IVDR Instruction for Use (IFU)

 IVDR Annex I GSPR Section 2o of IVDR have requirements regarding the information supplied by the manufacturer.

The following section provides requirements which are applicable for instruction for use,

1.     20.1. General requirements regarding the information supplied by the manufacturer

2.     20.4. Information in the instructions for use

IVDR brings lot of changes. As compared to IVDD, IVDR IFU requirements are more detailed, some NEW requirements are incorporated.

The below table shows some of major MDR IFU New requirements.

IFU General Requirements

20.1 IFUs shall be provided through manufacturer website.

20.1.(a) The medium, format, content, legibility, and location of the label and instructions for use shall be appropriate to the particular device, its intended purpose and the technical knowledge, experience, education or training of the intended user(s). In particular, instructions for use shall be written in terms readily understood by the intended user and, where appropriate, supplemented with drawings and diagrams.

20.1.(e) Where multiple devices, with the exception of devices intended for self-testing or near-patient testing, are supplied to a single user and/or location, a single copy of the instructions for use may be provided if so agreed by the purchaser who in any case may request further copies to be provided free of charge.

20.1.(f) When the device is intended for professional use only,instructions for use may be provided to the user in non-paper format (e.g. electronic), except when the device is intended for near-patient testing.

20.1(g) Residual risks which are required to be communicated to the user and/or other person shall be included as limitations, contra-indications, precautions or warnings in the information supplied by the manufacturer.

20.1(i) Apply hazard pictograms and labelling requirements of Regulation (EC) No 1272/2008.These information shall be given in IFU when there is insufficient space to put all the information on the device itself or on its label.

23.1.(j) The provisions of Regulation (EC) No 1907/2006 on the safety data sheet shall apply, unless all relevant information, as appropriate, is already made available in the instructions for use.

IFU Content Requirements

20.4.1(c)(i) What is detected and/or measured

20.4.1(c)(ii) function (e.g. screening, monitoring, diagnosis or aid to diagnosis, prognosis,  prediction, companion diagnostic)

20.4.1(c)(iii) The specific information that is intended to be provided in the context of: —a physiological or pathological state; —congenital physical or mental impairments; —the predisposition to a medical condition or a disease; —the determination of the safety and compatibility with potential recipients; —the prediction of treatment response or reactions; —the definition or monitoring of therapeutic measures;

20.4.1(c)(iv) automated or not

20.4.1(c)(v) qualitative, semi-quantitative or quantitative

20.4.1(c)(vii) testing population

20.4.1(c)(viii) For companion diagnostics, the International Nonproprietary Name (INN) of the associated medicinal product for which it is a companion test

20.4.1(e) The intended user, as appropriate (e.g. self-testing,near patient and laboratory professional use,healthcare professionals)

20.4.1(g) Description of the calibrators and controls and any limitation upon their use (e.g. suitable for a dedicated instrument only)

20.4.1(h) Description of the reagents and any limitation upon their use

20.4.1(i) List of materials provided and a list of special materials required but not provided

20.4.1(j) combinations of devices and equipment ·  validated and safe combination, including key performance characteristics, and/or ·   known restrictions to combinations of devices and equipment

20.4.1(m) Sterile devices ·       an indication of its sterile state ·       sterilisation method ·       instructions in the event of the sterile packaging being damaged before use

20.4.1(n)(i) Warnings, precautions and/or measures to be taken in the event of malfunction of the device or its degradation as suggested by changes in its appearance that may affect performance,

20.4.1(n)(ii) Warnings, precautions and/or measures to be taken as regards the exposure to reasonably foreseeable external influences or environmental conditions,such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, radiation associated with diagnostic or therapeutic procedures, pressure, humidity, or temperature.(IVDD 8.7(r) ,Highligted text added in IVDR)

20.4.1(n)(iii) Warnings, precautions and/or measures to be taken as regards the risks of interference posed by the reasonably foreseeable presence of the device during specific diagnostic investigations, evaluations, therapeutic treatment or other procedures such as electromagnetic interference emitted by the device affecting other equipment

20.4.1(n)(iv) Precautions related to materials incorporated into the device that contain or consist of CMR substances, or endocrine disrupting substances or that could result in sensitisation or an allergic reaction by the patient or user

20.4.1(n)(v) Single use devices If the device is intended for single use, an indication of that fact. A manufacturer’s indication of single use shall be consistent across the Union

20.4.1(n)(vi) Reusable devices ·       If the device is reusable, information on the appropriate processes to allow reuse, including cleaning, disinfection, decontamination, packaging and, where appropriate, the validated method of resterilisation ·       Information shall be provided to identify when the device should no longer be reused, such as signs of material degradation or the maximum number of allowable reuses (IVDD 8.7(q) ,Highligted text added in IVDR)

20.4.1(o) warnings and/or precautions related to potentially infectious material that is included in the device

20.4.1(p) Requirements for special facilities, such as a clean room environment. special training, such as on radiation safety, or particular qualifications of the intended user

20.4.1(r) Details of any preparatory treatment or handling of the device before it is ready for use, such as sterilisation,final assembly, calibration, etc., for the device to be used as intended by the manufacturer;(IVDD 8.7(o) ,Highligted text added in IVDR)

