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Advances in fill/finish for parenteral packaging address demands for efficiency and product safety.
The global market for injectable drug delivery is growing at a compound annual growth rate of 10.9% (1). A report from Future Market Insights attributes the anticipated growth rate to the rising prevalence of chronic diseases such as diabetes, cancer, and rheumatoid arthritis along with increasing demand for point-of-care devices where prefilled, needle-free injectors are most preferred (1).
Beyond self-dosing, other factors influencing market growth include shorter runs, sensitive products, and labor constraints, which are driving parenteral drug makers to streamline operations. Tactics include maximizing container quality and adoption of ready-to-fill technology. On the equipment side, robotics are assuming a bigger role as are integrated systems. Simulation expedites design and engineering on the front end and supports training, operation, and maintenance functions during and after installation. BioPharm International reviews new technologies for parenteral packaging, including several displayed at INTERPHEX (April 2–4, 2019, Javits Center, New York, NY).
To address rising demand for ready-to-use (RTU) containers, DWK Life Sciences has developed the Workflow Solutions portfolio of glass and plastic containers, with Solutions Packs for research and for production (2). The Wheaton Complete Pak provides a complete kit of off-the-shelf, RTU packaging components for short runs. Contents include approximately 220 certified sterile and particulate- and endotoxin-free, crimp-top vials in one of three sizes (2, 5, or 10 mL), with seals in red or blue and a coated, uncoated, or lyo stopper. “We are planning an amber version and also planning a ModPak six-pack,” says Jay Harkins, senior product manager at DWK Life Science.
For self-dosing, an on-body injector being developed by Nemera combines a disposable needle and drug container with a reusable element that contains the electronics and mechanics. “The device customizes infusion speed and depth of injection and communicates with a smartphone to track doses and provide reminders,” says Lauren Mudrak, business development manager at Nemera.
Also under development, the S.A.F.E. Syringe Kit from Morimoto Pharma combines a vial filled with liquid, a pre-attached needle syringe filled with powder, and a compact tube-shaped container. Expected to be commercial in a few years, the design allows injection preparation to be performed inside a closed environment, thereby protecting caregivers from accidental needlesticks and exposure to the drug (3). Dissolving the drug powder inside of the syringe rather than the vial is quicker and ensures all the drug is injected (zero-loss). According to the company, this design also allows a syringe size that is significantly smaller than recent dual-chamber syringes, which makes it easy to administer and lessens patient needle phobia. Because the syringe is returned to the container immediately after administration and extra supplies are not needed, waste is reduced and disposal is safer.
Although traditional fill/finish equipment continues to be popular, robotic systems and machines that handle nested, RTU vials, syringes, and cartridges appear to be gaining ground, as they streamline operations by eliminating the need for a washer and depyrogenation tunnel.
New options for handling nested containers include the Dara NFL/2-RDL aseptic filling and closing machine from NJM, a ProMach product brand. Designed for RTU vials and the RayDyLyo cap, the machine handles nests of pre-sterilized vials and eliminates the crimping required with traditional aluminum closures. The machine fills solutions, suspensions, diagnostics, or vaccines in glass or plastic vials in sizes ranging from 2R–50R with dose volumes from 0.1–50 mL and can be programmed for full stopper insertion for non-lyophilized products or half stopper insertion for lyophilized products. Developed for biotech companies and 503B pharmacies, the servo-driven system streamlines the packaging operation to reduce capital costs, minimize footprint, and speed changeover. Volume capabilities suit scale-up through small batch commercial manufacturing.
A highly configurable fill/finish system, the Flexicon FPC60 machine from Watson-Marlow Fluid Technology Group can be set up from outside the cleanroom via wi-fi or hard wiring and automatically adjusts for height and width for hands-free calibration (see Figure 1). “We want to remove the operator from the process as much as possible. Operators are the biggest source of contamination,” explains Peter Lambert, filling division manager at Watson-Marlow Fluid Technology Group. Each operator also tends to set up the machine differently, so automating changeover eliminates that variability. Compatible with a traditional or single-use product path, the unit handles a range of containers, stoppers, and caps with a minimum of change parts. Designed to handle a range of vial sizes (0.2–100 mL) without change parts, the system outputs up to 45 vials/min. Vibrator bowls for stoppers (injection or lyo) and caps (flip-off or plain) are similarly flexible and capable of handling either 13-mm or 20-mm diameters.
