Biotech & Bioengineering

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“…A similar finding was discovered with Trastuzumab, a HER2/neu antagonist commonly used for breast cancer [10]. Differential glycosylation patterns on the drug could lead to size and charge heterogeneity and may affect ultimate therapeutic effect.…”

Section: Glycosylating Pharmaceuticals For Delivery Improvementsupporting

confidence: 66%

Sweetening the Deal: Glycosylation and its Clinical Applications

Zhang¹,

Sun²

2020

IPJBS

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Glycosylation, an important and nearly ubiquitous form of post-translational modification in eukaryotes, has been studied for its clinical applications. Its complex nature and heterogeneity of functions in the human body has allowed researchers to take multiple approaches in applying it to modern medicine. These approaches include glycosylation of pharmaceuticals to improve delivery; using glycosylation as vaccine/drug targets; editing the glycosylation pattern of immune system components; and profiling glycosylation signatures of diseases for diagnostic tests. In addition, glycosylation has also been used as a tool in developing potential therapeutics for the Covid-19 pandemic. This review covers and summarizes recent, interesting findings associated with the various approaches in the clinical study of glycosylation and aims to inspire future research in this promising direction.

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“…The product attributes that are critical to the safety, efficacy, and potency of the product are classified as critical quality attributes (CQAs) ( Eon-Duval et al, 2012 ). This exercise that is conducted to establish comparability between the reference product and its intended biosimilar is known as similarity assessment (aka biosimilarity) and comprises detailed comparative physicochemical and functional characterization using appropriate, validated analytical methods ( Nupur et al, 2016 , 2018 ; Joshi and Rathore, 2020 ). As structural attributes are molecule-dependent, CQAs may vary to a certain degree amongst the different modalities.…”

Section: Introductionmentioning

confidence: 99%

Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms

Nupur

Joshi

Gulliarme

et al. 2022

Front. Bioeng. Biotechnol.

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Biopharmaceuticals are one of the fastest-growing sectors in the biotechnology industry. Within the umbrella of biopharmaceuticals, the biosimilar segment is expanding with currently over 200 approved biosimilars, globally. The key step towards achieving a successful biosimilar approval is to establish analytical and clinical biosimilarity with the innovator. The objective of an analytical biosimilarity study is to demonstrate a highly similar profile with respect to variations in critical quality attributes (CQAs) of the biosimilar product, and these variations must lie within the range set by the innovator. This comprises a detailed comparative structural and functional characterization using appropriate, validated analytical methods to fingerprint the molecule and helps reduce the economic burden towards regulatory requirement of extensive preclinical/clinical similarity data, thus making biotechnological drugs more affordable. In the last decade, biosimilar manufacturing and associated regulations have become more established, leading to numerous approvals. Biosimilarity assessment exercises conducted towards approval are also published more frequently in the public domain. Consequently, some technical advancements in analytical sciences have also percolated to applications in analytical biosimilarity assessment. Keeping this in mind, this review aims at providing a holistic view of progresses in biosimilar analysis and approval. In this review, we have summarized the major developments in the global regulatory landscape with respect to biosimilar approvals and also catalogued biosimilarity assessment studies for recombinant DNA products available in the public domain. We have also covered recent advancements in analytical methods, orthogonal techniques, and platforms for biosimilar characterization, since 2015. The review specifically aims to serve as a comprehensive catalog for published biosimilarity assessment studies with details on analytical platform used and critical quality attributes (CQAs) covered for multiple biotherapeutic products. Through this compilation, the emergent evolution of techniques with respect to each CQA has also been charted and discussed. Lastly, the information resource of published biosimilarity assessment studies, created during literature search is anticipated to serve as a helpful reference for biopharmaceutical scientists and biosimilar developers.

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Assessment of Structural and Functional Comparability of Biosimilar Products: Trastuzumab as a Case Study

Cited by 30 publications

References 36 publications

Antibody capture process based on magnetic beads from very high cell density suspension

Antibody capture process based on magnetic beads from very high cell density suspension

Sweetening the Deal: Glycosylation and its Clinical Applications

Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms

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