Prequalification TeamA RISK BASED APPROACH FOR THE
ASSESSMENT OF IN VITRO DIAGNOSTICS(IVDs)

Prequalification of Diagnostics

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Table of Contents
1. Introduction ................................................................................................................................. 3
2. Intended Audience and Scope ..................................................................................................... 3
3. Definitions .................................................................................................................................... 3
4. Abbreviations ............................................................................................................................... 4
5. Risk Classification ......................................................................................................................... 5
6. Assessing IVDs – Critical Elements ............................................................................................... 7
7. Performance Evaluations and Lot Release Testing .................................................................... 12
8. Conclusion .................................................................................................................................. 13
9. References.................................................................................................................................. 13
Annex 1. GHTF Classification Rules (refer to GHTF/SG1/N045:2008 “Principles of In Vitro
Diagnostic (IVD) Medical Devices Classification”) ............................................................................. 14

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1. Introduction
In vitro diagnostic medical devices (IVDs) play a critical role in both individual health and publichealth. Individual patient management depends upon the availability of reliable and accurate
IVDs for clinical decisions on diagnosis and treatment, as does screening of blood/blood products
for transfusion and human organs/tissues for transplantation. Likewise, good quality IVDs for thedetection of infectious agents, for example, are crucial to controlling their transmission and to theappropriate allocation of valuable and often limited resources (i.e. medicines, laboratory testing,clinical expertise). Therefore, incorrect test results carry with them the potential to have serious
health consequences. For this reason, a growing number of authorities assess IVDs for quality,
safety, and performance prior to acceptance for procurement (generally known as pre-market
assessment) and following their placing on the market (generally referred to as post-market
surveillance).
Whereas the clinical setting demands that IVD quality be high, it is not feasible that all IVDs be
assessed in the pre-market phase in the same manner, given both the number of products
available for a very broad range of analytes and the resources available to conduct assessments.
This has led to the use of a risk-based approach to assessment, in which IVDs are classified
according to the risk they pose to public and individual health, and taking into account thepotential outcomes and impact if the test does not perform properly or is not available. The risk
class then determines the level of scrutiny applied for the regulatory assessment, ensuring that
resources are focused on those IVDs associated with the greatest potential risk.

2. Intended Audience and Scope
This document provides information to WHO Member States, manufacturers submitting to the
WHO Prequalification of Diagnostics Programme, regulators and other stakeholders on aninternationally recognized risk-based approach to the regulatory assessment of IVDs to determine
the level of scrutiny of the assessment of an IVD and to assure there quality, safety andperformance in clinical use.
This approach describes a mechanism that can be adapted or applied by other bodies undertaking
the assessment of the quality, safety and performance of an IVD.

3. Definitions
Intended use (1)The objective intent of the manufacturer regarding the use of a product, process or service asreflected in the specifications, instructions and information provided by the manufacturer.
Note: Aspects that are considered in the intended use includewhat is detected

its function (e.g. screening, monitoring, diagnosis or aid to diagnosis);the specific disorder, condition or risk factor of interest that it is intended to detect, define
or differentiate;

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whether it is automated or not;

whether it is qualitative or quantitative;

the type of specimen(s) required (e.g. serum, plasma, whole blood, tissue biopsy, urine);

testing population ;

the intended user (e.g. lay person, highly trained laboratory professional, minimally trained
health care worker, self-testing);

the intended setting of use (e.g. point of care, reference or diagnostic laboratory setting,primary health care setting)In vitro diagnostic medical device (2)“A medical device, whether used alone or in combination, intended by the manufacturer for thein-vitro examination of specimens derived from the human body solely or principally to provide
information for diagnostic, monitoring or compatibility purposes. IVD medical devices include
reagents, calibrators, control materials, specimen receptacles, software, and related instruments
or apparatus or other articles.”Risk (3)“Combination of the probability of occurrence of harm and the severity of that harm.”
Risk assessment (3)“Overall process comprising a risk analysis and a risk evaluation.”

Conformity Assessment (4)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 of Medical Devices.
Conformity Assessment Body (4)A body engaged in the performance of procedures for determining whether the relevant
requirements in technical regulations or standards are fulfilled. A Conformity Assessment Body
(CAB) is authorized to undertake specified conformity assessment activities by a Regulatory
Authority (RA) that will ensure performance of the CAB is monitored and, if necessary, withdraw
designation.