20.4.1(s) The information needed to verify whether the device is properly installed and is ready to perform safely and as intended by the manufacturer, together with, where relevant:/ —details of the nature, and frequency, of preventive and regular maintenance, including cleaning and disinfection; —identification of any consumable components and how to replace them; —information on any necessary calibration to ensure that the device operates properly and safely during its intended lifetime; —methods for mitigating the risks encountered by persons involved in installing, calibrating or servicing devices. (IVDD 8.7(n) ,Highligted text added in IVDR)

20.4.1(u) The metrological traceability of values assigned to calibrators and control materials, including identification of applied reference materials and/or reference measurement procedures of higher order and information regarding maximum (self-allowed) batch to batch variation provided with relevant figures and units of measure;(IVDD 8.7(k)Point 2 ,Highligted text added in IVDR)

20.4.1(v) Assay procedure including calculations and interpretation of results and where relevant if any confirmatory testing shall be considered;where applicable, the instructions for use shall be accompanied by information regarding batch to batch variation provided with relevant figures and units of measure;(IVDD 8.7(g) ,Highligted text added in IVDR)

20.4.1(w) Analytical performance characteristics, such as analytical sensitivity, analytical specificity, trueness (bias), precision (repeatability and reproducibility),accuracy (resulting from trueness and precision),limits of detection and measurement range,(information needed for the control of known relevant interferences, cross-reactions and limitations of the method), measuring range, linearity and information about the use of available reference measurement procedures and materials by the user;(IVDD 8.7(h)Point 2 ,Highligted text added in IVDR)

20.4.1(x) Clinical performance characteristics as defined in Section 9.1 of this Annex(IVDD 8.7(d),Highligted text added in IVDR)

20.4.1(z) Where relevant, clinical performance characteristics, such as threshold value, diagnostic sensitivity and diagnostic specificity, positive and negative predictive value

20.4.1(ab) Information on interfering substances or limitations (e.g. visual evidence of hyperlipidaemia or haemolysis,age of specimen) that may affect the performance of the device

20.4.1(ac) Warnings or precautions to be taken in order to facilitate the safe disposal of the device, its accessories,and the consumables used with it, if any. This information shall cover, where appropriate:(IVDD 8.7(s),Highligted text added in IVDR)

20.4.1(ac)(i) Infection or microbial hazards, such as consumables contaminated with potentially infectious substances of human origin

20.4.1(ac)(ii) Environmental hazards such as batteries or materials that emit potentially hazardous levels of radiation)

20.4.1(ac)(iii) Physical hazards such as explosion

20.4.1(ad) The name, registered trade name or registered trade mark of the manufacturer and the address of its registered place of business at which he can be contacted and its location be established, together with a telephone number and/or fax number and/or website address to obtain technical assistance(Detailed in IVDR)

20.4.1(ae) Date of issue of the instructions for use or, if they have been revised, date of issue and identifier of the latest revision of the instructions for use, with a clear indication of the introduced modifications(IVDD 8.7(u),Highligted text added in IVDR)

20.4.1(af) A notice to the user that any serious incident that has occurred in relation to the device shall be reported to the manufacturer and the competent authority of the Member State in which the user and/or the patient is established

20.4.1(ag) Where device kits include individual reagents and articles that may be made available as separate devices, each of these devices shall comply with the instructions for use requirements contained in this Section and with the requirements of this Regulation

20.4.1(ah) For devices that incorporate electronic programmable systems, including software, or software that are devices in themselves, minimum requirements concerning hardware, IT networks characteristics and IT security measures, including protection against unauthorised access, necessary to run the software as intended.

20.4.1(ah) Self-testing

20.4.2(a) Details of the test procedure shall be given, including any reagent preparation, specimen collection and/or preparation and information on how to run the test and interpret the results

20.4.2(c) The device’s intended purpose shall provide sufficient information to enable the user to understand the  medical context and to allow the intended user to make a correct interpretation of the results;

20.4.2(e) Information shall be provided with advice to the user on action to be taken (in case of positive, negative or indeterminate result), on the test limitations and on the possibility of false positive or false negative result. Information shall also be provided as to any factors that can affect the test result such as age, gender,menstruation, infection, exercise, fasting, diet or medication(IVDD 8.7(t) Point 1,Highligted text added in IVDR)

20.4.2(f) The information provided shall include a statement clearly directing that the user should not take any decision of medical relevance without first consulting the appropriate healthcare professional, information on disease effects and prevalence, and, where available, information specific to the Member State(s) where the device is placed on the market on where a user can obtain further advice such as national helplines, websites(IVDD 8.7(t) Point 3,Highligted text added in IVDR)

 

Click below link to know more about MDR IFU requirements :https://meddev-info.blogspot.com/2021/01/mdr-instruction-fo-use-ifu-requirements.html

References:

REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU 

ROBYN MEURANT .EXPLORING THE RELATIONSHIP BETWEEN THE IVDR AND THE IVDD General Safety and Performance Requirements Versus Essential Requirements) [White paper]. NSF nternational.  https://d2evkimvhatqav.cloudfront.net/documents/md_wp_ivdr.pdf?mtime=20200716160253&focal=nones

