Page 13 - Shimadzu Journal vol.9 Issue2

Biopharmaceutical

Method Optimization for

the Analysis of Monoclonal Antibodies

by Size-Exclusion Chromatography

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Emiko Ando , Daiki Fujimura , Keiko Matsumoto 1
1 Analytical & Measuring Instruments Division, Shimadzu Corporation

Abstract Antibody drugs using monoclonal antibodies pose con­ The most common biopharmaceuticals are antibody drugs that
cerns over aggregates formed during production and storage and their
utilize monoclonal antibodies (mAbs). Due to their high level of
impact on safety and efficacy. During monoclonal antibody production,
specificity and affinity for target molecules, they offer the benefits
aggregates formation is monitored, and size-exclusion chromatography
is one of the most widely used techniques. However, size-exclusion of excellent therapeutic efficacy and mild side effects, and are used
chromatography is performed at relatively low flow rates and requires
to treat a variety of diseases including autoimmune diseases and
long analysis times. Analyses of monoclonal antibody drugs must also
cancer. However, unlike pharmaceuticals that can be controlled
take into account interaction between the monoclonal antibodies and
column packing materials. This Technical Report provides an example artificially in manufacturing processes such as chemical synthesis,
of using a column packed with small particle material to optimize an
biopharmaceuticals are manufactured using living cells. Therefore,
analytical method for analysis of monoclonal antibody aggregates. This
appropriate quality controls must be established at every produc-
article investigates the effect of mobile phase salt concentration, flow
rate, and pH on chromatographic separation and peak shape. Moreover tion step to ensure uniformity and quality of the final product.
we describe an example of method optimization by using a dedicated
software for improving separation, sensitivity and reducing analytical time.
There are numerous steps from development to production of anti-
Keywords size-exclusion chromatography, antibody drug, Nexera™ body drugs. The first step is to find an antibody effective against dis-
XS inert, method scouting system
ease based on its affinity and specificity to target molecules. The next
step introduces genetic information coding for the selected antibody
into cells and determines what culture conditions ensure efficient
Background protein expression. These culture conditions are then scaled up for
mass production and the target protein is isolated from cultured
Pharmaceuticals have recently diversified away from low-molecular- cells and purified to produce the bulk drug. In order to produce
weight compounds also to include macromolecular drugs. Biopharma- high-quality antibody drugs, consistent and robust manufacturing
ceuticals developed and produced with biotechnology have been methods are essential. The quality, efficacy, and safety of antibody
particularly effective in treating wide range of diseases. drugs are assured by performing purity tests in conformance with
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ICH-Q6B , including purity analysis and structural analysis of

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