Ivd webcast june 2012 for slide share

UL-UK

Notified Body – IVD

The Evolving IVDD Framework

Copyright ©2012 UL LLC UL and the UL logo are trademarks of UL LLC © 2012

Prepared: June 2012

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

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?

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.


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

Clinical evidence vs clinical utility

CLINICAL

EVIDENCE

CLINICAL

UTILITY

Scientific

Validity

Clinical

Performance Analytical

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


Classification of IVD products – will move from list based

approach to risk based (GHTF), i.e.

FROM

Annex II, list A

Blood screening products:

(HIV, HTLV, Hepatitis B, C, D)

Blood grouping reagents

Annex II, list B

CMV, Chlamydia, rubella, toxo

PSA, HLA typing, Trisomy 21

Self test devices, e.g. glucose

Anti-Duffy, anti-Kidd blood groups

TO

Class D – highest risk

Class C

Class B

Class A – lowest risk

Key benefit: Makes system future proof – covers new markers

…………… …new technologies, new applications

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:

2) Summary TEchnical Documentation (STED) will be required for all

products, with NB review before launch for class C & D.

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)

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

(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

RIS

K

Risk based classification

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

Class D

High Public Health Risk

and/or

High Individual Risk

Current Annex II, list A + others, e.g. CJD, Chagas?

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 that causes a life-threatening, often incurable, disease with a

high or currently undefined risk of propagation”.

“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

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)]”


Class C

High Individual Risk

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


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,

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

Rule 3


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


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


Class B

Moderate Individual Risk

and/or

Low Public Health Risk

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

Rule 6

“Devices not covered by the above mentioned classification rules are classified as Class B.”


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.


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

“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.

Design factors which address particular needs of the intended user population

Risk based classification – who decides?

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.

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.

6. If several classification rules apply to the same device the rule

resulting in the higher classification shall apply.

IMPLEMENTATION

The NB and/or Competent Authority will ensure consistency

of application (exact detail not yet determined)

See examples in next slide

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

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

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

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.

** Product for Performance Evaluation only is excluded

* Type Testing and verification may be used as an alternative

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

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

markers – kidney, sepsis?

X

Hospital acquired

infections, e.g. MRSA, C.

Diff., ESBL organisms

X

Other infections? -

Borrelia, Legionella,

Dengue, West Nile,malaria

(X)

Companion diagnostics X ?Some may be class D?

Clinical Genetic tests X

Vitamins, Hormones,

metabolic markers X ?Some may be class C?

Self tests (non-critical)

- pregnancy, fertility X

Specimen receptacles,

culture media?

X

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.

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

27

Thank you

28

Contact UL for CE Mark EU Notified Body services

E: [email protected]

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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