Emergent BioSolutions manufactures a portfolio of branded protein therapeutics and contract manufactured products at its Winnipeg, Canada site. In 2016 Emergent revamped its site quality plan and decided to replace the existing conventional filling equipment. They determined that an existing conventional filling system installed in an open Grade A cleanroom could not meet future production requirements or ensure long-term regulatory compliance.
Choosing technology leadership
Emergent assembled a project team consisting of engineering, manufacturing, regulatory and quality groups to determine their primary needs, as well as additional “wants” that would add capabilities or strengthen existing ones. After a thorough selection process, Cytiva’s SA25 aseptic filling workcell was chosen because it best met the team’s criteria.
The team determined that as a closed, robotic aseptic filling machine, the SA25 provided a sterility assurance advantage. It was not a system with which the project team had experience operating, so extensive due diligence was completed including comparative testing, literature review, failure mode and effects analysis (FMEA), interdepartmental strategic planning, long-term projects and forecasting, supplier relations and external negotiations. Much of the focus of this diligence process was on the eventual transfer of licensed commercials products on to the new technology. The workcell also satisfied the Emergent “wants” of flexibility for additional vial sizes, syringe and cartridge filling capability, and greater ease in bringing new products online.
Project timeline
October 2017 – Emergent buys the SA25 aseptic filling workcell
Emergent purchases the SA25 after almost a year of research and evaluation on different options.
February 2018 – Factory acceptance test (FAT) is completed
The Emergent team completed the FAT working with our technical services team in Vancouver. This milestone is 7 months from the company’s purchase of the system.
April 2018 – The SA25 is installed in Winnipeg
The cleanroom is ready and the SA25 is installed at the Winnepeg site.
June 2018 – Site acceptance test (SAT) completed
Following installation, the SAT is completed.
April 2019 – Validation activities completed
The Emergent team completed installation qualification (IQ), operational qualification (OQ), and performance qualification (PQ).
May 2019 – Media fills completed
The Emergent team completes their media fill processes with zero positive units.
July 2019 – Commercial products filled
Less than 2 years after its purchase, the SA25 is filling approved commercial drug products.
The transition to new primary packaging components
One of the key concerns of the project was to avoid interruption to the supply of commercial products. Nested containers and closures represent a change in terms of the production process, and it was recognized early that these components are important to the sterility assurance and flexibility aspects of the gloveless isolator.
To mitigate the risk of interruption, product characteristics as they related to storage conditions and expiry dates were analyzed to show that the new containers, stoppers, and press-fit closures showed equivalency to the existing ones. With the new filling machine, a more appropriately sized vial could also be selected so multiple vial sizes could be filled without the need for change parts.
Another difference introduced to product packaging was the use of press-fit vial closures with integrated stoppers supplied in a pre-sterilized nest, as a requirement of the gloveless isolator’s aseptic process. This combination of vial and press-fit closure met Emergent’s requirements, including those for container-closure integrity, low temperature storage and shelf life.
Process implementation
Many aspects of the aseptic process within the gloveless robotic isolator are different from the alternatives that were researched by the project team.
The workcell provides a highly automated handling, filling, and closing process. The project team spent extra time to understand how the process worked, and how areas of risk were mitigated in the process flow. Implementation of the workcell post-installation has focused on process development and product recipes—work which is ongoing.
Though the system is closed when in operation, the project team implemented contamination control specifications, and engineering and administrative controls to reduce particle introduction and bioburden contamination in the workcell’s interior.
Minimal aseptic technique is required, and there are much fewer areas for potential failure during the process. Operators have said that their job is much less physical than in the conventional filling suite. As a side effect, it has taken operators additional time to learn the Human-Machine Interface (HMI) and how recipes control different process parameters.
Key lessons from the implementation of a gloveless robotic isolator
There are many differences in implementing a gloveless robotic isolator into a production facility. These differences affect facility design and production processes, as well as requiring close regulatory attention if existing commercial products will be transferred into the new technology and primary packaging.
The key lesson from this experience was to involve supporting groups such as quality assurance, regulatory affairs, quality control and analytical development early in the process. This helped the larger project team better understand and solve obstacles. It was important that each group understood the risks and benefits of choosing a new aseptic filling technology.
“In revamping the aseptic filling operations at the Emergent site in Winnipeg, we wanted a machine that could provide superior product quality, sterility assurance and flexibility. For our own branded products and our contract manufacturing clients, we believe that the SA25 aseptic filling workcell meets all of these requirements and will position us well to manufacture next-generation therapies.”
– Kevin Gadient, Director of Manufacturing, Science and Technology at Emergent BioSolutions