Investigational Medical Device Dossier For In Vitro Diagnostic Medical Devices

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Authors
Name	Position and organisation	Responsible for the following part(s) of IMDD-IVD	

			

Table of contents

Scope
IMDD-IVD format
Information to be submitted
1.	Device description and specification, including variants and accessories
1.1	Device description and specification
1.2	Reference to previous and similar generations of the device
2.	Information to be supplied by the manufacturer
3.	Design and manufacturing information
3.1 	Design information
3.2	Manufacturing information
4.	General safety and performance requirements
5.	Benefit-risk analysis and risk management
6.	Product verification and validation
6.1	Information on the analytical performance of the device
6.1.1 Specimen type
6.1.2 Analytical performance characteristics
6.1.3 The analytical performance report referred to in Annex XIII
6.2	Information on clinical performance and clinical evidence. Performance Evaluation Report
6.3	Stability (excluding specimen stability)
6.3.1 Claimed shelf-life
6.3.2 In-use stability
6.3.3 Shipping stability
6.4	Software verification and validation
6.5	Additional information required in specific areas
References
Appendix I Table of contents for the IMDD-IVD to be submitted
Appendix II Checklist GSPRs
Appendix III Risk management

Abbreviations as used in this document

CE 		Conformité Européenne
CS		Common specifications
EN		European standard
GSPR		General safety and performance requirement
IMDD-IVD	Investigational medical device dossier for in vitro diagnostic medical devices
ISO		International standard
IVD		In vitro diagnostic medical device
IVDR		In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746
MREC		Medical Research Ethics Committee
NEN		Dutch standard
PMPF		Post-market performance follow-up
UDI-DI		Unique Device Identification device identifier
QMS		Quality management system
SSP		Summary of safety and performance

Scope
The investigational medical device dossier for in vitro diagnostic medical devices (IMDD-IVD) specifies all items that must be covered (if relevant) for an application to a Medical Research Ethics Committee (MREC) in the Netherlands. This document is written for non-CE-marked in vitro diagnostic medical devices (IVDs) within the scope of the In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR) [1], which are intended for a type of performance study as referred to in Article 58(1-2), i.e. which shall be subject to scientific and ethical review by an MREC. If a non-CE-marked IVD, manufactured and used only within a single health institution (in-house manufactured IVD), is subject to a performance study, all items specified in this IMDD-IVD are also considered applicable. A clear rationale and justification shall be provided for any deviation(s) from the IMDD-IVD. For CE-marked IVDs used outside the scope of its intended purpose as referred to in Article 70(2), the format of the IMDD-IVD can also be used, see also the paragraph on information to be submitted. 
Good study practice and the design and conduct of the performance study are outside the scope of the IMDD-IVD and shall be described in the clinical performance study plan. The requirements regarding personal data protection are also outside the scope of the IMDD-IVD. 
IMDD-IVD format
The requirements for information to be submitted by a sponsor of a performance study with a non CE-marked IVD are laid down in Annex XIV of the IVDR. However, the information to be submitted is mostly stated generally. Section 4.6 of Chapter I of Annex XIV allows the competent authority to request additional information to be submitted. Annex II of the IVDR contains detailed requirements for the technical documentation that a manufacturer has to compile to prove that IVDs meet the requirements of the IVDR. To facilitate uniform submission of documentation for IVDs for performance study, it was decided to use the technical documentation requirements as specified in Annex II of the IVDR as the basis for the documentation to be submitted. This IMDD-IVD guidance document provides additional guidance on the interpretation of some parts and provides information on the required documentation to be submitted, see paragraphs 1-6. 

The text of Annex II of the IVDR is presented in normal type font. Reference to annexes in that part of the IMDD-IVD refer to Annexes of the IVDR. For the IMDD-IVD, reference is made to appendices. Bold text is guidance to the required information in the IVDR.
Where it is mentioned in Annex II of the IVDR that a medical device is ‘placed on the market’, for the IMDD-IVD this should be read and understood as ‘used in the performance study’. The term ‘manufacturer’ could in several instances be read and understood as ‘sponsor of the performance study’ or in case of an in-house developed test ‘health institution’. 
Information to be submitted
The sponsor of the performance study, regardless whether it is a legal manufacturer or an investigator, shall use the IMDD-IVD format for submitting the required documentation to the MREC. The information in the IMDD-IVD and the information referred to in the IMDD-IVD can be submitted in English or in Dutch. 
To obtain adequate and complete information in the IMDD-IVD, active involvement of the manufacturer of the investigational IVD is highly recommended, as they should have all technical information required for the IMDD-IVD available. If an item is not available yet due to the stage of development of the IVD, a justification substantiating this shall be provided.

