Medical Device Regulation EU 2017/745 (MDR)

The Medical Device Regulation EU 2017/745 is a highly important document outlining the requirements for any medical device. Through this, you will be able to understand the key requirements within the Medical Device Regulation. Although the new device regulation of 2023 has also been introduced, you can read about it in a separate post. In this section, we are providing complete information on the EU Medical Device Regulation 2017/745, and we hope it will be of significant help to you.

Related: MDSAP Audit

1. DEVICE DESCRIPTION AND SPECIFICATION:

1.1 Device Description and Specification:

a. Provide a name of the product or a trade name and state the purpose of the device. Who will use it:

This section must define product name in a generic version that is approved by a local regulatory body. In India, Local regulatory body is Central Drug/Device Standard Control Organization (CDSCO). You have to ensure compliance with local regulations as well.

Brand/Trade Name: If your product has a brand/trade name, then mention it in this section. Your brand name must be approved by a local regulatory body before affixing to products.

Intended purpose/Use: Intended purpose/use means what exactly your product is used for. Mention possible use of the product. Note: Every product has an intended use but not all products have an indication for use. Example: Hand sanitizer/disinfectant/Antiseptic.

Intended user: It is the responsibility of a manufacturer to ensure that products marketed by him shall be used safely by adequate users and must achieve their intended purpose when used as per instruction for use. So, it is your responsibility to define the exact USER of your product for safe use.

b. The Basic UDI-DI as defined in subsection C of the annex VI that has been assigned to the device being implanted as soon as Udi the system which provides a unique identification to the device becomes the basis for identifying the device, or where there is a product code, catalog number, or other unambiguous reference which provides means for traceability:

This section is meant for device traceability.

Device name: Mention here your product’s generic name and brand name. The brand name must be
registered under trademark registration.

Device serial no.: It is a unique number for each device manufactured under a particular batch.
Give the reference number of standard operating procedure for device serial number system in this section.

Basic UDI-DI: UDI-DI is a numeric or alphanumeric code that is specific to a model of device and is also the ‘access key’ required to retrieve information from the UDI database. Part C requirement of Annex VI applies to all devices in the high-risk category.

Product code/catalog number: Code number assigned by manufacturer at the time of design development or finish good code. The code numbering system varies from manufacturer to manufacturer. Your product shall have a code for purpose of tracking.

Batch No. /Lot No.: Mention batch number of device on product labels. Give reference number of standard operating procedure for batch numbering system in this section.

Drawing/Design number: Mention drawing/design number as per approved standard
operating procedure and mention a reference to that.

GMDN code: Mention here the correct GMDN code

Barcode: Mention details of bard code information. Also, you can take reference of ISO 22742:2010

Implant card if applicable: If your product is implantable, it is mandatory to issue an implant card with a device to maintain traceability. Mention document number, issue number, and revision of implant card.

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, and warnings:

Intended patient population: The patient population for your device must be rigorously defined including but not limited to age, sex, anatomy, physiology, body weight, clinical condition of patient, etc.

Medical conditions to be diagnosed, treated, and/or monitored: Mention clinical conditions where your product may be used.

Patient selection criteria: Mention patient inclusion and exclusion criteria for a device in question. It may also consider contraindications. It must ensure safety and performance of the device.

Indications/ Indication for use: Define exact clinical conditions for a device in question for which it can be used. These defined indications must be proved by clinical data held by manufacturer. Indications refer to the clinical condition/stage that is to be diagnosed, prevented, monitored, treated, alleviated, compensated for, replaced, modified, or controlled by the medical device. Example: The Antegrade Femoral Nail with standard locking is indicated for fractures in the femoral shaft: – 32-A/B/C (except subtrochanteric fractures 32-A [1-3].1, 32-B [1-3].1, and 32-C [1-3].1).

Contraindications: Then explain with references, the contraindications for your device in question. These are the conditions that do not permit the use of the device, as the risks involved in the use of the device are much higher than the benefits. E.g. for the Antegrade Femoral Nail with standard locking, there are contraindications such as Isolated neck of femur fractures — supracondylar fractures (localisation 32) — Intertrochanteric and pertrochanteric fractures.

