A roadmap for analytical characterization of biotherapeutic proteins

During the development of proteins for use as biotherapeutics, the primary structure (amino acid sequence) is important in defining protein activity. It is also crucial to characterize the protein’s higher-order structure (HOS) to understand the protein’s stability, folding, structure, and functional activity.  This information is used to make decisions which drugs to move forward in development, and also as quality control and biocomparability studies.

A recently published book, Biophysical Characterization of Proteins in Developing Biopharmaceuticals (Houde and Berkowitz, authors, Elsevier, 2014), aims to help scientists successfully implement biophysical methodologies to characterize HOS of protein drugs. This includes describing the capabilities of these assays and what information they are able to deliver. Since protein drugs are complex biomolecules, this book also discusses the best practices to collect biophysical information, and avoid possible pitfalls, so scientists can make informed decisions during drug development.

Bioanalytical tools described in the book include: static light scattering, dynamic light scattering, nanoparticle tracking analysis, differential scanning calorimetry, size exclusion chromatography, resonant mass measurement (Archimedes), Raman spectroscopy, particle and viscosity assays.

The authors of each chapter are experts in the field, many currently working in the biopharmaceutical industry. I was invited to co-write the section on Differential Scanning Calorimetry (DSC) with Dr. Stephen Demarest, a scientist with Eli Lilly Biotechnology Center in San Diego, California.

DSC, including the MicroCal VP-Capillary DSC, is a tool to characterize thermal stability,  and DSC has an important role  in the discovery and development of protein and peptide therapeutics. Many biotherapeutics currently entering the clinic have undergone engineering to optimize desirable characteristics like immunogenic profiles, function/activity, and shelf life. Biophysical tools like DSC demonstrate that these engineered molecules maintain physical stability.  DSC also helps in process development and manufacturing of biotherapeutics , as well as  its formulation.  You can purchase a PDF of this chapter on the Science Direct website – more details here.

The book serves as a roadmap for scientists on which techniques to prioritize, and what they need to focus on, for successful development of new drugs in an efficient and cost effective manner – click here for more details.

View Verna Frasca’s profile on ResearchGate.

Further Resources:

Application Note: Accelerating the development of optimized therapeutic protein formulations using Differential Scanning Calorimetry

Whitepaper: Differential Scanning Calorimetry: Theory and Practice

Recorded Webinar: Solve stability problems in preformulation and process development using DSC