OR WAIT null SECS
© 2023 MJH Life Sciences™ and BioPharm International. All rights reserved.
Demand spurs innovations in syringes and syringe fill/finish operations.
The intense pressure to develop vaccines and treatments for COVID-19 has helped spur strong growth in the pre-filled syringe market and innovations in syringes and syringe fill/finish operations. “Pre-filled syringes reduce the number of steps for injection, lower the risk of injury and cross-contamination, and offer higher dose accuracy,” explains Silvia Gallina, Syringes Platform Product Management at Stevanato Group.
“Pre-filled syringes are now a widely accepted part of the drug life-cycle and are often considered as early as Phase II in the drug development process,” reports Michelle Deutsch, head of Global Product Management at SCHOTT Pharmaceutical Systems. She adds, “The need for differentiation and the move to homecare continue to be critical drivers of this evolution. New drugs enabling technologies at different stages of development are also beginning to open up new possibilities for pre-filled syringes as it becomes possible to deliver higher fill volumes and higher viscosity drugs as subcutaneous injections.”
As the market for pre-filled syringes expands, attention is being devoted to glass improvements, reducing glass-to-glass and glass-to-metal contact, using cameras and other inspection tools to maximize syringe quality, designing products applicable to autoinjectors, and addressing the needs of sensitive biologics.
“Biologics tend to have high chemical sensitivity, low stability, and high viscosity,” says Gallina. For biologics, control of silicone and tungsten levels is key to minimizing or eliminating particulates, extractables, and leachables. Stevanato Group offers two product lines for biologics, the SG Alba and SG Nexa platforms, and is organizing production so it can provide these syringes anywhere in the world. Both product lines have been developed to reduce risks when a sensitive drug product contacts the containers. “SG Nexa platform features an optimized silicone layer, maximum cosmetic quality, tight dimensional tolerances, and compatibility with autoinjectors on the market,” reports Enrico Barichello,Alba Platform product manager at Stevanato Group. “SG Alba platform offers similar characteristics but has been designed for improved integrity of the lubricant layer, reducing subvisible particles and providing a better functionality when integrated in a device, particularly for drugs that may be very sensitive to silicone oil.”
SCHOTT’s syriQ BioPure prefillable syringes offer minimum levels of tungsten and low or no silicone. “While most approaches to managing this risk are based on immobilizing the silicone layer, syriQ BioPure silicone-free offers an alternative system that uses no silicone, relying instead on tight dimensional specifications and superior hydrolytic resistance,” says Deutsch. Available in 1- and 2.25-mL sizes, the syriQ BioPure syringes meet dimensional tolerances that exceed ISO requirements.
Another glass syringe innovation, a flat-shoulder syringe from Gerresheimer, minimizes or eliminates residual volume, an important characteristic for extremely costly drugs. As storage temperatures have dropped, the bar has risen for glass pre-filled syringes. Deutsch explains, “[Messenger RNA] mRNA—at least for now—has changed the game. Some vaccines had required transport at -4 °C, but today, many customers want to see proof of much deeper cold temperature performance. These requirements are shaping a new kind of pre-filled syringe demand. In some cases, pre-filled syringes made of cyclic olefin copolymer (COC) are a suitable alternative to glass pre-filled syringes.”
Break-resistant and lightweight, COC offers a glass-like appearance and performance and better product stability and shelf-life. One company that has begun to adopt COC syringes is Nephron Pharmaceuticals. The 503B outsourcing operation and producer of generic products has introduced a 50-mL COC syringe, which is filled on automated equipment and is compatible with highly viscous drugs. A disconnected plunger simplifies storage. The first Nephron product to use the COC syringe is 8.4% sodium bicarbonate injection (USP 4.2 mg/50 mL) (1). Sodium bicarbonate is used in emergencies to regulate or increase a patient’s pH levels, and the COC syringe gives it a 365-day beyond-use date. Nephron plans to offer a variety of products in the COC syringe with the next launch scheduled to be 50% dextrose injection. Eventually, the 50-mL COC syringe will be joined by 5 mL, 10 mL, and other sizes.
For biologics that need an autoinjector, BD Medical–Pharma Systems has been developing an addition to its Intevia product line. The Intevia 2.25-mL disposable autoinjector is designed to dose accurately, operate easily and consistently, and minimize injection pain. The two-step, push-on-skin device integrates an autoinjector with a Neopak XtraFlow 2.25-mL glass pre-fillable syringe (2). To accommodate viscosities up to 40 cP and a range of injection volumes, the syringe may be equipped with a 29G Thin Wall, 27G Special Thin Wall, or 27G Ultra Thin Wall needle, which is hidden and protected. When in use, a large inspection window and plunger rod show injection progression. The unit also provides visual and audible feedback indicators (3).
