MDSAP: CURRENT STATUS AND FUTURE PLANS

MDSAP: CURRENT STATUS AND FUTURE PLANS Seminar hosted by DITTA in conjunction with IMDRF Monday, March 13 2017 Vancouver, BC, Canada

A few words about our friend Klaus Stitz:

MDSAP: CURRENT STATUS AND FUTURE PLANS OPENING REMARKS Patrick Hope Executive Director, MITA DITTA Chair Kimby Barton Interim Director of the Medical Devices Bureau, Health Canada

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 1: REGULATOR PERSPECTIVES Marc-Henri Winter Staff Fellow, MDSAP - Center for Devices and Radiological Health U.S. Food and Drug Administration Fabio Quintino Pereira Manager - Office of GMP Inspection Brazilian Health Regulatory Agency - ANVISA

Medical Device Single Audit Program Overview of the Program and its Mechanics Marc-Henri Winter, Staff Fellow FDA

Participants and Observers Participants Therapeutics Goods Administration (TGA) Agência Nacional de Vigilância Sanitária (ANVISA) Health Canada Observers World Health Organization (WHO) European Union MHLW* and PMDA** Food and Drug Administration (FDA) * Ministry of Health, Labor and Welfare ** Pharmaceuticals and Medical Device Agency 6

Operational Organization Regulatory Authority Council (RAC) MDSAP governing body: two senior managers from each participating jurisdiction. representation from observing jurisdictions. Subject Matter Experts (SME) Permanent or ad-hoc working groups to: Develop policies and documents. Develop tools. Implement the program. 7

Concept RA Assess and recognize AO Share audit reports Audit and certify Make regulatory decisions Mfr RA: Regulatory Authority; AO: Auditing Organization; Mfr: Manufacturer 8

Audit Criteria ISO 13485 (2003 2016) Regulatory requirements on Quality Systems Brazilian Good Manufacturing Practices (ANVISA RDC 16). Japanese requirements (MHLW MO 169). FDA s Quality System Regulation (21 CFR Part 820). Specific national requirements on: Registration of manufacturer sites. Licensing of medical device. Reporting adverse event and advisory notices. Device tracking. 9

Audit Method MDSAP Audit Model 10

Audit Method Recently updated to Align with ISO 13485:2016. Add clarifications on the audit of technical documentation. Add clarification on the audit of sterile products. Training modules: For auditors: Articulate-online (including quiz). For all: on the FDA CDRH Learn webpage. (http://www.fda.gov/training/cdrhlearn/default.htm) 11

Audit Nonconformity (NC) Grading GHTF/SG3/N19:2012 Quality management system Medical devices - Nonconformity Grading System for Regulatory Purposes and Information Exchange. QMS Impact Direct: 3 Indirect: 1 Repeat NC Yes: 1 No: 0 Lack of Document Yes: 1 No: 0 Released Device Yes: 1 No: 0 NC Grade = sum of 4 parameters, capped at 5 12

AO Journey To Recognition Assessment Activity Application reviewed favorably Status Application Received Stage 1 + Stage 2 (+ Critical Locations) + Response to any nonconformity deemed acceptable 3 Witnessed Audits + Response to any nonconformity deemed Recognition Decision acceptable Authorized to conduct MDSAP audits (the first 3 to be witnessed) Recognized 13

Auditing Organizations Application Received Authorized to Conduct MDSAP Audits Recognized 14

Manufacturer Participation Required to maintain Canadian Device Licences after 2018-12-31 Voluntary and encouraged to - Register devices in Australia especially combination products. Obtain ANVISA GMP certificate devices class III and IV. Substitute to PMDA audits. Substitute routine FDA inspections any devices. 15

International Value of MDSAP Europe will determine whether to become a participating member of the MDSAP coalition and if/ how they can use the outcomes of the program. WHO Prequalification of in vitro diagnostics use MDSAP audits to abbreviate or waive WHO inspections. Others advocacy towards the use of MDSAP certificates by non-participating Regulatory Authorities. 16

