Table 1.

Evolution of the PDS implant and ancillary devices during clinical development.

Device	Changes	Purpose/Rationale
Implant	RCE changed to optimize delivery of high-concentration ranibizumab for 6 months and beyond RCE material changed from stainless steel to titanium Implant packaging changed to provide carrier that enables ergonomic fill	Release rate target set to minimum of 2.3 µg/day at 6 months based on PK/PD simulations Titanium chosen for its corrosion resistance, MRI compatibility, and compatibility with the drug product New packaging minimizes handling of the implant and reduces the number of steps for use
Insertion tool	Improved design Material changed from stainless steel to plastic	Increases ease of use for the initial fill of the implant with self-alignment features Implant release design is more ergonomic, robust, and intuitive Reduce weight of the tool for improved ergonomics and ease of use
Refill needle	Custom refill needle with fluid collection reservoir added to allow simultaneous exchange of the contents of the implant with fresh drug product	The refill needle allows for removal of implant contents and minimizes the amount of drug bolus released into the vitreous humor during refilling of the implant
Explant tool	Material changed from stainless steel to plastic	Improved manufacturability Reduce weight of the tool for improved ergonomics and increased ease of use

Abbreviations: MRI: magnetic resonance imaging; PDS: Port Delivery System with ranibizumab; PD: pharmacodynamic; PK: pharmacokinetic; RCE: release control element.