Investigational Medical Device Dossier

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

			

Table of contents

Abbreviations
Scope
IMDD 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
4.	General safety and performance requirements
5.	Benefit-risk analysis and risk management
6.	Product verification and validation
6.1	Pre-clinical and clinical data
6.2	Additional information required in specific cases
References
Appendix I Table of contents for the IMDD to be submitted
Appendix II Checklist GSPRs
Appendix III Risk management

Abbreviations

CE 		Conformité Européenne
CMR 		Carcinogenic, mutagenic of toxic to reproduction
EN		European standard
GSPR		General Safety and Performance Requirement
IMDD		Investigational Medical Device Dossier
ISO		International standard or the International Organization for Standardization
MDR		Medical Devices Regulation 2017/745
MREC		Medical Research Ethics Committee
NEN		Dutch standard
PMCF		Post-market clinical follow-up
QMS		Quality Management System
SSCP		Summary of Safety and Clinical Performance
STED		Summary TEchnical Documentation

Scope
The Investigational Medical Device Dossier (IMDD) 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 medical devices within the scope of the Medical Devices Regulation 2017/745 (MDR) [1], which are intended for clinical investigation. If a non-CE-marked medical device, manufactured and used only within a single health institution (in-house manufactured medical device), is subject to a clinical investigation, all items specified in this IMDD are also considered applicable. A clear rationale and justification shall be provided for any deviation(s) from the IMDD. For CE-marked medical devices used outside the intended use, the format of the IMDD can also be used, see also the paragraph on information to be submitted. 
Good clinical practice and the design and conduct of the clinical investigation are outside the scope of the IMDD and shall be described in the clinical investigation plan. The requirements regarding personal data protection are also outside the scope of the IMDD. 
IMDD format
The requirements for information to be submitted by a sponsor of a clinical investigation with a non CE-marked medical device are laid down in Annex XV of the MDR. However, the information to be submitted is mostly stated generally. Section 4.6 of Chapter II of Annex XV allows the competent authority to request additional information to be submitted. Annex II of the MDR contains detailed requirements for the technical documentation that a manufacturer has to compile to prove that the medical devices meet the requirements of the MDR. To facilitate uniform submission of documentation for medical devices for clinical investigation, it was decided to use the technical documentation requirements as specified in Annex II of the MDR as the basis for the documentation to be submitted. This IMDD 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 first version of the IMDD was published in 2011 and was based on the Summary TEchnical Documentation (STED) drawn up by the Global Harmonization Task Force [2]. The required information in this updated version of the IMDD does not significantly differ from the information required in the first version of the IMDD. However, the structure and numbering of the items to be submitted are different. 
The text of Annex II of the MDR is presented in normal type font. Reference to annexes in that part of the IMDD refer to Annexes of the MDR. For the IMDD, reference is made to appendices. Bold text is guidance to the required information in the MDR.
Where it is mentioned in Annex II of the MDR that a medical device is ‘placed on the market’, for the IMDD, this should be read and understood as ‘used in the clinical investigation’. The term ‘manufacturer’ could in several instances be read and understood as ‘sponsor of the clinical investigation’. 

Information to be submitted
The sponsor of the clinical investigation, regardless whether it is a legal manufacturer or an investigator, shall use the IMDD format for submitting the required documentation to the MREC. The information in the IMDD and the information referred to in the IMDD can be submitted in English or in Dutch. 
To obtain adequate and complete information in the IMDD, active involvement of the manufacturer of the investigational medical device is advisable, as they should have all technical information required for the IMDD available.

The information requested in the IMDD 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 item is dealt with in another item or document supplied for the clinical investigation, for instance the investigator’s brochure, as described in NEN-EN-ISO 14155 [3], 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. Appendix I of the IMDD provides a table of contents for the documentation set. Using that table, cross references can be made between the items required by the IMDD and the documents submitted. If an item of the IMDD is not applicable for a medical device (e.g. ‘electrical safety’ or ‘medicinal substances’), this shall be clearly indicated.
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 imaging devices) 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 medical device and needs clinical investigation data to support the change, no full IMDD of the original medical device needs to be submitted. The documentation submitted shall contain a clear description of the change(s) as compared to the CE-marked medical device and its intended use(s) and a rationale for the change to the medical device. The documentation shall contain a description which items of the IMDD are affected by the change and updated documentation on these items shall be submitted. The items medical device description (item 1), instructions for use (item 2), risk benefit analysis (see item 5) and General Safety and Performance Requirements (GSPRs, see item 4) will always have to be submitted. This will provide insight into the changes and how all GSPRs are addressed for the new design/intended use and how additional risk related to the change have been addressed. 
If a Summary of Safety and Clinical Performance (SSCP) has been drawn up for a CE-marked medical device as described above, this SSCP shall also be supplied. 
In the IMDD, the use of harmonized standards for fulfilling requirements of the MDR is preferred. Therefore, harmonized 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 in the requirements in the MDR and therefore in the IMDD. 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 medical device shall be included, either a UDI, which is only required for medical devices to be brought onto the market, or another unambiguous reference. 	
	