MDSAP consortium: Current status, Timelines and Plans Fábio P. Quintino MDSAP RAC Chair Office of GMP Inspection for Medical Devices, Sanitizers and Cosmetics ANVISA-Brazil

CONTENT HISTORY STATUS PERSPECTIVES

HISTORY From GHTF, IMDRF launched at planning meeting in Ottawa in October 2011 where ToR was drafted Singapore meeting (March 2012) marked official inauguration of IMDRF One of the 5 inaugural work items

IMDRF MDSAP WG PURPOSE Develop standard set of requirements for auditing organizations performing regulatory audits of medical device manufacturers quality management systems Represented a critical step in establishing any Medical Device Single Audit Project

IMDRF MDSAP WG OUTCOME Documents for the Regulatory Authority assessments of AOs are based on: IMDRF/MDSAP WG /N5 FINAL:2013 Regulatory Authority Assessment Method for the Recognition and Monitoring of Medical Device Auditing Organizations IMDRF/MDSAP WG /N6 FINAL:2013 Regulatory Authority Assessor Competence and Training Requirements IMDRF/MDSAP WG/N8 FINAL:2015 Regulatory Authority Assessment Method Guidance IMDRF/MDSAP WG/N11 FINAL:2014 MDSAP Assessment and Decision Process for the Recognition of an Auditing Organization

IMDRF MDSAP WG OUTCOME Recognition, monitoring and re-recognition of Auditing Organizations documents: IMDRF/MDSAP WG/N3FINAL:2013 Requirements for Medical Device Auditing Organizations for Regulatory Authority Recognition IMDRF/MDSAP WG/N4FINAL:2013 Competence and Training Requirements for Auditing Organizations IMDRF/MDSAP WG/N24 MDSAP Audit Report Guidance

Timeline SoC 11/2012: Signature of the Statement of Cooperation for the development of a single audit program (TGA; ANVISA; HC; US FDA) 03/2013: Accelerated plan to develop the basic structure for the 3 year pilot program starting on 01/01/2014 06/2015: Japan (MHLW/PMDA) announces their participation in the pilot 12/2016: End of the pilot Transition to operational phase

CURRENT STATUS

MDSAP RECOGNIZED AOs BSI Group America Inc. Intertek Testing Services NA Inc. TŰV SŰD America Inc. 26

AOs AUTHORIZED TO PERFORM MDSAP AUDITS DEKRA Certification B.V. DQS Medzinprodukte GmBH LNE G-MED SAI Global Cert. Services PTY Ltd. SGS United Kingdom Ltd. TŰV Rheinland of North America Inc. TŰV USA Inc. UL Medical and Regulatory Services, UL LCC

AOs UNDER AUTHORIZATION PROCESS Lloid s Registry Quality Assurance Inc. - LRQA National Standards Authority of Ireland NSAI NSA Health Sciences Certification, LLC

As in march 9th

AUDIT NUMBERS 164 MDSAP Audits Reports to date 46 audits noted no nonconformities 118 audits had at least 1 nonconformity

Plans and Perspectives

Perspectives Pilot report to be issued An expected fast grow of the program in the transitional phase poses challenges Resource allocation MDSAP business model implementation Establishment of new RA

Regulatory Exchange Platform secure (REPs) IT solution to facilitate the exchange of confidential/non-public information (NPI), as well as the collaboration of regulators in a secure IT environment Starting with MDSAP module Partners: ANVISA Brazil, Health Canada, MHLW/PMDA Japan, TGA - Australia, US FDA and PAHO (Pan American Health Organization) Development phase started on March 2017 2 years are estimated for completion

Perspectives Increase of the use of program outcomes by each RA, maximizing value Learning curve, process improvements and program scale up may allow cost reduction

Perspectives Consolidation as a global, effective and resource wise tool for the regulatory oversight of Medical Device Manufacturer s QMS implementation.

