The number of gene therapies in different stages of clinical trials is increasing, driving the need for innovative process and analytical strategies. Viral vectors (e.g., adenoassociated viruses and lentiviruses) are used for delivery of gene therapies, so their production and purification are critical for gene therapy success. In this featured report, authors project future capacity needs for viral vectors and discuss the importance of selecting the best platform for their manufacture and scalability. Authors also discuss approaches for assay development and testing strategies.

Capacity Analysis for Viral Vector Manufacturing: Is There Enough?
Joseph Rininger, Ashley Fennell, Lauren Schoukroun-Barnes, Christopher Peterson, and Joshua Speidel
The number of advanced therapy medical products (ATMPs) in development has grown over the past five years. This growth has been spurred by dramatic clinical effectiveness data and the licensure of three gene therapies and three genetically-modified cellular therapies over the past seven years. An evolving and flexible regulatory environment has enabled rapid clinical development and licensure of products for patient populations with rare diseases. All licensed products either consist of adenoassociated virus gene therapy vectors, which are directly administered to the patient to replace a defective gene or rely on lentiviral vectors to engineer cells that are then expanded and become final products delivered to patients. The manufacturing of viral vectors requires specialized facilities and procedures. As a result, there is a limited pool of contract development manufacturing organizations (CDMOs) capable of accommodating growing demand. The number of products in this sector and CDMO capabilities for the manufacture of these two vectors were determined to build a forecast of viral vector demand for clinical stage programs. The analysis, detailed herein, indicates that the demand for CGMP viral vectors will exceed capacity within the next year, despite expansions undertaken by many of the CDMOs manufacturing these vectors. To reduce risk to drug product supply for clinical programs, developers of ATMPs that require viral vectors would do well to select a CDMO manufacturing partner earlier rather than later, as available capacity is at a premium due to numerous bidders and limited CDMO capacity.

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Analytical Testing Strategies for CAR-T Products
Maribel Rios, with Andrea Moore
Based on her presentation at the BioProduction Congress in June 2019, this article focuses on the assay method lifecycle development for chimeric antigen receptor (CAR) T-cell therapies. Moore highlights the differences between such methods to those of traditional biopharmaceuticals and provides a method case study for flow cytometry development.

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Measure Twice, Treat Once: Navigating the Regulatory Landscape of Assay Development to Ensure High-Quality CGT Products
Manoja Eswara, Sarah Kwon, Steven Loo-Yong-Kee, and Vaja Misic
Research and development of new cellular and gene therapy (CGT) products to treat different therapeutic indications is growing rapidly, and many candidates are progressing in clinical development. CGTs must be manufactured using processes that ensure a predefined quality of products. Careful monitoring of critical quality attributes and other product characteristics is needed in process development and in manufacturing to ensure product safety and efficacy. Product intermediaries and drug products are assayed using analytical assays that must be validated before regulatory approval. The authors discuss the use of analytical assays in process development and manufacturing, how tests are developed and validated, and current gaps in the analytical tool kit.

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AAV Vector Manufacturing Platform Selection and Product Development
Joseph Rininger, Ashley Fennell, Lauren Schoukroun-Barnes, and Joshua Spiedel
Adenoassociated virus vectors are the prominent delivery mechanism of corrective gene therapies. The authors focus on the factors to consider in mapping out an AAV gene therapy product development and manufacturing strategies for both phase 1-2 clinical evaluation and translation for commercial market supply. They review current cell lines and the process for AAV manufacturing platform selection, considering supply chain of critical raw materials, cell substrate manufacturing platform, and the decision to either outsource manufacturing or to establish internal manufacturing capabilities. Manufacturing scalability and limitation of some platforms and the process of transitioning from one platform to another are discussed.

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