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Produits de Nutrition
& de Santé
Expertise scientifique,
médicale et toxicologique
Expertise
à l’international
Stratégie
Règlementaire
KEY DIFFERENCES BETWEEN THE NEW MEDICAL DEVICE AND THE OTC REGULATIONS IN EUROPE
Anne Laure TARDY, PhD
26 October 2017
© RNI Conseil 2017Tous droits réservés
Toute reproduction interdite sans l'autorisation de l'auteur.
Table of content
Products regulatory frameworks & definition
Classification of the products
Key actors of the systems
Safety/ efficacy requirements & drafting application
Marketing procedure and authorization
Conclusion
PRODUCTS REGULATORY FRAMEWORKS & DEFINITION
Regulatory framework of medical devices
KEY DATES IN THE APPLICATION OF THE NEW MDR• Enter into force : 26 may 2017• Shall apply from 26 May 2020, with the exception of the
o Chapter IV on notified body: 26 november 2017o Chapter VIII on the cooperation with the MS : 26 may 2018
KEY OBJECTIVES OF THE NEW MDR• Improve security for patients and users• Improve the traceability of MD• Strengthen the role of notified bodies• Specify the obligations of manufacturers, importers and distributors• Strengthen the requirements for clinical evidence
Definition of medical device
According to the Article 2 of the Regulation (EU) 2017/745:
– “Medical device” means
• any instrument, apparatus, appliance, software, implant, reagent, material or other article intended by the manufacturer to be used, alone or in combination, for human beings for […] specific medical purposes:
– diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of disease,
– […],
– investigation, replacement or modification of the anatomy or of a physiological or pathological process or state,
– […],
• and which does not achieve its principal intended action by pharmacological, immunological or metabolic means, in or on the human body, but which may be assisted in its function by such means.
Definition of medical device
According to Annex 1 of the Regulation (EU) 2017/745 :– GENERAL REQUIREMENTS, devices should
• Achieve the performance intended by their manufacturer
• Be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose.
• Be safe and effective and shall not compromise the clinical condition or the safety of patients or of users
• Constitute acceptable risks when weighed against the benefits to the patient
– REQUIREMENTS REGARDING DESIGN AND MANUFACTURE
– REQUIREMENTS REGARDING THE INFORMATION SUPPLIED WITH THE DEVICE
Regulatory framework of medicinal products
KEY CONTENTS • Requirements and procedures for the marketing authorization • Rules for the constant supervision of products after their authorization• Harmonized provisions in areas such as the manufacturing or advertising
SPECIFIC RULES FOR CERTAIN TYPES OF MEDICINAL PRODUCTS• Regulation (EC) No 141/2000 : orphan medicinal products • Regulation (EC) No 1901/2006: medicinal products for children• Regulation (EC) No 1394/2007 : advanced therapy medicinal products • Directive 2004/24/EC : on specific provisions applicable to herbal medicinal products
Definition of medicinal products
According to Article 1(2) of the Directive 2001/83/EC:
– Medicinal product:
• (a) Any substance or combination of substances presented as havingproperties for treating or preventing disease in human beings
– presentation of the medicinal product and to the claims made for it
• (b) Any substance or combination of substances which may be used in oradministered to human beings either with a view to restoring, correctingor modifying physiological functions by exerting a pharmacological,immunological or metabolic action, or to making a medical diagnosis.
– its function and intended use.
• According to settled case law of the European Court of Justice (ECJ), 'aproduct is a medicinal product if it falls within either of those twodefinitions'.
CLASSIFICATION OF THE PRODUCTS
Classification rules of medical devices
According to Article 51 & Annex VIII of the Regulation (EU) 2017/745:– Devices are divided into classes I, IIa, IIb and III, taking into account
the intended purpose and their inherent risks.
– Any concern between the manufacturer and the notified body shall be referred for a decision to the competent authority
– Important definition:
• Duration of use
– Transient : continuous use for less than 60 minutes.
– Short term : continuous use for between 60 minutes and 30 days.
– Long term : continuous use for more than 30 days
• Invasive and active devices
Classification rules of medical devices
According to the Annex VIII of the Regulation (EU) 2017/745:
– 22 rules to determine the class of the MD (vs 18 rules in the currentregulation)
• Rules 1 to 4 : Non-invasive Devices (ex: rule 4: non-invasive devices which come into contact with injured skin or mucous membrane)
• Rules 5 to 8 : Invasive Devices
• Rules 9 to 13: Active Devices
• Rules 14 to 22 : Special rules
– Rule 14 : All devices incorporating, as an integral part, a substance which, if used separately, can be considered to be a medicinal product are classified as class III
– Rule 19 : Device containing nanomaterials
– Rule 21: Devices that are composed of substances or of combinations of substances that are intended to be introduced into the human body via a body orifice or applied to the skin and that are absorbed by or locally dispersed in the human body
Classification of medicinal products
According to Articles 70 to 75 of the Directive 2001/83/EC:– Art 70: CA specify the classification of the medicinal product into:
• a medicinal product subject to medical prescription,
• a medicinal product not subject to medical prescription.
