Contract development and manufacturing organizations (CDMOs) and biopharmaceutical companies are facing shortages in capacity for production of clinical trial material. Even as large-volume commercial biofilling capacity has increased significantly since the beginning of the pandemic, drug developers are forced to use inefficient and risky filling methods that leave them with unmet demand. John Harmer (Cytiva’s strategic initiatives leader for aseptic filling) addressed the need for flexibility and capacity for CDMOs and their clients by introducing two gloveless robotic isolator technology systems: the Cytiva Microcell vial filler and the Cytiva SA25 aseptic-filling workcell.
John explained that the Microcell and SA25 workcells use a robotic filling process that reduces contamination risk and provides a high degree of aseptic assurance. The system lacks glove ports, so it works without direct human intervention. Both systems have a common handling interface, requiring a small number of personnel to undergo a short qualification process. The systems are designed for complete automation. In the rare occurrence of an issue, operators can breach the isolator to fix any problems.
The Microcell vial filler is designed for multiple small batches and can fill vials from 2 mL to 50 mL. A standard batch cycle takes about an hour, filling three tubs of ready-to-use vials, totaling up to 300 units per batch. Operators can take capacity off of their large lines using the Microcell technology’s on-demand production capability to fill many small batches by exploiting its short setup time and turnover.
The larger SA25 system is able to run batches of 1,000–20,000 units and is ideal for late-stage clinical and commercial production. It can fill syringes, vials, and cartridges, enabling customers to switch from vials to syringes during a later phase and thus to launch products in a preferred final format. Clients can load prefilled syringes with different dosages and make smaller batches to save valuable material and supply clinical trials.
Cytiva’s robust supply chain and manufacturing experience help to ensure reliability, as do a standardized workcell design, a common database of best-practice information, an abundance of spare parts, and an enhanced customer-support process. Each system is delivered at the scheduled time, requires no onsite assembly, and can be installed easily in an ISO 8 cleanroom in the United States or a grade D cleanroom in Europe.
John said that eight workcell users presented environmental-monitoring data in a paper published by the American Association of Pharmaceutical Scientists (AAPS) PharmSciTech journal. The data showed that contamination risk was an order of magnitude lower than that seen in conventional isolated systems, resulting in what John described as “probably the lowest contamination risk in the industry.”
Cytiva has installed SA25 workcells at CDMOs all over the world, including Emergent BioSolutions (Winnipeg, Canada), WuXi Biologics (Wuxi, China), Eurofins (San Diego, CA), and Fujifilm Diosynth Biotechnologies (College Station, TX). These users have formed a group of collaborators that share knowledge and best practices.
Questions and Answers
How can CDMOs address the cost-intensive need to change the format on an existing filling machine? Most customers solve that problem by getting multiple container formats for their system. However, tooling for vials usually can handle a number of different sizes, and the same is true with some syringe formats. If you do need to install a new container format, it’s a relatively short process that generally requires the addition of only a few pieces.
Can the workcells be used for biosafety level 3 (BSL-3) and occupational exposure band (OEB) 5 products? Operators should perform a detailed risk assessment for such products, but using a workcell is possible theoretically. The systems are decontaminated, have positively pressurized isolators with extremely low leak rates that are tested at the beginning of every batch, and can be sprayed down afterward. Operators also can use safe-change exhaust filters if required.
How long does it take to process a 2,000-unit batch in an SA25 system? There is a standard processing time for a nest or tub of containers — typically around four minutes, but it depends on the container size. For small containers that fit 100 units to a nest, 20,000 units can be produced over a double shift. Larger containers (e.g., 12 units to a nest) would take longer than a day.
Can a single-use system filling bag with tubing and needles be installed without a glove port? Yes, it can be installed before system decontamination by an operator wearing cleanroom garb. It’s a simple process that requires no tools and takes under five minutes.
Find the full webinar online at www.bioprocessintl.com/category/webinars.