Warnings: It may be in the form of written text, pictorial, video, or audible. it is alert to a hazard. Examples: Read instructions for use before use, Do not use if the package is damaged, and Do not reuse and reprocess.

d. State the operational principles of the device, and its action, and if necessary prove with scientific demonstration:

It may be presented in the form of pictures, audio, video, diagram, or written text. Explain how will your medical device achieve its intended purpose.

e. The reasoning behind the qualification of the product as a device:

For this particular section, you can refer definition of a medical device as per Article 2 of MDR 2017. Your device in question shall fulfill any one of requirements laid down in definition of a medical device. If your device is not meeting such requirements, then your device will be a non-medical device.

f. The risk class of the device and the rule or rules used for classification with justification under Annex VIII:

Make heading as below and define risk class of your device as per Annex VIII and Article 51 by implementing classification rule applied to your device and add a justification as to why these rules are applied. Why is it non-invasive or invasive? Why is it a transient use/short-term use/long-term use device?

g. An explanation of any novel features:

If your product has any unique feature that makes it different from other existing brands in the market, then mention such features in this section. Such features must be covered under risk management reports and shall be part of post-market surveillance for monitoring device safety and performance.

Describe key elements of your product in minimum words to understand the concept of its parts/ components, material of construction, principle of operation/ how it works.

h. A description of the raw materials used in the main functional parts of the device as well as those that are in contact with human skin or are in contact with body fluids during their circulation for example during EC of Bodly Fluid:

Describe material of construction those making either direct contact with the human body or indirect contact with the body with a national or international grade, in-house identification code informing of number or color, or both.

l. Technical information, such as the ranges or metrics, performance specifications, and such other parameters or attributes of devices or their variations/configurations and accessories as are likely to be included in the product specifications made to the users for instance in brochures, catalogs, and the like:

Describe the matter as recommended in heading and mention their reference number in
technical documentation where possible put complete information in technical file itself.

1.2 Citation of the predecessor including the last and predecessor generations of the device:

a. A summary of the previously made device(s) by the manufacturer(‘s) if they are available:

State relevant information. It is enough to provide a compact and informative outline of the essence of burdensome previous generations.

b. A survey of reach market for such devices in the Union or international markets where such devices exist:

Describe relevant information. A brief description of the key features of similar devices is sufficient if exists.

2. Information to be supplied by MANUFACTURER:

Information supplied by manufacturer includes Product Labels i.e. unit pack/primary package; Duplex/Secondary pack; Transit package: Instruction for use, and sales records. All this information
must be in a language that is accepted by importing member states. Instruction for use and labels must be part of the quality management system which is in compliance to EN ISO 13485. You can refer to ISO 15223-1:2021 & ISO 20417:2021 for information on Labeling requirements and information to be supplied by the manufacturer.

Related: Documents Required for Class A Medical Device

3. DESIGN & MANUFACTURING INFORMATION:

a. Data that enables the various phases of the designing of the device to be comprehended:

What are design and development stages for your device in question? You can show these stages in flow chart form. Add SOP reference and Design History File number in your technical file. Referenced documents must be available to reviewer.

b. Comprehensive data and specifications including but not limited to the manufacturing processes and their validation: their excipients, the uninterrupted observation, and the product at the end. This data will be provided in full within the technical documentation:

Mention reference for the following but not limited to this in your technical file and these referenced documents must be available for reviewer:

In-coming material (raw material) specification: provide reference number

Work instruction for in-coming material (raw material) testing: provide reference number

In-coming material (packaging material) specification: provide reference number

Work instruction for Incoming material (packaging material): provide the reference number.

Specification for In-process inspection of product: provide reference number

Work instruction for in-process inspection: provide reference number

Specification for finished product: provide a reference number

Work instruction for finished product inspection: provide reference number

Work instruction for mfg. of device: provide reference number

Manufacturing process flow chart indicating critical process and site of operation: provide reference number

Work instruction for sterilization validation: provide reference number

Work instruction for packaging validation: provide reference number

Work instruction for stability study real-time, aging, and shipping: provide reference number

Work instruction for work environment control: provide reference number

Work instruction for validation of work environment: provide reference number

Each and every location, including vendors’ and sub-contractors locations, with regard to design and manufacturing activities:

Legal Manufacturer (as per EUDAMED registration): What is legal manufacturing site address approved by Local regulatory authority? Provide details of such manufacturing address in technical file. it may be in multiple numbers.

