Agreement was reached on the eagerly awaited new EU In Vitro Diagnostic Regulations (IVDR) earlier this year. The IVDR will significantly change the way IVDs bear the CE mark, and it will include a completely new risk-based classification system. Now 80% of all IVDs will need to be certified by a notified body under the IVDR where as before, only 20% needed to under the IVD Directive. The new IVDR is expected to be formally published in late 2016 or early 2017, and there will be a five-year transition period to be compliant. Many forward thinking IVD companies are already developing their plans for compliance now to gain strategic advantages over their competitors. This presentation includes: -Why the European regulations are changing -What does the new regulation mean for IVD manufactures -How to classify your IVD using the new risk-based classification system -How to evaluate your existing clinical evidence to know if new studies will be needed to support your CE mark -An overview of all the most significant changes brought by the IVDR -What IVD manufactures can do to start preparing now Watch the presentation here: https://www.greenlight.guru/webinar/eu-in-vitro-diagnostic-regulations-ivdr

1. Presented by:
Richard Young
Managing Director, ABC
How to Prepare for the New EU IVD
Regulations

2. greenlight.guru- The Only eQMS Software Designed Exclusively for the Unique Needs
of the Medical Device Industry

3. About the Presenter
Richard Young (BSc (Hon) MSc, AIQA, ) is the Managing
Director of Acclaim Biomedical Consulting Ltd, a specialist
consulting company, based in Europe, which aims to
support developing companies through the hurdles of
global regulatory compliance, marketing and clinical
research.
Richard has worked in the Medical Device and In Vitro
Diagnostic markets for over 25years with apersonal focus on
regulatory compliance, process validation and risk
management.
Richard has been an active member of many groupsthrough his
time in industry,including representingindustry in the
formation of the “beyond compliance initiative” and spending
many years on the Eucomed Standards Focus Group as well as
standards groups such as LBI 35.
Over the last few years,his consultingactivities haveincluded a
large proportion of training and education including teaching at
Sheffield Hallam Universityin the UK on aPost Graduate
DiplomaCourse.

4. Today’s Agenda
Introduction 5 min.
Why are European Regs Changing 5 min.
What are the changes? 60 min.
Questions 20 min.

5. • Gain an overview of the text being voted on
• Why was the Regulation created?
• What does the new Regulation mean for manufacturers?
• Where are we now?
We will cover

6. • Critical Strategic Impacts
• Examine the risk based approach to classification
• Roles within the new regulation
• Strategy for Technical Documentation Preparation
• A revised STED format?
• Routine operations in the new environment
We will cover

7. • Address regulatory weaknesses (NBs, availability of information) to increase confidence
• Concerns from regulators – addressing concerns from the various scandals on the Medical
Device side of the industry
• PIP
• ASR
• International harmonization – implementing GHTF/IMDRF
• Problems on implementation – lack of resources and lack of harmonization at the EU level
• Shift from DG Enterprise to DG Sanco = shift of emphasis from business
• Universal implementation across member states as a regulation
Why do we need a new regulation?

8. • Since the IVDD was published there have been changes in technology
and experience with the legislation and its implementation.
• There will be more focus on
• Genetic tests
• Point of Care testing devices
• Companion Diagnostics
• Software as an IVD
• In house tests and testing services provided directly to patients
Future regulatory framework
8

9. • (11b) Devices that are used with a view to monitoring a treatment
with a medicinal product in order to ensure that the concentration of
relevant substances in the human body is within the therapeutic
window are not considered companion diagnostics.
From introductory text Companion Diagnostics

10. • Classification – Shift to at least 80% products
• Needing extensive NB involvement
• Scrutiny Process –MDCG
• Designated Reference Laboratories
• Qualified Person requirements
• Unique Device Identification mandated (UDI)
• STED Technical Documents
Major Impacts

11. • Clinical utility and performance closely specified
• Broad changes to Economic Operators Roles
• Authorise Representative Roles Broadened
• EU Declaration of Conformity
• Extensive used of Central IT systems (EUDAMED)
• PMS and Risk Management mandated
• Periodic safety update reports
Impacts (cont.)

