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1. UL-UK
Notified Body – IVD
The Evolving IVDD Framework
Prepared: June 2012
Copyright ©2012 UL LLC UL and the UL logo are trademarks of UL LLC © 2012

2. IVDD Regulations are undergoing revision
EUROPEAN COMMISSION
HEALTH AND CONSUMERS DIRECTORATE-GENERAL
Consumer Affairs Cosmetics and Medical devices
Brussels, 29 June 2010
REVISION OF DIRECTIVE 98/79/EC OF THE EUROPEAN
PARLIAMENT AND OF THE COUNCIL OF 27 OCTOBER 1998
ON IN VITRO DIAGNOSTIC MEDICAL DEVICES
PUBLIC CONSULTATION
 Plans to modernise and update the IVD regulations have
been under discussion since mid-2010
 Input sought from industry, healthcare institutes, regulatory
bodies and other concerned individuals
 Revision to IVD Directive to be published autumn 2012

3. What is under consideration?
 Exemption for “in-house” tests - to be maintained?
 Batch Verification requirements – should these be maintained?
 Common Technical Specifications (CTS) - should these be
maintained for high risk IVDs and/or be extended to other products?
 Genetic testing – does the position of genetic testing within the
Directive need clarification?
 Diagnostic services – ensure these are covered by directive
 Point of Care (PoC) – are specific requirements needed?
 Clinical evidence – strengthen requirements?
 Should we move to a Risk based classification of IVDs?

4. Current status on specific areas
 Exemption for “in-house” tests - to be maintained.
 accommodates rare disease testing in specialist centres,
specific genetic mutations, low volume tests which would not
sustain a commercial market, etc.
BUT
 Proposal to exclude highest risk products (class D)
(contentious – opposed by UK – concern this could remove a
wide variety of tests from virology and hamper development
of new tests , e.g. for HIV drug resistance )
 Batch verification – to be retained for highest risk products
+ sampling of batches for some class C?
 Common Technical Specification (CTS) – support for extending
CTS to other higher risk product areas.

5. Current status on specific areas
 Genetic testing – clarification that genetic tests with medical
purpose (e.g. not paternity, forensic) are within scope of IVDD
and should meet essential requirements.
 N.B. Direct to consumer testing services would also be
expected to meet CE marking requirements.
 Diagnostic services – as above, tests used for such services
would be expected to conform to essential requirements
 Point of Care – intent is to consider PoC similar to self-test
with focus on requirements around user population, user
environment, data handling / connectivity.
 Clinical evidence – proposals are to strengthen requirements
with regard to clinical evidence following GHTF guidance.
See: http://www.ghtf.org/sg5/sg5-proposed.html

6. Clinical evidence vs clinical utility
Scientific
Validity
CLINICAL CLINICAL
EVIDENCE Clinical UTILITY
Analytical Performance
Performance
Clinical utility of an IVD medical device supports clinical decisions for
patient management such as effective treatment or preventive strategies.
Clinical evidence. The manufacturer is expected to demonstrate scientific
validity and clinical performance, a manufacturer is not required to
demonstrate clinical utility for premarket conformity assessment purposes.
See: http://www.ghtf.org/sg5/sg5-proposed.html

7. Current status on specific areas
 Classification of IVD products – will move from list based
approach to risk based (GHTF), i.e.
FROM TO
Annex II, list A
Blood screening products: Class D – highest risk
(HIV, HTLV, Hepatitis B, C, D)
Blood grouping reagents Class C
Annex II, list B
CMV, Chlamydia, rubella, toxo Class B
PSA, HLA typing, Trisomy 21
Self test devices, e.g. glucose
Class A – lowest risk
Anti-Duffy, anti-Kidd blood groups
Key benefit: Makes system future proof – covers new markers
…………… …new technologies, new applications

8. Key impacts
For IVD manufacturers, the proposed move to a risk based classification
will have two key impacts.
1) Greater interaction with Notified Bodies (NB) will be required:
 Some products that are currently self-certified will fall into new risk
categories requiring NB involvement (particularly risk class C)
 Some manufacturer’s who previously may have had no involvement
with NBs will now need to interact with NBs for product approvals
(e.g. manufacturer’s of Point of Care assays for critical care markers)
2) Summary TEchnical Documentation (STED) will be required for all
products, with NB review before launch for class C & D.