European Representatives:

Who is your European representative? Provide details in this section and also the agreement reference number.

Site with Design responsibility:

In case of multiple manufacturing sites, design, and development activity may be centralized and may be site specific/multiple site. It all depends on your organization’s feasibility. Provide adequate details in this section as applicable.

Sterilization Site:

The sterilization process may be in-house or outsourced. If your sterilization process is covered under outsourced activity. In INDIA, you have to get clearance from CDSCO in the form of a Loan License. This information should also be reflected in other technical documentation.

All suppliers and subcontractors shall be ISO 13485 certified and Local regulatory approval where required.

4. GENERAL SAFETY AND PERFORMANCE REQUIREMENTS:

The documentation for Contract Review includes elements that enable proving compliance with essential safety and performance requirements listed in Annex I that are appropriate for the device considering its intended use, together with the rationale, validation, and verification of the appropriate solutions that were used to meet these requirements. General safety and performance requirements are not applicable to your products, provide justification why these requirements are not applicable.

The demonstration of conformity includes:

a. The general safety and performance requirements that are placing obligations on the device and please explain why they are not placing obligations on other devices: Devices including an active substance which is incorporated in the device Substances which are absorbed or dispersed locally within the device.

• Performance and safety
• Reduction of risks
• Risk management system
• Risk control measures and residual risks
• Risks related to use/user
• Device lifetime
• Packaging, transport, storage
• Risk-benefit ratio
• Devices without a medical purpose
• Chemical, physical, and biological properties
• General considerations for materials (RM/PM)
• Risks from contaminants and residues
• Compatibility with materials and substances
• Substances contained in and released from the device
• Risk of unintentional ingress
• Risks related to particle size
• Infection and microbial contamination
• Risk of infection
• Design for reuse
• Devices with a specific microbial state
• Devices delivered sterile
• Validation for sterile devices
• Environmental controls
• Packaging for non-sterile devices
• Labeling for sterile state
• Devices composed of substances which are absorbed or dispersed localy within the device.
• Devices incorporating a medicinal product
• Devices incorporating materials of biological origin
• Devices composed of substances absorbed or locally dispersed
• Tissues, cells, or derivatives of human origin
• Tissues, cells, or derivatives of animal origin
• Other non-viable biological substances
• device design and the different environmental factors associated with the device and what risks it emits.
• Use in combination
• Risks of interaction with the environment
• Risks of fire or explosion
• Design for adjustment, calibration, and maintenance
• Design for compatibility
• Measurement, monitoring, or display scales
• Design and manufacture for safe disposal
• Devices with a diagnostic or measuring function
• Protection against radiation
• Electronic programmable systems and software.
• Active devices and devices connected to them
• Particular requirements for active implantable devices
• Particular risks in the case of active implantable devices that need to be minimised.
• Device compatibility and reliability of energy
• Identification of devices and components
• Identification code
• Protection against mechanical and thermal risks
• Protection against the risks posed to the patient or user by devices supplying energy or substances
• Protection against the risks posed by medical devices intended by the manufacturer for use by laypersons
• Label and instructions for use
• The instructions to be included with the device must describe the packages of active medical devices respective to the Manufacturer’s label requirements.
• Label requirements
• Sterile package label requirements
• Instructions for Use

b. Method or methods for demonstrating conformity with each applicable general safety and performance requirement as may be appropriate:

In this section, explain the methods, if any have been adopted demonstrative of conformity with each general safety and performance requirement that is applicable, detail the details in this section. Your method shall be in compliance with EN ISO/ ISO/ USP/In-house standards. In-house standards shall be validated for their adequacy.

c. The Harmonized standards, CS, or any other solutions used:

List out harmonized standards, in-house standards, common specifications, etc. applicable to your product.

d. Such standardized controlled documents which are relevant and which provide the required evidence for compliance with each standard applied or other methods used to show compliance with the requirements on general safety and performance requirements. This information referred to in this point shall have been cross-referenced with the point where such evidence appears in the complete technical documents, and if necessary, in the summary technical documents:

Each document shall have a control number which shall be part of your quality management system.

For each evidence provided in relation to the safety and performance requirement details used in the device application provide traceability.