4. Abbreviations
CAB

Conformity Assessment Body

EP

Essential Principles of Safety and Performance for Medical Devices

GHTF

Global Harmonization Task Force

IMDRFInternational Medical Device Regulators Forum

IVD

In vitro diagnostic medical device

QMS

Quality Management System

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5. Risk Classification
The risk posed by the use of an IVD can be categorized or classified according to a set ofclassification rules. (5) These rules were created by the Global Harmonization Task Force (GHTF), a
voluntary group of representatives from regulatory authorities (United States, Canada, European
Union, Japan, and Australia), as well as representatives from the medical device industry. In 2012
GHTF was replaced by a regulators-only group, the International Medical Device Regulators Forum(IMDRF), which has adopted the GHTF classification rules and other GHTF regulatory guidelines.
IMDRF continues to maintain GHTF guidelines and develop more guidance that will encourageinternational regulatory convergence and support innovation and timely access to safe andeffective medical devices globally. GHTF and IMDRF documents have been created and approvedby working parties comprised of both regulatory authorities and major industry groups, ensuringthat the recommendations are acceptable and implementable at a global level. Internationally, theoutputs of IMDRF and GHTF are being adopted by several countries introducing regulation of IVDs
and other medical devices. Additionally, established regulatory agencies are also converging
practices in line with the recommendations of GHTF and IMDRF, in recognition of the fact thatthese represent regulatory best practice for a global market.
GHTF created the risk classification rules to determine the level of pre-market regulatory
assessment that is required for an IVD, with the purpose that these controls are considered to be
sufficient for each risk class to safeguard the health and safety of patients, users and otherpersons. The outcome of the rules is to group IVDs into one of four classes representing increasing
individual and public health risk (Classes A to D), shown in Table 1.
Table 1: GHTF Risk Classes and Risk Level
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

This risk classification system is based on two regulatory principles. First, the level of scrutiny
afforded a device is dependent upon the risk the device presents. Second, the safety andperformance of medical devices can be best assessed through a balance of pre-market scrutiny,adequate manufacturer quality management systems, and the implementation of effective postmarket surveillance mechanisms.
It is the responsibility of the manufacturer to apply the risk classification rules and determine therisk class, based on the intended use of the IVD. The manufacturer should document the
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justification for placing the IVD into a particular risk class. However it is the responsibility of theregulatory authority or conformity assessment body to confirm that the risk class determined by
the manufacturer is consistent with applicable classification rules and appropriate for the intended
setting.
When applying the rules, risk considerations will vary depending upon the setting in which a
product is intended to be used. For example, several critical aspects are particular to risk
considerations for IVDs used in resource-limited settings compared to high-income countries.
These include differences in endemicity and prevalence of various diseases, the way the test result
is used for clinical-decision making, the level of treatment and care available for a patient with thedisease, the availability of follow-up or reference testing, and significant variations in the level oftraining of professional and non-professional staff utilizing the IVD. This means that the risk
classification of an IVD in a low- or middle-income country can be considerably different (usuallyposing higher risk) to that when evaluated for use of the IVD in a high-income country.
It is important to note that the risk classification does not determine the level of effort to beundertaken by the manufacturer to create sufficient evidence of safety and performance of the
IVD. All IVDs, no matter the risk class, should be designed and manufactured under conditions thatwill result in a quality product with an expected level of performance. Rather, risk classification isintended to provide the appropriate amount of oversight by a regulatory authority or conformity
assessment body. For instance, the classification does not determine the size and complexity of
the clinical performance studies to be undertaken. These are determined by other factors, guided
by an appropriate risk analysis conducted by the manufacturer that addresses factors such as thedesign of the IVD, as well as all performance claims related to intended use such as the intended
users and testing population. However, the risk classification may influence the type of
information required for assessment. For example, only summary data are usually required forlower risk products, whereas complete data sets are assessed for higher risk products, andinformation supporting the design and development of a IVD are needed to assess higher risk ornovel IVDs.
The following criteria are used to apply the GHTF rules for classification of IVDs:
 the intended use and indications for use as specified by the manufacturer (including
aspects such as the specific disorder, condition or risk factor for which the test isintended, the intended setting/environment for use)
 the technical/scientific/medical expertise of the intended user (lay person or
professional)
 the importance of the test result to the diagnosis (sole determinant or one of several),taking into consideration the natural history of the disease or disorder including
presenting signs and symptoms which may guide a physician
 the impact of the result (true or false) to the individual and/or to public health.
The risk classification rules for IVDs as described by GHTF are found in Annex 1. In some cases,
more than one classification rule may be applicable to an IVD; in this case the higher risk
classification is applied.

