Module 19 2021
©TOPRA ( The Organisation for Professionals in Regulatory Affairs) 2021
Please note that all printed material contained in the course handouts is, unless copyright is assigned elsewhere, the copyright of The Organisation for Professionals in Regulatory Affairs. Such materials are intended for the personal use of the registered students/delegates. Agreement must be reached with the Institute before any part of this material is reproduced, abstracted, stored in a retrieval system or transmitted in any form or by any means – that is, electronic, mechanical, photocopying, recording or otherwise.
First Name
Last Name
Company
Country
Novartis Pharma AG - Basel Orchid Orthopedic Solutions
Angelika
Hoenlinger
Switzerland
United Kingdom United Kingdom United Kingdom United Kingdom United Kingdom
Steven
Hollingworth
Saeed
Raoufmoghaddam AstraZeneca - Cambridge
George
Moore-Arthur
MHRA
Lisa
Agyemang
MHRA
Samera
Siddiqui
MHRA
Astellas Pharma Europe B.V.
Wybe
Hoffmann
Netherlands
United Kingdom
Gwyneth Rodrigues
Chriscilia
Tehupeiori
Sakura Finetek Europe B.V. Netherlands
United Kingdom
Lily
Martyn
Genomics plc
Tara
Fahy
Med-Di-Dia Limited
Ireland
Eva
Prevc
Amgen Ltd - Uxbridge
Austria
Module 19: Regulation of In Vitro Diagnostic Medical Devices 1 - 3 June 2021
LOCATION: ONLINE
Module Leader(s) : Nancy Consterdine
Date: 1 - 3 June 2021 Tuesday 1 st June 2021
Time: (BST)
Activity
Speaker
13.00 – 13.30
Introduction and Housekeeping
Stuart Angell
IVDeology
13.30 – 14.30
Lecture 1: Setting the Scene – EU Focus A regulatory and Industry Perspective To include UK CA
Stephen Lee
ABHI
Stuart Angell
IVDeology
14.30 - 15.30
Lecture 2: Classification of IVD Devices
Stephen Lee
ABHI
15.30 - 16.00
Refreshment Break
16.05 – 17.00
Lecture 3: Conformity Assessment:
Gill Morgan
What are the different routes and how does a manufacturer select the route which is appropriate for their device?
17.05 – 18.00
Lecture 4: Quality Management System
Stuart Angell
What is an ISO 13485 QMS? Why is it needed? In which countries is it recognised? What about CMCAS? What about MDSAP?
IVDeology
Date : Wednesday 2 nd June 2021
Module 19: Regulation of In Vitro Diagnostic Medical Devices 1 - 3 June 2021
Time: (BST)
Activity
Speaker
09.00 – 09.30
Review of Day 1: Interactive session to reflect on learnings from day 1, answer any questions and confirm understanding
09.30 – 10.30
Case Study: Apply learnings on classification, conformity assessment and QMS in a group setting using real life examples
Stuart Angell
Nancy Consterdine
10.30 – 10.45
Refreshment break
10.45 – 11.45
Lecture 5: Technical Documentation
Ben Jacoby
What is it? How should it be compiled? What is STED? How to write a DoC
Cambridge RA
11.45 – 13.00
Lecture 6: Performance Data & Product Claims: What is the difference between Scientific Validity, Analytical Performance and Clinical Performance and how should the data be collected and analysed? What is the significance of your claim?
Maurizio Suppo
Lunch
13.00 – 13.45
13.45 – 14.45
Lecture 7: Post Market Surveillance, Vigilance and FSCA
Stephen Lee
ABHI
14.45 – 15.45
Case Study including tea and coffee
Stephen Lee
Apply learnings on PMS, vigilance and FSCA in a group setting using real life examples
ABHI
15.30 – 15.45
Refreshment Break
15.45 – 16.45
Lecture 8: Risk Management
Stuart Angell
What is ISO 14179? When is it needed and why? How to establish a RM policy, procedure and plan. When is a risk acceptable?
IVDeology
Module 19: Regulation of In Vitro Diagnostic Medical Devices 1 - 3 June 2021
16.45 – 17.45
Lecture 9: Registration
Nancy Consterdine
What is required and why? What is EUDAMED and what are the requirements on UDI? Local country requirements versus EU – what is the difference?
IVDeology
Module 19: Regulation of In Vitro Diagnostic Medical Devices 1 - 3 June 2021
Date: Thursday 3 rd June 2021
Time: (BST)
09.00 – 09.30
Review of day 2 Interactive session to reflect on learnings from day 2, answer any questions and confirm understanding Case Study Apply learnings on performance data & product claims in a group setting using real life examples
Nancy Consterdine IVDeology
09.30 – 10.30
Refreshment Break
10.30 – 10.45
10.45 – 12.30
Lecture 10: Other Regulated Markets
Nancy Consterdine IVDeology
Which are they? How are they different? How can we drive harmonisation? Who are IMDRF
12.30 – 13.15
LUNCH
13.15 – 14.15
Lecture 11: Other Legislation Beyond IVDR. What about REACH, RoHS WEEE, GDPR, Machinery Directive and more
Nancy Consterdine IVDeology
14.15 – 14.45
Refreshment Break
Lecture 12: Companion Diagnostics and the IVDR What this means for co- development and personalised medicine
14.45 – 15.45
Shirley Hopper MHRA
15.45
Close of Module
02/06/2021
1
Module 19: IVD Regulation 1 - 3 June 2021
Stephen Lee Director, Diagnostic Regulation ABHI
2
1
02/06/2021
Setting the scene
3
Setting the scene
• Why regulate? • EU context • IVDR features • EC system changes • Brexit
4
2
02/06/2021
Why regulate medical devices? “Regulation is primarily concerned with enabling patient access to high quality, safe and effective medical devices, and avoiding access to products that are unsafe. When appropriately implemented, regulation ensures public health benefit and the safety of patients, health care workers and the community.”
