Assessment of the Effects of Glycosylation on the Pattern and Kinetics of Degradation of Lenograstim in Comparison to Filgrastim Using a Stability-Indicating Orthogonal Testing Protocol

Hassan, Lamiaa A.; Al‐Ghobashy, Medhat A.; Fathalla, Faten A.; Abbas, Samah S.

doi:10.1007/s10337-015-2910-2

Cited by 11 publications

(3 citation statements)

References 27 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering all of the evaluated degradation processes, the overall degradation reaction followed the first‐order reaction kinetics. The results agreed with the previously demonstrated data using the orthogonal testing protocol (Hassan, Al‐Ghobashy, Fathalla, & Abbas, ). The stability data using multiple time points provided a better understanding of the degradation behavior of adalimumab.…”

Section: Resultssupporting

confidence: 91%

Evaluation of the pattern and kinetics of degradation of adalimumab using a stability‐indicating orthogonal testing protocol

Hassan

Al‐Ghobashy

Abbas

2019

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

Forced degradation studies are crucial for the evaluation of the stability and biosimilarity. Here, adalimumab was subjected to oxidation, pH, temperature, agitation and repeated freeze-thaw in order to generate all possible degradation products. An orthogonal stability-indicating testing protocol comprising SE-HPLC, RP-HPLC, TapeStation gel electrophoresis, dynamic light scattering (DLS), and functional receptor binding assay was developed and validated. The assay protocol was used for the assessment of the pattern and kinetics of aggregation/degradation of adalimumab. SE-HPLC and DLS were used to show the formation of aggregates/fragments of adalimumab under nondenaturing conditions. TapeStation electrophoresis was performed under denaturing conditions to reveal the nature of aggregates. Results of the receptor binding assay agreed to those of SE-HPLC and DLS which indicated that it can be used as an activity-indicating assay for adalimumab. RP-HPLC demonstrated excellent selectivity for adalimumab in the presence of its oxidized forms. The kineticsof degradation was studied in each case and the results showed that it followed the first-order reaction kinetics. Correlation between the results supported the quality assessment of the tested product in industrial and clinical settings. This orthogonal protocol is a useful tool in stability assessment of monoclonal antibodies and a key criterion for the biosimilarity assessment.

show abstract

Section: Resultssupporting

confidence: 91%

Evaluation of the pattern and kinetics of degradation of adalimumab using a stability‐indicating orthogonal testing protocol

Hassan

Al‐Ghobashy

Abbas

2019

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

show abstract

“…Reliable analytical tools are crucial for economical process development, production and batch release of biopharmaceuticals [28][29][30]. In the case of the quadrivalent HPV vaccine a robust, precise and high throughput quantitation of the VLPs using HPLC was a challenging task since the four types of VLPs had almost identical physicochemical properties.…”

Section: Size Exclusion Chromatographymentioning

confidence: 99%

Immunoaffinity extraction using conformation-dependent antibodies coupled to SE-HPLC for the development of stability and potency-indicating assay for quadrivalent human papillomavirus vaccine

Mostafa

Al‐Ghobashy

Fathalla

et al. 2016

Journal of Chromatography B

Self Cite

View full text Add to dashboard Cite

“…Its mechanism relies on determination of the diffusion coefficient of molecules based on the scattered light intensity fluctuations caused by Brownian motion of macromolecules. DLS is also used for the T A B L E 1 System suitability parameters for proposed SE-HPLC for the analysis of ramucirumab Ghobashy et al, 2017;Hassan et al, 2015). The results of DLS estimation of RAMU control and incubated samples (pH 4.0 and pH 10.0) showed LMWS fragments clearly (Figure 3).…”

Section: Dynamic Light Scatteringmentioning

confidence: 99%

Stability assessment of FDA‐approved ramucirumab monoclonal antibody; validated SE‐HPLC method for degradation pattern evaluation

Abdelghaffar

Hegazy

Eltanany

2021

Biomedical Chromatography

View full text Add to dashboard Cite

Ramucirumab (RAMU) is a recently US Food and Drug Administration-approved monoclonal antibody that is included in various anticancer protocols. It has a structural complexity and high degradation risk that have a significant effect on its safety and effectiveness. The major aim of this work was to assess the degradation pattern of RAMU based on physicochemical characterization. Mechanical agitation, repeated freeze-thaw cycles, pH and temperature were the selected stress conditions to which RAMU samples were subjected. The SE-HPLC method was applied and validated to monitor the RAMU monomer along with its aggregates and/or fragments.The purity of the separated peaks together with system suitability parameters were determined through the calculation of percentage purity and percentage drop in RAMU concentration. The results were interpreted by correlating them with those of dynamic light scattering and reducing and non-reducing sodium dodecyl sulfatepolyacrylamide gel electrophoresis. Samples incubated at pH 2.0-10.0 and 37 C for up to 4 weeks were analysed, recording detection of reversed phase (RP) aggregates and low molecular weight peptide fragments. Similarly, samples under short-term storage conditions of 4 weeks at different temperatures (À20, 2-8, 25, 37 and 50 C) showed low molecular weight peptide fragments but to a lesser extent. These results highlight the alarming effect on RAMU multidose vial efficacy and safety.

show abstract

Assessment of the Effects of Glycosylation on the Pattern and Kinetics of Degradation of Lenograstim in Comparison to Filgrastim Using a Stability-Indicating Orthogonal Testing Protocol

Cited by 11 publications

References 27 publications

Evaluation of the pattern and kinetics of degradation of adalimumab using a stability‐indicating orthogonal testing protocol

Evaluation of the pattern and kinetics of degradation of adalimumab using a stability‐indicating orthogonal testing protocol

Immunoaffinity extraction using conformation-dependent antibodies coupled to SE-HPLC for the development of stability and potency-indicating assay for quadrivalent human papillomavirus vaccine

Stability assessment of FDA‐approved ramucirumab monoclonal antibody; validated SE‐HPLC method for degradation pattern evaluation

Contact Info

Product

Resources

About