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6. Assessing IVDs – Critical Elements
GHTF identifies elements that should be considered in the regulatory assessment of an IVD (4):






Quality management system
Post-market surveillanceTechnical documentation
Declaration of conformity to the Essential Principles of Safety and Performance
Registration of manufacturers and their devices

The following sections outline what GHTF identifies as the manufacturer’s responsibility for eachof these elements and what level of assessment of each element by either the regulatory authority
or the conformity assessment body (CAB) is most appropriate for each risk class of IVD. IVDs that
present the greatest risk (Classes C and D) typically require objective evidence of the safety,
quality, performance, benefits and risks of the IVD. Such evidence is usually documented in atechnical file available at the site of manufacture. An inspection of the manufacturer’s quality
management system would typically include the review of particular records from the technicalfile. In addition, a product dossier that includes selected records from the technicaldocumentation is assessed as part of the pre-market assessment. The GHTF document, “Summary
Technical Documentation for Demonstrating Conformity to the Essential Principles of Safety and
Performance of In Vitro Diagnostic Medical Devices” (this documentation is referred to as theSTED), provides recommendations for dossier content for Class C and D IVDs. (6) In somejurisdictions, an independent performance evaluation to verify the claims (performance andoperational characteristics) made by the manufacturer in the product dossier and associatedquality documentation may be performed.
6.1.

Assessment Element: Quality Management Systems

The responsibilities associated with this element are in Table 2 below.
Manufacturer’s Responsibility: An appropriate quality management system should be in place forall classes of IVDs. Quality management systems, when implemented effectively, will ensure the
manufacturer has in place mechanisms that not only ensure quality production (and an
uninterrupted supply), but also should ensure the IVD will be safe and effective. Such mechanisms
include the use of risk management procedures, with risks identified, monitored and addressed,
throughout the product life cycle.
The scope and complexity of the quality management system that a manufacturer needs toestablish is influenced by varying needs, objectives, the products provided, processes employed,
the size and structure of the organization, and specific regulatory requirements.
Examples of quality management standards for IVDs that have been acceptable to regulatory
authorities include ISO 13485:2003 (Medical devices -- Quality management systems -Requirements for regulatory purposes) and the United States Food and Drug Administration
Quality System Regulations (Code of Federal Regulations Title 21, Part 820).
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Regulatory Authority (RA)/Conformity Assessment Body (CAB) Responsibility: Assessment of theeffectiveness of a manufacturer’s quality management system is primarily influenced by the classof the IVD. For Class C and Class D IVDs, the assessment process will ensure that not only is there
an effective control of manufacturing and other processes, that there is also control of the designand development of the IVD that forms the basis for the manufacturing of the IVD. As shown in
Table 2, assessment for classes B to D can range from review of relevant certification tocomprehensive on-site inspection and auditing of the manufacturer’s quality management system.
Factors other than risk class that can influence the form and depth of the assessment include theregulatory authority or conformity assessment body’s knowledge of the manufacturer (assessed atprior inspections for other products), external reports of quality issues associated with the productor the manufacturer, and the findings of other inspection reports generated as part of acomprehensive regulatory review process.
Table 2: Assessment of Quality Management Systems According to Risk ClassificationClass

Manufacturer Responsibility

RA/CAB Responsibility

A

Establish and maintain a full QMS
ora QMS without design anddevelopment controls.

Premarket regulatory audit not required.

B

Establish and maintain a full QMS
ora QMS without designand development controls.

Be satisfied that a current and appropriate
QMS is in place or otherwise conduct a
QMS audit prior to marketing
authorization.

C

Establish and maintain a full QMS.

Be satisfied that a current and appropriate
QMS is in place or otherwise conduct a
QMS audit prior to marketing
authorization.

D

Establish and maintain a full QMS.

Be satisfied that a current and appropriate
QMS is in place or otherwise conduct a
QMS audit prior to marketing
authorization.

6.2.

Assessment Element: Technical Documentation

The responsibilities associated with this element are in Table 3 below.
Manufacturer’s Responsibility: Sufficient technical documentation should exist to prove that the
GHTF “Essential Principles of Safety and Performance of Medical Devices” (identified as simply the
Essential Principles [EP]) have been met. (7) Manufacturers of all classes of IVDs are expected todemonstrate conformity of the IVD to the EP through the preparation and holding of technical
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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 as necessary to reflect
the current status, specification, configuration and post-market experience of the IVD.
Regulatory Authority (RA)/Conformity Assessment Body (CAB) Responsibility: An assessment bodyassessing conformity to the EP (e.g. a regulatory authority) will review the STED at greater depth
as the risk class increases.
The GHTF document notes that the documentation for a Class C IVD medical device will containless elaborate information than the STED for a Class D device. The main difference for a Class D
STED would be in the level of details in the clinical/performance data and details of the
manufacturer’s QC release program. Although a regulatory authority/conformance assessment
body should not normally require more elaborate information for a Class C device, this does notpreclude the regulatory authority/conformity assessment body from requesting such informationin specific cases.
Table 3: Assessment of Technical Documentation According to Risk ClassificationClass

Manufacturer Responsibility

RA/CAB Responsibility

A

Upon request prepare STED.

