D.05.3 Medical Device Sterilization

Objective

• Promulgate NIST traceable empirically verified protocols for gamma and electron beam dosimetry used in medical device sterilization.

Actions

• Link to efforts of MPD D.8.2 High-energy Electron Beam Dosimetry to ensure medical sterilization is a considered metric. (Proposed in 2012)

• Derive a pilot structure for a proficiency test that measures how effectively facilities can deliver a specified dose. This will be based initially on a handful of companies to develop and refine a protocol. Upon initial completion, this will be opened to the larger community. (Proposed in 2012)

• Develop an industry recognized, broadly based standard method of test based upon the infra-red analysis of the development of the transvinylene content in polyethylene. This too must be subjected to inter-laboratory studies in order to determine the precision of this method. (Proposed in 2011)

Requirements

• A multi-national dosimetry task force should be formed to implement the above action items. This will require several person years of commitment over at least a three year time frame.

Background

The high growth medical device industry relies on a diversity of material constructions to perform unique and sometimes intricate functions. Radiation sterilization has gained increased acceptance as a fast and efficacious means for assuring the absence of any microbial contamination on such devices. Items as mundane as cotton balls and bandages to sophisticated transdermal drug delivery systems, wound care treatment coverings and complex plastic filtration units are being sterilized by radiation processes. Almost all major producers of medical devices and numerous small companies use radiation sterilization in their device manufacturing processes. Although in the United States the Food and Drug Administration’s Center for Devices and Radiological Health does not prescribe a preferred means for attaining sterility, it does require that medical devices be made under current Good Manufacturing Practices (GMP) and in doing so requires a complete protocol of record keeping, traceability, written procedures and the like. For sterilization, the FDA has accepted the standards and guidelines established by the Association for the Advancement of Medical Instrumentation (ww.aami.org). These along with specific dosimetry test methods and procedures developed by the ASTM International (www.astm.org) provide guidance to the practitioner of radiation sterilization to justify claims of product sterility and to do so within the context of GMP protocols. ASTM International lists about twelve different dosimetry methods which can be used to infer dose. However, there is no database founded on inter-laboratory testing to confirm the viability of these standards for commercial use and guide the end-user to apropos dosimeter selection based on data. This leaves the user with an incoherent metrology system and renders the user subject to competing vendor claims.

The International Atomic Energy Agency’s Collaborating Center for Radiation Processing and Industrial Dosimetry has conducted two inter-laboratory studies involving nine laboratories. These inter-laboratory tests showed that only alanine dosimeters would be suitable as reference and transfer dosimeters amongst laboratories. Other published results have shown that in particular film dosimeters based on photo-chromatic changes of dyes in films to be unstable and are not made to a modicum of industrial film quality. Thus, only alanine, whether in pellet form or coated onto films, is suitable for indicating compliance with any “dose” requirements. Other methodologies may be suitable for internal process control, but not for reference purposes.

The ASTM International committee F04 on Medical and Surgical Materials and Devices has developed a Standard Method of Test which can be used to infer “dose” based upon the development of a transvinylene double bond in polyethylene (ASTM standard F-2381). This technique, the use of infra-red analysis to determine transvinylene double bonds in polyethylene, is also used as the in-house control method by the two largest users of industrial electron beam processing. The observation of the transvinylene development in polyethylene goes back to the late 1950’s when it was first found that polyethylene would cross-link when exposed to ionizing radiation from an electron beam. Since transvinylene infra-red analysis technique has been successfully used by the major users of EB processing and has been adopted as a standard by the medical device community itself, a more broadly based standard should be developed which would be supported by inter-laboratory studies. The infra-red equipment needed for this type of analysis is less costly than the equipment needed to determine the spin resonance in alanine.

Discussion Topics

• Conduct more broadly based inter-laboratory international studies on the use of alanine as the appropriate reference dosimeter and publish the resulting database.

• Investigate the use of two real-time dosimetry systems currently available in the market (Monitorad and Cdose) and examine the use of transistors as real-time dosimetry systems as well as other possible semiconductor and optoelectronic devices.