Gene therapy: Importance of choosing rAAV systems

Gene therapy developers need to carefully assess their choice of production platform to make sure it best fits likely demand, clinical timelines, and target patient population size.

The advice comes from a study in Current Opinion in Biotechnology that looked at the pros and cons of currently available recombinant adeno-associated viral vector (rAAV) based production systems.

The authors compared transient transfection (TT) – which is the most widely used rAAV manufacturing methods – with baculovirus expression vector (BEV) based systems and an older approach that uses producer cell line (PCL).

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BrianAJackson

The key finding – they say – is that gene therapy firms need to choose the rAAV system based on the specific needs of their candidate product.

“When determining the ‘best-fitting’ production platform for a program, it is important to first evaluate the overall product demand, clinical trial timelines, target patient population size, and then reconsider the benefits and risks associated with each rAAV production platform.”

Each approach has advantages and disadvantages. For example, the authors point out that TT systems are fast to implement but challenging and expensive to scale up. PCL systems in contrast are scalable and cost effective but stable cell line generation can be time consuming and require additional expertise.

“Therefore, the TT system would be a better fit for programs with an aggressive timeline but relatively low drug demand, while a PCL system would be the choice for programs with high product demand and longer process development timelines.”

Guideline considerations

In addition to taking likely demand, clinical timelines and target patient population into account, gene therapy firms also need to keep an eye on safety data as it emerges the authors say.

“The gene therapy field is still learning about the impacts of production platform and process parameters on rAAV product safety and efficacy.

“Until more clear guidelines are established to ensure consistent product quality, switching between production platforms should be cautiously assessed before moving from first-in-human clinical trials to pivotal clinical trials and commercial manufacturing.”

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