Innovations Meet Growing Demand for Prefilled Syringes

BioPharm International, BioPharm International-06-01-2021, Volume 34, Issue 6
Pages: 32–35

Container and equipment innovations expand applications.

Prefilled syringes continue to evolve to enhance operation, support increased automation of the fill/finish line, and boost productivity and output. Syringe innovations also increase patient and caregiver safety and efficiency and reduce waste of product and packaging materials. “Since it is already packaged ready for the injection, the prefilled syringe saves time and avoids unneeded handling prior to the actual application, minimizing the risk of the injection errors, dilution errors, or non-sterility issues [that are a risk in] multi-dose containers,” explains Wenzel Novak, global senior director of business development at Gerresheimer Medical Systems.

Novak estimates that prefilled syringes currently account for 10–15% of the parenteral market and anticipates rising demand. A market study by Emergen Research predicts sales of prefilled syringes will expand at a compound annual growth rate of 8.9% between 2019 and 2027 to nearly double in value to $9.11 billion in 2027 (1). Driving forces include vaccine production as well as the adoption of self-administered biologics for chronic conditions such as diabetes and auto-immune diseases (1).

“If you look at the top 40 injectable products, all are being used with prefilled syringes,” reports Dr. Nicolas Brandes, director of product management, Polymer Prefilled Syringes and Vial Containment at West Pharmaceutical Services.

Prefilled syringes can be made of glass or plastic such as cyclic olefin polymer/cyclic olefin copolymer (COP/COC) or polypropylene (PP). Glass dominates in most markets. Novak predicts, however, that the share of co-injection-molded COP/COC prefilled syringes will grow from 2% to more than 5% during the next decade.

“We have seen more approvals for products in plastics especially during the past five years,” reports Brandes. He notes plastic syringes often are chosen for specific applications such as contrast imaging agents, hyaluronic acid, and Botox as well as for products that are sensitive to silicone oil. Plastic syringes also function well in auto-injectors.

According to Novak, about 60% of prefilled syringes are staked-in needle syringes, but there are considerable regional variations. The most common prefilled syringes are 1-mL long and 1-mL short. The most prevalent applications include anti-coagulant (glass 1-mL long), vaccines (glass 1-mL short), and isotonic solutions where PP is the material of choice. “With the existing COVID-19 challenge, a significant increase in vaccines is expected worldwide,” says Novak. This growth will stem from COVID-19 vaccines as well as heightened interest in established vaccines (e.g., flu).

Prefillable syringes are delivered as bulk goods or ready-to-fill (RTF). Gerresheimer’s bulk syringes are provided as unsterilized glass bodies in flat (Rondo) trays or customized packaging designs (e.g., bags). Its Gx RTF syringes are presented as washed, sterilized RTF components to pharmaceutical and contract manufacturing operations and are available in glass or plastic. Fill volumes range from 0.5 to 5.0 mL, with the most common volumes falling between 0.5 mL and 3.0 mL.

Prefilled syringe innovations

Innovations from suppliers accentuate the ease-of-use attributes of prefilled syringes and focus on adding sizes (particularly for larger volumes), reducing waste, and patient and caregiver comfort and safety.

Gerresheimer has expanded its range of prefillable polymer syringes for sensitive biologics, biosimilars, and biobetters to include a Gx RTF ClearJect COP needle syringe, 1.0-mL luer lock.

At West Pharmaceutical Services, line extensions include insert needle syringes (the plastic version of a staked needle glass syringe) and more needle sizes and product volume options. “In the past three to five years, we have seen more approvals in the larger 2.5-mL format,” reports Brandes. The larger volume reduces the number of syringes needed per dose and improves efficiency and comfort. There’s a trend toward finer needles too. “Smaller, thinner needles mean less pain,” he explains.

User-friendliness is the goal behind a collaboration between Gerresheimer and Stevanto Group whereby Stevanato supplies its ITC twist-off closure system for Gerresheimer’s Gx RTF luer lock syringes. The integrated seal cap consists of an elastomeric component, which is available in different formulations, and a rigid, translucent polymer cap. Advantages include greater stability and shelf-life protection versus traditional luer cone systems (2).