As the demand for injectables grows, non-traditional options are evolving such as pre-filled blow-fill-seal (BFS) syringes based on technology from ApiJect Systems. To support use of the technology, ApiJect has established a Technology Development Center near Orlando, FL. Plans call for doubling the footprint of the facility to 32,000 square feet and adding two BFS machines by mid-2023 (4). “This new facility is devoted to working with pharmaceutical and biotech companies to design, engineer and test how to fill and finish their injectable drug products in a new type of scalable, single-dose, pre-filled injector that is made using the ApiJect Platform,” reports Jay Walker, chairman and CEO at ApiJect. He explains, “By bringing together the high-speed, high-volume BFS manufacturing process with attachable components, including needle hubs, the ApiJect Platform is designed to make it possible for more injectable medicines and vaccines to efficiently be filled and delivered to patients in a pre-filled injection device. This facility provides capabilities to shorten supply chains and bring the development of critical injection device technologies back to the United States.”
Prevention of needlestick injuries and misdosing is another area of concern and development activity. The Innosafe syringe from Gerresheimer features an integrated safety device and is supplied in a standard tub and nest configuration, so it can run on existing filling lines without any significant line adaptations.
Nemera has expanded its Safe’n’Sound pre-filled syringe accessory lineup with the addition of a 2.25-mL size. Originally introduced for 1-mL, the passive Safe’n’Sound device prevents needlestick injuries. Compatible with low fill volumes and high viscosities, a large thumb pad enhances usage, and a rounded shape offers a larger labeling surface. Clear tip visibility simplifies drug inspection (5). The safety syringes can be assembled on Harro Höfliger Assembly Lab equipment. The semiautomatic machine quickly switches between 1- and 2-mL sizes and can be changed over in a few minutes to handle other devices such as pens or autoinjectors (6).
Protecting patients against painful or incorrectly performed injections is the goal behind the Luer Adapter Fixation concept from Schreiner MediPharm. It reduces the risk of incorrect or incomplete hypodermic needle screw-ins during a syringe’s insertion with a luer adapter (7). It’s particularly well-suited for medicines administered in emergency settings where hectic situations might cause application errors. “In the case of cosmetic medicine, the new adapter concept can help avoid needle pop-off—especially when injecting highly viscous hyaluronic acid, which requires higher exertion of force and pressure,” reports Gene Dul, president of Schreiner MediPharm US.
Developed specifically for glass syringes, the Luer Adaptor Fixation device and label are applied to the syringe during the secondary packaging process. “The plastic ring would be pushed onto the luer adapter of the pre-filled syringe and interlocked with it to equalize the different radii of the adapter and syringe body. The plastic ring and syringe body would then be connected by means of a label to fix the luer adapter in place,” explains Dul. The extended label area offers ample space for additional product information. The design is customized for each application (syringe size, etc.) and the user’s packaging process is evaluated to ensure there’s no impact on container/closure integrity (7). The Luer Adapter Fixation concept can replace shrink labels and avoid heat exposure to temperature-sensitive biotech drugs.
Another pre-filled syringe innovation from Schreiner MediPharm, the Cap-Lock security concept, combines a cap adapter and label. The label wraps around the syringe body and cap adapter. An integrated perforation provides irreversible tamper evidence. “This helps ensure the integrity of the container and prevents its undetected opening,” says Dul. This gives “pharmaceutical manufacturers ... a customized and validated full-service solution for equipping luer-lock syringes with reliable tamper evidence,” says Dul.
Better inventory management is the goal behind syringes equipped with radio frequency identification (RFID) tag-equipped labels. Kit Check technology from Fagron Sterile Services embeds a microchip in the label of ready-to-administer operating room syringes, enables accurate tracking and inventory records, and ensures the right drugs are available when needed (8).
With rising demand from oral, injectable, and veterinary products, the market for syringe fill/finish equipment has expanded significantly since 2019. Deborah Smook, vice-president of Marketing and Business Development for TurboFil Packaging Machines, attributes this growth to the ease of use and dosing accuracy the format can provide. She explains, “Precision dosing is increasingly important as some solutions require exact amounts to be optimally effective. Pre-filled syringes limit point of administration dosing errors either by healthcare personnel or patients themselves.”
