TY - JOUR

T1 - Reference Protocol to Assess Analytical Performance of Higher Order Structural Analysis Measurements

T2 - Results from an Interlaboratory Comparison

AU - Groves, K.

AU - Ashcroft, A.E.

AU - Cryar, A.

AU - Sula, A.

AU - Wallace, B.A.

AU - Stocks, B.B.

AU - Burns, C.

AU - Cooper-Shepherd, D.

AU - De Lorenzi, E.

AU - Rodriguez, E.

AU - Zhang, H.

AU - Ault, J.R.

AU - Ferguson, J.

AU - Phillips, J.J.

AU - Pacholarz, K.

AU - Thalassinos, K.

AU - Luckau, L.

AU - Ashton, L.

AU - Durrant, O.

AU - Barran, P.

AU - Dalby, P.

AU - Vicedo, P.

AU - Colombo, R.

AU - Davis, R.

AU - Parakra, R.

AU - Upton, R.

AU - Hill, S.

AU - Wood, V.

AU - Soloviev, Z.

AU - Quaglia, M.

PY - 2021/7/6

Y1 - 2021/7/6

N2 - Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate. © 2021 The Authors. Published by American Chemical Society.

AB - Measurements of protein higher order structure (HOS) provide important information on stability, potency, efficacy, immunogenicity, and biosimilarity of biopharmaceuticals, with a significant number of techniques and methods available to perform these measurements. The comparison of the analytical performance of HOS methods and the standardization of the results is, however, not a trivial task, due to the lack of reference protocols and reference measurement procedures. Here, we developed a protocol to structurally alter and compare samples of somatropin, a recombinant biotherapeutic, and describe the results obtained by using a number of techniques, methods and in different laboratories. This, with the final aim to provide tools and generate a pool of data to compare and benchmark analytical platforms and define method sensitivity to structural changes. Changes in somatropin HOS, induced by the presence of zinc at increasing concentrations, were observed, both globally and at more localized resolution, across many of the methods utilized in this study and with different sensitivities, suggesting the suitability of the protocol to improve understanding of inter- and cross-platform measurement comparability and assess analytical performance as appropriate. © 2021 The Authors. Published by American Chemical Society.

KW - Chemical analysis

KW - Analytical performance

KW - Biopharmaceuticals

KW - Higher-order structure

KW - Interlaboratory comparison

KW - Measurement comparability

KW - Measurements of

KW - Reference measurements

KW - Reference protocols

KW - Chemistry

U2 - 10.1021/acs.analchem.0c04625

DO - 10.1021/acs.analchem.0c04625

M3 - Journal article

VL - 93

SP - 9041

EP - 9048

JO - Analytical Chemistry

JF - Analytical Chemistry

SN - 0003-2700

IS - 26

ER -