Overcoming Challenges of Biologic Characterization

Biologic characterization can be complex and may prove challenging for scientists when there are pressures to deliver consistent and accurate results quickly. SCIEX recently announced the launch of the BioPhase 8800 system, a multi-capillary system for CE-SDS that processes eight samples simultaneously.

To learn more about the system and how it can help to overcome current bioanalytical challenges, Technology Networks spoke to Mani Krishnan, vice president and general manager, SCIEX CE and Biopharma. 

Ash Board (AB): What makes capillary electrophoresis (CE) particularly suitable for purity analysis in biologic drug development?

Mani Krishnan (MK): CE is very well suited for separation of large molecules such as proteins, nucleic acids and larger complexes like viruses or viral vectors. CE separates molecules based on their mobility in an electric field. That mobility is a function of the overall charge, size and drag (frictional) force experienced by the molecule; the stronger the applied field, the faster the mobility. This separation mechanism results in exceptional resolving power that is ideal for larger molecules. For example, CZE can separate a single amino acid change on a mAb while cIEF can resolve deamidation of one amino acid. CE, with the right sieving matrix, can resolve a single base difference in single stranded DNA. CE instruments harness this separation power to provide highly reproducible separations quickly and efficiently, particularly for large complex molecules such as biologic drugs. In addition to requiring minimal sample preparation, CE analyses are highly amenable to automation.

As the complexity of biologic drugs increases, there is a growing need for robust and ever more precise analytical methods that can provide purity, heterogeneity and post-translational modification data simply and quickly from drug discovery through process optimization and scaleup to QC and post-launch assessment. With its high separation efficiency, short analysis time, low injection volume requirements, ease of operation, optimized chemistries and demonstrated use with a number of different detection methods, CE has become a method of choice for both qualitative and quantitative analysis of even the most complex next-generation biologics.

AB: SCIEX has had great success with the PA 800 Pharmaceutical Analysis System; how does the new BioPhase 8800 system build on this?

MK: The PA 800 and PA 800 Plus solved critical questions for biopharma and transformed the way scientists analyze biologics. Even so, we never stopped listening to our customers, learning from their experiences, and experimenting to really understand the evolving challenges our customers face. Today, biopharmaceutical drug developers are working with increasingly complex molecules. They need to understand molecular liabilities much sooner in order to close the developability gap and ensure the manufacturability of robust, stable molecules prior to clinical trials. Biopharma scientists are under tremendous pressure to deliver confident results faster while existing approaches to detect and characterize changes during drug development take too long or require additional bridging studies.

The SCIEX BioPhase 8800 system is the next stage of our CE journey and delivers the same consistent data that our customers have relied on with the PA 800 systems. This entirely new CE platform was designed to help biologic drug developers take charge of their development pipelines, maximize efficiencies, and accelerate time to market. This enables parallel processing of multiple samples simultaneously using CE-SDS and CIEF with UV or LIF detection.   

AB: As biologic drug development moves beyond monoclonal antibodies, what are some of the challenges scientists face?

MK: Biologics are getting more complex in their structure, and samples are getting more numerous, and require more complex analytical methods that involve complex method set ups, but results are needed in less time. Sample stability is an ongoing concern for our customers, and high throughput analysis is needed to characterize and quantify their samples quickly. Methods are needed that allow for the generation of consistent, comparable data across their development continuum from bioprocessing, to research and development, all the way to QA/QC.

Existing approaches to detect and characterize changes during drug development take too long and are challenged to deliver the detailed information that is needed. High-throughput analytical techniques that can overcome these complexities are becoming essential.

AB: How does the BioPhase 8800 system help scientists overcome these challenges?

MK: With the SCIEX BioPhase 8800 System, scientists can run more complex samples in less time, with 8 samples running simultaneously on a single platform. It is possible, for the first time, to quickly develop methods for screening and characterizing traditional and newly engineered molecules, accelerating experimental design processes from months to as little as a week.

Scientists can now confidently deliver consistent, accurate, reliable data along their drug development pipelines, simplifying and facilitating tech transfer across the development continuum. Simply put, the BioPhase 8800 system accelerates analysis and dramatically shortens new therapy development timelines while providing the sensitive, high-resolution data expected in the biopharma industry.

In summary, it helps biologic drug developers take charge of their development pipelines, maximize efficiencies, and accelerate time to market.

Mani Krishnan was speaking to Ash Board, Editorial Director for Technology Networks.