Progress in Providing Guidance for the Industry AAMI

Progress in Providing Guidance for the Industry - AAMI, ASTM, and Others John A. Williams, Medtronic

Agenda • • • Role of Standards AAMI Overview ASTM Overview Standards Alignment Other Forums – Call to Action September 17, 2020 John A. Williams, Medtronic Continuing the Conversation 2

Role of Standards Why does my organization use standards? Compliance with voluntary consensus standards enhances our ability to bring products to the global marketplace by: • Making regulatory submissions more uniform, faster and more cost effective. • Reducing regulatory submission review and approval times. • Reducing the regulatory need for more than one product design worldwide. • Assisting in the production of products with the greatest possible reliability and quality. September 17, 2020 John A. Williams, Medtronic 3

AAMI Overview The Association for the Advancement of Medical Instrumentation® (AAMI) is a nonprofit organization founded in 1967. It is a diverse community of more than 9, 000 professionals united by one important mission—the development, management, and use of safe and effective health technology. AAMI is the primary source of consensus standards, both national and international, for the medical device industry, as well as practical information, support, and guidance for healthcare technology and sterilization professionals. September 17, 2020 John A. Williams, Medtronic 4

AAMI Overview ST - Sterilization Standards Committee (U. S. TAG to ISO/TC 198) Description The AAMI ST - Sterilization Standards Committee provides input into international standards by acting as the mirror committee and U. S. TAG to ISO/TC 198 - sterilization of healthcare products which develops standards on the processes and equipment for sterilization of health care products. (32 Working Groups) ST/WG 01 - Industrial EO sterilization Working Group ST/WG 13 - Washer Disinfectors Working Group ST/WG 85 - Human Factors for Device Reprocessing Working Group ST/WG 02 - Radiation Sterilization Working Group ST/WG 15 - Sterility Assurance Level (SAL) Working Group ST/WG 86 - Quality Systems for Device Reprocessing Working Group ST/WG 03 - Industrial Moist Heat Sterilization Working Group ST/WG 40 - Steam Sterilization Hospital Practices Working Group ST/WG 91 - Resistometer Working Group ST/WG 04 - Biological Indicators Working Group ST/WG 42 - Dry Heat Sterilization Working Group ST/WG 92 - Process Challenge Devices Working Group ST/WG 05 - Sterilization Terminology Working Group ST/WG 43 - Hospital Steam Sterilizer Working Group ST/WG 93 - Cleaning of Reusable Medical Devices Working Group ST/WG 06 - Chemical Indicators Working Group ST/WG 60 - EO Sterilization Hospital Practices Working Group ST/WG 94 - Rigid Sterilization Container Systems Working Group ST/WG 07 - Packaging Working Group ST/WG 61 - Chemical Sterilants Hospital Practices Working Group ST/WG 95 - Water Quality for Reprocessing Medical Devices Working Group ST/WG 08 - Microbiological Methods Working Group ST/WG 62 - Hospital Ethylene Oxide Sterilizer Working Group ST/WG 96 - Compatibility of Materials Subject to Sterilization Working Group ST/WG 09 - Aseptic Processing Working Group ST/WG 63 - Sterilization Residuals Working Group ST/WG 10 - Liquid Chemical Sterilization Working Group ST/WG 11 - General Criteria for Sterilization Processes and Sterilizing Equipment Working Group ST/WG 83 - Reusable Surgical Textiles Processing Working Group ST/WG 16 - Vaporized Hydrogen Peroxide Sterilization ST/WG 12 - Instructions for Reusable Device Reprocessing Working Group ST/WG 84 - Endoscope Reprocessing Working Group September 17, 2020 John A. Williams, Medtronic 5

AAMI Overview ST/WG 02 – Radiation Sterilization Working Group • Scope • Is focused on requirements for establishing, validating, implementing and monitoring radiation processes used to sterilize health care products with gamma, electron beam or x-ray • Is the US TAG to ISO/TC 198 Sterilization of health care products, providing US input to development of ISO standards and technical specifications on Radiation Sterilization • Authors Technical Information Reports (TIRs) to provide guidance on aspects of radiation sterilization • Membership • • • 65 member companies, more that 100 active individuals ~50% medical device manufacturers ~25% consultants ~20% service and equipment providers ~5% regulatory September 17, 2020 John A. Williams, Medtronic 6

