Clinical Evidence Guidelines: Medical Devices

1 Clinical Evidence guidelines for Medical Devices Version , November 2021 Therapeutic Goods Administration Clinical Evidence guidelines : Medical Devices November 2021 Page 2 of 164 Copyright Commonwealth of Australia 2021 This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so.

2 Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to Therapeutic Goods Administration Clinical Evidence guidelines : Medical Devices November 2021 Page 3 of 164 Contents About these guidelines _____ 6 Part 1 General Requirements _____ 7 Legislative framework _____ 7 ---------------------------------------- ----------------------------- 7 ---------------------------------------- ----------------------- 7 _____ 9 ---------------------------------------- ----------- 9 Therapeutic Goods Act Medical Device Regulations The Essential Principles Summary of the Essential Principles Demonstrating compliance with the Essential Principles ------------------------ 9 Compliance with standards ---------------------------------------- --------------------- 13 Clinical Evidence requirements _____ 15 Key definitions and concepts ---------------------------------------- ------------------- 15 Why Clinical Evidence is required ---------------------------------------- ------------- 18 Who is responsible for providing

3 Clinical Evidence ------------------------------ 18 When to submit Clinical Evidence ---------------------------------------- ------------- 18 Requirements for different device classifications -------------------------------- 18 Direct and indirect Evidence -------------------------------- ---------------------------- 19 Evidence strategies for different device types ------------------------------------- 19 Sources of Clinical data _____ 20 Clinical investigations ---------------------------------------- ---------------------------- 20 Literature review ---------------------------------------- ---------------------------------- 23 Post-Market Data ---------------------------------------- ---------------------------------- 25 Other Clinical experience data ---------------------------------------- ----------------- 27 Clinical evaluation _____ 28 Appraisal of the Clinical data ---------------------------------------- ------------------- 28 Analysis of the Clinical data ---------------------------------------- --------------------- 33 The Clinical Evaluation Report (CER)

4 _____ 34 Critical analysis and expert opinion ---------------------------------------- ---------- 34 CER content ---------------------------------------- ---------------------------------------- -- 35 Supporting documents ---------------------------------------- --------------------------- 42 Clinical Evidence checklist ---------------------------------------- ---------------------- 45 Part 2 Special topics _____ 47 Comparable Devices including substantially equivalent Devices _____ 47 Comparable Devices ---------------------------------------- ------------------------------- 47 Substantially equivalent Devices ---------------------------------------- -------------- 47 Therapeutic Goods Administration Clinical Evidence guidelines : Medical Devices November 2021 Page 4 of 164 Comparing device characteristics ---------------------------------------- ------------- 49 Clinical characteristics/intended purpose ---------------------------------------- - 49 Technical characteristics ---------------------------------------- ------------------------ 50 Biological characteristics ---------------------------------------- ------------------------ 51 Presentation of information regarding comparable Devices ------------------ 51 Magnetic resonance imaging (MRI)

5 Considerations _____ 54 Summary recommendations ---------------------------------------- ------------------- 55 Defining safety in the MR environment ---------------------------------------- ---- 55 Evidence requirements ---------------------------------------- -------------------------- 56 Defining active implantable Medical Devices -------------------------------------- 58 Summary of safety and performance data ---------------------------------------- -- 60 Part 3 - Requirements for specific device types ____ 63In vitro diagnostic (IVD) Medical Devices _____ 63 Total and partial joint prostheses _____ 63 Summary recommendations ---------------------------------------- ------------------- 63 Defining joint prostheses ---------------------------------------- ------------------------ 65 Clinical Evidence ---------------------------------------- ----------------------------------- 66 Compiling the CER ---------------------------------------- --------------------------------- 69 Defining Clinical success ---------------------------------------- ------------------------- 70 Summary of safety and performance data ---------------------------------------- -- 71 Cardiovascular Devices to promote patency or functional flow_____ 78 Summary recommendations ---------------------------------------- ------------------- 78 Defining CV flow implants ---------------------------------------- ----------------------- 80 Clinical Evidence

