By, Dalip Sethi, Scientific Affairs Director, Terumo Blood and Cell Technologies
Scaling product manufacturing throughout development is a strategic necessity for both clinical and
commercial drug supplies, especially for manufacturers performing fill and finish on cell and gene
therapies and advanced therapy medicinal products (ATMPs) at the commercial stage.
To see products successfully through approval, drug developers need the flexibility to ramp up
production during early phase development and to supply clinical phases and trials effectively.
Product processes and appropriate controls must be designed to scale up and out in response to
program milestones, regulators and eventual patient demand. Just as important, teams are keen to
capture key information and lessons learned throughout development that they can leverage later in
commercial formulation.
Reducing variation, as well as the potential for contamination, in the final product is a must to assure
regulators of process and production integrity at a commercial scale. Automation is one way to
achieve that. Read on about five potential factors for successfully scaling at the critical fill and finish
stage.
Scaling success step 1
Manage batch-to batch and process variability across operators and operations
Automated systems can reduce variability and increase quality by doing processes the same way
every time, with no differences from one operator to the next or between two facilities.
At the fill and finish step, reduced variability helps to achieve uniform cell concentrations in each bag
and consistent cell viability post-formulation, not to mention reduced contamination risk compared
to manual steps. And fewer manual processes mean fewer operators and reduced overall Cost of
Goods (CoG) in production. At least one system, the FINIA® Fill and Finish System from Terumo
Blood and Cell Technologies, also supports:
- Greater than 90% post-thaw viability for cell products from healthy T-cell donors
- Active cooling to maintain temperature during the process and have final product bags temperature within user-defined targets
- Automated air removal and sealing of final cryo-bags
Scaling success step 2
Identify critical quality attributes (CQAs) accurately
Automated digital access to data during operations lets you more accurately monitor CQAs
throughout the manufacturing process and identify trends early so you can act in time to correct
variances. Data automation can also help you identify additional CQAs and make comparisons
between iterative experimentations (both protocol updates and quality risk management process
upgrades) to see how they affect product quality.
Scaling success step 3
Set process controls early in development
By using automated data management methods and incorporating the data gathered at each step,
you can set process controls early in development. That lets you leverage automation throughout for
better scaling and compliant, accurate fill/finish operations.
Scaling success step 4
Enable application-based data management and integrity
Automating fill/finish cell processing operations is a way to make them easier to validate, with less
variability, to facilitate cGMP compliance.
One key component is a well-engineered software application that allows operators to:
- Specify processing protocols
- Configure materials and the device
- Define users and assign permissions
- Track tubing sets and materials
- Record alarms
- Capture electronic data
- Generate procedure reports
These capabilities promote current Good Manufacturing Practices (cGMP) for proactive regulatory
compliance: user authentication, data capture and reporting, and workflow configuration and
control.
Scaling success step 5
Manage skills, labor hours and materials more efficiently
For cell and gene therapies, scaling is one huge factor for success, with the ultimate goal of
increasing patient access to treatment. But scaling must be cost-efficient — production economies
and pricing can depend on it.
Automated, closed fill and finish systems reduce training time and the need for skilled labor. Pharma
professionals understand that automated processes and single-use technologies make each point of
processing more reliable and faster. That reduces error considerably and improves the ability to
track and trace the flow of material, timelines and operator actions.
Finia: The first-of-its-kind automated fill and finish system
The FINIA® Fill and Finish System is an automated system developed by Terumo Blood and Cell
Technologies that formulates and aliquots fluids, including cell suspensions, and prepares them for
cryopreservation. It consists of a device, a handheld barcode scanner, a monitor with a touch screen
and functionally closed single-use disposable tubing sets.
Finia facilitates cGMP compliance through:
- User authentication
- Data capture and reporting
- Workflow configuration and control
- Functionally closed process with automated air removal and sealing
- Gamma-sterilized, single-use disposable sets
The system optimizes processes and provides for custom formulations and dosage ranges. It also
offers an intuitive user interface to guide the operator and achieve an accurate, consistent final
product with less than 5% difference in cell concentration between bags. Other demonstrated
capabilities include the ability to maintain these results with just one operator per run:
- Post-thaw viability greater than 90% from healthy donors
- Post-process cell viability of greater than 95% of pre-process viability.
- Product temperature to within 3˚C (± 3˚C) of defined targets.
A Finia-based fill and finish solution can help therapeutic providers gain tighter control of their
processes and deliver higher-performing treatments compared to manual methods.