Analytical Procedures

Burdick, Richard K.; LeBlond, David; Pfahler, Lori B.; Quiróz, Jorge A.; Sidor, Leslie; Vukovinsky, Kimberly; Zhang, Lanju

doi:10.1007/978-3-319-50186-4_6

Cited by 1 publication

(1 citation statement)

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“…A predefined EAC is required to test for statistical equivalence by TOST. Various recommendations have been made for establishing the EAC limits including using prior knowledge of the analysis and using limits established by subject matter experts. , By design, the TOST for statistical equivalence considers the magnitude of Δ D and its uncertainty (i.e., the confidence interval). Therefore, prior knowledge of the variability in measurements is necessary to determine an appropriate EAC.…”

Section: Equivalence Testing Hx-ms Data With Tostmentioning

confidence: 99%

Statistical Equivalence Testing of Higher-Order Protein Structures with Differential Hydrogen Exchange-Mass Spectrometry (HX-MS)

2021

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Hydrogen exchange-mass spectrometry (HX-MS) is widely recognized for its potential utility for establishing the equivalence of the higher-order structures of proteins, particularly in comparability and similarity contexts. However, recent progress in the statistical analysis of HX-MS data has instead placed an emphasis on significance testing to identify regions of proteins where there are significant differences in HX between two or more protein states. In the cases involving assessment of similarity or equivalence of the higher-order structure of different protein samples (e.g., biosimilars), significance testing of HX-MS data is unsuitable. To meet this need, we have adapted the univariate two one-sided test (TOST) equivalence testing method for HX-MS data. Equivalence acceptance criteria were determined using maximum deviations from randomized resampling of truly equivalent samples to define hybrid equivalence criteria (maximum deviation of true equivalents, MDTE). Application of the TOST-MDTE test on differential HX-MS measurements of wild-type and mutated maltose-binding proteins demonstrates that the equivalence testing method was fit-for-purpose. Three infliximab biosimilars (Remsima, Renflexis, and Inflectra) were found to be equivalent to their Remicade reference product based on differential HX-MS measurements, while 5% deglycosylated NIST mAb was not statistically equivalent to the unmodified NIST mAb reference.

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Section: Equivalence Testing Hx-ms Data With Tostmentioning

confidence: 99%