Thanks for your Attention

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 1: REGULATOR PERSPECTIVES Q&A

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 2: ASSESSING ORGANIZATION (AO) PERSPECTIVES Gary Minks Vice President, Quality & Regulatory Affairs TÜV SÜD America Inc. Patricia Murphy Global Head, MDSAP Program BSI Healthcare

DITTA Seminar MDSAP; An Auditing Organization s Perspective Gary Minks TÜV SÜD America Inc Office: +1-978-573-2521 Mobile: +1-978-884-5019 Email: gminks@tuvam.com 2017-03-13 TÜV SÜD 14/03/2017 Corporate Presentation Slide 39

Our heritage: 150 years of business success 1866 1906 Establishment of a Mannheim-based steam boiler inspection association by 22 operators and owners of steam boilers, with the objective of protecting man, the environment and property against technology-related risks First vehicle periodic technical inspection (PTI) 1926 Introduction of the TÜV mark / stamp in Germany 1958 Development of a Bavaria-wide network of vehicle inspection centers in the late 1950s 1990s Conglomeration of TÜVs from the southern part of Germany to form TÜV SÜD and the expansion of business operations into Asia 2006 Expansion of services in ASEAN by acquiring Singapore-based PSB Group 2009 Launch of Turkey-wide vehicle inspection by TÜVTURK Today TÜV SÜD continues to pursue a strategy of internationalisation and growth TÜV SÜD 16-01-01 TÜV SÜD Corporate presentation Slide 40

Achieve market success Manufacturing & industrial machinery Consumer products & retail Healthcare & medical devices Telecommunications & IT Services for components manufacturers, contractors, installation providers, equipment & material manufacturers and operators include: Component testing Periodic inspection of equipment Failure analysis System certification Training Services for manufacturers, retailers, buyers and suppliers of electrical & electronics, food, health & beauty, hardlines, softlines, toys & children s products: Testing Auditing Inspection Product certification Knowledge services System certification Training Services for medical device manufacturers and healthcare providers include: Clinical approvals Market approvals and certification Testing Evaluation System certification Training Services for equipment manufacturers and operators of infrastructure equipment and radio frequency wireless equipment include: Design reviews Testing Software escrow Product certification System certification Training TÜV SÜD 16-01-01 TÜV SÜD Corporate presentation Slide 41

MDSAP - Successes Auditor on-line training for MDSAP program requirements. We are quickly ramping up our global MDSAP auditor capaciity. Collaboration between Regulators and Auditing Organizations during the pilot program Manufacturers have avoided US FDA and Australian TGA inspections. Manufacturers have used MDSAP audit reports to obtain ANVISA GMP certificates. TUV SUD is conducting combined MDSAP / European MDD audits. TÜV SÜD America 17-03-14 Slide 42

MDSAP - Challenges Auditor Mentoring is a challenge in these early audits (i.e., pairing experienced auditors with first time auditors) Coverage of all 94 core tasks and regulatory authority specific tasks while conducting a Process Audit. The Audit Model works but it takes some experience. The auditors that have done several MDSAP audits report that they do get more comfortable over time. Realign task numbers to more logically align with sequence of audits TÜV SÜD America 17-03-14 Slide 43

MDSAP - Challenges Combining MDSAP with European MDD (Medical Device Directive) audits. Adding MDD requirements into the Audit Model would help. Surveillance audit man-days for small organizations Manufacturer s concern with regulator information sharing Some customers change their attitude with MDSAP compared to previous audits. Scoping of multiple site audits (i.e., which sites to include) 15 day limit for manufacturers to respond to nonconformities Obtaining the correct DUNS numbers from manufacturers TÜV SÜD America 17-03-14 Slide 44

Program Distinctions Criteria ISO 13485 MDSAP Program Customer Manufacturer Regulator Output of success Auditing Organizations Qualification Certificate Competent Body Report & Certificate Regulators Audit Duration Employee count Fixed Timing Nonconformance grading Major/Minor 1, 2, 3, 4, 5

Program Launch Program Challenges 1. Jurisdictional requirements Interaction with ISO 13485 Complexity of differences Inclusion of CE 2. Locations How they interact Where they are located 3. Adoption by manufacturers 4. Length of audit Sufficient resources Organization of audit plan 5. Reporting Active voice All jurisdictions Specific timelines NCR grading Copyright 2017 BSI. All rights reserved 48 14/03/2017

