The NISTmAb Reference Material 8671 value assignment, homogeneity, and stability

John E Schiel,Abby Turner,Jason King,Dean Ripple,Srivalli Telikepalli,Karen Phinney,Katharina Yandrofski,Paul Derose,Trina Mouchahoir

doi:10.1007/s00216-017-0800-1

John E Schiel, Abby Turner + Show 7 more

Open Access

https://doi.org/10.1007/s00216-017-0800-1

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Abstract

The NISTmAb Reference Material (RM) 8671 is intended to be an industry standard monoclonal antibody for pre-competitive harmonization of best practices and designing next generation characterization technologies for identity, quality, and stability testing. It must therefore embody the quality and characteristics of a typical biopharmaceutical product and be available long-term in a stable format with consistent product quality attributes. A stratified sampling and analysis plan using a series of qualified analytical and biophysical methods is described that assures RM 8671 meets these criteria. Results for the first three lots of RM 8671 highlight the consistency of material attributes with respect to size, charge, and identity. RM 8671 was verified to be homogeneous both within and between vialing lots, demonstrating the robustness of the lifecycle management plan. It was analyzed in concert with the in-house primary sample 8670 (PS 8670) to provide a historical link to this seminal material. RM 8671 was verified to be fit for its intended purpose as a technology innovation tool, external system suitability control, and cross-industry harmonization platform.Graphical abstractThe NISTmAb Reference Material (RM) 8671 is intended to be an industry standard monoclonal antibody for pre-competitive harmonization of best practices and designing next generation characterization technologies for identity, quality, and stability testing.

Highlights

IntroductionQuality of biotechnology products is defined as the suitability of the drug substance or drug product for its intended use [1]
The NISTmAb Reference Material (RM) 8671 is intended as a product-agnostic control to support biopharmaceutical innovation, and was developed under a quality system of Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Gaithersburg, MD 20899, USA similar rigor to marketed biotechnology products
Physicochemical methods: Capillary zone electrophoresis (CZE) NISTmAb charge heterogeneity was evaluated by the qualified CZE assay [12], wherein mAb charge variants are separated according to differential electrophoretic mobility in free solution within a uniform electric field applied across a buffer-filled fused silica capillary

Summary

Introduction

Quality of biotechnology products is defined as the suitability of the drug substance or drug product for its intended use [1]. This term includes product quality attributes such as quantity, identity, biological activity, and purity. Appropriate specification setting to ensure quality for biotechnology products must be underpinned by rigorous characterization of physicochemical, biophysical, and immunochemical properties [2]. An expansive and continuously growing historical characterization dataset has been compiled as a foundation for these intended uses [3,4,5,6,7,8], a subset of which has been refined and qualified for quality monitoring [9,10,11,12], and used for quality attribute value assignment as part of the NISTmAb lifecycle management plan

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