Innovations in Prefilled Biologics

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Prefilled products, particularly prefilled biologics, are a growing sector in the pharmaceutical industry. “Prefilled syringes and pens offer precise dosing, reducing the risk of errors during administration. They also eliminate the need for reconstitution, making them more convenient for patients and healthcare professionals,” explains Ward Smith, director of marketing and business development at Keystone Folding Box Company, a manufacturer of paperboard packaging. Prefilling also improves product/patient safety because less handling means less chance of contamination.

Prefilled biologics address the growing demand for personalized medicine, homecare, and self-administration options, as well as the desire for an improved patient experience. “This allows patients to continue their treatment in the comfort of their homes while reducing the costs for the healthcare system as fewer trips to a hospital or doctor are needed,” notes Tom Van Ginneken, product manager of polymer solutions at SCHOTT Pharma, a manufacturer of containers used for prefilled biologics and other pharmaceutical products.

The latest innovations for prefilled biologics, including pens, auto-injectors, and on-body delivery systems, accommodate higher volumes, more viscous fluids, a proliferation of longer-acting injectables with longer dosage intervals (weekly, monthly, or even longer), smaller batches, and the ever-present need to reduce healthcare costs. As a result, manufacturers are focusing on user-friendly device designs with features such as ergonomic grips, intuitive mechanisms for injection, and safety features to prevent accidental needlesticks. One example, the Aidaptus auto-injector, developed by Owen Mumford and Stevanato Group, can accommodate a variety of drug viscosities. For added flexibility, the two-step, single-use auto-injector is compatible with 1-mL or 2.25-mL prefilled glass syringes (1).

“Some prefilled biologics packaging now integrates digital technologies, such as Bluetooth-enabled devices or smartphone apps,” reports Smith. These connected devices can track dosing history, provide reminders, and transmit data to healthcare providers, improving adherence and patient monitoring.

Finally, sustainability is an increasingly important consideration. Therefore, manufacturers are exploring ways to minimize environmental impact by moving away from non-renewable materials, optimizing packaging size and weight, incorporating recyclable, recycled-content, or biodegradable materials, and maximizing reusability.

Packaging innovations

Primary packaging developments include ready-to-use (RTU) containers and designs to address higher viscosity products, larger syringe volumes to meet the dosing requirements of longer-acting biologics, cryogenic storage and distribution, greater focus on self-administration and patient comfort, and container enhancements that minimize the risk of product/package interactions. “This minimized interaction risk ensures that the biologics maintain their efficacy and safety profiles,” says Van Ginneken.

With sensitive substances and challenging environmental requirements, biologics place special demands on primary and secondary packaging. Many APIs are light-sensitive, and the large, complex molecules in many new molecular entities are sensitive to oxygen. Cell and gene therapies as well as messenger RNA (mRNA) substances must be stored and transported at extremely low temperatures. Thus, syringe development has focused on designs capable of withstanding low-temperature conditions without losing functionality or container closure integrity. One example, the TOPPAC freeze prefilled syringe from SCHOTT Pharma, is designed for drugs that require storage and transport at temperatures approaching -100 °C. Another option from SCHOTT Pharma, EVERIC freeze vials, are available in sizes from 2–30 mL and can be supplied RTU. Strength-optimized geometry, designed into the structure of the vials, reduces the risk of breakage (2).

As drug products have moved toward more complex proteins and longer intervals between injections, “primary packaging needs to evolve,” says Daniel Martinez, product manager at Stevanato Group, a global provider of drug containment and delivery solutions. This evolution requires higher levels of inertness to minimize chemical interactions, which can cause aggregation that could trigger an immune response in a patient.