Pilot Phase - 2014 thru 2016 Audit Model Challenges Auditors Task-based Not ISO 13485 Plus Deep Dive into processes Regulatory Audit Risk key part of audit Manufacturers Confused by delivery Single audit Consistent flow Product - focused Risk focus support Copyright 2017 BSI. All rights reserved 49 14/03/2017

Pilot Program Successes 1. Auditing organizations jumped into the program and encouraged manufacturers to engage 2. Manufacturers recognized cost benefit 3. AO s embraced regulatory audit model 4. Five jurisdictions engaged 5. All stakeholders adapting to be successful Copyright 2017 BSI. All rights reserved 50 14/03/2017

Program settling in Changes evolved through the Pilot and into Operational Phase 1. Audit task timeline changes 2. Campus location defined 3. Additional auditing organizations progressing through qualifications 4. Manufacturers engagement growing dramatically in 2017, despite low numbers in Pilot phase Copyright 2017 BSI. All rights reserved 52 14/03/2017

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 2: ASSESSING ORGANIZATION (AO) PERSPECTIVES Q&A

MDSAP: CURRENT STATUS AND FUTURE PLANS BREAK: 30 MINUTES Refreshments served in foyer

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 3: REGULATED INDUSTRY PERSPECTIVES MDSAP Industry Participation Survey: Findings

MDSAP INDUSTRY PARTICIPATION SURVEY: FINDINGS Presented at MDSAP: Current Status and Future Plans Seminar hosted by DITTA in conjunction with IMDRF Monday, March 13 2017 Patrick Hope MITA Executive Director; DITTA Chair

MDSAP INDUSTRY PARTICIPATION SURVEY INTRODUCTION Objective: Improve industry participation in MDSAP Goal: Widespread adoption and use of MDSAP Survey methodology: Conducted online January 15-February 24 53 participants

MDSAP INDUSTRY PARTICIPATION SURVEY MAJOR THEMES Most respondents did NOT participate in MDSAP pilot Those that DID participate found value in the program

Most participants only signed up 1 facility/manufacturing site MDSAP INDUSTRY PARTICIPATION SURVEY MAJOR THEMES

although they are planning to add more MDSAP INDUSTRY PARTICIPATION SURVEY MAJOR THEMES

Overall experience of participants: POSITIVE! MDSAP INDUSTRY PARTICIPATION SURVEY MAJOR THEMES

55% did not attempt, deterred by cost or lack of interest 10.5% attempted, but deterred by issues with cost or AO MDSAP INDUSTRY PARTICIPATION SURVEY NON-PARTICIPANTS, EXPLAINED

MDSAP INDUSTRY PARTICIPATION SURVEY NON-PARTICIPANTS, EXPLAINED 34% report their decision not to participate was based on other, often complex factors However: none so complex that they can t be fixed!

MDSAP INDUSTRY PARTICIPATION SURVEY GENERAL INFORMATION Most survey respondents sell into all MDSAP countries

MDSAP INDUSTRY PARTICIPATION SURVEY GENERAL INFORMATION More of respondents business is covered by MDSAP than is not

MDSAP INDUSTRY PARTICIPATION SURVEY GENERAL INFORMATION Most respondents used US FDA s online resources

MDSAP INDUSTRY PARTICIPATION SURVEY GENERAL INFORMATION Most respondents reported that the survey touched all aspects of concern with MDSAP

MDSAP INDUSTRY PARTICIPATION SURVEY TAKEAWAYS & NEXT STEPS Survey respondents that participated in MDSAP liked it Those that did not participate were open or planning to participate in MDSAP in the future

MDSAP INDUSTRY PARTICIPATION SURVEY TAKEAWAYS & NEXT STEPS MDSAP success depends on: Regulators wide use MDSAP as total replacement for current QMS audits Auditors have sufficient capacity to carry out all MDSAP audits by deadline Industry has sufficient time for all facilities to undergo MDSAP audit