The information requested in the IMDD-IVD shall be compiled in a documentation set. The documentation set shall be presented in a clear, organised, readily searchable and unambiguous manner.
If an IMDD-IVD item is dealt with in another item or document supplied for the performance study, for instance the investigator’s brochure, as described in NEN-ISO 20916 [2], or technical construction file, reference to that item or document is acceptable when a brief description of the information in that item or document is provided in the IMDD-IVD. Appendix I of the IMDD-IVD provides a table of contents for the documentation set. Using that table, cross references can be made between the items required by the IMDD-IVD and the documents submitted. If an item of the IMDD-IVD is not applicable for the particular IVD (e.g. ‘software verification and validation’ or ‘devices containing tissues, cells, and substances of animal, human or microbiological origin’), this shall be clearly indicated, and where appropriate substantiated.
If separate documents are submitted, each document shall include a date/version number and identify author(s) that contributed significantly.
If the information to be submitted for one or more items (e.g. software validation for large analysers) is very extensive, the level of detail of the documentation for such items shall be agreed upon with the MREC. 

In case the sponsor intends to change (the intended purpose of) an already CE-marked IVD and needs clinical performance data to support the change, no full IMDD-IVD of the original IVD needs to be submitted. The documentation submitted shall contain a clear description of the change(s) as compared to the CE-marked IVD and its intended use(s) and a rationale for the change to the IVD. The documentation shall contain a description which items of the IMDD-IVD are affected by the change and updated documentation on these items shall be submitted. The items device description (item 1), instructions for use (item 2), general safety and performance requirements (GSPRs, item 4), and benefit-risk analysis (item 5) shall always be submitted. This will provide insight into the changes and how all GSPRs are addressed for the new design/intended use and how additional risks related to the change have been addressed. 
If a summary of safety and performance (SSP) has been drawn up for the CE-marked IVD which is changed by the sponsor as described above, this SSP shall also be supplied. 

In the IMDD-IVD, the use of harmonised standards for fulfilling requirements of the IVDR is preferred. Therefore, harmonised standards are referred to when applicable. Other solutions can be used, but a rationale shall be provided why this is considered similar to the approach in the harmonised standard.

Certain aspects, such as interoperability or usability, that are considered crucial by the MREC or investigators, might not be elaborated upon sufficiently in the requirements in the IVDR and therefore in the IMDD-IVD. Additional requirements can be discussed between the investigators, sponsor and MREC, as applicable.
1.	
Device description and specification, including variants and accessories
1.1	Device description and specification 
a.	product or trade name and a general description of the device including its intended purpose and intended users;
This shall include the name and contact details (visiting address, telephone number and e-mail address) of the manufacturer and, if not the same as the manufacturer, the sponsor.

b.	the Basic UDI-DI as referred to in Part C of Annex VI assigned by the manufacturer to the device in question, as soon as identification of this device becomes based on a UDI system, or otherwise a clear identification by means of product code, catalogue number or other unambiguous reference allowing traceability;
The method used to trace the IVD shall be included, either a UDI, which is only required for IVDs to be brought onto the market, or another unambiguous reference. 	
	
c.	the intended purpose of the device which may include information on:
i.	what is to be detected and/or measured; 
ii.	its function such as screening, monitoring, diagnosis or aid to diagnosis, prognosis, prediction, companion diagnostic; 
iii.	the specific disorder, condition or risk factor of interest that it is intended to detect, define or differentiate; 
iv.	whether it is automated or not; 
v.	whether it is qualitative, semi-quantitative or quantitative; 
vi.	the type of specimen(s) required; 
vii.	where applicable, the testing population; 
viii.	the intended user; 
ix.	in addition, for companion diagnostics, the relevant target population and the associated medicinal product(s). 	
	
d.	the description of the principle of the assay method or the principles of operation of the instrument;	
	
e.	the rationale for the qualification of the product as a device;
Please note that device in the context of the IVDR means every device that falls under the IVDR, i.e. an IVD or accessory.	
	
