The oncolytic virus market is expected to reach $609 million by 2028, growing at a compound annual growth rate of 26.2%.[1] This will be driven by the number of oncolytic virus therapies that are in the pipeline, with more than 70 companies working on more than 100 clinical candidates.[2]
Due to their considerable potential for the treatment of cancers, those in the biopharmaceutical industry are increasingly interested in the oncolytic virus space. Not only are these therapies able to selectively target cancer cells but they are also able to highlight the cells for destruction by the body’s own immune system, offering advantages as part of a combination treatment.
Despite the potential of the oncolytic virus market, there are challenges that need to be overcome for developers to bring these therapies to the clinic and then onto commercialization. The scale-up of manufacturing is one hurdle in particular that can be a significant difficulty for many oncolytic virus producers. For those rising to this challenge, the following areas are ones that need to be considered carefully to ensure the successful delivery of their therapeutic product.
Cell line selection
Viruses are heterogeneous and available cell lines will vary in suitability for the manufacture of different kinds of live viruses and viral vector products. As a result, there are many factors that must be considered when choosing a cell line, including:
- The kind of product being manufactured (e.g., an enveloped virus or non-enveloped virus)
- The productivity of the cell line
- Whether transportation of cells between different countries is needed, potentially impacting regulatory compliance and licensing.
When considering scaling, oncolytic virus manufacturers must also take time to determine the type of cell culture method that would be best for the project, relying on either suspension or adherent cell cultures.
Adherent cell culture
With adherent cell cultures, scaling is possible using cultivation units (e.g., roller bottles, T-flasks, and CellSTACKs) by increasing the required surface area for adherence via “scale-out” (using multiple vessels). However, scaling out requires a large area of facility floor space, which is not always available, as well as manual handling processes that can be associated with contamination risk.
To counter this challenge, many oncolytic virus developers are now relying on fixed-bed bioreactor systems as opposed to cell culture vessels. These bioreactors often offer higher surface-to-volume areas for growth and the potential for automated functions with minimal handling.
Suspension cell culture
Suspension cell culture platforms often possess certain benefits over adherent alternatives. As well as offering scalability, with bioreactor systems available in various sizes up to capacities of 5000 L, suspension platforms can also be automated relatively easily. Additionally, many single-use options are available for suspension cell cultures, reducing the potential for contamination between projects.
On scale-up, there are different bioreactor systems to consider, for example, cylindric or cubic-shaped, with capacities extending up to 5,000 L. Rocker-style bioreactors can be used as intermediate or final vessels, and wave bags with integrated perfusion membranes are also available.
Virus rescue and cloning
Virus rescue is the starting point for obtaining engineered viral clones to be applied in process development and production applications. This process involves generating first virus passage and necessitates different technology depending on virus type.
Virus cloning follows virus rescue and is carried out by plaque isolation, followed by one round of virus amplification. Decisions to be made at this stage surround procedural control and process safeguards, and whether animal-derived raw materials are necessary. It should be noted that during development and prior to a BLA filing, the genetic stability of the virus product should be assessed to determine suitability for commercial manufacture.
GMP cell and virus bank generation
Cell and virus seed materials are crucial, both at the start of the production process and throughout the product lifecycle. The factors to account for when considering scaling are the key parameters and bank size, with a typical master cell bank (MCB) established with 300-500 vials on average, and 500-1000 for working cell banks (WCB), with similar numbers for virus banks. Other considerations are to carry out pre-GMP feasibility studies and to determine long-term storage requirements.
Process development and DS/DP activities
Process development activities depend on the project’s objectives. Scale-up and volumetric production must be determined; this will involve estimating the final clinical or commercial scale of production, as well as determining cell-substrate and the production systems used.
Both an effective virus recovery strategy and a purification strategy must be developed. On the latter, the strategy will depend on whether the oncolytic viruses are generated on primary cells or primary chicken materials, as opposed to using continuous cell lines. Stability studies should be carried out to confirm the suitability of the production process as early as possible.
Analytical development
Analytical development is a crucial step in the product development strategy. A quality control (QC) program for an oncolytic virus product will test for product identity, potency, residuals, contaminants, safety, and relevant physicochemical parameters. The essential potency assay for an OV product is the infectious titer assay, which should be validated prior to clinical phase I/II. Some key considerations at this stage are to seek early regulatory advice, define timelines and scope for required assay validation, set the specification for QC release assays, and test for residual host-cell DNA.
Find a partner
Working with live viruses can be an especially complex task, but the potential reward of an effective oncology therapeutic makes this challenge worthwhile. Developing and manufacturing oncolytic virus can be challenging, particularly at scale, but there are contract developments and manufacturing organizations (CDMOs) that possess the expertise required to give an oncolytic virus candidate the best chance of success. The chosen partner must be able to provide support from the clinical stages through to commercialization while possessing an awareness of the global regulatory landscape and demonstrating compliance with these requirements.
As a CDMO with extensive expertise in oncolytic viruses, live virus, and viral vector development and manufacturing, Vibalogics possess the necessary experience to navigate and overcome the challenges that surround scaling. For more information, explore our Virotherapy Insider: Deep Dive into [GMP Manufacturing of Oncolytic Viruses], to review the critical steps involved in development, manufacturing, and testing.
References: [1] https://www.einnews.com/pr_news/581950285/oncolytic-virus-therapies-market-size-is-expected-to-reach-usd-609-7-million-at-a-steady-cagr-of-26-2-in-2028
[2] https://www.globenewswire.com/news-release/2022/05/18/2446316/0/en/Oncolytic-Virus-Cancer-Therapy-Pipeline-Shows-Rapid-Progress-in-Clinical-Trials-Assesses-DelveInsight.html
