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3 mL and 5 mL Prefilled Syringes: How Integrated Needle Safety Improves Usability, Sustainability, and Total Cost of Ownership

August 31, 2026

Pharmaceutical pipelines are creating growing demand for larger-volume injectable drug delivery. By accommodating greater delivery volumes, 3 mL and 5 mL prefilled syringes can provide greater flexibility in formulation and dose delivery and may reduce the need for higher drug concentrations or multiple injections.

Moving to a larger-volume prefilled syringe has implications beyond drug capacity. As syringe size increases, add-on safety devices become larger, increasing their impact on usability, manufacturing, packaging, logistics, material usage and cost. This increases the value of integrating passive needle safety directly into the syringe system.

Why Larger-Volume Prefilled Syringes Matter

The move toward 3 mL and 5 mL prefilled syringes is driven primarily by therapy and formulation needs, as well as longer dosing intervals.

Many injectable therapies, including biologics such as monoclonal antibodies and enzyme therapies require relatively high doses. Increasing drug concentration can help reduce injection volume, but it may also increase viscosity, affect stability, raise injection force, or create manufacturability challenges. When a drug cannot be concentrated further without compromising its performance profile, a larger-volume syringe may be the enabling delivery option.

Larger formats can also reduce the need for multiple injections. Rather than asking a patient or caregiver to administer two or more conventional syringes, a manufacturer may be able to provide the prescribed dose in one larger-volume presentation. Industry suppliers are increasingly developing large-volume staked-needle syringe systems specifically to support single-dose subcutaneous delivery of higher-volume injectables.

For pharmaceutical teams, however, moving to a larger syringe is not a simple scale-up. It requires evaluation of formulation compatibility, barrel geometry, plunger performance, needle design, injection force, packaging, distribution, safety considerations, and patient use. As syringe size increases, the choice of needle-safety solution also becomes increasingly important, as an add-on safety system can add size, material, and complexity to manufacturing, assembly, packaging, shipping, handling, and disposal.

Larger Volume Changes Device Design

A 3 mL or 5 mL prefilled syringe must be considered as part of a complete drug-device system. As volume and viscosity rise, device design becomes increasingly important to the patient, caregiver, healthcare professional, fill-finish team, and commercial organization.

Critical development considerations include:

  • Drug-container compatibility, including interactions with glass, silicone, elastomers, adhesives, and lubricants.
  • Container-closure integrity and maintenance of sterility through shelf life and distribution.
  • Break-loose and glide forces, which influence injection feel and dose delivery.
  • Needle gauge, needle wall thickness, and needle length.
  • Injection force and injection duration for higher-volume or more viscous formulations.
  • Human-factors performance across intended users and use environments.
  • Needlestick protection, post-use handling, disposal, and prevention of accidental reuse.
  • Sustainability considerations, including use of materials, burden of handling and shipping.
  • Total cost of ownership and manufacturing complexity.
  • Fill-finish integration, secondary assembly, packaging, shipping, and supply-chain requirements.

These factors are closely connected. A safety device that complicates use, adds post-fill operations, or requires an unfamiliar final action can introduce risk rather than reduce it.

What Integrated Needle Safety Means

Integrated needle safety describes how the safety mechanism is incorporated into the syringe system rather than added as a separate “add-on” external device. Passive safety describes how that mechanism is activated automatically as part of the injection sequence, without requiring a separate user action.

The Credence Companion® Platform combines both: passive needle safety integrated within the syringe system.

This differs from an add-on safety device, such as an external needle guard, shield, sleeve or clip, which is assembled to the syringe after filling.

By integrating the safety mechanism within the syringe system, the Companion® Platform can eliminate the need for a separate post-fill safety-device assembly step. This can simplify the manufacturing pathway, reducing additional components, processing and handling, with associated benefits for time, cost, and operational complexity.

Passive Versus Active Needle Safety

Needle-safety systems generally fall into two categories: passive and active.

Passive safety activates automatically as part of the injection sequence, without requiring a separate user action. In the Companion® Platform, passive safety activation occurs at the completion of injection. The user does not need to remember a separate post-injection step to cover or retract the needle. This can be particularly valuable when products are administered by patients and caregivers outside a clinical environment.

