Optimized Process and Analytical Controls Ensure the Successful Technical Transfer of Encapsulated Cell Technology (ECT) Capsule Manufacturing to a Contract Medical Device Manufacturer

Abstract

Purpose: : Encapsulated cell technology manufacturing consists of a two-stage process which will produce an intraocular medical implant capable of delivering therapeutic proteins to the back of the eye for up to two years. Prior to the final stage of filling the implant capsule with genetically transfected ARPE-19 cells producing therapeutic proteins, the pre-filled, pre-assembled capsule (PAC) requires precise manufacturing methodology and testing criteria. We report on the efforts to optimize the PAC manufacturing and testing processes and subsequent successful transfer of this technology to a well-known contract medical device manufacturer.

Methods: : In order to ensure consistency and repeatability of PAC manufacture, semi-automated, specialized equipment was developed to control each aspect of the assembly process. In addition, analytical relationships were created to quantify the manufacturing consistency of the assembled PACs and include x-ray analysis, gas permeability rate constant, break-force strength and the rate of gas pressure decay within the PAC. Stability and performance of cell filled implants comparing PACs built by Neurotech and the contract medical device manufacturer were evaluated. Assessment criteria included encapsulated cell CNTF secretion levels, DNA quantification, metabolic activity of the encapsulated cells and histological evaluation performed at 1, 2, 4, 8 and 12 weeks post encapsulation.

Results: : A linear correlation of 0.9450 relating internal capsule volume of manufactured PACs to the permeability rate constant of nitrogen flow through the assembled PACs was established. Break strength of the capsules, integrity of the assembled capsules based upon pressure decay testing, and geometric comparisons were determined to be statistically equivalent. At each stability time point all encapsulated cell performance criteria were statistically equivalent regardless of the source of PAC manufacture.

Conclusions: : Improvements to the manufacturing and testing of ECT PACs have been developed and resulted in the successful transfer of the manufacturing technology process to a contract medical device manufacturer.

Keywords: retinal degenerations: hereditary