https://www.who.int/medical_devices/safety/en/
5
UK Medicines and Medical Devices Act 2021
…the Secretary of State must have regard to— (a) the safety of medical devices; (b) the availability of medical devices; (c) the likelihood of the United Kingdom being seen as a favourable place in which to— (i) carry out research relating to medical devices, (ii) develop medical devices, or (iii) manufacture or supply medical devices.
6
3
02/06/2021
7
IVDR
I INTRODUCTORY PROVISIONS II MAKING AVAILABLE ON THE MARKET … III IDENTIFICATION AND TRACEABILITY OF DEVICES, REGISTRATION … IV NOTIFIED BODIES V CLASSIFICATION AND CONFORMITY ASSESSMENT VI CLINICAL EVIDENCE, PERFORMANCE EVALUATION AND PERFORMANCE STUDIES VII POST-MARKET SURVEILLANCE, VIGILANCE AND MARKET SURVEILLANCE VIII COOPERATION BETWEENMEMBER STATES… IX CONFIDENTIALITY, DATA PROTECTION, FUNDING AND PENALTIES X FINAL PROVISIONS
8
4
02/06/2021
Intended medical purpose
Now For the quantitative measurement of rhubarb in human serum on the SL+ instrument. For use in people with specific symptoms to help identify those with stage III rhubarb disease. Only for use by qualified laboratory professionals.
Previously For the measurement of serum rhubarb
Performance Evaluation Report
Analytical performance report
Clinical performance report Clinical performanc e studies Peer
Scientific validity report
Other device
Specimen type
Classification
IVDD risk categories
Examples
IVDR risk classification
Examples
Literature review
Annex II List A
ABO blood groups; HIV infections;
Class D ABO blood groups; HIV infections; Emergency epidemics
Accuracy
reviewed literature Published experience
Annex II List B
Blood glucose self tests PSA PKU Rubella, toxoplasmosis, CMV, chlamydia
Class C
Tests for cancer ; Tests for sexually
Sensitivity/ specificity Measuring range/ cut- off Novel markers
Expert opinion
transmitted infections ; Companion diagnostics; Human genetic tests; Most devices for self- testing Pregnancy self-tests; Cholesterol tests; Urine test strips;
Equivalence ?
Studies
Self testing Devices for self testing
Class B
General
Tests for cancer; Tests for sexually
Class A Clinical chemistry analyser;
transmitted infections; Companion diagnostics; Human genetic tests;
Specimen receptacles;
9
https://ec.europa.eu/health/md_sector/contact_en
https://ec.europa.eu/health/md_sector/new_regulations_en
https://ec.europa.eu/health/md_sector/new_regulations/guidance_en
https://ec.europa.eu/docsroom/documents?locale=en&keywords=medical%20device
10
5
02/06/2021
EUDAMED
11
EUDAMED3
actor registration UDI and device registration notified bodies and certificates clinical investigations and performance studies vigilance and post market surveillance market surveillance
12
6
02/06/2021
MDR/IVDR timelines
12 months
2016
2017
… 2020
2021
2022
… 2024
MDR
Original date of application
Revised date of application
Majority of AIMDD/MDD certificates
expire (c10K)
Regulations come into force
Text agreed
IVDR
Date of application IVDD certificates
IVDD certificates expire (c500)
start to expire*
Today
*Most IVDs (c10K+) have no certificate
13
IVDR/MDR Notified Bodies
https://ec.europa.eu/growth/tools-databases/nando/index.cfm?fuseaction=directive.notifiedbody&dir_id=35
14
7
02/06/2021
BREXIT, Medical Devices & IVDs
31 st December 2020 26 th May 2021
26 th May 2022
30 th June 2023
UK(NI) Mark UKCA Mark
UKCA Mark UK(NI) Mark
?Transition period?
MDR CE Mark
MDR CE Mark (NI only)
MDD CE Mark
IVDD CE Mark
IVDR CE Mark
IVDR CE Mark (NI only)
15
Thank you for listening
Any Questions?
stephen.lee@abhi.org.uk
www.linkedin.com/in/steveleeivd
16
8
02/06/2021
17
9
02/06/2021
1
Classification
2
1
02/06/2021
Classification (1 hour)
• Intended purpose • Risk classes • Classification rules • Case studies
3
4
2
02/06/2021
IVD function
Aid to diagnosis
Screening
Diagnosis
Monitoring disease status
Predisposition/ prediction
Prognosis
Companion diagnostic
5
• Qualification – is it an IVD?
