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  • 1.  Article 53 CEAR and Discussion

    Posted 16-Nov-2018 09:11
    Edited by Richard Vincins 16-Nov-2018 09:13
    Sorry Article 54 in the Subject Heading.  Good day and wanted to clarify some information on Article 54 of the MDR (EU) 2017/745 and some information that I heard recently.  I will not re-print Article 54 here in interest of space, but basically the Article says if you have a Class III implantable device or Class IIb active device for medicinal delivery than a clinical evaluation "consultation" is employed.  The Notified Body after review of a company's Clinical Evaluation Report for these specific devices generates this Clinical Evaluation Assessment Report (CEAR) that is uploaded to an electronic system (does not exist yet as far as I know).  This is then reviewed by an Expert Panel via MDCG who advises Commission and NB on acceptance of product for market, which then the NB can continue the review.

    All of that is fairly clear to me ... and I use the word "fairly" quite loosely.  What has confused me in a couple public forums in the last few months there has been some comments or indications that a CEAR would be generated for all classes of devices reviewed by a Notified Body.  Only the CEAR for Class III implant and Class IIb medicinal delivery would be uploaded to this electronic system, but the others would be maintained as part of the technical documentation review process.

    Has anyone heard similar?  Your own interpretations of Article 54?  Is this one of those Articles that industry really needs to be strong on to make sure it does not get out of control?  Do we expect this to be performed retroactively for all those legacy Class III implant and Class IIb medicinal delivery products out there - since none of these existing MDD CE Mark products will have a CEAR (point c and h of Annex IX, Section 5.1 seem to indicate as such)?

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    Richard Vincins RAC
    Vice President Global Regulatory Affairs
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  • 2.  RE: Article 53 CEAR and Discussion

    Posted 17-Nov-2018 10:11

    Hello Richard,

    Under the MDR, whenever a Notified Body (NB) is involved in the conformity assessment procedure, the NB is required to develop a clinical evaluation assessment report (CEAR). See Annex VII, Requirements to be met by Notified Bodies, Subsection 4.6, Reporting. In addition, the need to document an assessment of clinical evaluation in a CEAR is found in other parts of the MDR.

    Also, the EU guidance on clinical evaluation (MEDDEV 2.7/1 Rev 4) states that NBs should document the assessment of clinical evaluation in a CEAR. The previous revision of the guidance also indicates that a CEAR should be developed; whereas, the 2003 version states that the assessment should be in documented in a report.

    Under the directives, regarding legacy devices, NBs are expected to have documented their assessments either in a general report on the Technical Documentation or in a separate CEAR. Under the MDR, whenever NBs assess or reassess a clinical evaluation report (CER), including for legacy devices, NBs will need to document their assessments in CEARs.

    Best regards,

    Maria



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    Maria E Donawa, M.D.
    President, Donawa Lifescience Consulting Srl
    Rome, Italy
    medonawa@donawa.com
    +39 06 578 2665
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  • 3.  RE: Article 53 CEAR and Discussion

    Posted 17-Nov-2018 16:13
    Dear Colleagues,

    This is my understanding as well. What probably worth to add is a change in the evaluation of the Class II.b. implants, which forces the NBs to look through the technical documentation of all these devices. This may be also a painful exercise.

    "Manufacturers of class IIb devices, other than custom-made or investigational devices, shall be subject to a conformity assessment as specified in Chapters I and III of Annex IX, and including an assessment of the technical documentation as specified in Section 4 of that Annex of at least one representative device per generic device group.

    However, for class IIb implantable devices, except sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips and connectors, the assessment of the technical documentation as specified in Section 4 of Annex IX shall apply for every device. (Article 52. 4.)

    The notified body shall clearly document the outcome of its assessment in the clinical evaluation assessment report. (Annex IX. 4.8.)"

    My understanding is that this should take place for
    • new Class II.b. implantable devices, before they get marketed and
    • all Class II.b. implantable devices of the manufacturer during the 5 years of the certification period.

    Which means for me, that all (legacy) Class II.b. devices marketed under the MDD undergo a re-evaluation procedure after 2020 May 26 according to the EUMDR before they are re-certified and get listed in the manufacturer's new CE-certificate.

    For the pharmaceutical products similar process has been implemented during the extensions of the EU in the new Member States, when the medicines marketed in those countries have had to be thoroughly screened by the national Health Authorities, if they had matched the pharmaceutical requirements of the EU. A significant number of products failed to pass and had been withdrawn.

    Regards

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    Peter Mikó M.D
    ArtPharm Ltd.
    Gyermely
    Hungary
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  • 4.  RE: Article 53 CEAR and Discussion

    Posted 19-Nov-2018 00:20
    Maria thank you for the clarification on the reference to Annex VII, Section 4.6 because that is where I also interpret and some of the statements made that a Clinical Evaluation Assessment Report would be generated for all clinical evaluation report reviews.  Then it would only be the Class III implant and Class IIb medicinal that would be "uploaded" to this electronic system.  The MDR is quite difficult because there are requirements and not exactly clear references on requirements.  Thank you for your thoughts, they are inline with my thoughts as well ... though I have had discussions that others do not agree with the interpretation that a CEAR is only for Class III implant and Class IIb medicinal, not all devices.

