Classification under the IVD Regulation

Transcription

1 Classification under the IVD Regulation Nick Baker Head of IVD Notified Body LRQA Ltd Improving performance, reducing risk

2 IVD regulation shift in regulatory scrutiny Under the current IVD directive 10-15% IVD s require Notified Body assessment Under the new Regulation 85-90% will require Notified Body assessment (All IVD s except Class A unless sterile)

3 Classification rules The IVD Regulation introduces a new risk-rule based classification system based on the Global Harmonisation Task Force (now the International Medical Device Regulatory Forum) classification rules, document GHTF/SG1/N045:2008. This change to the classification system will have an impact on all manufacturers of IVDs The majority of IVDs currently self-certified will now require the services of a Notified Body in the conformity assessment process to ensure the safety and performance of IVDs placed on the market in the EU.

4 Classification rules Classification rules given in Chapter V and Annex VIII of the regulation In the new classification system, IVDs will be divided into four classes of risk: A (lowest risk), B, C and D (highest risk) The conformity assessment procedure for class A devices will be carried out, as a general rule, under the sole responsibility of the manufacturer For devices of class B, C and D an appropriate level of involvement of a Notified Body is compulsory, proportionate to the risk class

5 Rationale for classification rules CLASS RISK LEVEL EXAMPLES A Low individual risk and Low public health risk Clinical chemistry analyser Prepared selective culture media B Moderate individual risk and/or Low public health risk Vitamin B12 test Pregnancy self testing Anti-nuclear antibody Urine test strips C High individual risk and/or Moderate public health risk Blood glucose self testing HLA typing PSA screening Rubella test D High individual risk and High public health risk HIV blood donor screening HIV blood diagnostic

6 Classification rules Implementing rules for the classification rules Application of the classification rules shall be governed by the intended purpose of the devices If the device is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices Accessories are classified in their own right separately from the device with which they are used Software, which drives a device or influences the use of a device, falls automatically in the same class as the device. If standalone software is independent of any other device, it is classified in its own right.

7 Classification rules Calibrators intended to be used with a device shall be classified in the same class as the device 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 The manufacturer shall take into consideration all the rules in order to establish the proper classification for the device Where a device has multiple intended purposes stated by the manufacturer, which place the device into more than one class, it shall be classified in the higher class If several classification rules apply to the same device the rule resulting in the higher classification shall apply. Each of the rules applies to first line assays, confirmatory assays and supplemental assays

8 Classification rules Rule 1 Detection of transmissible agents in blood, blood components, cells, tissues or organs to assess their suitability for transfusion, transplantation or cell administration e.g. HIV, HBV, HCV, Chagas disease, Syphilis Detection of a transmissible agent that causes a life-threatening disease with a high or suspected high risk of propagation. e.g. HIV, HBV, HCV Class D Devices intended to be used to determine the infectious load of a life-threatening disease where it s monitoring is critical in the process of patient management. e.g. HIV RNA viral load

9 Classification rules Rule 2 Reagents for blood grouping or tissue typing to ensure immunological compatibility for transfusion, transplantation or cell administration. e.g. tissue typing Except Class C Determination of ABO, Rh, Kell, Kidd, Duffy systems Class D

10 Classification rules Rule 3 Detection of sexually transmitted agents e.g. CT, NG, Syphilis, Herpes Simplex 1 & 2 Detecting the presence in cerebrospinal fluid or blood of an infectious agent without a high risk or suspected risk of propagation e.g. Haemophilus influenzae type B (Hib) antigen, IgM antibodies to malaria parasites. Detection of an infectious agents if there is a significant risk that an erroneous results could cause sever disability or death to the individual or foetus being tested or the individuals offspring e.g. Zika virus, MRSA. Pre-natal screening of women to determine their immune status towards transmissible reagents e.g. Rubella Class C

11 Classification rules Rule 3 Determining infective status, or immune status if there is a risk that an erroneous result would lead to a patient management decision resulting in a life threatening situation for the patient or the patient s offspring e.g. Detection of systemic inflammatory response syndrome towards diagnosis of sepsis, detection of auto antibodies for the diagnosis of type 1 diabetes Devices intended to be used as companion diagnostics e.g. KRAS oncogene mutation test to identify CRC patients for treatment with cetuximab or panitumumab; Test for overexpression of HER-2 in breast cancer patients to identify patients who are suitable for treatment with trastuzumab. Class C

12 Classification Rules Rule 3 contd Devices intended to be used for disease staging, if there is a risk that an erroneous result would lead to a patient management decision resulting in a life threatening situation for the patient or their offspring e.g. biochemical tests to determine the disease stage progression for kidney, liver or heart. Devices intended to be used for screening, diagnosis or staging of cancer e.g. PSA, CEA, CA125. Human genetic testing e.g cystic fibrosis, Huntington s disease Monitoring of levels of medicinal products, substances or biological components, when there is a risk that an erroneous result will lead to a patient management decision resulting in a life-threatening situation for the patient or their offspring e.g cyclosporin, digoxin, Troponin I, Troponin T.. Class C

13 Classification Rules Rule 3 contd Management of patients suffering from a life-threatening disease or condition e.g. prognosis or monitoring of disease Screening of congenital disorders in the foetus e.g. trisomy 13, 18 & 21. Screening for congenital disorders in the newborn where failure to detect and treat such disorders could lead to lifethreatening situations or severe disabilities. e.g. PKU, Cystic Fibrosis Class C