Active safety requires the user to deliberately deploy the protection feature, such as sliding a shield over the needle after use. Active systems can provide effective sharps protection, but successful activation depends on correct and consistent user action.

For larger-volume syringe programs, removing nonessential post-injection actions can be particularly valuable. The user may already be managing a longer injection, more drug volume, and potentially higher plunger force; safety should not add a separate task at the moment the injection is completed.

The Credence Companion® Safety Syringe Platform uses an integrated passive mechanism designed to retract the needle into the barrel after injection. The system provides audible, tactile, and visual indicators of safety engagement and prevents reuse after activation.1

Improving Usability in Real-World Settings

Usability is a central development requirement for injectable combination products. As more therapies shift to home administration and alternate-care settings, devices must perform reliably for users with varied levels of training, confidence, dexterity, and injection experience.

Passive needle safety can support usability in several important ways. For 3 mL and 5 mL syringes, these advantages become more meaningful because the physical and procedural demands of administration can be greater than with a conventional 1 mL presentation.

Fewer Steps, Fewer Opportunities for Error

Every additional action after injection adds the possibility of confusion or incomplete activation. A user may forget to engage a manual needle shield, activate it incorrectly, or dispose of the device before protection is in place.

A passive integrated system reduces the number of critical post-injection actions. The user can focus on administering the full dose, while the safety mechanism activates as part of the normal delivery sequence, and the user is supported with end-of-dose cues.

Familiar Injection Technique

The Credence Companion® platform is an unencumbered syringe presentation intended to preserve familiar injection technique while simplifying the overall user process. The integrated approach allows the user to inspect the drug and syringe as well as observe the injection. For the drug manufacturer, ample labelling space is enabled by the removal of the add-on device.

Clear Confirmation of Dose Completion

For patient and caregiver use, it is important to provide clear feedback when injection is complete and when the safety feature is engaged. Audible, tactile, and visual cues can reduce uncertainty, reinforce correct use, and help confirm that the device is safe for disposal.

The FDA recommends that users be able to easily determine whether a needlestick-injury-prevention feature has been activated and that the feature remain protective through disposal. For active systems, FDA further recommends one-handed activation while keeping hands behind the exposed needle. Passive systems eliminate this additional post-injection action, helping reduce the opportunity for missed or incorrect safety activation—an important consideration for patient and caregiver use.2

Sustainability Starts with System Simplification

Sustainability in pharmaceutical packaging and drug delivery is not determined by a single material or component count. A meaningful assessment should account for materials, component weights, scrap, assembly, sterilization, packaging, shipping, and disposal.

Integrated safety can create clear sustainability opportunities because it can reduce the number of discrete components in a safety-enabled syringe system, and these benefits are heightened in 3 mL and 5 mL syringe presentations.

Potential benefits include:

  • Reduced material use by eliminating large add-on safety-device parts. In add-on systems, larger syringes require bigger, heavier add-on systems that consume more plastic and metal material.
  • Fewer secondary assembly operations.
  • Less component-related scrap and rework.
  • Simplified packaging and inventory management.
  • Reduced material handling resources.
  • Fewer suppliers and component shipments.
  • A more streamlined post-use waste stream.

The Credence Companion® Safety Syringe Platform can reduce manufacturing steps, extra scrap, and waste by integrating safety into the syringe system rather than relying on secondary safety-device assembly.

For manufacturers with corporate environmental goals, eliminating the need for a separate add-on safety device has the potential to reduce additional plastic components and associated material, assembly, packaging and transportation burdens. These impacts can extend across the product lifecycle and should be evaluated using established life-cycle assessment principles such as ISO 14040/14044.

Total Cost of Ownership

For 3 mL and 5 mL prefilled syringe programs, the choice of safety solution can have an increasingly significant impact on total cost of ownership. As syringe formats become larger, add-on safety systems require more material, larger components, additional assembly operations, and increased packaging and logistics requirements.

The Companion® Platform takes a different approach. Its passive safety mechanism is integrated within the syringe architecture and is consistent across the 1 mL to 5 mL platform, creating opportunities for manufacturing and supply efficiencies as pharmaceutical companies move into larger-volume formats.