Glass continues to dominate, but cyclic olefin copolymer (COC)/cyclic olefin polymer (COP) syringes are well-established alternatives due to their break resistance, lighter weight, lower chances of protein absorption, and compatibility with cryogenic conditions. Unfortunately, COC/COP’s barrier properties may not be sufficient for oxygen-sensitive biologics and

biosimilars. However, “… specialty labels with built-in barrier functions can overcome this challenge,” reports Corinna Endres, product manager drug protection solutions at Schreiner MediPharm, a Germany-based provider of functional labels. The company’s Gas-Protect-Labels can reportedly reduce oxygen transmission without changing processes or primary packaging. One Gas-Protect-Label design covers the syringe barrel. Another design, the Syringe-Closure-Wrap, enhances barrier protection by wrapping like a second skin around the syringe barrel and cap and sealing at the upper end. An integrated first-opening indication on the Syringe-Closure-Wrap also provides tamper evidence. Label structures can be customized for the barrier needs of the API in the syringe.

Schreiner Medipharm also offers a label for prefilled cell and gene therapies and mRNA substances stored and transported under cryogenic conditions. The Freeze-Light-Protect label reliably adheres to COC syringes at sub-zero temperatures and provides customizable light protection ranging from blocking pure ultraviolet (UV) rays, to blocking UV rays and blue light, to providing a total light barrier. Freeze-Light-Protect labels can be equipped with integrated functionalities such as detachable documentation labels, an inspection window for checking the syringe content in true color, and a graduation for exact dosing when performing the injection. “With the help of this multi-functional label solution, product and patient safety can be enhanced,” says Endres.

Although 1 mL remains the most common volume for auto-injectors, the range of prefilled syringe and cartridge sizes is expanding to include 2.25-, 5-, 10-mL, and greater volumes needed to handle more viscous products, higher volume injections, and products that can’t be concentrated and are destined for on-body delivery systems. SCHOTT Pharma, for example, has added a 5.5 mL size to its syriQ BioPure glass syringe family. Applications include larger volume medications for treating cancer and autoimmune diseases.

It’s also been necessary to optimize mechanical performance to accommodate higher impact forces without breakage. “More viscous products require higher injection forces,” explains Martinez.

The development of device platforms, like the two-step YpsoMate injector from Ypsomed or the Molly auto-injector from SHL Medical, is streamlining the introduction of combination products. Instead of performing Phase I and II clinical trials in vials and moving to a prefilled syringe for Phase III and commercial product, developers are adopting prefilled syringes as early as Phase I or II. “This … allows for earlier data gathering for the prefilled syringe presentation, and perhaps even more importantly, one can obtain valuable stability information at a much earlier stage,” says Justin Schroeder, global vice president, technical sales at PCI Pharma Services, a contract development and manufacturing organization (CDMO). Being able to include real-world data in regulatory filings can expedite regulatory approvals and shorten time-to-market.

The earlier transition to a prefilled syringe also helps ensure the patient self-doses properly, prevents medication errors, mitigates potential risks, improves patient adherence and persistence, and increases patient education and health literacy. “Well-orchestrated and integrated device, packaging, and labeling strategies can succeed on all [these fronts] if planned and executed synchronously,” explains Schroeder.

A customizable on-body delivery system, the Vertiva platform developed by Stevanato and Thermo Fisher Scientific, consists of a single-use pod with prefilled and pre-loaded 3-mL cartridge and a multi-use, smart controller. Stevanato supplies pre-sterilized EZ-fill cartridges and assembly equipment, while Thermo Fisher provides fill/finish and final assembly services (3). The highly flexible programmable device can deliver micro-precision basal doses or full-content bolus injections and is suitable for a wide range of therapies. It also accommodates volumes greater than 3 mL and offers Bluetooth connectivity for digital health applications. Reusability helps address sustainability concerns (4).

Fill/finish trends

The primary trends on fill/finish lines for biologic products are the growing adoption of RTU containers, higher levels of automation and flexibility, and increased reliance on CDMOs.

RTU containers result in a more flexible, leaner operation and improve contamination control. For example, EZ-fill Smart containers from Stevanato now rely on thermally welded polymer film tray lidstock. The change from traditionally used Tyvek lidstock requires minimal modification of the fill/finish line and eliminates any fiber or glue residue contamination associated with the removal of the Tyvek material.