12. Quantum leap in regulatory burden
Source: BSi

13. Impact of becoming a regulation
• Direct entry into force
• No transposition period
• i.e. no transposition into national law
• although there is a transition period
• Shorter timeline
• A regulation should result in more consistent application
IVDD will become a Regulation

14. • Original Goal was transposition in Q4 2014
• Most recent Drafts by Latvian Presidency June 2015
• Review Q4 2015
• Final Text agreed in May 2016
• Was due to be voted on in September 2016
Current program

15. • Council of the European Union
• Brussels, 12 June 2015
• (OR. en) 9770/15
• Interinstitutional File: 2012/0267 (COD)
• New version published in May 2016
• There were 24 Articles, there are now 90
• Now 14 Annex’s
The Text of the Regulation

16. Detail: The Articles &
Annex's

17. • I General safety and performance requirements
• II Technical documentation
• IIa Technical documentation on post-market surveillance
• III EU Declaration of conformity
• IV CE marking of conformity
• V Information to be submitted with the registration of devices and economic operators in
accordance with Article 23 and data elements of the UDI device identifier in accordance with
Article 22
• VI Minimum requirements to be met by Notified Bodies
• VII Classification criteria
The Annex's

18. • VIII Conformity assessment based on full quality assurance and design examination
• IX Conformity assessment based on type examination
• X Conformity assessment based on production quality assurance
• XI Minimum content of certificates issued by a notified body
• XII Clinical evidence and post-market follow-up
• XIII Interventional clinical performance studies and other clinical performance studies involving
risks for the subjects of the studies
• XIV Correlation table

19. Reference Labs and MDCG

20. • (a) to contribute to the assessment of applicant conformity assessment bodies and notified bodies;
• (b) to contribute to the scrutiny of certain conformity assessments
• (c) to contribute to the development of guidance aimed at ensuring effective and harmonised
• implementation of this Regulation, in particular regarding the designation and monitoring of notified bodies, application of
the general safety and performance requirements and conduct of the clinical evaluation by manufacturers, and the
assessment by notified bodies and the vigilance activities;
• (ca) to contribute to the to the continuous monitoring of the technical progress and assessment
• (cb) to contribute to the development of in vitro diagnostic medical devices standards and of Common Specifications;
• (d) to assist the competent authorities of the Member States in their coordination activities
• (e) to provide advice and assist the Commission
• (f) to contribute to harmonised administrative practice.
Article 76/77 Defines tasks for MDCG

21. • Designated through member states or EU Joint Research Centre
• Primarily for Class D but MS may request designation against CS for
Class C or other solutions adopted by the manufacturer
• Will have common standards and references and conduct peer
reviews
• Fees will be levied
Article 78 European Reference Laboratories

22. • Medical Device Coordination Group (MDCG). Chaired by the Commission, the group is composed
of representatives of Member States
• contribute to the assessment of applicant conformity assessment bodies and Notified Bodies;
• contribute to the scrutiny of certain conformity assessments under the scrutiny procedure;
• contribute to the development of guidance aimed at ensuring effective and harmonised
implementation of the regulation, in particular regarding the designation and monitoring of
Notified Bodies, application of the general safety and performance requirements and conduct of
the clinical evaluation by manufacturers and the assessment by Notified Bodies;
Article 7 CS via MDCG

23. • Very powerful addition to the regulations
• Continuous state of the art
• Un-budgeted expense of additional testing
• Significant impact on lead-times
COMMENT

24. Manufacturers Obligations

25. • Risk management is now explicit (1a)
• As is performance evaluation
• UDI compliance (3a)
• 10 year document retention after last product placed for certificates and
declarations
• STED now explicitly mentioned as an accepted format to provide requested data.
(Annex II)
• Authorised rep shall have this technical documentation “permanently available”
• A QMS system
Article 8 Manufacturer obligations