f.	the risk class of the device and the justification for the classification rule(s) applied in accordance with Annex VIII;

g.	the description of the components and where appropriate, the description of the reactive ingredients of relevant components such as antibodies, antigens, nucleic acid primers;

and where applicable:	
	
h.	the description of the specimen collection and transport materials provided with the device or descriptions of specifications recommended for use;	
	
i.	for instruments of automated assays: the description of the appropriate assay characteristics or dedicated assays;	
	
j.	for automated assays: a description of the appropriate instrumentation characteristics or dedicated instrumentation;	
	
k.	a description of any software to be used with the device;	
	
l.	a description or complete list of the various configurations/variants of the device that are intended to be made available on the market;
This concerns the various configurations/variants of the device to be used in the performance study. A rationale shall be included explaining why these configurations are used for the performance study.	
	
m.	a description of the accessories for a device, other devices and other products that are not devices, which are intended to be used in combination with the device.	
	
1.2	Reference to previous and similar generations of the device
a.	an overview of the previous generation or generations of the device produced by the manufacturer, where such devices exist;
A brief description of the key features of previous generations of the IVD is sufficient. 	
	
b.	an overview of identified similar devices available on the Union or international markets, where such devices exist.
A brief description of the key features of similar IVDs is sufficient.	
	
2.	Information to be supplied by the manufacturer
A complete set of
a.	the label or labels on the device and on its packaging, such as single unit packaging, sales packaging, transport packaging in case of specific management conditions, in the languages accepted in the Member States where the device is envisaged to be sold;	
	
b.	the instructions for use in the languages accepted in the Member States where the device is envisaged to be sold.	

The label(s) on the IVD(s) and the packaging and the instructions for use shall be the ones associated with the IVDs as used during the performance study. The packaging does not have to be the final sales packaging. The label shall include the words “device for performance study” or “hulpmiddel voor prestatiestudies”, as required by the IVDR, Annex I, clause 20.2.e or clause 20.4.1.d. The language requirement relates to Member States where the study is performed, instead of where the device is envisaged to be sold. For professional users, such as physicians, laboratory technicians and nurses in the Netherlands, both English and Dutch are accepted languages for the instructions for use.
The instructions for use shall comply with the requirements from paragraph 20.4 from Annex I of the IVDR. Important aspects to be included in the instructions for use are the required training and/or qualifications of the users or other persons and the warnings, precautions and contra-indications. 
Other instructions, apart from the instructions for use, accompanying the IVD, e.g. for installation, maintenance or maintaining hygienic standards, do not have to be submitted as part of the IMDD-IVD. 
Note 1: these documents should be included as part of the investigator’s brochure. 
Note 2: instructions for use have to be included. By way of exception, instructions for use are not required or may be abbreviated if the IVD can be used safely and as intended without any such instructions. When showing compliance to the GSPRs (see paragraph 4), omitting the instructions for use will be elaborated upon. 
3.	Design and manufacturing information
3.1 	Design information
Information to allow the design stages applied to the device to be understood shall include:
a.	a description of the critical ingredients of the device such as antibodies, antigens, enzymes and nucleic acid primers provided or recommended for use with the device;	
	
b.	for instruments, a description of major subsystems, analytical technology such as operating principles and control mechanisms, dedicated computer hardware and software;
Where appropriate, add graphic representations such as flow charts.	
	
c.	for instruments and software, an overview of the entire system;
Where appropriate, add graphic representations such as flow charts.	
	
d.	for software, a description of the data interpretation methodology, namely the algorithm;	
	
e.	for devices intended for self-testing or near-patient testing, a description of the design aspects that make them suitable for self-testing or near-patient testing.

3.2	Manufacturing information
a.	information to allow the manufacturing processes such as production, assembly, final product testing, and packaging of the finished device to be understood. More detailed information shall be provided for the audit of the quality management system or other applicable conformity assessment procedures;
Information shall be provided to obtain a general understanding of the manufacturing process for the IVD under investigation. It is not intended to replace the more detailed information required for a quality management system (QMS) audit or other conformity assessment activity. A process flow chart showing an overview of the different steps in the manufacturing process, instead of extensive documentation, is considered acceptable.	
	
b.	identification of all sites, including suppliers and sub-contractors, where manufacturing activities are performed.
The documentation shall contain information about the QMS for manufacturing. QMS certificates are considered acceptable and a clear copy of the original certificates shall be provided.
Note: NEN-EN-ISO 13485 [3] is the standard used for QMS by nearly all manufacturers of IVDs.

