This document provides an overview of global regulatory trends in 2017 and beyond for medical devices. Key points include increased emphasis on clinical data and post-market surveillance across regions. The EU is transitioning to the new Medical Device Regulation which increases requirements for technical documentation and quality management systems. Notified Bodies face challenges meeting demand under new rules. The US 21st Century Cures Act aims to streamline approval of certain lower-risk devices and accessories. Single audits through the Medical Device Single Audit Program may replace some regulatory inspections globally.

2. Global Regulatory Outlook:
2017 and Beyond
Evangeline Loh, Ph.D., RAC (US, EU)
EMERGO | Vice President, Global Regulatory Affairs

3. Global
• ISO 13485:2016 QMS standard
• Medical Device Single Audit Program
(MDSAP)
• International Medical Device
Regulators Forum (IMDRF)
European Union
• Medical Device Regulation (MDR)
• Notified Bodies
• Clinical Evaluation Reports (CER)

4. United States
• 21st Century Cures Act
• Post market surveillance
• Policy and political administration
Global Trends
• Improved premarket review timeframes
• Emphasis on clinical data
• Emphasis on post marketing surveillance
• New medical device regulatory systems
• Regulatory resources

5. ISO 13485:2016/EN ISO 13485:2016 QMS:
Requirements Regulatory Purposes
• Standard published March 2016
• No new certificates issued to ISO 13845:2003 after March 2018
• Transition complete March 2019
• “If appropriate” is used throughout standard for requirements, unless
otherwise justified...added consideration for:
• product to meet requirements
• compliance with applicable regulatory requirement
• the organization to carry out corrective action
• the organization to manage risks

6. Risk-based approach is applied to many areas
“Risk” term used in standard applies to:
• safety and performance requirements of
the device or
• meeting applicable regulatory
requirements
Process – decision making uses risk
based approach
• Changes to finished device
• Supplier qualification and controls
• Complaint handling
• Corrective action assignment

7. Risk-based approach is applied to many areas
• 4.1.2 Control of appropriate processes
• 4.1.5 Outsourcing controlled proportionate to the risk of the external party
• 4.1.6 Software validation proportionate to use of software system
• 6.2 Effectiveness of training proportionate to risk of work being performed
• 7.3.3 Risk management part of design inputs
• 7.3.9 Design changes include assessment of risk management
• 7.4.1 Purchasing requirements proportionate to the risk of the purchased
product and requirements
• 7.4.3 Verification proportionate to the risk of purchased product
• 7.5.6 Software validation proportionate to the risk of the software system
• 8.2.1 Feedback serves as an input to the risk management for monitoring of
the product realization process

8. Objective Evidence for Risk Based Approach
• Understand the processes that may have risk aspect involved – from previous
slide and others
• Appropriate to risk based thinking for decision steps
• Input or output of the risk management file(s)
• Review the applicable procedures for how risk concepts are applied or
determined
• This is an evolving concept that can be applied in numerous ways – not just
one right way
• Assess processes against risk levels/determinations instead of “yes/no”
categories
• Confirm there are definitions for the risk determination
• Risk level or determination documented on records

9. Understand Timing and Transition
• Understand timing for current
certification expiration
• No new ISO 13485:2003 certificates
issued after March 2018
• All must be transitioned
by March 2019
• Guidance from Notified Body/
Registrar on transition timing
• Awareness training
• Generate Quality Plan
and Gap Analysis

10. Establish Quality Plan and Gap Analysis
• Implement a quality plan (ISO 10005:2005 QMS-Guidelines for quality
plans) to manage transition
• Conduct a Gap Audit
• Identify the important gaps to address, revise and amend procedures
• Conduct internal audits to ensure gaps are closed
• Address non-conformities as appropriate from audit
• Communicate with NB/Registrar on scheduling
• Allow ample time for scheduling – many other companies and limited
NBs/Registrars resources

