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© 2018, All rights reserved. The CRO Group, Inc.

EU IVDR Update: Big Changes Coming in 202219 JUNE 2018ASQ – RAPS – MASSMEDICWaltham Woods

Glen Emelock

Sr. Partner, The CRO Group

Lead Auditor, Technical Expert, NSAI


All opinions expressed by Glen Emelock during and after this presentation are solely his and do not reflect the opinions of ASQ, RAPS, MassMedic, NSAI, or affiliates, and may have been previously disseminated by him in other presentations, or on the Internet or via another medium. You should not treat any opinion expressed by Glen as a specific requirement for certification or approval or part of a particular regulatory strategy for such certification or approval, but only as an expression of his opinion. Glen’s opinions are based upon information he considers reliable, but neither ASQ, RAPS, MassMedic, NSAI, nor affiliates and/or subsidiaries warrant the completeness or accuracy, and it should not be relied upon as such. Emelock, ASQ, RAPS, MassMedic, NSAI, and affiliates and/or subsidiaries are not under any obligation to update or correct any information provided during this presentation. This presentation is intended to provide specific requirements and details of the European IVD Regulation. As such, it cannot address all requirements or details of the EU IVDR, and thus, the information presented including but not limited to a sample of regulatory requirements, standards, guidances, and related information mentioned should be carefully reviewed and considered as part of a baseline towards establishing an overall, well‐balanced plan to address applicable essential requirements appropriate for your specific situation.

The Fine Print



What’s Changing?

When does the fun start?

Open Issues

It’s A Whole New IVD EU



From IVDD to IVDR: Stats

Summary of Changes

From IVDD to IVDR: Scope

From Annex IIA&B + Art 9 to A‐D

Dealing with Notified Bodies

What’s Changing?althConverge…or is it Collide?


From IVDD to IVDR ‐ Stats

• IVD Directive• CD 98/79/EC• 24 Articles• 31 Pages• 10 Annexes• Didn’t call out Software• ~ 80% of IVDs not requiring NB for CE Mark

• IVD Regulation• Regulation 2017/746• 113 Articles• 176 Pages• 15 Annexes• Calls out software• ~ 80% of IVDs will require NB for CE mark


From IVDD to IVDR: Summary of Changes• Greatly reduced scope of IVDs not needing NB for CE Marking – Class A• Attempts to deal with new IVD types since 1998: molecular/genetic, ‘near

patient’ (POC), Companion (Pharma), IVD Software (SaMD)• Conformity Assessment process expanded based on IVD risk Classification• Performance Evaluation expanded for higher IVD risk Classification• Regulatory Compliance Responsible Person (unless micro/sm

manufacturer)• Unannounced NB random inspections every 5 years by NB• Expanded product traceability (UDI), Vigilance and PMS• Expanded NB authority, NBs designated for NANDOs/classes (only a few

Class D’s), will lead to vast NB consolidation• More entities regulated (Economic Operator),


From IVDD to IVDR: ScopeIVDD – CD 98/79/ECany medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, equipment, 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:concerning a physiological or pathological state, orconcerning a congenital abnormality, orto determine the safety and compatibility with potential recipients, orto monitor therapeutic measures.


From IVDD to IVDR: ScopeIVDR – Regulation 2017/746 of 5 April 2017, published 5 May 2017 L117/176any 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:concerning a physiological or pathological process or state, concerning a congenital physical or mental abnormality impairment,concerning the predisposition to a medical condition or a diseaseto determine the safety and compatibility with potential recipients, to predict treatment response or reactions, orto define or monitoring therapeutic measures.


From Annex II A, II B, Article 9

To Annex VIII, 7 Rules, 4 Classes

From Annex IIA & B + Self Test to A B C D



IVDD: Annex IIA, IIB, Article 9


IIA:Reagents and reagent products, including related calibrators and control materials, for determining the following blood groups: ABO system, rhesus (C, c, D, E, e) anti‐Kell,

Reagents and reagent products, including related calibrators and control materials, for the detection, confirmation and quantification in human specimens of markers of HIV infection (HIV 1 and 2), HTLV I and II, and hepatitis B, C and D.