THANK YOU! www.globalditta.org

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 3: REGULATED INDUSTRY PERSPECTIVES Philip Steinborn Medtronic Emmett Deveraux Cook Medical Naoki Morooka Shimadzu Medical Systems Vijay Madikonda Johnson & Johnson Medical Devices

MEDTRONIC AND MDSAP Phil Steinborn VP, Quality/RA Americas

MDSAP IS HERE TO STAY MEDTRONIC IS COMMITTED TO PROGRAM 1. Achievements: Where are we with MDSAP? 2. 3. Challenges: What are the obstacles or risks as we see it? Suggestions: Our recommendations for industry and the program. 75

WHERE DO WE STAND WITH MDSAP? ACHIEVEMENTS 10+ FACILITIES ALREADY INSPECTED IN MDSAP PARTICIPATED IN PILOT PROGRAM NO OTHER INSPECTIONS AT MDSAP SITES TO DATE MDSAP CERTIFICATE ACCEPTED SEVERAL WITNESSED AUDITS. TO PERMIT AOs TO ATTAIN QUALIFICATION WORKING WITH MULTIPLE AOs SCHEDULING FOR OTHER FACILITIES PRIORITIZING CMDCAS SITES 76

WHAT ARE THE OBSTACLES OR RISKS? CHALLENGES CAPACITY OF PROGRAM CAN AOs MEET DEMAND? 4 AOs FULLY ACCREDITED 4 AOs IN WITNESSED AUDITS STAGE OF ACCREDITATION 5 AOs IN PRELIMINARY ASSESSMENT PROCESS DO AOs HAVE SUFFICIENT NUMBER OF MDSAP TRAINED AUDITORS? CAN WE GET TIMELY MDSAP AUDITS SCHEDULED? 77 COMPLEXITY OF AUDIT Significant preparation required. Audit to 5 different sets of regulations challenging. Annual inspection more frequent than usual for many of the participating regulators New process Experiencing some delays in getting audit reports can adversely impact registrations. Price tag for MDSAP audit significantly higher Are we saving with annual audits or does it balance out? RESPONSE FROM REGULATORS Regulators receiving annual MDSAP audit reports how will they react? FDA will treat Grade 4 and 5 findings as OAI (Official Action Indicated).. May result in Warning Letter. Regulators may send AOs back in to follow up on gaps in audit report (... or go themselves). Opportunity for regulators to uphold very particular requirements of their regulations.

OUR RECOMMENDATIONS FOR INDUSTRY AND PROGRAM SUGGESTIONS FOR INDUSTRY Prepare for the audits. Use the MDSAP Companion documents. Sticking points tend to be unique req ts of countries. Identify these! Engage AOs early. Get on their schedules and allow them to plan accordingly. Take AO findings seriously. Regulators are getting your reports. Don t forget about OEMs that are CMDCAS. They also need MDSAP. FOR PROGRAM Significant concerns about capacity. Availability of AOs and qualified auditors a real issue. Consider low risk manufacturers go to single surveillance over the 3 year cycle to help alleviate backlog. Current MDSAP model is not expandable. Audit is too complex with multiple sets of regulations. Need to align on a single audit standard (to meet local regulations) such as ISO 13485:2016. 78

GOVERNMENT AFFAIRS Global Regulatory Developments An Industry Perspective on the Medical Device Single Audit Programme (MDSAP) COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION.

Cook Medical s history with MDSAP Volunteered for the program in December 2014. First Inspection was in April, 2015 (Witnessed AO Inspection) Second MDSAP Inspection February 2016 (Non Witnessed) We believe we were one of the first in Europe and the first Irish Site. Two manufacturing sites in Europe but Ireland was chosen as the test site. Great Team at the Cook Ireland site and the success is down to them. COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

What this presentation is not going to be A detailed technical discussion on the Instead MDSAP it will be a very top level personal opinion of the MDSAP principle and achievements to-date COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION.