11. Medical Device Single Audit Program (MDSAP)
• IMDRF work group (2012) to establish a single, global audit program
(MDSAP) as a substitute for Regulatory Authority (RA) inspections
• Qualified Auditing Organizations (AOs) prepare audit reports
accepted by IMDRF participating RAs as evidence of compliance
• Reduce overall number of audits or inspections
• Enhance confidence third party audits
• Some RAs use audits as alternative to their own inspections
• MDSAP Pilot
• Started Jan 2014
• Concluded Dec 2016, exception Japan

12. Operational Phase 2017
• Program Objectives
• Medical Device manufacturer engage an AO to have a single regulatory/QMS audit
that meets the requirements of all participating RAs:
• Australia TGA
• Brazil ANVISA
• Health Canada
• US FDA
• Japan PMDA/MHLW
• Note that the MDSAP audit would only include the regulations applicable to
markets for the MD manufacturer. The MDSAP audit report is sent to all
participating countries.
• Each country defines how MDSAP outcomes are used within its jurisdiction in
accordance with its legislation and regulatory framework

13. MDSAP Structure
Regulatory Authorities (RA)
Assessments
Auditing Organizations (AO)
Manufacturers
Reports
Regulatory
Authorities (RA)
Assessments
Reports
Auditing
Organizations
(AO)
Audits
NC/CAPs
Manufacturers
NC/CAPs

14. United States
• FDA plans to accept MDSAP audit reports as a substitute for FDA
routine inspections (biannual by policy).
• MDSAP routine audits are announced, scheduled by the AO with the
manufacturer, with a pre-established duration;
• The FDA will review MDSAP audit reports with a level of scrutiny
commensurate to the significance of audit findings, taking into account
the review and follow-up performed by the AO;
• Firms have 1 month to provide their full response to critical
nonconformities (grade 4 and 5) to the AO (as opposed to 15 working
days following a FDA inspection);
• Certification documents issued by the AO will state compliance with
applicable US regulations, which may provide a marketing advantage.

15. Australia, Class IIa higher risk devices
• TGA will consider MDSAP reports whether a manufacturer has
demonstrated compliance with an Australian Conformity Assessment
Procedure (ACAP); or
• TGA will consider whether to issue or maintain a TGA CAC in relation
to manufacturers’ products. Under some circumstances a manufacturer
may avoid routine TGA inspections.
• TGA will accept MDSAP certificates as evidence of compliance with
ISO 13485 where the Standard has been used to demonstrate partial
compliance with the requirements of an ACAP. Australian Sponsors may
be required to submit to the TGA, additional technical documentation
to demonstrate compliance with the requirements of the EP of Safety
and Performance and the manufacturer’s chosen ACAP.

16. Brazil
• ANVISA will utilize the outcomes of the program, including the reports, to constitute
an important input on ANVISA’s pre-market and postmarket assessment
procedures, providing, when applicable, key information that are expected to
support regulatory technical evaluation on these issues.
• Due to recent regulatory changes, ANVISA will use MDSAP audits in lieu of a
premarket inspection by ANVISA to grant GMP Certificates to manufacturers
intending to put medical devices of class III or IV on the Brazilian market.
Undergoing an MDSAP audit may accelerate the GMP certification process, which
is a pre-requisite to the marketing authorization. ANVISA can also use MDSAP
audits to renew GMP Certificates bi-annually, as an alternative to an ANVISA
comprehensive inspection.
• Greatest benefit to Class III/IV applicants (i.e. those manufacturers who must be
audited for BGMP compliance by ANVISA as outlined in RDC 16/2013) as this is
expected to greatly accelerate the authorization process.

