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The move to large molecules in Pharma is accelerating, offering unprecedented opportunities to improve human health and expand into new markets. But for those with extensive experience with small molecule bioanalysis, the shift to biologics can be challenging, from Sample Prep to Instrumentation and Software, to Methods and Training:

Today, 30 monoclonal antibodies (mAbs), have been approved for the treatment of certain cancers, autoimmune and infectious diseases. Even more are in development, and perhaps you and your team of scientists are working on one now.  Keeping pace with fast development timelines while performing comprehensive characterization of biologic candidates can be challenging. However, more and more, scientists are tackling these challenges with new techniques to speed and simplify their characterization workflows. Read more in the application note, “Rapid Characterization of Biologics using a CESI 8000 – SCIEX TripleTOF® System,” found in the Biologics Analytical Characterization Compendium, which highlights how CESI separation coupled with high-resolution mass spectrometry can provide a comprehensive characterization of biotherapeutics.

Although the triple-stage quadrupole (QQQ) mass spectrometer remains the pillar for quantitative LC-MS/MS bioanalytical assays, due in part to the platforms’ high duty cycle when operated in multiple-reaction monitoring (MRM) mode, the applicability of high-resolution mass spectrometry (HRMS) has become of increasing importance for protein quantitation given the complexity of proteolytically digested samples in the surrogate peptide approach.  While the QQQ demonstrates high sensitivity and specificity, the relatively low-resolution measurement of m/z may fail to differentiate analyte response from nominally isobaric background interference.  In contrast, HRMS with accurate mass assignment of product ion allows interference to be resolved through judicious selection of a post-acquisition mass extraction window whose tolerance is largely dictated by the effective resolution and stability of mass calibration.

Fast LC-MS acquisition and automated data processing will help you speed up peptide mapping of your biotherapeutic, including critical disulfide bond and post-translational modification characterization. SCIEX helps you untangle the complexity of disulfide bonds, speeding up your characterization process.

During drug development, the removal of impurities and purification of a final drug product is absolutely essential in order to ensure the safety and efficacy of a therapeutic drug. Of particular concern for biologics are impurities that can stem from host cell proteins. Because biologics are developed through cell culture and fermentation within a host cell, proteins from this host cell can be co-purified with the final biologic. These host cell proteins or HCPs can cause the final product to have undesired side-effects such as eliciting an immune response in patients taking the drug, or affecting the drug’s stability or efficacy. As a result, regulating agencies require drug companies to monitor levels of HCPs during the development and purification of a biologic and to remove HCPs to an acceptable level in the final biotherapeutic product.

These days, everyone seems to be furiously scratching tickets to become instant winners, but I’ll bet you didn’t expect to find sample prep tips that way. For large molecule bioanalysis, preparing your samples can be one of the biggest challenges. It’s a whole different world from traditional small molecule bioanalysis. SCIEX has developed techniques and automation that make biologics sample prep simpler and faster, with reproducible results.

Since the 1982 approval of Eli Lilly’s recombinant human insulin, Humulin, biotherapeutic drug development has steadily grown into a global market valued at $140 billion in 2013, increased from $25 billion in 2001

Last week we posted a blog on Biologics Bioanalysis Key Challenges, where we presented a webinar on those key challenges.

Traditionally, the pharmacokinetic profile of biotherapeutics such as insulin glargine, adalimumab, trastuzumab and others, used gold standard LBAs to assess dose-response during drug discovery and development. However, LBAs require a specific antibody reagent to be developed for each mAb variant, a process that is often incompatible with the compressed timeframes encountered during the initial stages of drug development.