Prefilled syringes offer sustainability benefits by eliminating multi-dose vials and related production and handling as well as product waste associated with leftover product. Still, says Brandes, “there’s a lot of room for improvement. Current systems create a lot of waste.” But efforts are being made to reduce scrap rates and to recycle tubs that hold nested containers during the fill/finish process. 

To meet the priority of product safety, suppliers seek designs to prevent needlestick injuries and to protect product quality by minimizing particulates and eliminating product interaction with tungsten or silicone residues. For tungsten-sensitive products, Gerresheimer Biological Solutions offers a metal-free manufactured syringe. With this patented technology, the pin used for conical shaping is made of a ceramic rather than tungsten or another metal.

Silicone oil is commonly used to facilitate syringe performance but can cause aggregation and particulate problems for sensitive biologics. “There’s a push by ophthalmologists and regulatory bodies to move away from siliconized formats,” reports Brandes. “Some patients have reactions to silicone, and over time with repeated injections, the material can accumulate [in the eye],” he explains.

One silicone-free option combines ImproJect plungers from W.L. Gore & Associates with syriQ BioPure silicone-free syringes from SCHOTT. The system opens the door for many sensitive products to move into the prefilled syringe format. Until the advent of a silicone-free design, “Pharmaceutical manufacturers seeking to avoid silicone-induced aggregation and sub-visible particles have had to choose vials even when they wanted to offer other delivery options,” said Christiane Gumera, product specialist at W.L. Gore & Associates. Careful attention to syringe geometry and dimensions of the syriQ BioPure syringes helps ensure a consistent gliding force and injection duration over the shelf-life of the product and maintains container/closure integrity without the use of silicone. Ultra-low tungsten residuals and minimal cannula adhesive residuals further reduce the extractible profile and the risk of container/drug interactions (3). 

To prevent potentially hazardous accidental needlesticks and comply with regulations in various parts of the globe, some syringes like Gerresheimer’s InnoSafe product incorporate a pre-applied, passive safety device. With the pre-applied device, there’s no need for post-filling assembly equipment or for healthcare professionals to install a guard before an injection is given. Advantages include improved compatibility with auto-injectors and a completely hidden needle that gives patients with needle-phobia a better experience. The design also prevents accidental reuse and runs on existing fill/finish lines without any additional equipment or process steps.

Finally, COVID-19 has spurred the development of prefilled syringes, particularly with regard to low-temperature storage. Brandes predicts, “Right now all COVID-19 vaccines are in vials, but in the next two to four years we will see a novel type of syringe that handles -80 ºC.”

Fill/finish innovations

Innovations on the fill/finish line focus on automation and flexibility for higher output, greater efficiency, and faster return on investment. As batch sizes shrink, demand for flexibility rises. Brandes explains, “Flexibility makes it possible to fill a batch of 10,000 units in vials and then switch to a different packaging format and drug on the same line. There’s no need to invest in separate lines for vials, cartridges, and syringes.” 

Driving forces behind automation include consistency, regulatory needs, and labor requirements. “Automation greatly increases consistency and decreases the possibility for human error, and also can provide opportunities for enhanced inspection capabilities—including those that consider visual attributes, weight, and fill volume,” says Deborah Smook, vice-president of Marketing & Business Development at TurboFil Packaging Machines. She notes, “FDA preferences are another consideration. FDA prefers less—ideally no—touching of syringe components for aseptic filling/processing. Finally, automation decreases labor requirements, diminishes the difficulties of working in a cleanroom with full personal protective equipment, and reduces the likelihood of repetitive motion injuries.”

A $50-million expansion at Baxter Biopharma Solutions in Bloomington, Ind., will boost efficiency and enhance product quality with the installation of a high-speed automated syringe fill line capable of handling up to 600 units/min and other improvements (4). A fully automated debagging system for RTF syringes has been installed on the newest fill line, and an automated inspection machine has replaced an older system. “[Secondary] packaging lines also feature new packaging options that are plastic-free, as well as tamper-evident,” reports Wendy Saffell-Clemmer, lead scientist and senior director, Baxter. In addition, she says, “Both one-dimensional and two-dimensional online barcode printing is available. Lastly, information technology systems supporting serialization can communicate with the customer’s system to ensure that the serial numbers applied are unique and traceable across the network of product manufacturing sites the customer may be using.” 

