Physicochemical and biological assays for quality control of biopharmaceuticals: Interferon alfa-2 case study

被引：25

作者：

Silva, Marta M. C. G. ^{[1
]}

Lamarre, Baptiste ^{[2
]}

Cerasoli, Eleonora ^{[2
]}

Rakowska, Paulina ^{[2
]}

Hills, Anna ^{[2
]}

Bailey, Marc J. A. ^{[2
]}

Wheeler, Jun X. ^{[1
]}

Burns, Chris J. ^{[1
]}

Gaines-Das, Rose E. ^{[1
]}

Jones, Chris ^{[1
]}

Robinson, C. Jane ^{[1
]}

机构：

[1] Natl Inst Biol Stand & Controls, Blanche Lane, Potters Bar EN6 3QG, Herts, England

[2] Natl Phys Lab, Teddington TW11 0LW, Middx, England

来源：

BIOLOGICALS | 2008年 / 36卷 / 06期

关键词：

Interferon; Bioassay; Dynamic light scattering; Biopharmaceutical; qRT-PCR;

D O I：

10.1016/j.biologicals.2008.06.003

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

A selection of physicochemical and biological assays were investigated for their utility in detecting changes in preparations of Interferon alfa-2a and Interferon alfa-2b (IFN-alpha 2a, IFN-alpha 2b), which had been subjected to stressed conditions, in order to create models of biopharmaceutical products containing product-related impurities. The stress treatments, which included oxidation of methionine residues and storage at elevated temperatures for different periods of time, were designed to induce various degrees of degradation, aggregation or oxidation of the interferon. Biological activity of the stressed preparations was assessed in three different in vitro cell-based bioassay systems: a late-stage anti-proliferative assay and early-stage assays measuring reporter gene activation or endogenous gene expression by quantitative real time Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). Relevant physicochemical methods such as SDS-PAGE, reverse phase (RP) chromatography, size-exclusion chromatography (SEC) and dynamic light scattering (DLS), proved their complementarity in detecting structural changes in the stressed preparations which were reflected by reductions in biological activity. 2008 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

引用

页码：383 / 392

页数：10

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