Radiation and ethylene oxide terminal sterilization experiences with drug eluting stent products

Abstract

Radiation and ethylene oxide terminal sterilization are the two most frequently used processes in the medical device industry to render product within the final sterile barrier package free from viable microorganisms. They are efficacious, safe, and efficient approaches to the manufacture of sterile product. Terminal sterilization is routinely applied to a wide variety of commodity healthcare products (drapes, gowns, etc.) and implantable medical devices (bare metal stents, heart valves, vessel closure devices, etc.) along with products used during implantation procedures (catheters, guidewires, etc.). Terminal sterilization is also routinely used for processing combination products where devices, drugs, and/or biologics are combined on a single product. High patient safety, robust standards, routine process controls, and low-cost manufacturing are appealing aspects of terminal sterilization. As the field of combination products continues to expand and evolve, opportunity exists to expand the application of terminal sterilization to new combination products. Material compatibility challenges must be overcome to realize these opportunities. This article introduces the reader to terminal sterilization concepts, technologies, and the related standards that span different industries (pharmaceutical, medical device, biopharmaceuticals, etc.) and provides guidance on the application of these technologies. Guidance and examples of the application of terminal sterilization are discussed using experiences with drug eluting stents and bioresorbable vascular restoration devices. The examples provide insight into selecting the sterilization method, developing the process around it, and finally qualifying/validating the product in preparation for regulatory approval and commercialization. Future activities, including new sterilization technologies, are briefly discussed.

Fig. 1

Sterilization: a common need across evolving combination product sectors with sensitive materials (9)

Fig. 2

Log reduction of microorganism as a function of radiation dose

Fig. 3

Abbott Vascular two-pallet EO chamber

Fig. 4

Abbott Vascular self-shielded electron beam sterilization system

Fig. 5

Combination device drug loss as a function of EO sterilization cycle–one-way analysis of drug loss (micrograms per square centimeter) by EO sterilization

Fig. 6

Combination device analytical output as a function of EO sterilization cycle–one-way analysis of antioxidant concentration (micrograms per stent) by sterilization cycle

Fig. 7

Combination device physical property as a function of EO sterilization cycle–one-way analysis of distal max load (lb_f) by cycle