Systematic Literature Reviews Comparing the Long-Term Safety Outcomes for the Port Delivery System with Ranibizumab (PDS) Versus Other Ocular Implants

Objectives: To determine whether the types and rates of post-surgical complications associated with the Port Delivery System with ranibizumab (PDS) are comparable with those reported for other ocular implants that cross the sclera. // Methods: Systematic literature reviews were conducted to determine the long-term (≥ 18-month) safety of ocular implants that cross the sclera in clinical trials and real-world studies. Complication types and rates were compared with those reported for the PDS in phase III clinical trials (Archway, Pagoda, and Pavilion). // Results: Sixteen clinical trials (24 publications) and 43 real-world studies were identified reporting 30 complications in eyes with 15 implant types and 8 ocular diseases. Implants were associated with an acceptable, well-characterized safety profile, with most complications resolving spontaneously or with treatment. Device-related complications were reported in 0.7% (0.0–5.0%) of study eyes in clinical trials and 1.3% (0.0–14.5%) of eyes in real-world studies. Rates of conjunctival complications were 2.1% (0.0–22.8%) and 2.2% (0.9–4.6%), respectively. The overall types and rates of adverse events of special interest reported for the PDS in phase III trials (cataract, conjunctival bleb, vitreous hemorrhage, conjunctival erosion, conjunctival retraction, endophthalmitis, implant dislocation, retinal detachment, and hyphema) were within the ranges reported for other ocular implants. // Conclusions: The rates of complications reported in phase III clinical trials for the PDS were within the ranges reported for other ocular implants that cross the sclera. This suggests that the long-term safety of the PDS is consistent with other ocular devices established in ophthalmology clinical practice. Trial Registration PROSPERO international prospective register of systematic reviews: CRD5202234129, CRD42022343129

Structural Updates to the Implant and Refill Needle of the Port Delivery Platform

PURPOSE: The purpose of this study was to report the impact of component-level changes and manufacturing process improvements on septum durability in the ocular implant of the Port Delivery Platform (PD-P), more commonly known as the Port Delivery System with ranibizumab (PDS) with its current formulation. METHODS: Laboratory tests were conducted to determine (1) the bond strength of the septum to the overmold, (2) the amount of force utilized for the refill needle to puncture the septum, and (3) septum durability over 50 years. To simulate multiple refill-exchanges over long-term clinical use, implants were aged at elevated temperature in saline and the septum was repetitively punctured at random locations using the refill needle every 3.5 days, simulating 6 months of use. RESULTS: Updates to the septum-overmold interface of the implant and manufacturing process improvements doubled the bond strength between the overmold and septum (1.2 N to 2.4 N). Light lubrication of the refill needle reduced needle insertion force into the septum by \u3e50% (1 N to 0.4 N). Together, these modifications increased long-term septum durability, with no septum dislodgements being observed after over 50 years of simulated use. CONCLUSIONS: Structural updates to the PD-P implant and refill needle have met and exceeded performance specifications, mitigating the risk of future septum dislodgement in the updated product. TRANSLATIONAL RELEVANCE: Structural updates to the PD-P implant and refill needle resulted in the ability to withstand the equivalent of over 50 years of simulated use without septum dislodgement and should improve the longevity of the device in clinical use

The Port Delivery System with ranibizumab: a new paradigm for long-acting retinal drug delivery

The Port Delivery System with ranibizumab (PDS) is an innovative intraocular drug delivery system designed for the continuous delivery of ranibizumab into the vitreous for 6 months and beyond. The PDS includes an ocular implant, a customized formulation of ranibizumab, and four dedicated ancillary devices for initial fill, surgical implantation, refill-exchange, and explantation, if clinically indicated. Ranibizumab is an ideal candidate for the PDS on account of its unique physicochemical stability and high solubility. Controlled release is achieved via passive diffusion through the porous release control element, which is tuned to specific drug characteristics to accomplish a therapeutic level of ranibizumab in the vitreous. To characterize drug release from the implant, release rate was measured in vitro with starting concentrations of ranibizumab 10, 40, and 100 mg/mL, with release of ranibizumab 40 and 100 mg/mL found to remain quantifiable after 6 months. Using a starting concentration of 100 mg/mL, active release rate at approximately 6 months was consistent after the initial fill and first, second, and third refills, demonstrating reproducibility between implants and between multiple refill-exchanges of the same implant. A refill-exchange performed with a single 100-µL stroke using the refill needle was shown to replace over 95% of the implant contents with fresh drug. In vitro data support the use of the PDS with fixed refill-exchange intervals of at least 6 months in clinical trials.</p