Prequalification TeamRISK BASED CLASSIFICATION OF
DIAGNOSTICS FOR WHO PREQUALIFICATION
Prequalification of Diagnostics

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Table of Contents
1. Introduction ................................................................................................................................. 4
2. Intended Audience and Scope ..................................................................................................... 4
3. Definitions .................................................................................................................................... 4
4. WHO Prequalification of Diagnostics Requirements ................................................................... 4
5. The WHO Prequalification Risk-Based Assessment Approach ................................................... 6
6. Determining the Risk Classification for WHO Prequalification .................................................... 8
7. Using Risk Class to Determine Level of WHO Prequalification of Diagnostics Assessment ...... 13
8. Conclusion .................................................................................................................................. 14
9. References.................................................................................................................................. 14
Annex 1. GHTF Classification Rules (refer to GHTF/SG1/N045:2008 “Principles of In Vitro
Diagnostic (IVD) Medical Devices Classification”) ........................................................................... 15

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1. Introduction
The WHO Prequalification of Diagnostics Programme determines the depth of its prequalificationassessment of IVDs for priority diseases according to the risk posed by the product to the health ofthe public and/or an individual in WHO Member States, and to the risk of an incorrect result
arising from the use of the IVD in that setting. Therefore the level of assessment aims to provide
reasonable assurance of the safety, quality and performance of IVDs. This rational, risk-based
assessment approach ensures the goal of timely access to safe and effective IVDs and the judicious
use of WHO resources.
This document describes how WHO utilizes an internationally accepted regulatory mechanism todetermine the stringency of assessment of products submitted to the WHO Prequalification of
Diagnostics Programme. The risk based assessment approach utilizes a set of classification rulesthat will place IVDs into 4 risk classes. The higher the risk class, the greater the stringency ofassessment that is applied to a product. This approach is also used by regulatory authorities todetermine the level of pre-market control to apply to IVDs.

2. Intended Audience and Scope
This document is intended for use by WHO staff to determine the risk classification of IVDs
accepted for WHO prequalification to guide the depth of assessment. It provides information thatcan be used by regulatory authorities intending to regulate IVDs on how the WHO applies theclassification rules, and it informs manufacturers and other stakeholders of the risk-based
approach undertaken by the WHO Prequalification of Diagnostics Programme to determine thestringency required for the WHO prequalification assessment of a IVD product.

3. Definitions
In vitro diagnostic medical device (IVD) (1)A medical device, whether used alone or in combination, intended by the manufacturer for
the in-vitro examination of specimens derived from the human body solely or principally toprovide information for diagnostic, monitoring or compatibility purposes. IVD medical
devices include reagents, calibrators, control materials, specimen receptacles, software, andrelated instruments or apparatus or other articles.
Risk (1)Combination of the probability of occurrence of harm and the severity of that harm.

4. WHO Prequalification of Diagnostics Requirements
WHO requires manufacturers of IVDs undertaking WHO Prequalification to have objective
evidence of the safety, quality, performance, benefits and risks, and operational utility of the IVD.
This evidence is the subject of the assessment, which determines if the IVD conforms to the

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Essential Principles of safety and performance when used in WHO Member States (refer GHTF
document “Essential Principles of Safety and Performance of Medical Devices”. (2)Evidence of safety, quality and performance can be grouped into 4 assessable elements:
4.1.
Technical Documentation
Manufacturers of all classes of IVDs are expected to demonstrate conformity of the IVD to the
Essential Principles of safety and performance of IVDs (2) through the preparation and holding oftechnical documentation that shows how each IVD was developed, designed and manufactured
together with the descriptions and explanations necessary to understand the manufacturer’s
determination with respect to such conformity. This technical documentation is updated asnecessary to reflect the current status, specification and configuration of the IVD. Subsets of thisdocumentation should be available for assessment in the format of a product dossier. WHO
recognizes the Global Harmonization Task Force (GHTF) recommendations for dossier content for
IVDs. (3)
4.2.
Performance and operational utility
WHO expects that an IVD performs as it is intended to (e.g. sensitivity and specificity, precision,
trueness of measurement, etc.) when used by operators in WHO Member States. Special
considerations for the variable conditions encountered in such diverse settings must be
considered in the design and development of the IVD. Such considerations may include use of the
IVD in areas with extremes of temperature and humidity, and with operators of various skill levels.
The manufacturer should have considered these aspects in a thorough risk assessment process
and hold evidence through testing and other means that the benefits of using the IVD in a WHO
Member State will outweigh any residual risk.
4.3.
Quality Management Systems
An appropriate quality management system must be in place that, for high risk IVDs, includes in its
scope control of the design and development and manufacture of the IVD. WHO refers to ISO
13485:2003 (Medical devices -- Quality management systems -- Requirements for regulatory
purposes) and the United States Food and Drug Administration Quality System Regulations (Codeof Federal Regulations Title Part 820) as acceptable standards for the quality management
standards of IVDs. These quality management systems are recognized internationally as bestpractice.
4.4.
Post Market Surveillance
The manufacturer must have a system for post-market surveillance. Prior to placing the producton the market, the manufacturer will put in place, as part of its quality management system, aprocess to assess the continued safety and performance throughout the lifecycle of the IVD. This
process will include having procedures for, at a minimum, complaint handling, vigilance reporting,procedures for recalls, and corrective and preventive action.

