Impact of the IVD Regulations. Barbara Fallowfield Managing Director

Transcription

1 Impact of the IVD Regulations Barbara Fallowfield Managing Director

2 What will I cover today? Timelines Key Changes Classification Clinical Evidence Requirements Third Parties Vigilance and Post Marketing Surveillance Companion Diagnostics In-house tests

3 What is BIVDA? Trade Association representing in vitro diagnostic companies active in the UK Clinical market Established 1992 & based in central London Part of our role is to support member companies Other side of our role is to speak for the industry with Government & other stakeholders

4 In the beginning..no regulation in Europe Regulation in Europe IVD submission to the Commission April 1995 Commission proposal for a Directive December 1998 Publication in Official Journal 3 year transition and transposition phase (into UK law under Consumer Protection Act) 8 December 2001 Directive 98/79/EC came fully in force 2011 discussions started re new regulations

5 Final drafts made public in June 2016 Timelines Best guess for entry into force (publication in the Official Journal of the EU) in April months later, Class A products can be placed on the market under the new Regulation & Notified Bodies (NBs) can apply for re-designation 2 years after publication the first IVDR certificates can be issued by NBs After 5 years the Regulation is fully in force and all IVDs must comply

6 Transition periods Legal linguistic checks and formal votes Devices can be placed on the market under new Regs NBs can request redesignation Spring 2017 egulations formally adopted and enter into force Spring 2022 IVDR fully applied

7 Why five years? All Member State National laws have to be rescinded New Regulation is nearly 400 pages long existing IVD Directive was under 100 pages Lot of changes

8 IVDR Reclassification Major changes to how IVDs are classified Will be a risk-rule based system based on Global Harmonisation Task Force classification rules Impacts most IVD manufacturers very few exceptions

9 Current vs Future 98/79/EC List of Products Annex II A & B Self-Testing General IVD IVDr Risk Based Class D Class C Class B Class A

10 Device Classes D C B A High public health risk Blood safety / high risk infectious diseases High risk for individual patients e.g. cancer markers, dangerous infectious diseases, etc. Medium risk for individual patients e.g. blood chemistry, pregnancy tests, etc. Low risk for individual patients Instruments, accessories, specimen collection systems etc. 11

11 Class D Devices Batch release differences compared to IVD Directive: All batches will have to be tested IVDR doesn t allow for reducing the level of testing after a certain number of batches All batches will have to be tested by an external laboratory

12 Quantum Leap IVD Directive - 98/79/EC IVD Regulation Require a Notified Body Do not Require a Notified Body (80-90%) Require a Notified Body (80-90%) Do not Require a Notified Body

13 IVDR Classification Annex VII Rule 1 Rule 2 Rule 3 Rule 4 Rule 5 Rule 6 Rule 7 Infectious Disease Blood Screening High Risk Disease Blood or Tissue Compatibility Cancer Markers CDx Genetic tests Congenital Screening Self Testing High Risk Near Patient Tests Specific IVD Reagents Instruments Specimen Receptacles None of other Rules Controls no assigned values D C High Risk blood groups Self tests Specific List e.g Pregnancy C C A B B D B

14 Impact of Classification Cost Notified Body services are paid for by the manufacturer Shortage of Notified Bodies Manufacturers who don t already use a NB need to start the process of identifying one now Product portfolios may need to remove some products from the market if they become uneconomical to supply OR if their performance will not meet criteria under the Regulation Some products may face a big change in classification Eg Syphilis tests currently self-certified but will become Class D

15 Clinical Evidence New requirement with major impact demonstration of compliance with the general safety & performance requirements should be based on clinical evidence based on data on scientific validity and analytical performance and clinical performance of the device Sourced from performance studies Updated throughout the product s lifecycle Generated through a performance evaluation plan and collated into an annual Performance Evaluation Report

16 Clinical Evidence Analytical Performance the ability of an IVD medical device to correctly detect and measure a particular analyte Clinical Performance the ability to yield results that relate to a particular clinical condition or physiological state for the intended use, the target population and intended user Scientific Validity the association of an analyte to a clinical condition or physiological state

17 Clinical Evidence Analytical Performance Clinical Performance Scientific Validity Same as for IVD Directive Based on the essential requirements Partly covered by the IVDD Population effects of the device New requirement Established assays should be simple Novel assays may require more data 7

18 Impact on Existing Products Cannot grandfather existing products All existing products must be reclassified Need to perform a gap analysis on existing data May need to undertake additional performance studies Companies will need to notify end users of any products that may leave the supply chain in time for alternatives to be sourced pathology staff should be aware of this possibility

19 Third Parties Distributors and importers will now be covered by the Regulation The role of the Authorised Representative is more clearly defined (manufacturers outside the EU already need an AR within a member state to take legal responsibility for the product s compliance) they become economic operators with specific regulatory commitments This will impact Training Cost of reviewing contracts & auditing operators in the supply chain Will impact smaller manufacturers relying on independent distributors more than the multi-nationals