26. • Adoption of an ISO13485:2016 style system seems sensible.
• Could be quite a shift for some manufacturers
COMMENT

27. Economic Operators

28. • Article 11 Obligations for importers
• Obliged to verify devices are CE marked with an appropriate
declaration
• Authorised rep is in place
• Labelled correctly
• UDI
• Obligation to inform their CA if serious risk or falsified?
• Additional labelling identifying importer, or accompanying document
• Register according to article 23a
Economic Operators

29. • Article 12 Distributor obligations
• Same verification obligations as importers
• Register complaints
• Provide free samples to CA or grant access
• Check the importer and AR details are correct
• Sample as required

30. • Definition of responsibilities and contracts are critical
• Communications and document control also critical
• Major expense potentially to manage going forwards, treat as
approved distributors
• Consider certification requirements
• Note new definitions of requirements for Parallel Importers and re-
labellers
• Note definitions of obligations for in house diagnostics
COMMENT

31. Classification Rules

32. • Devices intended for the following purposes are classified as class D:
• Devices intended to be used to detect the presence of, or exposure to, a transmissible agent in blood, blood
components, cells, tissues or organs, or in any of their derivatives, in order to assess their suitability for
transfusion, transplantation or cell administration.
• Devices intended to be used to detect the presence of, or exposure to, a transmissible agent that causes a
life-threatening disease with a high or suspected high risk of propagation.
• Devices intended to be used to determine the infectious load of a life-threatening disease where its
monitoring is critical in the process of patient management.
Annex VII Classification rules Rule 1

33. • Devices intended to be used for blood grouping, or tissue typing to ensure the immunological
compatibility of blood, blood components, cells, tissue or organs that are intended for transfusion
or transplantation or cell administration, are classified as class C, except when intended to
determine any of the following markers:
• - ABO system [A (ABO1), B (ABO2), AB (ABO3)];
• - Rhesus system [RH1 (D), RHW1, RH2 (C), RH3 (E), RH4 (c), RH5 (e)];
• - Kell system [Kel1 (K)];
• - Kidd system [JK1 (Jka), JK2 (Jkb)];
• - Duffy system [FY1 (Fya), FY2 (Fyb)]
• in which case they are classified as class D.
Rule 2

34. • Devices are classified as class C if they are intended :
• (a) for detecting the presence of, or exposure to, a sexually transmitted agent;
• (b) for detecting the presence in cerebrospinal fluid or blood of an infectious agent without a high or suspected high risk
of propagation;
• (c) for detecting the presence of an infectious agent, if there is a significant risk that an erroneous result would cause
death or severe disability to the individual, foetus or embryo being tested, or to the individual's offspring;
• (d) for pre-natal screening of women in order to determine their immune status towards transmissible agents;
• (e) for determining infective disease status or immune status, if there is a risk that an erroneous result would lead to a
patient management decision resulting in a life-threatening situation for the patient or for the patient's offspring;
• (f) to be used as companion diagnostics;
Rule 3

35. • (fa) to be used for disease staging, if there is a risk that an erroneous result would lead to a patient management
decision resulting in a life-threatening situation for the patient or for the patient's offspring;
• (fb) to be used in screening, diagnosis, or staging of cancer;
• (g) for human genetic testing;
• (h) for monitoring of levels of medicinal products, substances or biological components, when there is a risk that an
erroneous result will lead to a patient management decision resulting in a life-threatening situation for the patient or for
the patient's offspring;
• (i) for management of patients suffering from a life-threatening disease or condition;
• (j) for screening for congenital disorders in the embryo or foetus;
• (k) for screening for congenital disorders in new-born where failure to detect and treat such disorders could lead to life-
threatening situations or severe disabilities.
Rule 3 Cont

36. • (a) Devices intended for self-testing are classified as class C, except for
devices for the detection of pregnancy, for fertility testing and for
determining cholesterol level, and devices for the detection of
glucose, erythrocytes, leucocytes and bacteria in urine, which are
Class B.
• (b) Devices intended for near-patient testing are classified in their
own right.
Rule 4