IVDD: Annex IIA, IIB, Article 9IIBReagents and reagent products, including related calibrators and control materials, ‐ for determining the following blood groups: anti‐Duffy and anti‐Kidd,‐ for determining irregular anti‐erythrocytic antibodies,‐ for the detection and quantification in human samples of the following congenital infections:

rubella, toxoplasmosis,‐ for diagnosing the following hereditary disease: phenylketonuria,‐ for determining the following human infections: cytomegalovirus, chlamydia,‐ for determining the following HLA tissue groups: DR, A, B,‐ for determining the following tumoral marker: PSA,‐ and software, designed specifically for evaluating the risk of trisomy 21,The following device for self‐diagnosis, including its related calibrators and control materials: device for the measurement of blood sugar.


IVDD: Annex IIA, IIB, Article 9Article 9For all devices for self‐testing other than those covered by Annex II and devices for performance evaluation, the manufacturer shall, prior to the drawing up of the aforementioned declaration of conformity, fulfill the supplementary requirements set out in Annex III, point 6. Instead of applying thisprocedure, the manufacturer may follow the procedure referred to in paragraphs 2 or 3.


Rule 1 Rule 2 Rule 3 Rule 4 Rule 5 Rule 6 Rule 7

Hi‐risk transmissible agent Blood/Cell/ Tissue/Organ Screening

Blood grouping/ tissue typing immuno‐compatibility except ABO Rh, Kell, Kidd, Duffy)

Intended for STD dx, infectious dx immune dx companion dx, cancer dx, genetic dx, hi‐risk pharma/bio levels

Intended for self testing exceptpregnancy, fertility, CHL, glucose, RBC, WBC, bacteria in urine

Intended for general lab use, solutions, stains for IVDs, instruments for IVD, specimen receptacles

Not covered by other rules

Controls w/o quan or qual assigned values

Class D Class C exc D Class C Class C exc B Class A Class B Class B

IVDR: Annex VIII, 7 Rules, 4 Classes


Or Not: Class A

Conformity Assessment Routes

Tech File Reviews/ Type Exams

Changes, Vigilance, PMCF, PMS

Dealing with Notified BodiesCollide?



‐ Mfr name, SRN (Art 28), EU‐AR, address where registered in the EU‐ DoC statement sole responsibility of MFR‐ UDI‐DI (Annex VI Part C)‐ Product/trade name, code (REF#) or other unambiguous reference (photo), intended purpose – may be met by UDI‐DI

‐ Risk Class per rule Annex VIII‐ Statement device in conformity w/IVDR + other appl regs (ex. GDPR)‐ References to CS used/conformed with‐ Place & Date of issue, name/function of person signing

IVDR, DoC for Class A (Annex IV)


IVDR: Conformity Assessment RoutesClass B Class C Class C Class D Class D

QMS (13485+An IX Ch I)

QMS (13485+An IX Ch I)

Type ExamInclude Tech File Review (An X)

QMS(13485+An IX Ch I)

Type Exam Include Tech File Review (An X)

Tech File Review(An IX Ch II)

Tech File Review(An IX Ch II)

+EU Ref Lab Performance

Verification w/CS (3j)

Self‐test & near PT Test (5.1)

Self‐test & near PT Test (5.1)

Companion Dx (5.2)

Companion Dx (5.2)

+Companion Dx Comp Auth opin

(3k)

Production QA (An XI)

Production QA (An XI)

Verification (An XI, 5)


Review of evidence of conformance with applicable GSPRs (An I)‐ Chapter I: General includes Risk Management, Usability‐ Chapter II: Performance, Design, Manufacture:

‐ Scientific Validity, Analytical & Clinical Performance, vs. Environment, Software, Self/near test

‐ Chapter III: Information supplied with device‐ Product labeling, Instructions for Use‐ Technical Files per Annex II‐ PMS Documentation per Annex III

Techical File Reviews/Type Exams


Substantial QMS or Product ChangesVigilance Reports (Adverse Events, Malfunctions, FSCAs)Post Market SurveillancePost Market Clinical/Performance Eval Follow upShort Notice, Unannounced, For Cause Inspections when product conformity or certification are likely at risk

Additional Notified Body Encounters


Designation of NBs

If no IVDD Cert

IVDD Cert Expires

When Does All this Fun Start?Converge…or is it Collide?