‘ in vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following: (a) concerning a physiological or pathological process or state; (b) concerning congenital physical or mental impairments; (c) concerning the predisposition to a medical condition or a disease; (d) to determine the safety and compatibility with potential recipients; (e) to predict treatment response or reactions; (f) to define or monitoring therapeutic measures. Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices;
6
3
02/06/2021
• Qualification – is it an IVD?
‘accessory for an in vitro diagnostic medical device’ means an article which, whilst not being itself an in vitro diagnostic medical device, is intended by its manufacturer to be used together with one or several particular in vitro diagnostic medical device(s) to specifically enable the in vitro diagnostic medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the in vitro diagnostic medical device(s) in terms of its/their intended purpose(s);
7
• MDR or IVDR?
Medical Device
MD accessory
IVD
IVD accessory
IVD accessory
8
4
02/06/2021
9
IVDR requirements
(c) the intended purpose of the device which may include information on: (i) what is to be detected and/or measured; (ii) its function such as screening, monitoring, diagnosis or aid to diagnosis, prognosis, prediction, companion diagnostic; (iii) the specific disorder, condition or risk factor of interest that it is intended to detect, define or differentiate; (iv) whether it is automated or not; (v) whether it is qualitative, semi-quantitative or quantitative; (vi) the type of specimen(s) required; (vii) where applicable, the testing population; (viii) the intended user; (ix) in addition, for companion diagnostics, the relevant target population and the associated medicinal product(s). Annex II 1.1c
10
5
02/06/2021
Intended purpose/ intended use
Now For the quantitative
Previously For the measurement of serum rhubarb
measurement of rhubarb in human serum on the SL+ instrument. For use in people with specific symptoms to help identify those with stage III rhubarb disease. Only for use by qualified laboratory professionals.
11
12
6
02/06/2021
Classification IVDD • 20/80
IVDD risk categories
Examples
Annex II List A
ABO blood groups; HIV infections;
Annex II List B Blood glucose self tests Rubella, toxoplasmosis, CMV, chlamydia Self testing Devices for self testing General Tests for cancer; Tests for sexually
transmitted infections; Companion diagnostics; Human genetic tests;
13
Classification IVDR
• four risk groups (D,C,B&A) • B, C & D require Notified body scrutiny • significant change (80:20) IVDD risk categories Examples IVDR risk classification
Examples
Annex II List A Annex II List B
Class D ABO blood groups; HIV infections; Emergency epidemics Class C Tests for cancer ; Tests for sexually
ABO blood groups; HIV infections;
Blood glucose self tests PSA PKU Rubella, toxoplasmosis, CMV, chlamydia
transmitted infections ; Companion diagnostics; Human genetic tests; Most devices for self- testing
Self testing Devices for self testing
Class B Pregnancy self-tests; Cholesterol tests; Urine test strips; Class A Clinical chemistry analyser;
General
Tests for cancer; Tests for sexually
Specimen receptacles;
transmitted infections; Companion diagnostics; Human genetic tests;
14
7
02/06/2021
Classification IVDR
MDD/MDR
• significant change (80:20) • four risk groups (A,B,C &D) • B, C & D require Notified body scrutiny IVDD risk categories Examples IVDR risk classification
– Some up-classification (eg software) – Same risk groups (I, IIa, IIb, III)
MDD/MDR risk classification
Examples
Premarket scrutiny by a Notified Body
Examples
Annex II List A Annex II List B
Class D ABO blood groups; HIV infections; Emergency epidemics Class C Tests for cancer; Tests for sexually
Class III
Heart valve;
Yes
ABO blood groups; HIV infections;
Blood glucose self tests Rubella, toxoplasmosis, CMV, chlamydia
Class IIb Lung ventilator;
Yes
Bone fixation plate;
transmitted infections; Companion diagnostics; Human genetic tests; Most devices for self- testing
Self testing Devices for self testing
Class B Pregnancy self-tests; Cholesterol tests; Urine test strips; Class A Clinical chemistry analyser;
Class IIa Hypodermic needles;
Yes
Suction equipment; Bandages; Tongue depressors;
General
Class I
No
Tests for cancer; Tests for sexually
Specimen receptacles;
transmitted infections; Companion diagnostics; Human genetic tests;
15
• Classification
CLASS
RISK LEVEL (IMDRF)
EXAMPLES
Low individual risk and Low public health risk
Clinical chemistry analyser Prepared culture media
A
10% self certify
Moderate individual risk and/or Low public health risk
Pregnancy self testing Urine test strips
B
R I S K
High individual risk and/or Moderate public health risk
Blood glucose self testing HLA typing PSA screening Rubella test ABO blood donor screening HIV blood diagnostic
C
90% NB scrutiny
High individual risk and High public health risk
D
16
8
02/06/2021
Courtesy of Philip Kelly, HPRA
17
18
9
02/06/2021
• Implementing rules
1.1. Application of the classification rules shall be governed by the intended purpose of the devices. 1.2. If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices. 1.3. Accessories for an in vitro diagnostic medical device shall be classified in their own right separately from the device with which they are used. 1.4. Software, which drives a device or influences the use of a device, shall fall within the same class as the device. If the software is independent of any other device, it shall be classified in its own right. 1.5. Calibrators intended to be used with a device shall be classified in the same class as the device.