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5. The WHO Prequalification Risk-Based Assessment Approach
The risk posed by the use of an IVD can be categorized or classified according to an internationallyaccepted classification system that was created by the GHTF and continues to be maintained by
the International Medical Device Regulators Forum (IMDRF). (4) For additional information on
using this risk-based approach for the evaluation of IVDs, see PQDx_152 “A Risk Based Assessment
Approach”.
The GHTF created the risk classification system to determine the level of pre-market regulatory
control that is required for an IVD, with the purpose that these controls are sufficient for eachclass to safeguard the health and safety of patients, users and other persons. The outcome of thesystem is to group IVDs into one of four risk classes (A to D), as shown in Table 1 below.
Table 1: The Risk Classes
Classification

Individual Health Risk

Public Health Risk

Class A IVD

Low

and

Low

Class B IVD

Moderate

and

Low

Class C IVD

High

and/orModerate

Class D IVD

High

and

High

WHO has adopted the GHTF classification system to guide the level of stringency and scope of theassessment required for an IVD product undergoing WHO prequalification. WHO applies thisclassification system by considering the risks posed when the IVD is used in WHO Member States,with particular emphasis on resource-limited settings. Several critical aspects are specific toresource limited settings compared to risk classification when applied in many high income
countries. These include differences in endemicity and prevalence of various diseases, theavailability of follow-up or reference testing, and significant differences in the level of training ofprofessional staff utilizing the IVD. This means that the risk classification of an IVD in resource
limited settings can be considerably different (usually posing higher risk) from that whenevaluated for use in a high income setting.
Table 2 below identifies the review procedures that WHO uses to assess each of the GHTF risk
classes, to illustrate how the assessment activities would differ if products in these risk classes
would be assessed for prequalification. This is consistent with GHTF recommendations that thedepth and timing of the review of the dossier is influenced by the class of the IVD, its complexity,
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Table 2: Summary of WHO Prequalification Assessment Activities by IVD Risk Class
WHO PQ
Requirement

Assessment
Element

Assessmentof Quality

Quality
Management
SystemManufacturer
Responsibility
Establish andmaintain a full
QMS

Class A*
Inspection
normally not
required

WHO PQ Assessment
Class B*Class C
Have confidence Confirm that athat a current
current andand appropriate appropriate
QMS is in place
QMS is in placeor otherwise
or otherwise
conduct a QMS
conduct a QMS
inspection.
inspection.
Confirm that a
Confirm that acurrent andcurrent andappropriate
appropriate
complaintcomplaint
reportingreportingprocedure is inprocedure is inplace as part ofplace as part of
the QMS.
the QMS.

Post-market
Surveillance

Establish andmaintain acomplaint
reportingprocedure

May inspecttoinvestigate
specificsafety or
performance
concerns.

Assessmentof IVD
manufacturer’s claims ofsafety &performance

Technical
Documentation

Establish andkeep up to date,technical
documentation,and prepare
and submit adossier for
review

Only subsets
ofinformation
to bereviewed todetermine
conformity
to Essential
Principles.

Only subsets of
information to
be reviewed todetermine
conformity to
Essential
Principles.