c.	the intended patient population and medical conditions to be diagnosed, treated and/or monitored and other considerations such as patient selection criteria, indications, contra-indications, warnings;
This concerns the contra-indications and warnings known prior to the start of the clinical investigation. 	
	
d.	principles of operation of the device and its mode of action, scientifically demonstrated if necessary;	
	
e.	the rationale for the qualification of the product as a device;
Please note that device in the context of the MDR means every device that falls under the MDR, i.e. a medical device, an accessory or an Annex XVI device.	
	
f.	the risk class of the device and the justification for the classification rule(s) applied in accordance with Annex VIII;

g.	an explanation of any novel features;
Novel should be interpreted as novel to previous versions of the medical device or similar products on the market.

h.	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 it;	
	
i.	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 medical device to be used in the clinical investigation.  A rationale shall be included explaining why these configurations are used for the clinical investigation.

j.	a general description of the key functional elements, e.g. its parts/components (including software if appropriate), its formulation, its composition, its functionality and, where relevant, its qualitative and quantitative composition. Where appropriate, this shall include labelled pictorial representations (e.g. diagrams, photographs, and drawings), clearly indicating key parts/components, including sufficient explanation to understand the drawings and diagrams;	
	
k.	a description of the raw materials incorporated into key functional elements and those making either direct contact with the human body or indirect contact with the body, e.g., during extracorporeal circulation of body fluids;	
	
l.	technical specifications, such as features, dimensions and performance attributes, of the device and any variants/configurations and accessories that would typically appear in the product specification made available to the user, for example in brochures, catalogues and similar publications.
This concerns the variants/configurations and accessories to be used in the clinical investigation. 	

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 medical device 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 medical devices 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; and	
	
b.	the instructions for use in the languages accepted in the Member States where the device is envisaged to be sold.	

The labels(s) on the medical devices and the packaging and the instructions for use shall be the ones associated with the medical devices as used during the clinical investigation. The packaging does not have to be the final sales packaging. The label shall include the words “exclusively for clinical investigations” or “uitsluitend voor klinisch onderzoek”, as required by the MDR, Annex I, clause 23.2(q) or clause 23.3(f). For professional users, such as physicians, laboratory technicians and nurses, both English and Dutch are accepted languages for the instructions for use.
The instructions for use shall comply with the requirements from paragraph 23.4 from Annex I of the MDR. 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 medical device, e.g. for installation, maintenance or maintaining hygienic standards, do not have to be submitted as part of the IMDD. 
Note 1: these documents should be included as part of the investigator’s brochure. 
Note 2: instructions for use have to be included for class IIb and class III medical devices. By way of exception, instructions for use are not required for class I and class IIa medical devices if such medical devices can be used safely 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
a.	information to allow the design stages applied to the device to be understood;
Information shall be provided to obtain a general understanding of the design process for the medical device 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 design process, instead of extensive documentation, is considered acceptable.	
	
b.	complete information and specifications, including the manufacturing processes and their validation, their adjuvants, the continuous monitoring and the final product testing. Data shall be fully included in the technical documentation;
The documentation shall contain information to allow a reviewer to obtain a general understanding of the manufacturing processes. 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 production, assembly, any final product testing, and packaging of the finished medical device, instead of extensive documentation, is considered acceptable.	
	
c.	identification of all sites, including suppliers and sub-contractors, where design and manufacturing activities are performed. 
The documentation shall contain information about the QMS for design and manufacturing. QMS certificates are considered acceptable and a clear copy of the original certificates shall be provided.
Note: NEN-EN-ISO 13485 [4] is the standard used for QMS by nearly all manufacturers of medical devices.

