An introduction to conformity assessment procedures for medical devices, good manufacturing practice (GMP), some of the problems commonly experienced by sponsors and TGA, and helpful hints.

1. Conformity Assessment Evidence
A Regulator’s Perspective
Dr Elizabeth McGrath
Medical Devices Branch
Medical Devices and Product Quality Division
TGA
2017 Device Sponsor Training Day

2. Presentation overview
Definition & Background
Important Concepts
The Evidence
Change is Coming
Conformity Assessment Evidence 2

3. What is conformity assessment?
Conformity Assessment: The systematic examination of evidence
generated and procedures undertaken by the manufacturer, under
requirements established by the Regulatory Authority, to determine
that a medical device is safe and performs as intended by the
manufacturer and, therefore, conforms to the Essential Principles of
Safety and Performance for Medical Devices. - GHTF
Conformity Assessment Evidence 3

4. What is conformity assessment?
• All Devices, unless exempt, Must Undergo Conformity
Assessment according to their risk classification.
• All Medical Device Manufacturers Must Undergo Conformity
Assessment certification for their QMS.
• All Devices must comply with the applicable essential
principles.
Conformity Assessment Evidence 4

5. CA certification can either be from TGA or
from a EU notified body
• Certain Devices and their Manufacturers Require TGA
certification
• Notified Bodies are designated (authorised) by Government
Regulators in the EU to certify conformity assessment
procedures (examine safety and performance information,
assess clinical data)

6. TGA conformity assessment required
For a device that… Regulation
Contains tissues of animal origin (non-viable) 4.1(a)
Contains tissues, cells or substances of microbial or
recombinant origin
4.1(b)
Contains stable derivatives of human blood or human
plasma
4.1(c)
Incorporates a substance that is considered to be a
medicine
4.1(d)
Is a Class 4 IVD 4.1(e)
Is a Class 4 in-house IVD (unless certain conditions met) 4.1(f)
6

7. Important concepts
Conformity Assessment Evidence 7

8. Important concept 1
“Begin at the beginning,” the King
said, very gravely, “and go on till
you come to the end, then stop.”
- Lewis Carroll
Regulator
Conformity Assessment Evidence 8

9. Important concept 1 (continued)
DEVICE LIFECYCLE
Conformity Assessment Evidence 9

10. Important concept 2
preparation
PREPARATION
PREPARATION
Conformity Assessment Evidence 10

11. Evidence
Conformity Assessment Evidence 11

12. The essential principles
• Schedule 1 – Medical Devices
Regulations
• Set out requirements relating to the
safety and performance of the
medical device
Conformity Assessment Evidence 12

13. Essential principles for safety and
performance
1. Use of medical devices not to compromise
health and safety
2. Design and construction of medical devices to
conform to safety principles
3. Medical devices to be suitable for intended
purpose
General principles
Conformity Assessment Evidence 13

14. Essential principles for safety and performance
4. Long-term safety
5. Medical devices not to be adversely affected by
transport or storage
6. Benefits of medical devices to outweigh any side
effects
General principles
Conformity Assessment Evidence 14

15. Essential principles for safety and performance
Principles about design and construction
7. Chemical, physical and biological properties
8. Infection and microbial contamination
9. Construction and environmental properties
10.Medical devices with a measuring function
11.Protection against radiation
Conformity Assessment Evidence 15

16. Essential principles for safety and performance
12. Medical devices connected to or equipped with
an energy source
13. Information to be provided with medical devices
14. Clinical evidence
15. Principles applying to IVD medical devices only
Principles about design and construction
Conformity Assessment Evidence 16

17. Demonstrating
compliance
Conformity Assessment Evidence 17

18. Demonstrating
compliance
https://www.tga.gov.au/book-page/part-1-general-requirementsConformity Assessment Evidence 18

19. Format
• Should be easy to understand/find where
information is located!
• Documents should be searchable
• Guidance on structuring a submission
– https://www.tga.gov.au/tga-pilot-imdrf-table-
contents-medical-device-
Conformity Assessment Evidence 19

20. Changes are on the way
Conformity Assessment Evidence 20

21. Aligning the EPs and GSPRs
Australian EPs @ European ERs
• Annex 1 of the new EU regulations
• Includes 23 ‘General Safety and
Performance Requirements’ (GSPR)
replacing ‘Essential Requirements’ (ER)
• Based on the GHTF Essential Principles
2012
Conformity Assessment Evidence 21

22. New requirements in the GSPR
GSPR 10 Substances:
§ Justification for CMR or endocrine-disrupting substances, when present >
0.1% (w/w);
§ Guidelines on phthalates;
§ Labelling requirement on devices and packaging for above substances.
– Reduce risks linked to the size and properties of particles released into
patient’s or use’s body, particularly nanomaterials.
Requirements regarding design and manufacture
Conformity Assessment Evidence 22

23. New requirements in the GSPR
• GSPR 11 – Infection and microbial contamination
– Reduce risks from unintended cuts and pricks;
– Design to facilitate safe cleaning, disinfection and/or re-sterilisation;
• GSPR 12 – Devices incorporating a substance considered to be a
medicinal product and devices that are composed of substances or of
combination of substance that are absorbed by or locally dispersed in the
human body
– Verified with the specified requirements laid down in Directive 2001/83/EC;
– Evaluation of ADME profile, local tolerance, toxicity, interaction with other
devices.
Requirements regarding design and manufacture
Conformity Assessment Evidence 23

