Nonclinical Toxicology and Biocompatibility Program Supporting Clinical Development and Registration of the Port Delivery System With Ranibizumab for Neovascular Age-Related Macular Degeneration. (April 2021)

• Record Type: Journal Article
• Authors: Bantseev, Vladimir; Horvath, Joshua; Barteselli, Giulio; Ranade, Shrirang; Maia, Mauricio; Yadav, Daniela Bumbaca; Schuetz, Chris; Shelton, Amy; Booler, Helen S.
• Other Names: Ramos Meg Ferrell guest-editor.; Schafer Kenneth guest-editor.; Sorden Steven guest-editor.
• Is Part Of: Toxicologic pathology. Volume 49:Number 3(2021)
• Page Start: 663
• Page End: 672
• Publication Date: 2021-04
• Subjects: biocompatibility -- clinical development -- neovascular age-related macular degeneration -- Port Delivery System with ranibizumab -- toxicology; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623320968079
• Languages: English
• ISSNs: 0192-6233

Abstract

The Port Delivery System with ranibizumab (PDS) is an investigational drug delivery system designed to provide continuous intravitreal release of ranibizumab for extended durations. The PDS consists of a permanent, surgically placed, refillable intraocular implant; a customized formulation of ranibizumab; and ancillary devices to support surgery and refill procedures. A toxicology program was conducted to evaluate the ocular toxicology and biocompatibility of the PDS to support its clinical development program and product registrational activities. PDS safety studies included a 6-month chronic toxicology evaluation in minipigs as well as evaluation of nonfunctional surrogate implants (comprised of the same implant materials but without ranibizumab) in rabbits. Biocompatibility of the implant and ancillary devices was evaluated in both in vitro and in vivo studies. Implants and extracts from implants and ancillary devices were nongenotoxic, noncytotoxic, nonsensitizing, and nonirritating. Ocular findings were comparable between implanted and sham-operated eyes, and no systemic toxicity was observed. The results of this nonclinical toxicology program demonstrated that the PDS was biocompatible and that intravitreal delivery of ranibizumab via the PDS did not introduce any new toxicology-related safety concerns relative to intravitreal injections, supporting ongoing PDS clinical development and product registrational evaluation.