19
• Implementing rules (contd)
1.6. Control materials with quantitative or qualitative assigned values intended for one specific analyte or multiple analytes shall be classified in the same class as the device. 1.7. The manufacturer shall take into consideration all classification and implementation rules in order to establish the proper classification for the device. 1.8. Where a manufacturer states multiple intended purposes for a device, and as a result the device falls into more than one class, it shall be classified in the higher class. 1.9. If several classification rules apply to the same device, the rule resulting in the higher classification shall apply. 1.10. Each of the classification rules shall apply to first line assays, confirmatory assays and supplemental assays.
20
10
02/06/2021
• Classification rules
NPT classed in own right
21
Words are important
Detecting the exposure to … / the presence of … Embryo/foetus/newborn/offspring Life-threatening Screening, monitoring Risk of propagation
22
11
02/06/2021
Thank you for listening
Any Questions?
stephen.lee@abhi.org.uk
www.linkedin.com/in/steveleeivd
23
24
12
24/05/2021
Conformity Assessment
Gill Morgan
The Organisation for Professionals in Regulatory Affairs
1
Learning Outcomes
To identify the routes for conformity assessment allowed within the IVDR To recognise routes linked to product risk classification To explore the conformity assessment procedure for each route
The Organisation for Professionals in Regulatory Affairs
2
1
24/05/2021
Conformity
• Article 17 – EU declaration of conformity – statement that a device conforms with all the relevant requirements of the IVD Regulation. • Conformity assessment procedures are detailed in Annexes IV*, IX, X and XI of the IVDR. • Legal manufacturer chooses the appropriate conformity assessment route (Annex) which will usually include the involvement of a Notified Body to audit and verify that the device does conform to the requirements of the IVDR that apply to it. • Legal Manufacturer signs the DoC having followed the appropriate conformity assessment procedure.
* Annex IV – Declaration of Conformity
The Organisation for Professionals in Regulatory Affairs
3
Involvement of a Notified Body
Device class determines Notified Body involvement Class A: Annex IV with no Notified Body involvement ● Exception: sterile Class A IVD Class B: Annex IX ● QMS audit, surveillance audit and unannounced audit ● Technical documentation (product) assessment: representative sample per category of device (not self test or near patient test) Class C: Annex IX or X + XI ● QMS audit with annual surveillance audit and unannounced audit ● Technical documentation assessment: representative sample per generic device group (not self test, near patient test or Companion Diagnostics) Class D: Annex IX or X + XI ● QMS audit with annual surveillance audit and unannounced audit ● Technical documentation assessment for each device ● Verification by Reference Lab ● Batch release managed through notified body
The Organisation for Professionals in Regulatory Affairs
4
2
24/05/2021
Conformity assessment options
A B
C
D
EU Declaration of Conformity Annex IV*
Quality Management
Quality Management
Quality Management
Type Examination Annex X (includes Technical Documentation)
Type Examination Annex X (includes Technical Documentation)
System Assurance Annex IX Ch I & III
System Assurance Annex IX Ch I & III
System Assurance Annex IX Ch I & III
* Except sterile
Assessment of Technical
Assessment of Technical
Assessment of Technical Documentation * Annex IX Ch II
Production Quality Assurance Annex XI
Production Quality Assurance Annex XI
Documentation per category device § - Annex IX Section 4
Documentation per generic device § - Annex IX Section 4
* Assessment of technical documentation - Class D, Class B, C, D self test and near patient tests and Companion Dx
For Companion Diagnostics CA consultation Annex IX 5.2 §
For Companion Diagnostics CA consultation Annex X 3
Verification by EU Reference Laboratory
Verification by EU Reference Laboratory
The Organisation for Professionals in Regulatory Affairs
5
Definitions from MDCG 2019-13
MDCG 2019-13 is the guidance issued for sampling of IVDs for assessment of technical documentation. Allows manufacturers to group together Class B and C devices for the purpose of technical documentation review.