Overall comment Yes! Positive and to be welcomed COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Like anything new there are some concerns. Capacity concerns within the Auditing Organisations. The expansion of the MDSAP Programme Full benefits to Industry, incl. SMEs, yet to be realised Full EU Participation COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Capacity within the Auditing Organisations (AO) COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

How many trained MDSAP Inspectors does each AO have? COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

How many actual inspectors with the AOs with the MDSAP skill set? CLASS STERI CLINICAL MDD LOG ACTIVE COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

The Global Expansion of the MDSAP Programme. COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Benefits for Industry yet to be fully realized It s a considerable expense so the benefits have to meet all expectations, incl SME s The principle is solid and its concept is one that industry and the patient will benefit from. The true benefit will come once the programme has developed and become truly global in nature. For now my advice is to stay involved but work with the Regulators to ensure that the benefits are realized for all stakeholders. COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Full EU Participation? EU have decided not to join the full programme. Resource Issues Industry would encourage that the EU come on board as a full member COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

How did Industry respond to the MDSAP request for action? YOUR REGULATOR WANTS YOU! COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Participating manufacturers (June 2016) COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Overall score for Industry (My opinion) 5/10 We Passed but with much to do and to learn! COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Why do I say that? IMDRF as you know replaced the GHTF model 5 years ago Industry comments on IMDRF have been consistent We need to be at the table and be more than just observers. IMDRF gave us this opportunity for MDSAP but unfortunately we were slow in joining the pilot. Lets learn from this and move on together. COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. GOVERNMENT AFFAIRS

Well done and please let it grow and expand and reach its full potential! COMPANY CONFIDENTIAL. DO NOT COPY. NOT FOR EXTERNAL DISTRIBUTION. CORP-D30444-EN GOVERNMENT AFFAIRS

Session 3 MDSAP Pilot Experience and Barriers to Participation in Japan Naoki Morooka Senior Manager, Quality Assurance Department Medical Systems Division, Shimadzu Corporation 13 March, 2017

Contents Introduction Consideration for implementation Steps for implementation Suggestion Additional Information of Speaker Naoki Morooka *SC member of DITTA *Chairman of QMS committee in JIRA. *Chairman of QMS committee in JFMDA. 97

Introduction - MDSAP Pilot in Japan Pilot stage in Japan 1 st Phase until 31 December 2016 2 nd Phase until 31 December 2018 For Approved Product Required documents by PMDA MDSAP report required for QMS inspection. Reduce the required documentation for Review by PMDA. For Certified Product Registered Certification Body also required to accept them. 98

Introduction -MDSAP Pilot in Japan Registered AOs Application Received Authorized to Conduct MDSAP Audits Recognition 13 organizations 11 organizations 3 organizations Almost AOs have local office in Japan. Ref.: List of AOs https://www.fda.gov/downloads/medicaldevices/internationalprograms/mdsappilot/ucm429978.pdf Implementation Japan into MDSAP pilot. Japanese QMS requirements were placed into Companion Document. And then, the auditors in AOs was trained according to Companion Document. PMDA received a few application for QMS inspection based on MDSAP report. Ref.: Companion Documents https://www.fda.gov/medicaldevices/internationalprograms/mdsappilot/ucm377580.htm 99

Introduction -Company Profile and Certification Scope Company Profile Shimadzu Corporation Medical Systems Division Location: Kyoto, Japan Product/Certification Scope Diagnostic X-ray Devices Angiographic X-ray Diagnostic Systems Nuclear Medicine Diagnostic Systems Medical Image Managements Systems Near infrared fluorescence Imaging System(NIRS) Tumor-Tracking Systems for Radiotherapy Systems Certification/Auditing ISO13485:2003/ ISO9001 Angiography Systems Fluoroscopy Systems PET Scanner for Mammography Imaging CMDCAS, MDD Annex II, Japan-PMD Act MO169 All certifications were issued by same Certification Body. <Single Audit/ Multi-Certification/Report> US-FDA 21CFRpart 820, ANVISA, CFDA, etc. Audited by RA. General Radiography Systems Mobile X-ray Systems NIRS Systems Tumor-Tracking Systems for Radiotherapy Systems 100