A tabletop fill/seal system for low-volume needs, the EDM3611 from Bausch+ Ströbel can be housed in a tent-like disposable isolator. A sterile connection provides air, carbon dioxide, nitrogen, or HEPA-filtered laminar flow. A touchscreen-equipped operator interface houses machine settings and provides 100% in-process control batch recording (4).
Robotics also minimize the need for operator intervention. The GENiSYS R filling and closing system from AST accommodates up to five robots in a compact footprint and minimizes moving parts. Designed to process small batches of presterilized, nested vials, syringes, or cartridges, the machine offers fast, tool-less changeover in less than 30 minutes. A high-definition, user-friendly human/machine interface holds recipes, step-by-step instructions, videos, and standard operating procedures and can eliminate paper documents. An in-process control system ensures accurate fills, minimizes waste, and maximizes product yield.
Decontamination systems work in conjunction with fill/finish systems. The Eziflow UV-C aseptic transfer from Ezidock sterilizes to log 6 within minutes using ultraviolet (UV)-C light to ensure that product or components transferring to the fill/finish machine are sterile.
Pulsed UV light treatment offers several advantages. Effective against all known microorganisms, including those that are chlorine resistant, the chemical-free process also can remove free chlorine and chloramines, break down ozone, and reduce total organic carbon without leaving any residue, odor, or coating on treated surfaces.
The Pulsed UV Light Chamber Type 411 from Bausch Advanced Technology Group mounts in the wall to serve as a pass-through to the cleanroom. When the door on the cleanroom side is closed, presterilized containers are placed in the chamber. The outer door is closed, and the pulsed-light decontamination cycle runs for approximately 30 seconds. When the cycle is complete, the inner door can be opened and the operator or a robotic arm removes the containers in preparation for the fill/finish process. The compact, easy-to-install system needs minimal maintenance and cleans quickly to minimize downtime. Energy costs are low (5).
The RTDS2 robotic tub decontamination system from Steriline also uses a pulsed UV light and is designed to decontaminate nests of RTU syringes, vials, or cartridges. The robotic arm ensures all tub surfaces are exposed to the lamp flashes. The system can operate as a standalone machine or be integrated with any RTU filling machine, particularly Steriline’s robotic nest filling machine (6).
As Industry 4.0 takes hold, simulation via virtual reality (VR) or augmented reality (AR) is assuming larger roles in machine design, engineering, construction, operation, and maintenance. VR offers an immersive experience in a fully simulated setting; AR overlays digital elements on a real-world environment.
Bausch & Ströbel is already using AR and VR technologies. VR is helping its design teams fix problems in the development phase before machine construction begins. Using VR, the design team can reduce turbulence and areas of low velocities, avoid cross-flows above containers, and show static pressure and upward flow to optimize air-flow and ensure the cleanest possible environment for filling. VR also can help check ergonomic features, such as reachability for machine access by short or tall operators. “VR allows earlier decision making and helps determine if adaptations are needed,” explains Florian Naser, an engineer in the Data Processing Organization, Systems Product Creation, Applications at Bausch & Ströbel.
VR can be used to train operators before the machine is installed and whenever new hires come onboard. There are several advantages. VR training doesn’t tie up the machine, and all operators are trained the same way. VR can also support maintenance because it can ensure that the proper spare parts are on hand and help optimize machine modifications.
AR also can assist with machine troubleshooting by highlighting the problem area on a tablet computer that is brought to the machine. AR can identify the correct part and part number, zoom in, offer different views, present the virtual view next to the actual machine, and provide visual instructions for the operator or maintenance person, eliminating the need to search through paper-based standard operating procedures. “Nothing is forgotten or out of sequence, and the program is easily edited if changes are needed,” says Naser.
Hallie Forcinio is BioPharm International’s Packaging Editor, email@example.com.
Vol. 32, No. 10
When referring to this article, please cite it as H. Forcinio, “New Technologies for Fill/Finish Streamline Operations,” BioPharm International 32 (10) 2019.