– Art 72: Subject to medical prescription if they:
• are likely to present a danger even when used correctly, if utilized without medical supervision
• are frequently used incorrectly and are likely to present a danger to human health
• contain substances thereof, the activity and/or adverse reactions of which require further investigation
• are normally prescribed by a doctor to be administered parenterally
– Art 73: Draw up a list of the medicinal products subject to medical prescription on their territory.
Products classification: where is the limit?
What are borderline products? – An increasing number of products may fall within the scope of two
definitions: medicinal products and food products/food supplements, medical devices, biocides or cosmetics
Tools to help the stakeholders:– Manual of Decision (Manual on borderline and classification in the
community regulatory framework for medical devices (Version 1.17 (09-2015))
– MEDDEV (Meddev 2.4/1 Rev 9 – June 2010. Classification of medical devices)
– Guidelines about «A GUIDELINE ON CHANGING THE CLASSIFICATION FOR THE SUPPLY OF A MEDICINAL PRODUCT FOR HUMAN USE) (EMA, 2006)
If uncertainty over the classification, the stricter regime of medicinal products applies: ultimate aim being to protect the user.
KEY ACTORS OF THE SYSTEMS
Key actors of the medical devices
NATIONAL COMPETENT AUTHORITYResponsible for market surveillance and / or vigilance (ex: materio-vigilance, product classification, control of advertisement …)
MANUFACTURER• a natural or legal person who
manufactures or fully refurbishes a device, and markets that device under its name or trademark
• Ensure that product is compliantwith requirements of the MDR (article 10)
IMPORTER AND DISTRIBUTOR
NOTIFIED BODY• Conformity assessment body
designated in accordance with the MDR
• Submission of applications: before December 1, 2017
• New requirements set out in Appendix VII
• Inspection (3 experts + Country Competent Authority) for documentation reviews and on-site audit of each candidate
• Designation : no later than 1 October 2018 (quite late for implementation of the Regulation as of May 2020)
Key actors of the medical devices
EUDAMED- European database on medical devices (Article 33 of the Regulation (EU) 2017/745):– Objectives
• Transparency and adequate access to information
• Provide a sound basis for regulatory decision-making
• Build confidence in the regulatory system
– Several level of access depending on the user : member states, notified body, manufacturer & public
– Eudamed shall include the following electronic systems:• the electronic system for registration of devices
• the UDI-database (Unique Device Identifier)
• the electronic system on registration of economic operators
• the electronic system on notified bodies and on certificates
• the electronic system on clinical investigations
• the electronic system on vigilance and post-market surveillance the electronic system on market surveillance
Key actors of the medicinal products
European Medicine Agency
– Draw up scientific opinions for the evaluation of medicines for the EUinstitutions and the Member States.
– Seven scientific committees :
• Committee for Medicinal Products for Human Use (CHMP)
• Committee for Medicinal Products for Veterinary Use (CVMP)
• Committee for Orphan Medicinal Products (COMP)
• Committee on Herbal Medicinal Products (HMPC)
• Committee for Advanced Therapies (CAT)
• Paediatric Committee (PDCO)
• Pharmacovigilance Risk Assessment Committee (PRAC)
National Medicine Agency
– For national authorization procedure: mutual recognition procedure anddecentralized procedure
– Equivalent missions of EMA but at national level
SAFETY/ EFFICACY REQUIREMENTS & DRAFTING APPLICATION
Safety/ efficacy requirements & technical file for medical devices
The technical file is mandatory for all the products (Annex II & III)– Device description and specification
– Label / packaging/ notice
– Design and manufacturing information
– General safety and performance requirements
– Benefit-risk analysis and risk management
– Product verification and validation (clinical, preclinical, additional information required in specific cases
– Technical documentation on post-market surveillance (Annex III)
Standards are not mandatory but they have a particular importance– meeting them when they exist makes it easier to meet the corresponding
general requirements.
– Some, known as "harmonized", even presume compliance with these requirements.