Total cost of ownership is considered across the full product lifecycle, including:

  • Primary-container and safety-device component costs.
  • Tooling, qualification, validation, and technology-transfer requirements.
  • Fill-finish compatibility and manufacturing-line impact.
  • Secondary assembly, automation, inspection, and quality-control requirements.
  • Packaging, distribution, storage, and logistics.
  • Supplier management, inventory, and supply-chain risk.
  • Training, instructions for use, customer support, and complaint handling.
  • Sharps-safety, accidental-reuse, and use-error risk management.

An integrated safety platform can create opportunities to reduce these system-level costs by consolidating components and minimizing secondary assembly. Fewer parts can mean fewer supplier relationships, inventory positions, assembly interfaces, and potential fit-and-function failures.

Innovation Without Change®

For pharmaceutical companies, introducing meaningful drug delivery innovation should not require unnecessary change to proven primary components, established fill-finish processes, and manufacturing infrastructure.

Innovation Without Change® is central to the Credence approach. The Companion® Platform integrates advanced passive needle safety while maintaining compatibility with proven primary components and established manufacturing processes wherever possible.

For 3 mL and 5 mL programs, this becomes particularly important. Pharmaceutical partners can address evolving larger-volume delivery requirements without introducing the additional components, secondary assembly, and operational burden associated with a larger add-on safety-device architecture.

Why Credence MedSystems

Credence solves injectable drug delivery challenges through platform technologies designed around the needs of patients and built for the realities of pharmaceutical development and manufacturing.

The Companion® Platform brings passive integrated needle safety and user-preferred drug delivery across industry-standard prefilled syringe formats from 1 mL to 5 mL. As pharmaceutical companies move towards larger-volume presentations, its integrated approach can deliver increasing value by avoiding the need for a separate add-on safety device and associated secondary assembly.

Through Innovation Without Change®, the Companion® Platform works with proven primary components and established manufacturing processes wherever possible, helping pharmaceutical partners introduce advanced drug delivery capabilities while minimizing implementation risk and operational disruption.

If you are developing a 3 mL or 5 mL prefilled syringe programme, talk to Credence about how passive integrated needle safety could support your success.

Frequently Asked Questions

Why are 3 mL and 5 mL prefilled syringes used?

They can support therapies requiring a higher delivered volume than a conventional 1 mL syringe can accommodate. They are particularly relevant when further drug concentration could create viscosity, stability, injectability, or patient-tolerability challenges. Larger formats may also reduce the need for multiple injections.3

What is integrated needle safety?

Integrated needle safety is a sharps-protection mechanism engineered into the syringe system rather than added as a separate external accessory. Depending on the design, it may retract or permanently shield the needle after injection.

What is the difference between passive and active safety?

Passive safety activates automatically during or at the completion of injection. Active safety requires the user to take a separate action, such as manually deploying a needle shield. Passive systems can reduce the risk that a final safety step is missed.

Can integrated needle safety improve home administration?

Yes. Passive integrated safety can simplify the injection sequence, reduce post-use needle exposure, preserve a familiar syringe experience, and provide feedback confirming injection completion and safety engagement. Devices should still undergo appropriate human-factors evaluation for their intended users and settings.2

Can integrated safety support sustainability goals?

Reducing separate safety components can reduce material use, secondary assembly, packaging complexity, scrap, and supply-chain burden. The actual environmental impact should be evaluated across the entire product lifecycle.

Does integrated needle safety reduce total cost of ownership?

It can. An integrated safety approach can create opportunities to reduce system-level costs by consolidating components and minimizing secondary assembly. Fewer parts and operations can reduce costs associated with materials, assembly, packaging, inventory, logistics, and supply-chain complexity

 

Sources

1. ONdrugDelivery, April 23, 2019. https://www.ondrugdelivery.com/credence-medsystems-credence-companion-safety-syringe-system/

2. U.S. Food and Drug Administration. “Medical Devices with Sharps Injury Prevention Features: Guidance for Industry and FDA Staff.” August 9, 2005.