Premarket submission of STED notrequired. May be requested to investigate
specific safety or regulatory concerns.

B

Upon request prepare STED.

Premarket submission normally not
required but if requested, receive andconduct a review of the STED to determine
conformity to Essential Principles.

C

Prepare and submit STED for review.

Receive and conduct a premarket reviewof the STED to determine conformity to
Essential Principles.

D

Prepare and submit STED for review.
A STED for this class should containmore extended information such as
full performance evaluation reports.

Receive and conduct a premarket reviewof the STED to determine conformity to
Essential Principles.

6.3.

Assessment Element: Post-Market Surveillance

The responsibilities associated with this element are in Table 4 below.
Manufacturer’s Responsibility: A system for post-market surveillance of the product should be inplace to monitor manufactured product quality, safety and performance. Prior to placing the
product on the market, the manufacturer will put in place, as part of its quality management
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system, a process to assess the continued safety and performance of the throughout the life cycleof the IVD. This process will include having procedures for, at a minimum, complaint handling,
vigilance reporting, procedures for recalls, and corrective and preventive action.
Regulatory Authority (RA)/Conformity Assessment Body (CAB) Responsibility: An assessment bodycan review the effectiveness of post-market surveillance mechanisms through inspection on site
and/or through the availability of relevant documentation (including existence of appropriate
standard operating procedures). The level of review should again be strongly influenced by the risk
class of the IVD as well as the additional factors identified above for assessment of the quality
management system.
It is important to note that an adverse event reporting procedure is a necessity for each regulatory
authority to maintain.
Table 4: Assessment of Post-Market Surveillance According to Risk ClassificationClass

Manufacturer Responsibility

A

Establish and maintain an adverse
event reporting procedure according
to GHTF SG2 guidance.

May audit post-market to investigate
specific safety or regulatory concerns.

B

Establish and maintain an adverse
event reporting procedure according
to GHTF SG2 guidance.

Be satisfied that a current and appropriate
adverse event reporting procedure is inplace as part of the QMS.

C

Establish and maintain an adverse
event reporting procedure according
to GHTF SG2 guidance.

Be satisfied that a current and appropriate
adverse event reporting procedure is inplace as part of the QMS.

D

Establish and maintain an adverse
event reporting procedure according
to GHTF SG2 guidance.

Be satisfied that a current and appropriate
adverse event reporting procedure is inplace as part of the QMS.

6.4

RA/CAB Responsibility

Assessment Element: Declaration of Conformity

The responsibilities associated with this element are in Table 5 below.
Manufacturer’s Responsibility: A declaration of conformity to the EPs is likewise a requirement,
providing assurance that the manufacturer is meeting appropriate standards for quality in thedesign and manufacture of its IVD.
Regulatory Authority (RA)/Conformity Assessment Body (CAB) Responsibility: Review forcompliance with the EPs is a necessity for three of the four risk classes.

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Table 5: Assessment of Declaration of Conformity According to Risk ClassificationClass

Manufacturer Responsibility

RA/CAB Responsibility

APrepare, sign and maintain.

On file with the manufacturer; available
upon request.

B

Prepare, sign and maintain.

Review and verify compliance withrequirements.

C

Prepare, sign and maintain.

Review and verify compliance withrequirements.

D

Prepare, sign and maintain.

Review and verify compliance withrequirements.

6.5

Assessment Element: Registration of Manufacturers and their Devices

The responsibilities associated with this element are in Table 6 below.
Registration of manufacturers and their devices is viewed as a basic regulatory requirement for
any IVD and therefore it is necessary that the manufacturer registers as appropriate for the
regulatory system and that the regulatory authority/conformity assessment body maintains theregistry and verifies registration as appropriate.
Table 6: Assessment of Registration of Manufacturers and their Devices According to Risk
ClassificationClass

Manufacturer Responsibility

RA/CAB Responsibility

A

Perform according to regulatory
requirements.

Maintain and verify as appropriate.

B

Perform according to regulatory
requirements.

Maintain and verify as appropriate.

C

Perform according to regulatory
requirements.

Maintain and verify as appropriate.

D

Perform according to regulatory
requirements.

Maintain and verify as appropriate.