Category of Device – As defined by the relevant IVR codes according to Regulation (EU) 2017/2185 designation codes for Notified Bodies
Generic Device Group – 3rd level of the EMDN (one letter (W) plus 4 digits with the most appropriate IVP code. MDCG 2019-13 Guidance also allows manufacturer and NB to group using 4th level (W + 6 digits)
Only Generic Device Group is actually defined in the IVDR – having the same or similar intended purpose or a commonality of technology allowing them to be classified in a generic manner not reflecting specific characteristics
The Organisation for Professionals in Regulatory Affairs
6
3
24/05/2021
MDCG 2019-13 (EU) 2017/2185
3rd /4th level of EMDN
The Organisation for Professionals in Regulatory Affairs
7
Conformity Assessment Procedures – Class A ● Declaration of Conformity (Art. 17) and Annex IV Meets requirements of Regulation including: ● Risk Management and all relevant General Safety and Performance Requirements (Annex I) ● Performance evaluation (Art. 56 and Annex XIII) ● Quality Management System (Art 10.8) ● Technical Documentation (Annexes II and III) including lifecycle maintenance (Annex III and XIII) ● Incident / Vigilance reporting procedures (Art 82-84) ● No notified body certification required unless for sterile products (either under Annex IX or XI)
The Organisation for Professionals in Regulatory Affairs
8
4
24/05/2021
Conformity Assessment Procedures – Class A
Manufacturer’s device
Sterile
Notified Body
Not sterile
Sterility (Annex IX or XI)
EC Declaration of Conformity (Annex IV)
The Organisation for Professionals in Regulatory Affairs
9
Conformity Assessment Procedures – Class B Annex IX only route available for Class B devices. Conformity Assessment based upon a Quality Management System and on assessment of Technical Documentation ● Technical documentation assessment prior to issue of EU QMS Certificate – At least one device per category of devices covered by application
● Technical documentation assessed of subsequent devices in group as part of NB surveillance audits over certification period
The Organisation for Professionals in Regulatory Affairs
10
5
24/05/2021
Conformity Assessment Procedures – Class B
Notified Body
Manufacturer
Annex IX (Quality Management System and Assessment of TD)
Notified Body issues an EU Quality Management System certificate – including TD assessment
NB #
The Organisation for Professionals in Regulatory Affairs
11
Conformity Assessment Procedures – Class C ● EU Quality Management System certificate (Annex IX) – Technical documentation assessment of at least one device made by Notified Body according to the generic device grouping plan – Technical documentation assessed of subsequent devices in group as part of NB surveillance audits over certification period ● OR : EC Type Examination certificate (Annex X) coupled to EU production quality assurance certificate (Annex XI)
The Organisation for Professionals in Regulatory Affairs
12
6
24/05/2021
Conformity Assessment Procedures – Class C
Notified Body
Manufacturer’s choice
Annex IX (Quality management system with assessment of technical documentation
EC Type Examination (Annex X)
Production QA (Annex XI)
Notified Body issues an EU Quality Management System certificate (includes TD assessment)
Notified Body issues an EU Type and Production Quality Assurance certificate
NB #
The Organisation for Professionals in Regulatory Affairs
13
Conformity Assessment Procedures – Class D
● EU Quality Management System certificate (Annex IX) and EU technical documentation assessment certificate. ● OR : EC Type Examination certificate (Annex X) coupled to EU production quality assurance certificate (Annex XI) ● No sampling, Technical Documentation reviewed and approved by NB for each device. ● Verification of design (conformity to Common Specifications) by EU Reference Lab (pre-approval) ● 60 day review period. NB must receive a positive opinion from the EU Ref Lab ● Batch verification (post-approval)
The Organisation for Professionals in Regulatory Affairs
14
7
24/05/2021
Conformity Assessment Procedures – Class D
Notified Body
Manufacturer’s choice
QMS with technical documentation assessment - Annex IX and EU Ref Lab
EC Type Examination (Annex X) and EU Ref Lab
Production QA (Annex XI)
Notified Body issues an EU Quality Management System certificate and an EU Technical Documentation certificate
Notified Body issues an EU Type and Production Quality Assurance certificate
NB #
The Organisation for Professionals in Regulatory Affairs
15
Conformity Assessment Procedures – special cases. Class B, C or D Devices for self-testing and near- patient testing ● NO sampling of technical documentation ● EU technical documentation assessment certificate issued for each device ● Specific requirements apply – Demonstrate usability – Show studies Class C or D Companion Diagnostics ● No sampling of technical documentation ● EU technical documentation assessment certificate issued for each device ● Involvement of European Medicines Agency (EMA) – guidance awaited
The Organisation for Professionals in Regulatory Affairs
16
8
24/05/2021
Art. 50 Mechanism for scrutiny of conformity assessment of Class D devices.
NB notifies the CA of certificates it has granted for all Class D devices.