If a company is not yet certified to NEN-EN-ISO 13485, the IMDD-IVD shall contain a statement, that procedures are available for the following (as applicable):
- Design control
- Supplier selection and control
- Production control for the study batches
- Performance evaluation / performance study
In this case, the manufacturer should also indicate the planning for obtaining the NEN-EN-ISO 13485 certification. 

For IVDs, manufactured and used only within a single health institution, information to allow an understanding of the QMS applied should be provided. The laboratory of the health institution has to provide proof of compliance with NEN-EN-ISO 15189 [4]. In addition, a rationale whether this QMS is considered appropriate for the design and manufacture of the IVD under investigation, or whether additional elements are deemed necessary (e.g. comparing to NEN-EN-ISO 13485). It is not intended to replace the more detailed information required for a QMS audit or other conformity assessment activity. A process flow chart showing an overview of the different aspects of the quality management process, instead of extensive documentation, is considered acceptable. 	
	
4.	General safety and performance requirements
The documentation shall contain information for the demonstration of conformity with the general safety and performance requirements set out in Annex I that are applicable to the device taking into account its intended purpose, and shall include a justification, validation and verification of the solutions adopted to meet those requirements. The demonstration of conformity shall include:
a.	the general safety and performance requirements that apply to the device and an explanation as to why others do not apply;	
	
b.	the method or methods used to demonstrate conformity with each applicable general safety and performance requirement;	
	
c.	the harmonised standards, CS or other solutions applied;

d.	the precise identity of the controlled documents offering evidence of conformity with each harmonised standard, CS or other method applied to demonstrate conformity with the general safety and performance requirements. The information referred to under this point shall incorporate a cross-reference to the location of such evidence within the full technical documentation and, if applicable, the summary technical documentation.

This information is usually reported in a checklist. Appendix II of the IMDD-IVD provides an example of such a checklist.
At the time of the submission of the IMDD-IVD to the MREC, all GSPRs need to be fully addressed, except for the GSPRs that require (additional) evidence intended to be obtained through the performance study. GSPRs, where the performance study will be providing (additional) evidence, shall be clearly identified, and it shall be explained how the data obtained in the study will contribute to fulfilling the specific GSPR. 
In the GSPR checklist, documents shall be referenced that demonstrate conformity to a specific GSPR. The documents referenced in the checklist do not need to be submitted, if not required in other items of the IMDD-IVD. 
5.	Benefit-risk analysis and risk management
The documentation shall contain information on:
a.	the benefit-risk analysis referred to in Sections 1 and 8 of Annex I, and

b.	the solutions adopted and the results of the risk management referred to in Section 3 of Annex I.

The documentation shall contain the latest versions of the document(s) containing the risks identified, analysed and evaluated, and how these risks have been mitigated or controlled to an acceptable level, usually the risk analysis. 
It should be identified which risks, related to the design and use of the device, are specifically investigated in the performance study. A justification shall be provided why it is considered acceptable to start the performance study in view of the uncertainties about these risks. Preferably, a multidisciplinary team has been involved in the risk analysis and the involvement of the team members that had a significant contribution to the risk analysis shall be mentioned in the risk analysis. 
NEN-EN-ISO 14971 [5] is the standard used for the risk management system by nearly all manufacturers of IVDs. If the standard NEN-EN-ISO 14971 is not used, a rationale shall be provided why this standard is not used and why the approach taken is considered to be at least as appropriate as using NEN-EN-ISO 14971.
See Appendix III of the IMDD-IVD for more information on risk management.
6.	Product verification and validation
The documentation shall contain the results and critical analyses of all verifications and validation tests and/or studies undertaken to demonstrate conformity of the device with the requirements of this Regulation and in particular the applicable general safety and performance requirements.
6.1	Information on the analytical performance of the device
6.1.1 Specimen type
This Section shall describe the different specimen types that can be analysed, including their stability such as storage, where applicable specimen transport conditions and, with a view to time-critical analysis methods, information on the timeframe between taking the specimen and its analysis and storage conditions such as duration, temperature limits and freeze/thaw cycles.
The information provided shall include a description of how the specimen types are obtained.