Assessmentof
performance– Laboratory
Evaluation

Laboratory
Evaluation

Undertakeperformancestudies should
support the safe
use andperformance of
the assay.

Nolaboratory
evaluation
undertaken.

Laboratory
evaluation
undertaken in
only exceptional
cases identified
by MemberState needs)

Undertake areview of the
product dossier
sufficient todetermine theproduct is safe
and should
perform as
intended,includingassessment ofconformity to
Essential
Principles. Also
ensure that thebenefit of using
the IVD in a
WHO Member
State outweighs
the risks
involved.
Laboratory
evaluation
undertaken in
the majority ofcases toindependently
evaluate
performanceand operational
characteristics.

Class D
Confirm that acurrent andappropriate
QMS is in placeor otherwise
conduct a QMS
inspection.
Confirm that acurrent andappropriate
complaint
reportingprocedure is inplace as part of
the QMS.

Undertake an indepth review ofthe productdossier todetermine theproduct is safe
and should
perform as
intended,includingassessment ofconformity to
Essential
Principles. Also
ensure that thebenefit of using
the IVD in a
WHO Member
State outweighs
the risks
involved.
Laboratory
evaluation
undertaken to
independently
evaluate
performanceand operational
characteristics.

*At time of print, IVDs undergoing WHO Prequalification do not fall into Classes A and B.

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The GHTF Principles of Conformity Assessment for In Vitro Diagnostic (IVD) Medical Devices
document on which Table 2 is based, recommends that the documentation submitted in a productdossier for a Class C IVD will contain less detailed information than the documentation for a Class
D device. (5) For WHO purposes, the main difference for a Class D dossier would be in the level ofdetails submitted in the clinical/performance data. However, the document also notes that
although a regulatory authority/conformity assessment body should not normally require moreelaborate information for a Class C IVD, this does not preclude the regulatory authority/conformity
assessment body from requesting such information in specific cases. WHO exercises this option for
diagnostics that present additional risk as a result of their role in clinical decision-making and theareas of use (see discussion of specific tests below).

6. Determining the Risk Classification for WHO Prequalification
GHTF has generated a set of risk classification rules that are used to assign a particular IVD to aparticular risk class. (4) When applying these rules to determine the risk class, WHO will also take
into consideration not only the rule specific to a given IVD, but also how the IVD is generally usedin clinical and laboratory (or non-laboratory testing settings) practice in its Member States. Thisuse, along with other factors particular to Member States such as the variable technical level
and/or training of the operator of the IVD, may result in a WHO risk classification higher than thatrecommended in existing GHTF risk classification rule examples.
The following subsections describe how IVDs are classified by WHO with reference to the relevant
GHTF Classification Rules (see Annex 1), and describes the reasoning for the risk classification
ultimately assigned by WHO for each type of IVD. Whereas this document identifies specificexamples of existing technologies, as new technologies arise WHO will consider the risk that theypose, which will in turn dictate the extent of the documentation to be submitted and the scope of
WHO review .
6.1.

How WHO classifies an HIV serology test (including rapid diagnostic test, enzyme
immunoassays and other formats)a. Applicable classification rule and classification:
Rule 1 – Class D (specifically identifies HIV IVDs for diagnosis and those forscreening of blood and blood products for transfusion as Class D)
b. Intended use:
For detection of antibodies to HIV-1/2 as an aid in the diagnosis of HIV infection.
For screening of blood and blood products.
c. Where the test is likely to be used in Member States:
For laboratory-based testing: In level II (district), level III (provincial or regional), andlevel IV (national) laboratories.

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For point-of-care testing: In level I (primary) laboratories and level 0 communitybased settings, including outside of a traditional laboratory setting (minimal
infrastructure, without temperature control).
d. Expertise of likely user in WHO Member States:
For laboratory-based testing: Trained laboratory professionals.
For point-of-care testing: Variable but likely to be minimal, if any, technicalbackground. Minimal training, if at all.
e. Clinical importance of test result:
Test results are used to decide on whether to enter individuals into treatment andcare using valuable resources (medicines, laboratory monitoring, clinical expertise,etc.) that may be in very limited supply.
Test results are used to determine if blood or blood products are safe to betransfused.
f. Impact of test result in WHO Member States:i.