AAMI Overview ST/WG 02 – Radiation Sterilization Working Group: Published Documents • AAMI/ISO 11137 series of standards on Sterilization of Healthcare products – Radiation • Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices • Part 2: Establishing the sterilization dose • Part 3: Guidance on dosimetric aspects of development, validation and routine control • TS Part 4: Guidance on process control • AND AAMI/ISO/TS 13004: Substantiation of selected sterilization dose: Method VDmax. SD • AAMI TIR 35, Sterilization of health care products – Radiation sterilization – Product adoption and alternative sampling plans for verification dose experiments and sterilization dose audits • AAMI TIR 40, Sterilization of health care products – Radiation – Guidance on dose setting utilizing a Modified Method 2 • Documents to be withdrawn • AAMI TIR 29, Guide for process characterization and control in radiation sterilization of medical devices – superseded by 11137 -4 • AAMI TIR 37, Sterilization of health care products – Radiation- Guidance on sterilization of biologics and tissue -based products – will be superseded by ISO/TS 22456, Sterilization of health care products – Microbiological Methods – Guidance on conducting bioburden determinations and tests of sterility for tissue-based products (in committee draft process), and ISO/TS 11137 -4 September 17, 2020 John A. Williams, Medtronic 7

AAMI Overview ST/WG 02 – Radiation Sterilization Working Group: Active Projects • AAMI TIR 76, Sterilization of health care products – Radiation – Substantiation of a selected sterilization dose at a specified sterility assurance level: Method VDmax. SD-S • Has passed final ballot and is being prepared for publication • Allows for the substantiation of a chosen dose and at a chosen SAL • Complication of calculating required doses as well as the potential for error in using multiple look up tables led to the development of a software tool to accompany the document • Is the first use of Saa. S (software as a service) as part of an AAMI publication, hopefully will lead to application for other dose setting methods • AAMI TIR 104, Guidance on transferring health care products between radiation sterilization sites or modalities • Initiated in response to business continuity planning opportunities in validating product to be radiation sterilized in multiple sites and/or multiple modalities • Provides guidance and clarification around the requirements in ISO 11137 -4 • References newly published data that will greatly simplify the transfer of sterilization dose • Guidance is provided on when testing should be done to transfer or reestablish maximum acceptable dose, and what tests may be appropriate September 17, 2020 John A. Williams, Medtronic 8

AAMI Overview ST/WG 02 – Radiation Sterilization Working Group: ISO Projects • Amendment to ISO 11137 -2 to reference ISO/TS 13004 • Regulators outside of the US have rejected sterilization doses substantiated using ISO/TS 13004 because this document is not referenced in 11137 -1 or 11137 -2, and because it is only a technical specification and not a standard • Proposal to convert ISO/TS 13004 to a standard rather than a technical specification • This is happening in parallel with the amendment to 11137 -2 with the hope that both will pass and 11137 -2 will then reference ISO 13004 • Revision to ISO 11137 -1 • Last full revision was 2006 • Multiple suggested updates have been compiled • Work program timeframe will be 36 months • Amalgamation of ISO 11137 -3 and 11137 -4 • Longer term project • Plan to work in conjunction with ASTM to provide complimentary HOW documents to accompany the AAMI/ISO WHAT requirements September 17, 2020 John A. Williams, Medtronic 9

AAMI Overview ST/WG 02 – Radiation Sterilization Working Group: How to participate • AAMI members get one vote regardless of company size • Each company can vote and provide comments on documents through a primary or alternate representative • Commenting is key! • Coordination through your company Primary or Alternate voter is key in making sure that your comments are put forward • All comments are given fair consideration and no comment will be rejected without feedback and discussion • If you want to drive change in the industry, and put forth best practice that will help provide better outcome for patients, then comment! • ISO participants are limited to 5 per country • US Experts are nominated from within AAMI membership • Preference goes to members who actively participate through productive discussions and comments • For more information please contact either WG 2 co-chair: • Emily Craven, Boston Scientific, emily. craven@bsci. com • Elaine Daniell, EDan-SA LLC Consulting, elaine. daniell@edan-sa. com September 17, 2020 John A. Williams, Medtronic 10

ASTM Overview ASTM International is a globally recognized leader in the development and delivery of voluntary consensus standards. Today, over 12, 000 ASTM standards are used around the world to improve product quality, enhance health and safety, strengthen market access and trade, and build consumer confidence. This leadership in international standards development is driven by the contributions of members: more than 30, 000 of the world’s top technical experts and business professionals representing 140 countries. Working in an open and transparent process and using ASTM’s advanced IT infrastructure, members create the test methods, specifications, classifications, guides and practices that support industries and governments worldwide. September 17, 2020 John A. Williams, Medtronic 11

