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Oligonucleotides are becoming increasingly important as therapeutic agents. Since the commercial launch of the first oligonucleotide therapeutic (ONT) in 1998 (Vitravene®), ten ONT products have received market approval, the majority of which were approved in the last four years. ONTs share properties with chemical (e.g. they are synthesized via chemical processes) and biological pharmaceuticals (e.g. in terms of selective tissue distribution), and therefore present unique development challenges. The preclinical safety evaluation for ONTs has generally followed the regulatory guidelines for small molecule pharmaceuticals. However, ONTs may elicit an immune response, just like biotechnology-derived products do, and therefore require the assessment of immunogenicity. Quantification of ONTs in biological matrices is also conducted using the techniques applied for biological drugs.
This document presents a short overview of the industry-standard techniques used for the measurement of plasma concentration, tissue distribution and immunogenicity of ONT products.
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