6 ---------------------------------------- ----------------------------------- 80 Compiling the CER ---------------------------------------- --------------------------------- 82 Defining Clinical success ---------------------------------------- ------------------------- 84 Summary of safety and performance data ---------------------------------------- -- 92 Implantable pulse generator systems _____ 99 Summary recommendations ---------------------------------------- ------------------- 99 Defining implantable pulse generator systems ---------------------------------- 100 Clinical Evidence ---------------------------------------- ---------------------------------- 100 Compiling the CER ---------------------------------------- -------------------------------- 102 Defining Clinical success ---------------------------------------- ------------------------ 103 Summary of safety and performance data ---------------------------------------- - 108 Heart valve replacements using a prosthetic valve _____ 112 Summary recommendations ---------------------------------------- ------------------ 112 Defining heart valve prostheses ---------------------------------------- -------------- 113 Therapeutic Goods Administration Clinical Evidence guidelines .

7 Medical Devices November 2021 Page 5 of 164 Clinical Evidence ---------------------------------------- ---------------------------------- 114 Compiling the CER ---------------------------------------- -------------------------------- 115 Defining Clinical success ---------------------------------------- ------------------------ 118 Summary of safety and performance data ---------------------------------------- - 120 Supportive Devices - Meshes, patches and tissue adhesives _____ 135 Summary recommendations ---------------------------------------- ------------------ 135 Defining supportive Devices ---------------------------------------- ------------------- 136 Clinical Evidence ---------------------------------------- ---------------------------------- 137 Compiling the CER ---------------------------------------- -------------------------------- 138 Defining Clinical success ---------------------------------------- ------------------------ 140 Summary of safety and performance data ---------------------------------------- - 144 Glossary and abbreviations _____ 150 Glossary _____ 150 Abbreviations _____ 155 Source material _____ 160 Search Method.

8 Identification and selection of Clinical studies _____ 160 Identified study designs _____ 162 Version history _____ 163 Therapeutic Goods Administration Clinical Evidence guidelines : Medical Devices November 2021 Page 6 of 164 About these guidelines These guidelines provide details and guidance on the Clinical Evidence requirements for Medical Devices , including in vitro diagnostic Medical Devices (IVDs), under Australian legislation. For IVDs, there is also a supplementary document titled Clinical Evidence guidelines supplement: In vitro diagnostic (IVD) Medical Devices , which should be reviewed in conjunction with these guidelines . The guidelines are intended to be a common reference point for both industry and the regulator assisting sponsors and manufacturers to collect, compile and present Clinical Evidence in a manner that meets regulatory requirements, while reflecting the TGA s approach to how it assesses Clinical Evidence .

9 These guidelines provide information on: Legislative framework The relevant Australian legislation for the regulation of Medical Devices particularly as it relates to the Essential Principles (EPs) and Clinical Evidence requirements to demonstrate compliance with the EPs. The Essential Principles The Essential Principles (EPs), including EP 14 regarding the requirement for Clinical Evidence , and the impact of Clinical Evidence on compliance with EPs. Clinical Evidence requirements Key concepts and approaches for different device classifications and types, including different Evidence strategies that can be used to demonstrate compliance with the EPs. Sources of Clinical data Sources of Clinical Evidence , including Clinical investigation studies (and a discussion of multiple study designs), literature reviews and Clinical experience data (including post-market data). Clinical evaluation and the Clinical Evaluation Report (CER) An explanation of the content and format requirements of the CER and supporting documents, including the role of critical analysis and expert opinion and a useful checklist.

10 Comparable Devices including substantially equivalent Devices An explanation of the steps involved in demonstrating substantial equivalence and information on the applicability of Clinical Evidence from comparable Devices . Requirements for specific device types Information on the specific requirements for certain types of Devices . International activities and alignment Australian regulatory processes are increasingly aligned with other international frameworks, subject to Australian legislative requirements and other limitations relevant to the Australian setting. For example, Australia takes part in the International Medical Device Regulators Forum (IMDRF) which is a voluntary group of Medical device regulators from around the world working towards international Medical device regulatory harmonisation. Consequently, some approaches taken by consensus groups such as the IMDRF and by regulators in other jurisdictions have been incorporated into these guidelines , particularly insofar as they relate to Clinical Evidence , with modifications as needed for the Australian setting.