In this case study, Advaxia Biologics, a specialist in GMP-compliant contract manufacturing and part of the IRBM group, overcame challenges it faced in its filling/capping suite using a Flexicon (part of Watson-Marlow Fluid Technology Solutions) FPC60 system with environmental barrier technology from Franz Ziel GmbH.
Branislav Mitrovic, Flexicon sales manager, describes the technology from Franz Ziel GmbH which provides a high-precision filling/capping solution for aseptic processing.
Key insights:
- Flexicon FPC60 vial fill/finish system, from WMFTS and environmental barrier technology from Franz Ziel GmbH provides a flexible, efficient, high-precision filling/capping solution for aseptic processing.
- The FPC60 automatic filling and capping machine is equipped with fully electric systems and does not require compressed air, saving Advaxia time and cost in installing a new compressed air line compliant with the Class A environment.
- The new system reduces contamination sources from critical processes, whilst also providing greater repeatability, greater quality assurance and high levels of traceability.
Advaxia Biologics faced challenges in its fill/finish suite
Advaxia Biologics has overcome challenges it faced in its filling/capping suite using a Flexicon FPC60 system with environmental barrier technology from Franz Ziel GmbH.
The Flexicon FPC60 fill/finish system was a necessary improvement to guarantee Advaxia Biologics an even higher level of quality and an enhancement of the services offered on the market.
The previous vial filling configuration at this site was focused on small batches and included the Flexicon PF6 peristaltic filler and Flexfeed 20 semi-automatic vial feeding system. The caps were placed manually before being crimped by the Flexseal 10 capping machine and installed on the benchtop under a Laminar Air Flow control system.
It was recognised that investment in new automatic filling/capping operations would provide multiple benefits to their process, including batch reporting and zero waste.
To maintain the highest level of quality, the challenge for Advaxia Biologics has always been to train, check and maintain the skill levels of operators, as they are responsible for much of the entire filling process, including a critical step of final filtration of the pharmaceutical drug product. Reducing the operators from the critical process, as well as operator input through recipe drive auto-adjustments, would help address this challenge.
A Franz Ziel and Flexicon collaboration
Working in collaboration, Flexicon and Franz Ziel developed a solution for Advaxia Biologics. An FPC60 filling/capping system was integrated with environmental barrier technology, to ensure both the product and the operators were fully protected and the platform met all regulatory requirements.
Advaxia Biologics works with two sizes of Stevanato Group EZ-Fill vials, 2R and 6R, pre-sterilised ready-to-use (RTU) vial trays for automatic loading, with caps and stoppers of 13 and 20 mm diameter. The fill volumes fall within a variable range between less than 1ml and 5ml. With the previous filling system, the batch sizes ranged up to 1000 vials; with the new FPC60 machine and the new suite, Advaxia Biologics is able to offer around 5000 vials.
To maintain aseptic conditions during filling and capping of a product particularly susceptible to external contamination, or considered bio-hazardous to operators, a closed Restricted Access Barrier System (cRABS) or isolator provides the highest level of protection.
The FPC60 automatic filling and capping machine is equipped with fully electric systems and does not require compressed air, saving Advaxia Biologics time and cost in installing a new compressed air line compliant with the Class A environment. The No Touch Transfer (NTT) compliant de-bagging system ensures that vial trays are unwrapped of their protective packaging and introduced into the critical filling area without human contact, while maintaining the required levels of safety and sterility at good production speeds.
The FPC60’s remote Human-Machine Interface (HMI) enables recipe and user creation from outside the cleanroom, providing ease of use and reducing time in the cleanroom. Once in the cleanroom, recipes simply need to be recalled and the machine fully adjusts itself based on the recipe parameters increasing repeatability and reducing risk.
Improvements in the Advaxia Biologics filling/capping procedures
The new system reduces contamination sources from critical processes, whilst also providing greater repeatability, greater quality assurance and high levels of traceability. A further advantage is given by the reduction of the number of operators required to fill a batch, compared to the previous process.
Traceability of the entire filling process takes place through software that controls all automated systems and keeps track of batch records and audit trails. Reducing rejection rate and zero waste start-up means vials filled during priming and calibration are viable.
Branislav Mitrovic, Flexicon’s sales manager, said significant challenges had to be overcome in the Factory Acceptance Testing (FAT) process for Advaxia’s FPC60 at the end of 2020, due to the Covid-19 pandemic.
He said: “Since it was not possible to travel around the world at the time the FPC60 was set up, it was necessary to perform the final FAT for the system remotely, using Advaxia’s vials, caps and tear-off caps. We perform the same tests according to FAT protocol documentation, regardless of whether the FAT is performed with the customer present, or remotely. Remote execution of FPC60 FAT typically takes four to five days (eight hours per day) and requires concentration, teamwork and commitment.
“Advaxia Biologics had previously used a Flexicon system, so the move to a much higher volume automated filling/capping system is a perfect example of known and reliable upscaling technology. It was a moment of great satisfaction when the test was successfully completed and the Advaxia Biologics FPC60 was ready to be shipped to Rome."