CA may apply further procedures in ● Art. 40 Monitoring and re-assessment of NBs ● Art. 41 Review of NB assessment of Tech Doc and of Performance Evaluation ● Art. 42 Changes to designations and notifications ● Art. 43 Challenge to the competence of NBs ● Art. 89, 90 and 92 related to dealing with devices presenting an unacceptable risk to health and safety and non-compliant products MDCG may request scientific advice from experts
The Organisation for Professionals in Regulatory Affairs
17
Annexes of Relevance
Annex IV EU Declaration of Conformity Annex IX Conformity Assessment based on a quality management system and on assessment of the technical documentation Annex X Conformity Assessment based on Type Examination Annex XI Conformity Assessment based on Production Quality Assurance Annex XII Certificates issued by a Notified Body
The Organisation for Professionals in Regulatory Affairs
18
9
24/05/2021
Annex IX – QMS and Techical Documentation
Chapter I: Quality Management System ● 1. QMS to be implemented according to art. 10.8 ● 2. Initial QMS assessment by NB. – Extensive list of QMS elements. – Audit will include processes for implementation of IVDR requirements (e.g. Art 10.8 (a) strategy for regulatory compliance) – Inform NB of substantial changes in the QMS ● 3. Surveillance – Surveillance audit at least every 12 months – Unannounced audit (at least once in 5 years) – Class B and C: include assessment of technical documentation based on sampling plan
The Organisation for Professionals in Regulatory Affairs
19
Annex IX – QMS and Tech Doc
Chapter II: Assessment of Technical Documentation ● Section 4. Assessment of Technical Documentation by sampling for Classes B and C – Complete review in accordance with Annexes II and III – Class B and C NB will issue a report on the assessment for device sampled ● Technical documentation assessment for Class D – Performance evaluation testing by EU Reference Lab for Class D devices(opinion within 60 days) – NB issues Technical Documentation Assessment Certificate following positive Performance Evaluation Assessment Report from EU Lab – Approval of changes (possibly with reference lab involvement) – Batch release
The Organisation for Professionals in Regulatory Affairs
20
10
24/05/2021
Annex IX – QMS and Tech Doc
Chapter II: Assessment of Technical Documentation ● 5. Specific types ● 5.1. Class C self-tests and Class B and C near-patient tests – Test reports, including studies with intended user – Where practical an example of the device – Data showing suitability of the device in view of intended purpose – Labelling and instructions for use – NB Issues Technical Documentation Assessment Certificate – Changes to product – may require pre-approval ● 5.2 Companion Diagnostics – NB consults with medicinal product CA or EMA (opinion within 60 days) – NB issues a technical documentation assessment certificate
The Organisation for Professionals in Regulatory Affairs
21
Annex IX – QMS and Tech Doc
Chapter III: Administrative Provisions ● Manufacturer or AR keep at the disposal of CA for at least 10 years after the last device has been
placed on the market: – the declaration of conformity,
– the documentation referred to in the fifth indent of Section 2.1 (QMS). and in particular the data and records arising from the procedures referred to in point (c) of Section 2.2., – the changes referred to in Section 2.4., – the documentation referred to in Sections 4.2 (TD required by Annex II
and III). and point (b) of Section 5.1., (ST/NPT) and – the decisions and reports from the notified body
The Organisation for Professionals in Regulatory Affairs
22
11
24/05/2021
Annex IX – QMS and Tech Doc
Chapter III: Administrative Provisions ● Each Member State shall make provision that this documentation is kept at the disposal of the competent authorities for the period indicated in the first sentence of the preceding paragraph in case the manufacturer, or his authorised representative, established within its territory goes bankrupt or ceases its business activity prior to the end of this period.
The Organisation for Professionals in Regulatory Affairs
23
Annex X – EU-Type
Upon application the manufacturer will provide ● Technical documentation referred to in Annexes II and III and outlined in Annex X ● Representative sample(s) of device The NB will ● Review all documentation and arrange for tests to verify the devcie meets the relevant GSPRs. ● Arrange for tests to verify that applied harmonised standards have been applied. ● Class D devices – involvement of EU reference labs ● Companion Diagnostics – involvement of EMA ● Certification issued for the specific device type examined.
The Organisation for Professionals in Regulatory Affairs
24
12
24/05/2021
Annex XI – Production Quality Assurance
Annex IX Section 2.1 (QMS) applies in full and includes technical documentation required by Annex II and III for types approved Annex IX Section 2.2 a, b, d, and e apply (i.e. excludes section on design controls) Annex IX Section 2.3 audit requirements apply except for sampling
review of technical documentation Annex IX Section 2.4 applies in full
Annex IX Section 3 surveillance shall apply with the exception of sampling of technical documentation and design risk management Annex IX Section 4 does NOT apply (assessment of the technical documentation ) Verification of manufactured Class D devices required (batch release).
The Organisation for Professionals in Regulatory Affairs
25
Manufacturer’s choice... Not all Notified Bodies will be designated for all Annexes. Check Nando listing to ensure your NB has been designated for your preferred choice of conformity assessment.
The Organisation for Professionals in Regulatory Affairs
26
13
24/05/2021
Learning Outcomes: Recap
To identify the routes for conformity assessment allowed within the IVDR To recognise routes linked to product classification To explore the conformity assessment procedure for each route
The Organisation for Professionals in Regulatory Affairs
27
Questions
The Organisation for Professionals in Regulatory Affairs
28
14
01/06/2021
Masterclass
Quality Management Systems
Stuart Angell, IVDeology LTD
www.ivdeology.co.uk info@ivdeology.co.uk
ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION
1
Learning Outcomes
What is a Quality Management System Why is it needed MDSAP
2
1
01/06/2021
What does Quality actually mean?
Why do we need a Quality Culture?
3
Why have a Quality Management System
Insight
“all manufacturers should have a quality management system and a post market surveillance systemwhich should be proportionate to the risk class and type of device in question” Art. 31
“There is no ‘one size fits all’ Quality Management System. The extent at which an organisation
controls their processes is
dependent on the nature, size and complexity of an organisation.”
4
2
01/06/2021
General Obligations
“The qualitymanagement system shall cover all parts and elements of a manufacturer's organisation dealing with the quality of processes, procedures and devices. It shall govern the structure, responsibilities, procedures, processes and management resources required to implement the principles and actions necessary to achieve compliance with the provisions of this Regulation” (paragraph 8)
Insight
“Establishing a documented, controlled, repeatable process for organisation operations is key to establishing a safe and effective product design, development and manufacture.”