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

For medical devices, manufactured and used only within a single health institution, information to allow an understanding of the QMS applied should be provided. 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, together with a rationale why this QMS is considered appropriate for the design and manufacture of the medical device under investigation (e.g. comparing to NEN-EN-ISO 13485). 	

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, common specification or other solutions applied; and	
	
d)	the precise identity of the controlled documents offering evidence of conformity with each harmonised standard, common specification 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 provides an example of such a checklist.
At the time of the submission of the IMDD to the MREC, all GSPRs need to be fully addressed, except for the GSPRs that require (additional) evidence intended to be obtained through the clinical investigation. GSPRs, where the clinical investigation will be providing (additional) evidence, shall be clearly identified, and it shall be explained how the data obtained in the investigation 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. 

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 (of the MDR), 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 clinical investigation. A justification shall be provided why it is considered acceptable to start the clinical investigation 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 medical devices. 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 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	Pre-clinical and clinical data
a.	results of tests, such as engineering, laboratory, simulated use and animal tests, and evaluation of published literature applicable to the device, taking into account its intended purpose, or to similar devices, regarding the pre-clinical safety of the device and its conformity with the specifications;
For the literature evaluation, a description of the search protocol, references to the publications included in the review, a summary of the review and conclusions shall be submitted. 	
	
b.	detailed information regarding test design, complete test or study protocols, methods of data analysis, in addition to data summaries and test conclusions regarding in particular:
For all applicable testing mentioned in the following bullet items, at least a summary of the tests conducted, the methodology, standards applied, results and conclusions shall be submitted. Detailed information regarding test design (e.g. test protocols) and test results is not required. 
Also, a short rationale for the selection of the tests conducted shall be provided.	
	
•	the biocompatibility of the device including the identification of all materials in direct or indirect contact with the patient or user;
At a minimum, tests shall be conducted on samples from the finished, sterilised (when supplied sterile) medical device. Data of previously tested medical devices/materials/products can be used to show biocompatibility. 
If biocompatibility testing has been undertaken on materials and/or previous versions of the medical device, this information can be used for the current device. A rationale shall be provided on the applicability of the available data and the testing still required for the current medical devices. This information should be available in the biological safety evaluation report (see the horizontal standard on biological safety testing, ISO 10993-1 [6]).
See 6.1.b for the level of detail required.	
	
•	physical, chemical and microbiological characterisation;
The applicable physical, chemical and microbiological specifications shall be provided, no further information on testing has to be submitted. 	
	
•	electrical safety and electromagnetic compatibility;
See 6.1.b for the level of detail required.	
	
•	software verification and validation (describing the software design and development process and evidence of the validation of the software, as used in the finished device. This information shall typically include the summary results of all verification, validation and testing performed both in-house and in a simulated or 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 information supplied by the manufacturer);
For software, a number of standards are available. Three standards are elaborate upon underneath, but this list is not exhaustive and other standards can also be applicable. 
NEN-EN-IEC 62304:2006 Medical device software – Software life cycle processes [7], 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 [8], 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 [9], 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. 
See 6.1.b for the level of detail required.	
	
•	stability, including shelf life; and
The manufacturer shall indicate the shelf life for the medical devices used during the clinical investigation and on which information/testing the determination of the shelf life was based. 	
	
•	performance and safety.
For a clinical investigation with a non-CE-marked device, other testing performed than mentioned above (e.g. on usability) prior to the commencement of the clinical investigation shall be submitted, which could include clinical data.
See 6.1.b for the level of detail required.	

Where applicable, conformity with the provisions of Directive 2004/10/EC of the European Parliament and of the Council shall be demonstrated.
Directive 2004/10/EC relates to the application of the principles of good laboratory practice and the verification of their applications for tests on chemical substances. 
Where no new testing has been undertaken, the documentation shall incorporate a rationale for that decision. An example of such a rationale would be that biocompatibility testing on identical materials was conducted when those materials were incorporated in a previous version of the device that has been legally placed on the market or put into service.
See also the requirements on biocompatibility, 6.1.b), first bullet point. 

c.	the clinical evaluation report and its updates and the clinical evaluation plan referred to in Article 61(12) and Part A of Annex XIV;
For a non-CE-marked medical device, a final clinical evaluation report will not be available at the time of submitting an application for a clinical investigation with that device. However, the sponsor shall submit the clinical evaluation plan, in which the clinical investigation is included [1], either as Annex to the IMDD or as separate document referenced in the IMDD. The clinical evaluation plan shall also indicate how other testing, as presented in 6.1 of the IMDD, is included in the clinical evaluation of the medical device. A clinical evaluation plan is not required for in-house manufactured medical devices (see Article 82 of the MDR). 
For a CE-marked medical device, the latest version of the clinical evaluation report can provide useful information for the MREC.	
	
d.	the PMCF plan and PMCF evaluation report referred to in Part B of Annex XIV or a justification why a PMCF is not applicable.
For a non-CE-marked medical device, a post-market clinical follow-up (PMCF) plan is not yet necessary.  	