9. How will the new risk based classification work?
Class D IVD - High Individual Risk and High Public Health Risk
e.g. HIV blood donor screening, HIV blood diagnostic, blood grouping
(Current Annex II, list A) + others, e.g. screening for Chagas disease?
Class C IVD – High Individual and/or Moderate Public Health
e.g. Blood glucose self-testing, HLA typing, PSA screening, CMV, Rubella
RISK
(Current Annex II, list B) + others, e.g. cardiac / cancer markers
Class B IVD – Moderate Individual and/or Low Public Health Risk
e.g. Vitamin B12, pregnancy self-testing, Anti-Nuclear Antibody
Class A IVD – Low Personal/No Public Health Risk
e.g. IVD instruments – e.g. Clinical Chemistry Analyser

10. Risk based classification
Class D High Public Health Risk
and/or
High Individual Risk
Includes IVDs that are used for:
 Screening of the blood supply and organ and tissue donations for
pathogens , e.g. IVDs for screening for HIV, HCV, HBV, HTLV
 Detecting the presence of, or exposure to, a transmissible agent that
causes a life-threatening illness with a threat to public health.
 Blood grouping or tissue typing to ensure compatibility where there
is an individual high risk, eg ABO, rhesus, Kell, Kidd, Duffy systems
Current Annex II, list A + others, e.g. CJD, Chagas?

11. Risk based classification – the rules
Class D
Rule 1
“Devices intended to be used to detect the presence of, or exposure to, a
transmissible agent in blood, blood components, cells, tissues or organs, in order
to assess their suitability for transfusion or transplantation,…or
Devices intended to be used to detect the presence of, or exposure to, a
transmissible agent that causes a life-threatening, often incurable, disease with a
high or currently undefined risk of propagation”.
Rule 2
“Devices intended to be used for…… the following markers ABO system [A
(ABO1), B (ABO2), AB (ABO3)]; Rhesus system [RH1 (D), RH2 (C), RH3 (E),
RH4 (c), RH5 (e)]; Kell system [Kel1 (K)]; Kidd system [JK1 (Jka), JK2 (Jkb)];
Duffy system [FY1 (Fya), FY2 (Fyb)]”

12. Risk based classification
High Individual Risk
Class C and/or
Moderate Public Health Risk
Includes IVDs that are used for:
 Detection of infectious agents with high individual risk
and transmissible agents with moderate public health risk:
e.g. STDs, hospital acquired infection – MRSA, C. Diff?
Congenital diseases in the feotus.
 Tests for patient management decisions in high risk
situations, e.g. cancer, heart disease, life threatening
infectious disease, monitoring of therapeutic drug levels
 Human genetic testing
 Self-testing, in determining a medically critical status
 Immune status in pregnancy

13. Risk based classification – the rules
Class C
Rule 2
“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, if not class D, are classified as Class C,
Rule 3
Devices are classified as Class C if they are intended for use:
a) in detecting the presence of, or exposure to, a sexually transmitted agent;
b) in detecting the presence in cerebrospinal fluid or blood of an infectious agent with a risk
of limited propagation;
c) in detecting the presence of, or exposure to, an infectious agent where there is a significant
risk that an erroneous result would cause death or severe disability to the individual or
foetus being tested, or to the individual's offspring

14. Risk based classification – the rules
Class C
Rule 3 (cont.)
d) in determining infective disease status or immune status, and where there is a risk that an
erroneous result will would lead to a patient management decision resulting in an imminent
life-threatening situation for the patient for the individual being tested, or to their offspring;
e) in screening for the selection of patients, i.e.
(i)Devices intended to be used as companion diagnostics; or
(ii)Devices intended to be used for disease staging; or
(iii)Devices intended for screening of, or in the diagnosis of cancer.
f) in human genetic testing;
g) to monitor levels of medicinal products, substances or biological components, when there
is a risk that an erroneous result will would lead to a patient management decision resulting in
an immediate life-threatening situation for the patient or for the patient's offspring;
h) in the management of patients suffering from a life-threatening infectious disease;
i) in screening for congenital disorders in the foetus