ASTM Overview Committee E 61 on Radiation Processing • Scope • To establish and maintain standard practices, methods, and guides for ionizing radiation processing and dosimetry for applications including medical products, pharmaceuticals, foods, polymers, and other consumer products. • To develop standard methods for characterizing and operating gamma ray, x-ray, and electron beam irradiators, and encourage use of these standards in radiation processing through meetings, workshops, and symposia. • To provide consultation in the application of dosimetry systems and identify areas for additional research. • Membership • 140 members • 21 countries represented • Six Subcommittees • E 61. 01 Dosimetry • E 61. 02 Dosimetry Systems • E 61. 03 Dosimetry Application September 17, 2020 • E 61. 04 Specialty Application • E 61. 05 Food Irradiation • E 61. 06 Gas & Heat Processing John A. Williams, Medtronic 12

ASTM Overview Committee E 61 on Radiation Processing: Published Documents (33) E 61. 01 Dosimetry E 61. 03 Dosimetry Application E 61. 01 Calibration of Routine Dosimetry Systems (51261) E 61. 02 Estimation of Measurement Uncertainty (51707) E 61. 03 Dosimetry in Radiation Processing (52628) E 61. 04 Performance Characterization of Dosimeters (52701) E 61. 03. 01 X-Ray (Bremsstrahlung) Facility for Energies between 50 ke. V and 7. 5 Me. V (51608) E 61. 03. 02 Electron Beam Facility at Energies Between 300 ke. V and 25 Me. V (51649) E 61. 03 Dosimetry in a Gamma Facility (51702) E 61. 03. 04 Dosimetry in an Electron Beam Facility for Energies Between 80 and 300 ke. V (51818) E 61. 03. 05 Absorbed-Dose Mapping (52303) E 61. 02 Dosimetry Systems E 61. 02. 01 Using the Fricke Dosimetry System (51026) E 61. 02 Ceric-Cerous Sulfate Dosimetry System (51205) E 61. 02. 03 Radiochromic Film Dosimetry System (51275) E 61. 02. 04 Polymethylmethacrylate Dosimetry System (51276) E 61. 02. 05 Radiochromic Optical Waveguide Dosimetry System (51310) E 61. 02. 06 Dichromate Dosimetry System (51401) E 61. 02. 07 Ethanol-Chlorobenzene Dosimetry System (51538) E 61. 02. 08 Radiochromic Liquid Dosimetry System (51540) E 61. 02. 09 Alanine-EPR Dosimetry System (51607) E 61. 02. 10 Calorimetric Dosimetry Systems for Electron Beam (51631) E 61. 02. 11 Cellulose Triacetate Dosimetry System (51650) E 61. 02. 12 Thermoluminescence-Dosimetry (TLD) Systems (51956) E 61. 02. 13 Li. F Photo-Fluorescent Film Dosimetry System (E 2304) September 17, 2020 E 61. 04 Speciality Application E 61. 04. 01 Radiation-Sensitive Indicators (51539) E 61. 04. 02 Dosimetry in Radiation Research on Food Products (51900) E 61. 04. 03 Blood Irradiation Dosimetry (51939) E 61. 04 Sterile Insect Release Programs (51940) E 61. 04. 05 Self-Contained Dry-Storage Gamma Irradiator (52116) E 61. 04. 06 Mathematical Methods for Calculating Absorbed Dose (E 2232) E 61. 05 Food Irradiation E 61. 05. 01 Irradiation of Fresh Agricultural Produce as a Phytosanitary Treatment (F 1355) E 61. 05. 02 Irradiation of Fresh, Frozen or Processed Meat and Poultry (F 1356) E 61. 05. 03 Selection and Use of Contact Materials for Foods (F 1640) E 61. 05. 04 Irradiation of Finfish and Aquatic Invertebrates Used as Food (F 1736) E 61. 05 Irradiation of Dried Spices, Herbs, and Vegetable Seasonings (F 1885) John A. Williams, Medtronic 13

