November-December 2019 Featured Report

Capacity Analysis for Viral Vector Manufacturing: Is There Enough?

Advanced therapy medicinal products (ATMPs) are engineered to replace defective, disease-causing genes to compensate directly for a genetic defect or to encode a therapeutic protein construct (e.g., chimeric antigen receptor, CAR) for disease treatment. In most instances, a viral vector delivers the engineered genetic payload, targeting cells in situ or ex vivo through cellular modification, expansion, and infusion into a patient. Clinical successes of ATMPs bolstered by regulatory approval of products such as Luxturna (voretigene neparvovec-rzyl, Spark Therapeutics), Kymriah (tisagenlecleucel,…

Analytical Testing Strategies for CAR T-Cell Products

Assay lifecycle development for traditional biopharmaceuticals such as vaccines and monoclonal antibodies (MAbs) has a clearly defined pathway, from preclinical method selection, development, and optimization through the milestones in preclinical phase trials, and finally to postlicensure method evaluations, comparability, and improvements. The analytical development roadmap for nontraditional biologics such as chimeric antigen receptor (CAR) T-cell therapies and gene therapies are not as clearly defined and can present many challenges along the way. Understanding the “what, how, and when” of analytical…

Measure Twice, Treat Once: Navigating the Regulatory Landscape of Assay Development to Ensure High-Quality CGT Products

Cell and gene therapies (CGTs) are a novel and fast-growing class of transformative therapies designed to address gaps in traditional treatment strategies of some of the most severe diseases. By definition, gene therapy “seeks to modify or manipulate expression of a gene to alter the biological properties of living cells for therapeutic use” (1). That can be either an in vivo delivery of a gene or delivery of a gene to a patient’s cells that are manipulated outside of the…

AAV Vector Manufacturing Platform Selection and Product Development

Adenoassociated virus (AAV) vectors have emerged as the prominent delivery mechanisms of corrective gene therapies. Three such products — Glybera (alipogene tiparvovec, uniQure), Luxturna (voretigene neparvovec-rzyl, Spark Therapeutics), and Zolgensma (onasemnogene abeparvovec-xioi, AveXis) — have been licensed, and a growing number of candidates are entering late-stage development. In mapping out an AAV gene therapy product development strategy, biomanufacturers should address fundamental considerations for their manufacturing strategies for both phase 1–2 clinical evaluation and translation for commercial market supply. A manufacturing…