Note: You have to mention the conclusion of each evidential report in this section to comply with the requirements.

5. Benefit-Risk Analysis and Risk Management:

a. The benefit-risk analysis alluded to in Sections 1 and 8 of Annex I:

Do the benefit-risk analysis for a device in question in compliance with ISO 14971 and provide a summary report in this section. You have to justify, how the clinical benefits of your device outweigh the risks.

b. The risk management Measures undertaken and the outcomes of these measures alluded to in Section 3 of Annex I:

Provide a risk management report summary in this section including risk level before and after control measures. Your summary report must have a method to monitor residual risks and review frequency/ scenario in which conditions risk management report shall be reviewed.

6. Product Verification and Validation:

6.1 Pre-clinical and clinical data:

a. Take into consideration evaluation of other literature where engineering processes including laboratory, simulated use of devices, and their trials on animals are carried out as well as evaluation of other literature sources just like those above but now focused on Pre clinical safety profile of the device under study and its specifications:

As mentioned tests in heading that are applicable to your device, provide a conclusion of tests in this section in a traceable manner. For those tests of requirements that are not applicable, provide a rationale for the applicability of those requirements for your specific device.

b. Describe in particular the detailed information concerning design of the test, complete test or study protocols, and data analysis methods, in addition to data and test conclusions concerning in particular:

In this aspect, one is supposed to describe the test protocols or methods employed in the testing of the device as well as how the data obtained was analyzed. The reference number, current revision number, and effective date can also be mentioned.

b1). Biosafety of the device including all materials coming into direct or indirect contact with the patient or user devices

First, categorize your medical device depending on contact and duration of use, further refer to ISO 10993-1:2018 for biological evaluation. Identify applicable biological evaluation tests on your device.

b2). Physical, chemical, and microbiological characterization:

Describe physical characteristics such as solid, liquid, gas, semisolid, tensile strength, length, width, diameter, internal diameter, density, color, hardness, melting and boiling points, electrical conductivity, etc, chemical characteristics such as composition, flammability, toxicity, acidity, reactivity (many types), and heat of combustion, biological characteristics include such as presence and risk of microbial contaminants, bio-compatibility, etc. both for the material of construction and packaging material including device accessories and device which is not a medical device.

b3). Electrical safety and electromagnetic compatibility:

If this requirement is applicable to your medical device, describe electrical safety and electromagnetic compatibility.

b4). Software Verification and Validation (describing the processes of design and development of the software and supporting evidence for the validity of the software in the equipment in which it is incorporated. This information can normally include overall summary of the results of all verifications, validations, and testing done in-house and during user-simulated or real environment over the product prior to final. It shall also address all of the different hardware configurations and, where appropriate, operating systems identified in the information supplied by the manufacturer:

Specify the procedures concerning the software design and development processes stated by the manufacturer. Include

the reference of the validation and verification report of programmed software applied in the finished product and a brief description of the test outcomes. Define what are hardware configurations required for your software and where applicable operating system.

b5). Stability, including shelf life:

Medical devices must remain stable during defined shelf life. Provide reference to stability study procedure organized by manufacturer and summary result of tests conducted to define shelf life both for accelerated and real time study.

b6). Performance and safety:

This section requires you to put information on device performance and safety when used as
intended by the manufacturer. Provide observation on residual risks remaining after risk control measures.

b7). In cases where no new testing has been performed, there also has to be a stated reason for that decision in the documents:

In case any of the prescribed tribology tests are not performed by the manufacturer, provide appropriate justification for such a decision as to why testing was not performed.

c. The clinical evaluation report, its amendments, and the clinical evaluation plan mentioned in Article 61(12) and Annex XIV Part A:

The outcome of the clinical examination should fulfill the established criteria in respect of the safety and effectiveness of the medical device. The medical device has a defined shelf life. Include references to a clinical development plan, clinical evaluation plan, and the clinical evaluation report.

d. The PMCF plan and PMCF evaluation report as described in Part B of Annex X!V or specific rationale regarding the non-application of PMCF:

It is a device-specific requirement, hence add adequate information with justification.