IVDR Clinical Performance Study

MDR Definitions:

‘performance study’ means a study undertaken to establish or confirm the analytical or clinical performance of a device;

 ‘analytical performance’ means the ability of a device to correctly detect or measure a particular analyte;

 ‘clinical performance’ means the ability of a device to yield results that are correlated with a particular clinical condition or a physiological or pathological process or state in accordance with the target population and intended user;

Clinical performance studies  requirements are defined in article 57 to 76 and Section 2 of Part A of Annex XIII

·       Article 57 General requirements regarding performance studies

·       Article 58 Additional requirements for certain performance studies

·       Article 59 Informed consent

·       Article 60 Performance studies on incapacitated subjects

·       Article 61 Performance studies on minors

·       Article 62 Performance studies on pregnant or breastfeeding women

·       Article 63 Additional national measures

·       Article 64 Performance studies in emergency situations

·       Article 65 Damage compensation

·       Article 66 Application for performance studies

·       Article 67 Assessment by Member States

·       Article 68 Conduct of a performance study

·       Article 69 Electronic system on performance studies

·       Article 70 Performance studies regarding devices bearing the CE marking

·       Article 71 Substantial modifications to performance studies

·       Article 72 Corrective measures to be taken by Member States and information exchange between Member States on performance studies

·       Article 73 Information from the sponsor at the end of a performance study or in the event of a temporary halt or early termination

·       Article 74 Coordinated assessment procedure for performance studies

·       Article 75 Review of the coordinated assessment procedure

·       Article 76 Recording and reporting of adverse events that occur during performance studies      

 Section 2 of Part A of Annex XIII

·       Data used to establish or confirm aspects of device performance which cannot be determined by analytical performance studies, literature and/or previous experience gained by routine diagnostic testing.

·       shall be carried out in accordance with recognised ethical principles.

·       Studies are e designed in such a way as to maximize the relevance of the data while minimising potential bias

Clinical performance study plan (CPSP)

Clinical performance studies shall be performed in accordance with the Clinical performance study plan (CPSP)

·       CPSP shall define the below

o   Rationale

o   Objectives

o   Design and proposed analysis

o   Methodology

o   Monitoring

o   Conduct and

o   Record-keeping

It shall contain the following information:

 

single identification number of the clinical performance study

Sponsor/ legal representative   ·       identification of the sponsor/ legal representative ·       name ·       address of the registered place of business ·       contact details

information on the investigator or investigators ·       Principle /coordinating or other investigator ·       Qualifications ·       contact details ·       investigation site or sites, such as number, qualification, contact details ·       location and number of lay persons involved (case of devices for self-testing)

starting date and scheduled duration

Device details ·       identification and description of the device ·       its intended purpose ·       analyte or analytes or marker or markers ·       metrological traceability ·       manufacturer

type of specimens used

synopsis of the clinical performance study, ·       design type, such as observational, interventional ·       objectives ·       hypotheses of the study ·       reference to the current state of the art in diagnosis and/or medicine

Expected risks and benefits of the device and of the clinical performance study in the context of the state of the art in clinical practice

·       instructions for use of the device or test protocol, ·       training and experience of the user ·       calibration procedures and means of control, ·       indication of any other devices, medical devices, medicinal product or other articles to be included or excluded and the specifications on any comparator or comparative method used as reference

Design of the clinical performance study ·       description of and justification ·       scientific robustness and validity, including the statistical design ·       details of measures to be taken to minimise bias, such as randomisation ·       management of potential confounding factors

analytical performance

parameters of clinical performance

study population: specifications of the subjects selection criteria size of performance study population representativity of target population if applicable, information on vulnerable subjects involved, such as children, pregnant women, immuno-compromised or elderly subjects

information on use of data out of left-over specimens banks, genetic or tissue banks, patient or disease registries etc.

monitoring plan

data management

decision algorithms

policy regarding any amendments

accountability regarding the device ·       control of access to the device ·       follow-up in relation to the device used in the clinical performance study ·       return of unused, expired or malfunctioning devices

statement of compliance with the recognised ethical principles

informed consent process, including a copy of the patient information sheet and consent forms (not applicable for studies using left-over samples)

procedures for safety recording and reporting

criteria and procedures for suspension or early termination

procedures for follow up of subjects (not applicable for studies using left-over samples)

procedures for communication of test results outside the study (not applicable for studies using left-over samples)

policy as regards the establishment of the clinical performance study report (not applicable for studies using left-over samples)

Technical and functional features of the device indicating those that are covered by the performance study

bibliography

 

Clinical performance study report(CPSR)

·       Signed by a medical practitioner or any other authorised person responsible

·       Transparent, free of bias and clinically relevant

·       Include the clinical performance study protocol plan, results and conclusions of the clinical performance study, including negative findings

·       Any protocol amendments or deviations, and data exclusions with the appropriate rationale

Click below link to know more about MDR Clinical Investigations :https://meddev-info.blogspot.com/2021/01/mdr-clinical-investigations.html

  Source: REGULATION (EU) 2017/746 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU