Modularity and Flexibility in Closed Systems
This is the fourth of a series of five blogs summarising key discussion points and outcomes from the latest automation Special Interest Group (SIG) sessions, held in June 2021.
This blog highlights the contributions of the fourth working group, focussed on ‘Modularity and Flexibility in Closed Systems’.
The Special Interest Group (SIG) on modularity and flexibility in closed systems came together in June with a goal of outlining current pain points related to automating cell and gene therapy processes.
Participants in the kick-off session included those developing these advanced modalities therapeutics as well as those developing technologies to support manufacturing processes, which made for a lively discussion. Ultimately, the group will draft recommendations on closing critical gaps in current processes and potential ways forward.
Among the challenges identified by the SIG members that need to be addressed include:
- The need for greater standardisation.
- Consensus among the participants is that across the industry, everyone is grasping for standardisation to make it easier to connect different technologies to work across platforms.
- Adoption of ‘do-it-yourself’ approaches when the technology is not available.
- An example was shared by a participant in which his organisation takes receipt of solid tumour tissue and processes it in a closed manner to then feed into a manufacturing process. They have taken the bold step of developing their own technology to process tissue in a closed manner from the point of receipt.
- The gap between therapeutics manufacturers and tools companies.
- Solutions offered by participants included proactively engaging technology providers saying, ‘this is what I need’ and partnering with them via an early access program to get on board with the product development process.
- The need for development of flexible solutions.
- It was noted that there are many similarities in certain modules of process operations and a technology should tick off as many of those as possible and have a platform that’s flexible for a range of nuances. Otherwise, as noted by a participant:
“it may be a customer of N=1 and there’s no business case for that.”
- The lack of universal connectivity between modules.
- Current state-of-the-art is sterile welding of PVC tubing, which is a manual process.
- Real time data capture related to critical quality attributes (CQAs) to guide process decisions.
- The ability to have output data captured in correlation with critical clinical data and analyse this in real time is needed.
- Supply chain of GMP materials.
- Having the tight control of critical reagents from the beginning is essential to avoid surprises as you look to scale up.
- Flexibility in the scaling of operations.
- Examples include the need to scale new technology from flask to bag to automated systems and the ability to perform larger scale up, such as having systems that can handle smaller autologous batches as well as much larger allogeneic batches. Additionally, if there is no way to scale down from large automated systems, there is no way to incorporate new reagents and technologies in different parts of the process.
- In-process sampling and QC.
- These processes still require manual sample taking and manual transportation of those samples to another room or another part of the building for QC testing and process control analysis.
Undoubtedly, companies developing cell and gene therapies are faced with decisions including whether to adopt an all-in-one type of closed system or a combination of modules. No matter the choice, there is a pipeline to serve as well as different end users, so changes are inevitable. Whether the change is evolving from autologous to allogeneic approaches, streamlining and closing portions of the process or tweaking the therapeutic modality, all of these impact manufacturing processes and influence the need for automation.
The team reached consensus on the need for flexibility to meet the needs of the rapidly evolving advanced therapies field. This is expected to remain a theme that guides further discussion as the team delves further into other key areas such as standardisation versus customisation, integration versus modularity, and strategies to drive cross-functional collaboration between therapeutics manufacturers and technologists.
The Automation Special Interest Group (SIG) was created by Phacilitate in 2017 to discuss and propose solutions to automation challenges presented by cell and gene therapy manufacturing. Since that time, we have advanced this mission by identifying key objectives, hosting meetings with industry experts to explore and address these objectives and releasing a report for the wider industry to use as guidance in their automation efforts. In 2021, we evolved the SIG into a parallel track of year-long working groups, each focused on a different area.
Catch up with what was discussed at the June 2021 meetings with this blog series:
1 – Manufacturing Digitisation in Advanced Therapies
2 – Vein-to-Vein Tracking and Supply Chain Digitisation
3 – Automating Release for Autologous Products
5 – Aligning the Automation and Technology Roadmap to the Regulatory and Process Development Roadmap