17. Japan
• Reduce the required
documentation for
Review by PMDA.
• Reduce inspections
Note: Japan in 2nd Phase of
Pilot until 31 December 2018

18. Medical Device Single Audit Program (MDSAP)
• Health Canada MDSAP certification required after 31 December 2018
for Medical Device License
• (March 2017) 215 MDL holders signed up/audited
(3,728 manufacturers have valid MDLs)
• Voluntary use encouraged: Australia TGA, Brazil ANVISA,
Japan MHLW/PMDA, US FDA
• MDSAP represents 4.7% of ANVISA GMP certificates
• Training available FDA portal
• CDRH Learn  Post market Activities  Inspections - Global Harmonization
• Focused on product related processes - similar US FDA QSIT inspections or
Unannounced Notified Body Audits, with addition of market authorization
and registration requirements

19. International Medical Device Regulators Forum
(IMDRF)
• Initiatives for global harmonization between regulators
• 2011: AUS, BR, Canada, China, EU, JP, RU, SG and USA
• MDSAP
• Roadmap for implementation of UDI
• Adverse event terminology
• Regulated Product Submission

20. Medical Device Regulation (MDR) Regulation (EU)
2017/745 Timelines
Publication in OJEU May 5, 2017
Entry into Force May 26, 2017
Date of Application May 26, 2020
CE certificates to MDD void May 26, 2024
Last day devices placed on market with valid
MDD certificate put into service
May 26, 2025

21. Differences between MDD and MDR
MDD 93/42/EEC
Directive – moderate oversight
Chapters – 0
Articles – 23
Annexes – 12
Pages – 60 (including Annexes)
Transition period of 3 years (5 years
total)
MDR Regulation (EU) 2017/745
Regulation – strong oversight
Chapters – 10
Articles – 123
Annexes – 17
Pages – 566 (including Annexes)
Transition period of 3 years, plus 4
year ‘grace period’ with valid CE
certificate to MDD

22. MDR highlights
• Development of Common Specifications (CS)
• Definition of the Economic Operators within the Union
• All manufacturers must have a QMS and conduct PMS
• Identification of a person responsible for regulatory
compliance (previously referred to as Qualified Person)
• Liability for defective products and access to information
to claim compensation
• Guidance from external sources taken into account
• Case-by-case handling of devices and borderline products

23. MDR highlights
• Claim damages during clinical investigations
• Reprocessing of single-use devices where
permitted by national law
• Public access to Eudamed
• Stronger emphasis on Notified Body oversight/requirements
• Scrutiny procedure for high (novel) risk devices
• More coordination between Members States / affected party
• Reusable surgical instruments are Class Ir (require NB)

24. Exemptions for certain orthopedic implants
• Screws, wedges, plates, wires,
pins, clips, connectors
• Implant card (Art 18(3))
• Clinical investigations (Art 61(6)(b))
• Conformity assessment each device
• (Art 52(4))

25. Main impact of future legislation
• Innovative, high risk devices delayed market entry
• Cost increase industry (MDCG review, unannounced visits,
traceability system review, UDI, implant card)
• Highly qualified staff required for manufacturer, notified body (and AR)
o NB assessment team: At least one expert in technology
• Documentation, review technical file, Summary of Safety and Clinical
Performance, Essential Requirements text change for General Safety
and Performance Requirements

26. Overall Summary of New Regulation
• Increased regulatory requirements
• Stronger emphasis in different areas
• Some expectations of compliance requirements are not necessarily new
• Changes required to technical documentation and QMS requirements
• Creating synergy between groups in EU

27. During the Transition
• Commence Quality Plan and Gap Analysis
• Develop regulatory strategy related to
transition timeline
• Don’t wait until months
before compliance date
• Notified Body scheduling critical
• Understand implications for product
families, CE Marking and QMS
• Resource limitations and current work load

28. Notified Body: Current State
• NANDO, 54 NBs are currently active
• AMTAC, SGS, BSI, Lloyd’s and UL International (UK) are UK-based
• TEAM NB has 21 Members
• Slow/no response from NBs, unable to schedule surveillance audits and
reviews, audit report absent or not closed
• No UAs performed within
recommended timeframe
• Orphaned manufacturers

29. MDR and Notified Bodies
• Earliest date of application for designation under MDR
(26 November 2017, Article 123(3)(a))
• Require at least one year before NBs are designated
• NBs likely be accredited to both MDD and MDR simultaneously
• Emphasis on Notified Body oversight/requirements

