Nonclinical Toxicology and Biocompatibility Program Supporting Clinical Development and Registration of the Port Delivery System With Ranibizumab for Neovascular Age-Related Macular Degeneration

Bantseev, Vladimir; Horvath, Joshua D.; Barteselli, Giulio; Ranade, Shrirang; Maia, Maurício; Yadav, Daniela Bumbaca; Schuetz, Chris; Shelton, Amy L.

doi:10.1177/0192623320968079

Cited by 9 publications

(12 citation statements)

References 20 publications

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“…Both in vitro and in vivo biocompatibility tests showed that PDS implant was non-cytotoxic, non-genotoxic, non-sensitizing, and non-irritating. 35 …”

Section: Resultsmentioning

confidence: 99%

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Ranibizumab port delivery system in neovascular age-related macular degeneration

Chandrasekaran¹,

Madanagopalan

2022

Ophthalmol Eye Dis

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Ranibizumab has proven its efficacy in various retinal diseases and particularly in neovascular age-related macular degeneration (nAMD). The number of injections and the frequent follow-up visits has been burdensome to patients particularly during the COVID era. Ranibizumab port delivery system (RPDS) seems to be a boon in prolonging the action of the drug without the need for frequent injections and follow-up visits. This review article highlights the dosage, adverse effects, and visual outcome associated with various trials of RPDS. For this article, we conducted a PubMed search and review of literature on nAMD, the incidence of AMD, anti-vascular endothelial growth factor (anti-VEGF) agents, RPDS, phase-1 trial of RPDS, phase-2 (LADDER trial) of RPDS, phase-3 (ARCHWAY trial) of RPDS, PORTAL trial of RPDS, results of phase-1 trial of RPDS, results of phase-2 (LADDER) trial of RPDS, and results of phase-3 (ARCHWAY) trial of RPDS.

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“…Both in vitro and in vivo biocompatibility tests showed that PDS implant was non-cytotoxic, non-genotoxic, non-sensitizing, and non-irritating. 35 …”

Section: Resultsmentioning

confidence: 99%

“…Toxicology and biocompatibility analysis of the PDS implant both in vitro and in vivo has shown that it is non-toxic, non-sensitizing, and non-inflammatory. 35 Long-term stability of ranibizumab under physiologic conditions was also favorable for ranibizumab when compared to bevacizumab and aflibercept. 36 …”

Section: Discussionmentioning

confidence: 99%

Ranibizumab port delivery system in neovascular age-related macular degeneration

Chandrasekaran¹,

Madanagopalan

2022

Ophthalmol Eye Dis

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“…The PDS implant is surgically placed at the pars plana and is intentionally designed to be biocompatible, permanent, and durable. The implant and extracts from the implant and ancillary devices have been determined to be nongenotoxic, noncytotoxic, nonsensitizing, and nonirritating (Bantseev et al., 2021 ). The drug reservoir and RCE reside within the vitreous, whereas the septum remains accessible under the conjunctiva and Tenon’s capsule for minimally invasive in-clinic refill-exchanges.…”

Section: The Pds Implant and Ancillary Devicesmentioning

confidence: 99%

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

Ranade¹,

Wieland

Tam³

et al. 2022

Drug Delivery

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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.

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“…Plastic embedding is not recommended for the whole eye in these situations, as the sections are somewhat thicker than those usually examined. 54…”

Section: General Points To Considermentioning

confidence: 99%

Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies

Booler

Lejeune²,

Sorden

et al. 2021

Toxicol Pathol

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A Working Group of the Society of Toxicologic Pathology’s Scientific and Regulatory Policy Committee conducted a technical and scientific review of current practices relating to the fixation, trimming, and sectioning of the nonrodent eye to identify key points and species-specific anatomical landmarks to consider when preparing and evaluating eyes of rabbits, dogs, minipigs, and nonhuman primates from ocular and general toxicity studies. The topics addressed in this Points to Consider article include determination of situations when more comprehensive evaluation of the globe and/or associated extraocular tissues should be implemented (expanded ocular sampling), and what constitutes expanded ocular sampling. In addition, this manuscript highlights the practical aspects of fixing, trimming, and sectioning the eye to ensure adequate histopathological evaluation of all major ocular structures, including the cone-dense areas (visual streak/macula/fovea) of the retina for rabbits, dogs, minipigs, and nonhuman primates, which is a current regulatory expectation for ocular toxicity studies. [Box: see text]

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Nonclinical Toxicology and Biocompatibility Program Supporting Clinical Development and Registration of the Port Delivery System With Ranibizumab for Neovascular Age-Related Macular Degeneration

Cited by 9 publications

References 20 publications

Ranibizumab port delivery system in neovascular age-related macular degeneration

Ranibizumab port delivery system in neovascular age-related macular degeneration

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

Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies

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