6.2 Additional information required in specific cases:

a. Where a device incorporates, as an integral part, a substance which if left on its own may fall under the definition of a medicinal product as that is specified in point 2 under article 1 of directive 2001/83/EC of the European Parliament, including a drug derived from human blood or human plasma as defined in paragraphs 1 under article 8, a indication to this effect. Then the documents shall explain how such a substance is obtained and provide evidence for the trials carried out to determine its safety, quality, and efficacy bearing in mind the end use of the device:

In your opinion, how could the device be improved based on the test results and the device’s intended use?

b. Where a device is defined as manufactured using tissues or cells originating from a human being or a living animal, or their derivatives, and this device is within the scope defined in accordance with points (f) and (g) of Article 1(6, and where a device includes, as integral part, tissues or cells of human origin or their derivatives which are used for an ancillary purpose to the device and the device is upon the scope of the Regulation in accordance with the first subparagraph of Article 1(10), a declaration to that effect. In such situations, the documentation must spell out all animal and human tissues utilized and explain how these are consistent with Sections 13.1 or 13.2 as the case may be, of Annex I:

Identify the source of material whether it is of animal or human origin and add information
concerning the conformity with Sections 13.1. or 13.2., respectively, of Annex-I.

c. For devices, that are composed of substances and/or a combination of substances that are intended to be introduced into the human body and which are absorbed or dispersed locally in the human body, there are specified that particularities include, but are not limited to, test design, complete test or study protocols, methods of analysis, and data summary and conclusions: these are what studies in relation to:

— absorption. distribution, metabolism, and excretion:

Define adequate pharmacokinetics.

— possible interactions of those substances, or of their products of metabolism in the the human body, with other devices, medicinal products, or other substances, considering the target population, and its associated medical conditions:

Define the medical target population (patients and users), intended purpose, and exact medical
conditions. The patient population shall cover a minimum but not be limited to age, sex, weight, exact clinical stages, race, etc. Define the user of your product e.g. Lay person, Nurse, Medical student, General public, Patient, Qualified medical practitioner, Surgeon, General Physician, Gynecologist, Dentist, etc.

— local tolerance:

Define minimum and maximum dose.

— toxicity, including but not limited to: single-dose toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, where applicable according to the exposure of the patient to the device. If such studies are not existent, a justification shall be provided:

Determine the parameters of single-dose toxicity, repeat-dose toxicity, genotoxicity, carcinogenicity, reproductive and developmental toxicity, where applicable according to the exposure of the patient to the device in the absence of such data explaining the reason why such studies have not been done.

d. However, in medical devices that contain CMR or endocrine-disrupting materials already mentioned in Requirements 10.4.1 of Annex I, Section 10.4.2 justification mentioned in this annex shall apply:

Invasive devices or devices administering/storing substances must contain a concentration below 0.1 percent by weight (stated in section 10.4.1 of Annex-I ) unless justified with reference to section 10.4.2 of Annex I. This includes carcinogenic, mutagenic, or toxic to reproduction (in total referred to as ‘CMR’) substances and substances with endocrine-disrupting properties. The general safety and performance requirements makes reference to substances categorized per EU Regulation 1272/2008 (Classification, Labelling and Packaging of Chemicals) and substances identified in EU Regulation 1907/2006 (REACH: Registration, Evaluation, Authorisation, and Restriction of Chemicals) or EU Regulation 528/2012 (Market and Use of Biocidal Products).

A justification as per section 10.4.2 of Annex | must be made if the CMR or endocrine-disrupting substances (for example: lead compounds, other heavy metals, phenols) are present above 0.1 percent by weight in these device types. This subsection 10.4.2 lists the aspects to be included in the justification for inclusion of these substances. Section 10.4.5 addresses the labeling requirements.

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, sterilization, and maintenance of sterility. The validation report shall address bioburden testing, pyrogen testing, and, if applicable, testing for sterilant residues:

Define environmental conditions for such medical device and shall meet the requirements laid down in general safety and performance requirements section 11.3 and 11.4 of Annex I. Provide information on methods used for sterilization, validation method packaging, sterilization, and maintenance of sterility, Bioburden tests and Pyrogen test results.

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:

The device shall conform to the requirement laid down in general safety and performance requirements section 15 of Annex |. Provide information on methods used to ensure accuracy.

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 device shall conform to the requirements laid down in general safety and performance requirements section 14 of Annex | and provide evidence of such compliance in this section.