Due to the complexity of proteins and their biological production, characterization of protein pharmaceuticals (biologics) poses much more demanding analytical challenges than do small-molecule drugs. Biologics are prone to production problems such as sequence variation, misfolding, variant glycosylation, and post-production degradation including aggregation and modifications such as oxidation and deamidation. These problems can lead to loss of safety and efficacy, so the biopharmaceutical industry would like to identify and quantify variant and degraded forms of the product down to low concentrations, plus have tertiary structure information. Because of the rapidly increasing power of mass spectrometry (MS), we can now conceive of an MS-based platform for comprehensive measurement of almost all the relevant drug's physical characteristics. A crucial piece of such a platform is data analysis software focused to address the needs of the biopharmaceutical industry. We propose commercial development of software, named Byologic, which will make major improvements in the characterization of biologics via a range of mass spectrometric assays. Both generic (biosimilar) and innovator drug companies stand to gain from Byologic. Public health, and regulatory agencies like the FDA charged with protecting the public, stand to gain too because better characterization will improve quality, safety, and increase the efficiency of drug development, leading to consumer and Government savings.
The proposed project will lead to commercial software for improved characterization of the detailed composition of therapeutic proteins, including degradative modifications, glycosylation and tertiary structural changes. More fully characterized protein drugs will lead to better assurance of efficacy, enhanced public safety, more informed regulatory decisions, and lower overall costs to the consumer.
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