The sterility assurance community is facing significant challenges. A relatively recent challenge is the pressure on manufacturing supply chains resulting from the limited availability of capacity for terminal sterilization of healthcare products. The current challenge is finding solutions for innovative new products, especially biologics and combination products, that offer great promise for patients around the world. This challenge will become more prevalent in the future as products advance. This article frames new paradigms and tools being developed to address these challenges. Foundational principles and current realities from each sector are reviewed so that sterility assurance professionals have a solid base from which to build strategies.

The ABSORB bioresorbable vascular scaffold (BVSs) has set the stage for the new bioresorbable era as the lead technology of its kind, demonstrating through novel endpoints that the potential advantages of this technology appear to be significant. This chapter details the design and performance features of the ABSORB BVSs. The ABSORB BVSs is coated with everolimus, a semisynthetic antiproliferative macrolide, in poly d,l-lactide in a 1:1 drug:polymer ratio. Development of a bioresorbable vascular scaffold and delivery system to meet the clinical and regulatory needs requires a broad cross-functional product development team. The performance profile of ABSORB BVSs is described by three phases that span its lifecycle: revascularization, restoration, and resorption. The ABSORB BVSs currently has Conformité Européenne (CE) approval and regulatory approval in multiple geographies including the United States, Japan, Korea, Taiwan, India, Brazil, Canada, and Australia and is seeking approval in China.

Objectives Using intravascular ultrasound (IVUS) and histomorphometry, this study sought to evaluate the potential of nonatherosclerotic porcine coronary arteries to undergo progressive lumen gain and a return of pulsatility after implantation with an everolimus-eluting bioresorbable vascular scaffold (BVS).Background Unique benefits such as lumen gain and restored vasomotion have been demonstrated clinically after treatment with BVS; however, a more rigorous demonstration of these benefits with a randomized clinical trial has not yet been conducted.Methods Seventy nonatherosclerotic swine received 109 everolimus-eluting BVS and 70 everolimus-eluting metal stents randomized among the main coronary arteries. Arteries were evaluated in vivo by angiography and IVUS and post-mortem by histomorphometry at time points from 1 to 42 months.Results From 1 to 6 months, both BVS- and everolimus-eluting metal stent-implanted arteries demonstrated stable lumen areas (LAs). From 12 months to 42 months, there was a progressive increase in the LA of arteries implanted with a BVS as assessed by histomorphometry and IVUS. This lumen gain in the implanted segment corresponded to an increase in the reference vessel LA. Normalization in the in-segment LA (LA: reference vessel LA) was observed qualitatively by angiography and quantitatively by IVUS. Additionally, BVS-implanted arteries demonstrated restored in-segment pulsatility on the basis of IVUS assessment of the differences in the mid-scaffold area between end-diastole to end-systole.Conclusions Starting at 12 months, BVS-implanted porcine coronary arteries underwent progressive lumen gain and showed restored pulsatility. These benefits demonstrated preclinically may translate into improvements in long-term clinical outcomes for patients treated with BVS compared with conventional drug-eluting stents. (C) 2014 by the American College of Cardiology Foundation

El desarrollo de las técnicas de intervencionismo coronario percutáneo se puede resumir en cuatro oleadas o revoluciones: la propia aparición de la técnica de angioplastia coronaria con balón, el desarrollo de las endoprótesis coronarias (stents) para solucionar las limitaciones de la angioplastia con balón, la adición de fármacos antiproliferativos en los stents farmacoactivos para evitar la reestenosis y, finalmente, la aparición de las endoprótesis vasculares bioabsorbibles. Este artículo comienza con una breve descripción de los dispositivos utilizados en el intervencionismo a lo largo de tres décadas que han conducido a la aparición final de las endoprótesis bioabsorbibles. Posteriormente, se revisan las principales características y dificultades en el desarrollo de estas endoprótesis. El núcleo de este artículo es una descripción de los productos en desarrollo y de los resultados preclínicos y clínicos disponibles actualmente. La conclusión refleja una visión del prometedor futuro del intervencionismo y las endoprótesis bioabsorbibles.

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.

Titan Scan Corporation has introduced its second generation of electron beam sterilization systems with the installation of the self contained, SureBeam On-Site System at Guidant Corporation’s Temecula, California manufacturing facility. The system is designed exclusively for the sterilization of medical products and meets all USFDA, ISO and EN certification requirements. The system has been in operation since July 1998, and meets all design specifications.

A Technical Information Report, TIR 17, entitled, "Radiation Sterilization Material Qualification" has been published by the Association for the Advancement of Medical Instrumentation (AAMI) to provide guidance in order to increase the quality and reduce the cost and amount of time required for performing medical device material qualifications. It contains four sections that cover the fundamentals of material selection, processing, testing and accelerated aging programs. The last of these sections, entitled "Accelerating Aging Programs," provides step-by-step guidance for simple, empirical accelerated programs of use to the medical device industry. The methods are based on van't Hoffs observation that the rate of chemical reactions increases by a factor of two for every 10 degrees C increase in temperature, the Q(10)=2 rule.With critical patient safety concerns in the medical device industry, it is appropriate for both device manufacturers and regulators to ask if simple, empirical methods such as those outlined in TIR 17 are reasonable and responsible. One reason for confidence in the methods is their success when used in aging environments that are much more severe than those commonly used in the medical device industry. Another reason for confidence in the methods is found from the observation that the working equations of the method can be derived from theory. This paper provides an overview of the thermal accelerated aging theory that forms the basis for the working equations of the accelerated aging programs of TIR 17. Assumptions used are examined and found reasonable; the theoretical foundation is established. While this foundation provides added confidence for the application of the methods of TIR 17 to the medical device industry, it is emphasized that application of the methods within appropriate boundaries is critical. Theoretical boundaries are explained and demonstrated by means of Arrhenius plots, and practical boundaries discussed. (C) 2000 Elsevier Science Ltd. All rights reserved.

This presentation provides an overview of the current status of the ISO radiation sterilization standards. The ISO standards are voluntary standards which detail both the validation and routine control of the sterilization process. ISO 11137 was approved in 1994 and published in 1995. When reviewing the standard you will note that less than 20% of the standard is devoted to requirements and the remainder is guidance on how to comply with the requirements.Future standards developments in radiation sterilization are being focused on providing additional guidance. The guidance that is currently provided in informative annexes of ISO 11137 includes: device/packaging materials, dose setting methods, and dosimeters and dose measurement, currently, there are four Technical Reports being developed to provide additional guidance:1. AAMI Draft TIR, "Radiation Sterilization Material Qualification"2. ISO TR 13409-1996, "Sterilization of health care products - Radiation sterilization - Substantiation of 25 kGy as a sterilization dose for small or infrequent production batches"3. ISO Draft TR, "Sterilization of health care products - Radiation sterilization Selection of a sterilization dose for a single production batch"4. ISO Draft TR, "Sterilization of health care products - Radiation sterilization-Product Families, Plans for Sampling and Frequency of Dose Audits."