6.1.2 Analytical performance characteristics
6.1.2.1 Accuracy of measurement

a) Trueness of measurement 
This Section shall provide information on the trueness of the measurement procedure and summarise the data in sufficient detail to allow an assessment of the adequacy of the means selected to establish the trueness. Trueness measures apply to both quantitative and qualitative assays only when a certified reference material or certified reference method is available.

b) Precision of measurement 
This Section shall describe repeatability and reproducibility studies.

6.1.2.2 Analytical sensitivity

This Section shall include information about the study design and results. It shall provide a description of specimen type and preparation including matrix, analyte levels, and how levels were established. The number of replicates tested at each concentration shall also be provided as well as a description of the calculation used to determine assay sensitivity.
This section should contain information about the limit of detection and limit of quantification.

6.1.2.3 Analytical specificity

This Section shall describe interference and cross reactivity studies performed to determine the analytical specificity in the presence of other substances/agents in the specimen. 

Information shall be provided on the evaluation of potentially interfering and cross-reacting substances or agents on the assay, on the tested substance or agent type and its concentration, specimen type, analyte test concentration, and results. 

Interferents and cross-reacting substances or agents, which vary greatly depending on the assay type and design, could derive from exogenous or endogenous sources such as:  
a)	substances used for patient treatment such as medicinal products; 
b)	substances ingested by the patient such as alcohol, foods; 
c)	substances added during specimen preparation such as preservatives, stabilisers; 
d)	substances encountered in specific specimen types such as haemoglobin, lipids, bilirubin, proteins; 
e)	analytes of similar structure such as precursors, metabolites or medical conditions unrelated to the test condition including specimens negative for the assay but positive for a condition that can mimic the test condition. 	

6.1.2.4 Metrological traceability of calibrator and control material values

6.1.2.5 Measuring range of the assay

This Section shall include information on the measuring range regardless of whether the measuring systems are linear or non-linear, including the limit of detection and describe information on how the range and detection limit were established.
This section should contain information about the limit of detection and limit of quantification.

This information shall include a description of specimen type, number of specimens, number of replicates, and specimen preparation including information on the matrix, analyte levels and how levels were established. If applicable, a description of any high dose hook effect and the data supporting the mitigation such as dilution steps shall be added.

6.1.2.6 Definition of assay cut-off

This Section shall provide a summary of analytical data with a description of the study design including methods for determining the assay cut-off, such as: 
a)	the population(s) studied: demographics, selection, inclusion and exclusion criteria, number of individuals included; 
b)	method or mode of characterisation of specimens; and 
c)	statistical methods such as Receiver Operator Characteristic (ROC) to generate results and if applicable, define grey-zone/equivocal zone.

6.1.3 The analytical performance report referred to in Annex XIII
6.2	Information on clinical performance and clinical evidence. Performance Evaluation Report
The documentation shall contain the performance evaluation report, which includes the reports on the scientific validity, the analytical and the clinical performance, as referred to in Annex XIII, together with an assessment of those reports.

The clinical performance study documents referred to in Section 2 of Part A of Annex XIII shall be included and/or fully referenced in the technical documentation.

For a non-CE-marked IVD, a final performance evaluation report will not be available at the time of submitting an application for a performance study with that device. However, the sponsor shall submit the performance evaluation plan, in which the performance study is included [1], either as Annex to the IMDD-IVD or as separate document referenced in the IMDD-IVD. A performance evaluation plan is not required for in-house manufactured IVDs. 
For a CE-marked IVD, the latest version of the performance evaluation report can provide useful information for the MREC. Also the PMPF plan and the PMPF evaluation report referred to in Part B of Annex XIII shall be included. If PMPF is not deemed appropriate for a specific device a justification shall be provided and documented within the performance evaluation report.

6.3	Stability (excluding specimen stability)
This Section shall describe claimed shelf life, in use stability and shipping stability studies.
6.3.1 Claimed shelf-life
This Section shall provide information on stability testing studies to support the shelf life that is claimed for the device. Testing shall be performed on at least three different lots manufactured under conditions that are essentially equivalent to routine production conditions. The three lots do not need to be consecutive. Accelerated studies or extrapolated data from real time data are acceptable for initial shelf life claims but shall be followed up with real time stability studies. 

