Journal of Blood Disorders & Transfusion

New platform technologies for biotherapeutics and emerging rewards and risks

12^th World Hematologists Congress

March 15-16, 2018 | London, UK

Chava Kimchi-Sarfaty

Center for Biologics Evaluation and Research, Food and Drug Administration, USA

Keynote: J Blood Disord Transfus

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. Recent Publications 1. Hamasaki Katagiri N, Lin B C, Simon J, Hunt R C, Schiller T, Russek Cohen E, Komar A A, Bar H and Kimchi Sarfaty C (2017) The importance of mRNA structure in determining the pathogenicity of synonymous and non-synonymous mutations in haemophilia. Haemophilia 23:8-17. 2. Hunt R C, Yalamanoglu A, Tumlin J, Schiller T, Hyen Baek J, Wu A, Fogo A, Yang H, Wong E, Miller P, Buehler P and Kimchi Sarfaty C (2017) A mechanistic investigation of thrombotic microangiopathy associated with intravenous abuse of Opana ER. Blood 129:896-905. 3. Lagassé H A, Alexaki A, Simhadri V L, Katagiri N H, Jankowski W, Sauna Z E, Kimchi Sarfaty C (2017) Recent advances in (therapeutic protein) drug development. F1000Res. 6:113. 4. Athey J, Alexaki A, Rostovtsev A, Santana Quintero L, Katneni U K, Simonyan V, Kimchi Sarfaty C (2017) A new and updated resource for codon usage tables. BMC Bioinformatics 18:391. 5. Katneni U K, Hunt R C, Hettiarachchi G, Katagiri N, Kimchi Sarfaty C and Ibla C J (2017) Compounding variants rescue the effect of a deleterious ADAMTS13 mutation in a child with severe congenital heart disease. Thrombosis Res. 158:98-101.

Biography :

Chava Kimchi-Sarfaty currently leads a group at the FDA within the Division of Plasma Protein Therapeutics, Office of Tissues and Advanced Therapies (OTAT) that investigates various blood coagulation factors with a specific focus on the genetic determinants of coagulation factor biosynthesis and structure. She is also the Acting Deputy Associate Director for Research of the Office. She reviews and chairs pre-INDs, INDs and BLAs for recombinant proteins and plasma derivatives products such as von Willebrand factor, ADAMTS13, factor VIII, FIX, thrombin and fibrinogen.
Email:Chava.Kimchi-Sarfaty@fda.hhs.gov