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7. Performance Evaluations and Lot Release Testing
GHTF also acknowledges that performance testing is another element to be considered as part ofconformity assessment. (5).
Manufacturer’s Responsibility: IVDs should have performance characteristics (such as sensitivity,
specificity, linearity, etc) appropriate for the intended setting when used by intended users.
Special considerations for the variable conditions encountered in diverse settings should beconsidered in the design and development of the IVD to ensure that these performance
characteristics can be achieved. Such considerations may include use of the IVD in areas withextremes of temperature and humidity, and with operators of various skill levels. The
manufacturer should have considered these aspects in a thorough risk assessment and holdevidence through performance testing and other means that the benefits of using the IVD in theintended use setting by intended users will outweigh any residual risk.
Additionally, the manufacturer should have in place effective lot release procedures to ensure
performance characteristics are maintained for each lot of product manufactured. Lot release
testing should thus ensure that where appropriate, the sensitivity and specificity, or other critical
performance characteristics remain unchanged for each lot by the testing of sufficient numbers of
relevant specimens. Maintenance of lot release panels is therefore a critical procedure within thequality management system to ensure ongoing consistency.
Regulatory Authority (RA)/Conformity Assessment Body (CAB): In many cases,
regulatory/evaluating bodies rely solely on information from studies conducted by, or on behalf of,
the manufacturer to evaluate the IVD’s performance. Others conduct their own independent
evaluation through performance studies to supplement or verify those performed by the
manufacturer.
The need to undertake independent evaluation should follow the risk based principles identified in
GHTF guidance “Principles of Conformity Assessment for In Vitro Diagnostic (IVD) Medical Devices”(8), taking into account considerations such as the risk class of the IVD, the novelty of thetechnology, the manufacturer’s experience level with the type of IVD and if the type of IVD raises
specific public health concerns. The evaluation can take the form of a performance study verifying
the manufacturer’s performance claims, and/or through lot testing to ensure each lot meets set
criteria. Performance studies for regulatory are different in their purpose than those for healthtechnology assessment (HTA) purposes. The goal for regulation usually encompasses verificationof clinical validity, whereas for HTA, clinical utility is being reviewed. HTA studies investigate
implementation aspects such as cost benefit ratios, taking into account aspects such as training,educational and facility requirements.
Lot testing can be performed by the RA or the CAB to ensure the quality of the assays before
distribution in view of the potential effect of transportation on product performance when it isshipped into country. Depending on the risk class of the product and its use in a particularjurisdiction, an alternative to lot testing by the regulatory authority is review of the
manufacturer’s lot release data for each of the lots accepted into that jurisdiction.

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8. Conclusion
By using an internationally recognized risk classification scheme for IVDs to determine routine
regulatory oversight, regulatory authorities and conformity assessment bodies ensure that thelevel of assessment is proportionate to the degree of risk, taking into account the benefits offeredby the IVD.
Such an approach to IVD assessment takes into account the number and diversity of IVDs available,
as well as the limited resources available to undertake assessment. Another proven advantage isthat the classification scheme is rules based and not prescriptive. This means it can accommodate
new and innovative IVDs. WHO recommends the adoption of this approach for WHO Member
States regulating IVDs and those considering doing so.
Because of its international acceptance, WHO has adopted this risk based assessment approachfor the purposes of WHO prequalification of IVDs. WHO undertakes PQ assessment activities
according to the risk class as determined by applying the GHTF classification rules. For more
information regarding this WHO activity , refer WHO PQDx_0172 “Risk Based Classification of
Diagnostics for WHO Prequalification”.
Any inquiries regarding this risk based assessment approach should be addressed to:
diagnostics@who.int

9. References
1. GHTF/SG1/N070:2011

Labels and Instructions for Use of Medical Devices

2. GHTF/SG1/N071:2012

Definition of the Terms ‘Medical Device’ and ‘In Vitro
Diagnostic (IVD) Medical Device

3. ISO/IEC Guide 51:1999

Safety aspects -- Guidelines for their Inclusion in Standards

4. GHTF/SG1/N046:2008

Principles of Conformity Assessment for In Vitro Diagnostic (IVD)
Medical Devices

5. GHTF/SG1/N045:2008

Principles of In Vitro Diagnostic (IVD) Medical Devices
Classification

6. GHTF/SG1/N063:2011

Summary Technical Documentation for Demonstrating
Conformity to the Essential Principles of Safety and Performanceof In Vitro Diagnostic Medical Devices

7. GHTF/SG1/N68:2012

Essential Principles of Safety and Performance of 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).

Rule 3:

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

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














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 ispreliminary 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.

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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:Rule 6:

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.

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 or
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severe 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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