SUTs manufactured from single-use components made from polymeric materials, sterilized, and ready to use, are widely used for various purposes, ranging from classical biomanufacturing of proteins, monoclonal antibodies (mAbs), and vaccines on a large scale; they are now being adopted for applications in the cell and gene therapy area and viral vector manufacturing.
A new guide from the Bio-Process Systems Alliance (BPSA), an industry-led international association focused on accelerating the adoption of SUTs in the production of biopharmaceuticals and vaccines, discusses present and future challenges in gene therapy manufacturing and how such technologies can improve the manufacturing process, including upstream production and downstream purification, among many other facets.
“SUT’s are essential to viral vector manufacturing success, and this guide provides insights that will enable biopharmaceutical manufacturers to make smart choices about where single use can improve outcomes and speed of therapies to market,” said Brendan Lucey, global director of Cross Business Unit Market Strategy, Entegris, and chair of the BPSA cell and gene therapy committee, which authored the review.
The paper, the culmination of an 18-month process, also sheds light on some of the future opportunities for SUTs in gene therapy production.
Chris Clark, BPSA executive director, said the association and the single-use supply chain will continue to work collaboratively to ensure a robust, safe, and reliable manufacturing base for cell and gene therapy production.
Insights
Viral vectors are challenging to make reliably and robustly. Often manufacturers of gene therapies have to decide whether to manufacture in house or use a contract development manufacturing organization (CDMO), and in some cases, a parallel path will be chosen to use both in house and CDMO for risk mitigation purposes, found the BPSA review.
Citing a prominent CDMO that manufactures viral vectors, the guide noted that the company in question reported that almost all unit operations other than chromatography and TFF are now single-use.
SUTs help address many of the challenges linked to viral vector manufacturing including providing ease of scale-up from early clinical through commercial phases and providing connectivity in an aseptic manner within and between certain unit operations, they said.
But while SUTs continue to shape the progress and advancement of viral vector manufacturing, future challenges remain for both suppliers and developers, reads the paper.
Several key themes that will continue to emerge in the coming years are scalability and the need for standardization to drive compatibility and interchangeability of technology, outlined the specialists.
Stronger collaboration and partnerships between suppliers and developers will drive more robust and reliable products to meet the intended applications, they said.
There is a need to design new closed-system solutions and automation to remove variability and lead to a more robust and consistent process, they added.
Their paper outlines some of the existing challenges for SUTs in relation to support viral vector manufacturing:
Scalability
Scalability, according to the document, is an important factor in developing cell and gene therapies and particularly the viral vector manufacturing processes. There continues to be an unmet need regarding commercially available components in building viral vector manufacturing processes. Many of the current cGMP commercially available single-use products were designed for large scale cGMP mAb processes.
Viral vector manufacturing starts in small scale, where cGMP ready single use products are not available; hence, laboratory components are used.
“The use of laboratory equipment which in most cases are used for R&D grade must now be validated for cGMP use. When development expands into cGMP scale operations, small scale, manual process of laboratory grade product will not meet future demands. A second round of validation process is required for larger volume process in cGMP operation.”
Standardization
Standardization of sizes for tubing, connectors, containers, and broader ranges of sizes for scaling the viral vector manufacturing process will be required as the industry continues to mature, found the BPSA report.
“Compatibility of components from multiple vendors is very complicated and often leads to higher complexity and risk when designing processes, understanding materials of construction, and conducting proper risk assessments will help mitigate this complication.”
Change management
Collaboration between different suppliers with respect to extractables and leachables of SUT components data will drive flexibility for end users, stressed the review.
“Making this data more readily available will allow use of SUT components from multiple vendors interchangeably or the same vendor interchangeably. Sole source components can increase supply chain risk in producing life-saving drugs. Changing components in the process can be very costly if equivalency studies are required. The recently developed IT tools can help to evaluate the influence of component or material changes.”
Robustness and reliability data
Robustness and reliability data and case histories on SUT technology will advance the design of systems by ensuring that the components used will meet the intended application, noted the specialists. Using components that are underspecified and fail integrity can cause major delays in DS or DP campaigns, they added.
“Better availability of technical data on commercial components and a common repository of this data would move the industry in the right direction.”
Ensuring quality
The manufacturing method for SUT systems and fluid pathways, which include components, tubing, bags, filters, etc., is a very manual process and has the potential to lead to high labor costs and potential variability in production.
Introducing automation into the manufacturing process of making these fluid pathways will increase manufacturing throughput, reduce labor costs, and drive additional capacity needed to meet future demand for single-use products and systems, acknowledged the report from the industry led association.
Closed process
Complete closure of the manufacturing process will allow developers to utilize a lower classification manufacturing environment. This can lead to a lower capital cost for a new production facility.
“Processes can now be designed to operate in ISO Class 7/8 environments, thereby lowering both capital and operating costs for the manufacturer.”
Concluding, the BPSA cell and gene therapy committee’s guide, noted that viral vector manufacturing is still in an early stage of development and that this emerging segment in biopharmaceutical manufacturing is benefiting from the tremendous experience gained from the production of mAbs and vaccines, especially now in terms of quicker and large-scale processes due to the outbreak of COVID-19.
"Viral vector manufacturing has almost completely adopted SUT at the commercial scale. Many challenges exist in the scale-up of viral vector manufacturing process components, and the SUT supply base is responding to these needs."
