Making therapies from monoclonal antibodies can go wrong in many directions. To reduce the risk of failure, scientists need technology that analyzes the antibodies along the way. One method to do that is with attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy.

Sergei G. Kazarian
Sergei G. Kazarian with an FTIR-imaging microscope. [Imperial College London]
As Sergei G. Kazarian, PhD, professor of physical chemistry at Imperial College London and his colleagues wrote, ATR-FTIR is “a label-free, non-destructive technique that can be applied to a vast range of biological applications, from imaging cancer tissues and live cells, to determining protein content and protein secondary structure composition.”

Kazarian explains that this review article explores “the use of a high throughput ATR-FTIR spectroscopic imaging as an in-situ method to investigate aggregation of IgG monoclonal antibodies—a commonly used biotherapeutic.” He adds, “This article is timely because in situ ATR-FTIR spectroscopy and imaging has the potential to provide understanding of therapeutic antibody behavior at key points in the manufacturing process.”

Although an increasing number of antibody-based therapies are available on the market, covering a range of conditions, from asthma and cancer to heart and neurodegenerative diseases, Kazarian notes that therapeutic antibodies “are problematic to produce.” His long-time collaborator, Bernadette Byrne, PhD, professor of molecular membrane biology at Imperial College London,  notes that “Protein aggregation in production severely affects quality, safety, and efficacy of monoclonal antibodies produced, and can occur in any step of the production pathway including cell culture, purification, and storage/transportation.”

By using ATR-FTIR spectroscopy, researchers could learn more about the changes in antibodies during production.

“ATR-FTIR spectroscopic imaging can be applied in situ and may play an important role in studying structural changes of biopharmaceuticals in processing, such as aggregation,” Kazarian says.

By using in situ ATR-FTIR spectroscopic imaging to investigate protein aggregation, states PhD student Hannah Tiernan, bioprocessors could determine “the suitability of individual antibody batches for further processing,” and  “a further understanding of aggregation behavior of antibodies close to surfaces provides a basis for rational optimization of the antibody-production pipeline.”

In Bioprocessing 4.0, biomanufacturers will rely increasingly on methods of analyzing therapeutics at various stages of production. ATR-FTIR spectroscopy provides an opportunity to improve the quality control while producing antibodies. This technology can also be used in R&D on new antibody-based therapies.

Kazarian and Byrne also have other lab members applying in situ ATR-FTIR spectroscopy to the behavior of purification resins used for isolation of therapeutic antibodies. Overall, ATR-FTIR spectroscopy could improve bioprocessing in many ways—pretty much from start to finish.

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