20 Regulatory Responsible Person Set out in Article 13 of the IVDR is the Person Responsible for Regulatory Compliance Manufacturers shall have available within their organization at least one person responsible for regulatory compliance who possesses the requisite expertise in the field of IVD s Experience is either Degree plus one year RA or QA experience in IVDs or four years RA or QA experience in IVDs First and only new role in the IVDR or MDR

21 Post Market Surveillance For any device,proportionate to the risk classification and appropriate to the type of device, manufacturers shall: Establish Document Implement Maintain Update A Post-Market Surveillance system which shall be an integral part of the Manufacturer s Quality Management System Proprietary and confidential November 2

22 Top Level Approach Quality Performance Safety Throughout Product Lifetime Systematically: Gather Record Analyse Relevant Data Draw Necessary Conclusions Determine, Implement & Monitor Any Preventative and Corrective Actions Proprietary and confidential November 2

23 Post Marketing Surveillance All classes of device must have a Post-Market Performance Follow-Up Plan Classes A and B must have an updated Post-Market Surveillance Report which is available on request Classes C and D must have a Periodic Safety Update Report and a Performance Evaluation Report both to be updated when necessary but at least annually Impact in additional costs and training of staff, plus time to complete reports

24 Vigilance Timelines have been reduced for reporting of serious incidents from 30 to 15 calendar days Manufacturer will report to a central data base and reports are then transmitted to the CA where the incident occurred There is a provision for an Implementing Act to establish electronic reporting forms Impact: May need additional staff to support shorter reporting times Cost & time in amending existing procedures

25 Reporting Timelines Article 59 Timelines should take account of the severity of the serious incident Incident MEDDEV Rev 8 IVDR - Article 59 Change Serious public health threat IMMEDIATELY (without any delay that could not be justified) but not later than 2 calendar days after awareness by the MANUFACTURER of this threat. the report shall be provided immediately, and not later than 2 days after awareness by the manufacturer of this threat. 2 days No Change Death or unanticipated serious deterioration in state of health IMMEDIATELY (without any delay that could not be justified) after the MANUFACTURER established a link between the device and the event but not later than 10 elapsed calendar days following the date of awareness of the event. immediately after the manufacturer established or suspected a causal relationship between the device and the serious incident but not later than 10 elapsed days following the date of awareness of the serious incident. 10 days No Change Includes suspected causal relationship Serious incident IMMEDIATELY (without any delay that could not be justified) after the MANUFACTURER established a link between the device and the event but not later than 30 elapsed calendar days following the date of awareness of the event. immediately after the manufacturer has established the causal relationship with their device or that such causal relationship is reasonably possible, and not later than 15 days after they have become aware of the serious incident. 15 days Reduced from 30 days Includes possible causal relationship Proprietary and confidential

26 Courtesy of Caroline Freeman, Quintiles Diagram of All Elements Required Proactive Adverse Events ISO/NB Complaints Voluntary FDA Audits/ Inspections Vigilance Reporting Field Safety Corrective Actions Enforced Post-Market Surveillance CAPA Supply Chain Audits Quality Management Risk Mgmt. End-user Buy back Product Sampling Health Tech. Assessments Literature Review Registry Studies Post-Market Clinicals Parts Usage User Feedback Scientific Journals Healthcare Articles Healthcare Guidelines Marketing Studies Non PM visits Failure Trends Focus Groups Customer Surveys Reactive

27 UDI & Registration UDI the EU system will hopefully be similar to the US system but there will be a separate EU database with potentially different data requirements The Manufacturer will need to notify all products to the Eudamed database and keep it updated Importers will need to add their details to the product registration Concerns over the speed of development & implementation of Eudamed database Impact to industry around the time and cost of inputting all of the required data, and keeping it updated 27

28 Companion Diagnostics means a device which is essential for the safe and effective use of a corresponding medical product to: - Identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product; or - Identify, before and/or during treatment, patients likely to be at increased risk for serious adverse reactions as a result of treatment with the corresponding medicinal product

29 Companion Diagnostics All companion diagnostics are Class C and require oversight by Notified Bodies Approval process requires interaction with EMA/CA, and they have 60 (+60) to review (potential for delay) Greater data requirements and Clinical Performance testing In-house tests are allowed Labelling requires clear link to medicine

30 In-house Manufacture An in-house test is one which is manufactured in a health institution; where the enduser deviates from the manufacturer s instruction for use; use of a Research Use Only product to generate a result used in clinical decision making The current exemption for in-house tests remains but with some additional requirements: If in-house test are used where there are commercial alternatives a justification will be required All in-house tests will be registered with the Competent Authority and any performance issues must be notified A quality management system and laboratory accreditation is required Class D analytes will require nearly all the same performance data and documentation as manufactured products A lot of issues are undecided and will depend on the Member State as to how they are implemented

31 Questions? Contact Information: Barbara Fallowfield BIVDA