Incorporating automation into your fill and finish procedure: an interview with Allison Hoffman
In this interview, Allison Hoffman, Global Product Manager for Cell Therapy Technologies at Terumo Blood and Cell Technologies, explains how automation can be incorporated into fill and finish procedures and the impact this has on factors such as the cost of producing cell therapeutics and the quality of the final product.
This interview is part of the RegMedNet In Focus on automated process. Discover expert opinions on this topic by visiting our feature homepage.
Please introduce yourself and your company/institution.
My name is Allison Hoffman, and I am the Global Product Manager for Cell Therapy Technologies at Terumo Blood and Cell Technologies. I have spent most of my career in the infusion pump and health care industries, but now support the future of cell therapy technologies, which I believe is more in line with my educational roots in molecular and cellular biology.
What are the main challenges of a manual fill and finish procedure, and how does this impact the final cell therapeutic?
Final formulation, fill and finish is a key step in the cell therapy manufacturing process. A loss of product at this stage would be costly, both financially and for the patient awaiting that critical therapy. Therefore, any occurring challenge during the fill and finish procedure may impact the final therapeutic.
Manual methods lack process controls that may impact cell viability and functionality. A manual process is susceptible to contamination due to open events during the process. The process also relies on operators accurately performing each step per standard operating procedure, making measurements and capturing data. Manual labor introduces the possibility of human error in the process.
Cryoprotectants, such as dimethyl sulfoxide (DMSO), are always a factor in the fill and finish process; manual or automated. While necessary for protecting cells during freezing, DMSO can also be toxic to the cells. A fill and finish process must consider DMSO exposure time and temperature management during formulation, fill and finish. A manual process must have time and temperature controls in place to reduce the negative impact on the cells.
A manual process will also have the resource challenges. Due to the risk of contamination, a manual process may require the use of a high-grade good manufacturing practice clean room. Furthermore, you would also need to train and maintain operators with adequate competencies to perform the process and maintain documentation. All of those adds cost to the product.
How can automation be incorporated into fill and finish procedures, and what are the benefits?
Automating can reduce risk in several key areas in a fill and finish procedure by eliminating many common error-prone parts of a manual process. A fully automated, closed or functionally closed system reduces the number of open events and the risk of product contamination.
Automating also reduces the risk of operator variability. These systems provide a user interface to guide the operator through device operation, enforcing a standard workflow. Many automated and semi-automated systems also allow for upload of customer protocols, so operators do not have to enter volume and temperature targets. This reduces the potential of variability concerns and repeatedly produces a viable product on a consistent basis. Automated systems also automatically capture procedural data, ensuring a complete and accurate record.
In addition to the product benefits, automating can lower the cost of producing a cell therapy by removing some of the resource requirements from the process. A closed or functionally closed system may not require high-cost cleanroom facilities for contamination prevention. And since these systems have a guided user interface, training time can be reduced.
In November 2021, the International Society for Pharmaceutical Engineering (ISPE) released its guide for Advanced Therapy Medicinal Products – Autologous Cell Therapy on manufacturing facility development and design for producing autologous cell therapies. ISPE’s recommendation was to automate wherever possible to mitigate risk.
What are the challenges of automation in fill and finish procedures, and how can we overcome them?
One of the biggest challenges is balancing flexibility with structure or finding a single solution that can take you from process development to commercial manufacturing. An automated process should be flexible enough to perform process development, or to take an already established process and automate it. But you do not want an operator making changes to the process in commercial manufacturing, so you need the ability to lock down the process once established.
The science is evolving at a faster pace than the technology used to manufacture cell therapies, so it is important to design some level of flexibility into the system for the future. We need to anticipate this in our tools development and actively collaborate with the industry to ensure we react to changing market needs quickly.
How does the Finia® Fill and Finish System enable best practices for packaging final cell therapy products according to ISPE, and why is this important?
Fill and finish is a very important step of the process. You have already invested a lot of time and money up to this point. It is important that the solution you choose maintains the best cell health for the patient, including viability and functionality.
According to ISPE, “a best practice is to fill volumetrically using an automated, closed system driven by a peristaltic pump with an inbuilt weight check and active cooling system.” The Finia System enables ISPE best practices for customers by meeting the recommendations outlined by ISPE for packaging final cell therapy products. Finia formulates and aliquots fluids in a closed and automated fashion using its peristaltic pumps to pump all fluids into the master mixing bag and product and quality control bags, and Finia records the volume of all pumped material by weighing the contents of the mixing bag and calculating volume based on the specific gravity of the material. Also, Finia actively cools and maintains temperature of the master mixing bag and final product and quality control bags. If the addition of materials causes the temperature to exceed the maximum threshold, Finia temporarily pauses material addition to cool the contents to the nominal temperature set point.
What is Terumo Blood and Cell Technologies’ overall mission, and how does health economics play into this?
Our objective at Terumo Blood and Cell Technologies is to enable as many patients as possible have the access to lifesaving blood and cell therapies and interventions. Health economics is key to achieving this objective. In order to accomplish our mission, we help payers, patient associations and physicians understand the value of blood and cell therapies. In achieving this objective, we can provide substantial clinical benefit to patients at a lower cost compared to what is offered today.
How is Terumo Blood and Cell Technologies improving patient access, with regard to health economics, i.e. clinical benefit vs cost?
Terumo Blood and Cell Technologies is improving patient access by making products that allow our customers to standardize and scale their products. Blood and cell therapies are not equally available to all patients around the world; patients may have to pay high out-of-pocket payments to gain access to these therapies. Manufacturers of cell therapies are also looking for ways to decrease costs and increase patient access.
The cell therapy manufacturing process must be consistent from operator to operator and in compliance with established quality standards to ensure that these therapies will meet patient needs. Process failure can have a significant impact on the cost of these treatments. Technologies, such as Finia, can help optimize the cell therapy process workflow. Cell and gene therapy manufacturers will experience the benefits of automating the cell therapy manufacturing process, including reducing the number of operators required, product labor cost, time per product run and risk.
Disclaimer
The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of RegMedNet or Future Science Group.
In association with Terumo Blood and Cell Technologies.