15. Risk based classification
Class A Low Individual Risk
and/or
Low Public Health Risk
Includes IVDs that are:
 Instruments intended by the manufacturer specifically to be
used for in vitro diagnostic procedures
 Specimen receptacles
Rule 5 – specifies these particular items as class A

16. Risk based classification
Class B Moderate Individual Risk
and/or
Low Public Health Risk
Rule 6
“Devices not covered by the above mentioned classification rules are classified as Class B.”
e.g. Includes IVDs that are used for:
 Self-testing, where results are not medically critical or require
confirmation (pregnancy testing, fertility testing, urine test strips)
 Purposes not covered by other Rules (blood gases, hormones,
vitamins, enzymes, metabolic markers), selective/differential
microbiological media, identification kits for cultured micro-organisms

17. Risk based classification – the rules
Additional Rules:
1.7. Rule 7
Devices which are controls without a quantitative or qualitative assigned value are classified as
Class B.
1.8. Rule 8
Stand alone controls with quantitative or qualitative assigned values intended for one specific
analyte or multiple analytes shall be classified in the same class as the device.
1.9. Rule 9
Calibrators intended to be used with a device shall be classified in the same class as the device.
1.10. Rule 10 (Software)
Where standalone software falls within the scope of the definition of an ‘IVD medical device’, it
shall be classified as follows:
-Where it drives a separate IVD medical device or influences the use of the device, the software
falls automatically in the same class as the device;
- Where it is not incorporated in an IVD medical device, it is classified in its own right in
accordance with the above-mentioned classification rules.

18. Risk based classification – the rules
Rule 4 (Point of Care):
“Devices intended for self-testing or near-patient testing shall be classified in
their own right.”
 Dependent on the risk presented by the particular analyte under test,…but also
 Design factors which address particular needs of the intended user population
“Devices intended for near-patient testing shall be designed and manufactured in such
a way that they perform appropriately for their intended purpose and should:”
- take into account the skills and the means available to the intended user
- account variation the user's technique and environment.
-provide information and instructions that is easy for the user to understand and apply.
-reduce the risk of error by the intended user in the handling of the device and, if
applicable, the specimen, and also in the interpretation of the results.
- include a procedure by which the intended user can verify that, at the time of use, the
product will perform as intended by the manufacturer.

19. Risk based classification – who decides?
IMPLEMENTATION
4. The manufacturer shall take into consideration all the rules in order
to establish the proper classification for the device based on its
intended use purpose.
 The NB and/or Competent Authority will ensure consistency
of application (exact detail not yet determined)
5. Where a device has multiple intended purposes stated by the
manufacturer, which place the device into more than one class, it shall
be classified in the higher class.
 See examples in next slide
6. If several classification rules apply to the same device the rule
resulting in the higher classification shall apply.

20. Risk classification – multiple Intended Use
“If there are multiple intended uses the device shall be classified in the higher class”.
1) hCG (human chorionic gonadotropin)
a. Elevated in pregnancy, basis of pregnancy tests (class B)
b. Also elevated in some germ cell tumours, e.g. gestational
trophoblastic disease, risk to the individual much higher (class C)
Specifically exclude tumour marker use from Intended Use if not supported?
2) VZV (Varicella Zoster Virus) – IgG / IgM (chickenpox and shingles)
a. For use in epidemiological studies, childhood illness (class B)
b. Much more serious / potentially fatal in immunocompromised hosts.
(class C)
 Testing pre-/post-vaccination status of healthcare workers
 Outbreak management for immunocompromised patients
- Consider reduction or withdrawal of immunosuppressive therapy
- Consider administration of ZIG* or antiviral therapy, e.g. acyclovir