24. New requirements in the GSPR
• GSPR 14 – Construction of Devices and Interaction with Environment
– designed and manufactured in such a way that adjustment, calibration, and
maintenance can be done safely and effectively.
– be designed and manufactured in such a way as to facilitate their safe
disposal and the safe disposal of related waste substances by the user,
patient or other person.
– manufacturers shall identify and test procedures and measures as a result of
which their devices can be safely disposed after use. Such procedures shall
be described in the instructions for use.
Requirements regarding design and manufacture
Conformity Assessment Evidence 24

25. New requirements in the GSPR
• GSPR 17 - Software
– Key changes:
§ software shall be developed and manufactured in accordance with the state
of the art taking into account the principles of development life cycle, risk
management, including information security, verification and validation.
§ requirements for software and mobile computing platforms – considerations
for size and contrast ratio of screen, level of light and noise in environment.
§ minimum hardware requirements, IT network characteristics, IT security
measures.
Requirements regarding design and manufacture
Conformity Assessment Evidence 25

26. GSPR Chapter II
• GSPR 18 - Active devices and devices connected to them
– Key improvements:
§ Immunity to electromagnetic interference;
• (currently– only minimise electromagnetic field generation)
§ Protect, as far as possible, against unauthorised access that could hamper
the device from functioning as intended
Requirements regarding design and manufacture – GSPR 10 - 22
Conformity Assessment Evidence 26

27. New Requirements in the GSPR
• GSPR 22 – Protection against the risks posed by medical
devices intended by the manufacturer for use by lay persons
− Important for home use devices;
− Safety, performance, design and manufacture considering the
skills and means available to the lay person, easy to understand
information.
Requirements regarding design and manufacture
Conformity Assessment Evidence 27

28. New Requirements in the GSPR
• GSPR 23
– Numerous Changes, Including
– a requirement for UDI
– in the case of implantable devices, the overall qualitative and quantitative
information on the materials and substances to which patients can be exposed;
– a notice to the user and/or patient that any serious incident that has occurred in
relation to the device should be reported to the manufacturer and the competent
authority of the Member State in which the user and/or patient is established;
– Implant card and information/warnings for patients
Requirements regarding information supplied with a device
Conformity Assessment Evidence

29. Conformity Assessment Evidence 29

31. Conformity Assessment Evidence
A SPONSOR’S PERSPECTIVE: PRACTICE & TIPS
Elizabeth Van Den Akker
Sponsor Information Day
11 | October | 2017

32. Concept 1: Begin at the beginning & go on till
you come to the end…….
Conformity Assessment Evidence: A Sponsor’s Perspective

33. Conformity Assessment Evidence: A Sponsor’s Perspective
Concept 1: Begin at the beginning and go on…..
October 11, 2017
Conformity Assessment Evidence
Sponsor Information Day 33

34. Conformity Assessment Evidence: A Sponsor’s Perspective
Concept 1: Begin at the beginning and go on…..
34
Early engagement
§ Become involved as early as possible in the product development to address EPs
§ Essential where classification differences exist in different jurisdictions
§ Proceduralise operational requirements in Quality Management System (QMS)
Device Lifecycle Changes
§ Establish formal change impact assessment process to determine CA evidence
requirements
§ Have written procedures as part of QMS to cater for change management, and to guide
their related decision making
§ Classify change(s) to determine if notifiable to the TGA
§ Clearly define design & process changes, their impact on EPs and any additional
associated risks
§ Ensure changes are validated or a justification for non-validation is available
Sponsor Information Day
PRACTICE
&TIPS
https://www.tga.gov.au/publication/substantial-changes-affecting-tga-
conformity-assessment-certificate-and-transfers-certificates
October 11, 2017

35. Conformity Assessment Evidence: A Sponsor’s Perspective
Concept 1: Begin at the beginning and go on…..
Post-market
§ Establish effective post-market reporting & analytics systems
§ Post-market data provides evidence of ongoing compliance with EPs
Conformity Assessment Certification Currency
§ Recertification to maintain TGA CA certification currency
§ Ongoing TGA audits of manufacturing facilities
Sponsor Information Day
PRACTICE
&TIPS
October 11, 2017 35

36. Concept 2: Preparation
Conformity Assessment Evidence: A Sponsor’s Perspective

37. Conformity Assessment Evidence: A Sponsor’s Perspective
Concept 2: Preparation
i
Information Resources
§ SME Assist for start-ups and small to medium enterprises
§ Pre-submission meetings with the TGA for complex CA submissions
§ TGA Guideline publications (e.g. Clinical Evidence Guidelines, Substantial Changes
to TGA Conformity Assessment Certificates, ARGMD)
§ TGA website
§ Industry Associations
Collating Conformity Assessment Evidence
§ Review CA evidence supplied by the manufacturer and identify any gaps in compliance
with EPs
§ Ensure compliance to the TGA guideline publications
§ Wherever possible demonstrate EP compliance with recognised standards published by
an Australian or International Standards Agency (e.g. ISO standards)
PRACTICE
&TIPS
Sponsor Information Day October 11, 2017 37

38. Conformity Assessment Evidence: A Sponsor’s Perspective
Concept 2: Preparation
Collating CA Evidence (cont.)
§ Where alternate or earlier versions of standards used by manufacturer include justification
and, if relevant, include any additional information/data that bridges identified gaps
§ Consider trends in TGA questions emerging from previous TGA conformity assessments of
similar device(s)
Dossier format
§ General dossier requirements at
§ Packaging option: PDF Portfolio
https://www.tga.gov.au/book-page/part-c-formatting-your-dossier#conformity
PRACTICE
&TIPS
Sponsor Information Day October 11, 2017 38

39. Conformity Assessment Evidence: A Sponsor’s Perspective Sponsor Information Day 11 | October | 2017