Public health impact of incorrect result: High
False negative result: High potential for onward transmission of HIV infection
on a large scale, when such a result occurs in screening for transfusion.
False positive result: Unnecessary use of limited resourcesii.

Individual health impact of incorrect result: High
False negative result: Delay in entry into treatment and care associated withpoorer health outcomes
False positive result: Misdiagnosis of HIV infection, risks associated with side
effects of treatment, psychological impact on the patient and the family.

6.2.

How WHO classifies a malaria rapid diagnostic test

a. Applicable classification rule and classification:
Rule 3 – Class C
b. Intended use:
For detection of antigen produced by the Plasmodium species parasite as an aid in
the diagnosis of malaria.
c. Where the test is likely to be used in WHO Member States:
For point-of-care testing: In level I (primary) laboratories and level (0) communitybased settings, including outside of a traditional laboratory setting (minimal
infrastructure, without temperature control).
d. Expertise of likely user in WHO Member States:
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Minimal, if any, technical background. Minimal training, if at all.
e. Clinical importance of test result:
Test results are used to decide on whether to enter individuals into care using
valuable resources that may be in very limited supply.
f. Impact of test result in WHO Member States:i.

Public health impact of incorrect result: Moderate
False positive result: Unnecessary use of limited resources (medicines), possible
contribution to drug resistance due to over-treatment
False negative result: Possible transmission of the disease, economic impact.

ii.

Individual health impact of incorrect result: High
False negative result: Not initiating treatment for an infected individual canhave profound implications for individual health, possibly leading to death
False positive result: Risks associated with side effects of treatment

Additional note: The epidemiology of malaria and the resultant public health response tothis infection are very different in a number of WHO Member States than in most countries
with established regulatory authorities (with concomitantly well developed health systems).
In high income countries, malaria is not endemic and rarely affects more than a select few
who typically acquired the disease from travel to or residing in an endemic region.
Individuals in these countries generally undergo extensive laboratory investigations
including other tests (e.g. molecular techniques) for malaria before a definitive diagnosis is
made. As such, in many jurisdictions with established regulatory systems, malaria rapid
diagnostic tests typically are assigned a lower risk classification due to the difference inhazards associated with the use of the test.
6.3.

How WHO classifies a HIV qualitative nucleic acid technology (including laboratorybased, point-of-care and near to point-of-care testing)a. Applicable classification rule and classification:
Rule 1 – Class D
b. Intended use:
As an aid in the diagnosis of HIV infection, including in infants.
c. Where the test is likely to be used in Member States:
For laboratory-based or near to point-of-care testing: In a level III (provincial orregional) or level IV (national) laboratories. In addition, in level II (district)laboratories for near to point-of-care.
For point-of-care testing: In level I (primary) laboratories and level (0) communitybased settings, including outside of a traditional laboratory setting (minimal
infrastructure, without temperature control).
d. Expertise of likely user in WHO Member States:

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For laboratory-based and/or near to point-of-care testing: Trained laboratory
professionals.
For point-of-care testing: Variable but likely to be minimal, if any, technicalbackground.
e. Clinical importance of test result:
Test results are used as a possible sole basis for determining whether infants are
infected with HIV and therefore entering into care and beginning antiretroviraltherapy.
f. Impact of test result in WHO Member States:i.

Public health impact of incorrect result: High
False positive result: Unnecessary use of limited resources (medicines,
laboratory monitoring, clinical expertise, etc.).

ii.

Individual health impact of incorrect result: High
False negative result: Not treating an infected infant can have profound
implications for individual health, possibly leading to death.
False positive result: Risks associated with side effects of treatment, especiallyin infants. Incorrect de facto diagnosis of infant’s mother who may or may not
be aware of her HIV status.

Additional note: An assay for EID is considered to be Class D because it is an HIV assay thatis used as an aid in the diagnosis of HIV infection, consistent with Rule 1, even though the
expected public health impact of misdiagnosing an HIV-infected infant is actually expected
to be low. WHO considers this to be an exception to the strict interpretation of the GHTF
risk classification.
6.4.

