But with the rapid growth of the cell and gene therapy sector the demand for innovative technologies to improve process development and facilitate manufacturing scale-up, currently outstrips supply and could delay the commercialization of rAAV products, says Polyplus-transfection.
Based in a science park near Strasbourg, the producer maintains that it is one of the few companies working with viral vector manufacturers to combat this problem. Last week, Polyplus announced the official release of its transfection reagent - FectoVIR-AAV GMP - specifically for large scale manufacturing, which is said to complement its existing reagent line.
The company has also been scaling up of late in order to ensure it can supply transfection reagents to the CGT sector for the next two decades; April 2020 saw a major investment in the developer from Warburg Pincus and ArchiMed. Then, in January 2021, Polyplus initiated construction of Vectura, its major new 4,000m2 HQ and central facility in Strasbourg, which is nearing completion. Furthermore, in March this year, it acquired Biowire, a firm specializing in supporting life sciences tool and reagent companies to expand into Asia-Pacific.
New transfection reagent
FectoVIR-AAV GMP has been added to its transfection reagent portfolio to help manufacturers alleviate major pain points with linear process scalability and flexibility. Users will be able to work from small scale process development stages to improve AAV production in suspension cell culture systems and more easily transition into large-scale GMP manufacturing activities, said the company.
We spoke to Roel Gordijn, COO, and Geraldine Guerin-Peyrou, director of marketing and technical support, Polyplus, to hear more about the product.
BioPharma-Reporter: How does this reagent differ from existing ones within Polyplus’ reagent line?
Polyplus: One of the major current bottlenecks in gene therapy is the cost of treatment. FectoVIR-AAV improves viral titers from 3-to-10-fold compared to conventional PEI based transfection reagents, and enables industrial scale manufacturing in large bioreactors, hence lowering the cost of manufacturing per dose.
The gene-therapy viral vectors that are currently manufactured will be tested in human patients. Therefore, the quality needs to be at the highest standards to assure patient safety. Polyplus has decided to manufacture FectoVIR-AAV GMP according to pharma grade good manufacturing practice (GMP). These GMP standards are followed for the manufacturing of the active substance as well as for the aseptic final fill and finish of the reagents. There are currently no other transfection reagents available of this GMP quality level.
BPR: How does the reagent support large scale manufacturing?
Polyplus: FectoVIR-AAV GMP has been specially developed with CGT needs in mind: Performance, cost-effectiveness, scalability, and accelerated time to market.
- Superior Performance: Highest AAV titers for increased number of doses per batch. FectoVIR-AAV users see 3-to-10-fold titer increase compared to conventional PEI based transfection reagents.
- Scalable: Robust and flexible to support small to large scale production. FectoVIR-AAV is using lower transfection reagent pDNA complex volumes and has a longer complex stability compared to conventional PEI based transfection reagents. It is therefore possible to scale processes up to suspension bioreactors of 500L and larger for industrial use. Larger batch sizes will reduce the cost per dose.
- Cost-effective: Reduced cost per dose for therapy affordability. The possibility to increase AAV titers 3-to-10 fold and to increase batch sizes up to 2000L will have a possibility to dramatically reduce the manufacturing cost per dose.
- Accelerated time to market: Performance and scalability for faster process development. FectoVIR-AAV is a reagent that allows customers to robustly scale up to larger volumes suspension cultures and therefore do not delay product launch due to extended process development time.
BPR: What type of demands is Polyplus encountering when engaging with customers?
Polyplus: The safety of the patients is a major concern, thus we have taken the route to manufacture FectoVIR-AAV GMP according the most stringent GMP guidelines in the industry. The product is filled through an aseptic process in a bag compliant to use in closed system. In addition, a residual test is currently under development and will soon be available to complete the regulatory package provided with FectoVIR-AAV GMP.
From a technical point of view, our customers are requesting higher viral titers and ease of use in an industrial setting. FectoVIR-AAV opens the possibility to increase AAV titers 3-to-10 fold and to increase batch sizes up to 2000L, thus the possibility to dramatically reduce the manufacturing cost per dose..