3. BioPharm International, June 7, 2024. https://www.biopharminternational.com/view/innovations-in-prefilled-biologics

Intravitreal Injections: How Dose-Assist Devices Support Safer, More Accurate Drug Delivery

August 25, 2026

Intravitreal biologics and other therapies have transformed the treatment of retinal disease, but they have also concentrated significant clinical stakes into a single, sub-100-microliter injection. Unlike a subcutaneous or intramuscular dose, an intravitreal injection is delivered directly into a small, delicate, and largely incompressible compartment of the eye, where even small variability in delivered volume, residual air, or plunger motion can affect patient safety, comfort, and treatment outcome.

For pharmaceutical and biotechnology companies developing ophthalmic biologics, the prefilled syringe is therefore more than a delivery vehicle, it is effectively part of the therapy. As more anti-VEGF agents, gene therapies, and next-generation ophthalmic biologics move through development, drug-delivery teams are re-examining how syringe design can reduce dosing variability and patient risk without disrupting proven primary packaging or established fill-finish processes.

The Credence Micro-Dose® Syringe Platform was purpose-built around these requirements. Rather than replacing a pharma company’s chosen prefilled syringe, Micro-Dose® is a precision-dosing attachment that assembles onto standard prefilled syringes after filling, adding mechanically guided air removal and dose delivery in support of precision, safety, and efficacy for intravitreal therapies.1

Solving the Intravitreal Drug Delivery Challenge

Intravitreal injection volumes are unusually small, commonly in the 50 µL range for many approved therapies, and lower still for some newer or investigational agents.2 At these volumes, a small absolute dosing error represents a comparatively large percentage error, which is why precision dosing is the foundational design requirement for any intravitreal delivery system: it helps the clinician avoid overdosing and its associated safety concerns, as well as underdosing, which can compromise therapeutic efficacy.

Precision Dosing, By Design

Micro-Dose® uses a defined mechanical hard stop to set the limit of plunger travel, so the delivered dose is determined by the design of the device itself rather than by a clinician visually aligning the plunger with a printed graduation line on the syringe barrel.2 This is intended to reduce a source of dosing variability that is otherwise dependent on user technique, particularly important given how little margin low-volume ocular dosing allows.

Plunger Recoil and the Risk of Vitreous Backflow

A less visible risk in conventional syringe use is the elastic recoil of the syringe stopper. Published research using standard prefilled syringes found that when a clinician applies additional plunger force and then releases it, the stopper’s elastic rebound can draw fluid, and potentially vitreous, back into the needle, a mechanism the authors observed produces a visible air bubble when it occurs outside the eye.3 The study’s authors specifically caution that this recoil effect, if it occurs while the needle remains within the vitreous cavity, could contribute to vitreous incarceration and place traction on the retina during needle withdrawal, and they recommend that excessive plunger force be avoided and that pressure not be released until after the needle has cleared the eye.3

Micro-Dose®’s mechanism of action is designed to address this risk directly. Because the dose-delivery motion is guided mechanically to a defined hard stop rather than relying on the clinician modulating and then releasing thumb pressure, the design is intended to reduce the plunger-recoil dynamics associated with conventional syringe use and the associated risk of vitreous backflow.

Controlled Air Removal and Patient Comfort

Removing air from a syringe before intravitreal injection is a routine but consequential step. Air injected into the eye can cause significant patient pain, and conventional manual debubbling requires the clinician to overcome the syringe’s break-loose force while judging by eye how much air remains, a process that can also lead to inadvertent drug spillage.2 At intravitreal volumes, the loss of even a small quantity of drug during debubbling can meaningfully underdose the patient.2

Micro-Dose® replaces this manual judgment with a mechanically controlled sequence. The clinician twists the device’s safety cover to prime the syringe, an action that purges the air bubble to a defined hard stop; the thumb pad is then revealed and pressed to deliver the dose to a second, independent hard stop.2 This two-stage, hard-stop design is also intended to guard against premature injection, since the dose-delivery step only becomes available once priming is complete.

Designed for the User: A Trusted Tool for the Clinician

For the retinal specialist, the value of any intravitreal delivery device is measured against a simple standard: does it make an already precise, time-pressured procedure more controlled, repeatable, and efficient, without adding complexity to an established workflow? The Micro-Dose® Platform is designed to add that value while integrating into the procedure clinicians already know.

