12^th World Hematologists Congress

Biography

Biography: Chava Kimchi-Sarfaty

Abstract

Therapeutic proteins now represent a growing and critical component of drug development. Biotherapeutics such as antibodies, recombinant enzymes, gene and cell therapies continue to revolutionize the treatment of many diseases. The production and regulatory approval of these complex molecules are not without their own inherent challenges. A growing list of protein engineering strategies exists to improve the circulating half-life, bioavailability, function and stability of recombinant protein therapeutics. To aid in biomanufacturing, protein therapeutics are often strategically designed with synonymous and/or non-synonymous mutations to eliminate rate-limiting transcriptional/translational features in the native expression sequence. In a technique known as codon optimization, hundreds of synonymous mutations are strategically incorporated into the expression vectors of recombinant therapeutic proteins. We seek to understand how protein biogenesis can be modulated by genetic variants in the coding sequence using model recombinant proteins regulated by CBER. To this end, we have evaluated existing and new laboratory assays that are sensitive to transcriptional, translational and posttranslational processes. These emerging technologies for recombinant protein design are regularly evaluated at FDA’s CBER, which encompasses a holistic view of protein therapeutic development and monitors the process from the bench to the bedside to ensure effective development and product licensing. CBER’s goals include development and enforcement of laboratory standards by evaluating technologies and reagents as well as the assessment of pre-clinical models and clinical approaches. These goals are in line with CBER’s vision to improve the safety of biological products and ultimately advance public health.