01/06/2021
www.ivdeology.co.uk
5
5
The Origins Backstory…
W. Edwards Deming: 14 Points for Quality Management
1.Create constancy of purpose for improving products and services.
2.Adopt the new philosophy.
3.Cease dependence on inspection to achieve quality.
4.End the practice of awarding business on price alone; instead, minimize total cost by working with a single supplier.
5.Improve constantly and forever every process for planning, production and service.
6.Institute training on the job.
7.Adopt and institute leadership.
8.Drive out fear.
9.Break down barriers between staff areas.
10.Eliminate slogans, exhortations and targets for the workforce.
11.Eliminate numerical quotas for the workforce and numerical goals for management. 12.Remove barriers that rob people of pride of workmanship, and eliminate the annual rating or merit system.
13.Institute a vigorous program of education and self-improvement for everyone.
This Photo by Unknown Author is licensed under CC BY-SA-NC
14.Put everybody in the company to work accomplishing the transformation.
6
3
01/06/2021
ISO13485:2016
ISO13485:2016 is still the standard of choice under IVD Regulation • Is specific for the In Vitro Medical Device and Medical Device industry • Not yet harmonized under IVDR • Concept of QMS has been extended to economic operators • Requirement for a QMS is included in the conformity assessment annexes IX, X and XI
This Photo by Unknown Author is licensed under CC BY-SA
7
The Systematic Approach…
Insight
“Understanding your inputs and outputs are essential for effective Quality Management. The processes within ISO13485 are interconnected and work collectively to ensure quality.”
8
4
01/06/2021
Where to begin..
• What does quality mean to you (Quality Policy)?
• What do your customers or regulations need from you? • Defining quality objectives relevant to company vision • Describe how quality processes are run and interact with each other (Quality Manual, procedures) • Who is responsible for quality processes? • How are you recording your actions?
This Photo by Unknown Author is licensed under CC BY-SA
9
The pushback…
Insight
“Why are we adding additional complexity?” “We can’t afford to do this!” “This is delaying getting products on market!” “We only have 3 people in the company!”
“Effective implementation of a QMS will add value to any organisation.
Much of what is described in the
standard is already performed as part of natural company growth.”
Here is why…
10
5
01/06/2021
The Benefits of a QMS: 3 examples
Document and Change Control
Risk Management
Supplier Management
Standardisation of processes and recording activity allows effective
Identification, assessing and controlling risk, allows the prevention of incidents that will have financial, safety and legal consequences
Organisations live or die on the quality of suppliers. A robust mechanism for supplier assessment and control will reduce risk of supply issues
delegation of actions, and enhanced ability to identify errors, risks and improvements
Consider the size, format and scope of the QMS specific to the requirements of the company
11
Auditing…
A quality management system can be assessed by a notified body for conformity The certificate can be a useful mark of quality
Dave Spud
But
Internal auditing is essential to assess the state of the organization. The more you review the QMS the more efficient and compliant it will be.
12
6
01/06/2021
Medical Device Single Audit Programme
• Demonstrate conformity of Quality Management Systems • Based on ISO13485:2016 • Essential for Canadian registration • Supports Japan, Australia, USA and Brazil registration
Insight
“Good example of global harmonisation approach, this is highly recommend is these markets are required as part of the portfolio. There is an additional cost for this service will allow less audit pressure and ease market access routes”
13
Learning Outcomes: Recap
Quality Management Systems are essential for the IVD industry How a QMS is used is highly dependent on the organisation, but based on ISO13485 requirements An effective QMS can add real value MDSAP is a useful addition to the process if applicable to your product portfolio
14
7
01/06/2021
Acknowledgements Mauricio Suppo - Qarad
15
8
24/05/2021
Tecs
Technical Documentation Documentation Module 19, Regulation of In Vitro Diagnostic Medical Devices Lecture 5 Ben Jacoby nd June 2021
Ben Jacoby, Cambridge RA Ltd.
