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Comparative stability study and aggregate analysis of Bevacizumab marketed formulations using advanced analytical techniques.

ABSTRACT: Bevacizumab (Bvz) is the most preferred recombinant humanized monoclonal antibody in biosimilar development due to its prominence as a standard treatment in the oncology space. Therapeutic monoclonal antibodies are typically more complex and unlikely to produce a replica. As a result, regulatory agencies allow approval of biosimilars that differ structurally and functionally from their reference product, but these differences should not have any clinical significance. To identify these significant discrepancies, it is essential to perform a thorough characterization of critical product attributes both in real-time and after storage until the product's expiration. In the present study, two Bvz biosimilar brands (Bio-1 and Bio-2) marketed in India were evaluated and compared with the reference product Avastin® to assess their degree of similarity. A comprehensive physicochemical characterization of biosimilars and reference product was performed using orthogonal techniques including LC-ESI-QTOF, MALDI-TOF, FTIR-ATR, iCIEF, rCE, nrCE, UV280, and RP-HPLC. Furthermore, Bvz formulations under study were subjected to various stress conditions of thermal (elevated temperature 50 ± 2 °C), chemical (acidic pH 3.0 ± 0.2, neutral pH 7.0 ± 0.2, and basic pH 10.0 ± 0.2), and mechanical (agitation 200 rpm) for comparative stability evaluation. Any alteration in the secondary structure of the native protein was detected and quantified using far-UV circular dichroism (CD), indicating an average of 15% and 11% loss in native antiparallel β-sheet conformation respectively in Bio-1 and Bio-2 upon exposure to elevated temperature and high pH. Additionally, covalent or non-covalent aggregates formed as a function of elevated temperature and agitation were quantified using SEC-MALS.

SUBMITTER: Bana AA

PROVIDER: S-EPMC10558615 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Comparative stability study and aggregate analysis of Bevacizumab marketed formulations using advanced analytical techniques.

Bana Arpit Arunkumar AA Sajeev Nithin N Halder Sabyasachi S Abbas Masi Haidar H Patel Shikha S Mehta Priti P

Heliyon 20230828 9

Bevacizumab (Bvz) is the most preferred recombinant humanized monoclonal antibody in biosimilar development due to its prominence as a standard treatment in the oncology space. Therapeutic monoclonal antibodies are typically more complex and unlikely to produce a replica. As a result, regulatory agencies allow approval of biosimilars that differ structurally and functionally from their reference product, but these differences should not have any clinical significance. To identify these significa ...[more]

PMID: 37810070

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Project description:The complex chemical composition of crude oils presents many challenges for rapid chemical characterization in the case of a spill. A number of approaches are currently used to "fingerprint" petroleum-derived samples. Gas chromatography coupled with mass spectrometry (GC-MS) is the most common, albeit not very rapid, technique; however, with GC-MS alone, it is difficult to resolve the complex substances in crude oils. The present study examined the potential application of ion mobility spectrometry-mass spectrometry (IMS-MS) coupled with chem-informatic analyses as an alternative high-throughput method for the chemical characterization of crude oils. We analyzed 19 crude oil samples from on- and offshore locations in the Gulf of Mexico region in the United States using both GC-MS (biomarkers, gasoline range hydrocarbons, and n-alkanes) and IMS-MS (untargeted analysis). Hierarchical clustering, principal component analysis, and nearest neighbor-based classification were used to examine sample similarity and geographical groupings. We found that direct-injection IMS-MS performed either equally or better than GC-MS in the classification of the origins of crude oils. In addition, IMS-MS greatly increased the sample analysis throughput (minutes vs hours per sample). Finally, a tabletop science-to-practice exercise, utilizing both the GC-MS and IMS-MS data, was conducted with emergency response experts from regulatory agencies and the oil industry. This activity showed that the stakeholders found the IMS-MS data to be highly informative for rapid chemical fingerprinting of complex substances in general and specifically advantageous for accurate and confident source-grouping of crude oils. Collectively, the present study shows the utility of IMS-MS as a technique for rapid fingerprinting of complex samples and demonstrates its advantages over traditional GC-MS-based analyses when used for decision-making in emergency situations. Environ Toxicol Chem 2021;40:1034-1049. © 2020 SETAC.

Project description:PurposeGeneric versions of bevacizumab are commonly used in India in patients with advanced/metastatic colorectal cancers (mCRCs), but there is limited real-world evidence (RWE) about their efficacy in comparison to the innovator bevacizumab.MethodsPatients diagnosed with mCRC between January 2017 and January 2022 and receiving a combination of chemotherapy and bevacizumab were retrospectively analyzed for demographic variables and survivals. The primary endpoint of the study was the estimation and comparison of median progression-free survival (mPFS) between patients receiving innovator versus generic bevacizumab as first-line therapy (CT1) by the Kaplan-Meier method.ResultsA total of 944 patients were included in the analysis, of whom 652 patients (69%) received bevacizumab as CT1, 449 patients (48%) during second-line chemotherapy (CT2), and 74 patients (8%) during third-line therapy (CT3). The innovator was administered to 132 patients (14%), while the remaining 812 patients (86%) received a generic molecule. With a median follow-up of 18 months, there was no difference in mPFS between patients receiving the innovator or biosimilar (10 vs. 9.3 months, p = 0.62). Similarly, there was no difference in median overall survival (mOS) between patients receiving the innovator or biosimilar during CT1 (17.8 vs. 18 months, p = 0.85). Among the patients who received bevacizumab during CT2, there was no statistically significant difference in mPFS between the innovator and the biosimilar (5.5 vs. 5.8 months, p = 0.97), nor was there a difference in mOS between patients receiving the innovator or biosimilar during CT2 (8.15 vs. 8.58 months, p = 0.16).ConclusionThe current study offers RWE to suggest similar outcomes with innovator and generic bevacizumab when combined with chemotherapy in mCRCs. This has significant implications in India and other low- and middle-income countries besides providing oncologists with greater confidence to use these molecules in their clinical practice.

Dataset Information

Comparative stability study and aggregate analysis of Bevacizumab marketed formulations using advanced analytical techniques.

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Comparative stability study and aggregate analysis of Bevacizumab marketed formulations using advanced analytical techniques.

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