ASTM Overview Committee E 61 on Radiation Processing: Active Projects • E 61. 03. 06 Process Control (WK 46751) Scope: This document provides guidance for the statistical analysis of the irradiation process from dosimetric data. • E 61. 03. 07 Operational Qualification of Gamma Irradiators (WK 65046) Scope: This document provides guidance on operational qualification tests for gamma irradiators. The tests are not requirements but may help the user gain an increased understanding of operational aspects of their irradiator. Based on facility-specific assessments for routine operation, certain tests listed in this document may be deemed to be unnecessary and omitted. Requirements for OQ when sterilizing healthcare product can be found in ISO 11137 -1. • E 61. 03. 08 Operational Qualification of Ebeam/X-Ray Irradiators (WK 72480) Scope: This document provides guidance on operational qualification tests for accelerator-based electron beam irradiators. The tests are not requirements but may help the user gain an increased understanding of operational aspects of their irradiator. Based on facility-specific assessments for routine operation, certain tests listed in this document may be deemed to be unnecessary and omitted. Requirements for OQ when sterilizing healthcare product can be found in ISO 11137 -1. September 17, 2020 John A. Williams, Medtronic 14

ASTM Overview Committee E 61 on Radiation Processing: How to participate • A membership fee of $75 • Join Committee E 61 on Radiation Processing • Join as many technical committees you desire at no extra cost • One Complimentary Volume of Annual Book of Standards ($230 value) • Access to the Web-based Committee Information • Upcoming Meetings • Dates: 6 -9 December 2020; Location: Renaissance Orlando at Sea. World; Orlando, FL US. Virtual meeting • Dates: June 2 -4 2021; Location: Jackson Hole, WY (Snow King) • Dates: September 18 -23, 2021 (in conjunction with the 10 th Workshop on Radiation Processing); Location: Prague, CZ • Dates: 15 -18 May, 2022; Location: Hyatt Regency Seattle; Seattle, WA US September 17, 2020 John A. Williams, Medtronic 15

Standards Alignment – What & How ASTM E 61 Standards Alignment with ISO/TC 198 WG 2 Scope: To develop a process between SDO working groups (ASTM E 61 and ISO/TC 198 WG 2) that ensures ASTM E 61 standards are written, reviewed and published in a manner to provide complimentary guidance and practices in direct support of delivering the requirements established in the ISO 11137 series of standards. Charter: To deliver a complimentary series of standards from ASTM E 61 that can be directly referenced in ISO 11137 series of standards and will deliver industry best practices for meeting the requirements of the radiation sterilization of healthcare products. September 17, 2020 John A. Williams, Medtronic 16

Standards Alignment – What & How ASTM E 61 Standards Alignment with ISO/TC 198 WG 2 • There are four areas of focus to get alignment between ISO 11137 and ASTM E 61 documents: 1) Dosimetry system calibration, performance characterization and dosimetry uncertainty 2) Operational Qualification 3) Performance Qualification 4) Radiation Process Control • An exploratory committee will evaluate options for meeting this alignment proposal and will report to ASTM Committee E 61 at the December 2020 meeting with a recommendation. September 17, 2020 John A. Williams, Medtronic 17

Other Forums Promoting new technologies – A call to action • Industry Events like this one • Kilmer Conference 2022 • International Meeting on Radiation Processing • Publications • AAMI - Industrial Sterilization: Process Optimization and Modality Changes • Industry Associations • The Council on Ionizing Radiation Measurements and Standards (CIRMS) • International Irradiation Association (ii. A) • The Panel on Gamma and Electron Beam Irradiation • Society for Sterility Assurance Professionals (Sf. SAP) September 17, 2020 John A. Williams, Medtronic 18

Other Forums Promoting new technologies – A call to action “We need science to push the advances in standards and not the standards to push science. If we do not publish our experiences in application of these methodologies, we will not be able to advance and improve the standards for products of the future. ” Joyce M. Hansen Vice President, Johnson & Johnson Microbiological Quality & Sterility Assurance September 17, 2020 “Sharing this type of knowledge and best practices doesn’t take away from the development of company-specific products or threaten intellectual property, so I'd like to encourage others in my position and similar positions to think about contributing to a frequent crosspollination of information, which allows us all to learn and grow as a community. ” John A. Williams, Medtronic 19

Thank you for your attention. Special thanks to: Denise Cleghorn & Emily Craven, Boston Scientific Joyce Hansen & John Logar, Johnson & Johnson Questions / Comments? September 17, 2020 John A. Williams, Medtronic 20