ENABLING AND PROMOTING EXCELLENCE IN THE HEALTHCARE REGULATORY PROFESSION
The Organisation for Professionals in Regulatory Affairs
1
Scope
The focus is on European legislation:
Regulation (EU) 2017/746 on in vitro diagnostic medical devices IVD Regulation, abbreviated ‘IVDR’
Directive 98/79/EC on in vitro diagnostic medical devices IVD Directive, abbreviated ‘IVDD’ More emphasis on IVDR than IVDD
The Organisation for Professionals in Regulatory Affairs
2
1
24/05/2021
Learning Outcomes / agenda
General introduction Impact of Brexit Technical documenation – What is it? – How should it be compiled? – What is STED ? – How to write a DoC
The Organisation for Professionals in Regulatory Affairs
3
General introduction
Transition from Directive to Regulation
The Organisation for Professionals in Regulatory Affairs
4
2
24/05/2021
Transition from Directive to Regulation
New MDR DOA May 2021
Source: MHRA, https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/640404/MDR_IVDR_guidance_Print_13.pdf
The Organisation for Professionals in Regulatory Affairs
5
Increased regulatory scrutiny under IVDR
IVD directive ~15% of IVD’s require intervention of notified body
IVDR ~85% of IVD’s require intervention of notified body (All except Class A)
The Organisation for Professionals in Regulatory Affairs
6
3
24/05/2021
Review of technical documentation under IVDD
Annex II Most technical files reviewed by NB
Non-Annex II Few if any technical files reviewed by NB
The Organisation for Professionals in Regulatory Affairs
7
Notified body expertise under IVDD
Annex II NB’s generally familiar with these products
Non-Annex II NB’s mostly unfamiliar with these products which are self- certified by the manufacturer
The Organisation for Professionals in Regulatory Affairs
8
4
24/05/2021
Notified bodies under IVDD
‘
The Organisation for Professionals in Regulatory Affairs
9
Notified bodies under IVDR (As of March 2021)
The Organisation for Professionals in Regulatory Affairs
10
5
24/05/2021
Some potential transition issues (IVDD to IVDR)
• Impact on legacy devices especially re-classification • Conversion to IVDR and/or STED format • How far should technical documentation follow the exact order and structure of Annexes II and III? • Conformity with IVDR general safety and performance requirements rather than IVDD essential requirements • Number of technical files which might need revision • Availability and resources of notified bodies • How soon to engage with notified body • Additional clinical evidence which might be required • Impact of common specifications, implementing acts, updated guidance • Resources required to maintain technical documentation
The Organisation for Professionals in Regulatory Affairs
11
Technical documentation Impact of Brexit
The Organisation for Professionals in Regulatory Affairs
12
6
24/05/2021
Technical documentation & Brexit
• In GB IVD’s will continue to be regulated by the IVD directive until June 2023. • But manufacturers of non-certificated CE- marked IVD’s must transition from the IVDD to the IVDR by 26 May 2022: • Unless they only want to market devices to Great Britain (GB) only. • Manufacturers can also obtain the UKCA mark by obtaining a certificate from a UK approved body or by self-certifying a general IVD.
The Organisation for Professionals in Regulatory Affairs
13
Technical documentation & Brexit
• The CE mark will continue to be accepted in GB until June 2023. • Northern Ireland will accept the CE mark or the CE UKNI mark. • But GB will transition to new regulations requiring a mandatory UKCA mark as of 1 July 2023. • Although no details have been made public it is possible that the new regulations will be based broadly around the existing IVDR.
The Organisation for Professionals in Regulatory Affairs
14
7
24/05/2021
Technical documentation transition timelines
• It follows that it will be desirable to have a good understanding of IVDR requirements. • Notified bodies are under great pressure and may have long lead times. • In order to meet the timelines for NI / EU, manufacturers of legacy devices should have started work on their transition plan to IVDR already as the deadlines are: • Devices self-certified under IVDD, by 26 May 2022 • Devices with NB certificates under IVDD, by the expiry date of the certificate or 26 May 2024, whichever comes first.
The Organisation for Professionals in Regulatory Affairs
15
Technical documentation
What is it?
The Organisation for Professionals in Regulatory Affairs
16
8
24/05/2021
Technical documentation IVDR
‘ 1.’When placing their devices on the market or putting them into service, manufacturers shall ensure that they have been designed and manufactured in accordance with the requirements of this Regulation. 4. Manufacturers shall draw up and keep up to date* the technical documentation for those devices. The technical documentation shall be such as to allow the conformity of the device with the requirements of this Regulation to be assessed. The technical documentation shall include the elements set out in Annexes II and III.’ Article 10 ‘General obligations of manufacturers’ * Highlighting added here to draw attention to this need.
The Organisation for Professionals in Regulatory Affairs
17
Technical documentation versus summary technical documentation Source: http://www.imdrf.org/documents/doc-ghtf-sg1
The Organisation for Professionals in Regulatory Affairs
18
9
24/05/2021
Technical documentation
How should it be compiled?
The Organisation for Professionals in Regulatory Affairs
19
How should it be compiled?
‘The technical documentation and, if applicable, the summary thereof to be drawn up by the manufacturer shall be presented in a clear, organised, readily searchable and unambiguous manner and shall include in particular the elements listed in this Annex.’ (IVDR Annexes II and III)
The Organisation for Professionals in Regulatory Affairs
20
10
24/05/2021
Comment on format of technical documentation
‘clear, organised, readily searchable …’ Whilst the wording of Annexes II and III don’t specifically exclude use of paper formats it could be interpreted to mean that electronic formats should be used
The Organisation for Professionals in Regulatory Affairs
21
How should it be compiled?
• How closely should summary technical documentation follow the order and content of IVDR Annexes II and III? • Will notified bodies expect a high level of concordance to make it easier to assess compliance (check-box approach)?
The Organisation for Professionals in Regulatory Affairs
22
11
24/05/2021
The IVDD has no fixed format for technical documentation. By contrast IVDR Annexes II and III are quite prescriptive. This should drive more consistency around the content of technical documentation for example both within and between different manufacturers. Format of technical documentation
The Organisation for Professionals in Regulatory Affairs
23
Format of technical documentation
The following slides show the main headings of IVDR Annexes II and III. Comments are also provided in a few places in purple to highlight changes from the IVDD.
The Organisation for Professionals in Regulatory Affairs
24
12
Made with FlippingBook flipbook maker