Researchers recently reported successful structural and manufacturing updates to the Port Delivery Platform, also known as the Port Delivery System with ranibizumab. These changes address prior issues with septum dislodgement and are now being used in trials with other molecules.
The Port Delivery System (PDS) is an intraocular, refillable implant designed to deliver ranibizumab 100 mg/mL continuously. It is intended to reduce treatment burden for patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and diabetic retinopathy (DR). Following its U.S. Food and Drug Administration (FDA) approval in 2021 for nAMD, the PDS has demonstrated clinical equivalency to monthly injections and was favored by patients across multiple trials.
However, in 2022, Genentech and Roche voluntarily recalled the PDS implant and insertion tools as a result of cases of septum dislodgement—specifically, incidents of the implant’s self-sealing septum detaching into the drug reservoir. These incidents occurred exclusively in phase III trial implants and didn't affect commercial or phase II devices.
Further, lead study author Dante J. Pieramici, of California Retina Consultants in Santa Barbara, and colleagues wrote: “[I]t is worth noting that no safety issues were reported due to this event. Patient preference for this treatment [vs] intravitreal injections remains high, with the majority of patients electing to have the malfunctioning device removed and replaced with the updated implant."
Following the recall, engineers identified two key factors that contributed to septum dislodgement:
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Weak bond strength between the septum and the overmold
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Excessive force from the refill needle during drug replenishment procedures.
To address these issues, several component-level updates and manufacturing process improvements were implemented:
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The septum-overmold bond strength doubled from 1.2 N to 2.4 N following an increase in the contact area and optimized epoxy usage.
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A thin, immobilized silicone-based lubricant was applied to the refill needle and reduced insertion force from 1.0 N to 0.4 N.
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Optical coherence tomography inspection was performed during manufacturing and updated surgical training materials were introduced to prevent procedural misuse such as needle twisting.
Laboratory simulations using ASTM F1980-21 guidelines accelerated aging by storing implants in saline at 80°C. The septum was punctured at 3.5-day intervals, which mimicked clinical use in which 1 week of aging with two punctures simulated 1 year of clinical use.
With the previous needle, 47% of recalled implants survived 21 punctures (10 years simulated use). When recalled implants had their needle updated, 92% survived 21 punctures. All updated implants with the updated needle survived the simulated 10 years of use, and no septum dislodgements were reported. One updated implant experienced leakage after 68 punctures, but the septum remained intact.
The researchers described further concerns regarding accumulation of silicone microdroplets. They noted that only a small amount of silicone accumulated following 50 simulated refill-exchanges in a laboratory environment. It was also unlikely that silicone microdroplets would accumulate in the vitreous because the refill needle didn't enter the vitreous and was inserted directly into the implant instead.
In July 2024, the FDA approved the updated PDS implant and refill needle. Clinical implantation resumed earlier in February 2024 across global trials. A clinical observation study reported successful refill-exchange procedures using the updated needle in all 34 cases without adverse events.
The updated PDS is now being investigated for delivery of new agents such as zifibancimig in the phase I/II BURGUNDY trial (NCT04567303), which targets VEGF and angiopoietin-2 pathways for retinal diseases.
“By combining these component and manufacturing updates with the purposeful evolution of the surgical techniques involved in implantation and the refill-exchange procedure based upon continually growing surgical experience and meticulous analyses of these techniques, the [PDS] may support better patient outcomes in clinical practice compared with those achieved with currently available anti-VEGF therapies,” the study authors concluded.
A full list of author disclosures can be found in the published research.