Such detailed information shall include: 
a)	the study report including the protocol, number of lots, acceptance criteria and testing intervals; 
b)	where accelerated studies have been performed in anticipation of the real time studies, the method used for accelerated studies shall be described; 
c)	the conclusions and claimed shelf life.

6.3.2 In-use stability
This Section shall provide information on in-use stability studies for one lot reflecting actual routine use of the device, regardless of whether real or simulated. This may include open vial stability and/or, for automated instruments, on board stability.

In the case of automated instrumentation, if calibration stability is claimed, supporting data shall be included. 

Such detailed information shall include: 
a)	the study report (including the protocol, acceptance criteria and testing intervals); 
b)	the conclusions and claimed in-use stability.

6.3.3 Shipping stability
This Section shall provide information on shipping stability studies for one lot of devices to evaluate the tolerance of devices to the anticipated shipping conditions. 

Shipping studies may be done under real and/or simulated conditions and shall include variable shipping conditions such as extreme heat and/or cold. 

Such information shall describe: 
a)	the study report (including the protocol, acceptance criteria); 
b)	the method used for simulated conditions; 
c)	the conclusion and recommended shipping conditions.

6.4	Software verification and validation
The documentation shall contain evidence of the validation of the software, as it is used in the finished device. Such information shall typically include the summary results of all verification, validation and testing performed in-house and applicable in an actual user environment prior to final release. It shall also address all of the different hardware configurations and, where applicable, operating systems identified in the labelling.
For software, a number of standards are available. The list with standards below is not exhaustive, other standards can also be applicable. 
NEN-EN-IEC 62304:2006 Medical device software – Software life cycle processes [6], covers both software as a component of a medical device and standalone software (a medical device in its own right). 
NEN-EN-IEC 82304-1:2017 Health Software – Part 1: General requirements [7], provides requirements for the safety and security of health software products.
NEN-EN-IEC 60601-1:2005 Medical electrical equipment – Part 1: General requirements for basic safety and essential performance [8], contains a section specifically on programmable electrical medical systems.

For the choice of methods and standards used for software verification and validation, the manufacturer shall provide a rationale. 

6.5	Additional information required in specific areas
(a) In the case of devices placed on the market in a sterile or defined microbiological condition, a description of the environmental conditions for the relevant manufacturing steps. In the case of devices placed on the market in a sterile condition, a description of the methods used, including the validation reports, with regard to packaging, sterilisation and maintenance of sterility. The validation report shall address bioburden testing, pyrogen testing and, if applicable, testing for sterilant residues.
Information shall be submitted to show that the efficacy of the sterilization process used is sufficient for this specific IVD. Such information is usually provided in a validation report. If other testing was performed or additional testing was not considered necessary, a rationale to substantiate that decision shall be provided. A summary of the results of other testing shall be submitted. 
Note 1: for ethylene oxide sterilization, specific guidance for sterilizing small batches, e.g. for products used during performance studies, has been developed as an annex to standard NEN-EN-ISO 11135 [9].
Note 2: for reusable devices, the validated method for reprocessing shall be included in the instructions for use. The validation report of the reprocessing method should be made available upon request.

(b) In the case of devices containing tissues, cells and substances of animal, human or microbial origin, information on the origin of such material and on the conditions in which it was collected.
The documentation shall contain information on the tissues, cells or substances, the specific risk management in relation to the tissues, cells or substances, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the IVD.

(c) In the case of devices placed on the market with a measuring function, a description of the methods used in order to ensure the accuracy as given in the specifications.

(d) If the device is to be connected to other equipment in order to operate as intended, a description of the resulting combination including proof that it conforms to the general safety and performance requirements set out in Annex I when connected to any such equipment having regard to the characteristics specified by the manufacturer.
The description of this combination/configuration used in the performance study shall be submitted, including a rationale why this combination is considered safe and effective.