Consideration Timing and Cycle for Certification Audit MDSAP Certification Audit For implementation of MDSAP, Certification Scope Extension was not considered in Audit Model. Full Audit required. Timing for Certification Audit Synchronize with existing Certification Cycles. in order to reduce the auditing cost. Transition period for Key Standards/Regulation MDSAP pilot 31 December 2016. ISO 9001:2015 14 September 2018. CMDCAS 31 December 2018. ISO13485:2016 28 February 2019. 101

Consideration Certification Cycles in our company Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Certification Audit Certification Audit Certification Audit Certification Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit 2018.09.14 Surveillance Audit 2019.2.28 2018.12.31 Certification Audit Certification Audit Certification Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Surveillance Audit Certification Audit ISO13485:2003 Cert. 3 years Cycle ISO13485:2016 Transition Period 2019.2.28 CMDCAS 3years Cycle MDSAP Transition Period 2018.12.31 ISO9001:2008 Cert. 3 years Cycle ISO9001:2015 Transition Period 2018.9.14 Surveilla Audit Our AO was not recognized yet. 2016.0 5 Surveillance Audit Our Current Target Schedule Certification Audit 2018.05 Surveillance Audit Surveillance Audit MDSAP ISO13485:2016 ISO9001:2015 MDD or J-PMDAct 5years Cycle Surveillance Audit 102

Steps for implementation Steps Decision for schedule for Certification Audit as MDSAP Selection of AO Gap Analysis/Impact Assessments Modification/Adjustment for QMS Internal Audit Management Review Certification Audit by AO 103

Steps for implementation -Key elements Gap Analysis/Impact Assessments Details Audit Model MDSAP AU P0002.003 Audit Model (PDF - 882KB) (ISO 13485:2003) MDSAP AU P0002.004 Audit Model (PDF - 770KB) (ISO 13485 :2016) New Companion Document MDSAP AU G0002.1.003: Companion Document (PDF - 1.5MB) (ISO 13485 :2003) MDSAP AU G0002.1.004: Companion Document (PDF - 1.2MB) (ISO 13485 :2016) New Difference of Auditing Approach Top down approach Review for Subsystem (FDA-QSIT oriented) 104

Steps for implementation - key elements Sample description in Companion Document Chapter 1 - task 8. Verify that procedures have been defined, documented, and implemented for the control of documents and records of both internal and external origin required by the quality management system. Confirm the organization retains records and at least one obsolete copy of controlled documents for a period of time at least equivalent to the lifetime of the device, but not less than two years from the date of product release. Clause and Regulation: [ISO 13485:2016: 4.1.4, 4.2.1, 4.2.4, 4.2.5; TG(MD)R Sch3 P1 1.4(4); RDC ANVISA 16/2013: 3.1; MHLW MO169: 5, 6, 8, 9,; 21 CFR 820.40, 820.180] Additional country-specific requirements: Australia (TGA): Confirm that Quality Management System documentation and records in relation to a device described in TG(MD)R Sch3 P1 1.9 are retained by the manufacturer for at least 5 years. Brazil (ANVISA): Verify that change records include a description of the change, identification of the affected documents, the signature of the approving individual(s), the approval date, and when the change becomes effective [RDC ANVISA 16/2013: 3.1.5]. Japan (MHLW) Confirm that Quality Management System documentation and records in relation to a device are retained for the following. 105

Steps for implementation -Key elements Consideration for Reporting For Deviation, Grading system was applied according to GHTF/SG3/N19:2012 Nonconformity Step 1 Grading Matrix Step 2 Escalation Rules Final Nonconformity Grade Grading Overview Grading Matrix Ref: http://www.imdrf.org/docs/ghtf/final/sg3/technical-docs/ghtf-sg3-n19-2012-nonconformity-grading-121102.doc 106

Suggestion For Regulators Scope Extension Audit Scope Extension Audit for ISO13485 Certification was not considered in Audit Model. Implementation Guide for Manufacturer. Manufacturer might need Implementation Guide for Manufacturer for better understanding for MDSAP. For Regulators and AOs Capacity of AOs in 2018/2019? So many company will request certification audit in 2018 or 2019. Do AOs have capability for them? For Industry Benefit We are considering to reduce auditing by US-FDA and ANVISA. 107