How WHO classifies a HIV quantitative nucleic acid technology (including laboratorybased, point-of-care and near to point-of-care testing)a. Applicable classification rule and classification:
Rule 3 – Class C
b. Intended use:
As an aid for patient management of individuals diagnosed as infected with HIV
through quantitative detection of HIV total nucleic acid.
c. Where the test is likely to be used in Member States:
For laboratory-based and/or near to point-of-care testing: In a level III (provincial orregional) or level IV (national) laboratories. In addition, in level II (district)laboratories for near to point-of-care.
For point-of-care testing: In level I (primary) laboratories and level (0) communitybased settings, including outside of a traditional laboratory setting (minimal
infrastructure, without temperature control).
d. Expertise of likely user in WHO Member States:
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For laboratory-based and/or near to point-of-care testing: Trained laboratory
professionals.
For point-of-care testing: Variable but likely to be minimal, if any, technicalbackground.
e. Clinical importance of test result:
Test results are used as a basis for deciding whether to initiate and monitor
antiretroviral therapy.
f. Impact of test result in WHO Member States:
iii.

Public health impact of incorrect result: Moderate
Downwards misclassification (result incorrectly low): Possible contribution to
drug resistance due to prolonged use of ineffective regimen, may lead toonward transmission, including of resistant HIV strains to other individuals.
Upwards misclassification (result incorrectly high): Leads to unnecessary
switching to more expensive regimens (2nd and 3rd line) and therefore
unnecessary use of limited resources.

iv.

Individual health impact of incorrect result: High
Downwards misclassification: Compromised ability to identify lack of adherence
to antiretroviral therapy. Treatment failure not identified which can haveprofound implications for individual health, possibly leading to death.
Upwards misclassification: N/A

6.5.

How WHO classifies a CD4 enumeration technology (including laboratory-based, pointof-care and near to point-of-care testing)a. Applicable classification rule and classification:
Rule 3 – Class C
b. Intended use:
As an aid for patient management of individuals diagnosed as infected with HIV
through enumeration of CD4+ lymphocytes.
c. Where the test is likely to be used in WHO Member States:
For laboratory-based and/or near to point-of-care testing: In a level III (provincial orregional) or level IV (national) laboratories. Level II (district) laboratories for near topoint-of-care.
For point-of-care testing: In level I (primary) laboratories and level (0) communitybased settings, including outside of a traditional laboratory setting (minimal
infrastructure, without temperature control).
d. Expertise of likely user in WHO Member States:
For laboratory-based and/or near to point-of-care testing: Trained laboratory
professionals.
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For point-of-care testing: Variable but likely to be minimal, if any, technicalbackground.
e. Clinical Importance of test result:
Test results are used as a basis for deciding whether to start (initiate) antiretroviraltherapy, substitute for toxicity, or switch after suspected treatment failure.
f. Impact of test result in WHO Member States:i.

Public health impact of incorrect result: Moderate
Downward misclassification of patients (result incorrectly low): Unnecessary
use of limited resources (medicines, laboratory monitoring, clinical expertise,
etc.)

ii.

Individual health impact of incorrect result: High
Upward misclassification of patients (result incorrectly high): : Not initiating
antiretroviral therapy or switching therapy (in the case of treatment failure) canhave profound implications for individual health, possibly leading to death.
Downward misclassification of patients: Risks associated with side effects oftreatment.

Additional note: CD4 is often the only marker available for decision-making associatedwith initiation of antiretroviral therapy in low and middle income countries. This meansthat the hazards to the individual are high if an incorrect result is obtained. CD4 tests are
regulated as the equivalent of Class B in many high income settings because of the low
impact of an erroneous result these countries. This is due to a relatively low prevalence of
HIV infection and policies of immediate initiation of treatment upon serodiagnosis,
irrespective of the CD4 count (i.e. test and treat). In settings where HIV viral load(quantitative NAT) is available , CD4 generally not used as the primary determinant inmonitoring of response to antiretroviral therapy. However, where there are inadequate
health resources, and where CD4 provides the sole determinant for the initiation oftreatment and/or monitoring response to antiretroviral therapy, the impact of incorrectclassification of disease status would have a more significant potential impact on individual
health.

