Abstract
Purpose :
The NT-501 Implant uses Neurotech’s encapsulated cell technology to provide a long-term intraocular drug delivery to the retina for treatment of Macular Telangiectasia. The integrity of each NT-501 pre-assembled capsule (PAC) is confirmed before encapsulating with cells, sealing the implant, and holding it in media. Historically, the integrity of the NT-501 implants could not be evaluated other than by gross visual inspection. Therefore, forced degradation studies were performed and as assay to evaluate in vitro integrity was developed.
Methods :
Forced degradation studies on the NT-501 implant raw materials (membrane, scaffolding, and adhesive) were performed in the following conditions: hydrolytic, acidic, basic, and oxidative, and on the NT-501 PACs in the basic condition. After different incubation periods in the above conditions, raw materials were tested for tensile strength to evaluate physical degradation, and NT-501 PACs were integrity tested to evaluate functional degradation.
Additionally, QTOF-GCMS/LCMS was used to identify potential target degradant molecules, and an HPLC-MS method was developed to evaluate the adhesive degradant molecule 4-4’-methylenebis(cyclohexylamine) (HMDA). This method was used in parallel to compare the sensitivity of detecting chemical degradation compared to physical and functional degradation.
Results :
Tensile strength of the membrane and scaffolding was stable for up to 6 months in the oxidative condition, and for several years in the remaining conditions. Tensile strength of the adhesive was stable for up to 12 hours in the basic condition, and up to 72 hours in the remaining conditions. An 8-hour incubation or the adhesive and NT-501 PAC in the basic condition resulted in the following: a reduction in tensile strength of 6-12%, 0% of NT-501 PAC integrity failure, and HMDA degradant detection above the lower limit of quantitation at 0.11-0.14 µg/mL.
Conclusions :
A validated quantitative HPLC-MS limit test was developed to evaluate in vitro NT-501 implant integrity, with a lower limit of detection of 0.05 µg/mL and a lower limit of quantitation of 0.097 µg/mL of HMDA in the hold media matrix. The assay can detect the target degradant before any significant physical or functional changes in the adhesive or NT-501 PAC is detected.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.