Cell/Gene Therapies

Viral Clearance in a Downstream AAV Process: Case Study Using a Model Virus Panel and a Noninfectious Surrogate

Over the past decade, adenoassociated virus (AAV) vectors have become established as leading gene-delivery vehicles. In 2017, the pipeline for gene therapies included 351 drugs in clinical trials and 316 in preclinical development (1–4). As those candidates advance, significant efforts are being made in process development and manufacturing for viral vectors, with the overall goal of reducing process impurities while maintaining the highest possible process yield. To address that goal, industry suppliers have developed innovative AAV-specific separation technologies. Thermo Fisher…

Rapid Development of Viral Vector Production Processes: Iterative Parameter Optimization

With recent developments and successes in cell and gene therapy, the biopharmaceutical industry is facing increased demand for safe and efficient delivery systems (1). Viral vectors, including adenoviruses (AV), adenoassociated viruses (AAV), and lentiviruses (LV), are among the most common delivery agents because they infect mammalian cells efficiently. Suspension cultures have become a popular choice for robust and scalable viral manufacturing systems. Using stable cell lines that integrate all or part of the viral production elements adds further benefits by…

Improving Cell Manufacturing Outcomes Using In-Line Biomarker Monitoring

Cell-based advanced therapies are changing modern medicine dramatically. Immunotherapies such as chimeric antigen receptor (CAR) T-cell therapies are treating different forms of cancer. Gene therapies are reversing the course of inherited diseases, and tissue-engineered medical products are restoring, maintaining, and replacing damaged organs (1–4). The development of new advanced therapies is booming. As of January 2020, the US Food and Drug Administration (FDA) has reported more than 900 investigational new drug (IND) applications for cell and gene therapy products. However,…

Optimization of Processes and Advanced Platforms for Viral Vector Processing

Viral vectors are synonymous with gene therapies, so their development, production, and processing are of upmost importance to all gene therapy researchers and manufacturers. Every year, I look forward to attending the Cell and Gene Bioprocessing and Commercialization conference in Boston and talking to leaders in industry and academia about their current approaches to advancing gene therapies. Like most other meetings this year, the conference was entirely online and had to provide a shortened agenda. Nonetheless, there was no shortage…

Manufacture and Regulation of Cell, Gene, and Tissue Therapies, Part 1: Chemistry, Manufacturing, and Control Challenges

Cell, gene, and tissue (CGT) therapies and other advanced-therapy medicinal products (ATMPs) have made tremendous progress over the past decade. They are different from other biologics and small molecules because of their inherent complexity and variability. Although many unknowns remain about the development of these products, their clinical success has enabled the CGT therapy and ATMP fields to advance rapidly. We are seeing an increase in the number of marketing authorization applications (MAAs) filed in the European Union and new…

Streamlining Industrial Purification of Adeno-Associated Virus

With its first licensed therapeutic now marketed worldwide (1), adeno-associated virus (AAV) has become a preferred vector for gene therapy. However, unlocking its full potential still poses challenges, many of which are associated with purification. The first involves the transition from upstream to downstream processes. AAV-bearing lysates are laden with debris that foul filtration media and limit or prevent concentration. Another challenge involves reduction of soluble host-cell DNA, which is complicated by its strong association with nucleoproteins. A third involves…

Making Safe and Effective CAR T Cells: How Droplet Digital PCR Can Improve Their Quality Control

Chimeric antigen receptor (CAR) T cells first entered US clinics in 2017 (1), and this therapeutic modality holds tremendous potential as one of the most effective forms of personalized cancer care ever to reach patients. The revolutionary impact of CAR T-cell therapy comes from its ability to rewire our own immune defenses to kill cancer cells: It essentially modifies a patient’s naturally existing immune cells to boost their recognition and attack of cancer cells so that the person’s own immune system…

Innovations in the Manufacturing of Cell and Gene Therapies

Advancements in next-generation cell and gene therapies are fulfilling the promise of personalized medicine and attempting to cure and heal patients. Multiple approved products have been launched in global markets and the number of clinical trials continues to grow. Developing innovative advanced therapies is one of the biopharmaceutical industry’s greatest opportunities to dramatically improve patients’ lives. WuXi Advanced Therapies is a contract testing, development, and manufacturing organization (CTDMO) that has launched several innovative world-class platforms. It offers integrated platforms to…

Technology to Transform AAV Manufacture

Adenoassociated virus (AAV) vectors are a popular choice for modern gene therapies because of their favorable safety profile, low immunogenicity, and the ease with which they can be transduced into different cell and tissue types. An AAV genome is a single strand of DNA comprising a replication (rep) gene, which encodes regulatory proteins involved in genome replication, and a capsid (cap) gene, which produces three capsid proteins. However, AAVs cannot replicate alone. In nature, AAV shares an exquisite relationship with…

eBook: Viral Vector Purification — A Discussion of Current Challenges and Methods

Adenoassociated viral (AAV) vectors have become synonymous with gene therapy delivery. However, because they are produced in such small quantities and because their upstream processes carry comparatively large amounts of host-cell DNA and other impurities, AAV purification can be challenging. Several researchers have applied different chromatographic strategies, but no universal method has been adopted in the biopharmaceutical industry. This eBook features a discussion among several industry experts that explores challenges specific to AAV purification, shedding light on whether current strategies…