37. • The following devices are classified as class A:
• (a) products for general laboratory use, accessories which possess no critical characteristics,
buffer solutions, washing solutions, and general culture media and histological stains, intended
by the manufacturer to make them suitable for in vitro diagnostic procedures related to a specific
examination;
• (b) instruments intended by the manufacturer specifically to be used for in vitro diagnostic
procedures;
• (c) specimen receptacles.
Rule 5

38. • Devices not covered by the above-mentioned classification rules are
classified as class B.
Rule 6

39. • Devices which are controls without a quantitative or qualitative
assigned value are classified as class B.
Rule 7

40. • Majorly important for most products, a clear classification
rationale against these requirements should be a priority as it
defines organisational exposure
• Note specific additions including software
COMMENT

41. • STED LIKE FORMAT
• 1. DEVICE DESCRIPTION AND SPECIFICATION, INCLUDING VARIANTS AND
• ACCESSORIES
• 1.1. Device description and specification
• Including UDI
• 2. INFORMATIONSUPPLIED BY THE MANUFACTURER
• 3. DESIGN AND MANUFACTURING INFORMATION
• 3.1. Design information
• 3.2. Manufacturing information
• 4. GENERALSAFETY AND PERFORMANCE REQUIREMENTS
• 5. RISK/BENEFIT ANALYSIS AND RISK MANAGEMENT
Annex II Technical Documentation

42. • 6.1. Information on analytical performance
• 6.1.2. Analytical performance characteristics
• 6.1.2.1. Accuracy of measurement
• 6.1.2.2. Analytical sensitivity
• 6.1.2.3. Analytical specificity
• 6.1.2.4. Metrological traceability of calibrator and control material values
• 6.1.2.5. Measuring range of the assay
• 6.1.2.6. Definition of assay cut-off
• 6.1.3. The Analytical Performance Report according to Annex XII.
• 6.2. Information on clinical performance and clinical evidence. Performance Evaluation Report
• 6.3. Stability (excluding specimen stability)
• 6.3.1. Claimed shelf-life
• 6.3.2. In-use stability
• 6.3.3. Shipping stability
• 6.4. Software verification and validation
• 6.5. Additional information in specific cases
6. PRODUCT VERIFICATION AND VALIDATION

43. • TECHNICAL DOCUMENTATION ON POST-MARKET SURVEILLANCE
• 1.1. Post-market surveillance plan in accordance with Article 58b.
• 1.2. Post-market performance follow-up evaluation report in accordance with
Part B of Annex XII.
• 1.3. Periodic safety update report referred to in Article 58c. (for C and D)
• D submitted annually electronically
ANNEX IIa

44. • Major ongoing impact for all organisations
• Clinical and technical resources will be a premium!!!!
• Annual requirement, large portfolio impact
• Data is king!!
• These resources will be scarce given the need to experienced persons
across Notified Bodies and medical device sector in general
COMMENT

45. Essential Requirements

46. • Massive expansion in essential requirements especially in
labelling
• Will be particularly challenging retrospectively applying these to
existing products
• Internet documentation will be an important strategic option but
must be controlled and maintained
COMMENT

47. • How do we go forwards?..................
Implementation and evaluation

48. • There are some things we do know – start planning!
• No grandfathering for existing products 2 years on existing
certified products
• There will be rules based classification – how will this affect your
catalogue?
• Now is the time for teamwork – your RA colleagues will be
crucial
Analyse

49. • Classify Devices (any significant changes?)
• Collect Data
• Consider Authorised Representative
• Verify Distribution Chain
• Work with Notified Body
• Consider Qualified Persons
• Unique Device Identification
• Impact on global strategy

50. • Impact on Clinical Evidence program
• Consider product portfolio?
• Product pipeline and development cycle

51. Closing

52. Questions
Contact Acclaim Biomedical
Consulting for Your EU IVD
Regulation Training Needs
www.acclaimbiomedical.co.uk