References
[1] Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Council Directives 98/79/EC and Commission Decision 2010/227/EU

[2] NEN-ISO 20916:2019 In vitro diagnostic medical devices – Clinical performance studies using specimens from human subjects – Good study practice

[3] NEN-EN-ISO 13485:2016 Medical devices – Quality management systems – Requirements for regulatory purposes

[4] NEN-EN-ISO 15189:2023 Medical laboratories – Requirements for quality and competence

[5] NEN-EN-ISO 14971:2019 Medical devices – Application of risk management to medical devices

[6] NEN-EN-IEC 62304:2006 Medical device software – Software life-cycle processes

[7] NEN-EN-IEC 82304-1:2017 Health software – Part 1: General requirements for product safety

[8] NEN-EN-IEC 60601-1:2005 Medical electrical equipment – Part 1: General requirements for basic safety and essential performance

[9] NEN-EN-ISO 11135:2014 AMD 2018 Sterilization of health care products – Ethylene oxide – Requirements for the development, validation and routine control of a sterilization process for medical devices 

[10] ISO/TR 24971:2020 Medical devices – Guidance on the application of ISO 14971

Appendix I Table of contents for the IMDD-IVD to be submitted
Paragraph
IMDD-IVD	Description	Applicable
(yes/no)	Reference to submitted documentation (document(s) number/annex number)	
1.1	Device description and specification			
1.2	Reference to previous and similar generations of the device			
2.a	Label(s) on the device and on its packaging			
2.b	Instructions for use			
3.1	Design information (flow chart)			
3.2	Manufacturing information (flow chart)			
4	Checklist GSPRs			
5	Benefit-risk analysis and risk management			
6.1.1	Specimen type			
6.1.2.1	Accuracy of measurement			
6.1.2.2	Analytical sensitivity			
6.1.2.3	Analytical specificity			
6.1.2.4	Metrological traceability of calibrator and control material values			
6.1.2.5	Measuring range of the assay			
6.1.2.6	Definition of assay-cut-off			
6.1.3	Analytical performance report referred to in Annex XIII			
6.2	Information on clinical performance and clinical evidence. Performance Evaluation Report			
6.3.1	Claimed shelf-life			
6.3.2	In-use stability			
6.3.3	Shipping stability			
6.4	Software verification and validation			
6.5.a	Devices delivered sterile or in a defined microbiological condition			
6.5.b	Devices containing tissues, cells, and substances of animal, human or microbiological origin			
6.5.c	Measuring function			
6.5.d	Connection to other equipment			
				
Optional for CE-marked device	SSP of class C and D CE-marked IVDs			

 Appendix II Checklist GSPRs 
Example layout Checklist GSPRs:
Note: this is just an example, tables with a different format, but containing all necessary information, can also be acceptable. 

Location				
Dated				
Title or reference of documentary evidence				
Relevant applied standard(s) used for this product				
Description of fulfilment of requirement				
Applicable/ 
not applicable				
GSPRs	Chapter I: General requirements	1 Devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose. They shall be safe and effective and shall not compromise the clinical condition or the safety of patients, or the safety and health of users or, where applicable, other persons, provided that any risks which may be associated with their use constitute acceptable risks when weighed against the benefits to the patient and are compatible with a high level of protection of health and safety, taking into account the generally acknowledged state of the art. 	Etc.	

The GSPRs in Annex I of the IVDR cover the following elements. Each element can consist of multiple separate items:

CHAPTER I: 
General Requirements
GPSR 1-8:	General requirements, mainly related to risk management and benefit-risk ratio
CHAPTER II:
Requirements regarding performance, design and manufacture
GSPR 9:	Performance characteristics
GSPR 10:	Chemical, physical and biological properties
GSPR 11:	Infection and microbial contamination
GSPR 12:	Devices incorporating materials of biological origin
GSPR 13:	Construction of devices and interaction with their environment
GSPR 14:	Devices with a measuring function
GSPR 15:	Protection against radiation
GSPR 16:	Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves
GSPR 17:	Devices connected to or equipped with an energy source
GSPR 18:	Protection against mechanical and thermal risks
GSPR 19:	Protection against the risks posed by devices intended for self-testing or near-patient testing
CHAPTER III:
Requirements regarding information supplied with the device
GSPR 20:	Label and instructions for use

Appendix III Risk management 
The following table is an example of a table that can be used for the risk analysis. 

Example layout of a table with hazard identification, estimation and mitigation etc.
Note: this is just an example, tables with a different format, but containing all necessary information, can also be acceptable. 

Residual risks, if applicable			
Comment
			
Acceptable/not acceptable 			
Residual risk estimated			
Mitigation measures			
Risks estimated			
Causes			
Hazard			

A risk analysis, which can consist of one document or be composed of several documents covering different types of risk, shall cover all possible hazards for the IVD concerned. Examples are given for several types of hazards that could be applicable in ISO/TR 24971 [10].