14 Classification rules Rule 4 Devices for self-testing, except for the detection of pregnancy, fertility testing and for determining cholesterol, detection of glucose, erthrocytes, leucocytes and bacteria in urine which are Class B Devices for near patient testing are classified in their own right. Class C Rule 5 Products for general laboratory use, accessories which possess no critical characteristics e.g. buffer solutions, washing solutions and general culture media and histological stains intended by the manufacturer to make them suitable for in-vitro diagnostic procedures related to a specific examination. Instruments used in IVD procedures Specimen receptacles. Class A

15 Classification rules Rule 6 Devices not covered elsewhere in the classification rules e.g. most biochemistry tests for blood gases, hormones, enzymes etc Class B Rule 7 Devices which are controls without a quantitative or qualitative assigned value e.g. non-assay specific control serum containing multiple biochemical analytes;. Class B

16 Interpretation of the classification rules IVD WG classification subgroup (from MDEG) formed to discuss classification issues Classification will depend upon intended use i.e., screening claims and the level of risk to the patient and the public (taking into account the likelihood of harm and the severity of that harm) Identical devices may be classified differently if they are to be used for different diagnostic purposes. This is why the manufacturer s intended use of the device is critical to determining the appropriate class? MEDDEV guidance to be issued as for MDD.

17 Conformity assessment for Class D devices Class D Annex IX Conformity assessment based on a quality management system, and on assessment of the technical documentation plus testing at a Reference Laboratory and Batch Verification OR Annex X: Conformity assessment based on Type Examination plus testing at a Reference Laboratory + Annex XI: Conformity assessment based on Production Quality Assurance including Batch Verification

18 Conformity assessment for Class C devices Class C Annex IX Conformity assessment based on a quality management system and on assessment of the technical documentation on a representative basis, sections in Chapter II. OR Annex X: Conformity assessment based on Type Examination + Annex XI: Conformity assessment based on Production Quality Assurance

19 Conformity assessment for Class B & A devices Class B Annex IX Conformity assessment based on a quality management system and on assessment of the technical documentation on a representative basis, sections in Chapter II. Class A Non-Sterile Technical documentation according to Annexes II & III Sterile Annex IX or XI, limited to establishing, securing and maintaining sterile conditions

20 Conformity assessment requirements Class D devices Requirement for Notified Bodies to notify the Commission of certifications granted for Class D devices have to submit IFU & summary of safety and performance. Competent Authority has the authority to review the conformity assessment performed by the Notified Body. Products will be selected based on novelty of device, incidents or change in risk benefit profile Notified Body has to consult the expert panel if the device type is certified for the first time and there are no CS available

21 Conformity assessment requirements Class D devices Notified Bodies also have to request that reference laboratories verify that Class D devices comply with the applicable Common Specification (CS) currently CTS only available for Annex II List A devices and vcjd, or solutions that are equivalent to the CTS Reference laboratory must respond within 60 days Reference laboratory also has to be consulted on changes that could affect compliance with the CS Requirement to send samples to a reference laboratory at regular intervals.

22 Conformity assessment requirements for companion diagnostics For Companion Diagnostics (Class C) the Notified Body has to consult a Competent Authority (CA) for medicines or European Medicines Agency (EMA), submitting a the draft summary of safety and performance and IFU CA or EMA has to respond within 60 days, can be extended for another 60 days on scientifically valid grounds Notified Body has to consider the opinion of the CA or EMA and notify them of it s decision Notified Body issues a technical documentation certificate for the device Also have to consult with the CA or EMA for any changes to the device Not defined what should be included in the summary of safety and performance report.

23 Performance Evaluation requirements Performance Evaluation Scientific Validity Refers to the association of an analyte to a clinical condition or physiological state Analytical Performance Refers to the ability of an IVD to correctly detect or measure a particular analyte Clinical Performance refers to it s ability to yield results that relate to a particular clinical condition/physiological state for the intended use and in accordance with the target population and where applicable the intended user For established analytes, this may be from the literature but needs to be established for novel analytes Sensitivity/specificity, LoD, linearity, reproducibility Data to support reference ranges etc Performance Evaluation under the IVDR

24 Impact for manufacturers Classification of device will affect conformity assessment requirements Almost all IVD devices will require some form of Notified Body assessment Choice of conformity routes for Class D & C devices All conformity routes involve Audit of the quality system Review of technical documentation Assessment of clinical evidence, performance evaluation and performance studies All IVD s will have to meet the General Safety and Performance requirements. Conformity to these requirements will be assessed by a Notified Body

25 Recommended Actions for Manufacturers Classify existing products identify any conflicts or borderline products Discuss with your Notified Body or make contact if you think you will need one. There is no grandfathering clause All products will have to meet the requirements of the regulation.

26 Questions?

27 Nick Baker Technical Manager Medical Directives T +44 (0) E nick.baker@lrqa.com LRQA 1 Trinity Park, Bickenhill Lane, Birmingham, B37 7ES Improving performance, reducing risk Lloyd s Register and variants of it are trading names of Lloyd s Register Group Limited, its subsidiaries and affiliates. Copyright Lloyd s Register Quality Assurance Limited A member of the Lloyd s Register group.