6.2	Additional information required in specific cases 
a.	Where a device incorporates, as an integral part, a substance which, if used separately, may be considered to be a medicinal product within the meaning of point 2 of Article 1 of Directive 2001/83/EC, including a medicinal product derived from human blood or human plasma, as referred to in the first subparagraph of Article 1(8), a statement indicating this fact. In this case, the documentation shall identify the source of that substance and contain the data of the tests conducted to assess its safety, quality and usefulness, taking account of the intended purpose of the device.
The documentation shall contain information on the medicinal substance and the specific risks related to the substance and the management of such risks, as well as evidence for the added value of incorporation of such constituent in relation to the clinical benefit and/or safety of the medical device. 
If a scientific opinion of the national competent authority or the European Medicines Agency is available, this is considered sufficient. The scientific opinion concerns the quality and safety of the registered medicinal product including the clinical benefit/risk profile of the incorporation of the substance into the medical device. No further information required in this case.	
	
b.	Where a device is manufactured utilising tissues or cells of human or animal origin, or their derivatives, and is covered by this Regulation in accordance with points (f) and (g) of Article 1(6), and where a device incorporates, as an integral part, tissues or cells of human origin or their derivatives that have an action ancillary to that of the device and is covered by this Regulation in accordance with the first subparagraph of Article 1(10), a statement indicating this fact. In such a case, the documentation shall identify all materials of human or animal origin used and provide detailed information concerning the conformity with Sections 13.1. or 13.2., respectively, of Annex I.
The documentation shall contain information on the tissues, cells or their derivatives, and the specific risk management in relation to the tissues, cells or their derivatives, as well as evidence for the added value of incorporation of such constituents in relation to the clinical benefit and/or safety of the medical device.	
	
c.	In the case of devices that are composed of substances or combinations of substances that are intended to be introduced into the human body and that are absorbed by or locally dispersed in the human body, detailed information, including test design, complete test or study protocols, methods of data analysis, and data summaries and test conclusions, regarding studies in relation to:
•	absorption, distribution, metabolism and excretion;
•	possible interactions of those substances, or of their products of metabolism in the human body, with other devices, medicinal products or other substances, considering the target population, and its associated medical conditions;
•	local tolerance; and
•	toxicity, including single-dose toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity and reproductive and developmental toxicity, as applicable depending on the level and nature of exposure to the device.

In the absence of such studies, a justification shall be provided.
See 6.1.b for the level of detail required. 	
	
d.	In the case of devices containing CMR or endocrine-disrupting substances referred to in Section 10.4.1 of that Annex I, the justification referred to in Section 10.4.2 of that Annex.	
	
e.	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 respect 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 medical device. 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 clinical studies, has been developed as an annex to standard NEN-EN-ISO 11135 [10].
Note 2: for reusable medical 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.	
	
f.	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.	
	
g.	If the device is to be connected to other device(s) in order to operate as intended, a description of this combination/configuration including proof that it conforms to the general safety and performance requirements when connected to any such device(s) having regard to the characteristics specified by the manufacturer.
The description of this combination/configuration used in the clinical investigation shall be submitted, including a rationale why this combination is considered safe and effective. 	

References
[1] Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002 and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC

[2] GHTF/SG1/N011:2008 Summary technical documentation for demonstrating conformity to the essential principles of safety and performance of medical devices (STED)

[3] NEN-EN-ISO 14155:2020 Clinical investigation of medical devices for human subjects – Good clinical practice

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

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

[6] ISO 10993-1:2018 Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process
Note: during the development of this version of the IMDD, ISO 10993-1 was recently published and the European version (EN ISO 10993-1) was not yet available. 

