We've updated our Privacy Policy to make it clearer how we use your personal data. We use cookies to provide you with a better experience. You can read our Cookie Policy here.
Advances in Monoclonal Antibody Purification and Analysis
eBook
Last Updated: May 21, 2024
(+ more)
Published: May 3, 2024
Credit: Thermo Fisher Scientific
As the scientific understanding of traditional monoclonal antibody (mAb) therapeutics has advanced, researchers are now engineering proteins to create next-generation antibody modalities including antibody fragments, bispecific antibodies, antibody–drug conjugates and Fc-fusion scaffolds.
These innovations are accompanied by advances in the biotechnologies designed to develop and manufacture them. However, each biomanufacturing process must ensure product purity and efficacy, among other quality criteria, in order to be approved for clinical use.
This eBook addresses common mAb purification, analysis and quality evaluation challenges and offers solutions for improving process efficiency and reliability.
Download this eBook to explore:
Affinity purification in monoclonal antibody manufacturing
Process analytics to ensure quality and safety
Innovative uses of single-domain antibodies in mAb therapeutic research and development
Progress in antibody therapeutics in recent years has been revolutionary.
Although the US Food and Drug Administration approved the first monoclonal
antibody (mAb) therapeutic in 1986, only 13 more had been approved by the
end of 2002. Over the next 20 years, more than 100 mAbs would be approved
(figure 1).1
This growing interest in antibody therapeutics has propelled the
growth of the global market, which had a value of about $200 billion in 2022.2
Figure 1: Antibody therapies approved by the US Food and Drug Administration by year.
Gray indicates conventional antibodies and blue indicates engineered antibodies, including
antibody-drug conjugates, bispecific antibodies, and Fc-fusion scaffolds.
Source: Reference 1.
INTRODUCTION
THE STATE OF MONOCLONAL
ANTIBODY MANUFACTURING
Conventional antibodies Engineered antibodies
4
Antibody therapeutics provide cell-specific recognition customized for a patient
and the potential to modulate an immune response. They offer the ability to
treat cancers and autoimmune diseases with fewer side effects than traditional
treatments such as chemotherapy. Many mAb therapeutics are made from socalled conventional antibodies, Y-shaped proteins with specific binding sites at
the end of each arm of the Y.
As the scientific understanding of traditional mAb therapeutics has advanced,
researchers have moved into engineering proteins to create next-generation
antibody modalities. Antibody fragments, bispecific antibodies, antibody-drug
conjugates (ADCs), and Fc-fusion scaffolds have all received FDA approval
since 2019.1
Innovations in the field of mAb therapeutics are accompanied by advances in
the biotechnologies designed to develop and manufacture them. Engineered
antibodies are produced in cultured cells. Research and development teams
must show that their entire biomanufacturing process is reliable before
receiving approval (figure 3). This effort includes instituting measures to
ensure purity and confirming that analytical techniques effectively test for
contamination, activity, and other quality concerns. As the saying goes: the
process is the product.
Figure 2: While most antibody-based therapeutics are conventional antibodies (left), an increasing
number of engineered antibodies have received regulatory approval. Engineered antibodies include
antibody-drug conjugates, bispecific antibodies that have two different recognition sites, and various
antibody fragments.
Credit: C&EN BrandLab
Figure 3: The process of antibody manufacturing involves cell culture, separation, purification, and filling.
Credit: Thermo Fisher Scientific
Conventional
antibodies
Antibody-drug
conjugates
Bispecific
antibodies
Engineered antibodies
Fragments
Fab single
domain
antibodies
Cell culture
development
Scale up to
production
Harvest and
collection Purification Bulk storage
and final fill
5
The purification step of antibody manufacturing provides an example of the
need for technology evolution. A common purification technique involves a
bacterial protein called protein A. Protein A binds to the stem, or Fc region, of
immunoglobulin G (IgG) antibodies, which are the antibody type most used
for therapeutics. By preparing a chromatographic resin with protein A, it is
possible to separate mAbs from other cellular materials. Protein A affinity
chromatography remains a popular and effective tool for purifying conventional
mAbs. But protein A is ineffective at purifying newer antibody-derived
therapies, such as fragments or bispecifics.3
For this increasingly diverse class
of biotherapeutics, scientists must find alternative methods to meet the purity
requirements without losing yield.
Now, pharmaceutical manufacturers that produce mAb-based therapeutics
face a complex set of scientific and business challenges. Part of the
commercial success of antibody-derived therapeutics depends on efficient
purification and analytical techniques. Companies that implement state-ofthe-art technology can improve their time to market, reduce the chance of
quality issues, and lower manufacturing costs. This e-book addresses common
purification, analysis, and quality evaluation challenges when manufacturing
modern antibody-derived therapies. Tools such as affinity chromatography,
quantitative polymerase chain reaction (qPCR), and single-domain antibodies
provide effective and flexible solutions for improving the efficiency and reliability
of antibody biomanufacturing practices.
References:
1. Xiaochen Lyu et al., “The Global Landscap
Brought to you by
Download this eBook for FREE Below
Information you provide will be shared with the sponsors for this content.
Technology Networks or its sponsors may contact you to offer you content or products based on your interest in this topic. You may opt-out at any time.