Hyaluronic acid in pre-filled syringes.
Hyaluronic acid pre-filled syringes combine a thermally sensitive formulation with a pressure-sensitive container-closure system. Product performance depends on the molecular weight and rheological behaviour of the formulation, while moist heat progressively reduces viscosity as exposure continues. At the same time, heating increases the internal pressure of the filled syringe through liquid expansion and vapour pressure, potentially causing plunger movement, leakage or loss of container integrity.
Achieving sterility without sacrificing the viscosity that defines product performance. Manufacturers therefore need to achieve the required lethality without applying unnecessary thermal stress, while protecting the syringe throughout heating, exposure and cooling. The challenge is not only sterility, but preserving the functional properties expected after processing.
Steam-air technology provides controlled counterpressure to limit plunger movement, while F₀-based cycle development balances the required microbial lethality against viscosity degradation.
We identify the sterilization profile that best protects the product—not simply the lowest processing temperature.
At our Technology Centers, we profile product response across sterilization strategies at 115°C, 121°C and 130°C, comparing different time-temperature combinations at equivalent lethality. This determines which profile best preserves viscosity and PFS integrity, rather than assuming that the lowest temperature is necessarily the gentlest.
Independent pressure and temperature control applies counterpressure through heating and cooling, protecting 5–7 N seals while delivering effective terminal sterilization
Magazines leave the sterilizer and transfer directly toward secondary packaging, sustaining line continuity and eliminating manual product handling after treatment.
Robotic handling moves magazines from primary packaging to the sterilizer without product extraction or operator contact, maintaining throughput and a touchless production flow
Compatible reusable parts are packaged in bags or loaded into closed canisters before steam sterilization. The process is developed around the complete load configuration to govern air removal, steam penetration, condensate management and drying. Once treated, the selected packaging or transfer system preserves the sterile state during unloading, movement and introduction into the aseptic processing environment.
For reusable parts that cannot withstand steam, low-temperature H₂O₂ sterilization provides an alternative route when supported by material, geometry and packaging compatibility. The complete configuration is evaluated to establish sterilant access, microbial reduction, aeration and residual removal. The treated load then follows a protected transfer route designed to preserve its required state up to the aseptic interface.
Bulk stoppers are washed and steam sterilized in one integrated process developed to control cleanliness, sterility and residual moisture. Following treatment, the closures are discharged directly into a sterile transfer tank. This eliminates intermediate bagging and creates the starting point for a closed route from stopper preparation to automated delivery at the isolator.
Washing and steam sterilization are integrated within one system to establish cleanliness and sterility through a coordinated process. This architecture reduces equipment interfaces, material movements and classified-space requirements while strengthening control between the two treatments. It is selected for compatible reusable loads when layout efficiency, operator protection or a more contained process route drives the transfer strategy.
RTU components and other pre-sterilized materials already contain a protected sterile product within sealed packaging. The low-temperature H₂O₂ process treats the external surfaces before introduction into the aseptic environment without reopening the package or altering its internal sterile state. Cycle development addresses packaging geometry, surface accessibility, load arrangement and aeration as part of the complete transfer configuration.
The automated manipulator connects treatment and point of use through controlled loading, unloading, movement and delivery operations. Depending on the selected route, it handles canisters, sterile tanks or treated materials and manages their interface with the isolator or filling line. Automation removes avoidable manual interventions precisely where exposure, repeated handling and open connections create the greatest vulnerability.
Validated washing removes process residues and establishes the required cleanliness state for reusable product-contact, machine and format parts. Cycle parameters, load configuration and mechanical action are developed around the materials and geometries involved, preparing every surface for the selected downstream treatment and preventing cleaning from becoming an uncontrolled variable within the aseptic-transfer route.
Steam-air technology allows temperature and counterpressure to be governed independently throughout heating, sterilization and cooling. F₀-based control limits unnecessary exposure, while air support pressure counterbalances the pressure developing inside the syringe and constrains plunger movement. The time-temperature profile is configured around the actual behaviour of the formulation and PFS, protecting both the rheological properties of the product and the integrity of the container-closure system.
A pre-filled syringe is a hermetically sealed container with a movable plunger. During thermal sterilization, the liquid expands, part of it vaporizes, dissolved gases are released and the gas already present in the headspace increases in pressure.
An aqueous solution expands by approximately 6% when heated from ambient temperature to 121°C, while the volume of a glass syringe increases by only about 1%.
Not necessarily. A lower temperature requires a longer exposure to achieve the same F₀. In the documented comparison, the 115°C cycle caused the greatest viscosity reduction because of its prolonged duration.
Heat can reduce the molecular weight and viscosity of sodium hyaluronate. Because viscosity contributes directly to product behaviour, the cycle must achieve the required lethality while limiting accumulated thermal exposure.
A peak cycle uses a higher temperature for a much shorter period. For the tested formulation, this strategy achieved approximately the same F₀ while reducing viscosity loss compared with longer, lower-temperature cycles.
No. The appropriate profile depends on formulation, molecular weight, concentration, fill volume, syringe geometry, plunger behaviour and product acceptance criteria. It must be developed and validated for the actual product-container system.
Steam-air technology applies controlled air support pressure to counterbalance the pressure developing inside the filled syringe during heating, exposure and cooling.
Thermal measurements inside a representative PFS confirm the accumulated F₀, while rheological analysis compares the viscosity of sterilized samples with untreated product. Stability and container-closure assessments complete product-specific validation.
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