‐ Expected to be a general fall out of NBs for IVDR.‐ NBs doing all they can to get MDR designation sorted‐ NBs must have technical competence for all the IVDD NANDO Codes, but can use external staff

‐ BUT NBs must have permanent, sufficient administrative, technical, and scientific staff, and oversee assessments by externals

‐ Designation for Class D IVD verification testing after EU Reference Labs established

Designation by Notified Bodies



Article 100 EU reference labs / Class D tests from 25 Nov 2020Regulation mandatory date starts 26 May 2022 – but see next slideClass D devices Article 24(4) (UDI) from 26 May 2023Class B/C devices Article 24(4) (UDI) from 26 May 2025Class A devices Article 24(4) (UDI) from 26 May 2027

Article 113 Entry into Force/Date of Application


IVDD Certs issued prior to 25 May 2017 remain valid until expiry of certificate unless IVDD Annex VI valid at latest to 27 May 2025.IVDD Certs issue after 25 May 2017 shall become void by 27 May 2024.Devices legally placed on the market prior to 26 May 2022 and devices with a valid certificate after 26 May 2022 can continue to be made available or put into use until 27 May 2025NBs notified for IVDD may continue to issue certificates prior to 26 May 2022.

Article 110 Transition


Good News

Other News

So Plan Already

Open Issuesnverge…or is it Collide?



Good News

There really isn’t any


IVDR Not Just for MFRs, NBs, Comp Auth’s• “Economic Operators” (Art 30) required to: register (Art 27),

maintain traceability records (Art 30), subject to Market Surveillance (Art 88), and required to ‘cooperate’ with Competent Authorities (Art 89), and take relevant corrective action (Art 90)

• Health Institutions ‘manufacturing’ IVDs for use only within the health institution (ex. Home‐Brew Kits, Commercial Testing Labs/Proprietary Tests) subject to Article 5


What happens when:• NBs totally consumed with getting designated under MDR are

forced to delay designation under IVDR until 2020 or later?• NBs which HAD expertise for IVDD devices but not for specific

devices under IVDR are designated for just the NANDO codes of their expertise?

• EU Reference Labs are not established by 25 Nov 2020 or are but so few are, they are severely backlogged with test queues for Class D devices?

• Not enough NBs are designated or designated for the NANDO for your NEW IVD by/before 26 May 2022?

• Not enough NBs are designated so IVD manufacturers with expiring IVDD certs can get certified to IVDR by 27 May 2024?


So Plan Already• Which IVD devices currently placed on EU Market or planned to

be placed on EU Market are Class B – D?• What is the IVDR status of your current IVDD NB (or if you

don’t have a IVDD NB, your ISO 13485 registrar) – ex. did they apply for IVDR NB when they could have (Nov 2017)? If not, when will they? If they don’t know, maybe time to research alternatives.

• Form Project Teams – review GSPRs, standards compliance, decide on Annex IX (Full QMS) vs Annex X (Type Exam) + XI (Production QS), and PREPARE


Q & AIn the unlikely event you continue to have questions, or if your particular concern was not addressed during this presentation, please feel free to contact your MassMedic/ASQ NEDG/RAPS representative. It’s entirely likely a future event will address EU IVDR in more excruciating detail.

For More Info:IVDD Notified Bodies websitesCompetent Authorities websitesRAPS websiteMDR/IVDR Consultants websites

eu ivdr update - massmedic · self testing except pregnancy, fertility, chl, glucose, rbc, wbc,...

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