The new systems were carefully evaluated with particular attention to prior experience with the instrument manufacturer, anticipated customer requirements, and the available footprint for installation. “New automation technologies were selected to enhance efficiency as well as product quality,” says Saffell-Clemmer. “For example,” she reports, “the newly installed inspection machine has the latest vision systems, which can reduce the false detection rate as well as offer a solution to detect particles in heavy suspension products such as vaccines.”

Civica Rx is building a greenfield, 120,000-ft2 aseptic fill/finish operation in Petersburg, Va., as part of a manufacturing partnership with Phlow Corporation, AMPAC Fine Chemicals, and Virginia Commonwealth University’s Medicines for All Institute. The plant in Petersburg will start up with one syringe- and one vial-filling line with space available for another vial or syringe line. The syringe line is rated at up to 50 million units/yr. Isolator-equipped automated fillers with automatic vision inspection are designed to minimize manual intervention and maximize quality, compliance, and assurance levels. Automation “allows the product to be washed and filled at tight tolerances with no human touch,” reports Stan Benson, vice-president and general manager, Civica Petersburg.

In-process control and weighing of each syringe before and after filling ensure precise fill volumes. Automatic micro-adjustments maintain fill accuracy throughout the batch. Vacuum-assist stoppering minimizes oxygen levels within the headspace (i.e., the distance between the product and the plunger). The low oxygen levels and small headspace enhance product stability and protect product potency.

All product contact surfaces—from the compounding vessel to the filling needles—are single-use and arrive gamma-sterilized and ready to use. “Single-use systems eliminate the need for clean-in-place and sterilization processes that consume testing and energy [resources],” explains Benson. Each syringe will undergo automated visual inspection to confirm container and closure integrity and fill volume and check for container flaws and particulates. High-voltage leak testing will help check for glass deterioration.

On the equipment side, TurboFil Packaging Machines offers several syringe filling options including rotary indexing monoblocks, walking beam fillers, and robot-assisted parts assembly. “Syringe formats are more varied than vials and require a more flexible approach to overcome the challenging filling issues surrounding product viscosity, air evacuation, leakage, and of course, accuracy,” explains Smook.

Employing a versatile yet precise setup that accurately fills syringes via a ceramic piston, peristaltic pump, or direct draw from a reservoir bag, TurboFil’s SimpliFil syringe filling and assembly system handles small to medium batches. Its walking beam indexing configuration provides intuitive operation and simplified, recipe-based changeover. For heightened precision, TipFil technology allows syringes of all types to be filled through the tip—a step-saving innovation that eliminates the need to insert plungers post-filling.

Offering full control of filling parameters in single or dual operation, the benchtop TipFil syringe filler accurately and consistently fills up to 12 units/min. A servo-driven piston mechanism draws the needle back via the plunger, with the distance the plunger is moved dictating the amount of drug filled. Among other benefits, this method eliminates the need to clean an extraneous metering device. A key attribute of the system is its versatility. The unit can perform through-the-tip filling for liquids or viscous products for typical infeed scenarios including hoppers and reservoirs. An optional attachment makes it possible to fill bottles or vials. Suckback control heightens fill accuracy, and all product contact parts are fully disposable. 

References

1. Emergen Research, “Prefilled Syringes Market Share Growing Rapidly with Recent Trends and Outlook 2020 – 2027,” Press Release, April 5, 2021.

2. Stevanato Group, “Stevanato Group Sings an Agreement with Gerresheimer to Provide Its Integrated Twist-off Closure System Solution, ITC, for Gx RTF Syringes,” Press Release, Oct. 6, 2020,

3. Pharm.Tech., “Glass Syringe System Reduces Injection Force without Silicone,” PharmTech.com, Nov. 21, 2019.

4. Baxter International Inc., “Baxter BioPharma Solutions Announces $50 Million Investment to Expand Sterile Fill/Finish Manufacturing Site in Bloomington, Ind.,” Press Release, Nov. 24, 2020.

About the author

Hallie Forcinio is packaging editor of BioPharm International.

Article details

BioPharm International
Vol. 34, No. 6
June 2021
Pages: 32–35

Citation

When referring to this article, please cite it as H. Forcinio, “Innovations Meet Growing Demand for Prefilled Syringes,” BioPharm International 34 (6) 2021.