30. Notified Body: Recommendations
• Assess your current NB
• further demise of NBs is unavoidable
• over then next year, scope of many
NBs may change  transfers!
• when considering a NB
transfer, carefully review
• NB timing as it relates
to accreditation to MDR
• NB also an AO under MDSAP

31. MEDDEV 2.7/1, Rev. 4
• Rev. 4, June 2016 (65 pages)
• Rev. 3, December 2009 (46 pages)
• GHTF SG5/N2R8 2007
• Rev. 2, April 2003 (19 pages)

32. MEDDEV 2.7/1, Rev. 4: Highlights
• Emphasis and clarifications
• ER for performance, safety and risk benefit supported
by clinical evidence and specific and measurable
• Current knowledge/state-of-the art assessment
• Relationship between RM, labeling, PMS and CER
• Frequency updates CER
• Equivalence
• New
• Qualifications evaluators, Declarations of Interest

33. Equivalence: Notified Body shall
challenge access to data
Rev. 4, Appendix A.12, A 12.2.3
• “level of access technical and clinical data from an equivalent device”
• “relevant information may be commercially sensitive/confidential
and not available to manufacturer”
• “challenge ability manufacturer access information”
• “might be limited or impossible in case of limited
access to the technical documentation”
MDR, Art 61 (5)
• “contract in place…full access to the tech documentation on
ongoing basis” (implantable and Class III medical devices)
MDR Annex XIV, Part A, 3
• “sufficient levels of access to the data”

34. Clinical Evaluation Recommendations
• Review MEDDEV 2.7/1 Rev. 4, perform gap assessment
• Remediate CER and procedures
• Review MDR, perform gap assessment
• clinical evaluation
• PMS processes
• Develop MDR clinical data strategy

35. FDA 21st Century Cures Act (Pub. L. 114-255)
• Enacted December 13, 2016
• Changes to FDA process
• Subtitle F, Medical Device Innovations (Sec. 3051-3060)
• Sec. 3051 Breakthrough device pathway
• Sec. 3053 Recognition of standards
• Sec. 3054 Certain Class I and Class II Devices
• “Classify an accessory based on the intended use”

36. FDA Class I devices exempt from 510(k) (PMN)
• FDA Notice (Docket No. FDA-2017-N-1610,
FR Doc. 2017-07468 dated April 7, 2017)
• 71 product codes
• most codes zero products cleared last five years
• 171 devices cleared
• 71 JJX, 44 JJY (analyze controls)
• None of the product codes from Part 888 Orthopedic devices

37. FDA Classify accessories according to use
• Some accessories lower risk profile than parent device
• FDA Final Guidance Medical Device Accessories-Describing
Accessories for Classification Pathway for New Accessory Types
• December 30, 2016
• Accessory: Finished device intended to support, supplement
and/or augment the performance of one/more parent devices
• De Novo Process for new accessory types
• Not classified under existing regulation
• Not subject of PMA or 510(k)
• No legally marketed predicate

38. FDA Post market Surveillance (PMS)
• Section 522 Federal Food, Drug, and Cosmetic Act
• FDA guidance issued May 16, 2016
• Issuance of 522 Order any time device lifecycle
• Manufacturer 30 days submit PMS Plan
• Manufacturer commence PMS study not later 15 months
• FDA website 522 PMS Studies
• 26 orders
• 5 orthopedic

39. FDA Policy and Political Administration
• Cybersecurity
• Guidance Postmarket Management
Cybersecurity, December 28, 2016
• J&J Animas OneTouch Ping Insulin Pump, Hospira Symbiq Infusion,
SJM implantable cardiac devices and Merlin@home Transmitter
• President Trump administration
• Executive Order (January 30, 2017): One new reg, revoke two regs
• FDA Commissioner Scott Gottlieb, M.D. (May 11, 2017)
• Anticipated repeal of Device Tax
• MDMA Survey (2017) 75% executives invest more in jobs and R&D

40. Questions?
Thank you for your time and attention
My information:
Evangeline Loh, Ph.D., RAC (US, EU)
EMERGO | Vice President, Global Regulatory Affairs