7. Using Risk Class to Determine Level of WHO Prequalification of Diagnostics
Assessment
Similar to systems implemented by stringent regulatory authorities, the WHO prequalificationassessment is designed to safeguard the health and safety of patients and users of IVDs. The levelof confidence that the WHO Member States will have in a IVD for a priority disease will be basedon the safety and performance of these products throughout their life cycle.
It is the manufacturer’s responsibility to ensure that the IVD meets WHO requirements. However,
it is the role of WHO to ensure, by review and assessment, compliance with these requirements.
Dossier assessment, manufacturing site inspection, the independent WHO laboratory evaluation,
as well as post-market surveillance of IVDs for priority diseases, are complementary review and
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assessment activities of WHO prequalification. In general, the extent of review for WHO
prequalification is proportional to the risk class associated with that IVD.
By aligning with the GHTF risk based classification and assessment recommendations, WHO review
and assessment processes are aligned with international best practice. (4,5)

8. Conclusion
By using an internationally acknowledged classification scheme for IVDs, and taking into accountthe specific attributes associated with the use of these IVDs in many WHO Member States, WHO
Prequalification of Diagnostics processes ensure that the level of assessment is proportionate to
the degree of risk, taking into account the benefits offered by use of the IVD.
Any inquiries regarding the risk classification of IVDs should be addressed to: diagnostics@who.int

9. References
1. GHTF/SC/N4:2011 Glossary and Definitions of Terms Used in GHTF Documents
2. GHTF/SG1/N68:2012 Essential Principles of Safety and Performance of Medical Devices
3. GHTF/SG1/N063:2011 Summary Technical Documentation for Demonstrating Conformity to
the Essential Principles of Safety and Performance of In Vitro Diagnostic Medical Devices
4. GHTF/SG1/N045:2008 Principles of In Vitro Diagnostic (IVD) Medical Devices Classification
5. GHTF/SG1/N046:2008 Principles of Conformity Assessment for In Vitro Diagnostic (IVD)
Medical Devices

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Annex 1. GHTF Classification Rules (refer to GHTF/SG1/N045:2008 “Principles of In
Vitro Diagnostic (IVD) Medical Devices Classification”)
Rule 1:

IVD medical 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, blood derivatives, cells, tissues or organs in order toassess 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 risk ofpropagation

Rationale: The application of this rule as defined above should be in accordance with therationale that follows: Devices in this Class are intended to be used to ensure thesafety of blood and blood components for transfusion and/or cells, tissues and organs
for transplantation. In most cases, the result of the test is the major determinant as towhether the donation/product will be used. Serious diseases are those that result indeath or long-term disability, that are often incurable or require major therapeuticinterventions and where an accurate diagnosis is vital to mitigate the public healthimpact of the condition.
Examples: Tests to detect infection by HIV, HCV, HBV, HTLV. This Rule applies to first-line assays,
confirmatory assays and supplemental assays.

Rule 2:

IVD medical 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, are classified as Class C, except for
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)] and Duffy
system [FY1 (Fya), FY2 (Fyb)] determinations which are classified as Class D.

Rationale: The application of this rule as defined above should be in accordance with therationale for this rule which is as follows: A high individual risk, where an erroneous
result would put the patient in an imminent life-threatening situation places the device
into Class D. The rule divides blood grouping devices into two subsets, Class C or D,
depending on the nature of the blood group antigen the IVD medical device isdesigned to detect, and its importance in a transfusion setting.
Examples: HLA, Duffy system (other Duffy systems except those listed in the rule as Class D are inClass C).

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Rule 3:

IVD medical devices are classified as Class C if they are intended for use:















in detecting the presence of, or exposure to, a sexually transmitted agent. Examples:
Sexually transmitted diseases, such as Chlamydia trachomatis, Neisseria gonorrhoeae.
in detecting the presence in cerebrospinal fluid or blood of an infectious agent with arisk of limited propagation. Examples: Neisseria meningitidis or Cryptococcus
neoformans.
in detecting the presence of an infectious agent where there is a significant risk that anerroneous result would cause death or severe disability to the individual or fetus being
tested. Examples: diagnostic assay for CMV, Chlamydia pneumoniae, Methycillin
Resistant Staphylococcus aureus.
in pre-natal screening of women in order to determine their immune status towards
transmissible agents. Examples: Immune status tests for Rubella or Toxoplasmosis.
in determining infective disease status or immune status, and where there is a risk thatan erroneous result will lead to a patient management decision resulting in an
imminent life-threatening situation for the patient. Examples: Enteroviruses, CMV and
HSV in transplant patients.
in screening for selection of patients for selective therapy and management, or for orfor disease staging, or in the diagnosis of cancer. Example: personalized medicine.
NOTE: those IVD medical devices where the therapy decision would usually be madeonly after further investigation and those used for monitoring would fall into class B
under rule 6.
in human genetic testing. Examples: Huntington’s Disease, Cystic Fibrosis.
to monitor levels of medicines, substances or biological components, when there is arisk that an erroneous result will lead to a patient management decision resulting in an
immediate life-threatening situation for the patient. Examples: Cardiac markers,
Cyclosporin, Prothrombin time testing.
In the management of patients suffering from a life-threatening infectious disease.
Examples: HCV viral load, HIV Viral Load and HIV and HCV geno- and subtyping.
In screening for congenital disorders in the fetus. Examples: Spina Bifida or Down
Syndrome.