She adds, “More specific to the syringes sector, though, are issues regarding regulatory foresight. By this, we mean that the pathway to final product approval isn’t always immediately evident. This is largely because the [equipment] solutions we provide are highly customized and therefore might require individualized guidelines.”
Equipment is becoming more automated and flexible. The push toward automation is driven by manpower shortages and labor costs, and flexibility is demonstrated by a syringe barrel feed system from Shibuya Hoppmann. It can handle six barrel sizes and two tip styles. Feeding and orienting occur at 80 parts/min.
Flexibility is built into benchtop machines capable of handling syringes, cartridges, or vials. Designed to address lab, clinical trial, personalized medicine, and other low-volume needs, the four Labworx machines from Groninger fill with a peristaltic pump, fill with a rotary piston pump, stopper, or crimp. The semiautomatic units feature a laminar-
flow-friendly design, two-button operation, wireless control via tablet or smartphone, and automated batch records (9).
To ensure parenteral products are safe, quality control is essential in product development and production and highly regulated. Data integrity also is required and an area of weakness that often prompts warnings from regulators. A growing role is being played by robotics, which can provide the material handling needed to perform 100% inspection.
Interest in 100% inspection has been given impetus by United States Pharmacopeia (USP) <1207> Package Integrity Evaluation–Sterile Products (10). While USP <1207> is not a requirement, Oliver Stauffer, president of PTI–Packaging Technologies & Inspection, says, “USP <1207> uses strong language and lays out very fundamental principles for container/closure integrity testing (CCIT) … [and] makes a clear case for adopting deterministic methods.” As a result, parenteral packaging operations are shifting to more accurate and reliable CCIT methods. “For pre-filled syringes,” he says, “operations are using methods like helium tracer gas to determine container component seal performance in the design phase, deploying high-voltage leak detection in the production setting, and using vacuum decay to qualify assembled autoinjectors.”
To prevent future regulatory complications, regulatory filings must focus on the science of the test methodology rather than the technology. Stauffer explains, “If a regulatory filing properly identifies scientific reasoning behind the application and lays a foundation for the method deployed, the science and the method are what shall remain constant within the filing. If a filing does not focus on the science and applies a stronger focus on the technology or even the equipment used, the filing is not adaptable to the changing technology landscape. … The scientific fundamentals of a method provide quality, while technology is simply the tool to achieve it.”
With supply chain issues a constant concern, all suppliers of syringes and fill/finish equipment are taking action to prevent delays and shortages. Machine builders have expanded inventories, particularly for electronic components. At TurboFil, “Warehousing certain electronic components, including programmable logic controllers … has limited the adverse impact,” reports Smook.
On the syringe side, Stefan Verheyden, global vice-president Gerresheimer Biological Solutions, reports, “We have done everything needed to secure tubing and component supply while in parallel, we have been, and still are, investing heavily in ready-to-fill capacity expansion on a global level.”
Stevanato Group has taken steps to mitigate supply chain issues and is working closely with suppliers and customers, increasing capacity in its plants and continuing to expand operations. A new plant in Indiana is expected to start production in 2023, and a new plant in China is planned.
Like its counterparts, SCHOTT is boosting operations worldwide with an expansion in St. Gallen and a new facility in Hungary. As a vertically integrated company, SCHOTT produces its own glass tubing but must source other materials and components. To improve sourcing security for components such as syriQ Rigid Cap closures and needles, the company has implemented continuous improvement programs that couple design improvements with supply risk mitigation. Other steps being taken to prevent supply chain snafus include “identifying areas where we can become more self-reliant, standardizing components, and broadening our sources of supply,” says Deutsch. Another tactic, the FastTrack program, maintains minimum stocks in inventory. “With this program, we target a two-week order-to-shipping lead time window,” concludes Deutsch.
SCHOTT also recently announced a substantial investment in a new manufacturing facility in Müllheim, Germany, which will produce prefillable COC syringes. “Our validated polymer syringe systems meet the demanding requirements of new drug categories, including ultra-low temperature storage applications needed for mRNA-based applications,” said Mario Haas, vice-president for the Polymer Solutions division of SCHOTT’s Pharma business unit (11).
Hallie Forcinio is a contributing editor to BioPharm International.
BioPharm International Vol. 35, No. 6 June 2022 Pages: 28-31
When referring to this article, please cite it as. H. Forcinio, “Pre-filled Syringes Show Strong Growth,” BioPharm International 35 (6) (2022).