A Guided, Repeatable Sequence

The mechanically guided sequence is intended to remove areas of variability from the procedure in two stages. First, the controlled twisting action that primes the device and purges air is designed to help overcome the higher break-loose forces that can result from the low- or no-silicone syringes increasingly preferred for ophthalmic use. Second, during dose delivery, the clinician presses the thumb pad to a defined hard stop, removing the need to manually judge dosing against printed syringe graduation lines during the injection itself.

Addressing the Silicone Trade-off

Silicone oil has long served as a lubricant that helps a syringe plunger glide smoothly, but its use in intravitreal syringes carries a well-documented downside: agitation, transport, and even the injection process itself can release silicone oil droplets into the eye, where they may cause visible floaters and, in some published research, have been associated with post-injection ocular inflammation.4 This has led ophthalmic specialists and syringe manufacturers to increasingly favor low-silicone or silicone-oil-free syringe designs, and manufacturer safety notices have recommended using syringes and needles specifically labeled for intravitreal use to help reduce this risk.5

The trade-off is that reduced or specialized siliconization typically raises the break-loose and glide forces a clinician must overcome to operate the syringe, which can make an injection feel less consistent from procedure to procedure.5 Micro-Dose® is designed to address both sides of this tension at once: its mechanically guided priming step is engineered to help overcome the elevated break-loose forces associated with low-silicone syringes, allowing pharma companies to pursue reduced-silicone or specialized siliconization strategies for patient safety without asking the clinician to absorb a corresponding increase in procedural difficulty.

Supporting Procedural Efficiency

Because Micro-Dose® eliminates the need to manually approximate a dose against a printed line and shifts priming and preparation into a controlled mechanical sequence, an assistant or technician may be able to prepare the system in advance of the retinal surgeon’s involvement. This division of labor is intended to allow the surgeon to focus more fully on the injection itself, an efficiency consideration that could matter increasingly as intravitreal injection volumes continue to rise across anti-VEGF and other retinal therapy classes.

Built for Pharma: Practical Integration Across the Supply Chain

For a pharmaceutical or biotechnology manufacturer, a delivery device’s value is not confined to the injection room. A device that offers a meaningful, demonstrable advantage over the current standard of care can become an important source of product differentiation, supporting adoption, market share, and, ultimately, commercial success in an increasingly competitive intravitreal therapeutic landscape.

Compatibility Without Disruption

The Micro-Dose® Platform is designed to deliver that differentiation without requiring a pharma partner to re-engineer its existing drug-product supply chain. The platform supports compatibility with different prefilled syringe and stopper configurations, and because it is assembled onto the syringe after filling, it leaves the aseptic filling process itself completely unchanged.1 It also avoids the need for syringes with printed dose-graduation lines and is engineered with sterilization integrity in mind: Micro-Dose®’s mechanism is designed to help prevent retrograde motion of the plunger during terminal sterilization, addressing a potential route to a break in sterility of the drug product.

Because it is added post-fill, Micro-Dose® also supports specialized siliconization approaches chosen for patient safety, including reduced-silicone or baked-on siliconization strategies,  without requiring the pharma company to alter validated primary packaging or filling-line qualification.1

From Molding to Post-Fill Assembly

Credence’s understanding of pharmaceutical manufacturing spans the full supply chain: from initial design and development, through molding and component manufacture, to post-fill secondary assembly, labeling, and packaging. That end-to-end perspective is intended to help pharma partners implement a differentiated delivery experience for clinicians and patients while minimizing new validation burden, new supplier relationships, or new risk introduced into an already-approved manufacturing pathway.

Innovation Without Change® Ties It Together

Precision, safety, and efficacy for the therapy and patient; a genuinely useful tool for the clinician; and practical, low-disruption implementation for pharma, these three outcomes are the result of Credence’s Innovation Without Change® philosophy. Rather than asking pharmaceutical companies to choose between innovation and operational continuity, Innovation Without Change® is built on the premise that meaningful drug-delivery advances should work with proven primary components and established manufacturing processes, not against them.