Rationale: The application of this rule as defined above should be in accordance with therationale for this rule which is as follows: Devices in this Class present a moderate
public health risk, or a high individual risk, where an erroneous result would put thepatient in an imminent life-threatening situation, or would have a major negative
impact on outcome. The devices provide the critical, or sole, determinant for thecorrect diagnosis. They may also present a high individual risk because of the stressand anxiety resulting from the information and the nature of the possible follow-up
measures.

Rule 4:

IVD medical devices intended for self-testing are classified as Class C, except thosedevices from which the result is not determining a medically critical status, or is

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preliminary and requires follow-up with the appropriate laboratory test in which casethey are Class B.
IVD medical devices intended for blood gases and blood glucose determinations fornear-patient testing would be Class C. Other IVD medical devices that are intended fornear-patient should be classified in their own right using the classification rules.
Rationale: The application of this rule as defined above should be in accordance with therationale for this rule which is as follows: In general, these devices are used byindividuals with no technical expertise and thus the labelling and instructions for use
are critical to the proper outcome of the test.
Example for self-testing class C: Blood glucose monitoring,
Example for self-testing class B: Pregnancy self test, Fertility testing, Urine test-strips.

Rule 5:

The following IVD medical devices are classified as Class A:




Note:

Reagents or other articles which possess specific characteristics, intended by the
manufacturer to make them suitable for in vitro diagnostic procedures related to a
specific examination.
Instruments intended by the manufacturer specifically to be used for in vitro diagnostic
proceduresSpecimen receptacles
Any product for general laboratory use not manufactured, sold or represented for use
in specified in vitro diagnostic applications are not deemed to be IVD medical devices,
as defined in this document. However, in certain jurisdictions products for generallaboratory use are considered to be IVD medical devices.

Rationale: The application of this rule as defined above should be in accordance with therationale for this rule which is as follows: These devices present a low individual risk
and no or minimal public health risk.
Examples: Selective/differential microbiological media (excluding the dehydrated powders which
are considered not to be a finished IVD medical device), identification kits for cultured
microorganisms, wash solutions, instruments and plain urine cup.
Note 1:
Note 2:
Note 3:

In certain jurisdictions there may be differences as to whether a device classified in thisrule is considered an IVD medical device.
The performance of software or an instrument that is specifically required to performa particular test will be assessed at the same time as the test kit.
The interdependence of the instrument and the test methodology prevents the
instrument from being assessed separately, even though the instrument itself is stillclassified as Class A.

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Rule 6:

IVD medical devices not covered in Rules 1 through 5 are classified as Class B.

Rationale: The application of this rule as defined above should be in accordance with therationale for this rule which is as follows: These devices present a moderate individual
risk as they are not likely to lead to an erroneous result that would cause death orsevere disability, have a major negative impact on patient outcome or put theindividual in immediate danger. The devices give results that are usually one of several
determinants. If the test result is the sole determinant however other information isavailable, such as presenting signs and symptoms or other clinical information which
may guide a physician, such that classification into Class B may be justified. Other
appropriate controls may also be in place to validate the results. This Class also
includes those devices that present a low public health risk because they detect
infectious agents that are not easily propagated in a population.
Examples: Blood gases, H. pylori and physiological markers such as hormones, vitamins, enzymes,
metabolic markers, specific IgE assays and celiac disease markers.
Rule 7:

IVD medical devices that are controls without a quantitative or qualitative assigned
value will be classified as Class B.

Rationale: For such controls, the qualitative or quantitative value is assigned by the user and not
the manufacturer.

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