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

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

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

[10] 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 

Appendix I Table of contents for the IMDD to be submitted

Paragraph
IMDD	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.a	Design information (flow chart)			
3.b	Manufacturing information (flow chart)			
3.c	QMS documentation			
4	Checklist GSPRs			
5	Benefit-risk analysis and risk management			
6.1.a	Results of testing			
6.1.b	Information of biocompatibility testing			
6.1.b	Physical, chemical and microbiological characterization			
6.1.b	Electrical safety and electromagnetic compatibility			
6.1.b	Software verification and validation			
6.1.b	Stability, including shelf life			
6.1.b	Performance and safety			
6.1.c	Clinical evaluation report and clinical evaluation plan			
6.1.d	PMCF plan and PMCF evaluation report			
6.2.a	Medicinal substance			
6.2.b	Tissues/cells of human or animal origin			
6.2.c	Substances intended to be absorbed or locally dispersed in the human body 			
6.2.d	CMR or endocrine-disrupting substances			
6.2.e	Product delivered sterile or in a defined microbiological condition			
6.2.f	Measuring function			
6.2.g	Connection to other devices			
				
Optional for CE-marked device	SSCP for implantable or class III CE-marked medical devices			

 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 MDR cover the following elements. Each element can consist of multiple separate items:

CHAPTER I: 
General Requirements
GPSR 1-9:	General requirements, mainly related to risk management and benefit-risk ratio
CHAPTER II:
Requirements regarding design and manufacture
GSPR 10:	Chemical, physical and biological properties
GSPR 11:	Infection and microbial contamination
GSPR 12:	Devices incorporating a substance considered to be a medicinal product and devices that are composed of substances or of combinations of substances that are absorbed by or locally dispersed in the human body
GSPR 13:	Devices incorporating materials of biological origin
GSPR 14:	Construction of devices and interaction with their environment
GSPR 15:	Devices with a diagnostic or measuring function
GSPR 16:	Protection against radiation
GSPR 17:	Electronic programmable systems — devices that incorporate electronic programmable systems and software that are devices in themselves
GSPR 18:	Active devices and devices connected to them
GSPR 19:	Particular requirements for active implantable devices
GSPR 20:	Protection against mechanical and thermal risks
GSPR 21:	Protection against the risks posed to the patient or user by devices supplying energy or substances
GSPR 22:	Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons
CHAPTER III:
Requirements regarding the information supplied with the device
GSPR 23:	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 medical device concerned. In the table underneath, examples are given for several types of hazards that could be applicable (NEN-EN-ISO 14971:2019, Table C.1). 

ENERGY HAZARDS 	BIOLOGICAL AND CHEMICAL HAZARDS 	FUNCTIONALITY AND INFORMATION HAZARDS 	
Acoustic energy
•	infrasound
•	sound pressure
•	ultrasonic
Electric energy
Electric fields
Leakage current
•	earth leakage
•	enclosure leakage
Magnetic fields
Static discharge
Voltage
Mechanical energy
Kinetic energy
•	falling objects
•	high pressure fluid injection
•	moving parts
•	vibrating parts
Potential (stored) energy
•	bending
•	compression
•	cutting, shearing
•	gravitational pull
•	suspended mass
•	tension
•	torsion
Radiation energy
Ionizing radiation
•	accelerated particles (alpha particles, electrons, protons, neutrons)
•	gamma
•	x-ray
Non-ionizing radiation
•	infrared
•	laser
•	microwave
•	ultraviolet
Thermal energy
Cryogenic effects
Hyperthermic effects	Biological agents
Bacteria
Fungi
Parasites
Prions
Toxins
Viruses
Chemical agents
Carcinogenic, mutagenic, reproductive
Caustic, corrosive
•	acidic
•	alkaline
•	oxidants
Flammable, combustible, explosive
Fumes, vapours
Osmotic
Particles (including micro-and nano-particles)
Pyrogenic
Solvents
Toxic
•	asbestos
•	heavy metals
•	inorganic toxicants
•	organic toxicants
•	silica
Immunological agents
Allergenic
•	antiseptic substances
•	latex
Immunosuppressive
Irritants
•	cleaning residues
Sensitizing	Data
•	access
•	availability
•	confidentiality
•	data transfer
•	integrity
Delivery
•	quantity
•	rate
Diagnostic information
•	examination result
•	image artefacts
•	image orientation
•	image resolution
•	patient identity / information
Functionality
•	alarm
•	critical performance
•	measurement