    As mentioned, there are requirements stuck in all different sections without clear references, I saw that too Peter, so thank you for referencing again - I mentioned that in a training with a company and they were quite shocked.  They had not seen or read that - regarding Class IIb implantables requiring review for all devices - so they were a bit exasperated.  Thank you for your comments as well, I see requirements in some Articles, Annex VII, Annex IX/X/XI and others that is leading me to think of all the work that must be done in the next few years for compliance.

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    Richard Vincins RAC
    Vice President Global Regulatory Affairs
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  • 5.  RE: Article 53 CEAR and Discussion

    Posted 19-Nov-2018 17:17
    There are some cases in which the manufacturer produces a document, the NB reviews it, and then transmits the manufacturer's document, the NB's review, or both using Eudamed. I've identified three situations described below.

    The manufacturer prepares the clinical evaluation information and includes it in the Annex II technical file. The NB reviews the technical file and prepares a clinical evaluation assessment report, CEAR, and provides a copy to the manufacturer. Remember that for some types of devices the NB reviews the technical file on a sampling basis (yet to be specified), so there won't be a CEAR for every device. However, under Annex IX, section 5.1, for Class III implantable devices, and for Class IIb active devices intended to administer and/or remove a medicinal product, the NB transmits the CEAR to the Commission. Article 54(1) has the review requirement, Article 54(2) has some exceptions, and Article 54(3) says that the NB notifies, through Eudamed, the Competent Authorities and Commission about the use of the exception and includes the CEAR.

    The manufacturer prepares a periodic safety update report, PSUR, under Article 86 for all devices except Class I. For Class IIb and for Class III devices, the manufacturer updates it annually. For Class III devices or implantable devices, Article 86(2), the manufacturer transmits it to the NB using Eudamed. The NB reviews the report, adds its evaluation, and makes both of them available to the Competent Authority through Eudamed.

    The manufacturer prepares a summary of safety and clinical performance, SSCP, for an implantable device or a Class III device and submits it to the NB. The NB validates the SSCP and loads it to Eudamed. The manufacturer includes the SSCP location in Eudamed on the label or the IFU.

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    Dan O'Leary
    Swanzey NH
    United States
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  • 6.  RE: Article 53 CEAR and Discussion

    Posted 18-Nov-2018 10:52

    There is a lot going on here, so I'll make a short summary.

    The manufacturer implements a clinical evaluation system as part of the QMS. For each device there is a clinical evaluation plan, a clinical evaluation report, and means to update the clinical evaluation information. All of this is in the Annex II technical documentation. This applies to all device types. (For me, a device type is the class plus attributes. For example, a Class I device with a measuring function is a device type.)

     

    Under Annex IX, the NB audits the QMS and reviews the technical documentation, which includes the Annex II clinical evaluation information.

     

    The NB activities include preparing a clinical evaluation assessment report and submitting it to an Article 106 expert panel. The question is what are the conditions under which the NB performs each of the activities.

     

    According to Annex VII, 4.5 the NB implements procedures for conformity assessment. (This is a detailed section that all manufacturers need to understand.) Annex VII, 4.5.5 describes how the NB assesses clinical evaluation. Annex VII, 4.6 on reporting, first paragraph, 3rd indent requires the NB to clearly document the conclusions of its assessment of clinical evaluation in a clinical evaluation assessment report.

     

    In short, whenever the NB assess Annex II technical document it assesses the clinical evaluation information and prepares a clinical evaluation assessment report.

     

    For class III implantable devices, and for class IIb active devices intended to administer and/or remove a medicinal product, the NB transmits the clinical evaluation assessment report, along with the manufacturer's clinical evaluation documentation to the Commission. [Annex IX, 5.1.a, second paragraph]

     

    The Commission transmits it to the Article 106 Expert Panel. [Annex IX, 5.1.a, third paragraph]

     

    The Article 106 Expert Panel decides whether or not to issue a scientific opinion.

     

    This should answer the questions of the NB's preparing a clinical evaluation assessment report and when it goes to Article 106 Expert Panel.

     

    You ask, "Do we expect this to be performed retroactively for all those legacy Class III implant and Class IIb medicinal delivery products out there …?"

     

    The best answer is that there are no legacy products and no concept of retroactivity. To put a CE Mark on a device under the EU-MDR, the manufacturer must start with a "clean piece of paper". There may be (a lot) of work done under the MDD that could be brought over, but it is a fresh start. Every such device will have clinical evaluation information following the EU-MDR, an NB clinical evaluation assessment report, and an Article 106 Expert Panel decision on offering a scientific opinion.

     

    As said on TV, "BUT WAIT – THERE IS MORE!!!!"

    For Class III devices and Class IIb active devices intended to administer and/or remove a medicinal product, the manufacturer may decide to have a consultation with an Article 106 Expert Panel. [Article 61, section 2]

     

    The NB's Competent Authority reviews the NB's assessments of the manufacturers' technical documentation, in particular the clinical evaluation documentation, on a sampling basis. [Article 44, section 8 and Article 45, section 1]

     

    The Commission prepares an annual review of the devices subject to Annex IX, Section 5.1 and submits it to the European Parliament, to the Council, and to the MDCG. [Article 54, section 4]

     

    In short, clinical evaluation is a big deal in the EU-MDR and subject to many levels of scrutiny.



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    Dan O'Leary
    Swanzey NH
    United States
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