For intravitreal drug delivery specifically, that philosophy translates into a device that gives the clinician confidence and control, gives the patient a lower-risk, more comfortable procedure, and gives the pharma manufacturer a differentiated system that fits into the process it has already validated.

Why Credence MedSystems

Credence MedSystems is an industry-recognized innovator in injectable drug delivery, developing platform technologies designed around the needs of patients and built for the realities of pharmaceutical development and manufacturing.6 The Micro-Dose® Syringe Platform extends that platform approach to ocular and intravitreal delivery, adding precision micro-dosing and controlled air purging to standard prefilled syringes without disrupting a manufacturer’s existing primary package or fill-finish investment.1

If you are developing an intravitreal or other low-volume ophthalmic injectable program, talk to Credence about how the Micro-Dose® Syringe Platform will support precision, safety, and clinician confidence in your delivery strategy.

Frequently Asked Questions

What is the Micro-Dose® Syringe System?

Micro-Dose® is a precision-dosing device designed for ocular and intravitreal injections. It assembles onto a standard prefilled syringe after filling and provides mechanically guided air removal and dose delivery to defined hard stops, supporting precise low-volume dosing.1

Why does dosing precision matter so much for intravitreal injections?

Intravitreal doses are commonly delivered in the 50 µL range or lower, so even small absolute variations in delivered volume represent comparatively large percentage errors. Precision dosing helps protect against both overdosing, which raises safety concerns, and underdosing, which can compromise treatment efficacy.2

How does Micro-Dose® address the risk of vitreous backflow?

Conventional syringe use can involve manually applying and releasing plunger force, and published research shows that the resulting elastic recoil of the syringe stopper can draw fluid, and potentially vitreous, back into the needle, a mechanism researchers link to a risk of vitreous incarceration.3 Micro-Dose®’s hard-stop delivery mechanism is designed to reduce reliance on this kind of manual force modulation.

Does Micro-Dose® help with air-related patient pain?

Yes. Air injected into the eye can cause significant patient pain.2 Micro-Dose® guides air removal through a controlled twist-to-prime action rather than manual debubbling, which is intended to reduce both the risk of injecting air and the drug spillage that can accompany conventional debubbling.2

Does using Micro-Dose® require pharma companies to change their existing syringe or fill-finish process?

No. Micro-Dose® is designed to support compatibility with different prefilled syringe and stopper configurations and is assembled post-fill, leaving the filling process unchanged. It is intended to support pharma companies pursuing specialized siliconization approaches without new primary packaging validation.1

Can Micro-Dose® support low-silicone or silicone-free ophthalmic syringes?

Yes. Reduced- or no-silicone syringes are increasingly favored in ophthalmology to help limit silicone oil droplets in the eye, but they typically require higher break-loose and glide forces.4,5 Micro-Dose®’s mechanically guided priming step is designed to help overcome these elevated forces, supporting the clinician while enabling the safety-focused syringe choice.

Sources

  1. Credence MedSystems, Inc. “Micro-Dose® Syringe System.” https://www.credencemed.com/micro-dose-syringe-system/
  2. Dubin, Cindy H. “Injection Devices: Wearables, Connectivity & Patient-Centric Designs Empower Self-Administration” (featuring John A. Merhige, Credence MedSystems). Drug Development & Delivery, September 2019, Vol 19 No 6. https://www.credencemed.com/wp-content/uploads/2020/01/Article-B-Micro-Dose.pdf
  3. Raevis, Joseph J., Colin A. Lemire, David J. Ramsey, James Riccobono, and Efren Gonzalez. “Deformation of Aflibercept and Ranibizumab Syringes Causes Variation in Intravitreal Injection Volume and Risks Retinal Tear Formation.” Ophthalmology Science, July 15, 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC9754977/
  4. Melo, Gustavo B., et al. “The Risks Behind the Widespread Use of Siliconized Syringes in Ophthalmology.” International Journal of Retina and Vitreous, October 30, 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8557543/
  5. “Exploring Syringe Selection for Intravitreal Injections.” Retinal Physician, October 2021. https://retinalphysician.com/issues/2021/october/exploring-syringe-selection-for-intravitreal-injections/