The dramatic growth in the development and manufacturing of personalized therapies including biologics, cell and gene therapies and those designed to treat rare diseases, is changing the way treatments are manufactured. There is a focus on more patient-centric delivery forms such as pre-filled syringes and auto injectors as well as the more traditional vials. Greater product complexity and the need to ensure patient safety have led the FDA to advocate for less human intervention in sterile processing. As a result, the industry is looking for advanced ways to improve efficiency, reduce cost and increase sterility assurance. Robotic aseptic fill-finish technology is emerging as key to keeping pace with these developments.

Aseptic fill-finish aims to eliminate and control sources of contamination, particularly those potentially generated by humans, to ensure sterility and patient safety. The process achieves this goal via a fully automated gloveless GMP filling process and the use of ready-to-use (RTU) components, thus removing operator intervention and delivering batch manufacture within contained sterile isolator technologies. Robotic technology and the use of “isolator-barrier systems” are the core technologies that are advancing sterile fill-finish delivering product purity assurance.

PCI Pharma Services has invested significantly in these state-of-the-art robotic technology platforms at both our San Diego, CA, and Melbourne, Australia facilities to further complement our global sterile fill-finish and lyophilization manufacturing capabilities across North America and Europe. These technologies are positioned at locations where a high volume of early phase clinical trials take place and also allow our clients to benefit from a 43% tax rebate for clinical trials conducted in Australia. Utilizing the latest advancements, we deliver a flexible aseptic fill-finish solution for both small- and large-scale production runs across a variety of dosage forms including vials, prefilled syringes and cartridges for use in auto injectors, helping to meet our clients’ needs and get products to patients safely and efficiently. Investment in multiple robotic technologies delivers a scalable solution meeting requirements from smaller Phase I trials all the way through to commercialization and beyond.

The Robotic Fill-Finish Process

Sterile fill-finish transfers a sterile liquid formulation from a filling needle to a sterile container, such as a vial or syringe. Stoppering (closing) of a container typically happens after the filling process, except when a drug requires lyophilization (freeze drying), in which case, the sterile solution is frozen with the removal of water. Lyophilization is often used to address stability challenges with vaccines and other biologic therapies.

While traditional small molecules can be subject to terminal sterilization, this is not an option for all products and so aseptic filling solutions are required. Robotic aseptic fill-finish is the completely automated GMP process of filling and closing of the dosage form within an isolated chamber. Aseptic fill-finish via a robotic platform removes human intervention, reducing potential cross-contamination of the product and providing greater aseptic assurance. Given the direct route of administration to the patient and the often high cost and/or limited available quantities of these life-changing products, reducing fill risk is critical as the slightest error can mean production failure and significant financial loss.

Robotic Fill-Finish Technology

Sponsors aim to accelerate their sterile drug development lifecycle and seek readily available capacity, reducing time to clinic and ultimately commercial launch. They require experienced partners able to meet their fill demands with state-of-the-art technology, minimizing the risk of failure particularly in the early-stage development of complex, high value products that by nature can be difficult to handle. Failures during the aseptic fill-finish process can lead to product degradation affecting a drug’s efficacy and safety. The importance of mitigating risk cannot be overstated: failure in a batch can mean significant time to replace it at substantial cost and may put the entire timeline in jeopardy, delaying clinical trials, launch plans, commercialization and ultimately impacting patient lives.

The addition of these innovative robotic aseptic fill-finish platforms in PCI’s San Diego and Australian facilities enhances our existing sterile and lyophilization capabilities across our global network.  These advanced technologies expedite the filling process with automation and can pivot between filling different sterile medications into multiple dosage formats, bringing even broader sterile fill-finish solutions to PCI clients across the entire product lifecycle and allowing them to bring their life-changing therapies to market with increased speed and safety.

The Microcell platforms in San Diego and Australia offer fully automated, gloveless filling, performed through closed robotic isolator technology that provides both small batch flexibility and standardized manufacturing. The fast changeover and agility of the technology make it suitable for the production of both personalized medicine batches and clinical trial supplies delivering true speed to patients. Superior drug product quality is assured through advanced automation, removing the need for operator intervention during the filling process and limiting product contact. Importantly, the Microcell technology can fill up to 1,200 units per batch with fill volumes ranging from 1.0 – 50mL.

Providing a scalable aseptic solution in support of clients progressing through the clinical lifecycle towards commercialization, the SA25 Aseptic Filling Workstation is a larger-scale, gloveless, isolator-based filling technology offering small- and large-scale batch production of up to 20,000 units, supporting fill volumes from 0.2 – 50mL. It provides flexible and standardized manufacturing, and the ability to fill multiple delivery device formats including vials, syringes and cartridges through an aseptic process.

For both the Microcell and SA25 technologies, precise, programmable robotic functions cover all aspects of the filling process, including isolator leakage tests, VHP sterilization of the container closures, filling into the CCS of choice, capping and batch delivery. They are also compatible with ready-to-use containers and closures, removing the container and closure preparation stage aiding speed of delivery of a quality and sterility assured drug product.

A More Reliable Fill: Robotic Advantages

The robotic platforms with high-precision Dynamic Peristaltic Pumps ensure accurate fill volumes with minimal product losses, expediting the filling process with automation while also increasing accuracy and quality assurance, and achieving the highest standards of sterility. With a robot performing the processes in a validated system and utilizing single-use parts, a pre-sterilized flow path and ready-to-use containers, multiple sources of risk are eliminated including cross-contamination, electro-mechanical filling and closure activity failures, environmental control failures, and cleaning and set-up errors. All this combined means clients are able to move more rapidly through the clinical stages and provide life-changing therapies to patients.

Particle risk, such as aluminum particle contamination is also reduced with the robotic platforms using press-fit vial closures with integrated rubber stoppers. Simplifying the manufacturing process, the press-fit closures are a one-step application that presses closures on top of the vials, versus the traditional two-step process of stoppering and aluminum crimp capping.

Robotic sterile fill-finish can produce many different products and process multiple projects with minimal changeover time between batches, saving even more time and allowing high flexibility, so we are able to better support clients who have urgent supply needs. As a product progresses through the clinical lifecycle towards commercialization, this can be supported, providing a seamless journey.

Integration is Key

This technology is an important addition to PCI’s global sterile fill-finish manufacturing solutions, helping to accelerate sterile drug products through the clinical lifecycle and ultimately to commercialization.

By providing integrated end-to-end solutions and helping to reduce supply chain complexity and risk, clients can access the expert secondary packaging, labeling and distribution solutions available across an extensive global network and biotech centers of excellence, leveraging the benefits of working with a single supplier.

Combining expertise in sterile fill-finish manufacturing with specialist biologic packaging, labeling and cold chain distribution provides a valuable end-to-end solution, simplifying the supply chain while delivering time and cost efficiencies.

Looking Ahead

Sterile fill-finish is a mainstay in pharmaceutical manufacturing. As research discovers more biological-based therapies such as antibody, mRNA and SRNA treatments, the need for sterile fill-finish will continue to increase, and, along with it, the need to de-risk the supply chain.

Robotic platforms will be a true differentiator offering an additional level of assurance and delivering products as rapidly as possible without compromising drug product quality and patient safety.