Solutions for
combination products
Drug-device combination products can bring together a thermosensitive drug, a complex delivery system and a protective package within a single sterilization challenge. For blistered prefilled syringes, the process must reach external surfaces, recessed areas and partially enclosed geometries without exposing the filled product to damaging temperatures. Sterilant penetration through the Tyvek® layer must therefore be demonstrated, together with microbial effectiveness inside the blister and around critical syringe components.
At the same time, manufacturers must protect drug stability, material compatibility and container-closure integrity, while ensuring that neither the product nor its packaging retains unacceptable sterilant residues.
SAL 10⁻⁶
sterility assurance level achieved for the documented blistered prefilled-syringe configuration
<0.15ppm
residual H₂O₂ in the drug product, measured by UV-visible spectrometry
<0.05ppm
residual H₂O₂ in the blister, measured by UV-visible spectrometry
3 hours
total cycle time for the documented vH₂O₂ sterilization process

WE DEVELOP THE STERILIZATION PROCESS AROUND THE COMPLETE FILLED-SYRINGE AND BLISTER CONFIGURATION
proving microbial effectiveness while protecting the drug, device and packaging.
For this thermosensitive combination product, vaporized hydrogen peroxide is selected as the low-temperature sterilant. But sterilant selection is only the first step. The Tyvek® layer, the syringe lumen adjacent to the plunger stopper, the area beneath the backstop and the internal blister surfaces present distinct penetration challenges.
By combining vH₂O₂ exposure with controlled deep-vacuum pulses, we remove trapped air and promote sterilant penetration throughout the packaged system, achieving the required microbial reduction while preserving drug quality and combination-product integrity.
Reusable heat-sensitive parts whose material, geometry, packaging and microbial-reduction requirements support a validated low-temperature route.
Steam sterilization for compatible reusable parts packaged in bags or canisters before protected or closed transfer.
Compact layouts, fewer equipment interfaces, reduced classified-space demand or a single integrated route for compatible reusable loads.
Sealed RTU or pre-sterilized materials whose internal sterile state must be preserved while the outer packaging is treated before entry.
Deep-vacuum H₂O₂ pulses penetrate the Tyvek® layer and reach recessed external surfaces while avoiding the temperatures associated with steam sterilization.
Integrated washing and sterilization of bulk closures, followed by closed transfer in a sterile tank.
Controlled loading, unloading, movement, connection and delivery to reduce exposure and avoidable manual intervention.
Reduced exposure, controlled connection to the barrier and readiness for closed or robotic reassembly.
Validated washing establishes the required cleanliness state for reusable product-contact, machine and format parts before downstream treatment.
Maintains treated bulk stoppers within a closed sterile environment during transfer from the washing and sterilization system to the automated manipulator.
Automated unloading and downstream transfer preserve load traceability, increase sterilizer utilization and support continuous production flow.
emerge sterile, dry and ready for immediate use.
Why use H₂O₂ instead of steam for blistered prefilled syringes?
Steam may expose thermosensitive drugs, polymeric components and Tyvek® packaging to unsuitable temperatures and humidity. Vaporized H₂O₂ enables microbial reduction at lower temperatures while treating the external surfaces of the closed syringe within its blister.
Is the drug product itself sterilized by H₂O₂?
No. The objective is to sterilize the accessible device and blister surfaces while the drug remains protected by the syringe container-closure system. Nevertheless, potential H₂O₂ transfer into the drug must be analytically investigated during process development.
How does H₂O₂ enter a sealed blister?
The Tyvek® lid is porous to the sterilant. Deep vacuum removes air from the blister and recessed geometries, creating the conditions for vaporized H₂O₂ to penetrate the porous layer and contact the enclosed external surfaces.
Why is deep vacuum important?
Air trapped inside the blister, syringe lumen or beneath assembled components can obstruct sterilant distribution. Deep-vacuum and pressure-pulse sequences improve air removal and support H₂O₂ penetration into these difficult locations.
Can the same cycle be used for every prefilled syringe?
No. Syringe materials, drug formulation, stopper position, backstop geometry, blister volume, Tyvek® specification and load arrangement can all affect penetration, absorption and aeration. The cycle must be developed and validated around the actual commercial configuration.
Does the blister remain sterile after treatment?
The Tyvek® layer allows sterilant penetration during the cycle and subsequently functions as part of the microbial barrier. Seal integrity and packaging performance must be validated for the specific blister configuration and sterilization process.
How is product protection demonstrated?
Microbial effectiveness is assessed together with drug-product analysis, residual H₂O₂ testing, product-loss evaluation and container-closure integrity. This prevents achievement of SAL from being considered independently of combination-product quality.
At what point does sterilization occur?
In this application, H₂O₂ treatment occurs after the filled and assembled syringe has been sealed inside the Tyvek® blister and before final cartoning and serialization.