– It is necessary to identify the applicable standards and to motivate their possible non-application
An
nex
II
Safety/ efficacy requirements & technical file for medical devices
Standard for risk management– NF EN ISO 14971: 2013 Application of risk management to medical devices
• Global evaluation to manage all the risk link to the product (at each step of the life of the product): identification, evaluation, control, residual risk assessment
Standards for safety evaluation– ISO 10993-1:2009 - Biological evaluation of medical devices
Standards for performance evaluation – NF EN ISO 14155: 2012 on clinical investigation– MEDDEV Guidances 271 rev 4 for drafting clinical evaluation report
Standards for quality management– NF EN ISO 13485: 2016 : on quality management
Safety/ efficacy requirements & technical file for medical devices
Biological evaluation report– ISO 10993-1:2009 - Biological evaluation of medical devices
Safety/ efficacy requirements & technical file for medical devices
Clinical efficacy & safety: clinical evaluation report
KEY CONTENTS • Must be draft for all MD class (advise : follow the MEDDEV 271 rev 4)• Objective: Compile, evaluate and analyse the clinical data to justify the performance and
safety through the entire life of the product • Appendix A9 : Example of template
• Equivalence demonstrated based on MEDDEV guidelines
• Data in the literature available to answer General requirements (safety, performance, benefit / risk ratio, secondary effects) based on the MEDDEV criteria
DRAFT OF CLINICAL EVALUATION REPORT
• Equivalence not demonstrated
• Data from the literature are insufficient
Clinical investigation is required
DRAFT OF CLINICAL EVALUATION REPORT
Safety/ efficacy requirements & technical file for medical devices
Clinical efficacy & safety: clinical evaluation report
Guidance 271 rev 4 du MEDDEV
• Data issued by the manufacturer (pre & post marketing, pre clinical studies….)
• Data issued from the literature on the MD or on an equivalent MD (must be clear and justified)
Conformity assessment with requirement on:• safety• acceptable benefit/risk
profile • performance• acceptability of
undesirable side-effects
• sample size and power calculation• relevance of endpoints • inclusion and exclusion criteria• methods used for quantifying
symptoms and outcomes• reporting of serious adverse events
Safety/ efficacy requirements & CTD dossier for medicinal products
Common technical document– Since July 2003, mandatory format for new drug applications in the EU
– The dossier is organized into five modules : Module 1 is region specific and modules 2, 3, 4 and 5 are intended to be common for all regions.
Safety/ efficacy requirements & CTD dossier for medicinal products
Non clinical overview and non clinical summaries
Safety/ efficacy requirements & CTD dossier for medicinal products
Cinical overview and clinical summaries
MARKETING PROCEDURE AND AUTHORIZATION
Marketing procedure and authorizationfor medical devices
‘CE marking of conformity’ or ‘CE marking’ – Definition = a marking by which a manufacturer indicates that a
device is in conformity with the applicable requirements set out in the Regulation
– For class I medical devices
• Autocertification by the manufacturer
– For the other classes
• Evaluation by the notified bodies
– Obtention of CE marking gives the autorisation to commercialize in all the EU Member States
Marketing procedure and authorizationfor medicinal products
Required before launching a drug on the European market– EU authorization are granted by the EC through the centralized
procedure following an application to the EMA.
– National authorizations are granted by the Member States through the national competent authorities
Centralized procedure (Regulation (EC) N° 726/2004)– A single scientific assessment procedure of the highest standard for
the medicinal products falling within its scope
– Mandatory for certain drugs & optional for other
– Results in a single marketing authorization that is valid in all Member States and offers, among other things, the benefit of direct access to the EU market.
Marketing procedure and authorizationfor medicinal products
Decentralized procedure (Directive 2001/83/EC)– For products that have never been marketed in a MS
– The 'reference Member State‘ carries out the initial evaluation and issues a draft assessment report.
– The other MS in which applications were submitted either agree with the evaluation or ask further questions.
– Once all issues are resolved and the application is successful, national marketing authorizations will be issued in the reference MS and the other MS concerned
Mutual recognition procedure (Directive 2001/83/EC)– Applies to medicinal products that have already been authorized in a MS.
– The MS that issued the original national marketing authorization submits its evaluation to the MS in which the stakeholder wants to market its product
– These are then asked to mutually recognize the marketing authorization. If the applicant is successful, each MS concerned will issue a national marketing authorization.
CONCLUSION: KEY MESSAGES TO BRING HOME
Conclusion: key messages to bring home
MEDICAL DEVICES MEDICINAL PRODUCTS/ OTC
Indication Medical purposes Medical purposes
Mode of action « Mechanic » Pharmacological
ActorsManufacturer/ Notified Body/ National competent agency
Manufacturer/ National& EuropeanCompetent Agency
DossierTechnical File+ standards & guidances (advised +++)
CTD Dossier (mandatory)
Marketing autorisation
Auto- certification & notifiedbody
National& European CompetentAgency
Procedure CE marking -> all MSCentralized -> all MSDecentralized & mutual recognition procedure -> specific MS
A lot of other things : quality assessment, post marketing surveillance … have to be taken into account
Mail: [email protected]