21. Practical impact – specific requirements
 STED = Summary Technical Documentation will be required
• Technical documentation is to be prepared for all IVDs according
SG1(PD)/N063 (early draft)
• For Class C and D – review of STED required prior to launch:
- Submission of the STED and Declaration of Conformity
- Pre-Market Review by the Regulatory Authority or the Conformity
Assessment Body (3rd party) of documentation and performance
of the product to ensure Essential Principles and claims are met.
- May be reviewed offsite or at on-site pre-market audit

22. Practical impact – STED
The STED does not represent the full technical documentation
(controlled under QMS) – Tech File-Lite?
• Depth and detail may be dependant on classification and risk, whether it
is novel technology or already marketed. Expectations:
 General description and list of specified features
 Set of labels and list of language variants
 Summary of technical docs concerning design and manufacturing
 Essential Requirement Checklist
 Summary of risk analysis and mode of control
 Summary of verification and validation studies – Performance
Evaluation

23. Conformity assessment – design examination*
1. Prior to placing a device on the market, manufacturers shall undertake an
assessment of its conformity
2. Class D devices - full quality assurance, design dossier examination and product
verification.
3. Class C devices - full quality assurance and design dossier examination
4. Class B devices - production quality assurance as specified in Annex… after
drawing up the technical documentation.
5. Class A devices - may issue a declaration of conformity after drawing up the
technical documentation (i.e. self-declaration)
6. Self-testing and near-patient testing the manufacturer shall, in addition to the
relevant conformity assessment procedure, fulfil the supplementary requirements
set out in Annex [full quality assessment], Section 5.2.1.
* Type Testing and verification may be used as an alternative
** Product for Performance Evaluation only is excluded

24. Practical impact
 Biggest change will be for Risk Class C
 Many categories of product previously without NB
involvement will fall into this category, e.g.
 Much wider range of infectious disease tests, e.g. hep A & D,
borrelia, TB, MRSA, C. Diff., gonorrhoea? VZV, EBV?
 Cancer markers, cardiac markers. Renal markers?
 Markers for above on PoC devices, not previously subject to
NB involvement
 Human genetic tests

25. Potential risk classification groupings
IVD or Cluster IVDs Class D Class C Class B Class A Comment
HIV, HTLV X
Hepatitis B, C. X
CJD, Chagas X
Tumor markers X
Cardiac markers X
Other critical care X
markers – kidney, sepsis?
Hospital acquired X
infections, e.g. MRSA, C.
Diff., ESBL organisms
Other infections? - (X)
Borrelia, Legionella,
Dengue, West Nile,malaria
Companion diagnostics X ?Some may be class D?
Clinical Genetic tests X
Vitamins, Hormones, X ?Some may be class C?
metabolic markers
Self tests (non-critical) X
- pregnancy, fertility
Specimen receptacles, X
culture media?

26. IVDD changes - summary
 When will the changes happen?
 Formal proposals to be submitted autumn 2012
 Implementation expected late 2013/14
 2yr transition period for industry (2016?)
 What will be the impact?
 Greater diversity of products requiring NB involvement
 What do you need to do to prepare?
 Consider which of your products will fall into which risk categories
 Consider how you will work with the Notified Body to meet requirements
 Plan ahead / prepare early
 What will UL be doing?
 We will use the extensive and diverse industry experience of our in-house staff,
and our network of clinical specialists, to help ease the transition for our clients.

27. UL Services for CE Marking
www.ul.com/medical-cemark
Notified Body for IVD and MDD
Batch Testing
Integrated Audits to include ISO 13485 under CMDCAS,
ISO 14971, Japan PAL, and more.
Own Brand Labeling
Training
Biocompatibility testing
Sterility Validation
Safety, EMC, Wireless RF Testing and Certification
Usability and Human Factors testing
Risk Management gap analysis
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28. Thank you
Contact UL for CE Mark EU Notified Body services
E: Medical.Inquiry@UL.com
W::.ul.com/medical-cemark
Download UL’s Notified Body Toolkit – a 27 page reference
document on the EU Notified Body system at
www.ul.com/medical-cemark under “Additional Resources”
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