Flexibility, especially to handle the smaller batches needed for clinical trials or personalized medicine, is becoming an essential attribute of the fill/finish process. One filling system installed at PCI Pharma Services, the SA-25 aseptic filling workcell from Cytiva, handles vials or syringes. “These advanced robotic isolator systems are Annex 1-compliant and offer very small line losses, [and] are attractive for those developing high-value drug substances such as biologics and antisense oligonucleotides,” reports Schroeder.

When automating, some companies transition to fully automated systems, while others take a semi-automated approach. One semi-automated example, a custom-built benchtop draw filler from Turbofil Packaging Machines, offers a system that is more accurate and less labor-intensive than manual filling. Plus, it fits under a laminar flow hood, making it suitable for aseptic filling. The machine fills the syringes through the tip directly from intravenous bags via a disposable fluid path. This “saves time and resources while reinforcing sterility,” explains Deborah Smook, vice-president of marketing and business development at TurboFil Packaging Machines. Draw-filling not only enhances accuracy but also improves operator safety, simplifies changeover, accommodates a variety of syringe sizes and product types, and eliminates the need to clean a metering device.

For fully automated operations, a servo-driven, intermittent-motion TipFil monoblock model loads, fills, caps, inspects, and labels syringes and prints lot number and expiration date and other information such as QR codes or usage instructions at up to 50 pieces/min. Interchangeable pucks accommodate syringe sizes from 1–60 mL, and the machine can handle a wide range of product viscosities (5).

However, Smook warns, “… automation is rarely as simple as devising a machine to replace a manual process. Adjacent issues such as sterility and inspection, which can become more challenging at higher line speeds, also must be addressed.”

Automated inspection needs can be met by the high-speed Visual Rotating Inspection (VRI) series from Antares Vision Group. Capable of checking liquid-filled glass or plastic containers at speeds up to 400 containers/min, the machines combine sophisticated particle and cosmetic detection with closure integrity verification. VRI units can inspect liquids with viscosities from water-like to gels and emulsions, as well as lyophilized and powder products. Vials also are inspected for cosmetic defects related to crimping quality, flip-off color, neck-shoulder sidewall flaws, and stopper position (6).

Conclusion

Overall, drugs are becoming more complex and thereby more sensitive. Thus, “… the prefilled biologics packaging industry is characterized by ongoing innovation aimed at enhancing safety, convenience, and patient experience, while also addressing regulatory compliance and sustainability concerns,” says Smith.

“It is therefore essential for pharma companies and containment suppliers to work hand-in-hand from the beginning to ensure that the medication is stored and administered safely,” concludes Van Ginneken.

References

1. Stevanato Group. Aidaptus Manufacturing. www.stevanatogroup.com (accessed March 4, 2024).
2. SCHOTT Pharma. Protecting Drugs at Deep-Cold Temperatures: SCHOTT Pharma Launches New Vials for mRNA and Gene Therapy. Press Release. Jan. 24, 2024.
3. Stevanato Group. Stevanato Group Collaborates with Thermo Fisher Scientific to Bring Its Innovative On-Body Delivery System Platform to Market. Press Release. March 21, 2023.
4. Stevanato Group. Vertiva. www.stevanatogroup.com (accessed March 4, 2024).
5. TurboFil Packaging Machines. TurboFil Introduces Fully Automatic Version of Popular Syringe Filling System. Press Release. Dec. 5, 2023.
6. Antares Vision Group. At INTERPHEX, Antares Vision Group to Showcase Automatic Inspection Machines for Vials, Pre-filled Syringes, and Other Small-Volume Containers. Press Release. Feb. 13, 2024.

About the author

Hallie Forcinio is packaging editor for Pharmaceutical Technology.

Article details

Pharmaceutical Technology
Vol. 48, No. 4
April 2024
Pages: 24–27

Citation

When referring to this article, please cite it as Forcinio, H. Innovations in Prefilled Biologics. Pharmaceutical Technology, 2024, 48 (4) 24–27.