Medical Device Single Audit Program (MDSAP) Ethicon Experience Vijay Kumar Madikonda Ethicon Compliance March 13, 2017

Agenda Ethicon Inc. Achievements Audit Experience & Challenges Suggestions/Feedback on the MDSAP Program Confidential For J&J Use Only 10 9

Achievements: MDSAP Pilot Update Ethicon and Mentor Business units of J&J participated in the MDSAP Pilot Program. Details of the sites piloted for the MDSAP are as follows: SITE Ethicon LLC, San Lorenzo Most recent MDSAP audit dates May 19-22, 2015 & Mar 15-18, 2016 Type of Audit Site Activities Product supply MDSAP Surveillance MDSAP Surveillance Manufacturer WW supply including US, Canada, Australia, Brazil & Japan Ethicon SARL, Neuchatel Aug 25-27, 2015 & June 28-July 1, 2016 Ethicon Inc., Somerville Dec 1-2, 2015 Jun 1-3, 2016 MDSAP Certification MDSAP Surveillance MDSAP Surveillance MDSAP Surveillance Manufacturer Design, Regulatory, PMS, Complaint handling WW supply including US, Canada, Australia, Brazil & Japan WW supply including US, Canada, Australia, Brazil & Japan Ethicon Inc., Durango, Juarez Jun 7-8, 2016 MDSAP Surveillance Manufacturer WW supply including US, Canada, Australia, Brazil & Japan Mentor Irving July 14-18, 2015 June 21-24, 2016 MDSAP Certification MDSAP Surveillance Design, RA, PMS, CQ, Mfg. WW supply including US, Canada, Australia, Brazil & Japan MDSAP Plans for 2017: Added 6 more Ethicon sites to the MDSAP program and inspections scheduled in 2017. Multiple J&J Medical device sites are moving into MDSAP program. Confidential For J&J Use Only 11 0

Audit Experience & Challenges Audit Process: Transparent and Task-based Audit Model follows Companion Document Very thorough audits and evaluated compliance to all regulations Audit Duration: Longer audit times No significant difference between Recertification and Surveillance audit time. Challenges: Challenges in scheduling of the Audits due to limited trained auditors. Review of some information not related to the site scope (design, complaint handling, Regulatory, Quality systems) required Franchise participation in each site audits. Confidential For J&J Use Only 11 1

Feedback on the MDSAP Program: Positive: Well trained auditing organizations conducting audits in a consistent way. Suggestions/Opportunities: Train more auditors to support full MDSAP implementation. Training materials and Guidance available of MDSAP website. Timely issuance of audit reports and MDSAP certificates. Reduction in the number of Audits & Less business disruption. Harmonization of requirements. Expand the scope of MDSAP acceptability to include For cause inspections as AO s can conduct Special audits to follow-up on Post market issues, significant findings from previous audits and based on request from participating regulatory authorities. Post audit timeline of D 0 +30 for providing evidence of implementation of remediation actions addressing Grade 4 or 5 observations is too short if robust actions are to be implemented. Confidential For J&J Use Only 11 2

Thank you Confidential For J&J Use Only 11 3

MDSAP: CURRENT STATUS AND FUTURE PLANS SESSION 3: REGULATED INDUSTRY PERSPECTIVES Q&A

MDSAP: CURRENT STATUS AND FUTURE PLANS CLOSING SESSION: PANEL DISCUSSION Moderator: Brian Lewis, MEDEC Marc-Henri Winter - USFDA Jun Kitahara PMDA Japan Nancy Shadeed Health Canada Cheryl McCrae TGA Australia Fabio Quintino Pereira ANVISA Brazil Gary Minks TÜV SÜD America Inc. Patricia Murphy BSI Healthcare

MDSAP: CURRENT STATUS AND FUTURE PLANS CLOSING SESSION: PANEL DISCUSSION Q&A

MDSAP: CURRENT STATUS AND FUTURE PLANS Thank you!